research studies on gbs

• Open access
• Published: 11 November 2021

Global, regional, and national burden of Guillain–Barré syndrome and its underlying causes from 1990 to 2019

• Nicola Luigi Bragazzi 1 ,
• Ali-Asghar Kolahi 2 ,
• Seyed Aria Nejadghaderi 3 ,
• Piergiorgio Lochner 4 ,
• Francesco Brigo 5 ,
• Andrea Naldi 6 ,
• Paola Lanteri 7 ,
• Sergio Garbarino 8 ,
• Mark J. M. Sullman 9 , 10 ,
• Haijiang Dai 1 ,
• Jianhong Wu 1 ,
• Jude Dzevela Kong 1 ,
• Haitham Jahrami 11 ,
• Mohammad-Reza Sohrabi 2 &
• Saeid Safiri   ORCID: orcid.org/0000-0001-7986-9072 12 , 13  

Journal of Neuroinflammation volume  18 , Article number:  264 ( 2021 ) Cite this article

13k Accesses

25 Citations

3 Altmetric

Metrics details

This article presents the first detailed analysis of the prevalence and disability burden of Guillain–Barré syndrome (GBS) from 1990 to 2019 by cause, age, sex, and Socio-demographic Index (SDI) in 204 countries and territories.

Data from the Global Burden of Diseases Study (GBD) 2019 were used. GBD 2019 modelled the prevalence of GBS using hospital and claims data. Years lived with disability (YLDs) were estimated as the product of the GBS prevalence and the disability weight. This article also reported proportions in the age-standardised prevalence rate that were due to six underlying causes of GBS.

In 2019, there were 150,095 [95% uncertainty intervals (UI) 119,924 to 188,309] total cases of GBS worldwide, which resulted in 44,407 (95% UI 28,016 to 64,777) YLDs. Globally, there was a 6.4% (95% UI 3.6 to 9.5) increase in the age-standardised prevalence of GBS per 100,000 population between 1990 and 2019. High-income Asia Pacific [1.9 (95% UI: 1.5 to 2.4)] and East Asia [0.8 (95% UI: 0.6 to 1.0)] had the highest and lowest age-standardised prevalence rates (per 100,000), respectively, in 2019. Nationally, Japan [6.4 (95% UI: 5.3 to 7.7)] and China [0.8 (95% UI: 0.6 to 1.0)] had the highest and lowest age-standardised prevalence rates (per 100,000). The age-standardised burden of GBS increased with increasing age and was higher in males in all age groups. Furthermore, the age-standardised prevalence of GBS (per 100,000) had a positive association with the level of development, as measured by SDI, although this association was not strong. Upper respiratory infections and unknown causes accounted for the highest proportions of underlying causes.

Conclusions

Globally, the prevalence of GBS continues to increase. Geographical differences and strategies aimed at preventing infectious diseases should be considered in future health policy planning and decision-making processes. This study had several limitations, such as using the same disability weight for all causes and a reliance on hospital- and self-reported data, which should be addressed in future research.

Introduction

Guillain–Barré syndrome (GBS) is an acute immune-mediated polyneuropathy. It represents an aberrant autoimmune response to a preceding infection or other immune stimulation, which leads the immune system to attack the myelin sheaths or axons of the peripheral nerves and their spinal roots, due to molecular mimicry [ 1 , 2 ]. GBS occurs worldwide with an overall incidence rate of 1–2 cases per 100,000 people per year, affecting all age groups, but is slightly more common in males than in females [ 3 , 4 , 5 ]. Mortality, or severe disability due to GBS, occurs in around 20% of patients [ 6 ].

Clinically, GBS manifests itself with progressive muscle weakness associated with decreased or absent deep tendon reflexes, as well as mild to severe sensory signs and symptoms [ 1 ]. Symptoms usually start in the lower limbs and gradually ascend to involve the arms and facial muscles [ 1 ]. Dysfunction in the autonomic system occurs in approximately 70% of patients and can lead to death [ 7 ]. GBS follows a monophasic course, usually progressing over a period of about 2 weeks, with symptoms reaching the nadir around 4 weeks after onset. Most patients require hospitalization and some of them ventilator assistance in intensive care units [ 8 ]. Overall, more than 80% have a complete or nearly complete recovery; the prognosis is worse in elderly patients and in cases with axonal involvement [ 2 ]. However, some patients have a protracted recovery, resulting in disability which can be permanent or lasting several years [ 1 ]. Respiratory or gastrointestinal infection, infection with the Zika virus, and autoimmunity are some of the suggested etiologies for the development of GBS [ 6 ].

To develop and implement specific strategies aimed at improving the health outcomes for people with GBS, it is important to systematically evaluate the burden of this condition. However, to the best of our knowledge, no prior research has provided estimates for the burden and trends associated with GBS at the global level. The primary aim of this report was to present the first detailed analysis of the prevalence and disability burden of GBS by cause, age, sex, and Socio-demographic Index (SDI) in 204 countries and territories from 1990 to 2019, using data from the Global Burden of Diseases Study (GBD) 2019.

This study is part of the GBD 2019 project, which was conducted by the Institute for Health Metrics and Evaluation (IHME) to provide a systematic investigation of the burden of 369 diseases and injuries and 87 behavioural, environmental, occupational, and metabolic risk factors [ 9 , 10 , 11 ]. GBD 2019 included data for seven super-regions, 21 regions, and 204 countries and territories from 1990 to 2019. Full details of the methods used in GBD 2019 are described in existing GBD literature [ 9 , 10 , 11 ]. As GBD 2019 used de-identified aggregated data, a waiver of informed consent was reviewed and approved by the University of Washington, Seattle, Washington, United States of America, Institutional Review Board. All data on the burden of GBS, for all countries and regions and from the period 1990 to 2019, are publicly available on the IHME website [Available from: http://ghdx.healthdata.org/gbd-results-tool ].

Data sources

The International Classification of Disease (ICD) codes of G61.0 (GBS) and 357.0 (Acute infective polyneuritis) were considered by IHME to be GBS. In this study, inpatient hospital data were extracted using the ICD codes listed above. Only primary diagnoses were considered, with the reasoning being that GBS should appear as a primary diagnosis and IHME did not wish to include follow-up visits that may be listed as secondary or tertiary codes. In addition, two additional years of claims data from the United States of America (USA) (2015, 2016) and 3 years of claims data from Poland (2015, 2016, 2017), for the first time, were also included in GBD 2019 [ 9 ]. More detailed information on the data sources used for the estimations of GBS can be found on the GBD 2019 Data Input Sources Tool website [ http://ghdx.healthdata.org/gbd-2019/data-input-sources ].

Prevalence and underlying cause estimation

The prevalence of GBS for each location, year, age, and sex were estimated using DisMod-MR 2.1, a Bayesian meta-regression tool developed for GBD analyses [ 12 ]. Unlike the last GBD iteration, the hospital data were not adjusted in this study, as they were quite similar to the data from the literature. To divide the overall prevalence of GBS according to the underlying cause, a systematic review of the literature was conducted to identify studies on the proportion of GBS cases attributable to any described aetiological cause, including influenza, upper respiratory infections, diarrheal diseases, and other infectious diseases. Based on these studies, an aetiological proportion model was developed using DisMod-MR 2.1 and used to divide the prevalent cases of GBS by cause. A random effects meta-analysis was used to pool these proportions. The proportions for influenza, upper respiratory infections, diarrheal diseases, and other infectious diseases were squeezed to add to the proportion for all identified underlying infectious diseases [ 12 ]. Finally, the remaining proportion with any underlying infectious disease were assigned to the “idiopathic GBS” category, which is classified under unknown causes [ 12 ].

YLDs estimation

To calculate the YLDs for GBS, the prevalence of GBS (in number of cases) was multiplied by their disability weight, which quantifies the magnitude of health loss associated with GBS. The YLD rate is defined as the number of YLDs expressed per 100,000 population. Disability weights are measured on a scale from 0 to 1, where 0 represents full health and 1 is equivalent to death. More information about the process of disability weight estimation has been described in detail elsewhere [ 9 , 10 ]. In GBD 2019, GBS attributed causes (i.e., lower respiratory infections, upper respiratory infections, diarrheal diseases and other infectious diseases) were all assigned the same disability weight, which was 0.296 (0.198–0.414) (Additional file 1 : Table S1) [ 9 ].

Socio-demographic Index (SDI)

We used SDI to explore the relationship that the development level of a region or country has with GBS prevalence and YLDs [ 9 ]. Smoothing splines models were used to examine the association between the burden of GBS, computed in terms of YLDs, and SDI for 21 regions and 204 countries and territories [ 13 ]. The SDI, a composite indicator that quantifies the development level, ranges from 0 (the worst) to 1 (the best). It is calculated based on the average educational attainment in the population aged 15 years or older, total fertility rate under 25 years, and lag-distributed income per capita. The cutoff values used to determine SDI quintiles were computed using estimates from countries with populations over 1 million. The 204 countries and territories were divided into five groups, according to SDI quintile: low SDI, low-middle SDI, middle SDI, high-middle SDI, and high SDI [ 9 ].

Uncertainty analysis

IHME propagated uncertainty through all calculations by sampling 1000 draws at each step of the calculations [ 9 ]. Final estimates were determined using the mean estimate across 1000 draws, and the 95% uncertainty intervals (UIs) were defined as the 25th and 975th values of the 1000 ordered draws. For all estimates, a 95% UI excluding zero was considered to be statistically significant.

Global level

In 2019, there were 150,095 (95% UI: 119,924 to 188,309) cases of GBS globally, with an age-standardised point prevalence of 1.9 per 100,000 population (95% UI: 1.5 to 2.4), which represents a 6.4% increase since 1990 (95% UI: 3.6 to 9.5). GBS accounted for 44,407 (95% UI: 28,016 to 64,777) YLDs in 2019, with an age-standardised rate of 0.6 (95% UI: 0.4 to 0.8), which has increased 6.5% since 1990 (95% UI: 3.6 to 9.5) (Table 1 ).

Regional level

In 2019, the age-standardised point prevalence of GBS (per 100,000 population) was highest in High-income Asia Pacific [6.4 (95% UI: 5.2 to 7.7)], High-income North America [4.2 (95% UI: 3.5 to 5.1)] and Central Latin America [3.9 (95% UI: 3.1 to 4.9)]. East Asia [0.8 (95% UI: 0.6 to 1.0)], Oceania [1.0 (95% UI: 0.8 to 1.4)] and Southeast Asia [1.1 (95% UI: 0.8 to 1.4)] had the lowest age-standardised rates (Table 1 ).

High-income Asia Pacific [1.9 (95% UI: 1.2 to 2.8)], High-income North America [1.3 (95% UI: 0.8 to 1.8)] and Central Latin America [1.2 (95% UI: 0.7 to 1.7)] had the highest age-standardised YLD rates from GBS. The rates were lowest for East Asia [0.2 (95% UI: 0.1 to 0.4)], Oceania [0.3 (95% UI: 0.2 to 0.5)] and Southeast Asia [0.3 (95% UI: 0.2 to 0.5)] (Table 1 ). The age-standardised point prevalence and YLD rates of GBS, for all GBD regions in 2019, are presented in Additional file 4 : Figures S1 and Additional file 5 : S2, respectively.

Most regions showed an increase in the age-standardised point prevalence of GBS, from 1990 to 2019, except Tropical Latin America [− 40.3% (95% UI: − 49.9 to − 31.3)] and Andean Latin America [− 6.8% (95% UI: − 8.6 to − 4.7)] (Table 1 ). In the same period, most regions showed an increase in the age-standardised YLD rates of GBS from, except Tropical Latin America [− 40.3% (95% UI: − 49.9 to − 31.3)] and Andean Latin America [− 6.8% (95% UI: − 8.6 to − 4.7)] (Table 1 ). The percentage change, from 1990 to 2019, in the age-standardised point prevalence and YLD rates for GBS are presented in Additional file 6 : Fig. S3 and Additional file 7 : Fig. S4, respectively.

The global number of cases of GBS increased from 90,249 (95% UI: 70,747 to 114,487) in 1990 to 150,095 (95% UI: 119,924 to 188,309) in 2019. South Asia, High-income North America and East Asia experienced the largest number of cases in 2019 (Additional file 2 : Table S2). The global number of YLDs due to GBS increased from 26,696 (95% UI: 16,714 to 39,628) in 1990 to 44,407 (95% UI: 28,016 to 64,777) in 2019, with South Asia, High-income North America and East Asia having the highest numbers of YLDs, due to GBS, in 2019 (Additional file 3 : Table S3).

National level

In 2019, the national age-standardised point prevalence of GBS ranged from 0.8 to 6.4 cases per 100,000 population. Japan [6.4 (95% UI: 5.3 to 7.7)], Brunei Darussalam [6.3 (95% UI: 5.0 to 7.8)] and Singapore [6.3 (95% UI: 5.0 to 7.8)] had the highest age-standardised point prevalences (per 100,000) of GBS in 2019. In contrast, China [0.8 (95% UI: 0.6 to 1.0)], the Democratic People's Republic of Korea [0.9 (95% UI: 0.6 to 1.1)], and Kiribati [1.0 (95% UI: 0.8 to 1.3)] had the lowest point prevalences (per 100,000) (Fig.  1 and Additional file 2 : Table S2).

Age-standardised point prevalence of Guillain–Barre syndrome per 100,000 population in 2019, by country. (Generated from data available from http://ghdx.healthdata.org/gbd-results-tool )

The national age-standardised YLD rates of GBS varied in 2019 from 0.2 to 1.9 cases per 100,000 population. The highest YLD rates (per 100,000) were observed in Japan [1.9 (95% UI: 1.2 to 2.8)], Brunei Darussalam [1.9 (95% UI: 1.2 to 2.7)] and Singapore [1.9 (95% UI: 1.2 to 2.7)], while the lowest YLD rates (per 100,000) were found in China [0.2 (95% UI: 0.1 to 0.4)], the Democratic People’s Republic of Korea [0.3 (95% UI: 0.2 to 0.4)], and Kiribati [0.3 (95% UI: 0.2 to 0.5] (Fig.  2 and Additional file 3 : Table S3).

Age-standardised years lived with disability (YLDs) rate of Guillain–Barre syndrome per 100,000 population in 2019, by country. (Generated from data available from http://ghdx.healthdata.org/gbd-results-tool )

The percentage change in the age-standardised point prevalence (per 100,000), from 1990 to 2019, differed substantially between countries, with the United Kingdom [104.7% (95% UI: 90.1 to 124.4)], Sweden [102.6% (95% UI: 85.8 to 122.4)] and Austria [53.5% (95% UI: 32.4 to 83.0)] showing the largest increases during the measurement period. In contrast, Brazil [− 40.7% (95% UI: − 50.4 to − 31.6)], Ecuador [− 26.1% (95% UI: − 32.0 to − 19.0)] and Nepal [− 15.7% (95% UI: − 22.5 to − 7.4)] showed the largest decreases in the age-standardised point prevalence (per 100,000) (Additional file 2 : Table S2).

The United Kingdom [104.7% (95% UI: 90.1 to 124.4)], Sweden [102.6% (95% UI: 85.8 to 122.4)] and Austria [53.5% (95% UI: 32.4 to 83.0)] showed the largest increases in the age-standardised YLD rates (per 100,000) of GBS over the measurement period (Additional file 3 : Table S3). Conversely, Brazil [− 40.7% (95% UI: − 50.4 to − 31.6)], Ecuador [− 26.1% (95% UI: − 32.0 to − 19.0)] and Nepal [− 15.8% (95% UI: − 22.5 to − 7.4)] showed the largest decreases in YLDs (per 100,000) over the same period (Additional file 3 : Table S3).

Age and sex patterns

In 2019, the global point prevalence of GBS (per 100,000) broadly showed an increase with advancing age. More specifically, the total number of cases was highest in the 5–9 year age group, but decreased from there to the 25–29 age group, then increased up to the 60–64 age group, before decreasing again to the oldest age group. Furthermore, the global point prevalence of GBS (per 100,000) was higher in males in all age groups, while the total number of cases was higher in males up to the 75–79 age group, after which the pattern was reversed (Fig.  3 ).

Global total number of cases and the prevalence of Guillain–Barre syndrome per 100,000 population, by age and sex in 2019. The error bars represent 95% uncertainty intervals for total number of cases. Dotted and dashed lines indicate 95% uncertainty intervals for prevalence (per 100,000). (Generated from data available from http://ghdx.healthdata.org/gbd-results-tool )

In 2019, the global YLD rate of GBS (per 100,000) was highest in those aged 95 + years and was higher among males. However, the total number of YLDs was highest in the 5–9 age group for both males and females (Additional file 8 : Figure S5).

Association with the Socio-demographic Index (SDI)

At the regional level there was a positive association between SDI and the age-standardised YLD rate of GBS, suggesting that the burden of GBS was higher in regions with higher socio-economic development. High-income Asia Pacific, Central Latin America, Southern Sub-Saharan Africa, Western Sub-Saharan Africa, Central Sub-Saharan Africa, Southern Latin America and Andean Latin America had higher than expected YLD rates, from 1990 to 2019, based upon their level of socio-demographic development (as measured by the SDI). In contrast, Western Europe, Central Europe, Australasia, Southeast Asia, East Asia and Oceania had lower than expected burdens from 1990 to 2019 (Fig.  4 ).

Age-standardised years lived with disability (YLDs) rates of Guillain–Barre syndrome for 204 countries and territories, by Socio-demographic Index (SDI) in 2019; Expected values based on the Socio-demographic Index and disease rates in all locations are shown as the black line. Each point shows the observed age-standardised YLD rate for each country in 2019. (Generated from data available from http://ghdx.healthdata.org/gbd-results-tool )

At the country-level, in 2019 the burden of GBS increased with increasing socio-economic development, up to an SDI of around 0.3, but then decreased slightly up to an SDI of about 0.7, then increased up to an SDI of 0.9, before decreasing again (Additional file 9: Figure S6). Countries and territories, such as Japan, Brunei Darussalam, Singapore, the Republic of Korea, the USA and Mexico had much higher than expected burdens, whereas countries and territories such as China, Fiji, Taiwan and Guam had much lower than expected burdens (Additional file 9 : Fig. S6).

The global point prevalence of GBS was stable from 1990 to 2000, and from 2000 it began to gradually increase. Up to about 2010, the low SDI quintile and high SDI quintile both had point prevalence rates which were higher than the global level, while middle, low–middle and high–middle SDI quintiles had rates which were lower than the global level. Furthermore, the age-standardised point prevalence of GBS was stable in all SDI quintiles over 1990–2019 except the high-SDI quintile, which had an increase in its point prevalence rate from 2005 (Additional file 10 : Fig. S7). The age-standardised YLD rates had a similar pattern to the point prevalence rates for the different SDI quintiles (Additional file 11 : Fig. S8).

Underlying causes

Although the proportion of the GBS YLDs attributable to the individual underlying causes differed by age group, globally upper respiratory infections and unknown causes accounted for most of the YLDs. The highest proportion of attributable YLDs were in the 5–9 age group for all GBS causes. Furthermore, the global YLD rate of GBS attributable to all causes, especially unknown causes and upper respiratory infections, increased with advancing age, except for the Zika virus (Fig.  5 ). The proportion of GBS prevalence attributable to the individual underlying causes showed a similar pattern to the YLDs by age group (Additional file 12 : Fig. S9).

Global number of years lived with disability (YLDs) and YLDs due to Guillain–Barre syndrome per 100,000 population attributable to each underlying cause by age in 2019. (Generated from data available from http://ghdx.healthdata.org/gbd-results-tool )

In this study we reported the levels and trends in the global burden of GBS from 1990 to 2019, making comparisons across different regions and countries. Our analyses were based on the 2019 dataset provided by the GBD project, which is the most comprehensive worldwide observational epidemiological study aimed at reporting mortality and disability from major diseases, at the global, national and regional levels [ 14 ]. We found a worldwide increase of 6.4% in the age-standardised prevalence of GBS from 1990 to 2019. This slight increase in the age-standardised prevalence may partly reflect the increased life expectancy among GBS patients, due to improved care and earlier diagnosis of this condition [ 4 ]. The observed increase in the prevalent cases of GBS can be explained by population growth and aging. However, future studies using decomposition analysis are needed to clarify the roles that population growth and aging had on the number of prevalent cases of GBS. Furthermore, higher exposure to potential underlying causes of GBS, such as infection with Campylobacter jejuni , Haemophilus influenzae , Cytomegalovirus, Zika virus, and some other respiratory or gastrointestinal infections could be another reason for the observed increase [ 1 , 15 ]. Nevertheless, future research is required to determine the probable causes of the increased prevalence of GBS over the period 1990–2019.

For both sexes, the prevalence rate of GBS was bimodal, with the highest age-standardised values among the elderly and the lowest in children aged < 4 years. Nevertheless, the absolute number of prevalent GBS cases was highest in children aged 5–9 years, highlighting the need for more health resource allocation and efforts to improve surveillance systems for children, especially for those with underlying causes of GBS. In addition, a “ceiling effect” was found in the age-standardised prevalence rates among women, with the prevalence rate remaining stable after the age of 70. This finding could be attributed to changes of the immune system of women after the menopause [ 16 ].

The age-standardised prevalence rates of GBS in 2019 varied considerably by geographic region. The highest age-standardised prevalence rates were observed in High-income Asia Pacific and High-income North America, while the lowest were found in East Asia and Oceania. This variation in the burden of GBS between different regions may be as a result of differing levels of hygiene and variations in local exposure to the risk factors, especially gastrointestinal and respiratory infections [ 17 ]. Interestingly, there was considerable variation in the age-standardised prevalence rates of GBS within the countries that comprise Tropical Latin America. Although exposure to the Zika virus was recently identified as an arbovirus infection associated with GBS [ 18 , 19 ], there is insufficient epidemiological data in the GBD database to conclusively explain these differences.

The highest age-standardised prevalence rate of GBS was found in Japan, probably due to the high frequency of Campylobacter jejuni infections and presumably also due to genetic and environmental predispositions [ 20 , 21 , 22 ]. The percentage increase in the age-standardised prevalence rate of GBS from 1990 to 2019 in different regions and countries may be due to the recent outbreak of the Zika virus in several countries from the Western Sub-Saharan Africa, Central Latin America and Caribbean regions, such as the Virgin Islands, the USA, Dominica and Puerto Rico. Strategies aimed at controlling the spread of the Zika virus can effectively reduce the burden of GBS in these countries. Although Brazil was one of the countries which was most severely affected by the Zika virus epidemic [ 23 , 24 ], the age-standardised prevalence rate of GBS decreased significantly (by 40.7%) between 1990 and 2019, due to reductions in cases from other causes. Again it is worth mentioning that, there is insufficient epidemiological data in the GBD database to conclusively explain these differences.

Between 1990 and 2019, GBS was associated with a worldwide increase in both absolute numbers and the age-standardised rate of YLDs, while also being consistently higher in males. Worldwide, GBS was associated with a substantial burden in terms of disability, but there were also regional differences in the GBS-associated disability, the reasons for which should be identified and used to implement specific geographical strategies to improve the health outcomes of people with GBS. Despite the lack of a clear association between development level (regional or country level) and the GBS burden, an observed high in YLDs was found in the High-income Asia Pacific and High-income North American countries. Although the GBD findings could not determine the reasons for higher prevalence of GBS in two mentioned regions, further studies on burden of GBS by type and its attributable underlying causes are recommended.

Strengths and limitations of the study

Our study is one of the first and most comprehensive epidemiological studies to provide an insight into the burden of GBS at the global, regional and national levels, as well as its trend over the period 1990 to 2019. However, despite its high methodological rigor, the present study is not without limitations. The largest shortcoming is the dearth of data and reliable information for many countries, especially those in developing countries. In resource-limited settings, diagnostic codes may not be entirely accurate, resulting in an underestimation of GBS cases. In these situations, missing data were inferred using statistical approaches by performing covariate-driven modeling. This warrants further action and research in the field, such as establishing ad hoc registries and pursuing nationwide community-based epidemiological surveys. Moreover, the data used to estimate the burden of GBS was based on hospital- and self-report data, which can lead to a high degree of variability and overestimation of the disease burden, as GBS patients who are quite debilitated in hospital may recover significantly. It is also important to recognise that severe cases of GBS in resource limited countries may die prior to getting to a hospital, resulting in a selection bias of less severe cases in the inpatient hospital data. Moreover, the same disability index of 0.296 was used in all countries, GBS disease causes, and ages. This could be inaccurate, as the survival, disability and recovery associated with GBS could vary significantly from country to country, by: level of socioeconomic development, access to tertiary care hospitals with GBS management expertise, proportion of patients with different variants of GBS, and the age of patients with GBS and the proportion with other comorbidities. Similarly, attributing the same disability weight to different causes may not be accurate, as it is known that certain causes (e.g., Campylobacter jejuni gastroenteritis) may be associated with higher disability and mortality rates. In addition, the burden of the different subtypes of GBS, such as acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy (AMAN) and acute motor sensory axonal neuropathy (AMSAN), were not reported in this study [ 26 ]. Due to variations in the outcomes of different GBS variants, providing data on the burden of different GBS variants might be useful for health policy makers and should be taken into account in future research. Furthermore, no data was available for the burden of GBS in some countries and this must be taken into account when interpreting the results of this study.

The present study examined trends in the burden of GBS from 1990 to 2019 across different regions and countries and found a large burden, in terms of the worldwide prevalence and disability, especially among young children and the elderly. Strategies aimed at preventing infectious diseases and improving hygiene conditions may be effective in reducing the prevalence of GBS. Furthermore, the effects of emergent infectious diseases, such as coronavirus disease 2019 (COVID-19), on the incidence of GBS should be evaluated in future research [ 27 , 28 ]. Efforts to improve data collection and sharing, especially in low SDI countries, and the implementations of different disability weights for each location and underlying cause for estimation of the burden of GBS should be taken into account in future studies. Finally, geographic differences in the burden of GBS should be considered in future health-related decision-making and planning processes. In addition, the epidemiology of anti-ganglioside antibodies, as one of the associated factors with GBS, is recommended to be discussed in future epidemiological research.

Availability of data and materials

Publicly available datasets were analysed in this study. This data can be found here: http://ghdx.healthdata.org/gbd-results-tool .

Abbreviations

• Guillain–Barré syndrome

Socio-demographic Index

Global burden of diseases

Institute for Health Metrics and Evaluation

International Classification of Disease

United States of America

• Years lived with disability

Uncertainty intervals

Acute inflammatory demyelinating polyradiculoneuropathy

Acute motor axonal neuropathy

Acute motor sensory axonal neuropathy

Coronavirus disease 2019

Willison HJ, Jacobs BC, van Doorn PA. Guillain–Barre syndrome. Lancet. 2016;388(10045):717–27.

Article   Google Scholar  

van den Berg B, Walgaard C, Drenthen J, Fokke C, Jacobs BC, van Doorn PA. Guillain–Barre syndrome: pathogenesis, diagnosis, treatment and prognosis. Nat Rev Neurol. 2014;10(8):469–82.

Sejvar JJ, Baughman AL, Wise M, Morgan OW. Population incidence of Guillain–Barre syndrome: a systematic review and meta-analysis. Neuroepidemiology. 2011;36(2):123–33.

Yuki N, Hartung HP. Guillain–Barre syndrome. N Engl J Med. 2012;366(24):2294–304.

Article   CAS   Google Scholar  

Leonhard SE, Mandarakas MR, Gondim FAA, Bateman K, Ferreira MLB, Cornblath DR, et al. Diagnosis and management of Guillain–Barre syndrome in ten steps. Nat Rev Neurol. 2019;15(11):671–83.

Jasti AK, Selmi C, Sarmiento-Monroy JC, Vega DA, Anaya J-M, Gershwin ME. Guillain–Barré syndrome: causes, immunopathogenic mechanisms and treatment. Expert Rev Clin Immunol. 2016;12(11):1175–89.

Flachenecker P. Autonomic dysfunction in Guillain–Barre syndrome and multiple sclerosis. J Neurol. 2007;254(Suppl 2):96–101.

Google Scholar  

Dirlikov E, Major CG, Medina NA, Lugo-Robles R, Matos D, Munoz-Jordan JL, et al. Clinical features of Guillain–Barre syndrome with vs without zika virus infection, Puerto Rico, 2016. JAMA Neurol. 2018;75(9):1089–97.

Vos T, Lim SS, Abbafati C, Abbas KM, Abbasi M, Abbasifard M, et al. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1204–22.

Murray CJL, Aravkin AY, Zheng P, Abbafati C, Abbas KM, Abbasi-Kangevari M, et al. Global burden of 87 risk factors in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1223–49.

Wang H, Abbas KM, Abbasifard M, Abbasi-Kangevari M, Abbastabar H, Abd-Allah F, et al. Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950–2019: a comprehensive demographic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1160–203.

Disease GBD, Injury I, Prevalence C. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1789–858.

Wang Y. Smoothing splines: methods and applications. Wang Y, editor. Chapman and Hall/CRC; 2011.

Murray CJ, Lopez AD. Measuring the global burden of disease. N Engl J Med. 2013;369(5):448–57.

Zbrun MV, Rossler E, Romero-Scharpen A, Soto LP, Berisvil A, Zimmermann JA, et al. Worldwide meta-analysis of the prevalence of Campylobacter in animal food products. Res Vet Sci. 2020;132:69–77.

Gameiro CM, Romao F, Castelo-Branco C. Menopause and aging: changes in the immune system—a review. Maturitas. 2010;67(4):316–20.

Doets AY, Verboon C, van den Berg B, Harbo T, Cornblath DR, Willison HJ, et al. Regional variation of Guillain–Barré syndrome. Brain. 2018;141(10):2866–77.

Krauer F, Riesen M, Reveiz L, Oladapo OT, Martinez-Vega R, Porgo TV, et al. Zika virus infection as a cause of congenital brain abnormalities and Guillain–Barre syndrome: systematic review. PLoS Med. 2017;14(1): e1002203.

Leonhard SE, Bresani-Salvi CC, Lyra Batista JD, Cunha S, Jacobs BC, Brito Ferreira ML, et al. Guillain–Barre syndrome related to Zika virus infection: a systematic review and meta-analysis of the clinical and electrophysiological phenotype. PLoS Negl Trop Dis. 2020;14(4): e0008264.

Rees JH, Soudain SE, Gregson NA, Hughes RA. Campylobacter jejuni infection and Guillain–Barre syndrome. N Engl J Med. 1995;333(21):1374–9.

McCarthy N, Andersson Y, Jormanainen V, Gustavsson O, Giesecke J. The risk of Guillain–Barre syndrome following infection with Campylobacter jejuni . Epidemiol Infect. 1999;122(1):15–7.

Bae JS, Yuki N, Kuwabara S, Kim JK, Vucic S, Lin CS, et al. Guillain–Barre syndrome in Asia. J Neurol Neurosurg Psychiatry. 2014;85(8):907–13.

Campos GS, Bandeira AC, Sardi SI. Zika virus outbreak, Bahia, Brazil. Brazil Emerg Infect Dis. 2015;21(10):1885–6.

Metsky HC, Matranga CB, Wohl S, Schaffner SF, Freije CA, Winnicki SM, et al. Zika virus evolution and spread in the Americas. Nature. 2017;546(7658):411–5.

Collaborators GBDB. Burden of disease in Brazil, 1990–2016: a systematic subnational analysis for the Global Burden of Disease Study 2016. Lancet. 2018;392(10149):760–75.

Leonhard SE, Mandarakas MR, Gondim FAA, Bateman K, Ferreira MLB, Cornblath DR, et al. Diagnosis and management of Guillain–Barré syndrome in ten steps. Nat Rev Neurol. 2019;15(11):671–83.

Zhao H, Shen D, Zhou H, Liu J, Chen S. Guillain–Barré syndrome associated with SARS-CoV-2 infection: causality or coincidence? Lancet Neurol. 2020;19(5):383–4.

Keddie S, Pakpoor J, Mousele C, Pipis M, Machado PM, Foster M, et al. Epidemiological and cohort study finds no association between COVID-19 and Guillain–Barré syndrome. Brain. 2021;144(2):682–93.

Download references

Acknowledgements

We thank all members of the Institute for Health Metrics and Evaluation (IHME), University of Washington, and all collaborators involved in GBD 2019 study.

This study is based on publicly available data and solely reflects the opinions of its authors and not that of the IHME.

The Bill and Melinda Gates Foundation, who were not involved in any way in the preparation of this manuscript, funded the GBD study. The Shahid Beheshti University of Medical Sciences, Tehran, Iran (Grant No. 24660) also supported the present report.

Author information

Authors and affiliations.

Centre for Disease Modelling, York University, Toronto, ON, Canada

Nicola Luigi Bragazzi, Haijiang Dai, Jianhong Wu & Jude Dzevela Kong

Social Determinants of Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Ali-Asghar Kolahi & Mohammad-Reza Sohrabi

Systematic Review and Meta-Analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran

Seyed Aria Nejadghaderi

Department of Neurology, Saarland University Medical Center, Homburg, Germany

Piergiorgio Lochner

Department of Neurology, Franz Tappeiner Hospital, Merano, Italy

Francesco Brigo

Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Turin, Italy

Andrea Naldi

Neurophysiology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

Paola Lanteri

Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal/Child Sciences (DINOGMI), Polyclinic Hospital San Martino IRCCS, University of Genoa, Genoa, Italy

Sergio Garbarino

Department of Social Sciences, University of Nicosia, Nicosia, Cyprus

Mark J. M. Sullman

Department of Life and Health Sciences, University of Nicosia, Nicosia, Cyprus

College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain

Haitham Jahrami

Neurosciences Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran

Saeid Safiri

Department of Community Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

You can also search for this author in PubMed   Google Scholar

Contributions

NLB, MRS, HD, AAK and SS designed the study. NLB, HD and SS analyzed the data and performed the statistical analyses. NLB, AAK, SAN, PL, FB, AN, PL, SG, MJMS, HD, JW, JDK, HJ and SS ,  drafted the initial manuscript. All authors reviewed the drafted the manuscript for critical content. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Ali-Asghar Kolahi or Saeid Safiri .

