Update on Guillain‐Barré syndrome

Understanding of Guillain‐Barré syndrome (GBS) has progressed substantially since the seminal 1916 report by Guillain et al. Although Guillain, Barré, and Strohl summarised the syndrome based on observations of two French infantrymen, 2012 saw the beginning of an ambitious collaborative study designed to collect detailed data from at least 1,000 patients worldwide (IGOS, www.gbsstudies.org/about‐igos ). Progress has been made in many areas even since GBS was last reviewed in this journal in 2009. GBS subsequently received prominent attention in light of concerns regarding H1N1 influenza vaccinations, and several large‐scale surveillance studies resulted. Despite these developments, and promising pre‐clinical studies, disease‐modifying therapies for GBS have not substantially altered since intravenous immunoglobulin was introduced over 20 years ago. In other areas, management has improved. Antibiotic prophylaxis in ventilated patients reduces respiratory tract infection, thromboprophylaxis has reduced the risk of venous thromboembolism, and there is increasing awareness of the benefit of high‐intensity rehabilitation. This article highlights some of the interesting and thought‐provoking developments of the last 3 years, and is based on a plenary lecture given at the 2012 Peripheral Nerve Society (PNS) meeting.     

Incidence of Guillain‐Barré syndrome in Chile: a population‐based study

The Guillain‐Barré syndrome (GBS) incidence rate (IR) varies between 0.16 and 3.00 cases per 100,000 inhabitants. Little data exist on the epidemiology of GBS in Latin American countries. Our objective was to describe GBS epidemiology based on a national database in a Latin American country and to contribute to the global map of GBS epidemiology. This was a retrospective study that included all reported GBS cases in Chile between 2001 and 2012. Gender, age, seasonal occurrence, and geographical distribution were analyzed. A total of 4,158 GBS cases were identified from 19,513,655 registries. The mean age was 37 ± 24 years, and 59% of patients were male (male to female ratio of 1.5 : 1). Gender IR was 2.53/100,000 for males and 1.68/100,000 for females. The overall standardized IR was 2.1/100,000, although this varied between 1.61/100,000 (2001) and 2.35/100,000 (2010). The seasonal distribution was as follows: autumn 22%; winter 25%; spring 27%; and summer 26%. The geographical IR were as follows: far North 1.49/100,000; North 1.94/100,000; Central 1.97/100,000; South 3.18/100,000; and far South 2.78/100,000. The reported IR of GBS in Chile was similar to other studies based on national databases. In Chile, IR was greater in men and in the south.     

Guillain‐Barré syndrome in the elderly

The aim of the study was to analyze specific features of Guillain‐Barré syndrome (GBS) in old people. The study included 403 GBS patients (62% young [<60 years], 35% young‐old [60–80 years], and 3% old‐old [>80 years]). Diagnosis of GBS was made according to the National Institute of Neurological Disorders and Stroke (NINDS criteria). Severe disability (GBS disability score of >3) at nadir was more common in old compared with young patients (p = 0.0001) as was mortality (9% vs. 2%, respectively). Acute motor and sensory axonal neuropathy and hyponatremia were more common in old compared with young patients (12% vs. 6% and 27% vs. 18%, respectively, p = 0.04). A positive history for malignancy was more than three times more common in old than young patients (11% vs. 3%, respectively, p = 0.01). Disability on nadir was similar in young‐old and old‐old subjects with disability on discharge being more severe in old‐old (p = 0.04) suggesting slower recovery in this subgroup. Bulbar symptoms were more common in old‐old compared with young‐old (50% vs. 19%, respectively, p = 0.01). Comorbidities were present in virtually all old‐old patients compared with 66% of young‐old patients (p = 0.04). In conclusion, Elderly patients, and especially old‐old patients, with GBS have more severe disease with slower recovery than do younger patients.     

Paraparetic Guillain‐Barré syndrome: Nondemyelinating reversible conduction failure restricted to the lower limbs

Introduction: Paraparetic Guillain‐Barré syndrome (GBS) is a rare subtype of GBS characterized by leg weakness and areflexia in the absence of neurological involvement of the arms, cranial nerves, or respiratory muscles. Onset is characterized by lower back, buttock, or leg pain, followed by development of symmetric flaccid limb weakness in the absence of sensory disturbance. Methods: We describe an elderly woman who developed postinfectious symmetric flaccid leg weakness in the absence of sensory disturbance. Serial nerve conduction studies were carried out over 5 months. Results: Antecedent infection, a monophasic disease course, and the presence of cerebrospinal fluid albuminocytological dissociation suggested a diagnosis of paraparetic GBS. Serial nerve conduction studies demonstrated nondemyelinating reversible conduction failure, which was restricted to the legs. Axonal neuropathy was supported by the presence of anti‐GM1 IgG antibodies. Conclusions: These findings suggest that patients with paraparetic GBS have axonal neuropathy, which is restricted to the lower limbs. Muscle Nerve 55 : 281–285, 2017     