Ethics declarations

Ethics approval and consent to participate.

The present study was approved by ethical committee of Shahid Beheshti University of Medical Sciences, Tehran, Iran (IR.SBMU.RETECH.REC.1400.075).

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1: table s1..

Sequelae for Guillain–Barre syndrome and the corresponding disability weights in the GBD 2019 study.

Additional file 2: Table S2.

Total number of Guillain–Barre syndrome cases in 1990 and 2019 and the percentage change in the age-standardised rates (ASRs) per 100,000, by location (Generated from data available from http://ghdx.healthdata.org/gbd-results-tool ).

Additional file 3: Table S3.

Years lived with disability (YLDs) due to Guillain–Barre syndrome in 1990 and 2019 and the percentage change in the age-standardised rates (ASRs) per 100,000, by location (Generated from data available from http://ghdx.healthdata.org/gbd-results-tool ).

Additional file 4: Figure S1.

The age-standardised point prevalence of Guillain–Barre syndrome in 2019 for the 21 Global Burden of Disease regions, by sex. The error bars represent 95% uncertainty intervals for the age-standardised prevalence per 100,000 population. (Generated from data available from http://ghdx.healthdata.org/gbd-results-tool ).

Additional file 5: Figure S2.

The age-standardised years lived with disability (YLDs) rates of Guillain–Barre syndrome in 2019 for the 21 Global Burden of Disease regions, by sex. The error bars represent 95% uncertainty intervals for the age-standardised YLD rate per 100,000 population. (Generated from data available from http://ghdx.healthdata.org/gbd-results-tool ).

Additional file 6: Figure S3.

The percentage change in the age-standardised point prevalence of Guillain–Barre syndrome from 1990 to 2019 for the 21 Global Burden of Disease regions, by sex. The error bars represent 95% uncertainty intervals for the percentage change in age-standardised prevalence per 100,000 population between 1990 and 2019. (Generated from data available from http://ghdx.healthdata.org/gbd-results-tool ).

Additional file 7: Figure S4.

The percentage change in the age-standardised years lived with disability (YLDs) rates of Guillain–Barre syndrome from 1990 to 2019 for the 21 Global Burden of Disease regions, by sex. The error bars represent 95% uncertainty intervals for the percentage change in age-standardised YLD rates per 100,000 population between 1990 and 2019. (Generated from data available from http://ghdx.healthdata.org/gbd-results-tool ).

Additional file 8: Figure S5.

Global number of years lived with disability (YLDs) cases and years lived with disability (YLDs) of Guillain–Barre syndrome per 100,000 population, by age and sex in 2019. The error bars represent 95% uncertainty intervals for total number of YLDs. Dotted and dashed lines indicate 95% uncertainty intervals for YLD (per 100,000). (Generated from data available from http://ghdx.healthdata.org/gbd-results-tool ).

Additional file 9: Figure S6.

Age-standardised prevalence rates of Guillain–Barre syndrome for 204 countries and territories, by Socio-demographic Index (SDI), in 2019; Expected values based on the Socio-demographic Index and disease rates in all locations are shown as the black line. Each point shows the observed age-standardised YLD rate for each country in 2019. (Generated from data available from http://ghdx.healthdata.org/gbd-results-tool ).

Additional file 10: Figure S7.

Age-standardised prevalence rates of Guillain–Barre syndrome, by Socio-demographic Index (SDI) quintiles, from 1990 to 2019; (Generated from data available from http://ghdx.healthdata.org/gbd-results-tool ).

Additional file 11: Figure S8.

Age-standardised years lived with disability (YLDs) rates of Guillain–Barre syndrome, by Socio-demographic Index (SDI) quintiles, from 1990 to 2019; (Generated from data available from http://ghdx.healthdata.org/gbd-results-tool ).

Additional file 12: Figure S9.

Global total number of cases and prevalence due to Guillain–Barre syndrome per 100,000 population attributable to each underlying cause, by age in 2019. (Generated from data available from http://ghdx.healthdata.org/gbd-results-tool ).

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ . The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article.

Bragazzi, N.L., Kolahi, AA., Nejadghaderi, S.A. et al. Global, regional, and national burden of Guillain–Barré syndrome and its underlying causes from 1990 to 2019. J Neuroinflammation 18 , 264 (2021). https://doi.org/10.1186/s12974-021-02319-4

Download citation

Received : 07 July 2021

Accepted : 07 November 2021

Published : 11 November 2021

DOI : https://doi.org/10.1186/s12974-021-02319-4

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• Global burden of disease

Journal of Neuroinflammation

ISSN: 1742-2094

• Submission enquiries: [email protected]

Nerve conduction studies in Guillain-Barré syndrome: Influence of timing and value of repeated measurements

Affiliations.

• 1 Department of Neurology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. Electronic address: [email protected].
• 2 Department of Neurology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
• PMID: 33352506
• DOI: 10.1016/j.jns.2020.117267

Objective: Nerve conduction studies (NCS) are essential to differentiate between demyelinating and axonal subtypes in Guillain-Barré syndrome (GBS). However, it is debated to which extent the delay of NCS after symptom onset and repeated measurements during the disease course influence the diagnostic accuracy.

Methods: We evaluated NCS in 93 patients with a classical GBS applying two widely used criteria (Hadden's and Rajabally's). The initial measurements after symptom onset were compared to follow-up studies where available (n = 43). We analyzed the influence of NCS timing after symptom onset and clinical severity on fulfilling the electrophysiological criteria for axonal or demyelinating subtypes and evaluated the impact of repeated measurements. We further evaluated the presence of reversible conduction failure.

Results: A higher GBS disability scale at nadir correlated with a successful subclassification whereas the delay of the first NCS after symptom onset did not influence the diagnostic yield (75% for Hadden's and 68% for Rajabally's criteria for the first assessment). A second measurement allowed the additional successful classification in 19% and 14% of patients, respectively. On the other hand, a repeated measurement in patients with an initial successful classification resulted in a different subtype in 5% and 7%, respectively. Reversible conduction failure was found in 7% of patients.

Conclusion: Clinical severity but not timing of NCS influenced the fulfilment of electrophysiological criteria for either the axonal or demyelinating subtype. Repeated electrophysiological measurements led to a further specification or a change in subtype classification in a relevant proportion of patients.

Keywords: Criteria; Guillain-Barré syndrome; Nerve conduction study; Subtype.

Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

• Disease Progression
• Follow-Up Studies
• Guillain-Barre Syndrome* / diagnosis
• Neural Conduction*
• Neurologic Examination

Guillain-Barré Syndrome

What is guillain-barré syndrome.

Guillain-Barré syndrome (GBS) (pronounced Ghee-yan Bah-ray) is a rare neurological disorder in which a person’s immune system mistakenly attacks part of their peripheral nervous system—the network of nerves that carries signals from the brain and spinal cord to the rest of the body.

GBS begins suddenly and can increase in intensity over a period of hours, days, or weeks until certain muscles cannot be used at all. Some cases of GBS are very mild and only marked by brief weakness. Others cause nearly devastating paralysis, leaving the person unable to breathe on their own. In these cases, the disorder is life-threatening—potentially interfering with breathing, blood pressure, or heart rate. Fortunately, most people eventually recover from even the most severe cases of GBS. After recovery, people may continue to have some weakness.

Symptoms of Guillain-Barré syndrome

• Weakness : The weakness seen in GBS usually comes on quickly and worsens over hours or days. Often, feet are affected first, and weakness may move up the body to eventually impact the legs, arms, face, and breathing muscles. The person may first notice unexpected difficulty climbing stairs or walking. Less commonly, symptoms start in the face and move down to the legs and feet. Most people reach the greatest stage of weakness within the first two weeks after symptoms appear; by the third week 90% of affected people are at their weakest.
• Sensation changes : In GBS, the brain may receive abnormal sensory signals from the rest of the body due to the nerve damage associated with the condition. This results in unexplained, spontaneous sensations, called paresthesias, that the person may feel as tingling, a sense of insects crawling under the skin (called formications), and pain. Some people with GBS feel a deep muscular pain in the back and/or legs. Unexplained sensations often happen first, such as tingling in the feet or hands, or even pain (especially in children), often starting in the legs or back. Children will also begin to have difficulty walking and may refuse to walk. These sensations tend to disappear before the major, longer-term symptoms appear. 

Other symptoms of Guillain-Barré syndrome may include:

• Difficulty with eye muscles and vision
• Difficulty swallowing, speaking, or chewing
• Pricking or pins and needles in the hands and feet
• Pain that can be severe, particularly at night
• Coordination problems and unsteadiness
• Abnormal heartbeat heartrate, or blood pressure
• Problems with digestion and/or bladder control

Who is more likely to get Guillain-Barré syndrome?

GBS can affect anyone of any gender or age, but most often affects adults and people older than 50.  GBS is not contagious or inherited, and the exact cause is unknown.

Since the body's own immune system does the damage, GBS is called an autoimmune disease (“auto” meaning “self”). Normally the immune system uses antibodies (molecules produced in an immune response) and special white blood cells to protect us by attacking infecting bacteria and viruses. In GBS, however, the immune system mistakenly attacks the healthy nerves. This attack may start as a fight against an infection. One possible reason for this is that some chemicals seen on bacteria and viruses resemble those on nerve cells. The immune system may not be able to distinguish bacteria and viruses from healthy nerve cells which also become targets of attack. 

The body’s nerves have a central conducting core called the axon that carries an electric signal. The axon is surrounded by an insulating layer (or sheath) called myelin. The myelin sheath surrounding the axon speeds up the transmission of nerve signals and allows the transmission of signals over long distances. In most cases of GBS, the immune system damages the myelin sheath; it also may damage the axons themselves. As a result, the nerves cannot transmit signals efficiently and the muscles begin to lose their ability to respond to the brain's commands, which causes weakness.

GBS usually starts a few days or weeks following a respiratory or gastrointestinal bacterial or viral infection. One of the most common risk factors for GBS is infection with the bacteria Campylobacter jejuni , which causes gastroenteritis (including nausea, vomiting, and diarrhea). Sometimes, surgery will trigger the syndrome. In very rare cases certain vaccinations may increase the risk of GBS. Some countries worldwide reported an increased incidence of GBS following infection with the COVID, Zika, cytomegalovirus, or Epstein-Barr viruses.

How is Guillain-Barré syndrome diagnosed and treated?

Diagnosing gbs.

Cases of GBS begin differently for different people, and there are several disorders with similar symptoms. Therefore, it may be difficult to diagnose GBS in its earliest stages. Doctors may perform the following:

• History and physical exam : A doctor will perform a physical exam and review the person’s medical history. They will assess how the person’s muscles and nerves are working. The doctor will note whether symptoms appear on both sides of the body (which is typical in GBS) and how fast the symptoms appeared. This is helpful because in other disorders, muscle weakness may progress over months rather than days or weeks. They will also check the reflexes, as some reflexes are lost in people with GBS.
• Nerve conduction velocity test (NCV) : This test measures the nerve's ability to send a signal. In GBS, the signals traveling along the damaged nerves are slowed because of damage to the myelin sheath.
• Cerebrospinal fluid analysis : A doctor may also conduct an analysis of the cerebrospinal fluid that bathes the spinal cord. This fluid contains more protein and fewer immune cells in people with GBS.
• Imaging : In some cases, an MRI (magnetic resonance imaging) of the spinal cord or even brain may help find any other potential causes of muscle weakness.

Treating GBS

Currently, there is no cure for GBS. However, some therapies can reduce its severity and shorten recovery time. There are also several ways to treat the complications of the disease.

People with GBS are usually admitted to the hospital and treated in the intensive care unit due to possible complications of muscle weakness. At the hospital, people with GBS are closely monitored to track the progression of their muscle weakness, breathing, and heart rate. If an intervention is needed, it can be quickly provided by the hospital staff.

Acute care for Guillain-Barré syndrome

Two treatments are commonly used to interrupt immune-related nerve damage. Both are equally effective if started within two weeks of GBS symptoms.

• Plasma exchange (PE) , also called plasmapheresis, involves removing some blood through a catheter. Plasma (the liquid part of the blood) is separated from the blood cells. These cells, along with replacement fluid, are returned to the body. PE may work by removing the bad antibodies in the plasma that have been damaging the nerves.
• Intravenous immunoglobulin therapy (IVIg) involves injections of immunoglobulins—proteins that your immune system naturally makes to attack infecting organisms. The immunoglobulins are developed from a pool of thousands of healthy donors. IVIg can lessen the immune attack on the nervous system and shorten recovery time. Researchers believe this treatment also reduces the effectiveness of antibodies that attack the nerves by both “diluting” them with non-specific antibodies and reducing the harmful antibodies.

Anti-inflammatory steroid hormones called corticosteroids have also been tried to reduce the severity of GBS, but clinical trials have showed this treatment is not effective.

Supportive care is very important to address the many complications of paralysis as the body recovers, and damaged nerves begin to heal. Since respiratory failure can occur in GBS, a person’s breathing should be closely monitored. Sometimes a mechanical ventilator is used to help support or control breathing. The autonomic nervous system (that regulates the functions of internal organs and some of the muscles in your body) can also be disturbed, causing changes in heart rate, blood pressure, digestion, or sweating, so the person should be put on a heart monitor or other equipment that measures and tracks body function. If the person has problems swallowing, they may also need special care to prevent choking, which can cause pneumonia.

Rehabilitative care

As people with GBS begin to improve, they may be transferred from the acute care unit at a hospital to a rehabilitation setting where they can regain strength, receive physical rehabilitation and other therapy to resume activities of daily living. 

Because GBS can affect several parts of the body, different methods and approaches may be needed to prevent or treat complications. For example, a physical therapist can manually move and position the person’s limbs to help keep the muscles flexible and prevent muscle shortening. Muscle strength may not return in the same way; muscles that get stronger faster may take over a function that weaker muscles normally perform—in a process called substitution. A physical therapist can select specific exercises to improve the strength of weaker muscles so their original function can be regained.

Occupational and vocational therapy helps people learn new ways to handle everyday functions that may be affected, as well as work demands and the need for assistive devices and other adaptive equipment and technology.

Long-term outlook for people with GBS

GBS can be a devastating disorder because of its sudden and rapid, unexpected onset of weakness—and often paralysis. Fortunately, most people with GBS have a full recovery. With careful intensive care and successful treatment of infection, autonomic dysfunction, and other medical complications, even people who have respiratory failure usually survive.

Recovery can be slow–anywhere from a few weeks to a few years. Some people do not recover completely and experience long-term weakness, numbness, fatigue, or pain. People recovering from GBS may face physical challenges and emotionally painful periods. It can be extremely difficult to adjust to sudden paralysis and dependence on others for help with routine daily activities. Some people with GBS need mental health counseling to help them adapt. Support groups can often ease emotional strain and provide valuable information.

What are the latest updates on Guillain-Barré syndrome?

NINDS, a part of the National Institutes of Health (NIH), is the nation's leading federal funder of research on neurological disorders. NINDS, the National Institute of Allergy and Infectious Diseases (NIAID), and several other components of NIH conduct research on disorders including GBS and fund research at major institutions and universities. Neuroscientists, immunologists, virologists, and pharmacologists are working collaboratively to learn how to prevent GBS and to make new and better therapies.

Scientists are looking at how the immune system works to find which cells are responsible for beginning and carrying out the attack on the nervous system. The fact that GBS often begins after a viral or bacterial infection suggests that certain features of some viruses and bacteria may activate the immune system inappropriately. Investigators are searching for what those triggers may be. Certain proteins or peptides in viruses and bacteria may appear similar to the immune system as those found in myelin, and the production of antibodies to neutralize the invading viruses or bacteria could trigger the attack on the myelin sheath. Researchers are studying a treatment to stop the disruption of myelin junctions (gaps) to prevent myelin from being removed (demyelination) when the immune system damages the myelin sheath.

Some studies show that normal variations in certain genes could increase risk of developing GBS; however, more research is needed to identify and confirm associated genes. Since many of the genes that may increase the risk of GBS are involved in the immune system, their roles in fighting infection might contribute to the development of the condition.           

NIH-funded researchers make use of a mouse model with an altered autoimmune regulator gene that generates autoimmunity against the peripheral nervous system (PNS). Using this model, scientists hope to identify which PNS proteins are at greatest risk of autoimmune attack and which parts of the immune system contribute to the autoimmune response against the PNS. A greater understanding of how the immune system damages the PNS could lead to better treatments for autoimmune disorders such as GBS.    

Other NINDS-funded researchers are investigating the mechanisms by which IVIg treatment lessens the symptoms of GBS. By understanding these mechanisms, it may be possible to develop more effective treatments. For example, even with IVIg treatment, some people with GBS are left permanently disabled. Antibodies from the immune system directed against axonal or myelin antigens (substances that trigger an immune system reaction) play an important role in inflammatory responses and the eventual damage to the nerve fibers. Researchers are testing a new treatment that can reduce macrophage inflammation in the nerves of animal models .  

For research articles and summaries on GBS, search  PubMed , which contains citations from medical journals and other sites.

How can I or my loved one help improve care for people with Guillain-Barré syndrome?

Consider participating in a clinical trial so clinicians and scientists can learn more about Guillain-Barré syndrome. Clinical research uses study participants to help researchers learn more about a disorder and perhaps find better ways to safely detect, treat, or prevent disease.

All types of participants are needed— those who are healthy or may have an illness or disease— of all different ages, sexes, races, and ethnicities to ensure that study results apply to as many people as possible, and that treatments will be safe and effective for everyone who will use them.

For information about participating in clinical research visit  NIH Clinical Research Trials and You . Learn about clinical trials currently looking for people with GBS at  Clinicaltrials.gov , a database of past and current clinical trials.

Where can I find more information about Guillain-Barré syndrome?

The following resources may provide information about Guillain-Barré syndrome :

GBS/CIDP Foundation International Phone: 610-667-0131 or 866-224-3301

MedlinePlus

Learn about related topics

• Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)  

• Introduction
• Conclusions
• Article Information

A, Bars represent the number of confirmed cases of GBS after Ad.26.COV2.S vaccination (N = 11). The x-axis denotes the numbers of days between Ad.26.COV2.S vaccination and GBS symptom onset. The 84-day follow-up period has elapsed for all Ad.26.COV2.S vaccinations. A statistically significant cluster was identified from days 1 to 14 after Ad.26.COV2.S vaccination using scan statistics ( P  = .003). 16

B, Bars represent the number of confirmed cases of GBS after mRNA vaccination (N = 36). The x-axis denotes the numbers of days between most recent mRNA vaccination and GBS symptom onset. The 84-day follow-up period has elapsed for all mRNA vaccinations.

See More About

Sign up for emails based on your interests, select your interests.

Customize your JAMA Network experience by selecting one or more topics from the list below.

• Academic Medicine
• Acid Base, Electrolytes, Fluids
• Allergy and Clinical Immunology
• American Indian or Alaska Natives
• Anesthesiology
• Anticoagulation
• Art and Images in Psychiatry
• Artificial Intelligence
• Assisted Reproduction
• Bleeding and Transfusion
• Caring for the Critically Ill Patient
• Challenges in Clinical Electrocardiography
• Climate and Health
• Climate Change
• Clinical Challenge
• Clinical Decision Support
• Clinical Implications of Basic Neuroscience
• Clinical Pharmacy and Pharmacology
• Complementary and Alternative Medicine
• Consensus Statements
• Coronavirus (COVID-19)
• Critical Care Medicine
• Cultural Competency
• Dental Medicine
• Dermatology
• Diabetes and Endocrinology
• Diagnostic Test Interpretation
• Drug Development
• Electronic Health Records
• Emergency Medicine
• End of Life, Hospice, Palliative Care
• Environmental Health
• Equity, Diversity, and Inclusion
• Facial Plastic Surgery
• Gastroenterology and Hepatology
• Genetics and Genomics
• Genomics and Precision Health
• Global Health
• Guide to Statistics and Methods
• Hair Disorders
• Health Care Delivery Models
• Health Care Economics, Insurance, Payment
• Health Care Quality
• Health Care Reform
• Health Care Safety
• Health Care Workforce
• Health Disparities
• Health Inequities
• Health Policy
• Health Systems Science
• History of Medicine
• Hypertension
• Images in Neurology
• Implementation Science
• Infectious Diseases
• Innovations in Health Care Delivery
• JAMA Infographic
• Law and Medicine
• Leading Change
• Less is More
• LGBTQIA Medicine
• Lifestyle Behaviors
• Medical Coding
• Medical Devices and Equipment
• Medical Education
• Medical Education and Training
• Medical Journals and Publishing
• Mobile Health and Telemedicine
• Narrative Medicine
• Neuroscience and Psychiatry
• Notable Notes
• Nutrition, Obesity, Exercise
• Obstetrics and Gynecology
• Occupational Health
• Ophthalmology
• Orthopedics
• Otolaryngology
• Pain Medicine
• Palliative Care
• Pathology and Laboratory Medicine
• Patient Care
• Patient Information
• Performance Improvement
• Performance Measures
• Perioperative Care and Consultation
• Pharmacoeconomics
• Pharmacoepidemiology
• Pharmacogenetics
• Pharmacy and Clinical Pharmacology
• Physical Medicine and Rehabilitation
• Physical Therapy
• Physician Leadership
• Population Health
• Primary Care
• Professional Well-being
• Professionalism
• Psychiatry and Behavioral Health
• Public Health
• Pulmonary Medicine
• Regulatory Agencies
• Reproductive Health
• Research, Methods, Statistics
• Resuscitation
• Rheumatology
• Risk Management
• Scientific Discovery and the Future of Medicine
• Shared Decision Making and Communication
• Sleep Medicine
• Sports Medicine
• Stem Cell Transplantation
• Substance Use and Addiction Medicine
• Surgical Innovation
• Surgical Pearls
• Teachable Moment
• Technology and Finance
• The Art of JAMA
• The Arts and Medicine
• The Rational Clinical Examination
• Tobacco and e-Cigarettes
• Translational Medicine
• Trauma and Injury
• Treatment Adherence
• Ultrasonography
• Users' Guide to the Medical Literature
• Vaccination
• Venous Thromboembolism
• Veterans Health
• Women's Health
• Workflow and Process
• Wound Care, Infection, Healing

Get the latest research based on your areas of interest.

Others also liked.

• Download PDF
• X Facebook More LinkedIn
• CME & MOC

Hanson KE , Goddard K , Lewis N, et al. Incidence of Guillain-Barré Syndrome After COVID-19 Vaccination in the Vaccine Safety Datalink. JAMA Netw Open. 2022;5(4):e228879. doi:10.1001/jamanetworkopen.2022.8879

Manage citations:

© 2024

• Permissions

Incidence of Guillain-Barré Syndrome After COVID-19 Vaccination in the Vaccine Safety Datalink

• 1 Marshfield Clinic Research Institute, Marshfield, Wisconsin
• 2 Kaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California, Oakland, California
• 3 Immunization Safety Office, Centers for Disease Control and Prevention, Atlanta, Georgia
• 4 The Permanente Medical Group, Oakland, California
• 5 Kaiser Permanente Washington Health Research Institute, Seattle, Washington
• 6 Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California
• 7 Kaiser Permanente Colorado Institute for Health Research, Denver, Colorado
• 8 Ambulatory Care Services, Denver Health & Hospital Authority, Denver, Colorado
• 9 HealthPartners Institute, Minneapolis, Minnesota

Question   Are COVID-19 vaccines associated with Guillain-Barré syndrome (GBS)?

Findings   In this cohort study of surveillance data from the Vaccine Safety Datalink that included 15.1 million doses of COVID-19 vaccines, the unadjusted incidence rate of confirmed GBS in the 1 to 21 days after receiving the Ad.26.COV2.S (Janssen) vaccine was 32.4 per 100 000 person-years, which was significantly higher than the background rate of GBS. The unadjusted incidence rate of confirmed GBS in the 1 to 21 days after mRNA vaccines was 1.3 per 100 000 person-years, which did not differ from the background rate.

Meaning   These findings suggest an increased risk of GBS after Ad.26.COV2.S vaccination.

Importance   Postauthorization monitoring of vaccines in a large population may detect rare adverse events not identified in clinical trials such as Guillain-Barré syndrome (GBS), which has a background rate of 1 to 2 per 100 000 person-years.

Objective   To describe cases and incidence of GBS following COVID-19 vaccination and assess the risk of GBS after vaccination for Ad.26.COV2.S (Janssen) and mRNA vaccines.

Design, Setting, and Participants   This cohort study used surveillance data from the Vaccine Safety Datalink at 8 participating integrated health care systems in the United States. There were 10 158 003 participants aged at least 12 years. Data analysis was performed from November 2021 to February 2022.

Exposures   Ad.26.COV2.S, BNT162b2 (Pfizer-BioNTech), or mRNA-1273 (Moderna) COVID-19 vaccine, including mRNA vaccine doses 1 and 2, December 13, 2020, to November 13, 2021.

Main Outcomes and Measures   GBS with symptom onset in the 1 to 84 days after vaccination, confirmed by medical record review and adjudication. Descriptive characteristics of confirmed cases, GBS incidence rates during postvaccination risk intervals after each type of vaccine compared with the background rate, rate ratios (RRs) comparing GBS incidence in the 1 to 21 vs 22 to 42 days postvaccination, and RRs directly comparing risk of GBS after Ad.26.COV2.S vs mRNA vaccination, using Poisson regression adjusted for age, sex, race and ethnicity, site, and calendar day.

Results   From December 13, 2020, through November 13, 2021, 15 120 073 doses of COVID-19 vaccines were administered to 7 894 989 individuals (mean [SE] age, 46.5 [0.02] years; 8 138 318 doses received [53.8%] by female individuals; 3 671 199 doses received [24.3%] by Hispanic or Latino individuals, 2 215 064 doses received [14.7%] by Asian individuals, 6 266 424 doses received [41.4%] by White individuals), including 483 053 Ad.26.COV2.S doses, 8 806 595 BNT162b2 doses, and 5 830 425 mRNA-1273 doses. Eleven cases of GBS after Ad.26.COV2.S were confirmed. The unadjusted incidence rate of GBS per 100 000 person-years in the 1 to 21 days after Ad.26.COV2.S was 32.4 (95% CI, 14.8-61.5), significantly higher than the background rate, and the adjusted RR in the 1 to 21 vs 22 to 42 days following Ad.26.COV2.S was 6.03 (95% CI, 0.79-147.79). Thirty-six cases of GBS after mRNA vaccines were confirmed. The unadjusted incidence rate per 100 000 person-years in the 1 to 21 days after mRNA vaccines was 1.3 (95% CI, 0.7-2.4) and the adjusted RR in the 1 to 21 vs 22 to 42 days following mRNA vaccines was 0.56 (95% CI, 0.21-1.48). In a head-to-head comparison of Ad.26.COV2.S vs mRNA vaccines, the adjusted RR was 20.56 (95% CI, 6.94-64.66).

Conclusions and Relevance   In this cohort study of COVID-19 vaccines, the incidence of GBS was elevated after receiving the Ad.26.COV2.S vaccine. Surveillance is ongoing.

Three vaccine products are available in the US to prevent COVID-19, including BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and Ad.26.COV2.S (Janssen). 1 - 3 BNT162b2 and mRNA-1273 are both messenger RNA (mRNA) vaccines and administered as 2-dose primary series, whereas Ad.26.COV2.S is a replication-incompetent adenoviral vector vaccine and administered as a single dose primary series. mRNA vaccines were authorized for use in adults in December 2020, and use of BNT162b2 was expanded to adolescents in May 2021. Ad.26.COV2.S was authorized for use in adults on February 27, 2021; however, use of Ad.26.COV2.S was temporarily paused in mid-April 2021 due to concerns about a rare condition called thrombosis with thrombocytopenia syndrome (TTS) that was reported after Ad.26.COV2.S vaccination. 4 In July 2021, data from the Vaccine Adverse Event Reporting System (VAERS) indicated that the reporting rate of Guillain-Barré syndrome (GBS), a rare neurological disorder, was higher after Ad.26.COV2.S than after mRNA vaccines. 5 The Food and Drug Administration subsequently added a warning about GBS to the Ad.26.COV2.S vaccine fact sheet. On December 16, 2021, the Advisory Committee on Immunization Practices made a preferential recommendation for use of mRNA vaccines over Ad.26.COV2.S as the benefit-risk balance was determined to be more favorable for mRNA vaccines than Ad.26.COV2.S, in part due to safety concerns regarding GBS and TTS after Ad.26.COV2.S. 6

Postauthorization monitoring of vaccines in a large population can detect rare adverse events not identified in clinical trials. GBS is being monitored in the Vaccine Safety Datalink as part of ongoing rapid and prospective COVID-19 vaccine safety surveillance efforts. 7 Our objectives for this study were to (1) describe GBS cases and incidence following COVID-19 vaccinations from December 13, 2020, through November 13, 2021, and (2) assess the risk of GBS after vaccination for Ad.26.COV2.S and mRNA vaccines.

The Vaccine Safety Datalink is a collaboration between 9 US integrated health care systems and the Centers for Disease Control and Prevention (CDC). 8 , 9 Eight data-contributing organizations (Kaiser Permanente: Colorado, Northern California, Northwest, Southern California, and Washington; Marshfield Clinic; HealthPartners; and Denver Health) have access to comprehensive medical records, including vaccinations, for 10 158 003 people aged at least 12 years as of November 10, 2021.

This activity was approved by the institutional review boards with a waiver of informed consent at Kaiser Permanente: Colorado, Northern California, Northwest, Southern California, and Washington; Marshfield Clinic; HealthPartners; and Denver Health. Per 45 CFR part 46.111(f)(3), this study was granted a waiver of informed consent because it posed minimal risk to participants and could not feasibly be conducted without the waiver. The CDC determined that this activity was public health surveillance (45 CFR part 46.102[l][2]) and thus did not require institutional review board review. This report followed the Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) reporting guideline. 10

Since December 2020, the Vaccine Safety Datalink has been conducting safety surveillance of COVID-19 vaccines, monitoring GBS and 22 other prespecified, serious outcomes after COVID-19 vaccines on a weekly basis. Methods are described in the study protocol and in a prior publication that includes interim results for mRNA vaccines. 7 , 11 Weekly analyses compared outcome incidence observed during a risk interval after vaccination (eg, 1-21 days after Ad.26.COV2.S) with outcome incidence expected. Analyses were conducted separately by vaccine type. The expected was derived from 1 of 2 types of comparators: (1) similar vaccinated persons who were concurrently (on the same calendar day) in a postvaccination comparison interval following the same vaccine type (eg, 22-42 days after Ad.26.COV2.S) (vaccinated concurrent comparators), and (2) similar persons who were concurrently (on the same calendar day) unvaccinated (ie, had not received any doses of COVID-19 vaccine) (unvaccinated concurrent comparators), where similar means comparators were of the same age group, sex, race or ethnicity, and site as the vaccine recipient. Race and ethnicity data were captured in Vaccine Safety Datalink files in fixed categories based on self-reported data from the participating sites. Race and ethnicity data were used to adjust for confounding that may have arisen if the factor was associated with vaccination dates and outcome events. By protocol, vaccinated concurrent comparators were considered primary and unvaccinated concurrent comparators were considered supplemental owing to concerns about possible bias from unmeasured differences between vaccinated and unvaccinated individuals. This surveillance approach used 2 postvaccination risk intervals, 1 to 21 days and 1 to 42 days, with corresponding postvaccination comparison intervals for vaccinated concurrent comparator analyses, 22 to 42 days and 43 to 84 days, respectively. The 1 to 21–day risk interval allowed for timelier analyses and avoids bias introduced from the short interval between doses for mRNA vaccines. However, a 1 to 42–day risk interval was also used, because this interval is often used in vaccine safety studies of GBS and other outcomes. 12 Individuals who received 2 doses of an mRNA vaccine contributed to analyses of mRNA vaccines when they were 1 to 21 (or 1 to 42) days after dose 1 and again when they were 1 to 21 (or 1 to 42) days after dose 2. However, receipt of dose 2 resulted in censoring of follow-up time after dose 1, therefore most comparison time in the vaccinated concurrent comparator analyses was after dose 2.

We reported on data through November 13, 2021, including descriptive characteristics of COVID-19 vaccine recipients and GBS cases, weekly analyses of GBS with vaccinated and unvaccinated concurrent comparators (previously described) for Ad.26.COV2.S and mRNA vaccines, and additional GBS analyses including comparisons of the incidence of GBS postvaccination by vaccine type to the incidence expected from prior studies, evaluation of the temporal clustering of GBS cases following Ad.26.COV2.S, and head-to-head comparisons of GBS incidence after Ad.26.COV2.S with GBS incidence after mRNA vaccination.

Potential cases of GBS were identified among Vaccine Safety Datalink members aged at least 12 years using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) code G61.0 in the emergency department or inpatient setting, specifically when G61.0 first appeared in an individual’s record in the 1 to 84 days after dose 1 or dose 2 of an mRNA vaccine or after dose 1 of Ad.26.COV2.S. Because disease onset may begin before a diagnosis is recorded in the medical record, potential cases with the ICD-10 code in the 85 to 98 days postvaccination were also reviewed. After review, all cases underwent adjudication according to the Brighton Collaboration criteria. 13 Briefly, GBS cases meeting Brighton level 1 had the highest level of diagnostic certainty, whereas level 4 included cases of suspected GBS (ie, insufficient information was available in the medical record to meet Brighton level 1-3). In this analysis, we considered Brighton level 1 to level 4 cases as confirmed and sensitivity analyses were conducted excluding level 4 cases. Cases of GBS among unvaccinated concurrent comparators were identified by applying the same algorithm to unvaccinated members of the Vaccine Safety Datalink population during the period of interest. Unvaccinated comparators did not undergo medical record review and adjudication.

As previously described, 7 primary weekly monitoring of GBS after each type of COVID-19 vaccine used conditional Poisson regression to compare individuals during a postvaccination risk interval with similar individuals who had been vaccinated earlier and were concurrently in a comparison interval. These analyses estimated rate ratios (ie, ratios of incidence rates in a risk interval divided by incidence rates in a comparison interval) that were adjusted for 5-year age group, sex, race and ethnicity, site, and calendar day by conditioning the Poisson regression on strata (risk sets) defined by these factors. Similarly, conditional Poisson regression was used in supplementary weekly analyses to compare individuals in a postvaccination risk interval with similar individuals who were concurrently unvaccinated. One-sided sequential testing was conducted weekly for vaccinated concurrent comparator analyses, with a signaling threshold of P  < .0048 (prespecified to keep the overall chance of making a type I error below .05 during 2 years of weekly analyses).

Although our primary weekly analyses of GBS have not met the criterion for a safety signal, concerns about GBS after Ad.26.COV2.S arose from supplementary analyses with unvaccinated comparators and from reports to VAERS. To further investigate we conducted additional analyses. We computed unadjusted incidence rates and 95% CIs of confirmed GBS in the 1 to 21 days and 1 to 42 days following COVID-19 vaccination per 100 000 person-years (PY) by vaccine type and used exact Poisson regression to compare observed incidence rates to the historical background rate of GBS (2 per 100 000 PY). 14 , 15 We also examined the temporal clustering of the GBS cases within 56 days of Ad.26.COV2.S by day of symptom onset, using a scan statistic. 16 Lastly, we conducted head-to-head comparisons of the 21-day and 42-day risk intervals after Ad.26.COV2.S vs the 21-day and 42-day risk intervals after mRNA vaccination, using conditional Poisson regression to estimate rate ratios (ie, the ratio of GBS incidence after Ad.26.COV2.S divided by GBS incidence after mRNA vaccination), adjusted for age group, sex, race and ethnicity, site, and calendar day as described above. All analyses of mRNA vaccines combined both products (BNT162b2 and mRNA-1273) and primary series doses (1 and 2) to increase statistical power. Analyses were 2-sided with a .05 level of significance unless otherwise specified and were conducted using SAS version 9.4 (SAS Institute) from November 2021 to February 2022.

From December 13, 2020, through November 13, 2021, 15 120 073 COVID-19 vaccines were administered to 7 894 989 individuals who were at least 12 years of age (mean age [SE] age, 46.5 [0.02] years; 8 138 318 doses received [53.8%] by female individuals; 3 671 199 doses received [24.3%] by Hispanic or Latino individuals, 2 215 064 doses received [14.7%] by Asian individuals, 6 266 424 doses received [41.4%] by White individuals), including 483 053 first doses of Ad.26.COV2.S, 8 806 595 first and second doses of BNT162b2, and 5 830 425 first and second doses of mRNA-1273; mRNA vaccines accounted for 96.8% of all doses (14 637 020 of 15 120 073). Compared with mRNA vaccine recipients, a higher proportion of Ad.26.COV2.S vaccine recipients were male (6 721 529 [45.9%] vs 260 226 [53.9%]) and a smaller proportion were at least 65 years of age (3 139 195 [21.5%] vs 55 901 [11.6%]) ( Table 1 ). Ad.26.COV2.S vaccination was concentrated during the 7-week period that corresponded with the period between initial authorization and the pause in use due to concerns about TTS, with 63.5% of Ad.26.COV2.S doses (306 590 of 483 053) administered from February 28, 2021, through April 17, 2021.

During the 1 to 84 days after individuals received Ad.26.COV2.S, 22 potential cases of GBS were identified: all were reviewed and adjudicated, and 11 (50%) were confirmed. Symptom onset ranged from 1 to 77 days after Ad.26.COV2.S; 9 cases (82%) had symptom onset in the 1 to 21 days postvaccination, 1 (9%) had symptom onset in the 22 to 42 days postvaccination, and 1 (9%) had symptom onset in the 43 to 84 days postvaccination ( Figure A). Scan statistics identified days 1 to 14 after vaccination as a statistically significant cluster ( P  = .003). Ten patients were hospitalized (91%) and all were treated with intravenous immune globulin. Patients with confirmed GBS after Ad.26.COV2.S had a mean (range) age of 50 (32-63) years, 9 (82%) were male, 10 (91%) were non-Hispanic White, and 10 (91%) had facial weakness or paralysis in addition to bilateral weakness or paralysis of the limbs ( Table 2 ).

The unadjusted incidence rate of confirmed cases of GBS per 100 000 PY was 32.4 (95% CI, 14.8-61.5) during the 1 to 21 days after Ad.26.COV2.S and 18.0 (95% CI, 8.6-33.1) during the 1 to 42 days after Ad.26.COV2.S; both estimates were significantly higher than the background rate of GBS ( P  < .001) ( Table 3 ). When excluding Brighton level 4 cases, incidence rates were lower (28.8 [95% CI, 12.4-56.8] and 16.2 [95% CI, 7.4-30.8] per 100 000 PY, respectively) but still significantly higher than the background rate ( P  < .001).

In weekly surveillance using vaccinated concurrent comparators, as of November 16, 2021, the RR of confirmed GBS, adjusted for age, sex, race and ethnicity, site, and calendar day in the 1 to 21 vs 22 to 42 days following Ad.26.COV2.S was 6.03 (95% CI, 0.79-147.79; 2-sided P  = .09; 1-sided P  = .08). The adjusted RR of confirmed GBS in the 1 to 42 vs 43 to 84 days following Ad.26.COV2.S was 8.64 (95% CI, 1.18-207.32; 2-sided P  = .03; 1-sided P  = .03). Neither result met the prespecified signaling criteria of a 1-sided P  < .0048. In supplemental weekly analyses with unvaccinated concurrent comparators, the adjusted RR of GBS was 10.57 (95% CI, 5.15-20.16; P  < .001) in the 1 to 21 days following Ad.26.COV2.S and 10.05 (95% CI, 5.75-16.96; P  < .001) in the 1 to 42 days following Ad.26.COV2.S.

During the 1 to 84 days after first and second doses of mRNA vaccines, 78 potential cases of GBS were identified: all were reviewed and adjudicated, and 36 (46%) were confirmed, including 23 after BNT162b2 and 13 after mRNA-1273. Patients with confirmed GBS after mRNA vaccines had a mean (range) age of 53 (14-92) years ( Table 2 ) and symptom onset ranged from 0 to 84 days after vaccination ( Figure B). Eleven cases (31%) had symptom onset in the 1 to 21 days postvaccination, 15 cases (42%) had symptom onset in the 22 to 42 days postvaccination, and 9 cases (25%) had symptom onset in the 43 to 84 days postvaccination. One case had symptom onset on the same day as mRNA vaccination (day 0) and was excluded from analyses.

The unadjusted incidence rate of confirmed cases of GBS per 100 000 PY in the 21 days after mRNA vaccines was 1.3 (95% CI, 0.7-2.4) and did not differ from the background rate of GBS ( P  = .20) ( Table 3 ). Results were similar when excluding Brighton level 4 cases and when using a 42-day risk window, with incidence rates ranging from 1.1 to 2.0 cases of GBS per 100 000 PY.

In weekly surveillance conducted on November 16, 2021, the adjusted RR of confirmed GBS in the 1 to 21 vs 22 to 42 days following mRNA vaccination was 0.56 (95% CI, 0.21-1.48; 2-sided P  = .25, 1-sided P  = .93). In supplemental weekly analyses with unvaccinated concurrent comparators, the adjusted RR of GBS was 0.83 (95% CI, 0.50-1.33; P  = .45) in the 1 to 21 days following mRNA vaccination and 0.85 (95% CI, 0.57-1.27; P  = .44) in the 1 to 42 days following mRNA vaccination.

During the 1 to 21 days after vaccination, the adjusted RR of confirmed GBS after Ad.26.COV2.S vs mRNA vaccination was 20.56 (95% CI, 6.94-64.66; P  < .001), with 15.5 excess GBS cases in the risk interval per million Ad.26.COV2.S vaccine recipients ( Table 4 ). When using a 1 to 42-day risk interval, the adjusted RR was lower, 11.46 (95% CI, 4.83-26.16; 2-sided P  < .001), otherwise results were similar.

In this cohort study’s interim analyses conducted in a large population-based surveillance system that included medical record review of all potential GBS cases after COVID-19 vaccination through November 13, 2021, findings were consistent with an increased risk of GBS after Ad.26.COV2.S. The incidence of GBS in the 21 days after Ad.26.COV2.S was 32.4 per 100 000 person-years, which was substantially greater than the expected background rate of 1 to 2 per 100 000 person-years. 14 , 15 GBS incidence in the 21 days after mRNA vaccination was 1.3 per 100 000 person-years, similar to the overall expected background rate. In an adjusted head-to-head comparison, GBS incidence during the 21 days after Ad.26.COV2.S was 20.6 times higher than the GBS incidence during the 21 days after mRNA vaccination, amounting to 15.5 excess cases per million Ad.26.COV2.S vaccine recipients. The majority of cases of GBS after Ad.26.COV2.S occurred during the 1 to 21-day risk interval, with the period of most increased risk in the 1 to 14 days after Ad.26.COV2.S.

None of the primary analyses conducted in routine weekly safety surveillance of GBS after Ad.26.COV2.S met the criterion for a safety signal. However, these analyses had low power not only because the uptake of Ad.26.COV2.S was low, but also because Ad.26.COV2.S uptake was concentrated in a brief calendar period, meaning that relatively few vaccinated concurrent comparators were available while vaccine recipients were in their risk interval. The rate ratio estimate in the primary analyses of the 21-day risk interval after Ad.26.COV2.S had a very wide confidence interval extending from less than 1.0 to greater than 100; the CI was narrower for the corresponding supplemental analyses, ranging from 5 to 20. Because our primary analyses for GBS after Ad.26.COV2.S were less powerful than our supplementary analyses (as evidenced by wider CIs), we gave more consideration to supplemental analyses, consistent with the study protocol. Nevertheless, results of supplemental analyses should be interpreted with caution because of concerns about unmeasured differences between vaccinated and unvaccinated individuals, and because cases of GBS in unvaccinated comparators did not undergo medical record review and adjudication.

Our finding of an elevated risk of GBS after Ad.26.COV2.S was consistent with an observed-to-expected analysis in VAERS which found that the GBS reporting rate after Ad.26.COV2.S exceeded the background rate. 17 Our analyses also included GBS cases confirmed by medical record review and adjudication, and thus provide validation of the preliminary VAERS findings based on presumptive GBS.

Interestingly, nearly all patients with GBS after Ad.26.COV2.S identified in this surveillance had facial weakness or paralysis, in addition to weakness and decreased reflexes in the limbs. Reports describing cases of GBS following Ad.26.COV2.S and ChAdOx1 (AstraZeneca) COVID-19 vaccine, another adenoviral vector vaccine used outside of the US, have also noted a preponderance of cases with unilateral or bilateral facial weakness or plegia, 18 - 21 with some suggesting that the presentation of GBS after COVID-19 adenoviral vector vaccine may be novel. However, a study in the United Kingdom did not find a significant difference in presence of unilateral or bilateral facial weakness between those with GBS onset in the 42 days after COVID-19 vaccination (majority first doses of ChAdOx1) and those with GBS onset more than 42 days after COVID-19 vaccination or those with GBS onset during the same period that were not vaccinated. 22 More research is needed to determine if the presentation of GBS after adenoviral vector vaccine differs from GBS after other exposures such as Campylobacter jejuni , and to investigate the mechanism for how adenoviral vector vaccines may cause GBS.

In contrast to Ad.26.COV2.S, the unadjusted incidence rates of GBS in the 1 to 21 days and 1 to 42 days after mRNA vaccines were similar to the published background rate. 14 , 15 In weekly analyses, the incidence of GBS following mRNA vaccination was also not significantly higher in the 1 to 21 days postvaccination compared with 22 to 42 days postvaccination, a finding consistent with similar results reported through June 22, 2021, from this same surveillance. 7 These updated results provide further evidence that mRNA vaccines do not appear to be associated with GBS.

This study had several limitations. First, as mentioned previously, substantially fewer doses of Ad.26.COV2.S were administered relative to mRNA vaccines, resulting in reduced statistical power and wide confidence intervals for some analyses. Second, in this observational study recipients of Ad.26.COV2.S may have differed from recipients of mRNA vaccines in unknown ways that affect GBS risk but were not adjusted for in analyses. Third, the incidence rate of confirmed GBS during the COVID-19 pandemic has not been established, and may differ from prepandemic background rates. Fourth, we could not identify subgroups who may be at greatest risk for GBS after Ad.26.COV2.S given the small number of confirmed GBS cases identified in this surveillance. Fifth, this analysis only included GBS cases after primary COVID-19 vaccination and results may not be generalizable to additional or booster doses.

In this interim analysis of surveillance data of COVID-19 vaccines, findings were consistent with an elevated risk of GBS after primary Ad.26.COV2.S vaccination. No difference in GBS risk was found for mRNA vaccines. Surveillance is ongoing.

Accepted for Publication: March 8, 2022.

Published: April 26, 2022. doi:10.1001/jamanetworkopen.2022.8879

Open Access: This is an open access article distributed under the terms of the CC-BY License . © 2022 Hanson KE et al. JAMA Network Open .

Corresponding Author: Nicola P. Klein, MD, PhD, Kaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California, One Kaiser Plaza, 16th Flr, Oakland, CA 94612 ( [email protected] ).

Author Contributions : Ms Hanson had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Hanson, Goddard, Lewis, Fireman, Bakshi, Weintraub, Klein.

Acquisition, analysis, or interpretation of data: Hanson, Goddard, Lewis, Fireman, Myers, Bakshi, Weintraub, Donahue, Nelson, Xu, Glanz, Williams, Alpern.

Drafting of the manuscript: Hanson, Fireman, Alpern.

Critical revision of the manuscript for important intellectual content: Goddard, Lewis, Fireman, Myers, Bakshi, Weintraub, Donahue, Nelson, Xu, Glanz, Williams, Klein.

Statistical analysis: Hanson, Lewis, Fireman, Weintraub, Xu, Glanz.

Obtained funding: Hanson, Goddard, Donahue, Nelson, Klein.

Administrative, technical, or material support: Hanson, Goddard, Myers, Weintraub, Donahue, Nelson.

Supervision: Goddard, Weintraub, Xu, Klein.

Conflict of Interest Disclosures: Dr Donahue reported receiving grants from Janssen Vaccines & Prevention Funding for a study unrelated to COVID-19 vaccines outside the submitted work. Dr Nelson reported receiving grants from GlaxoSmithKline (2019-2020), nonfinancial support from ACIP/CDC as a member of COVID-19 Vaccine Safety Technical Subgroup, and grants from Moderna as a member of mRNA-1273 (COVID-19 vaccine candidate) External Safety Advisory Board for Moderna's COVID-19 vaccine program outside the submitted work. Dr Klein reported receiving grants from Pfizer research support for COVID vaccine clinical trial as well as other unrelated studies, grants from Merck, grants from GlaxoSmithKline, grants from Sanofi Pasteur, and grants from Protein Science (now Sanofi Pasteur) outside the submitted work. Dr Alpern reported receiving funding from Arnold Ventures for unrelated work. No other disclosures were reported.

Funding/Support: This study was supported by the Centers for Disease Control and Prevention (CDC), contract number 200-2012-53587-0014.

Role of the Funder/Sponsor: The study sponsor, CDC, participated as a co-investigator and contributed to protocol development; conduct of the study; interpretation of the data; review and revision of the manuscript; approval of the manuscript through official CDC scientific clearance processes; and the decision to submit the manuscript for publication. CDC authors must receive approval through the CDC scientific clearance process to submit an article for publication. Final decision to submit rests with the first author. The study sponsor does not have the right to direct the submission to a particular journal.

Disclaimer: The findings and conclusions in this paper are those of the authors and do not necessarily represent the official position of the CDC. Mention of a product or company name is for identification purposes only and does not constitute endorsement by the CDC.

Additional Contributions: We thank Ousseny Zerbo, PhD (Kaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California) for contributions to study design and concurrent comparator analyses. We thank Burney Kieke, MA (Marshfield Clinic Research Institute) for contributions to observed-to-expected analyses. We thank Malini DeSilva, MD (HealthPartners Institute), Elyse Kharbanda, MD, MPH (HealthPartners Institute), and Allison Naleway, PhD (Center for Health Research, Kaiser Permanente Northwest) for oversight of data collection and interpretation of data. We thank Rachael Burganowski, MS (Kaiser Permanente Washington Health Research Institute), Bradley Crane, MS (Center for Health Research, Kaiser Permanente Northwest), Sungching Glenn, MS (Research and Evaluation, Kaiser Permanente Southern California), Tat’Yana Kenigsberg, MPH (Immunization Safety Office, Centers for Disease Control and Prevention), Yingbo Lou, MS (Ambulatory Care Services, Denver Health), John Mayer, PhD (Marshfield Clinic Research Institute), Erica Scotty, MS (Marshfield Clinic Research Institute), Gabriela Vazquez Benitez, PhD (HealthPartners Institute), Arnold Yee, BS (Kaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California), and Jingyi Zhu, PhD (HealthPartners Institute), for their contributions to data collection and preparation. We thank Dawn Asamura, BS (Research and Evaluation, Kaiser Permanente Southern California), Radha Bathala, MS (Research and Evaluation, Kaiser Permanente Southern California), Nancy Canul-Jauriga (Research and Evaluation, Kaiser Permanente Southern California), Alexander Carruth (Research and Evaluation, Kaiser Permanente Southern California), Jennifer Covey, BS (Kaiser Permanente Washington Health Research Institute), Susie Flores, RN (Research and Evaluation, Kaiser Permanente Southern California), Joy Gelfond (Research and Evaluation, Kaiser Permanente Southern California), Stacy Harsh, BSN, RN (Center for Health Research, Kaiser Permanente Northwest), Linda Heeren, BS (Marshfield Clinic Research Institute), Sunhea Kim, MPH (Research and Evaluation, Kaiser Permanente Southern California), Kate Kurlandsky, BA (Center for Health Systems Research, Denver Health), Jose Pio, MD, MPH (Research and Evaluation, Kaiser Permanente Southern California), Pat Ross, BA (Kaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California), Marycania Saparudin, MPH (Research and Evaluation, Kaiser Permanente Southern California), Karen Schenk, BA (Research and Evaluation, Kaiser Permanente Southern California), Sarah Simmons, MPH (Research and Evaluation, Kaiser Permanente Southern California), Laura Sirikulvadhana, MPH (Research and Evaluation, Kaiser Permanente Southern California), and Melena Taylor, BA (Research and Evaluation, Kaiser Permanente Southern California), for their contributions to medical record review. We also thank Laurie Aukes, RN (Kaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California), Jonathan Block, MEd (Ambulatory Care Services, Denver Health), Cheryl Carlson, MPH (Research and Evaluation, Kaiser Permanente Southern California), Stephanie Irving, MHS (Center for Health Research, Kaiser Permanente Northwest), Mara Kalter, MA (Center for Health Research, Kaiser Permanente Northwest), Tia Kauffman, MPH (Center for Health Research, Kaiser Permanente Northwest), Erika Kiniry, MPH (Kaiser Permanente Washington Health Research Institute), Leslie Kuckler, MPH (HealthPartners Institute), Denison Ryan, MPH (Research and Evaluation, Kaiser Permanente Southern California), and Lina Sy, MPH (Research and Evaluation, Kaiser Permanente Southern California), for their contributions to overall project management. All non-CDC personnel received financial compensation through CDC Vaccine Safety Datalink grant funding for their work on this project. CDC personnel were not compensated for their role in the study.

• Register for email alerts with links to free full-text articles
• Access PDFs of free articles
• Manage your interests
• Save searches and receive search alerts

Learn how UpToDate can help you.

Select the option that best describes you

• Medical Professional
• Resident, Fellow, or Student
• Hospital or Institution
• Group Practice
• Patient or Caregiver
• Find in topic

RELATED TOPICS

INTRODUCTION

The pathogenesis, clinical features, and diagnosis of GBS will be discussed here. Other aspects of GBS are presented separately.

● (See "Guillain-Barré syndrome in adults: Treatment and prognosis" .)

● (See "Guillain-Barré syndrome in children: Epidemiology, clinical features, and diagnosis" .)

● (See "Guillain-Barré syndrome in children: Treatment and prognosis" .)

Log in using your username and password

• Search More Search for this keyword Advanced search
• Latest content
• Current issue
• BMJ Journals More You are viewing from: Google Indexer

You are here

• Volume 86, Issue 1
• Electrophysiological diagnosis of Guillain–Barré syndrome subtype: could a single study suffice?
• Article Text
• Article info
• Citation Tools
• Rapid Responses
• Article metrics

• Yusuf A Rajabally 1 ,
• Marie-Christine Durand 2 ,
• James Mitchell 1 ,
• David Orlikowski 3 ,
• Guillaume Nicolas 4
• 1 Regional Neuromuscular Clinic, Queen Elizabeth Neurosciences Centre, University Hospitals of Birmingham , Birmingham , UK
• 2 Department of Neurophysiology , Hôpital Raymond-Poincaré (AP-HP), Université Versailles-Saint-Quentin-en-Yvelines , Garches , France
• 3 Medical Intensive Care Unit , Hôpital Raymond-Poincaré (AP-HP), Université Versailles-Saint-Quentin-en-Yvelines , Garches , France
• 4 Department of Neurology , Hôpital Raymond-Poincaré (AP-HP), Université Versailles-Saint-Quentin-en-Yvelines , Garches , France
• Correspondence to Dr Yusuf A Rajabally, Regional Neuromuscular Clinic, Queen Elizabeth Neurosciences Centre, University Hospitals of Birmingham, Birmingham B15 2WB, UK; Yusuf.Rajabally{at}uhb.nhs.uk

Background Serial electrophysiology has been suggested as essential for accurate diagnosis in Guillain–Barré syndrome (GBS). However, whether more adapted electrophysiological criteria may allow a single study to be sufficient is unknown.

Methods We retrospectively reviewed records of 365 consecutive patients with GBS from Birmingham, UK, and Garches, France, admitted between 1998 and 2013. Electrophysiology was analysed using existing criteria as well as a set of modified criteria, developed using sensitive and specific cut-off values for demyelination and incorporating new knowledge on electrophysiology of axonal GBS. We compared diagnostic rates and classification changes using modified criteria with published literature relating to serial studies.

Results With existing criteria, we found similar proportions of acute inflammatory demyelinating polyradiculoneuropathy (AIDP) (71.5% vs 72%; p=1), axonal GBS (17.5% vs 14.7%; p=0.62) and equivocal forms (9.9% vs 13.3%; p=0.41) to the previous studies considered. With modified criteria, we identified comparable rates of AIDP (56.2% vs 58.7%; p=0.70), axonal GBS (35.1% vs 36%; p=0.89) and equivocal forms (7.7% vs 5.3%; p=0.63) with a single nerve conduction study as compared with when serial electrophysiology was used in previous analyses. We observed an identical diagnostic shift from AIDP to axonal GBS with modified criteria as that described with serial studies (21.5% vs 18.5%; p=0.72). Classification changes with modified criteria correlated significantly with performing of electrophysiology ≤7 days after symptom onset (p=0.045), indicating their greater usefulness in earlier disease stages.

Conclusions A single electrophysiological study may suffice to establish the ultimate electrodiagnosis of GBS subtype if the proposed modified electrodiagnostic criteria are used.

• GUILLAIN-BARRE SYNDROME
• NEUROMUSCULAR
• NEUROPHYSIOL, CLINICAL

https://doi.org/10.1136/jnnp-2014-307815

Statistics from Altmetric.com

Request permissions.

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Introduction

Guillain–Barré syndrome (GBS) consists of different subtypes, including acute inflammatory demyelinating polyradiculoneuropathy (AIDP), and axonal forms (acute motor axonal neuropathy (AMAN) and acute axonal sensory and motor neuropathy (AMSAN)). In those axonal forms, nodal and paranodal involvement resulting from antibody-mediated attack result in diverse electrophysiological phenomena that are now well described. 1 These include axonal loss with reduced compound muscle action potentials (CMAPs), acute motor conduction block (CB) with or without subsequent reversible conduction failure or isolated F-wave absence. 1 , 2 Combinations of those features may be present in different nerves of the same patient at one study.

It has been shown that a single electrophysiological study is probably inadequate for correct ultimate diagnosis of disease subtype. 3 , 4 However, use of current electrophysiological criteria for GBS may represent the main reason for this due to their lack of specificity for demyelination relating to cut-off values used, particularly for distal motor latency (DML) and motor conduction velocity (MCV). These criteria furthermore do not allow appropriate consideration of the various forms of axonal GBS that are now recognised. Whether the use of more adapted electrophysiological criteria could make earlier accurate diagnosis possible with a single nerve conduction study has not, to our knowledge, been studied.

We retrospectively reviewed our institutional databases of patients admitted with a diagnosis of GBS between 2007 and 2012 (Birmingham, UK) and 1998 and 2013 (Garches, France).

The diagnosis was made in each case in accordance with established clinical criteria. 5 Patients included had undergone electrophysiological testing of at least four motor and two sensory nerves within 21 days of symptom onset. Electrophysiology was performed according to standard methods by a qualified senior physician trained and experienced in electromyography using routine procedures and different neurophysiological equipment over the years of the study. The CMAPs were evoked from the median nerve (stimulating at wrist and elbow, and recording at the Abductor Pollicis Brevis muscle), ulnar nerve (stimulating at wrist and below elbow, and recording at the Abductor Digiti Minimi muscle), common peroneal nerve (stimulating at ankle and fibular neck and recording at the Extensor Digitorum Brevis muscle) and tibial nerve (stimulating at ankle only or ankle and popliteal fossa and recording at the Abductor Hallucis muscle). Measured parameters were MCV, DML, minimum F-wave latency, distal CMAP amplitude and presence of CB as defined within the criteria considered. Results were analysed with our laboratories’ normal values. Fulfilment of each set of electrodiagnostic criteria was ascertained in each case.

Hadden et al 's 6 electrodiagnostic criteria for Guillain–Barré syndrome

(All the following in all nerves tested)

DML ≤100% ULN

F-wave present with latency ≤100% ULN

MCV ≥100% LLN

Distal CMAP ≥100% LLN

Proximal CMAP ≥100% LLN

Proximal CMAP/distal CMAP ratio >0.5

Primary demyelinating

(At least one of the following in each of at least two nerves, or at least two of the following in one nerve if all others inexcitable and distal CMAP ≥10% LLN)

MCV <90% LLN (85% if Distal CMAP <50% LLN)

DML >110% ULN (120% if Distal CMAP <100% LLN)

Proximal CMAP/distal CMAP ratio <0.5 and distal CMAP ≥20% LLN

F-response latency >120% ULN

Primary axonal

None of the above features of demyelination in any nerve (except one demyelinating feature allowed in one nerve if distal CMAP <10% LLN) and

Distal CMAP <80% LLN in at least two nerves

Inexcitable

Distal CMAP absent in all nerves (or present in only one nerve with distal CMAP <10% LLN)

Does not exactly fit criteria for any other group

CMAP, compound muscle action potentials; DML, distal motor latency; LLN, lower limit of normal; MCV, motor conduction velocity; ULN, upper limit of normal.

Proposed modified set of electrodiagnostic criteria for Guillain–Barré syndrome (based on Van den Bergh and Piéret, 7 for demyelinating cut-offs and incorporating use of new knowledge on axonal GBS to define primary axonal forms 1 , 2 )

Proximal CMAP/distal CMAP ratio >0.7 (excluding the tibial nerve)

Acute inflammatory demyelinating polyradiculoneuropathy (AIDP)

At least one of the following in at least two nerves:

MCV <70% LLN

DML >150% ULN

F-response latency >120% ULN, or >150% ULN (if distal CMAP <50% of LLN)

F-wave absence in two nerves with distal CMAP ≥20% LLN, with an additional parameter, in one other nerve

Proximal CMAP/distal CMAP ratio <0.7 (excluding the tibial nerve), in two nerves with an additional parameter, in one other nerve

Axonal GBS including inexcitable forms

Axonal GBS :

None of the above features of demyelination in any nerve (except one demyelinating feature allowed in one nerve if distal CMAP <10% LLN), and at least one of the following:

Distal CMAP <80% LLN in two nerves

F-wave absence in two nerves with distal CMAP ≥20% LLN, in absence of any demyelinating feature in any nerve

Proximal CMAP/distal CMAP ratio <0.7, in two nerves (excluding the tibial nerve)

F-wave absence in one nerve with distal CMAP ≥20% LLN OR proximal CMAP/distal CMAP ratio <0.7 (excluding the tibial nerve), in one nerve; with IN ADDITION, distal CMAP <80% LLN in one other nerve

Inexcitable:

If distal CMAP absent in all nerves (or present in only one nerve with distal CMAP <10% LLN)

Abnormal range findings however not fitting criteria for any other group

CMAP, compound muscle action potentials; DML, distal motor latency; GBS, Guillain–Barré syndrome; LLN, lower limit of normal; MCV, motor conduction velocity; ULN, upper limit of normal.

We classified patients with AIDP, axonal GBS or with ‘equivocal’ electrophysiology with current criteria and established diagnostic rates and classification changes with use of modified criteria. Findings were compared with recent published literature on the resulting classification modifications from the use of serial electrophysiological studies. 3 , 4 Comparison of proportions was performed using Fisher's exact tests. Changes in diagnostic sensitivity were assessed by McNemar's test. Correlations of electrophysiological findings were performed with timing of nerve conductions using Spearman's rank correlation analysis. Significance level was set at p values <0.05.

This study, which was part of a larger retrospective analysis of clinical and electrophysiological features of GBS at our institutions, was registered and approved by our respective relevant institutional boards. Ethics committee approval was not required.

We included 365 patients (48 from Birmingham from 2007 to 2012 and 317 from Garches from 1998 to 2013). One hundred and nine patients were excluded in total on the basis of incomplete clinical details, delayed electrophysiology performed >21 days after disease onset, insufficiently exhaustive electrophysiology (<4 motor nerves and <2 sensory nerves tested), a diagnosis of Miller–Fisher syndrome or a diagnosis of acute-onset CIDP. There were 210 males and 155 females, corresponding to a gender ratio of 4:3. Mean age was 52.1 years (SD 17.8). The median interval between symptom-onset and performing of the electrophysiological studies was 9 days (IQR 6).

The main findings are shown in figure 1 . In the initial analysis, using Hadden et al 's criteria, 71.5% of patients (261/365) were diagnosed with AIDP, 17.5% (64/365) had axonal GBS and 9.9% (36/365) had equivocal electrophysiology. Four patients (1.1%) had normal electrophysiology. Using modified criteria, the number of patients with AIDP decreased from 261 to 205 (70.9% to 56.2%). The number of patients with axonal GBS increased from 64 to 128 (17.5% to 35.1%). Among those, 97 (75.8%) had a pure motor form and 31 (24.2%) had a sensory and motor form (AMSAN). The number of equivocal cases was reduced from 36 to 28 (9.9% to 7.7%). The number of cases with normal electrophysiology remained unchanged at 4 (1.1%). The main classification shift occurred from an initial diagnosis of AIDP to a subsequent one of axonal GBS (56 patients; ie, 21.5% of initially diagnosed AIDP cases). There was also a proportion of patients diagnosed with equivocal electrophysiology by Hadden et al 's criteria, who were rediagnosed with axonal GBS (eight patients; 22.2% of the equivocal group). There were no shifts from an initial diagnosis of axonal GBS or equivocal electrophysiology to AIDP. All abovementioned results obtained were comparable in our two centres considered individually.

• Download figure
• Open in new tab
• Download powerpoint

Proportions of Guillain–Barré syndrome subtypes and changes in the electrophysiological, classification in 365 patients with Guillain–Barré syndrome from Birmingham, UK, and Garches, France, by, use of proposed modified criteria after initial application of Hadden et al 's 6 criteria.

An initial diagnosis of equivocal electrophysiology with Hadden et al 's criteria otherwise correlated significantly with performing of early electrophysiology, defined as ≤7 days after symptom-onset (Spearman's r=0.134; p=0.017). Similarly, there was a significant correlation between the occurrence of classification changes with use of the modified criteria and early electrophysiology (Spearman's r=0.113; p=0.045), with 43/64 (67.2%) of all diagnostic changes occurring in patients having undergone electrophysiology ≤7 days. There was a significant increase in diagnostic sensitivity for non-equivocal GBS (89% to 91.3%), resulting from the reduction in number of equivocal cases (McNemar's test: p=0.013).

A comparative analysis with previous serial studies 3 , 4 is shown in table 1 . There were no significant differences for proportions of AIDP (71.5% vs 72%; p=1.0), axonal GBS (17.5% vs 14.7%; p=0.62) or equivocal forms (9.9% vs 13.3%; p=0.41) using Hadden et al 's criteria. Use of the modified criteria with a single set of nerve conductions demonstrated similar rates of AIDP (56.2% vs 58.7%; p=0.70), axonal GBS (35.1% vs 36%; p=0.89) and equivocal electrophysiology (7.7% vs 5.3%; p=0.63) with those obtained with these serial electrophysiological studies using Hadden et al 's criteria. The rate of classification change was comparable (17.5% vs 24%; p=0.20), and the rate of reclassification from AIDP to axonal GBS was also similar (21.5% vs 18.5%; p=0.72).