Clinical features of patients with Guillain‐Barré syndrome at seven hospitals on the East Coast of Australia

To document the clinical features of Guillain‐Barré syndrome (GBS) in Australia, we performed a retrospective analysis of all patients admitted to several hospitals along the East Coast of Australia from 2000 to 2012. Using hospital records, we reviewed all patients with a diagnosis of GBS admitted to seven hospitals. From these, we report information of subjects who fulfilled standard diagnostic criteria. We excluded patients where inadequate information was available or who were under the age of 18. We report the features of 335 patients, in 228 of whom neurophysiological data were available. There were 168 cases of acute inflammatory demyelinating polyneuropathy (AIDP), 17 of acute motor axonal neuropathy (AMAN), 4 of acute motor and sensory axonal neuropathy (AMSAN), and 35 of Miller‐Fisher syndrome (MFS). The median age at onset was 52.5 years (18–89 years) with a male : female ratio of 1.61 : 1. Upper respiratory tract infections were the most frequently identified trigger (151 subjects, 44.5%). Most patients were severely affected, with 42.7% of subjects bedbound, and an additional 24% requiring ventilatory support. GBS affects adults of all ages and usually follows a severe clinical course. In contrast to other autoimmune diseases, males are more frequently affected. A wide variety of triggering factors leads to a relatively stereotypical clinical syndrome. The most common variant of GBS in Australia is AIDP. This study shows that the clinical features of GBS in Australia are similar to that previously reported and confirms the male predominance, increased incidence with age, and frequent evidence of peripheral nerve demyelination as features of GBS.     

Motor nerve excitability after childhood Guillain‐Barré syndrome

Residual motor nerve dysfunction after pediatric Guillain‐Barré syndrome (GBS) was determined in an observational cross‐sectional cohort study in patients who previously developed GBS during childhood (<18 years). Ulnar motor nerve dysfunction was defined by compound motor action potential (CMAP) scan in patients after a follow up of at least 1 year compared with age‐matched healthy controls, in relation to clinical course and outcome. A total of 37 persons previously diagnosed with GBS in childhood were included with a mean age at current examination of 20.6 years (4–39 years). The median time between diagnosis and follow‐up was 11 years (range: 1–22 years). CMAP scanning indicated ulnar motor nerve dysfunction in 25 (68%) participants. The most frequent abnormality was a reduction in nerve excitability observed both in those with residual limb weakness and in the majority of those with complete recovery. CMAP scan characteristics were not related to prognostic factors or outcome. In conclusion, GBS in childhood results in residual motor nerve excitability disturbances, even in those completely recovered, probably reflecting altered physiology of regenerated peripheral nerves.     

Guillain‐Barré syndrome in France: a nationwide epidemiological analysis based on hospital discharge data (2008–2013)

Guillain‐Barré syndrome (GBS) is potentially life threatening and typically occurs after an infection. No detailed information is available concerning the epidemiological characteristics of GBS in France. We estimated age‐ and sex‐specific incidence rates (IRs) based on a French nationwide hospital discharge database. All patients hospitalized for GBS between 2008 and 2013 were identified by International Classification of Diseases‐10 code G61.0 as principal diagnosis. Patients previously hospitalized for GBS in 2006 and 2007 were excluded. Sensitivity analyses were performed by considering alternative case definitions, based on more restrictive sets of codes. A total of 9,391 patients were identified, leading to an overall crude IR of 2.42 per 100,000 person‐years (world standardized IR = 2.00). IRs increased with age, reaching a peak in the 70–79‐year age group. IR was 46% higher in men than in women, and 44% higher in winter than in summer. In children, the highest IR was observed at the age of 2 years. These patterns were not modified by the use of alternative case definitions. This French nationwide study showed similar GBS epidemiological patterns in adults to those reported in other countries. We also report a childhood incidence peak around the age of 2 years, as previously observed in Latin American and Chinese populations.     