• View inline

Changes in the electrophysiological classification in 365 patients with Guillain–Barré syndrome from Birmingham, UK, and Garches, France, by use of a proposed modified set of electrophysiological criteria compared with that resulting from the use of serial studies with use of Hadden et al 's criteria, 6 in a total of 75 patients from Italy and Malaysia 3 , 4

The main finding of our study is that use of the proposed modified criteria for GBS alters, in this large patient cohort from two tertiary centres, the electrodiagnosis in similar proportions and in an identical manner to that resulting from serial studies. This suggests the modified electrodiagnostic criteria may be more adequate, enabling improved early and accurate electrodiagnosis using a single nerve conduction study performed in the first 3 weeks after symptom onset. The use of the modified criteria appears of maximal diagnostic benefit in the first 7 days of the disease. This latter result is consistent with the modified criteria allowing earlier accurate electrodiagnosis, comparable with that which may be achieved with delayed studies at 3–10 weeks. 3 Also, with the modified criteria, the proportion of equivocal cases is reduced, resulting in an improved sensitivity for a non-equivocal diagnosis of GBS, that is, of AIDP or axonal GBS. This is helpful as it offers a greater likelihood, with a single study, of reaching a firm diagnosis, which remains in practice the main purpose of electrophysiology in the clinical setting. 12

Our study has a number of limitations starting with its retrospective design. The long study period, number of different electromyographers, use of different electrophysiological equipment and absence of a pre-established nerve conduction study protocol may all have impacted upon the findings. Disease severity and timing of treatment was not considered specifically here. We were in addition unable to consider both distal and proximal temporal dispersion within the modified criteria, which however clearly represent sensitive markers of demyelination. 7 , 13 Preferably also, it could be argued that our results should have been internally validated by a subgroup of patients having undergone serial studies to ascertain confirmation of our findings with the modified criteria on a case-by-case basis. We are now considering such an analysis that was unfortunately not possible due to serial electrophysiology not being performed routinely at set intervals at our institutions in the past. Finally, a further limitation of our study was its purely electrophysiological focus, without, in particular, microbiological and immunological components. These may have been of interest particularly in the cases diagnosed with axonal GBS after an initial diagnosis of AIDP, given the significantly higher rate of antiganglioside antibody positivity described in axonal compared with demyelinating forms. 3 , 14

A comparative analysis with existing published data relating to delayed diagnostic change with serial electrophysiology, as we did in this study, represents, in our opinion, a necessary starting point in validating the use of the proposed modified criteria. The justification for serial studies in rectifying the diagnostic subtype in a proportion of cases of GBS has convincingly been put forward in recent years, 3 , 4 and comparison with such serial analyses therefore appears a logical validating method for any new set of criteria. No definite gold standard is available for determining correctness of the electrodiagnosis of GBS, as AIDP and axonal forms cannot be distinguished on clinical grounds or therapeutic response and do not have absolute biomarkers. In terms of cut-off values we used for each parameter, it appears difficult, despite the limitations of such methods, not to use predefined limits to diagnose demyelination or nodo-paranodopathy, as we have done here, in order to have a meaningful interpretation of the electrophysiological data. For that purpose, use of cut-offs that have shown robustness in CIDP, or that are based on newly available and well-documented data on axonal GBS subtypes, as we used here, although potentially arbitrary, does as a result, appear ultimately appropriate. Our results seem to confirm this in the present study.

We believe that despite the drawbacks, our findings bring new insight into the electrodiagnosis of GBS, indicating for the first time in a large series that a single, early, nerve conduction study may suffice for precise subtype classification with use of the proposed modified criteria. Outside considerations of elucidation of pathophysiology, long-term outcome or of clinico-electrophysiological correlations, this importantly indicates that, from a purely clinical and diagnostic point of view, only a single study may be needed in over 90% of patients with GBS for an accurate diagnosis. Further, prospective studies are now required to test the validity of our new proposed criteria.

• Kuwabara S ,
• Ogawara K ,
• Manzoli C ,
• Notturno F ,
• Shahrizaila N ,
• Abdullah S ,
• Asbury AK ,
• Cornblath DR
• Hadden RDM ,
• Cornblath DR ,
• Hughes RAC ,
• Van den Bergh PY ,
• Hadden RD ,
• Rajabally YA ,
• Nicolas G ,
• Breiner A ,
• Brannagan TH III .
• Feasby TE ,
• Sekiguchi Y ,

Contributors YAR: conception, organisation and execution; design, statistical analysis; writing of manuscript. M-CD: organisation and execution; design, review and critique of manuscript. JM: organisation and execution; review and critique of manuscript. DO: design, review and critique of manuscript. GN: conception; organisation and execution; design, writing of manuscript.

Competing interests YAR has received speaker/consultancy honoraria from LfB France, Griffols and BPL and has received educational sponsorships from LfB France, CSL Behring and Baxter. M-CD, JM and DO have no disclosures. GN has received departmental research support/honoraria from Debiopharm, GSK, LfB France, Ipsen and Novartis.

Ethics approval Clinical Audit Registration Office.

Provenance and peer review Not commissioned; externally peer reviewed.

Linked Articles

• Editorial commentary Electrodiagnosis of GBS subtypes by a single study: not yet the squaring of the circle Antonino Uncini Filippo Zappasodi Francesca Notturno Journal of Neurology, Neurosurgery & Psychiatry 2014; 86 5-8 Published Online First: 05 Jun 2014. doi: 10.1136/jnnp-2014-308220

Read the full text or download the PDF:

Internet Book of Critical Care (IBCC)

Online Medical Education on Emergency Department (ED) Critical Care, Trauma, and Resuscitation

Guillain Barre Syndrome (GBS)

July 6, 2022 by Josh Farkas

• Definition and variants
• Epidemiology
• Signs & symptoms
• Differential diagnosis (neuromuscular chapter)
• CSF examination
• Electromyography
• Ganglioside serology
• Diagnostic criteria
• IVIG versus plasmapheresis
• Management of dysautonomia
• Monitoring pulmonary function tests
• Noninvasive respiratory support
• GBS in COVID-19
• Questions & discussion

(back to contents)

Guillain Barre Syndrome (GBS) refers to a group of acute, autoimmune polyneuropathies. This chapter is predominantly about AIDP, AMAN, and AMSAN – since these are most often encountered in the ICU. However, the pharyngeal-cervical-brachial variant and facial-diplegia-with-paresthesia variant are also important to be aware of, as they might potentially compromise the airway.

Acute Inflammatory Demyelinating Polyneuropathy (AIDP)

• Epidemiology : Most common cause of GBS in North America and Europe (~90% of patients).
• Pathophysiology : Diffuse demyelination of nerves, with inflammation directed towards the myelin sheaths.
• Clinical presentation : Classic manifestations of GBS.
• Prognosis : Patients often can recover relatively rapidly (over several weeks to months).

Acute motor axonal neuropathy (AMAN)

• Epidemiology : Second most common cause in North America and Europe (<10% of patients). More common in Asia, South America, and Central America. ( 33002998 )
• Pathophysiology : Inflammation directed towards the axons , which is centered at the Nodes of Ranvier (where the axons are more exposed).
• Mainly motor deficiency (e.g., no pain or sensory involvement).
• Cranial nerves are uncommonly involved (<20%). ( 33995011 )
• Reflexes may be preserved initially.
• Autonomic involvement is less common than in AIDP. ( 33002998 )
• Prognosis : This often progresses more rapidly than AIDP, with an increased risk of requiring mechanical ventilation. Subsequently, the process of axonal regeneration is slow and often incomplete, so the recovery may be worse. ( 34618763 )

Acute motor and sensory axonal neuropathy (AMSAN)

• Epidemiology : Least common in North America and Europe, but more frequently seen in Asia and South America.
• Pathophysiology : Similar to AMAN, but involves sensory and motor nerves. Axonal degeneration may occur.
• Similar to AMAN, but with sensory deficits. ( 33995011 )
• Usually severe disease course.
• Greater likelihood of autonomic involvement. ( 33002998 )
• Prognosis : This form carries the worst prognosis, with the potential for delayed and incomplete recovery.

Pharyngeal-Cervical-Brachial variant

• Oropharyngeal weakness that may involve ptosis, ophthalmoplegia, facial muscles, and/or pharyngeal muscles.
• Neck flexor  weakness.
• May spread to involve the arms .
• Epidemiology:  Accounts for 3% of cases of Guillain-Barre syndrome. ( 31279384 )
• Usually preceded by upper respiratory tract or diarrheal infection. ( 31279384 )
• Subsequently, this presents with rapidly progressive oropharyngeal, neck, and arm weakness associated with areflexia. ( 31279384 )
• Sensation is unaffected.
• Differential diagnosis:  May mimic botulism, myasthenia gravis, or a brainstem stroke.
• Diagnostic tests:  Electromyography will show acute motor axonal neuropathy. ( 31279384 )

Miller Fisher syndrome

• This is the second most common variant in United States (~10%).
• Its classic clinical triad involves areflexia , external ophthalmoplegia , and cerebellar ataxia .
• Extremity weakness can occur. However, patients usually don't develop respiratory failure .  Bulbar dysfunction doesn't occur. ( 31279384 )
• Anti-GQ1b antibodies have been implicated with this disease entity and can be assessed from CSF.

Bickerstaff brainstem encephalitis

• This is extremely rare, possibly representing a variant or subset of Miller Fisher syndrome (both are associated with anti-GQ1b).
• The typical triad consists of ophthalmoplegia , ataxia , and depressed consciousness (which may include coma).
• Hyperreflexia is a feature, unlike other forms of GBS.
• MRI is usually normal, but may show scattered T2 hyperintensities in the brainstem and basal ganglia, with limited enhancement and mild diffusion restriction. ( 33293366 )

Facial diplegia with paresthesia variant

• May cause bilateral facial paralysis and paresthesias. 📄

• GBS is the most common cause of generalized neuromuscular paralysis.
• Genders are affected roughly equally. The risk may increase somewhat with increased age.
• Specific risk factors include lymphoma, lupus, and HIV.
• A trigger of GBS often occurs 5 days to four weeks before the onset of neurologic symptoms. (Louis 2021)

upstream triggers

• Campylobacter jejuni.
• Mycoplasma pneumoniae, Haemophilus influenzae. ( 33647239 )
• Herpesviruses (CMV, EBV, VZV).
• Hepatitis E virus, Hepatitis A virus.
• HIV – among all these etiologies, HIV is unique in that it will require ongoing treatment.
• Zika virus.
• Influenza A.
• Checkpoint inhibitors (may require different treatment 📖 ).
• Immunizations ( extremely rare, and much less common than GBS due to infection ). ( 33647239 )

usual presentation

• Paresthesias are common, especially in the fingers and toes. ( 34618763 )
• Pain can result from nerve root inflammation (e.g., in back or extremities, low back pain). Pain may be radicular or neuropathic. ( 34798967 )
• Sensory loss can occur, but this is mild compared to motor dysfunction.
• An exception is the AMAN variant (Acute Motor Axonal Neuropathy), which doesn't involve sensation.
• Relatively symmetric.
• Speed of progression correlates with disease severity.
• The ascending pattern is thought to be due to nerve length, with longer nerves at higher risk of injury.
• 25% of patients develop weakness leading to respiratory failure. ( 34618763 )
• Facial weakness, ophthalmoplegia.
• Difficulty swallowing.
• Blood pressure may be extremely labile.
• Posterior reversible leukoencephalopathy syndrome (PRES) 📖 .
• Takotsubo cardiomyopathy 📖 .
• Parasympathetic activation can occur (with bradycardia, facial flushing, vasodilation).
• Other features may include constipation, diarrhea, and urinary retention.
• Objective muscle weakness.
• Loss of deep tendon reflexes is a hallmark finding (~90% sensitive).

disease course

• Ongoing disease progression for longer periods suggests an alternative, related disorder: chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).
• Usually GBS is a monophasic illness (with deterioration followed by improvement). However, occasionally patients may improve following therapy and then suffer a subsequent deterioration. This is termed “treatment related fluctuation” and discussed further below. 📖

Normal CSF analysis doesn't exclude GBS, especially early in the disease course. To confuse matters further, IVIG therapy may increase CSF protein and white blood cell counts. ( 33002998 )

albuminocytological dissociation

• The classic finding in GBS is albuminocytologic dissociation (elevated protein, despite normal cell count). Protein is usually elevated, up to very high levels (100-1,000 mg/dL)
• Elevated protein has a sensitivity of ~50% during the first week, but this increases over time (to ~80% by 3-4 weeks).
• There is a very broad differential diagnosis of albuminocytologic dissociation, as explored further here: 📖
• Cell count in GBS is generally normal (<5 cells/uL).
• Cell count of roughly ~10-50/uL is consistent with GBS, but should raise some suspicion for alternative diagnoses.(as listed below).
• Viruses involving the anterior horn of the spinal cord. (Historically, cell count was used as the main tool to differentiate between polio and GBS.).
• HIV. In the context of HIV, GBS causes a lymphocytic pleocytosis rather than the classic albuminocytological dissociation. ( 34623100 )
• Leptomeningeal carcinomatosis.
• Sarcoidosis.

This is the most sensitive and specific test. Electromyography may initially be normal, but a normal study >1-2 weeks after onset suggests an alternative diagnosis.

AIDP: Demyelination is a predominant feature.

• Absent or prolonged F-waves latency (F-wave latency may be the earliest sign).
• Prolonged distal compound muscle action potential latency (CMAP).
• Excessive temporal dispersion of compound muscle action potentials (CMAP).
• Reduced motor nerve conduction velocity.

AMAN (Acute motor axonal neuropathy)

• Decreased compound muscle action potential (CMAP) amplitudes with relatively preserved velocities.
• Decreased compound muscle action potential (CMAP) amplitudes.
• Decreased sensory nerve action potential (SNAP) amplitudes.
• In cases without cranial nerve involvement, the differential includes spinal cord lesions. MRI may be useful to exclude these.
• Contrast enhancement of spinal nerve roots is sensitive for GBS but nonspecific (for example, it may also be seen in acute flaccid myelitis due to various viral infections). ( 34618763 )
• The role of ganglioside serologies in diagnosis is not well established. Given their long turnaround time, these labs should ideally return after the initiation of treatment. That being said, positive results might help point one of the following conditions:
• AIDP : Ganglioside antibodies are usually absent . ( 33995011 )
• AMAN or AMSAN is associated with antiganglioside antibodies against GM1a, GM1b, GD1a, and GalNAc-GD1a. ( 33002998 , 33995011 )
• Miller Fisher syndrome is associated with Anti-GQ1b (often cross-reactive with anti-GT1a) occurs in >80% of patients.
• Cervical brachial variant is associated with anti-GT1a.
• HIV serology – consider obtaining to exclude HIV as a cause of GBS.

Ultimately, the diagnosis of GBS involves a combination of excluding alternative possibilities as well as matching the patient's findings to the diagnosis of GBS. The following criteria may provide a helpful scaffolding to approaching the diagnosis, but aren't necessarily intended for rigid application. They are only relevent for major/paralytic forms of GBS. ( 33002998 )

required and supportive features

• Progressive weakness in more than one limb with relative symmetry (initially only legs may be involved).
• Diminished reflexes in weak limbs (although this may be absent in the acute motor axonal neuropathy variant).
• No other clear explanation for these findings.
• “Supportive” features include the following.

features to consider in GBS diagnosis

• Deterioration lasts days to a month (usually <2 weeks).
• Recovery starts 2-4 weeks after deterioration halts (nadir).
• 🚩 Inconsistent with GBS: Maximum weakness reached within <24 hours or >4 weeks.
• Consistent with GBS: Relatively symmetric.
• 🚩 Inconsistent with GBS: Substantial asymmetry.
• Consistent with GBS: Mild sensory involvement, often involving pain (can be absent in motor variant).
• Severe sensory signs, with little or no weakness at onset.
• Absence of any sensory symptoms. ( 35863882 )
• Consistent with GBS: No fever at onset.
• 🚩 Inconsistent with GBS: Fever at onset.
• Elevated CSF protein (after one week).
• Cell count <50/mm3 (and usually <10/mm3).
• CSF white cell count >50/mm3.
• Neutrophils elevated.
• Consistent with GBS: Cranial nerve involvement (especially bilateral facial palsy).
• Sensory level suggestive of a focal spinal cord lesion.
• Bowel and bladder dysfunction at onset; severe and persistent bowel and bladder dysfunction (this may suggest myelopathy).
• Consistent with GBS: Should lack findings localizing to the brain (except for Miller Fisher syndrome-Bickerstaff brainstem encephalitis spectrum disorders)
• 🚩 Inconsistent with GBS: Other deficits that localize to the brain.
• Autonomic dysfunction.
• Electrodiagnostic studies consistent with GBS
• 🚩 Severe pulmonary dysfunction with little or no limb weakness at onset (this might suggest myasthenia gravis).
• 🚩 Normal nerve conduction tests after two weeks. ( 35863882 )

These are cornerstone therapies for GBS.

indications

• The exact indications are unclear, but any critically ill or hospitalized patient with new-onset GBS merits treatment.
• Treatment should begin when there is a clinical diagnosis of GBS, rather than awaiting confirmation from lumbar puncture or nerve conduction studies. ( 30743297 )

selection of IVIG or plasma exchange

• Both appear to be equally effective. Importantly, the combination of treatments hasn't been found to be superior to one treatment alone (e.g., plasmapheresis followed by IVIG). ( 33002998 , 33896522 )
• If there is no improvement after 1-2 weeks, a second repeated course of therapy does not appear to be beneficial. One randomized controlled trial among patients with severe GBS found that a repeat course didn't cause benefit – but did increase the risk of harm due to thromboembolic events. ( 33743237 )
• IVIG. 📖
• Plasma exchange. 📖
• Selection of IVIG versus plasma exchange. 📖

treatment-related fluctuations

• These occur in up to 10% of patients. Patients stabilize or improve following treatment, but then subsequently deteriorate (within 8 weeks of disease onset).
• There is no evidence regarding management, but consensus is to retreat with the original treatment modality. ( 33002998 , 33647239 )
• If more than three relapses occur, or if relapse occurs after 8 weeks of disease onset, this suggests an alternative diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP). ( 33647239 )

dysautonomia basics

• Dysautonomia is more frequent in patients with severe weakness. It can occur in patients with different types of GBS including demyelination (i.e., Acute Inflammatory Demyelinating Polyneuropathy) or axonal disease (i.e., Acute Motor Axonal Neuropathy). ( 31996626 )
• Some patients may have alternating episodes of sympathetic hyperactivity (e.g., hypertension and tachycardia) and parasympathetic hyperactivity (e.g., bradycardia). This may be very dangerous, as bradyasystole is a potential cause of death in Guillain-Barre Syndrome.
• Some patients experience sustained hypertension . This is easier to manage than patients with hemodynamic fluctuations – hypertension may be treated with a long-acting vasodilator (e.g. with oral isradipine or nifedipine XR 💉 ).
• Persistent hypertension can cause target organ damage (e.g., Takotsubo cardiomyopathy or posterior reversible encephalopathy syndrome).

hemodynamic management

• (1) Blood pressure swings are often short-lived, so avoid treatment when possible. Aggressive treatment of hemodynamic fluctuations may merely worsen the hemodynamic roller-coaster (e.g., initiation of a vasopressor during a hypotensive episode exacerbates a subsequent episode of hypertension).
• (2) Avoid beta-blockers, as these may increase the risk of bradycardia.
• Administer fluid if there is evidence of true hypovolemia (e.g., negative fluid balance, poor PO intake for days).
• May use vasopressor, at the lowest dose possible.
• Avoid treatment unless there is target-organ damage or ongoing severe hypertension (e.g., MAP > ~120 mm).
• Avoid beta-blockers (these may aggravate subsequent bradycardia).
• 1st line treatment : Remove the stimulus for hypertension if possible (e.g., ensure that pain and agitation are adequately treated).
• 2nd line treatment : For prolonged and severe hypertension, consider a short-acting vasodilator (e.g., nicardipine 💉 or clevidipine 💉 infusion). If patients respond adequately and are stable for a period of time, this may be transitioned to oral calcium-channel blockers (e.g., nifedipine XR or isradipine 💉 ).
• Avoid triggers of bradycardia if possible (e.g., endotracheal suctioning).
• Discontinue negative chronotropes (e.g., beta-blockers).
• IV atropine may be useful.
• In severe cases, electrical pacing may be needed.

other autonomic problems

• Urinary retention and incontinence can occur. Depending on the context, either a Foley catheter or frequent bladder scanning with straight catheterization may be needed.
• Gastroparesis 📖 can occur, potentially requiring treatment with pro-motility agents or a post-pyloric feeding tube.
• An aggressive bowel regimen is recommended to avoid obstipation (which may in turn trigger additional autonomic instability).
• For patients receiving opioids, therapies such as oral naloxone or peripheral IV methylnaltrexone may be helpful (along with limitation of the opioid dose as much as possible).
• A rectal tube may be helpful.
• Extreme caution and close monitoring is needed if neostigmine is utilized for treatment of colonic pseudo-obstruction, given its potential for causing autonomic swings (e.g., bradycardia and asystole). Pre-treatment with 0.4 mg glycopyrrolate prior to administration of neostigmine (2 mg over 5 minutes) may reduce the risk of bradycardia. ( 28893807 , 18338263 )
• Neuropathic pain is common and potentially debilitating. ( 33896522 ) For neuropathic-type pain, gabapentin may be useful.
• Scheduled acetaminophen is often beneficial, especially among intubated patients.
• Opioid may be used, but exercise caution as patients are prone to develop ileus.

Obsessive, repetitive, and uninformed measurement of respiratory mechanics is a common pitfall in the management of GBS. Like many data points in medicine (e.g., troponin), respiratory mechanics can be useful if utilized appropriately.

forced vital capacity (FVC)

• FVC is the largest volume of gas that a patient can exhale. Patients are asked to take a full breath in and then exhale maximally, with measurement of the exhaled volume. FVC reflects a global measurement of the patient's ventilatory ability, which takes into account inspiratory and expiratory muscle strength as well as pulmonary compliance.
• FVC is the most reproducible and clinically useful measurement of pulmonary function.
• A normal forced vital capacity is ~60 ml/kg. Values below roughly 30 ml/kg suggest a risk of atelectasis or hypoventilation.
• Absolute values are less valuable than the trend , which may help determine in what direction the patient is going.
• Excessive performance may cause diaphragmatic fatigue.
• The maneuver is effort dependent.
• Measuring FVC may be impossible in a patient with bulbar weakness, as the patient is unable to close their lips around the mouthpiece.
• There is no high-quality evidence that any particular value has any specific meaning (traditionally utilized cutoff values are not evidence-based).

negative inspiratory force (NIF)

• This is the greatest negative pressure the patient can generate (also known as the minimum inspiratory pressure or MIP). A pressure gauge is used to measure the negative pressure generated by the patient when asked to inhale as hard as they can. This is a measurement of the strength of the inspiratory muscles, primarily the diaphragm.
• (1) The NIF doesn't add statistically independent or useful information beyond measurement of the forced vital capacity alone. ( 11405803 , 21748507 ) What this means is that it introduces a source of noise , without adding meaningful information.
• (2) The NIF is more fatiguing and uncomfortable than the forced vital capacity.

use #1 of respiratory mechanics: triage

• Determining which patients require observation in an ICU versus a ward is primarily dependent on history and overall gestalt impression.
• However, pulmonary function testing could play a role in risk-stratification and triage. For example, an FVC under roughly 30 ml/kg might suggest a higher risk of deterioration and the need for closer monitoring.

use #2 of respiratory mechanics: tracking trajectory

• Serial measurement of forced vital capacity (FVC) is often used to determine disease trajectory (e.g., 2-3 times daily during waking hours).
• Serial FVC is only one piece of information to help assess the patient, in addition to numerous others (e.g., subjective impression and strength of other muscle groups).
• The key is probably early initiation of noninvasive support, before respiratory exhaustion occurs.
• If a patient is completely dependent on BiPAP and entirely unable to breathe without it, then they should simply be intubated.  However, nocturnal BiPAP might be useful to off-load respiratory muscles at night, facilitating rest.
• Titration and selection depends largely on patient tolerance.
• BiPAP may be ideally restricted to nocturnal use, possibly with use of high-flow nasal cannula support during the day.

pulmonary function (forced vital capacity)

• As discussed above, this provides only one piece of information.
• For example, poor patient effort can cause aberrantly low values.
• ⚠️ Several “rules” exist suggesting that specific cutoff values indicate when to intubate (e.g., below 15-20 ml/kg). These rules are not evidence based and should not be blindly followed. 🌊

weakness of other muscle groups

• i) Neck flexion weakness, for example the patient's ability to lift their head off the pillow. (Neck flexion is innervated by the same cervical nerve roots that innervate the diaphragm, correlating with diaphragmatic weakness.) (Torbey, 2019)
• ii) Facial or bulbar weakness.
• iii) Limb weakness (this is unlike myasthenia gravis). ( 35863882 )
• Progressive weakness of multiple muscle groups is concerning.

clinical evaluation of respiratory status and the decision to intubate

• Many criteria for intubation exist, but none are based on high-quality evidence. Ultimately the decision to intubate is a clinical one that should be based on the integration of multiple sources of information. Important parameters to track include the following:
• (1) Evidence of increased work of breathing (e.g., accessory muscle use, subjective dyspnea).
• (2) Difficulty controlling secretions.
• (3) Cough strength.
• (4) Overall course of muscle weakness.
• (5) Trends in forced vital capacity.

intubation procedure

• Intubation procedure carries risk of inducing a vagal episode (prepare push-dose epinephrine ahead of time, but avoid its use if possible). Evaluate for volume status prior to intubation and consider some fluid resuscitation if the patient is grossly volume depleted (as may occur due to bulbar weakness and poor oral intake).
• ⚠️ Succinylcholine is contraindicated (denervation of muscles may lead to excessive potassium release).

mode of ventilation and weaning

• Patients can be ventilated using standard ICU protocols .
• There is no evidence that patients with Guillain Barre syndrome are better managed with SIMV or other modes of ventilation. (Indeed, SIMV is poorly supported by evidence overall and should arguably be avoided.)

weaning from ventilation

• Overall, this may be pursued in the same manner as liberating other patients from the ventilator. Ideally, strength will improve over several days, leading to the ability to extubate.
• 💡 Diaphragm strength may improve before extremity muscle strength, so it may be possible to extubate patients with persistent extremity weakness.

post-extubation support

• Extubating to BiPAP or high-flow nasal cannula may reduce the work of breathing, reducing the reintubation risk.

tracheostomy

• Many patients will require tracheostomy, due to inability to wean off mechanical ventilation within <1-2 weeks.
• Acute Motor Axonal Neuropathy (AMAN) form of GBS. ( 34618763 )
• Inability to lift the arms after one week. ( 34618763 )
• Rapid progression to severe weakness (in <1 week). ( 30516604 )
• GBS can occur following infection with COVID-19. This generally occurs within two weeks after the initiation of other COVID-19 symptoms (coincident with development of adaptive immunity). ( 33647239 )
• Some patients may lack respiratory symptoms due to COVID upon presentation, presenting instead with weakness or even back pain as a primary complaint.
• Demyelination have been reported most frequently (AIDP), but axonal variants and Miller Fisher variant may also occur. ( 33647239 )
• Weakness is the predominant clinical finding (most often ascending paralysis). Dysautonomia doesn't seem to be a prominent issue.
• Diagnosis can be challenging for patients who are already admitted with COVID pneumonia, since GBS will tend to blend in with other causes of respiratory dysfunction present in these patients (e.g., critical illness neuropathy/myopathy, COVID pneumonia, pulmonary embolism, ventilator acquired pneumonia). In some patients, GBS could be an occult cause of inability to wean from mechanical ventilation.
• Intravenous immune globulin (IVIG) is generally the front-line therapy for Guillain Barre Syndrome (with equal efficacy compared to plasmapheresis and superior tolerability).

Follow us on iTunes

To keep this page small and fast, questions & discussion about this post can be found on another page here .

• Over-aggressive treatment of autonomic swings.
• Excessive focus on forced vital capacity and excessive measurement of the forced vital capacity.
• Use of the negative inspiratory force.
• Failure to consider GBS in a patient admitted to ICU with viral illness who develops weakness.
• Assuming that a patient with GBS and respiratory failure has neuromuscular respiratory failure (as opposed to other possible causes of respiratory failure which may occur, such as heart failure).

Acknowledgement: Thanks to Dr. Richard Choi (@rkchoi) for thoughtful comments on this chapter.

Guide to emoji hyperlinks

• 11405803 Lawn ND, Fletcher DD, Henderson RD, Wolter TD, Wijdicks EF. Anticipating mechanical ventilation in Guillain-Barré syndrome. Arch Neurol . 2001;58(6):893-898. doi:10.1001/archneur.58.6.893 [ PubMed ]
• 18338263 Rosman AS, Chaparala G, Monga A, Spungen AM, Bauman WA, Korsten MA. Intramuscular neostigmine and glycopyrrolate safely accelerated bowel evacuation in patients with spinal cord injury and defecatory disorders. Dig Dis Sci . 2008;53(10):2710-2713. doi:10.1007/s10620-008-0216-z [ PubMed ]
• 19938102 Kuitwaard K, de Gelder J, Tio-Gillen AP, et al. Pharmacokinetics of intravenous immunoglobulin and outcome in Guillain-Barré syndrome. Ann Neurol . 2009;66(5):597‐603. doi:10.1002/ana.21737 [ PubMed ]
• 21748507 Prigent H, Orlikowski D, Letilly N, et al. Vital capacity versus maximal inspiratory pressure in patients with Guillain-Barré syndrome and myasthenia gravis. Neurocrit Care . 2012;17(2):236-239. doi:10.1007/s12028-011-9575-y [ PubMed ]
• 28893807 Adiamah A, Johnson S, Ho A, Orbell J. Neostigmine and glycopyrronium: a potential safe alternative for patients with pseudo-obstruction without access to conventional methods of decompression. BMJ Case Rep . 2017;2017:bcr2017221249. Published 2017 Sep 11. doi:10.1136/bcr-2017-221249 [ PubMed ]
• 30074496 Doets AY, Jacobs BC, van Doorn PA. Advances in management of Guillain-Barré syndrome. Curr Opin Neurol . 2018;31(5):541-550. doi:10.1097/WCO.0000000000000602 [ PubMed ]
• 30516604 Greene-Chandos D, Torbey M. Critical Care of Neuromuscular Disorders. Continuum (Minneap Minn). 2018 Dec;24(6):1753-1775. doi: 10.1212/CON.0000000000000682 [ PubMed ]
• 30743297 Edmundson C, Bird SJ. Acute Manifestations of Neuromuscular Disease. Semin Neurol. 2019 Feb;39(1):115-124. doi: 10.1055/s-0038-1676838 [ PubMed ]
• 31279384   Matayeva E, Henson T, Alaverdian A, Iqbal J, Akella J. A 48-Year-Old Man With Excessive Drooling and Descending Paralysis Requiring Mechanical Ventilation. Chest. 2019 Jul;156(1):e9-e13. doi: 10.1016/j.chest.2019.01.026  [ PubMed ]
• 31541214 Leonhard SE, Mandarakas MR, Gondim FAA, et al. Diagnosis and management of Guillain-Barré syndrome in ten steps. Nat Rev Neurol . 2019;15(11):671-683. doi:10.1038/s41582-019-0250-9 [ PubMed ]
• Torbey, M. T. (2019). Neurocritical Care (2nd ed.). Cambridge University Press.
• 31996626 Rabinstein AA. Autonomic Hyperactivity. Continuum (Minneap Minn). 2020 Feb;26(1):138-153. doi: 10.1212/CON.0000000000000811 [ PubMed ]
• 32302082 Toscano G, Palmerini F, Ravaglia S, et al. Guillain-Barré Syndrome Associated with SARS-CoV-2. N Engl J Med . 2020;382(26):2574-2576. doi:10.1056/NEJMc2009191 [ PubMed ]
• 32490966 Munhoz RP, Pedroso JL, Nascimento FA, et al. Neurological complications in patients with SARS-CoV-2 infection: a systematic review. Arq Neuropsiquiatr . 2020;78(5):290-300. doi:10.1590/0004-282×20200051 [ PubMed ]
• 32533876 Kilinc D, van de Pasch S, Doets AY, Jacobs BC, van Vliet J, Garssen MPJ. Guillain-Barré syndrome after SARS-CoV-2 infection [published online ahead of print, 2020 Jun 13]. Eur J Neurol . 2020;10.1111/ene.14398. doi:10.1111/ene.14398 [ PubMed ]
• 33002998 Sheikh KA. Guillain-Barré Syndrome. Continuum (Minneap Minn). 2020 Oct;26(5):1184-1204. doi: 10.1212/CON.0000000000000929 [ PubMed ]
• 33647239 Shahrizaila N, Lehmann HC, Kuwabara S. Guillain-Barré syndrome. Lancet. 2021 Mar 27;397(10280):1214-1228. doi: 10.1016/S0140-6736(21)00517-1 [ PubMed ]
• 33896522 Singh TD, Wijdicks EFM. Neuromuscular Respiratory Failure. Neurol Clin. 2021 May;39(2):333-353. doi: 10.1016/j.ncl.2021.01.010 [ PubMed ]
• 33995011 Shang P, Feng J, Wu W, Zhang HL. Intensive Care and Treatment of Severe Guillain-Barré Syndrome. Front Pharmacol. 2021 Apr 27;12:608130. doi: 10.3389/fphar.2021.608130 [ PubMed ]
• 34618763 Birch TB. Neuromuscular Disorders in the Intensive Care Unit. Continuum (Minneap Minn). 2021 Oct 1;27(5):1344-1364. doi: 10.1212/CON.0000000000001004 [ PubMed ]
• 34798967 Varadhachary AS. Recognition and Management of Neuromuscular Emergencies. Neurol Clin. 2022 Feb;40(1):157-174. doi: 10.1016/j.ncl.2021.08.010 [ PubMed ]
• Dangayach N, Classen J, O'Phelan K (2022) : Neurologic Intensive Care: Brain, acute spinal cord injury, and neuromuscular disease . Presentation at the American Academy of Neurology Conference, Seattle 2022.
• 34950409 Nguyen AM, Decker JA, Dupuis JE, Little AA, Ottenhoff LD, Rajajee V, Sheehan KM, Williamson CA. A 57 Year-Old Man With HIV Presenting With Severe Headache and Progressive Weakness. Neurohospitalist. 2022 Jan;12(1):171-176. doi: 10.1177/1941874420980630 [ PubMed ]
• 35863882 Walters J. Weakness in the intensive care unit. Pract Neurol. 2022 Jul 21:pn-2022-003422. doi: 10.1136/pn-2022-003422 [ PubMed ]

The Internet Book of Critical Care is an online textbook written by Josh Farkas ( @PulmCrit ), an associate professor of Pulmonary and Critical Care Medicine at the University of Vermont.

We are the EMCrit Project , a team of independent medical bloggers and podcasters joined together by our common love of cutting-edge care, iconoclastic ramblings, and FOAM.

Resus Leadership Academy

Subscribe by Email

Insert/edit link.

Enter the destination URL

Or link to existing content

Research Portal

The GBS|CIDP Foundation International is committed to supporting research happening for GBS, CIDP, and variants such as MMN. Sometimes, that research is done by doctors at academic institutions. Other times, it is done by researchers and doctors working for biotechnology, engineering, or pharmaceutical companies. The Foundation also believes that any research being done for GBS, CIDP, or variants such as MMN should include the perspective of patients living with that condition. By clicking one of the links below, you will find opportunities to be involved in the research process.

Research & Clinical Trials

Read on to learn more about the basics of clinical research & why it is important to participate. Alternatively, click here to learn more about the ongoing clinical trials currently recruiting participants.

The Research Process: Bench to Bedside

The practice of medicine and treating patients involves a great deal of work “behind the scenes”. Many doctors, biologists, chemists, pharmacists, and other researchers dedicate their ideas, knowledge, and expertise to study potential new treatment options to treat, and possibly cure, medical conditions. This usually takes years, sometimes decades, and plenty of funding. Before a potential new treatment moves into the clinical trial phase, where it is given to human patients, the safety profile of the potential new treatment is studied extensively in the lab and often tested in animal models. This way, patients that take part in clinical trials can be assured that only the best, and most safe, potential new treatments make it to the clinical trial phase.

Before Clinical Trials in humans can start, investigators must submit all the data generated in the laboratory and in animals, for review by the scientists at FDA, to see whether there is any indication that this treatment might potentially be harmful.  Investigators must also share some manufacturing details and characterization of the new chemical entity proposed to be tested in humans. The FDA must either request additional information from the investigator within 30 days or allow the clinical trials to begin.

Million in Research Grants Awarded

Researchers funded since 2004.

Learn More About Our National Walk & Roll Fundraising Program

• Case Report
• Open access
• Published: 25 April 2024

Guillain–Barre syndrome following scrub typhus: a case report and literature review

• Shijun Hu 1   na1 ,
• Zhichuan lin 1   na1 ,
• Tao Liu 1 ,
• Shixiong Huang 1 &
• Hui Liang 1  

BMC Neurology volume  24 , Article number:  137 ( 2024 ) Cite this article

Metrics details

Scrub typhus is an acute infectious disease caused by Orientia tsutsugamushi. Guillain–Barre syndrome (GBS) is an autoimmune-mediated peripheral neuropathy with a frequent history of prodromal infections, but GBS associated with scrub typhus is very rare.

Case presentation

We report a 51-year-old male patient who developed dysarthria and peripheral facial paralysis following the cure of scfrub typhus. CSF examination and electrophysiological findings suggested a diagnosis of GBS. After treatment with intravenous immunoglobulin, the patient’s neurological condition improved rapidly.

Conclusions

Scrub typhus infection is likely to be a potential predisposing factor in GBS, while scrub typhus-associated GBS has a favorable prognosis.

Peer Review reports

The etiological agent of scrub typhus is Orientia tsutsugamushi, which is characterized clinically by fever, eschar, splenomegaly, hepatomegaly, pneumonia, meningitis, and even multiple organ dysfunction [ 1 ]. Guillain–Barre syndrome (GBS) is an immune-mediated acute polyradiculoneuropathy associated with prodromal infections, injectable vaccines, malignancies, etc [ 2 ]. GBS has prodromal symptoms of infection that are mostly respiratory and gastrointestinal and is very rare in association with scrub typhus. To our knowledge, this is the first case of a GBS patient with elevated anti-sulfatide antibodies associated with scrub typhus infection.

The patient was a 51-year-old male who was hospitalized due to fever for 10 days. The highest body temperature was approximately 39.0 ℃, and the fever had no obvious regularity, accompanied by head pain when fever was present. On examination, it was noted that there was an eschar over the right inguinal area, and several yellow bean-sized lymph nodes were palpable over the right inguinal area, with mild tenderness. Routine blood tests suggested a white blood cell count of 12.52 *10 9 /L, with 0% eosinophils. Meanwhile, metagenomic next-generation sequencing (mNGS) technology was used to detect pathogenic microbial DNA in blood, and as a result, 11,260 Orientia tsutsugamushi-specific sequences were detected. The patient was given intravenous treatment with doxycycline, and the patient was discharged after the resolution of symptoms of infection and continued oral doxycycline treatment as directed after discharge.

On the third day after discharge, also on the 15th day of presentation with febrile symptoms, the patient developed dysarthria, accompanied by salivation, weakness with closed eyes, and no limb weakness or numbness. Examination revealed that the patient had bilateral peripheral facial palsy, unclear articulation, dysphagia, pharyngeal reflexes were present, tendon reflexes of both lower limbs were reduced, and muscle strength of the four limbs was normal. The patient’s vital signs were uneventful, afebrile, conscious, bilateral pupils of consistent size, sensitive to light reflexes, and negative for signs of meningeal stimulation. Sensory and cerebellar examination was normal. CSF protein quantification was 2.04 g/L, white blood cell count was 6 *10 6 /L, CSF pressure, sugar and chloride were within normal ranges, and no pathogenic sequences were detected by mNGS of CSF. Serum anti-sulfatide IgM and IgG antibodies (western blot) were positive. CSF anti-sulfatide antibody IgG (western blot) was positive. Nerve conduction studies showed slowing of NCV in the peripheral nerves of all four limbs, mild prolongation of motor nerve conduction latencies, low distal SNAP amplitude, and marked prolongation of the F-wave latency in both median and tibial nerves in electrophysiological findings, suggesting demyelination. The patient was given intravenous administration of immunoglobulin (IVIG) therapy (0.4 g/kg/day) for 5 days, and after treatment, the patient’s neurological deficit improved significantly, and no significant sequelae were left at the follow-up visits.

Discussion and conclusions

The patient presented with clinical manifestations of cranial neuropathy and albuminocytological dissociation in CSF with elevated anti-sulfatide antibodies in serum and CSF, which may be considered atypical GBS. Although the typical clinical picture of GBS syndrome with limb weakness and numbness was not present, decreased tendon reflexes in the lower extremities and peripheral neuropathy of the extremities suggested by electromyography were present.

Anti-sulfatide antibodies are associated with autoimmune neuropathy diseases and may play a role in demyelinating pathogenesis [ 3 ]. Elevated anti-sulfatide antibodies have been reported in cases of GBS [ 4 ]. Most of the patients with anti-sulfide antibody positivity had sensory or sensorimotor neuropathy in the distal extremities, and only a few of them had demyelinating neuropathy [ 5 ]. Although this patient with positive anti-sulfide antibodies had cranial nerve damage as the primary clinical manifestation, a nerve conduction study was suggestive of the presence of a demyelinating peripheral neuropathy involving motor and sensory nerves in the extremities. In fact, patients with anti-sulfatide IgM antibody positivity often present different neurophysiological and pathological findings and therapeutic responses in the peripheral nervous system [ 6 ].

Scrub typhus, a febrile disease caused by the gram-negative coccal bacterium Orientia tsutsugamushi, is transmitted to humans through the bites of infected larval mites and is commonly characterized clinically by fever, eschar, rash, splenomegaly, hepatomegaly, and lymphadenopathy and, in severe cases, meningoencephalitis, multiorgan dysfunction, and disseminated intravascular coagulation [ 1 , 7 ]. Scrub typhus infection can usually involve the central nervous system, and approximately one-fifth to three-thirds of patients with scrub typhus suffer from neurological complications, but the appearance of symptoms of peripheral neuropathy is very rare [ 8 , 9 , 10 ]. A summary of sixteen case reports of GBS associated with scrub typhus, including the present case, is provided in Table  1 [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. Among all the cases with available details of medical history, all patients developed GBS-related symptoms at least 7 days after presenting symptoms of scrub typhus infection and most concentrated at 10 to 17 days, with a mean of 10.6 days. The mean age of the reported patients was 46 years (7–74 years), and most of them were men (12 men out of 16 cases: 75%). Symptoms of these scrub typhus-associated cases of GBS include muscle weakness, cranial nerve palsy, hypotonia, decreased or absent tendon reflexes, sensory disturbances, abducens nerve palsy, and in severe cases, respiratory failure and disturbance of consciousness. For patients with GBS and persistent scrub typhus infection, fever and meningeal irritation signs may be positive. Albuminocytological dissociation (by the Brighton criteria [ 21 ]) was present in 14 of these 16 patients with CSF results and in 2 with CSF results within the normal range, although it is not clear on the basis of the current data that these CSFs were sampled in the weeks after the onset of peripheral neurological symptoms.

From Table  1 , 10 patients developed GBS-related symptoms at the same time as scrub typhus infection, and the remaining 6 patients developed symptoms after the cure of scrub typhus. Among all the cases with available treatment details, 10 patients had concomitant scrub typhus infection, 3 used antibiotics, 2 used antibiotics, IVIg and prednisolone, 4 used antibiotics and IVIg, and 1 used IVIg (unclear whether antibiotics were used). Of the 6 patients with GBS following scrub typhus infection, 5 received IVIg, and 1 received plasmapheresis. Four patients used mechanical ventilation because of respiratory failure due to respiratory muscle weakness. This suggests that antibiotic therapy is essential in cases of GBS with persistent scrub typhus infection, that the addition of prednisolone and immunoglobulin may be considered when treatment is suboptimal and that treatment with immunoglobulins or plasmapheresis can be routinely administered in cases of GBS following scrub typhus infection. All the reviewed patients experienced near complete improvement of their peripheral nerve symptoms, and none died or had sequelae affecting daily tasks, implying a better prognosis for scrub typhus-associated GBS.

Numerous infectious agents have been associated with the onset of GBS and consequently with the production of antiganglioside antibodies [ 22 ]. Antiganglioside antibodies are detected in more than half of GBS patients, and their detection strongly supports the diagnosis of GBS [ 23 ]. Although antiganglioside antibodies assist in GBS diagnosis, their signal is not strong in GBS caused by scrub typhus infection. Only two patients out of 7 cases in which ganglioside-related antibody testing was performed were positive [ 11 , 13 , 15 , 19 , 20 ]. Furthermore, only GM1, GD1a, GD1b, GT1b, GalNAc-GD1a and anti-sulfatide antibodies were detected in the current reviewed cases of GBS associated with scrub typhus infection. The underlying mechanism may be an immune-mediated type 2 hypersensitivity reaction against self-antigens [ 10 ].

In conclusion, scrub typhus infection is likely to be a potential predisposing factor in GBS, although the immunological mechanisms involved are not clear. The possibility of GBS should be considered in patients who present with symptoms of peripheral neuropathy at the time of scrub typhus infection or after a recent cure. Meanwhile, assessment of whether scrub typhus infection is still present may be necessary. The timely use of antibiotics to treat scrub typhus may improve the symptoms of GBS. For GBS after the cure of tsutsugamushi disease, treatment means such as IVIg or plasmapheresis receive relatively good results. Finally, combined with the current literature that has been reviewed, scrub typhus-associated GBS has a favorable prognosis.

Data availability

Not applicable.

Musa TH, Ahmad T, Wana MN, Li W, Musa HH, Sharun K, et al. The epidemiology, diagnosis and management of scrub typhus disease in China. Hum Vaccines Immunother. 2021;17:3795–805.

Article   CAS   Google Scholar  

Papri N, Islam Z, Leonhard SE, Mohammad QD, Endtz HP, Jacobs BC. Guillain-Barre syndrome in low-income and middle-income countries: challenges and prospects. Nat Rev Neurol. 2021;17:285–96.

Article   PubMed   PubMed Central   Google Scholar  

Meehan GR, McGonigal R, Cunningham ME, Wang Y, Barrie JA, Halstead SK, et al. Differential binding patterns of anti-sulfatide antibodies to glial membranes. J Neuroimmunol. 2018;323:28–35.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Rinaldi S, Brennan KM, Kalna G, Walgaard C, van Doorn P, Jacobs BC, et al. Antibodies to heteromeric glycolipid complexes in Guillain-Barre syndrome. PLoS ONE. 2013;8:e82337.

Dabby R, Weimer LH, Hays AP, Olarte M, Latov N. Antisulfatide antibodies in neuropathy: clinical and electrophysiologic correlates. Neurology. 2000;54:1448–52.

Article   CAS   PubMed   Google Scholar  

Campagnolo M, Ferrari S, Dalla Torre C, Cabrini I, Cacciavillani M, Lucchetta M, et al. Polyneuropathy with anti-sulfatide and anti-MAG antibodies: clinical, neurophysiological, pathological features and response to treatment. J Neuroimmunol. 2015;281:1–4.

Lv Y, Guo XG, Jin DC. Research progress on Leptotrombidium deliense . Korean J Parasitol. 2018;56:313–24.

Rana A, Mahajan SK, Sharma A, Sharma S, Verma BS, Sharma A. Neurological manifestations of scrub typhus in adults. Trop Doct. 2017;47:22–5.

Article   PubMed   Google Scholar  

Misra UK, Kalita J, Mani VE. Neurological manifestations of scrub typhus. J Neurol Neurosurg Psychiatry. 2014;86:761–6.

Garg D, Manesh A. Neurological facets of scrub typhus: a comprehensive narrative review. Ann Indian Acad Neurol. 2021;24:849–64.

Lee SH, Jung SI, Park KH, Choi SM, Park MS, Kim BC, et al. Guillain-Barre syndrome associated with scrub typhus. Scand J Infect Dis. 2007;39:826–8.

Lee MS, Lee JH, Lee HS, Chang H, Kim YS, Cho KH, et al. Scrub typhus as a possible aetiology of Guillain-Barre syndrome: two cases. Ir J Med Sci. 2009;178:347–50.

Ju IN, Lee JW, Cho SY, Ryu SJ, Kim YJ, Kim SI, et al. Two cases of scrub typhus presenting with Guillain-Barre syndrome with respiratory failure. Korean J Intern Med. 2011;26:474–6.

Sawale VM, Upreti S, Singh TS, Singh NB, Singh TB. A rare case of Guillain-Barre syndrome following scrub typhus. Neurol India. 2014;62:82–3.

Kim KW, Kim YH, Kim BH, Lee CY, Oh MS, Yu KH, et al. Miller Fisher syndrome related to orientia tsutsugamushi infection. J Clin Neurosci. 2014;21:2251–2.

Gangula RS, Stanley W, Vandanapu A, Prabhu MM. Guillain-Barre syndrome with falciparum malaria and scrub typhus mixed infection-an unusual combination. J Clin Diagn Res. 2017;11:OD10–1.

PubMed   PubMed Central   Google Scholar  

Dev N, Kumar R, Kumar D. Guillain–Barre syndrome: a rare complication of leptospirosis and scrub typhus co-infection. Trop Doct. 2019;49:248–9.

Juneja A, Anand K, Shah M. Guillain–Barre syndrome: a rare occurrence following scrub typhus. Niger J Med. 2020;29:337–8.

Article   Google Scholar  

Sakai K, Ishii N, Ebihara Y, Mochizuki H, Shiomi K, Nakazato M. Guillan-Barre syndrome following scrub typus: two case reports. Rinsho Shinkeigaku. 2016;56:577–9.

Pandey S, Chaudhari D, Renjen PN, Ahmad K. Guillain-Barre’ syndrome following scrub typhus: a rare case. Ann Indian Acad Neurol. 2021;24:451–2.

Sejvar JJ, Kohl KS, Gidudu J, Amato A, Bakshi N, Baxter R, et al. Guillain-Barre syndrome and Fisher syndrome: case definitions and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine. 2011;29:599–612.

Cutillo G, Saariaho AH, Meri S. Physiology of gangliosides and the role of antiganglioside antibodies in human diseases. Cell Mol Immunol. 2020;17:313–22.

Koga M, Takahashi M, Yokoyama K, Kanda T. Ambiguous value of anti-ganglioside IgM autoantibodies in Guillain-Barre syndrome and its variants. J Neurol. 2015;262:1954–60.

Raghunathan V, Dhaliwal M, Singhi P, Singhi S. Scrub typhus associated with guillain-barre syndrome (GBS). Indian J Pediatr. 2022;89:1129–30.

Modi T, Sood T, Moudgil S, Arora NAO. Neurological manifestations of scrub typhus: encephalitis and Guillain-Barré syndrome (GBS). BMJ Case Rep. 2023;16:e253350.

Download references

Acknowledgements

This study was supported by Hainan Province Clinical Medical Center, Natural Science Foundation of Hainan Province (Ref No.: 823QN343; 821RC675), Hainan Academician Innovation Platform Scientific Research Project (YSPTZX202135) and The innovation platform for Academicians of Hainan Province.

Author information

Shijun Hu and Zhichuan lin have contributed equally to this work and share first authorship.

Authors and Affiliations

Department of Neurology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, P. R. China

Shijun Hu, Zhichuan lin, Tao Liu, Shixiong Huang & Hui Liang

You can also search for this author in PubMed   Google Scholar

Contributions

Shijun Hu and Zhichuan lin carried out the data collection, literature review and drafting of the manuscript. Tao Liu and Shixiong Huang contributed to the drafting of the manuscript and aided in the literature review. Hui Liang help to draft the manuscript and revised the final version of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hui Liang .

Ethics declarations

Ethics approval and consent to participate.

The patient was treated in accordance with the Declaration of Helsinki. The patient provided informed consent for all procedures. Informed consent was obtained from the patient for inclusion in this study.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

The authors report no disclosures relevant to the manuscript.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ . The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article.

Hu, S., lin, Z., Liu, T. et al. Guillain–Barre syndrome following scrub typhus: a case report and literature review. BMC Neurol 24 , 137 (2024). https://doi.org/10.1186/s12883-024-03645-9

Download citation

Received : 04 April 2023

Accepted : 18 April 2024

Published : 25 April 2024

DOI : https://doi.org/10.1186/s12883-024-03645-9

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• Guillain–Barré syndrome
• Anti-sulfatide antibodies
• Scrub typhus
• Case report

BMC Neurology

ISSN: 1471-2377

• General enquiries: [email protected]

• Skip to main content
• Keyboard shortcuts for audio player

• Your Health
• Treatments & Tests
• Health Inc.
• Public Health

How to Thrive as You Age

A cheap drug may slow down aging. a study will determine if it works.

Allison Aubrey

A drug taken by millions of people to control diabetes may do more than lower blood sugar.

Research suggests metformin has anti-inflammatory effects that could help protect against common age-related diseases including heart disease, cancer, and cognitive decline.

Scientists who study the biology of aging have designed a clinical study, known as The TAME Trial, to test whether metformin can help prevent these diseases and promote a longer healthspan in healthy, older adults.

Michael Cantor, an attorney, and his wife Shari Cantor , the mayor of West Hartford, Connecticut both take metformin. "I tell all my friends about it," Michael Cantor says. "We all want to live a little longer, high-quality life if we can," he says.

Michael Cantor started on metformin about a decade ago when his weight and blood sugar were creeping up. Shari Cantor began taking metformin during the pandemic after she read that it may help protect against serious infections.

Shari and Michael Cantor both take metformin. They are both in their mid-60s and say they feel healthy and full of energy. Theresa Oberst/Michael Cantor hide caption

Shari and Michael Cantor both take metformin. They are both in their mid-60s and say they feel healthy and full of energy.

The Cantors are in their mid-60s and both say they feel healthy and have lots of energy. Both noticed improvements in their digestive systems – feeling more "regular" after they started on the drug,

Metformin costs less than a dollar a day, and depending on insurance, many people pay no out-of-pocket costs for the drug.

"I don't know if metformin increases lifespan in people, but the evidence that exists suggests that it very well might," says Steven Austad , a senior scientific advisor at the American Federation for Aging Research who studies the biology of aging.

An old drug with surprising benefits

Metformin was first used to treat diabetes in the 1950s in France. The drug is a derivative of guanidine , a compound found in Goat's Rue, an herbal medicine long used in Europe.

The FDA approved metformin for the treatment of type 2 diabetes in the U.S. in the 1990s. Since then, researchers have documented several surprises, including a reduced risk of cancer. "That was a bit of a shock," Austad says. A meta-analysis that included data from dozens of studies, found people who took metformin had a lower risk of several types of cancers , including gastrointestinal, urologic and blood cancers.

Austad also points to a British study that found a lower risk of dementia and mild cognitive decline among people with type 2 diabetes taking metformin. In addition, there's research pointing to improved cardiovascular outcomes in people who take metformin including a reduced risk of cardiovascular death .

As promising as this sounds, Austad says most of the evidence is observational, pointing only to an association between metformin and the reduced risk. The evidence stops short of proving cause and effect. Also, it's unknown if the benefits documented in people with diabetes will also reduce the risk of age-related diseases in healthy, older adults.

"That's what we need to figure out," says Steve Kritchevsky , a professor of gerontology at Wake Forest School of Medicine, who is a lead investigator for the Tame Trial.

The goal is to better understand the mechanisms and pathways by which metformin works in the body. For instance, researchers are looking at how the drug may help improve energy in the cells by stimulating autophagy, which is the process of clearing out or recycling damaged bits inside cells.

Shots - Health News

Scientists can tell how fast you're aging. now, the trick is to slow it down.

You can order a test to find out your biological age. Is it worth it?

Researchers also want to know more about how metformin can help reduce inflammation and oxidative stress, which may slow biological aging.

"When there's an excess of oxidative stress, it will damage the cell. And that accumulation of damage is essentially what aging is," Kritchevsky explains.

When the forces that are damaging cells are running faster than the forces that are repairing or replacing cells, that's aging, Kritchevsky says. And it's possible that drugs like metformin could slow this process down.

By targeting the biology of aging, the hope is to prevent or delay multiple diseases, says Dr. Nir Barzilai of Albert Einstein College of Medicine, who leads the effort to get the trial started.

The ultimate in preventative medicine

Back in 2015, Austad and a bunch of aging researchers began pushing for a clinical trial.

"A bunch of us went to the FDA to ask them to approve a trial for metformin,' Austad recalls, and the agency was receptive. "If you could help prevent multiple problems at the same time, like we think metformin may do, then that's almost the ultimate in preventative medicine," Austad says.

The aim is to enroll 3,000 people between the ages of 65 and 79 for a six-year trial. But Dr. Barzilai says it's been slow going to get it funded. "The main obstacle with funding this study is that metformin is a generic drug, so no pharmaceutical company is standing to make money," he says.

Barzilai has turned to philanthropists and foundations, and has some pledges. The National Institute on Aging, part of the National Institutes of Health, set aside about $5 million for the research, but that's not enough to pay for the study which is estimated to cost between $45 and $70 million.

The frustration over the lack of funding is that if the trial points to protective effects, millions of people could benefit. "It's something that everybody will be able to afford," Barzilai says.

Currently the FDA doesn't recognize aging as a disease to treat, but the researchers hope this would usher in a paradigm shift — from treating each age-related medical condition separately, to treating these conditions together, by targeting aging itself.

For now, metformin is only approved to treat type 2 diabetes in the U.S., but doctors can prescribe it off-label for conditions other than its approved use .

Michael and Shari Cantor's doctors were comfortable prescribing it to them, given the drug's long history of safety and the possible benefits in delaying age-related disease.

"I walk a lot, I hike, and at 65 I have a lot of energy," Michael Cantor says. I feel like the metformin helps," he says. He and Shari say they have not experienced any negative side effects.

Research shows a small percentage of people who take metformin experience GI distress that makes the drug intolerable. And, some people develop a b12 vitamin deficiency. One study found people over the age of 65 who take metformin may have a harder time building new muscle.

Millions of women are 'under-muscled.' These foods help build strength

"There's some evidence that people who exercise who are on metformin have less gain in muscle mass, says Dr. Eric Verdin , President of the Buck Institute for Research on Aging. That could be a concern for people who are under-muscled .

But Verdin says it may be possible to repurpose metformin in other ways "There are a number of companies that are exploring metformin in combination with other drugs," he says. He points to research underway to combine metformin with a drug called galantamine for the treatment of sarcopenia , which is the medical term for age-related muscle loss. Sarcopenia affects millions of older people, especially women .

The science of testing drugs to target aging is rapidly advancing, and metformin isn't the only medicine that may treat the underlying biology.

"Nobody thinks this is the be all and end all of drugs that target aging," Austad says. He says data from the clinical trial could stimulate investment by the big pharmaceutical companies in this area. "They may come up with much better drugs," he says.

Michael Cantor knows there's no guarantee with metformin. "Maybe it doesn't do what we think it does in terms of longevity, but it's certainly not going to do me any harm," he says.

Cantor's father had his first heart attack at 51. He says he wants to do all he can to prevent disease and live a healthy life, and he thinks Metformin is one tool that may help.

For now, Dr. Barzilai says the metformin clinical trial can get underway when the money comes in.

7 habits to live a healthier life, inspired by the world's longest-lived communities

This story was edited by Jane Greenhalgh

In-situ study of the effect of grain boundary misorientation on plastic deformation of Inconel 718 at high temperature

• Metals & corrosion
• Published: 24 April 2024

Cite this article

• Jutian Chen 1 ,
• Junxia Lu   ORCID: orcid.org/0000-0003-3365-4716 1 ,
• Xiaopeng Cheng 1 ,
• Yuefei Zhang 2 &
• Ze Zhang 2  

The effect of the grain boundary (GB) misorientation on plastic deformation of Inconel 718 (IN718) alloy was investigated in this paper, using in-situ tensile experiment at 650 °C in combination with crystal plasticity finite element method (CPFEM). The results indicate that dislocations tend to accumulate at GBs to form stress concentration, but the degree of stress concentration does not necessarily increase with the increase of the GB misorientation. It is attributed to the slip transfer at the GBs, determined by the angle between the slip systems of the two adjacent grains. There is a significant uncertainty in the slip transfer for GB misorientation larger than 10°. However, the \(m_{{{\alpha \beta }}}^{\prime} \left( {{\text{SF}}_{\alpha } + {\text{SF}}_\beta } \right)\) criterion, which is a function of the Luster and Morris \(m_{{{\alpha \beta }}}^{\prime}\) combining the Schmid factors of the two slip systems with the GB misorientation, has some statistical separation significance. Slip transfer tends to appear at GB misorientation less than 30° and \(m_{{{\alpha \beta }}}^{\prime} \left( {{\text{SF}}_{\alpha } + {\text{SF}}_\beta } \right) > 0.78\) . This study clarifies the mechanism of the influence of GB misorientation on IN718 microplastic deformation and provides a new strategy to study the deformation behavior of superalloys.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price includes VAT (Russian Federation)

Instant access to the full article PDF.

Rent this article via DeepDyve

Institutional subscriptions

Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

Gao WJ, Lu JX, Zhou JL, Liu LE, Wang J, Zhang YF, Zhang Z (2022) Effect of grain size on deformation and fracture of Inconel718: An in-situ SEM-EBSD-DIC investigation. Mater Sci Eng A 861:144361. https://doi.org/10.1016/j.msea.2022.144361

Article   CAS   Google Scholar  

Alqawasmi L, Bijjala ST, Khraishi T, Kumar P (2023) Mechanical property heterogeneity in Inconel 718 superalloy manufactured by directed energy deposition. J Mater Sci. https://doi.org/10.1007/s10853-023-09249-x

Article   Google Scholar  

Lyu H, Ruimi A (2023) Synergetic effect of initial shear texture and grain size gradient on plastic deformation of gradient interstitial free (IF) steel. J Mater Sci. https://doi.org/10.1007/s10853-023-09045-7

Kheradmand N, Knorr AF, Marx M, Deng Y (2016) Microscopic incompatibility controlling plastic deformation of bicrystals. Acta Mater 106:219–228. https://doi.org/10.1016/j.actamat.2016.01.006

Kobayashi S, Terakado M, Ebata K, Tsutsui H, Yamamuro T, Tsurekawa S (2023) Low-angle grain boundary engineering based on texture control for enhancement of corrosion and fatigue resistance in 436L type ferritic stainless steel. J Mater Sci. https://doi.org/10.1007/s10853-023-09227-3

Demir E, Gutierrez-Urrutia I (2021) Investigation of strain hardening near grain boundaries of an aluminum oligocrystal: Experiments and crystal based finite element method. Int J Plast 136:102898. https://doi.org/10.1016/j.ijplas.2020.102898

Zhou H, Wang P, Lu S (2021) Investigation on the effects of grain boundary on deformation behavior of bicrystalline pillar by crystal plasticity finite element method. Crystals 11:923. https://doi.org/10.3390/cryst11080923

Sperry R, Harte A, da Fonseca JQ, Homer ER, Wagoner RH, Fullwood DT (2020) Slip band characteristics in the presence of grain boundaries in nickel-based superalloy. Acta Mater 193:229–238. https://doi.org/10.1016/j.actamat.2020.04.037

Pai NM, Prakash A, Samajdar I, Patra A (2022) Study of grain boundary orientation gradients through combined experiments and strain gradient crystal plasticity modeling. Int J Plast 156:103360. https://doi.org/10.1016/j.ijplas.2022.103360

Hall EO (1951) The deformation and ageing of mild steel: III discussion of results. Proc Phys Soc B 64:747. https://doi.org/10.1088/0370-1301/64/6/305

Kedharnath A, Kapoor R, Sarkar A (2023) Dislocation–grain boundary interactions in Ta: numerical, molecular dynamics, and machine learning approaches. J Mater Sci. https://doi.org/10.1007/s10853-023-09167-y

Luster J, Morris MA (1995) Compatibility of deformation in two-phase Ti-Al alloys: dependence on microstructure and orientation relationships. Metall Mater Trans A 26:1745–1756. https://doi.org/10.1007/BF02670762

Malyar NV, Dehm G, Kirchlechner C (2017) Strain rate dependence of the slip transfer through a penetrable high angle grain boundary in copper. Scripta Mater 138:88–91. https://doi.org/10.1016/j.scriptamat.2017.05.042

Weaver JS, Li N, Mara NA, Jones DR, Cho H, Bronkhorst CA, Fensin SJ, Gray GT III (2018) Slip transmission of high angle grain boundaries in body-centered cubic metals: micropillar compression of pure Ta single and bi-crystals. Acta Mater 156:356–368. https://doi.org/10.1016/j.actamat.2018.06.046

Heller M, Gibson JSK-L, Pei R, Korte-Kerzel S (2020) Deformation of µm-and mm-sized Fe2.4wt% Si single-and bi-crystals with a high angle grain boundary at room temperature. Acta Mater 194:452–463. https://doi.org/10.1016/j.actamat.2020.04.011

Rizwan M, Lu JX, Ullah R, Zhang YF, Zhang Z (2022) Microstructural and texture evolution investigation of laser melting deposited TA15 alloy at 500 ℃ using in-situ EBSD tensile test. Mater Sci Eng A 857:144062. https://doi.org/10.1016/j.msea.2022.144062

Cai W, Sun CY, Wang CH, Qian LY, Li YM, Fu MW (2022) Modelling of the intergranular fracture of TWIP steels working at high temperature by using CZM–CPFE method. Int J Plast 156:103366. https://doi.org/10.1016/j.ijplas.2022.103366

Lu JX, Chang L, Wang J, Sang LJ, Wu SK, Zhang YF (2018) In-situ investigation of the anisotropic mechanical properties of laser direct metal deposition Ti6Al4V alloy. Mater Sci Eng A 712:199–205. https://doi.org/10.1016/j.msea.2017.11.106

Wang J, Lu JX, You XX, Ullah R, Sang LJ, Chang L, Zhang YF, Zhang Z (2019) In-situ comparison of deformation behavior at 23 ℃ and 650 ℃ of laser direct melting deposited Ti-6Al-4V alloy. Mater Sci Eng A 749:48–55. https://doi.org/10.1016/j.msea.2019.01.111

Chen JT, Lu JX, Cai W, Zhang YF, Wang YF, Jiang WX, Rizwan M, Zhang Z (2023) In-situ study of adjacent grains slip transfer of Inconel 718 during tensile process at high temperature. Int J Plast 163:103554. https://doi.org/10.1016/j.ijplas.2023.103554

He WL, Lu JX, Li FQ, Jiang WX, Wang J, Zhang YF, Zhang Z (2022) In situ SEM study of creep deformation behavior of nickel-based single-crystal superalloys. J Mater Sci 57:13647–13659. https://doi.org/10.1007/s10853-022-07397-0

Sang LJ, Lu JX, Wang J, Ullah R, Sun XC, Zhang YF, Zhang Z (2021) In-situ SEM study of temperature-dependent tensile behavior of Inconel 718 superalloy. J Mater Sci 56:16097–16112. https://doi.org/10.1007/s10853-021-06256-8

Blum W, Eisenlohr P (2009) Dislocation mechanics of creep. Mater Sci Eng A 510:7–13. https://doi.org/10.1016/j.msea.2008.04.110

Kubin L, Devincre B, Hoc T (2008) Modeling dislocation storage rates and mean free paths in face-centered cubic crystals. Acta Mater 56:6040–6049. https://doi.org/10.1016/j.actamat.2008.08.012

Zhang WJ, Lu JX, Wang J, Sang LJ, Ma JY, Zhang YF, Zhang Z (2020) In-situ EBSD study of deformation behavior of Inconel 740H alloy at high-temperature tensile loading. J Alloy Compd 820:153424. https://doi.org/10.1016/j.jallcom.2019.153424

Saravanan K, Sharma VMJ, Ramesh Narayanan P, Sharma SC, Koshy MG (2015) On the measurement of dynamic elastic and internal friction properties of nickel based super alloys up to 650 ℃ temperature. Mater Sci Forum 830–831:203–206. https://doi.org/10.4028/www.scientific.net/MSF.830-831.203

Reuber C, Eisenlohr P, Roters F, Raabe D (2014) Dislocation density distribution around an indent in single-crystalline nickel: comparing nonlocal crystal plasticity finite-element predictions with experiments. Acta Mater 71:333–348. https://doi.org/10.1016/j.actamat.2014.03.012

Cordero B, Gómez V, Platero-Prats AE, Revés M, Echeverría J, Cremades E, Barragán F, Alvarez S (2008) Covalent radii revisited. Dalton T. https://doi.org/10.1039/B801115J

Jia N, Roters F, Eisenlohr P, Kords C, Raabe D (2012) Non-crystallographic shear banding in crystal plasticity FEM simulations: example of texture evolution in α-brass. Acta Mater 60:1099–1115. https://doi.org/10.1016/j.actamat.2011.10.047

Zhang C, Zhang L-W, Shen W-F, Xia Y-N, Yan Y-T (2017) 3D crystal plasticity finite element modeling of the tensile deformation of polycrystalline ferritic stainless steel. Acta Metall Sin-Engl 30:79–88. https://doi.org/10.1007/s40195-016-0488-9

Guo Y, Collins DM, Tarleton E, Hofmann F, Wilkinson AJ, Ben Britton T (2020) Dislocation density distribution at slip band-grain boundary intersections. Acta Mater 182:172–183. https://doi.org/10.1016/j.actamat.2019.10.031

Taylor GI (1938) Plastic strain in metals. J Inst Metals 62:307–324

Google Scholar  

Zaefferer S, Kuo J-C, Zhao Z, Winning M, Raabe D (2003) On the influence of the grain boundary misorientation on the plastic deformation of aluminum bicrystals. Acta Mater 51:4719–4735. https://doi.org/10.1016/S1359-6454(03)00259-3

Zhou BJ, Li YJ, Wang LY, Jia HL, Zeng XQ (2022) The role of grain boundary plane in slip transfer during deformation of magnesium alloys. Acta Mater 227:117662. https://doi.org/10.1016/j.actamat.2022.117662

Mayeur JR, Beyerlein IJ, Bronkhorst CA, Mourad HM (2015) Incorporating interface affected zones into crystal plasticity. Int J Plast 65:206–225. https://doi.org/10.1016/j.ijplas.2014.08.013

Tiba I, Richeton T, Motz C, Vehoff H, Berbenni S (2015) Incompatibility stresses at grain boundaries in Ni bicrystalline micropillars analyzed by an anisotropic model and slip activity. Acta Mater 83:227–238. https://doi.org/10.1016/j.actamat.2014.09.033

Download references

Acknowledgements

The authors gratefully acknowledge the support of Beijing Natural Science Foundation (2232042), Basic Science Center Program for Multiphase Media Evolution in Hypergravity of the National Natural Science Foundation of China (No. 51988101), and Key projects of Beijing Natural Science Foundation (Kz202110005006).

Author information

Authors and affiliations.

College of Materials Science and Engineering, Beijing University of Technology, Beijing, 100124, China

Jutian Chen, Junxia Lu & Xiaopeng Cheng

School of Materials Science and Engineering, Zhejiang University, Hangzhou, 310058, China

Yuefei Zhang & Ze Zhang

You can also search for this author in PubMed   Google Scholar

Contributions

Jutian Chen performed investigation, data curation, and writing—original draft preparation. Junxia Lu prepared writing—reviewing and editing. Xiaopeng Cheng approved conceptualization and supervision. Yuefei Zhang provided methodology. Ze Zhang did methodology and Supervision.

Corresponding authors

Correspondence to Junxia Lu or Yuefei Zhang .

Ethics declarations

Conflict of interest.

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Ethical approval

Not Applicable.

Additional information

Handling Editor: Sophie Primig.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 4239 kb)

Rights and permissions.

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Chen, J., Lu, J., Cheng, X. et al. In-situ study of the effect of grain boundary misorientation on plastic deformation of Inconel 718 at high temperature. J Mater Sci (2024). https://doi.org/10.1007/s10853-024-09627-z

Download citation

Received : 03 January 2024

Accepted : 30 March 2024

Published : 24 April 2024

DOI : https://doi.org/10.1007/s10853-024-09627-z

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Advertisement

• Find a journal
• Publish with us
• Track your research

About 1 in 4 U.S. Adults Over 50 Say They Expect to Never Retire, Study Finds

(WASHINGTON, D.C.) — About one-quarter of U.S. adults over age 50 say they expect to never retire and 70% are concerned about prices rising faster than their income, an AARP survey finds.

About 1 in 4 have no retirement savings, according to research released Wednesday by the organization that shows how a graying America is worrying more and more about how to make ends meet even as economists and policymakers say the U.S. economy has all but  achieved a soft landing  after two years of record inflation.

Everyday expenses and housing costs, including rent and mortgage payments, are the biggest reasons why people are unable to save for retirement.

The data will matter this election year as Democratic President Joe Biden and Republican rival Donald Trump are trying to win support from older Americans, who traditionally turn out in high numbers, with their policy proposals.

The AARP's study, based on interviews completed with more than 8,000 people in coordination with the NORC Center for Public Affairs Research, finds that one-third of older adults with credit card debt carry a balance of more than $10,000 and 12% have a balance of $20,000 or more. Additionally, 37% are worried about meeting basic living costs such as food and housing.

“Far too many people lack access to retirement savings options and this, coupled with higher prices, is making it increasingly hard for people to choose when to retire,” said Indira Venkateswaran, AARP's senior vice president of research. “Everyday expenses continue to be the top barrier to saving more for retirement, and some older Americans say that they never expect to retire.”

The share of people older than 50 who say they do not expect to retire has steadily increased. It was 23% in January 2022 and 24% that July, according to the study, which is conducted twice a year.

"We are seeing an expansion of older workers staying in the workforce," said David John, senior strategic policy advisor at the AARP Public Policy Institute. He said this is in part because older workers “don't have sufficient retirement savings. It's a problem and its likely to continue as we go forward.”

Based on the 2022 congressional elections,  census data released Tuesday  shows that voters 65 and older made up 30.4% of all voters, while Gen Z and millennials accounted for 11.7%.

Biden has tried to court older voters by  regularly promoting  a  $35 price cap  on insulin for people on Medicare. He trumpets  Medicare’s  powers to negotiate directly with drugmakers on the cost of prescription medications.

Trump, in an interview with CNBC in March, indicated he would be open to cuts to Social Security and Medicare. The former president said “there is a lot you can do in terms of entitlements, in terms of cutting.”

Karoline Leavitt, press secretary for Trump's campaign, said in a statement to The Associated Press on Tuesday that Trump “will continue to strongly protect Social Security and Medicare in his second term."

In the AARP survey, 33% of respondents older than 50 believe their finances will be better in a year.

A looming issue that will affect Americans' ability to retire is the financial health of Social Security and Medicare.

The latest annual report from the program's trustees says the financial safety nets for millions of older Americans will run short of money to pay full benefits within the next decade.

Medicare, the government-sponsored health insurance that covers 65 million older and disabled people, will be unable to pay full benefits for inpatient hospital visits and nursing home stays by 2031, the report forecast. And just two years later, Social Security will not have enough cash on hand to pay out full benefits to its 66 million retirees.

An AP-NORC poll from March 2023 found that most U.S. adults are opposed to proposals that would cut into Medicare or Social Security benefits, and a majority support raising taxes on the nation’s highest earners to keep Medicare running as is.

More Must-Reads From TIME

• The 100 Most Influential People of 2024
• Coco Gauff Is Playing for Herself Now
• Scenes From Pro-Palestinian Encampments Across U.S. Universities
• 6 Compliments That Land Every Time
• If You're Dating Right Now , You're Brave: Column
• The AI That Could Heal a Divided Internet
• Fallout Is a Brilliant Model for the Future of Video Game Adaptations
• Want Weekly Recs on What to Watch, Read, and More? Sign Up for Worth Your Time

Contact us at [email protected]

About 1 in 4 US adults 50 and older who aren't yet retired expect to never retire, AARP study finds

WASHINGTON — About one-quarter of U.S. adults age 50 and older who are not yet retired say they expect to never retire and 70% are concerned about prices rising faster than their income, an AARP survey finds.

About 1 in 4 have no retirement savings, according to research released Wednesday by the organization that shows how a graying America is worrying more and more about how to make ends meet even as economists and policymakers say the U.S. economy has all but achieved a soft landing after two years of record inflation.

Everyday expenses and housing costs, including rent and mortgage payments, are the biggest reasons why people are unable to save for retirement.

The data will matter this election year as Democratic President Joe Biden and Republican rival Donald Trump are trying to win support from older Americans, who traditionally turn out in high numbers, with their policy proposals.

The AARP’s study, based on interviews completed with more than 8,000 people in coordination with the NORC Center for Public Affairs Research, finds that one-third of older adults with credit card debt carry a balance of more than $10,000 and 12% have a balance of $20,000 or more. Additionally, 37% are worried about meeting basic living costs such as food and housing.

“Far too many people lack access to retirement savings options and this, coupled with higher prices, is making it increasingly hard for people to choose when to retire,” said Indira Venkateswaran, AARP’s senior vice president of research. “Everyday expenses continue to be the top barrier to saving more for retirement, and some older Americans say that they never expect to retire.”

The share of people 50 and older who say they do not expect to retire has remained steady. It was 23% in January 2022 and 24% that July, according to the study, which is conducted twice a year

“We are seeing an expansion of older workers staying in the workforce,” said David John, senior strategic policy advisor at the AARP Public Policy Institute. He said this is in part because older workers “don’t have sufficient retirement savings. It’s a problem and its likely to continue as we go forward.”

Based on the 2022 congressional elections, census data released Tuesday shows that voters 65 and older made up 30.4% of all voters, while Gen Z and millennials accounted for 11.7%.

Biden has tried to court older voters by regularly promoting a $35 price cap on insulin for people on Medicare. He trumpets Medicare’s powers to negotiate directly with drugmakers on the cost of prescription medications.

Trump, in an interview with CNBC in March, indicated he would be open to cuts to Social Security and Medicare. The former president said “there is a lot you can do in terms of entitlements, in terms of cutting.”

Karoline Leavitt, press secretary for Trump’s campaign, said in a statement to The Associated Press on Tuesday that Trump “will continue to strongly protect Social Security and Medicare in his second term.”

In the AARP survey, 33% of respondents 50 and older believe their finances will be better in a year.

A looming issue that will affect Americans’ ability to retire is the financial health of Social Security and Medicare.

The latest annual report from the program’s trustees says the financial safety nets for millions of older Americans will run short of money to pay full benefits within the next decade.

Medicare, the government-sponsored health insurance that covers 65 million older and disabled people, will be unable to pay full benefits for inpatient hospital visits and nursing home stays by 2031, the report forecast. And just two years later, Social Security will not have enough cash on hand to pay out full benefits to its 66 million retirees.

An AP-NORC poll from March 2023 found that most U.S. adults are opposed to proposals that would cut into Medicare or Social Security benefits, and a majority support raising taxes on the nation’s highest earners to keep Medicare running as is.

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

• Advanced Search
• Journal List

Patients’ experiences and perceptions of Guillain-Barré syndrome: A systematic review and meta-synthesis of qualitative research

Despina laparidou.

1 Community and Health Research Unit, School of Health and Social Care, University of Lincoln, Lincoln, Lincolnshire, United Kingdom

Ffion Curtis

2 Lincoln International Institute for Rural Health, University of Lincoln, Lincoln, Lincolnshire, United Kingdom

Joseph Akanuwe

Jennifer jackson.

3 Lincoln International Business School, University of Lincoln, Lincoln, Lincolnshire, United Kingdom

Timothy L. Hodgson

4 School of Psychology, University of Lincoln, Lincoln, Lincolnshire, United Kingdom

A. Niroshan Siriwardena

Associated data.

All relevant data are within the manuscript and its Supporting Information files.

Guillain-Barré syndrome (GBS) is an immune-mediated polyradiculoneuropathy, with an incidence of 1-2/100,000 per year. Its severity is variable, ranging from very mild cases with brief weakness to severe paralysis, leading to inability to breathe independently, or even death. Currently there is limited evidence exploring the experiences of GBS patients. The aim of this study was to review patients’ experiences and perceptions of GBS and its variants at diagnosis, discharge and during recovery, by conducting a systematic review and thematic meta-synthesis of qualitative studies of patients’ experiences of GBS (and its variants).

We searched twelve electronic databases, supplemented with internet searches and forward and backward citation tracking from the included studies and review articles. Data were synthesised thematically following the Thomas and Harden approach. The CASP Qualitative Checklist was used to assess the quality of the included studies of this review.

Our search strategy identified a total of 5,282 citations and after removing duplicates and excluding citations based on title and abstract, and full-text screening, five studies were included in the review and meta-synthesis; all included studies were considered of acceptable quality. Through constant discussions and an iterative approach, we developed six analytical themes following a patient’s journey from suspecting that they had a health problem, through to being hospitalised, experiencing ongoing difficulties, slowly recovering from GBS, adjusting to their new circumstances, and re-evaluating their lives.

Conclusions

Despite the variety of experiences, it was evident from all included studies that being diagnosed with and surviving GBS was a life-changing experience for all participants.

Trial registration

Protocol was registered ( CRD42019122199 ) on the International Prospective Register of Systematic Reviews ( http://www.crd.york.ac.uk/PROSPERO ).

Guillain-Barré syndrome (GBS) is an immune-mediated polyradiculoneuropathy, with an incidence of 1-2/100,000 per year [ 1 ]. GBS can affect anyone and at any age, although it is more frequent in adults and older people [ 2 ]. It has a highly variable onset, clinical severity and course, and there are several variants of GBS (including chronic inflammatory demyelinating polyradiculoneuropathy and Miller-Fisher syndrome) [ 3 ]. In most cases, GBS has an acute (4 hours) to subacute (up to 1 week) onset with symmetrical weakness and numbness of the limbs progressing proximally, usually over 2–4 weeks, causing loss of reflexes [ 3 ]. Although most patients recover (70% eventually experience full recovery), for some recovery can be slow or incomplete; for example, about 30 percent of individuals diagnosed with GBS have residual weakness after 3 years and about 15 percent experience long-term weakness [ 2 ]. So even though GBS is not considered a chronic condition, it often has long-term effects and patients may have ongoing neurological deficits that affect their quality of life, their work and social lives [ 4 , 5 ].

Currently there is limited evidence exploring the experiences of individuals who have had GBS. Previous research highlights the significant impact of GBS on individuals and their families. One study [ 6 ] exploring the presence of residual symptoms and the long-term effect of GBS on patients’ daily lives, working activities, hobbies and social status, showed that, at follow-up, most patients had made a complete functional recovery; however, almost a third had to make substantial changes in their daily lives including jobs, hobbies or social activities. Similarly, Khan and colleagues [ 7 ], examining factors impacting long-term health-related outcomes in GBS survivors, found that it had moderate to extreme impact on ability to participate in work, family, and social activities for 16% of participants. GBS also had a substantial impact on mood, confidence and ability to live independently for 22% of their sample, while moderate to extreme depression, anxiety and stress were also reported. Another study [ 8 ] exploring utilization of and satisfaction with healthcare resources, informal help and the burden of care on family caregivers during the first 2 years after onset, found that although most participants were satisfied with their overall care, they were less satisfied with the information they received about GBS or with the cost of care. At 2 years after onset, almost a third of participants still depended on informal carers and their spouses, often expressing increased concern and responsibility for their household and family. Finally, a systematic review [ 9 ] of the literature on GBS patients’ quality of life after onset of the disease concluded that many patients felt limited by their condition, even years after the onset, and that GBS had a lasting psychosocial impact, affecting patients’ mental well-being, daily activities and work life.

Theoretical perspective

We used two theoretical models to facilitate data gathering, analysis and interpretation of the experiences of patients with GBS, the Illness Trajectory Framework (ITF) [ 10 ] and Taylor’s [ 11 ] theory of cognitive adaptation to threatening events.

According to the ITF [ 10 ], chronic illnesses follow a course or trajectory which, although different for each individual, have eight common trajectory phases , which involve changes in health and the type of interventions or trajectory scheme needed: pre-trajectory, trajectory onset, crisis, acute, stable, unstable, downward, and dying. Overall, the ITF argues that chronic illness (and management) has an effect on different aspects of individual’s identity, forcing patients to make identity adaptations to live ( come to terms ) with their chronic condition, its consequences and their own mortality.

The [ 11 ] theory of adaptation can be viewed as complementary to ITF, focusing particularly on the individual’s cognitive response when faced with a threat. According to Taylor [ 11 ], when individuals are faced with a threatening event, such as a serious illness like GBS, they go through a readjustment process, during which they try to understand why the event happened, what caused it, and how it has affected their lives. Patients also try to regain mastery over their illness, while avoiding something similar happening again, as well as find ways to feel good about themselves again and enhance, or restore, their self-esteem. Often, making favourable social comparisons is the key to such enhancing attempts to regain control, whereby patients try to cope by feeling better off than others in the same situation, thus, making more positive self-evaluations and ultimately feeling better adjusted and able to cope with their illness.

The findings of this review will provide insights into the patient journey, which could be useful in informing patient care and support services.

Aim of the study

Given the severity of GBS and how variable its onset and course are, it is imperative to explore in depth the patients’ experiences of GBS at the time of diagnosis, during their hospitalisation, in the period post-discharge from hospital and on their return to the community, in order to better understand this patient group’s health and social care needs, as well as explore any potential facilitators and barriers to recovery and return to function. Furthermore, based on our preliminary searches, to date no systematic reviews of qualitative studies exploring patients’ experiences of GBS have been published.

The aim of this study was to review patients’ experiences and perceptions of GBS and its variants at diagnosis, discharge and during recovery, by conducting a systematic review and thematic meta-synthesis of qualitative studies of patients’ experiences of GBS (and its variants).

We followed ENTREQ guidelines for enhancing transparency in reporting the synthesis of qualitative research [ 12 ]. The review protocol was registered with the PROSPERO International prospective register of systematic reviews [ 13 ] and is available from: http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42019122199 .

Our review question was: What are patients’ experiences and perceptions of GBS and chronic inflammatory demyelinating polyneuropathy (CIDP) and its care at diagnosis, discharge and during recovery?

Inclusion criteria

Studies were eligible for inclusion if they had a qualitative research design (e.g. interviews, focus groups, ethnography) and reported on patients’ lived experience of GBS and CIDP. Healthcare services (including the treatment, care and support they provide) have changed considerably in the last 20 years and consequently so has patient experience of care. To ensure that the reviewed patient experiences are relevant to the present day and can inform improvements in current practice, only studies published between January 2000 and May 2020 were eligible for inclusion. In addition, only peer reviewed studies, written in English were considered for eligibility.

Qualitative studies published outside these dates or in other languages were excluded. Quantitative studies were also not eligible for inclusion, since we were interested in patients’ lived experience of GBS and CIDP and we wanted to include in depth accounts of their experiences (preferably expressed in their own words, i.e. by using quotes).

Information sources and search strategy

Electronic database searches were performed in the Cochrane Library, Joanna Briggs Institute Evidence-Based Practice Database, PROSPERO, MEDLINE, Academic Search Complete, AMED, CINAHL, Humanities International Index, PsycARTICLES, PsycINFO, EMBASE, and PubMed. All databases searches were supplemented with internet searches (i.e. Google Scholar), and forward and backward citation tracking from the included studies and review articles.

The search strategy used in all the above databases included a combination of two sets of keywords and related terms: 1) Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), acute inflammatory demyelinating polyneuropathy (AIDP); combined with 2) qualitative research, interview, focus group, experiences, perceptions, attitudes, and views. The search terms were entered using Boolean operators and truncation, wherever deemed necessary. Medical Subject Headings (MeSH) were also employed in forming the search strategy. For the full search strategy used for the Medline database, see Table 1 .

Study selection and data extraction

All references were reviewed and screened by three reviewers (FC, DL, JA) independently. Titles and abstracts were initially screened for relevance and final eligibility was assessed through full-text screening against the inclusion criteria, using a pre-designed study selection form. Any disagreement between the reviewers over the eligibility of references was resolved through discussion between the reviewers, and in consultation with a fourth reviewer (ANS) when necessary.

A standardised, pre-piloted form was used to extract data from the included studies for assessment of quality and data synthesis. Extracted information included: study details (title, authors, date, country), methods (aims, objectives, research questions, study design, setting, data collection methods), participant characteristics (demographics, inclusion/exclusion criteria, method of recruitment, sample selection, sample size), and study findings (main and secondary outcomes, data analysis, conclusions). One reviewer extracted data and a second reviewer checked the data extractions for accuracy. Any discrepancies were resolved through discussion and missing data were requested from study authors.

Data synthesis

Data were entered into NVivo 11 qualitative data analysis software to facilitate analysis. We used thematic synthesis to synthesise the data, following the Thomas and Harden [ 14 ] approach. Initially, three reviewers (DL, FC, JA) independently coded the ‘results’ sections (and ‘discussion’ sections, where new concepts were introduced) of the included papers line-by-line, according to meaning and content, using an inductive approach. Consequently, these free codes of findings were organised into 'descriptive' themes that encompassed the meaning of groups of the initial codes. Finally, based on the codes and ‘descriptive’ themes and through discussion with the wider review team, the final 'analytical' themes were developed.

We followed an inductive approach to analyse and synthesise the data, rather than imposing the illness trajectory framework (ITF) or Taylor’s theory of cognitive adaptation onto our results. Instead, we used both these models to interpret the results and describe the patient journey from experiencing the first GBS symptoms to hospital discharge and recovery (see Discussion below).

Quality assessment of studies

The Critical Appraisal Skills Programme (CASP) Qualitative Checklist [ 15 ] was used to assess the quality of the included studies of this review. Low quality, however, was not a criterion for exclusion of a study, since we were interested in the synthesis and interpretation of all relevant and sufficiently rich data. The CASP qualitative checklist aims to assess various elements of qualitative research studies, including research aims, appropriate methodology, research design and strategy, methods of data collection and communication between researchers and participants, ethical considerations, rigor of data analysis, and the clarity and value of study findings.

Three reviewers (JA, FC, DL) independently assessed the quality of the included studies. Discrepancies were resolved by discussion and consensus, and in consultation with a fourth reviewer when needed (ANS).

Reflexive statement

Reflexivity enables authors to recognise the assumptions and preconceptions they bring into the research and may influence the research process, while allowing the reader to understand the dynamics between the researcher and the researched. This review was commissioned and developed in discussion with the chief executive and chair of the board of trustees of the charity ‘Guillain-Barré and associated Inflammatory Neuropathies’ (GAIN). GAIN was the main funder of the study and helped develop the review’s main objectives: exploring GBS patients’ experience of care, particularly focussing on the period following discharge from hospital and return to the community.

The reviewers (except for ANS and JA) had no prior knowledge of or experience with GBS. DL, a psychologist by background and a researcher in health services, has experience in quantitative systematic reviews and in the analysis of qualitative data. FC is a research fellow whose research predominantly focuses on non-pharmacological interventions for the prevention and management of chronic conditions. She has experience conducting systematic reviews of both quantitative and qualitative studies. JA has a background in clinical nursing and public health with expertise in qualitative and quantitative research methods, and systematic reviews. As a nurse, JA has general clinical knowledge of GBS. JJ is a community researcher with interest in the patient and service user experience, as well as extensive experience of qualitative and engaged research within the public sector, community and voluntary groups. TLH is a psychologist with interest in cognitive deficits in patients with neurodegenerative disorders, with experience of analysis of quantitative data and knowledge of the neurology of cognition and perception. ANS is a clinical academic general practitioner (GP) by background with expertise in social science methods, including systematic reviews, qualitative meta-syntheses and qualitative studies more generally. He has general clinical expertise and insight into GBS but is not an expert on the condition itself.

Familiarisation with the papers included in this review, together with being aware of the existence of GBS-dedicated charities, may have influenced the authors’ suggestions regarding potential sources of support for patients in the future; such support may be available from multiple sources, and our view may have been influenced by the funding for this study.

The search strategy identified a total of 5,282 citations. After removing duplicates and excluding citations based on title and abstract, 63 articles remained for full-text screening. A further 58 articles were excluded based on inclusion/exclusion criteria (main reasons for exclusion: paper not written in English, and/or a quantitative design), leaving five studies to be included in the review and meta-synthesis. Fig 1 presents a flowchart illustrating the results of the selection process.

Characteristics of included studies

The five included studies ( Table 2 ) were published between 2003 and 2015 and were from four countries: Australia [ 16 ], Sweden [ 17 , 18 ], UK [ 19 ], and, USA [ 20 ]. One study [ 20 ] was a PhD thesis. All studies interviewed people living with GBS; none of the studies included participants diagnosed with other variants of GBS, such as CIDP or Miller-Fisher syndrome. All studies contained both men and women, but there were more male participants overall (55/94). Participants’ ages ranged from 16 to 80 years. Studies were based on individual semi-structured interviews only; none included focus groups. Various methods of analysis were employed in the studies, including content analysis [ 17 , 18 , 20 ], interpretative phenomenological analysis [ 19 ], and the constant comparative method [ 16 ]. Most of the studies focused on the overall experiences of people during hospital care or recovering from GBS, whereas one study [ 19 ] focused specifically on their experiences returning to work following recovery from GBS.

* PhD thesis.

Table 3 presents the results of the critical appraisal of the five studies, using the CASP criteria for qualitative research. All included studies were considered of acceptable quality. It should be noted here that three [ 16 , 17 , 20 ] of the five studies performed less well on the reflexivity question (CASP 06) and one study [ 17 ] performed less well on four CASP questions, since not enough relevant information was reported in the papers.

After initial coding and development of descriptive themes, we developed six analytical themes ( Table 4 ). We organised the themes chronologically into a model representing a patient’s journey from their initial suspicion that they had a health problem, through to being hospitalised, experiencing ongoing difficulties, slowly recovering from GBS, and resuming their everyday lives.

From uncertainty to hope

Participants tried to ignore initial strange sensations due to GBS [ 17 , 20 ]. As the condition deteriorated, they attempted to explain their symptoms as the result of normal everyday activities or occurrences (such as medication side effects or tiredness), or feared having better known conditions, such as cancer [ 17 , 19 , 20 ]. On occasions, healthcare professionals either misdiagnosed their symptoms (e.g. thinking the participant was having a stroke) or felt they were feigning illness [ 20 ].

Uncertainty for participants often became overwhelming, making them eager to find out what was happening to them [ 17 , 20 ].This feeling of uncertainty was made worse by a general lack of information and knowledge of GBS, among patients and healthcare professionals [ 16 , 17 , 20 ]. Most participants had never heard of GBS and felt that healthcare professionals were lacking knowledge of and experience with GBS, which they did not find comforting, and left them needing more information about their illness [ 20 ]. Often patients’ families and friends that had to find information about GBS themselves, mainly through searching on the internet [ 16 , 20 ]. Many participants would have liked to have received more information about GBS to improve their understanding of their condition, but also because they found information about GBS, especially on prognosis and recovery, to be reassuring [ 16 , 17 , 20 ].

Although some participants were sad and disappointed about the long recovery ahead of them, many relied on the prospect of a positive prognosis and hoped for a full recovery [ 17 ]; indeed, participants’ hope of recovery was their main motivation, giving them the courage to continue [ 16 – 18 ].

Feeling lost in a changing life

Having GBS affected every aspect of participants’ daily lives [ 16 – 20 ]. A variety of physical symptoms and problems were experienced at onset, starting with numbness or tingling in hands and feet, pain, leading to full paralysis requiring ventilation support [ 16 – 20 ]. Participants’ experiences varied, but many had ongoing difficulties, such as fatigue and memory difficulties, that still limited them in their everyday activities even two years after the onset of their illness [ 16 – 20 ].

As a result, some participants felt they had lost their identity as an independent person [ 17 , 19 ], while others felt helpless through loss of independence [ 16 , 18 ]. These feelings were accompanied by shame or embarrassment, especially when help with hygiene was needed or appearance had altered as a result of GBS [ 17 , 19 , 20 ]. Participants described many emotions as a result of being diagnosed with and needing care for GBS, such as frustration, guilt, elation, anger, and gratitude [ 19 , 20 ]. Other common psychological responses were: feeling lost; feeling abandoned; anxiety when in the intensive care unit or connected to a ventilator; sadness; depression; and fear [ 17 – 20 ].

Having GBS influenced participants’ family lives. Participants were worried about their family’s wellbeing, while they were hospitalised [ 20 ], or felt sad and frustrated about how limited mobility had forced them to accept changed family responsibilities [ 18 ]. Living with GBS made it harder for them to participate in society and restricted their social lives considerably, restricting visits to friends and travel [ 18 ]. Finally, another area affected by a participant’s condition was their work, since physical restrictions and residual GBS symptoms affected function or prevented them from returning to work [ 18 , 19 ].

Fractured care

Participants were generally dissatisfied with healthcare service support which they considered a key barrier preventing recovery from GBS. Participants felt that there was lack of personalised and person-centred care, lack of continuity of care, lengthy waits for referrals, and staff shortages, which made it harder for participants to receive the care they needed [ 18 , 20 ].

Participants also felt not listened to by healthcare staff and experienced poor communication from healthcare professionals [ 18 , 20 ]. They sometimes felt doctors’ attitudes were ‘cavalier’ or healthcare professionals lacked time to discuss their condition with them properly [ 20 ]. Specific needs, whether physical and psychological, were often not met [ 20 ].

Participants also identified a want of publicity about GBS as a main factor contributing to the lack of support they received, especially when returning to work, as the public did not have any insight into the long term effects of GBS or what to expect when interacting with the participants [ 19 ].

Positivity towards recovery

In contrast, participants variously expressed an overall satisfaction with the care they received from community and hospital healthcare, commending kind staff attending to their physical care needs with efficient treatments [ 16 , 18 , 20 ]. More specifically, participants were often very satisfied with nursing care for their physical, psychological and social problems [ 16 , 20 ].

Another facilitator to recovery from GBS was the invaluable support from their family and friends, including both practical (e.g. help with the home and transportation) and psychosocial support (e.g. gathering information about GBS or being emotionally supportive) [ 16 , 18 , 20 ]. However, in one study [ 18 ] participants expressed frustration over the lack of understanding from family and friends in relation to their physical limitations and the effect on the participants’ capacity and everyday life in general.

Support from colleagues was also viewed very highly by participants and motivated them to go back to work, as they often considered their colleagues as friends as well [ 19 ]. Often, however, participants were ambivalent towards their co-workers, initially being grateful for their support, but finding them over-protective at the same time [ 19 ]. When this support soon decreased, participants found it difficult to perform their jobs, demonstrating how important such support had really been for participants [ 19 ].

Peer support was also viewed as really important by participants [ 16 , 20 ], who valued being able to talk with and receive information from others who had also been ill with and survived GBS, as this communication filled them with hope about recovery and the future [ 20 ]. Equally, participants would have gladly done the same for others in their situation, as they considered peer support to be better received and more impactful [ 20 ].

Finally, participants’ positive attitude was a major facilitator to their recovery from GBS and helped them realise that life wasn’t over and that things would eventually improve [ 17 , 20 ]. Hope and confidence in recovery were huge motivators, especially once their functions started to return, motivating them further [ 16 , 17 ].

There was wide variation in participants’ experiences of recovery, coping with and adjusting to their new situation. For some recovery lasted months and was full, whereas others were still experiencing residual symptoms years later [ 18 ]. Those with continuing symptoms felt they had been forced to take over the responsibility for managing and treating their own symptoms and developed personal strategies to overcome physical difficulties, such as walking more slowly to save energy or using hydrotherapy to strengthen and relax their bodies [ 18 ]. During recovery, many participants described their need for increased control and independence [ 20 ], which they associated with improved physical capabilities [ 16 ]. Achieving independence was inspiring to participants and, together with their inner strength, were the key factors in gaining full recovery [ 16 , 17 , 20 ].

Setting and achieving ‘milestones’ was another major motivating factor, with different participants viewing different points in their patient journey as milestones [ 16 , 17 , 19 , 20 ]. For some, it was being able to walk again [ 17 ] or becoming independent [ 20 ], while for others it was moving to the rehabilitation ward [ 16 ] or going back to work [ 19 ].

Adjusting to their new situation required participants to first accept their new circumstances [ 18 – 20 ] and this was a complicated process for many, with some neglecting the influence of the consequences of the disease on their life situation, and others reappraising their new situation and trying to find new ways to manage their residual difficulties [ 18 ]. For some participants that meant remaining positive, often despite persisting symptoms [ 18 , 20 ], or choosing to focus on the positive prognosis, and not thinking about a possible negative outcome (i.e. not recovering fully) [ 17 ].

Towards a new self

A recurring theme was participants’ attempts and eagerness to return to their ‘normal’ pre-GBS selves and everyday lives. Often, going back to an acceptably ‘normal’ identity and avoiding the potential stigma of GBS required rejection of overt disability, with participants trying to conceal their impairments or avoid discussing them [ 19 ], especially once they were back to work [ 19 ]. As a result, participants sometimes did not inform current or prospective employers about their residual difficulties [ 19 ].

Participants were sensitive to other’s reactions at work, especially when colleagues’ behaviour changed towards them [ 19 ]. In order to maintain their identity and cope with threats to their self-image, different coping strategies were used. One participant went as far as entering a ‘supernormal’ phase on his return to work, doing as much work as possible, and refusing extra help [ 19 ]. Others monitored colleagues’ behaviour for possible negative responses, and sought to exert some control over these, for example by using humour [ 19 ]. And for one participant, it was having a senior position in the company and positive relationships with colleagues that were the contributory factors that helped him be open about his diagnosis and residual difficulties [ 19 ].

Despite these concerns, returning to work was seen positively, as going back to their ‘normal’ selves again, and offered a distraction from the participants’ residual difficulties [ 19 ]. Reconnecting with colleagues was viewed as another benefit [ 19 ]. Other motivations for going back to work were financial, recovering physically, and having a purpose and structure to everyday life [ 19 ]. Some participants, however, reported feeling vulnerable returning to work, as they were worried that discussing their health difficulties would sound like complaining [ 19 ].

The main factor facilitating participants’ return to work was workplace adaptations. For some, such accommodations included having the right workplace resources or limiting their responsibilities, especially if they considered stress as a factor in their illness, by being able to change or reduce working hours [ 19 ]. For those who were more senior in their workplace, modifying their role was even easier [ 19 ].

Some workplaces did not have any appropriate resources, such as a quiet place for resting, and when participants went back to work, they were offered only short term flexibility, being expected to soon fully return to their previous responsibilities [ 19 ]. Furthermore, not all participants considered work adaptations positively, making them feel vulnerable and threatening their re-established, pre-illness, ‘normal’ selves [ 19 ]. For others, accepting continued support went against their personal values or diminished their sense of achievement [ 19 ].

Overall, it was evident from all five studies that living with GBS had been a life-changing experience [ 16 – 20 ], often making participants re-evaluate or change their life accordingly [ 18 ].

This systematic review and thematic meta-synthesis explored patients’ experiences and perceptions of GBS at diagnosis, discharge and during recovery. Participants’ experiences of recovery varied significantly, many still experiencing residual (physical, psychological and social) difficulties even years after their discharge from hospital. These results are closely aligned with concepts suggested by both the Illness Trajectory Framework (ITF), proposed by Corbin & Strauss [ 10 ], and Taylor’s [ 11 ] theory of cognitive adaptation to threatening events.

Our results showed that the trajectory of GBS was uncertain and varied significantly from patient to patient, depending on the severity of their condition, the care and support they received, and their own attitudes towards recovery [ 11 ]. During the first phase of pre-trajectory and the trajectory onset , delayed diagnosis and/or misdiagnosis were often reported, a finding that has been well documented previously. For example, Dubey and colleagues [ 21 ] reported that on initial emergency department visit, GBS was suspected in only 49.3% of the cases; this increased significantly when the patient was evaluated by a neurologist (67.5%) rather than the emergency department physician.

Although the crisis and acute phases left the participants fighting for their lives, once their condition had stabilised ( stable phase ), participants slowly started to recover. However, not all participants recovered fully and GBS continued affecting every aspect of their life, leaving them feeling lost in a changing, and often incomprehensible, life ( unstable phase ). These results echo those found in previous studies [ 6 , 7 , 9 ], which have also documented GBS’ lasting effects.

There are many factors that affect how an illness progresses and how recovery can be affected positively or negatively. Our results, for example, showed that patients struggled with the lack of knowledge among healthcare professionals and the lack of information about GBS they received. Similar results were also found in past studies [ 8 ]. Our findings also showed that participants felt that their needs were not being met, mainly due to fractured care, lack of continuity and of personalised care. Uprichard and colleagues [ 22 ] also highlighted the importance of, and need for, an individualised approach to care for patients with GBS and how such care is essential for reducing the traumatic experience of recovery from such a severe illness.

Another facilitator to recovery was support from family and friends, also found in past studies [ 23 ]. Seeing how past GBS patients were able to get better and recover successfully (peer support) was also beneficial, by providing patients with models of good adjustment and giving them hope for their recovery and their future. One possible mechanism of having achieved this may have been by making upward social comparisons to others who were doing better than they were, thus, contributing to their self-enhancement and helping restore their self-esteem [ 11 ]. Past studies with patients in recovery from stroke have also documented the importance of support from stroke survivors in helping patients feel empowered, encouraged, motivated, validated, and less alone [ 24 , 25 ].

More importantly, our meta-synthesis found novel factors that might positively affect recovery. Maintaining a positive attitude, for example, was the first step towards recovery from GBS and helped participants take control of their situation, try to manage their symptoms themselves and regain their independence; a finding in accordance with Taylor’s theory [ 11 ], which argues that one of the main pathways to adjustment is by gaining a feeling of control over the threatening event.

Achieving major milestones also helped participants adjust to and come to terms with their new situation. Returning to work was especially seen as a really important step in going back to their ‘normal’ selves again, even though sometimes participants had to make accommodations before being able to return to their previous role. Such accommodations were necessary due to residual physical difficulties, but can also be seen as an attempt to control the situation by making changes in their lives that would allow them to adapt to their new situation successfully [ 11 ]. Being diagnosed with and surviving GBS was a life-changing experience for all participants that often made them search for meaning in their new situation, re-appraise their lives and re-order their priorities [ 11 ].

For the majority of GBS cases there is no real downward or dying phase ; mortality in GBS patients varies widely with rates between 1–18% [ 26 ]. However, the experience of illness will be present until death.

Strengths and limitations

This review has brought together papers discussing different aspects of people’s experience (such as during an acute episode [ 20 ] or the initial phase of GBS [ 17 ], the recovery phase [ 16 , 18 ], and their experiences returning to work [ 19 ]) and has synthesised them for the first time into a comprehensive overview of the illness and recovery journey of people diagnosed with GBS.

The study followed a rigorous pre-specified protocol (registered with PROSPERO), which ensured that the review process was transparent and replicable. We conducted a comprehensive search for published and unpublished work, through twelve electronic databases, internet searches and scanning of bibliographies. The five included studies were of acceptable quality and included rich data.

A potential limitation of this review was including exclusively English-language papers, as important evidence may have been excluded due to language restrictions. However, methods for translating concepts across languages, in addition to the initial challenge of translating them across studies, have not been sufficiently developed [ 27 ]. Finally, all five studies interviewed people living with GBS, but none included other variants of GBS, such as CIDP or Miller-Fisher syndrome. Future studies should also aim to include participants diagnosed with other variants of GBS, as these sub-groups of participants may have different experiences and needs.

Implications for policy and practice

Exploring this literature has enabled us to identify how patients may need extra support to cope better with their recovery and also identify ways that healthcare professionals and services can help facilitate further such a recovery.

One of the most important areas that needs to be addressed is the lack of knowledge about GBS among many healthcare professionals, including the lack of provision of information to patients about their condition and prognosis. Offering additional training on GBS for healthcare professionals might be an appropriate first step towards improving their knowledge, while providing educational resources and information for the public could be another helpful action. Informing patients of available support services (such as financial aid, health and social care services, as well as relevant charities) would further ensure that people receive appropriate and personalised care, facilitate their transition from hospitalisation to returning to their everyday lives and, potentially, aid recovery.

Patients’ psychological needs were often not met by healthcare services, while maintaining a positive attitude was identified as essential for participants to be able to cope with and successfully recover from GBS. It would be useful, therefore, to add psychological therapies to patients’ treatment regimens, if needed and wanted by patients.

We found that participants also viewed peer support as important in their road to recovery. Peer support could help address both areas discussed earlier, regarding lack of information and emotional support offered to patients with GBS. This could also be an area for future research, exploring how peer support should be provided and that it was clinically beneficial before planning for peer support to be widely available to patients with GBS, potentially through hospitals or GBS charities.

Finally, patients often reported requiring extra support to enable them going back to work. This, according to our results, would include increased awareness of GBS and its sequelae for employers, which in turn would increase understanding of the condition by employers and, therefore, making them more inclined to provide adaptations at work for patients wanting to return to their jobs (e.g. flexible working hours/days, areas for rest, etc.).

This systematic meta-synthesis explored patients’ experiences of GBS at diagnosis, discharge and during recovery. One factor that positively influenced management and eventually outcomes was having a positive attitude and thinking towards recovery. Other key factors influencing management were receiving adequate information about GBS, having support from valued others (such as family members, friends or peer support), and receiving satisfactory care from healthcare services (especially nursing care). Despite the variety of experiences, it was evident from all included studies that being diagnosed with and surviving GBS was a life-changing experience for all participants.

Supporting information

Acknowledgments.

We would like to thank the members of the Community and Health Research Unit (CaHRU) study review group (University of Lincoln) for their valuable comments on a draft of this paper.

Funding Statement

This systematic review is part of a study funded by a grant from the GAIN (Guillain-Barré & Associated Inflammatory Neuropathies) charity, United Kingdom ( https://gaincharity.org.uk/ ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Data Availability

• PLoS One. 2021; 16(2): e0245826.

Decision Letter 0

27 Apr 2020

PONE-D-19-33700

Patients’ experiences and perceptions of Guillain-Barré syndrome: a systematic review and meta-synthesis of qualitative research

Dear Dr Aloysius Niroshan Siriwardena

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

We would appreciate receiving your revised manuscript by 30 days. When you are ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Federico Bilotta

Academic Editor

Journal requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. We note that your search concludes in November 2018.

It is not clear why studies published in the last 12 months were not included for consideration.

Please provide a rationale for the search window, or update the search to include studies from the last 12 months.

Additional Editor Comments:

In this SR and meta-synthesis, the Authors have discussed the patients’ experiences and perceptions of Guillain-Barré syndrome (GBS) and its variants at diagnosis, discharge and during recovery, by conducting a systematic review and thematic meta-synthesis of qualitative studies of patients’ experiences of GBS (and its variants).

The Authors searched 12 electronic databases, supplemented with internet searches and forward and backward citation tracking from the included studies and review articles. Data were synthesised thematically following the Thomas and Harden approach.

The Authors identified a total of 4,204 citations and after removing duplicates and excluding citations based on title and abstract, and full-text screening, five studies were included in the review and meta-synthesis; all included studies were considered of acceptable quality. Through constant discussions and an iterative approach, we developed six analytical themes following a patients journey from suspecting that they had a health problem, through to being hospitalised, experiencing ongoing difficulties, slowly recovering from GBS, adjusting to their new circumstances, and re-evaluating their lives.

The Authors concluded that, that being diagnosed with and surviving GBS was a life-changing experience for all participants.

Editor’s comments: this SR is interesting, but provide some methodological limitations.

The main outcome of the study should be summarize as last sentence of the introduction.

The subchapter “Theoretical perspective” should be shortened by 50%, the introduction section is lengthily and not focused on the primary end point.

The Table should be reported at the end of the manuscript, and cited in the text.

The Result section is composed by 20 pages. The Section is too lengthily. Please report only the results statistically significant in the text, the all results should be reported only in the Table.

The first sentence of the Discussion section should summarize the main results of the study.

Also the Discussion section is long and lengthily. Please shortened by 30 to 40% and focused it on the primary end points of the study.

Reviewer 1: I've read with great interested this work by Siriwardena et al. dedicated to patients’ perceptions of Guillain-Barré syndrome. Undoubtedly, the data presented in this article are of great interest for specialists working with such patients. However, in my opinion, this article is extremely overloaded with data, which makes it really huge and looks like small book or thesis but not journal article. For instance, discussion section essentially repeats, in an abbreviated version, most of the theses set out in the results.

The design of the study is not completely looks optimal to me, because it is not clear what new information this meta-synthesis provides us, compared to the five qualitative studies that were included in the analysis. What has changed in our understanding of the problem after this work? It is also not entirely clear why the authors excluded quantitative works, because, at least, discussion sections of them could also contain some useful information.

In my opinion, the work needs a serious revision aimed at systematization and more concise presentation of data. Major revision

Reviewer 2: I enjoyed reading this review and found many useful features. I particularly appreciated its attempt to engage with underlying theory regarding disease trajectories.

Overall the review is sound and has the potential to make an important contribution to understanding. Unfortunately there are some elementary miscarriages in its execution that would need addressing before publication. Some of the minor issues are listed in more detail below but for ease of identification here are my major concerns:

1. The authors confuse Reporting Standards with Standards of Conduct. Following good reporting standards does not ensure a good review and so it would be good to only cite reporting standards to affirm what they are intended for.

2. Certain points betray gravitation towards a quantitative paradigm e.g. discussion of "risk of bias", "blinding to authors", numbers of participants supporting a finding and numbers of studies required in a qualitative synthesis. Particularly missing (to address some of these) is a "reflexive statement" see example below given from this same target journal. This will also address potential influence of the charity as funder (see below)..

3. The authors present a "bricolage" of findings in the Results. Not only does it engage with the conventions of quantitative research (e.g. "most" participants and "many" participants) but it attributes specific individual statements to groups of individuals misrepresenting an individually worded comment as if an agreed common experience. The whole Results section needs rewriting framing findings as overall statements followed by illustrative verbatim extracts (judiciously selected). In practical terms the authors should look at each verbatim extract and ask: does this capture a common experience? can I frame these related extracts in my own words as generalities, or is this a unique insight? does this wording express the experience better than I can myself? At the moment these results are knitted togeher from the reviewers, the source authors and the verbatim extracts of participants.

4. Although studies are not excluded on the basis of quality it would be useful to at least comment on CASP questions that the collective set of five studies performed less well against (typically reflexivity performs less well).

Specific comments:

“Due to the rarity of this condition there is limited evidence exploring the experiences of individuals who have had GBS.” This sentence perpetrates a common fallacy i.e. that the prevalence of research is linked to prevalence of a condition. In many cases the reverse is true (and this has been particularly recorded for neurological disorders) ie. That rare conditions are more attractive to research than common ones. This is partly attributable to the fact that journals are part scientific documentation and part journalism, partly to the “politics” of research funding and partly to other factors.

“CIDP” – this appears in the Review question without being written in full. The review question should have both conditions in full with respective abbreviations in brackets. (Otherwise CIDP is used twice BEFORE being written in full). It is not appropriate to use unexplained abbreviations in the review question.

“January 2000 and November 2018, to ensure relevance to the present day,” This reads as a weak justification for date limit (cynically, I would say that you have probably selected an easily memorable but topically meaningless start date!).

“Joanna Briggs Institute” – It is unclear what this Data Source is.

“The search terms were entered in all possible combinations using Boolean operators and truncation, wherever deemed necessary” Not true! They would have been kept in sets of related concepts i.e. the GBS concept, the qualitative research concept. Not ALL possible combinations. Search terms should also best be presented as two sets for greater clarity. E.g. “(i) Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), acute inflammatory demyelinating polyneuropathy (AIDP) combined with (ii) qualitative research, interview, focus group, experiences, perceptions, attitudes, and views”.

“All studies were reviewed and screened by three reviewers” This is very unclear. Does this mean that “all references were reviewed and screened”. In a review “studies” don’t become “studies” until they are included. Before that they are first “references” and then “(full text) papers”

“Qualitative Checklist [15] was used to assess risk of bias in included studies of this review” – The CASP checklist is not validated for “risk of bias”. Indeed what “risk of bias” means in a qualitative sense is epistemologically unclear anyway. Describe it only as “quality assessment”.

“Quality, however, was not a criterion for exclusion of a study” This is a sound decision but requires a sentence or clause of explanation e.g. “given that the intent was interpretative….” Or something similar. Also, being accurate “quality” is not a criterion. “Poor quality” would be.

“Blinding to the names of the authors, journals, and results of each study was not possible,

since the same authors performed the screening and data extraction of the studies to be

included in the meta-synthesis.” You don’t typically see this spelled out, particularly as you don’t explain why this could be an issue. In my view this is a very quantitative way of handling a legitimate concern. In a QUALITATIVE synthesis like this I would expect instead a reflexivity statement that talks about all the authors positionality to the data.

See the following example from PLOS One:

“Reflexive statement. Reflexive accounting allows the reader of the final research product to assess the degree to which the prior views and experiences of the researcher may have influenced the design, data collection and data interpretation of the study or in this case, the synthesis of the findings of multiple studies. This review was conceived with an informed knowledge of caesarean section and a degree of professional distance, which arguably limited bias based on the team’s own experiences. APB is a medical officer with over 15 years of experience in maternal and perinatal health research and public health in general, and caesarean section in particular. CK, a medical sociologist, came to the project with prior beliefs about the complexity and interdependency of social factors driving caesarean section rates, principally informed Stakeholder views of interventions to reduce unnecessary caesareans targeted at organisations and systems by undertaking earlier primary research with women and health professionals in the UK. SD, a Professor of Midwifery, believed that maternity care organisations are complex adaptive systems, and that the organisational ethos can exert either toxic or enhancing effects that have real consequences for staff morale, engagement, attitudes, behaviours and performance”.

https://journals.plos.org/plosone/article/file?type=printable&id=10.1371/journal.pone.0203274

“Initially, participants from most included studies” Avoid this quantitative reporting , especially when you then attribute multiple studies to a single verbatim extract as in this example. This should be reported as:

“Participants variously described initial experiences associated with their first awareness of their condition: “strange or odd sensations or peculiar feelings”, such as tingling in their feet or having difficulty opening the lid of orange juice containers etc

Similarly with “Most participants, “tried to ignore the strangeness of their bodies” whereas”. Especially be aware that “most participants” or “many participants” from one study may not be “many” or “most” across the five studies. This is particularly important because an experience is not judged important or not simply on the basis of whether it is a common experience or unique to that individual.

“Given that not many (especially not qualitative) studies were found that incorporated the

experiences of GBS from onset of symptoms and onwards” – this sentence is difficult to interpret – by using words such as Qualitative/focus groups etcetera in your search strategy you were only looking for QUALITATIVE studies. The fact that you retrieved some that weren’t qualitative isn’t a valid basis for making pronouncements about the quantitative studies which would not be representative of the ones you did not retrieve. Focus only on what you were studying, not what you accidentally retrieved along the way.

“well established guidelines (ENTREQ), which limited the potential for bias” You make the mistake here (and above in Methods) of assuming that following ENTREQ REPORTING guidelines somehow has an impact on the quality of the CONDUCT of your review. What reporting guidelines do is make it easier for a Reader to detect threats to bias (however that can be defined within a qualitative paradigm); they don’t make your review better.

“A potential limitation of this review was only five studies met the inclusion criteria for meta

synthesis” – this is largely an irrelevancy – you should consider the adequacy of your data (cp GRADE CERQual on adequacy) which is a function of both numbers of studies and their richness. So reframe as adequacy – they could still be adequate even if not plentiful. If, however they are neither rich nor plentiful then you should specifically identify what data were missing.

Similarly the reason why there are no guidelines on how many studies should be included is that this is bringing in a quantitative criterion to a qualitative phenomenon. Why are MORE studies needed? Not because the numbers aren’t sufficient – if you are going to recommend more studies then you must state which perspectives or elements of the experience are missing and therefore need more data. Otherwise you are simply advocating wasted research monies!

“Including exclusively English-language papers could be considered a weakness, as

important evidence may have been excluded due to language restrictions” This is true but you might wish to rebut this by saying “However, methods for translating concepts across languages, in addition to the initial challenge of translating them across studies, have not been sufficiently developed”.

There are several mentions of the role of “charities” in the Discussion. Given the funding for this study it would be good for the Reflexivity statement (as recommended above) to specifically address this. E.g. “The authors consider provision of information and support from charities as an important resource for patients, particularly with rare conditions, but such support may be available from multiple sources, and our view on potential sources may have been influenced by the funding for this study”. Major revision

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Partly

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: N/A

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: I've read with great interested this work by Siriwardena et al. dedicated to patients’ perceptions of Guillain-Barré syndrome. Undoubtedly, the data presented in this article are of great interest for specialists working with such patients. However, in my opinion, this article is extremely overloaded with data, which makes it really huge and looks like small book or thesis but not journal article. For instance, discussion section essentially repeats, in an abbreviated version, most of the theses set out in the results.

In my opinion, the work needs a serious revision aimed at systematization and more concise presentation of data.

Reviewer #2: I enjoyed reading this review and found many useful features. I particularly appreciated its attempt to engage with underlying theory regarding disease trajectories.

There are several mentions of the role of “charities” in the Discussion. Given the funding for this study it would be good for the Reflexivity statement (as recommended above) to specifically address this. E.g. “The authors consider provision of information and support from charities as an important resource for patients, particularly with rare conditions, but such support may be available from multiple sources, and our view on potential sources may have been influenced by the funding for this study”.

6. PLOS authors have the option to publish the peer review history of their article ( what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy .

Reviewer #1: No

Reviewer #2: Yes: Andrew Booth

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at gro.solp@serugif . Please note that Supporting Information files do not need this step.

Author response to Decision Letter 0

22 May 2020

See uploaded file: Response to reviewers

Submitted filename: Response to reviewers.docx

Decision Letter 1

17 Nov 2020

PONE-D-19-33700R1

Dear Dr. Siriwardena,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we invite you to undertake some minor revision and submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Jan 01 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at gro.solp@enosolp . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see:  http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

Kathleen Finlayson

Additional Editor Comments (if provided):

Thank you for addressing the reviewers' comments, the review is well written and addresses a significant area of research. Please note the recommendation below to further condense the article. I would recommend this for the introduction, and adding in the recommendations for policy and practice within the discussion.

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

2. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Partly

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: N/A

4. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #1: Yes

5. Is the manuscript presented in an intelligible fashion and written in standard English?

6. Review Comments to the Author

Reviewer #1: I thank authors for their efforts to improve the paper but from my point of view manuscript is still too long for publication as a journal article, especially it important for intro and results sections.

7. PLOS authors have the option to publish the peer review history of their article ( what does this mean? ). If published, this will include your full peer review and any attached files.

Reviewer #1: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool,  https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at  gro.solp@serugif . Please note that Supporting Information files do not need this step.

Author response to Decision Letter 1

18 Dec 2020

Dear Dr Bilotta,

Article title: Patients’ experiences and perceptions of Guillain-Barré syndrome: a systematic review and meta-synthesis of qualitative research

Thank you for your further feedback on the paper and advice from editors and reviewers on minor revision of the paper following our previous major revision.

We have substantially shorted the introduction and results and adjusted the discussion in line with the advice given. Details of our response are below.

Thank you for reconsidering the revised paper for publication.

Yours sincerely,

Prof A. N. Siriwardena on behalf of the authors

Editor/reviewer comments Response

Additional Editor Comments (if provided): Thank you for addressing the reviewers' comments the review is well written and addresses a significant area of research. Please note the recommendation below to further condense the article. I would recommend this for the introduction and adding in the recommendations for policy and practice within the discussion. Thank you. We have condensed the text considerably and added recommendations for policy and practice in the discussion.

Reviewer #1: I thank authors for their efforts to improve the paper but from my point of view manuscript is still too long for publication as a journal article especially it important for intro and results sections.

Thank you. We have shortened the article as far as possible without changing the meaning of the text. The Background has been reduced from 1042 to 893 words and the Results from 2528 to 2103 words. The other sections

Submitted filename: Response to reviewers 16.12.20.docx

Decision Letter 2

11 Jan 2021

PONE-D-19-33700R2

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/ , click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at gro.solp@gnillibrohtua .

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact gro.solp@sserpeno .

Additional Editor Comments (optional):

Thank you for your response to the reviewers' suggestions. The manuscript is more succinct and provides a valuable contribution to understanding of this area.

Acceptance letter

13 Jan 2021

Dear Dr. Siriwardena:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact gro.solp@sserpeno .

If we can help with anything else, please email us at gro.solp@enosolp .

Thank you for submitting your work to PLOS ONE and supporting open access.

PLOS ONE Editorial Office Staff

on behalf of

Dr. Kathleen Finlayson

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

• View all journals
• My Account Login
• Explore content
• About the journal
• Publish with us
• Sign up for alerts
• Open access
• Published: 07 March 2023

Real-world data on the incidence and risk of Guillain–Barré syndrome following SARS-CoV-2 vaccination: a prospective surveillance study

• Jongmok Ha 1   na1 ,
• Suyeon Park 2 , 6   na1 ,
• Hyunwook Kang 1 ,
• Taeeun Kyung 1 ,
• Namoh Kim 1 ,
• Dong Kyu Kim 1 ,
• Hyeonjoon Kim 1 ,
• Kihoon Bae 1 ,
• Min Cheol Song 1 ,
• Kwang June Lee 1 ,
• Euiho Lee 1 ,
• Beom Seuk Hwang 6 ,
• Jinyoung Youn 3 , 4 ,
• Jin Myoung Seok 5 &
• Kunhee Park 1  

Scientific Reports volume  13 , Article number:  3773 ( 2023 ) Cite this article

8961 Accesses

6 Citations

54 Altmetric

Metrics details

• Diseases of the nervous system
• Neurological disorders
• Neuromuscular disease

Increasing evidence suggests an association between SARS-CoV-2 vaccines and Guillain–Barré syndrome (GBS). Nevertheless, little is understood about the contributing risk factors and clinical characteristics of GBS post SARS-CoV-2 vaccination. In this prospective surveillance study of 38,828,691 SARS-CoV-2 vaccine doses administered from February 2021 to March 2022 in the Gyeonggi Province, South Korea, 55 cases of GBS were reported post vaccination. We estimated the incidence rate of GBS per million doses and the incidence rate ratio for the vaccine dose, mechanism, age, and sex. Additionally, we compared the clinical characteristics of GBS following mRNA-based and viral vector-based vaccinations. The overall incidence of GBS following SARS-CoV-2 vaccination was 1.42 per million doses. Viral vector-based vaccines were associated with a higher risk of GBS. Men were more likely to develop GBS than women. The third dose of vaccine was associated with a lower risk of developing GBS. Classic sensorimotor and pure motor subtypes were the predominant clinical subtypes, and demyelinating type was the predominant electrodiagnostic subtype. The initial dose of viral-vector based vaccine and later doses of mRNA-based vaccine were associated with GBS, respectively. GBS following SARS-CoV-2 vaccination may not be clinically distinct. However, physicians should pay close attention to the classic presentation of GBS in men receiving an initial dose of viral vector-based SARS-CoV-2 vaccines.

Similar content being viewed by others

Association between BNT162b2 vaccination and reported incidence of post-COVID-19 symptoms: cross-sectional study 2020-21, Israel

Real-world treatment of adult patients with Guillain-Barré syndrome over the last two decades

Long-term neurologic outcomes of COVID-19

Introduction.

As the struggle to overcome the aftermath of the COVID-19 global pandemic continues, nearly 12 billion doses of SARS-CoV-2 vaccines have been administered worldwide as of June 2022 1 ; currently, we are faced with the consequences of mass vaccination, both developed and deployed at an unprecedented speed.

The nationwide SARS-CoV-2 vaccine rollout in South Korea began in February 2021. Vaccines from four different manufacturers were approved sequentially: viral vector-based ChAdOx1-S/nCoV-19 (Oxford-Astrazeneca), Ad26. COV2.S (Janssen), mRNA-based BNT162b2 (Pfizer-BioNTech), and mRNA-1273 (Moderna) vaccines (Fig.  1 ). Due to thrombotic thrombocytopenia syndrome (TTS) following ChAdOx1-S/nCoV-19 2 and Ad26. COV2.S 3 vaccines, viral vector-based SARS-CoV-2 vaccines have been contraindicated in South Korea for individuals under 30 years of age since April 2021.

Vaccination timeline in South Korea; approval of four different types of vaccines; time-series of number of vaccinated people; and reported adverse events in the Gyeonggi province. A nationwide vaccination campaign for SARS-CoV-2 in South Korea was initiated on February 26th, 2021. Vaccines from four different manufacturers were approved: the viral vector-based ChAdOx1-S/nCoV-19 (Oxford-Astrazeneca) vaccine on February 10th, 2021; the BNT162b2 (Pfizer-BioNTech) vaccine on March 5th, 2021; the Ad26. COV2.S (Janssen) vaccine on April 7th, 2021; and the mRNA-1273 (Moderna) vaccine on May 21st, 2021. The initiation of each vaccine is represented by red and blue markers (red indicates mRNA-based and blue indicates viral vector-based). The slashed square area represents a temporary halt in the BNT162b2 vaccination in May 2021, owing to problems with vaccine supply. From the beginning of October, booster shots were given; most were mRNA vaccines (bold green line and arrow), and viral-vector vaccines (third dose of ChAdOx1-S/nCoV-19, an additional dose of Ad26.COV2.S) only represented a minority of vaccinated people (green dotted line and arrow). The gray bars in the background represent the total number of vaccinated people in the Gyeonggi province, South Korea, in the respective months.

To address the growing safety concerns regarding SARS-CoV-2 vaccination, the provincial governments of South Korea have cooperated with the Korea Disease Control and Prevention Agency (KDCA) to gather data on adverse events following immunization (AEFI) and adverse events of special interest (AESI), including Guillain–Barré syndrome (GBS). Additionally, pharmacovigilance review meetings were held by interdisciplinary experts to discuss the link between vaccination and potential adverse events.

GBS is an acute-onset, progressive, monophasic, immune-mediated peripheral neuropathy that is frequently associated with diverse antecedent respiratory and gastrointestinal infections 4 , 5 . Historically, the potential link between GBS and vaccination (e.g. influenza, MMR, hepatitis B, diphtheria, etc.) has been addressed in multiple studies over decades 6 , 7 , 8 , 9 , 10 ; influenza A (H1N1) in particular, has been postulated to be associated with an increased risk of GBS in some occasions 11 , 12 . However, there has been an increasing body of evidence suggesting an association between viral vector-based SARS-CoV-2 vaccines and GBS 13 , 14 . mRNA-based vaccines have also been suspected to have an association 15 , 16 , 17 , 18 , 19 , but controversies have remained 14 , 20 .

While studies thus far have focused profoundly on reviewing individual cases or analyzing large patient databases, only few studies have simultaneously gathered large population data and meticulously reviewed individually reported GBS cases from a clinical perspective. With limited data, policymakers and physicians struggle to recommend the most suitable vaccine for individual recipients, who may be at an increased risk for certain vaccines. Hence, to tip the scales of risk–benefit in the recipient’s favor, clinically oriented studies that unveil patient-specific risk factors have become crucial.

In light of these unmet needs, this study aimed to: (1) report the crude incidence rate of GBS following SARS-CoV-2 vaccination, (2) evaluate how vaccine dose, mechanism, age, and sex may affect the risk of GBS following SARS-CoV-2 vaccination, and (3) clinically compare head-to-head GBS cases following two major mechanisms of vaccines. We believe that our study can validate previous large-scale database-driven studies and provide a neurologist’s perspective on real-world data.

Study design and population data of vaccinated inhabitants

We conducted a prospective regional surveillance study for the occurrence of GBS in the Gyeonggi Province, South Korea, from February 26th, 2021, to March 15th, 2022.

The Gyeonggi Province is one of the largest local government bodies in South Korea, inhabited by approximately 13 million people, almost one-third of the nation’s population. As of March 2022, 85.9% of its residents had been fully vaccinated and 86.8% had been vaccinated at least once against SARS-CoV-2. Owing to its large population, the Gyeonggi Province has served as a centerpiece for the surveillance of adverse events following SARS-CoV-2 vaccination in South Korea.

The Gyeonggi province population data on vaccine dose (first, second, and third), mechanism (mRNA-based versus viral vector-based), age, and sex for individual vaccination events (per dose) were mined and reconstructed from a centralized, conjoined database formed by 48 community health centers in charge of SARS-CoV-2 vaccinations performed in designated vaccination centers, hospitals, and nursing homes in the respective city jurisdictions. The final merged dataset was used for statistical analysis.

Passive AEFI/AESI surveillance and data collection of GBS cases

From the start of the nationwide vaccine rollout, as part of a government led passive surveillance program, patients and physicians were asked to report relevant AEFI/AESI to the local government authorities for post-marketing survey of SARS-CoV-2 vaccines. The Korean government motivated both physicians and patients with expert feedback and monetary compensation in case of a plausible association between the reported adverse event and the vaccine. Additionally, in an effort to overcome the shortcomings of passive surveillance, Gyeonggi Province has periodically monitored reporting rates in all province hospitals and issued updated education resources to in-hospital infection control centers to aid in prompt reporting of cases.

The Gyeonggi Infectious Disease Control Center has dealt with all reported individual cases of AEFI/AESI following SARS-CoV-2 vaccination, including GBS, and reviewed electronic medical records from hospitals and drug utilization review (DUR) records provided by the Korean Health Insurance Review and Assessment Service. It also interviewed the patient or the primary caregiver, and engaged in discussions with the relevant medical personnel to arrive at a conclusion on the diagnosis. The adverse events reported by the patient, their legal guardian, or the attending physician were classified as serious or non-serious, and serious adverse events were classified as severe or non-severe (Fig.  2 ). The validity of the diagnoses was confirmed through weekly expert consensus meetings. Cumulative data from the individual reports were pooled and reviewed.

Flow diagram of study participants.

Upon gathering relevant cases, we included patients diagnosed with GBS within 42 days after the last dose of SARS-CoV-2 vaccine. Also, we excluded the following participants from the study: (1) aged less than 12 years, (2) cases in which other vaccinations (e.g., seasonal influenza, hepatitis B) were administered within 3 months, (3) cases with relevant competing causes of paraparesis or quadriparesis, (4) cases with previous SARS-CoV-2 infection, and (5) previous diagnosis of GBS. In total, two patients satisfying the third criterion due to compressive myeloradiculopathy and myelopathy were excluded from the study.

From a total of 38,828,691 SARS-CoV-2 vaccine doses administered from February 26th, 2021, to March 15th, 2022, 105,409 adverse events were reported. A total of 688 cases had severe adverse reactions and 6331 cases had non-severe serious or non-serious adverse events, warranting further investigation. A total of 55 cases of GBS post SARS-CoV-2 vaccination were identified, as illustrated in Fig.  2 . The electrophysiological data were available for 33 cases.

Review of pooled data and GBS diagnosis

The Brighton Collaboration Case Definition 21 and NINDS GBS criteria 22 for classic sensorimotor types, as well as the panel suggested by Leonhard et al. 23 for GBS variant subtypes, were used to reconfirm the validity of the diagnosis of GBS with temporal association to SARS-CoV-2 vaccination. The raw data of nerve conduction studies (NCS) were reviewed using the criteria proposed by Rajabally et al. 24 Two neurology experts were involved in confirming the validity of the GBS diagnosis and the classification of clinical and electrodiagnostic subtypes.

Moreover, for a deeper understanding of the clinical course and characteristics of GBS following SARS-CoV-2 vaccination, we collected data on the time from vaccination to symptom onset, laboratory findings such as CSF leukocyte count and protein level, anti-ganglioside antibodies (anti-GM1 IgG, anti-GM1b IgG, and anti-GQ1b IgG), markers of severity, such as GBS disability scale (Hughes scale) at nadir and at 1 month post-treatment, Medical Research Council (MRC) sum score at nadir, ICU stay, mechanical ventilator requirement, and death.

Statistical analyses

In this study, descriptive statistics were determined according to data attributes. Continuous data are displayed as means with standard deviations or medians with ranges, whereas categorical variables are displayed as absolute and relative frequencies. We analyzed the differences between the groups (mRNA-based versus viral vector-based) using Student’s t test or Mann–Whitney U test for continuous variables and Chi-square test or Fisher's exact test for categorical variables.

The incidence rate (IR) used in our study was defined as the number of new GBS adverse events per million doses of vaccines administered during the study period 13 , 25 , 26 . The 95% confidence intervals (CIs) for the IR were estimated using the Fay-Feuer method for gamma-based central CIs for directly standardized rates 27 . Poisson regression analysis was performed considering dose (first, second, or third), vaccine mechanism (mRNA-based or viral vector-based), age (< 30, 30–59, or ≥ 60), and sex (women or men) variables, and it was not significant ( p  = 0.9589) in the over-dispersion test. The results were expressed as the incidence rate ratio (IRR) and 95% CI. All statistical analyses were performed using a two-sided test and were considered statistically significant at a significance level of 0.05. Statistical analyses were performed using IBM SPSS Statistics (version 24.0; IBM, Armonk, NY, USA) and Rex (version 3.6.0, RexSoft Inc., Seoul, Korea). Forest plots were drawn using the R statistical software program (version 4.1.2; R Core Team 2021).

Declarations

Ethics approval and consent to participate.

The Korean Public Institutional Review Board granted exemption for this study because it involved analysis of de-identified data already obtained through epidemiological investigation, presented minimal risk to the participants, and met the needs of the current public health interest (identifier: P01-202204-01-006). Informed consent was obtained from all subjects and/or their legal guardian(s). All methods were carried out in accordance with relevant guidelines and regulations.

Incidence rate of GBS post SARS-CoV-2 vaccination

A total of 38,828,691 doses were administered in the Gyeonggi province, and the overall incidence of GBS following SARS-CoV-2 vaccination was 1.42 per million doses (95% CI 1.04–1.79). The incidence of GBS following SARS-CoV-2 vaccination decreased from the first (IR, 2.06; 95% CI 1.32–2.79) to third dose (IR, 0.38, 95% CI 0.01–0.76). Upon evaluation based on the mechanism of vaccine, the incidence rate of GBS after viral vector-based vaccines was 4.49 per million doses (95% CI 2.85–6.12), higher than that after mRNA-based vaccines, which was 0.80 per million doses (95% CI 0.49–1.11). In terms of age, people aged 60 years or above exhibited a higher incidence of GBS (IR 2.24; 95% CI 1.45–3.03), compared to younger age groups (IR, 1.11; 95% CI 0.14–2.08). Men showed a higher incidence of GBS (IR, 1.98, 95% CI 1.35–2.62) compared to women (IR, 0.86; 95% CI 0.45–1.27) (Fig.  3 ).

Incidence rate of GBS following SARS-CoV-2 vaccination, stratified by number of doses, vaccine types, age group and sex. Total doses of each vaccines administered, the number of events reported, and the incidence rate (IR) of GBS per dose, vaccine mechanism, age group, and sex are illustrated here.

Risk factors for GBS following SARS-CoV-2 vaccination

In univariate analysis, both the second and third doses of the vaccines tended to reduce the risk of GBS from the first, but only the third dose demonstrated a statistically significant decrease in risk (crude IRR, 0.187; 95% CI 0.066–0.529). People who received viral vector-based vaccines were significantly more likely to develop GBS than those who received mRNA-based vaccines (crude IRR, 5.584; 95% CI 3.289–9.480). There was no statistically significant difference by age group (crude IRR 0.835; 95% CI 0.312–2.236 for the 30–59 age group, crude IRR 2.020; 95% CI 0.786–5.196 for the ≥ 60 age group). Men were more likely to develop GBS following SARS-CoV-2 vaccination than were women (crude IRR, 2.299; 95% CI 1.297–4.072). Finally, as a result of multivariate analysis, only dose (adjusted IRR 0.804; 95% CI 0.458–1.411 for second, adjusted IRR 0.331; 95% CI 0.110–0.997 for third), vaccine mechanism (adjusted IRR 3.745; 95% CI 1.979–7.087), and sex (adjusted IRR 2.285; 95% CI 1.289–4.051) showed statistically significant differences in the incidence of GBS (Table  1 ).

Clinical characteristics of GBS following SARS-CoV-2 vaccination

The mean age of GBS patients was 57.6 years (SD: 17.3); 38 (69.1%) were men, and 17 (30.9%) were women. The mean time from vaccination to symptom onset was 18.2 days (SD: 16.2) days. Rarer clinical phenotypes were observed, but classic sensorimotor and pure motor phenotypes prevailed (N = 23, 41.8% and N = 23, 41.8%, respectively). Electrodiagnostic classification revealed 20 demyelinating types (60.6%) and 7 axonal types (21.2%). Two patients in the viral vector-based vaccine group were positive for either GM1 or GD1b IgG. Albuminocytologic dissociation was observed in all cases in which CSF analysis was available. The median MRC sum score at nadir was 46.0 (IQR: 33.0–54.0), and the GBS disability scale at nadir was 4.0 (IQR: 2.8–4.0). Of the nine (16.7%) patients who needed ICU care, seven (13%) required mechanical ventilation and among them, five (9.1%) died (Table  2 ).

There were no significant differences between the groups based on the mechanism of vaccines (mRNA-based and viral vector-based). Classic sensorimotor and pure motor subtypes were the predominant clinical phenotypes for both mRNA-based and viral vector-based vaccines, and there were no statistically significant differences in these phenotypes ( p  = 0.525). Demyelinating type was the dominant electrodiagnostic subtype in both the mRNA-based and viral vector-based vaccines, and there were no statistically significant differences in electrodiagnostic classification ( p  = 0.793). Nevertheless, GBS following mRNA-based vaccines was associated with later doses, whereas GBS following viral-vector-based vaccine was associated with the initial dose ( p  = 0.022). In addition, a higher number of mechanical ventilator requirements and ICU stay were observed for mRNA-based vaccines than for viral vector-based vaccines, but the difference was not statistically significant ( p  = 0.243 and p  = 0.286, respectively). In terms of motor symptom severity at the nadir, no significant difference between the two vaccine mechanisms was detected for the GBS disability scale and MRC sum scale ( p  = 0.420 and p  = 0.992, respectively). For prognostics, no significant difference between the two vaccine mechanisms were detected for GBS disability scale at 1-month post-treatment and number of deaths ( p  = 0.285 and p  = 1.000).

We performed a large population-based prospective surveillance study featuring 38 million doses of the SARS-CoV-2 vaccine. Specifically, we meticulously reviewed each reported GBS case following SARS-CoV-2 vaccination; comprehensively assessed the clinical characteristics; and evaluated the contribution of variables such as vaccine dose, mechanism, age, and sex in developing GBS to improve internal validity and provide a clinical perspective. We believe our study is the first to concomitantly provide a broad view of the occurrence of GBS in a large, vaccinated population and delve deeper into each confirmed case. The key findings of this study are as follows: (1) GBS following SARS-CoV-2 vaccination was not clinically distinct from GBS pre-dating the COVID-19 pandemic; (2) viral vector-based vaccines were associated with a higher risk of developing GBS; and (3) the third dose of vaccine was associated with a lower risk of developing GBS.

In terms of the demographic and clinical characteristics of GBS post SARS-CoV-2 vaccination, they do not differ significantly from independent cases of GBS. First, men were associated with an increased risk of GBS following SARS-CoV-2 vaccination compared with women. This finding has previously been reproduced in large-scale epidemiological studies, regardless of vaccination 28 , 29 . Despite reports of diverse clinical subtypes, classic sensorimotor and pure motor types remain the most common. Likewise, when nerve conduction studies were reviewed, the demyelinating type was the most common electrodiagnostic subtype; these results are in accordance with previous epidemiological studies of the pre-pandemic era 30 . Notably, bifacial weakness with distal paresthesia subtypes increased in India and the UK following SARS-CoV-2 vaccination 31 , 32 , but a large-scale epidemiological study on the ChAdOx1nCoV-19 vaccine demonstrated no significant increase in these rare subtypes 14 . We also performed an in-depth analysis of clinical symptoms and signs of the GBS patients at initial visit and nadir, to address this concern (Supplementary Table S1). Among the five early facial palsy patients, four patients had isolated cranial nerve involvement; at nadir however, one patient developed pure motor type GBS and two patients developed classic sensorimotor GBS. Only one patient who received a viral vector-based vaccine was found to have BFP variant GBS at nadir. Additionally, in the same analysis, mRNA-based vaccine group showed lower extremity dominant involvement, whereas viral vector-based vaccine group showed equal involvement of upper and lower limbs at nadir—the clinical significance of this finding however, remains unclear. In fact, we might be dealing with the same kind of demon; only the trigger had changed. GBS following SARS-CoV-2 vaccination is not a clinically distinct type because there were no significant differences in age, sex, latency to symptom onset, clinical phenotype, electrodiagnostic subtype, severity, or prognosis when stratified by vaccine mechanisms (mRNA-based versus viral vector-based).

The incidence rate of post-vaccination GBS in our study was 4.49 per million doses of viral vector-based vaccines and 0.8 per million doses of mRNA-based vaccines. Our results follow the same propensity as those from a nationwide, database-driven study on GBS following SARS-CoV-2 vaccination, which has reported a markedly high incidence rate of GBS following the Ad26. COV2.S vaccine but a much lower incidence rate for mRNA-based vaccines 13 .

Upon assessing the risk factors for GBS post SARS-CoV-2 vaccination, the viral vector-based vaccine was associated with a three-to-four fold increased risk of GBS compared to mRNA-based vaccines, a finding consistent with previous studies 13 , 14 , 20 . GBS following the viral vector-based vaccine was associated with the initial dose, while GBS following the mRNA vaccine was associated with the latter doses (second and third). This finding parallels the reactogenicity of each vaccine mechanism; BNT162b2 and mRNA-1273 vaccines exhibited increased reactogenicity after the second and third doses of vaccination 33 , 34 , 35 , 36 , while the ChAdOx1nCoV-19 vaccine exhibited increased reactogenicity after the first dose of vaccination 37 . As an analogy, a similar result has been observed for vaccine-associated myocarditis, where an increased incidence of vaccine-associated myocarditis has been reported in the younger male population after the second dose of mRNA-based vaccination 38 . Hence, this finding may support the hypothesis that GBS following vaccination has a plausible immunological basis. A possible—but not yet firmly elucidated—mechanism behind the immunopathogenesis of GBS may be a complex interplay between CD4 + /CD8 + T-cells and B-cells; it is induced primarily by innate immunity and T-cell response and followed by a progressive nerve injury due to humoral immunity 39 , 40 . At a molecular level, SARS-CoV-2 vaccines induce Th1 skewed immune response post vaccination 41 , 42 , inducing the release of cytokines such as IFN-γ and IL-2. IFN-γ is elevated in the acute phase of GBS 43 and responsible for recruiting primed macrophages. IL-2 is responsible for sustaining both cell- and antibody-mediated humoral immunity inducing clonal expansion of both B- and T-cells 39 . While there is no tangible evidence of molecular mimicry between vaccine-targeted proteins (e.g. spike protein) and myelin, paranode, or nodal proteins yet, the possibility should be addressed in future studies.

Finally, the third dose, or a booster dose of the SARS-CoV-2 vaccine, was associated with a lower risk of GBS. This finding can be attributed to several factors; first and foremost, a combination of a decrease in booster shot recipients and attrition of an already susceptible population following the first and second doses. Second, mRNA-1273 booster shots were carried out using half the usual dose (0.5 mL/100 µg to 0.25 mL/50 µg). As a smaller amount of substrate for the immune response was administered into the recipient’s blood, it is possible that the resulting immune reaction was weaker than that after the previous doses, potentially reflecting a dose–response relationship. However, in our population, mRNA-1273 vaccine doses accounted for only up to 3% of the whole vaccination; therefore, the effect of this modification in the protocol may not suffice to explain our findings and a national-scale analysis involving a larger population is required to validate this hypothesis. Lastly, there has been an absolute decrease in the number of booster shot recipients since October 2021, largely due to the increase in public COVID-19 risk tolerance and vaccine hesitancy. Furthermore, these booster shots were mostly mRNA-based vaccines, which, as previously discussed, were associated with a lower risk of GBS following vaccination. Nevertheless, this finding directly opposes previous results on immunogenicity and reactogenicity of the third dose of vaccines, as studies have revealed augmented immunogenicity after the booster shot (higher IgG levels compared to the second dose) in both types of vaccines 37 , 44 , and reactogenicity in mRNA-based vaccines 35 , 36 , 45 . Therefore, this finding should be interpreted with caution.

This study had several limitations that need to be acknowledged. First, although the temporal association suggested in our study may provide valuable insight into causality assessment, an observational study inherently discovers only associations and not causality. Additionally, since our population data were collected per vaccine dose, it is difficult to directly compare our results with previous epidemiological studies which mostly report incidence by per person basis. Nevertheless, the total incidence of GBS after SARS-CoV-2 vaccination in our study is comparable to the numbers reported by García–Grimshaw and colleagues, where they observed an incidence of 1.19/1,000,000 doses 26 . To conclude the risk of GBS from SARS-CoV-2 vaccination, further studies with incidence per person might compare directly with the incidence before vaccination. Regardless, the selection bias was minimal because our study was based on a large community population with more than 38 million doses. Although our study was not performed in a carefully controlled setting and potential unidentified confounders may still exist, we show real-world data of a heterogeneous, unselected population, a strength rather than a weakness in assessing the incidence rate and associated risks. Second, the prospective surveillance design is vulnerable to under-reporting bias. However, in order to increase sensitivity, we undertook efforts to overcome this limitation as described in the method section. Third, concurrent infections could have been better addressed using viral and bacterial panel in these patients. However, these patients did not present with symptoms suggestive of infection and SARS-CoV-2 infection was ruled-out in all GBS patients upon admission to the hospital regardless. Finally, we did not account for the differences between homologous and heterologous vaccination and the different immunogenicity and reactogenicity conveyed by each method 46 , 47 . In our study, only one case of GBS following SARS-CoV-2 vaccination presented after heterologous vaccination (received ChAdOx1-S/nCoV-19 for the first dose and BNT162b2 for the second dose). Future studies should focus on whether increased immunogenicity and reactogenicity after heterologous vaccination increase the risk of GBS and other immune-mediated adverse events.

In conclusion, GBS following SARS-CoV-2 vaccination is a growing concern as some cases may lead to significant morbidity or even mortality. It is imperative that physicians closely monitor patients following SARS-CoV-2 vaccination, especially men who are vaccinated with an initial dose of viral-vector-based vaccine. Future studies should focus on integrating clinical and large epidemiological perspectives to generate an individualized risk in taking SARS-CoV-2 vaccination to recommend the most suitable type of vaccine with the lowest risk of adverse events. Furthermore, countries should try to foster pharmacovigilance on immune-mediated subacute-onset neurological complications and try to provide clearer, digestible information to the public to guide upcoming vaccination campaigns.

Data availability

The datasets generated and/or analysed during the current study are not publicly available due to the sensitive nature of the data and patient confidentiality, but the derived data are available from the corresponding author on reasonable request.

Mathieu, E. et al. A global database of COVID-19 vaccinations. Nat. Hum. Behav. 5 , 947–953. https://doi.org/10.1038/s41562-021-01122-8 (2021).

Article   PubMed   Google Scholar  

Greinacher, A. et al. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. N. Engl. J. Med. 384 , 2092–2101. https://doi.org/10.1056/NEJMoa2104840 (2021).

Article   CAS   PubMed   Google Scholar  

See, I. et al. US case reports of cerebral venous sinus thrombosis with thrombocytopenia after Ad26.COV2.S vaccination, March 2 to April 21, 2021. JAMA 325 , 2448–2456. https://doi.org/10.1001/jama.2021.7517 (2021).

Bragazzi, N. L. et al. Global, regional, and national burden of Guillain–Barré syndrome and its underlying causes from 1990 to 2019. J. Neuroinflammation 18 , 264. https://doi.org/10.1186/s12974-021-02319-4 (2021).

Article   PubMed   PubMed Central   Google Scholar  

Huang, W. C., Lu, C. L. & Chen, S. C. A 15-year nationwide epidemiological analysis of Guillain–Barré syndrome in Taiwan. Neuroepidemiology 44 , 249–254. https://doi.org/10.1159/000430917 (2015).

Salmon, D. A. et al. Association between Guillain–Barré syndrome and influenza A (H1N1) 2009 monovalent inactivated vaccines in the USA: A meta-analysis. Lancet 381 , 1461–1468. https://doi.org/10.1016/s0140-6736(12)62189-8 (2013).

Marks, J. S. & Halpin, T. J. Guillain–Barré syndrome in recipients of A/New Jersey influenza vaccine. JAMA 243 , 2490–2494 (1980).

Martín Arias, L. H., Sanz, R., Sáinz, M., Treceño, C. & Carvajal, A. Guillain-Barré syndrome and influenza vaccines: A meta-analysis. Vaccine 33 , 3773–3778. https://doi.org/10.1016/j.vaccine.2015.05.013 (2015).

Sanz Fadrique, R., Martín Arias, L., Molina-Guarneros, J. A., Jimeno Bulnes, N. & García Ortega, P. Guillain–Barré syndrome and influenza vaccines: Current evidence. Rev. Esp. Quimioter 32 , 288–295 (2019).

CAS   PubMed   Google Scholar  

Chen, Y., Zhang, J., Chu, X., Xu, Y. & Ma, F. Vaccines and the risk of Guillain–Barré syndrome. Eur. J. Epidemiol. 35 , 363–370. https://doi.org/10.1007/s10654-019-00596-1 (2020).

Lehmann, H. C., Hartung, H. P., Kieseier, B. C. & Hughes, R. A. Guillain–Barré syndrome after exposure to influenza virus. Lancet Infect. Dis. 10 , 643–651. https://doi.org/10.1016/s1473-3099(10)70140-7 (2010).

Prestel, J. et al. Risk of Guillain–Barré syndrome following pandemic influenza A(H1N1) 2009 vaccination in Germany. Pharmacoepidemiol. Drug Saf. 23 , 1192–1204. https://doi.org/10.1002/pds.3638 (2014).

Hanson, K. E. et al. Incidence of Guillain–Barré syndrome after COVID-19 vaccination in the vaccine safety datalink. JAMA Netw Open 5 , e228879. https://doi.org/10.1001/jamanetworkopen.2022.8879 (2022).

Keh, R. Y. S. et al. COVID-19 vaccination and Guillain–Barré syndrome: Analyses using the National Immunoglobulin Database. Brain J. Neurol. https://doi.org/10.1093/brain/awac067 (2022).

Article   Google Scholar  

Anjum, Z. et al. Guillain–Barré syndrome after mRNA-1273 (Moderna) COVID-19 vaccination: A case report. Clin. Case Rep. 10 , e05733. https://doi.org/10.1002/ccr3.5733 (2022).

Waheed, S., Bayas, A., Hindi, F., Rizvi, Z. & Espinosa, P. S. Neurological complications of COVID-19: Guillain–Barre syndrome following Pfizer COVID-19 vaccine. Cureus 13 , e13426. https://doi.org/10.7759/cureus.13426 (2021).

Takahashi, K. et al. Guillain–Barré syndrome after BNT162b2 (Pfizer-BioNTec) vaccination. QJM 115 , 331–333. https://doi.org/10.1093/qjmed/hcac102 (2022).

Chun, J. Y. et al. Guillain–Barré syndrome after vaccination against COVID-19. Lancet Neurol. 21 , 117–119. https://doi.org/10.1016/s1474-4422(21)00416-6 (2022).

Kim, J. E. et al. Guillain–Barré syndrome and variants following COVID-19 vaccination: Report of 13 cases. Front. Neurol. 12 , 820723. https://doi.org/10.3389/fneur.2021.820723 (2021).

Patone, M. et al. Neurological complications after first dose of COVID-19 vaccines and SARS-CoV-2 infection. Nat. Med. 27 , 2144–2153. https://doi.org/10.1038/s41591-021-01556-7 (2021).

Article   CAS   PubMed   PubMed Central   Google Scholar  

Sejvar, J. J. et al. Guillain–Barré syndrome and Fisher syndrome: Case definitions and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine 29 , 599–612. https://doi.org/10.1016/j.vaccine.2010.06.003 (2011).

Asbury, A. K. & Cornblath, D. R. Assessment of current diagnostic criteria for Guillain–Barré syndrome. Ann. Neurol. 27 (Suppl), S21-24. https://doi.org/10.1002/ana.410270707 (1990).

Leonhard, S. E. et al. Diagnosis and management of Guillain–Barré syndrome in ten steps. Nat. Rev. Neurol. 15 , 671–683. https://doi.org/10.1038/s41582-019-0250-9 (2019).

Rajabally, Y. A., Durand, M. C., Mitchell, J., Orlikowski, D. & Nicolas, G. Electrophysiological diagnosis of Guillain–Barré syndrome subtype: Could a single study suffice?. J. Neurol. Neurosurg. Psychiatry 86 , 115–119. https://doi.org/10.1136/jnnp-2014-307815 (2015).

Klein, N. P. et al. Surveillance for adverse events after COVID-19 mRNA vaccination. JAMA 326 , 1390–1399. https://doi.org/10.1001/jama.2021.15072 (2021).

García-Grimshaw, M. et al. Incidence of Guillain–Barré syndrome following SARS-CoV-2 immunization: Analysis of a nationwide registry of recipients of 81 million doses of seven vaccines. Eur. J. Neurol. 29 , 3368–3379. https://doi.org/10.1111/ene.15504 (2022).

Fay, M. P. & Feuer, E. J. Confidence intervals for directly standardized rates: A method based on the gamma distribution. Stat. Med. 16 , 791–801. https://doi.org/10.1002/(sici)1097-0258(19970415)16:7%3c791::aid-sim500%3e3.0.co;2-# (1997).

Sejvar, J. J., Baughman, A. L., Wise, M. & Morgan, O. W. Population incidence of Guillain–Barré syndrome: A systematic review and meta-analysis. Neuroepidemiology 36 , 123–133. https://doi.org/10.1159/000324710 (2011).

Sipilä, J. O. T., Soilu-Hänninen, M., Ruuskanen, J. O., Rautava, P. & Kytö, V. Epidemiology of Guillain–Barré syndrome in Finland 2004–2014. J. Peripher. Nerv. Syst. 22 , 440–445. https://doi.org/10.1111/jns.12239 (2017).

Doets, A. Y. et al. Regional variation of Guillain–Barré syndrome. Brain 141 , 2866–2877. https://doi.org/10.1093/brain/awy232 (2018).

Maramattom, B. V. et al. Guillain–Barré syndrome following ChAdOx1-S/nCoV-19 vaccine. Ann. Neurol. 90 , 312–314. https://doi.org/10.1002/ana.26143 (2021).

Allen, C. M. et al. Guillain–Barré syndrome variant occurring after SARS-CoV-2 vaccination. Ann. Neurol. 90 , 315–318. https://doi.org/10.1002/ana.26144 (2021).

Polack, F. P. et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N. Engl. J. Med. 383 , 2603–2615. https://doi.org/10.1056/NEJMoa2034577 (2020).

Baden, L. R. et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 384 , 403–416. https://doi.org/10.1056/NEJMoa2035389 (2021).

Chu, L. et al. Immune response to SARS-CoV-2 after a booster of mRNA-1273: An open-label phase 2 trial. Nat. Med. 28 , 1042–1049. https://doi.org/10.1038/s41591-022-01739-w (2022).

Moreira, E. D. Jr. et al. Safety and efficacy of a third dose of BNT162b2 Covid-19 vaccine. N. Engl. J. Med. 386 , 1910–1921. https://doi.org/10.1056/NEJMoa2200674 (2022).

Flaxman, A. et al. Reactogenicity and immunogenicity after a late second dose or a third dose of ChAdOx1 nCoV-19 in the UK: A substudy of two randomised controlled trials (COV001 and COV002). Lancet 398 , 981–990. https://doi.org/10.1016/s0140-6736(21)01699-8 (2021).

Oster, M. E. et al. Myocarditis cases reported after mRNA-based COVID-19 vaccination in the US from December 2020 to August 2021. JAMA 327 , 331–340. https://doi.org/10.1001/jama.2021.24110 (2022).

Che, Y. et al. Circulating memory T follicular helper subsets, Tfh2 and Tfh17, participate in the pathogenesis of Guillain–Barré syndrome. Sci. Rep. 6 , 20963. https://doi.org/10.1038/srep20963 (2016).

Article   ADS   CAS   PubMed   PubMed Central   Google Scholar  

Hagen, K. M. & Ousman, S. S. The neuroimmunology of Guillain–Barré syndrome and the potential role of an aging immune system. Front. Aging Neurosci. 12 , 6628. https://doi.org/10.3389/fnagi.2020.613628 (2020).

Article   CAS   Google Scholar  

Sahin, U. et al. COVID-19 vaccine BNT162b1 elicits human antibody and T(H)1 T cell responses. Nature 586 , 594–599. https://doi.org/10.1038/s41586-020-2814-7 (2020).

Article   ADS   CAS   PubMed   Google Scholar  

Ewer, K. J. et al. T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial. Nat. Med. 27 , 270–278. https://doi.org/10.1038/s41591-020-01194-5 (2021).

Hohnoki, K., Inoue, A. & Koh, C. S. Elevated serum levels of IFN-gamma, IL-4 and TNF-alpha/unelevated serum levels of IL-10 in patients with demyelinating diseases during the acute stage. J. Neuroimmunol. 87 , 27–32. https://doi.org/10.1016/s0165-5728(98)00053-8 (1998).

Lustig, Y. et al. Superior immunogenicity and effectiveness of the third compared to the second BNT162b2 vaccine dose. Nat. Immunol. 23 , 940–946. https://doi.org/10.1038/s41590-022-01212-3 (2022).

Chapin-Bardales, J., Gee, J. & Myers, T. Reactogenicity following receipt of mRNA-based COVID-19 vaccines. JAMA 325 , 2201–2202. https://doi.org/10.1001/jama.2021.5374 (2021).

Barros-Martins, J. et al. Immune responses against SARS-CoV-2 variants after heterologous and homologous ChAdOx1 nCoV-19/BNT162b2 vaccination. Nat. Med. 27 , 1525–1529. https://doi.org/10.1038/s41591-021-01449-9 (2021).

Khoo, N. K. H. et al. Differential immunogenicity of homologous versus heterologous boost in Ad26.COV2.S vaccine recipients. Med. (N. Y.) 3 , 104-118.e104. https://doi.org/10.1016/j.medj.2021.12.004 (2022).

Download references

Acknowledgements

The authors would like to acknowledge the assistance of every working colleague at the Gyeonggi Infectious Disease Control Center for their dedication to public health and overall support for this project. The authors received no financial support for the research, authorship, or publication of this manuscript.

Author information

These authors contributed equally: Jongmok Ha and Suyeon Park.

Authors and Affiliations

Infectious Disease Control Center, Gyeonggi Provincial Government, Suwon, Korea

Jongmok Ha, Hyunwook Kang, Taeeun Kyung, Namoh Kim, Dong Kyu Kim, Hyeonjoon Kim, Kihoon Bae, Min Cheol Song, Kwang June Lee, Euiho Lee & Kunhee Park

Department of Biostatistics, Soonchunhyang University Seoul Hospital, Seoul, Korea

Suyeon Park

Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-Gu, Seoul, 06351, Korea

Jinyoung Youn

Neuroscience Center, Samsung Medical Center, Seoul, Korea

Department of Neurology, Soonchunhyang University Hospital Cheonan, Soonchunhyang University College of Medicine, Cheonan, Korea

Jin Myoung Seok

Department of Applied Statistics, Chung-Ang University, Seoul, Republic of Korea

Suyeon Park & Beom Seuk Hwang

You can also search for this author in PubMed   Google Scholar

Contributions

J.H. contributed to the acquisition and analysis of the data and drafted a significant portion of the manuscript and figures. S.P. contributed to the conception and design of the study and drafted a significant portion of the manuscript and figures. H.W.K., T.K., N.K., D.K.K., H.J.K., K.B., M.C.S., K.J.L., and E.L. contributed to the acquisition and verification of data; B.S.H. contributed to the design of the study and interpretation of data; and J.Y., J.M.S., and K.P. contributed to the conception and design of the study, interpretation of data, and revision of the manuscript.

Corresponding authors

Correspondence to Jinyoung Youn , Jin Myoung Seok or Kunhee Park .

Ethics declarations

Competing interests.

The authors declare no competing interests.

Additional information

Publisher's note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Supplementary information., rights and permissions.

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ .

Reprints and permissions

About this article

Cite this article.

Ha, J., Park, S., Kang, H. et al. Real-world data on the incidence and risk of Guillain–Barré syndrome following SARS-CoV-2 vaccination: a prospective surveillance study. Sci Rep 13 , 3773 (2023). https://doi.org/10.1038/s41598-023-30940-1

Download citation

Received : 13 October 2022

Accepted : 03 March 2023

Published : 07 March 2023

DOI : https://doi.org/10.1038/s41598-023-30940-1

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

This article is cited by

Guillain–barré syndrome and covid-19 vaccination: a systematic review and meta-analysis.

• Stefano Censi
• Giandomenico Bisaccia
• Antonino Uncini

Journal of Neurology (2024)

By submitting a comment you agree to abide by our Terms and Community Guidelines . If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Quick links

• Explore articles by subject
• Guide to authors
• Editorial policies

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Less Than 30% of Asians and Pacific Islanders in the U.S. Feel Properly Represented on Screen, Study Finds

By Selena Kuznikov

Selena Kuznikov

• Key Takeaways From Variety’s Entertainment Marketing Summit: ‘You Have to be Reactive and Agile’ 7 hours ago
• Less Than 30% of Asians and Pacific Islanders in the U.S. Feel Properly Represented on Screen, Study Finds 21 hours ago
• Lionsgate Television Signs New Multi-Year Deal With Head of Production Gary Goodman 2 days ago

A new study from McKinsey & Co. and non-profit organization Gold House found that while Asian and Pacific Islander representation in the entertainment industry has made significant gains over the past several decades, most API consumers do not perceive API representation in film and television as authentic or reflecting their own stories.

The report states that accurate API representation in media could potentially lead to an additional $2 to $4.4 billion increase in industry revenues, as half of API consumers would be willing to spend more money and time on films and television shows that more authentically represent their experiences.

Popular on Variety

“If you have an API person at the top, you are far more likely to see API folks in other roles,” an industry association leader said in the report. “The traditional executives and buyers are not from our community, and it will be hard to make changes until we see more of them greenlighting shows and heading departments.”

According to the study, almost two-thirds of major films with API leads do not tell API race-specific stories — which does not necessarily mean the entire show centers solely around these characters’ API identities. The report points to “Beef,” which “reflected the experiences of its characters’ ethnicities without feeling ‘the need to contextualize or overexplain itself for viewers outside the Asian American community.'”

The study concluded by suggesting ideas that could potentially enable the film and television industry to tap into more authentic API representation: increasing the odds of greenlighting and distributing API projects, increasing financial support for API projects and creators, investing in API off-screen talent, expanding the criteria for evaluating projects and continuing to understand the state of API representation.

“There is no silver bullet available to the industry,” researchers wrote. “Instead, it requires real change in how the production ecosystem operates—from decision making to pipeline development to how potential API projects are evaluated.”

More From Our Brands

Donna kelce calls taylor swift’s ‘the tortured poets department’ her ‘best work’, royal huisman is building the world’s tallest sailing yacht, caleb williams goes solo in nfl representation debate, be tough on dirt but gentle on your body with the best soaps for sensitive skin, ahs: delicate finale delivers ominous, abrupt ending — grade it, verify it's you, please log in.