Epidemiology of Guillain‐Barré syndrome in Finland 2004–2014

At total mean incidence of 0.84–1.1/100,000 the occurrence of Guillain‐Barré syndrome (GBS) is reported to be low in Finland compared to other Caucasian populations. However, a recent study from Southwestern Finland reported an incidence of 1.82/100,000 which is comparable to other Caucasian populations. We analyzed discharge data covering the years 2004 through 2014 on all neurological admissions in all Finnish university and central hospitals with a primary diagnosis of GBS. A total of 989 admissions due to GBS (917 individuals) were identified. The standardized (European population) annual incidence rate was 1.70/100,000 person‐years (95% confidence interval 1.60–1.81). GBS incidence had an increasing trend with age. The likelihood of GBS was higher among girls and adolescent women than boys and men of same age (male:female incidence rate ratio [IRR] 0.56), while in the older age groups (>19 years) the occurrence of GBS was higher among males than females (male:female IRR 1.59). The incidence of GBS remained stable during the study period. There was no seasonal variation in GBS admission frequencies (p = 0.28). No significant effect of the 2009–2010 H1N1 influenza or vaccination against it for GBS occurrence was observed. We suggest that GBS is as common, and has similar age‐distribution in Finland as in other European countries. Sex‐associated susceptibility for GBS appears to be different in children‐adolescents and adults.     

Long‐term outcome of Guillain‐Barré syndrome in children

The objective of this study is to determine the long‐term outcome and consequences of Guillain‐Barré syndrome (GBS) in children. This is an observational cross‐sectional cohort study of children diagnosed with GBS (0–18 years old) at the Sophia Children's Hospital in Rotterdam from 1987 to 2009. All patients were invited for a structured interview, questionnaires, and full neurologic exam to record their current clinical condition focused on complaints and symptoms, neurological deficits, disabilities, behavior, and quality of life. Thirty‐seven patients participated, 23 were now adults, with a median age of 20 years (range 4–39 years) and a median follow‐up time of 11 years (range 1–22 years). Residual complaints were reported by 24 (65%) patients, including paresthesias (38%), unsteadiness of gait in the dark (37%), painful hands or feet (24%), and severe fatigue (22%). Four patients had severe neurological deficits, including facial diplegia and limb weakness. Two patients had had a recurrence of GBS. In 10 patients (26%), GBS had a negative impact on their school career. Questionnaires identified a wide range of behavioral problems. Quality of life was below normal on the subscale vitality, and above normal on the subscales social functioning and positive emotions in the adult group. Most children show good recovery of neurological deficits after GBS, but many have persisting long‐term residual complaints and symptoms that may lead to psychosocial problems interfering with participation in daily life.     

High mortality from Guillain‐Barré syndrome in Bangladesh

Although Guillain‐Barré syndrome (GBS) has higher incidence and poor outcome in Bangladesh, mortality from GBS in Bangladesh has never been explored before. We sought to explore the frequency, timing, and risk factors for deaths from GBS in Bangladesh. We conducted a prospective study on 407 GBS patients who were admitted to Dhaka Medical College Hospital, Dhaka, Bangladesh from 2010 to 2013. We compared deceased and alive patients to identify risk factors. Cox regression model was used to adjust for confounders. Of the 407 GBS patients, 50 (12%) died, with the median time interval between the onset of weakness and death of 18 days. Among the fatal cases, 24 (48%) were ≥40 years, 36 (72%) had a Medical Research Council sum score ≤20 at entry, 33 (66%) had a progressive phase <8 days, and 27 (54%) required ventilation support. Ten patients (20%) died due to unavailability of ventilator. The strongest risk factor for deaths was lack of ventilator support when it was required (HR: 11.9; 95% confidence interval [CI]: 4.6–30.7). Other risk factors for death included age ≥40 years (HR: 5.9; 95% CI: 2.1–16.7), mechanical ventilation (HR: 2.3; 95% CI: 1.02–5.2), longer progressive phase (>8 days) (HR: 2.06; 95% CI: 1.1–3.8), autonomic dysfunction (HR: 1.9; 95% CI: 1.05–3.6), and bulbar nerve involvement (HR: 5.4; 95% CI: 1.5–19.2). In Bangladesh, GBS is associated with higher mortality rates, which is related to lack of ventilator support, disease severity, longer progressive phase of the disease, autonomic dysfunction, and involvement of the bulbar nerves.     

Increased incidence of axonal Guillain‐Barré syndrome in La Spezia area of Italy: A 13‐year follow‐up study

Guillain‐Barré syndrome (GBS) is an acute immune‐mediated polyradiculoneuropathy with a worldwide incidence of 0.81‐1.89 per 100 000 person‐years. In Europe and North America only 5% of patients with GBS have axonal subtypes, which in South America and Asia account for 30%‐47% of cases. The aim of our study is to assess the annual incidence and clinical features of GBS in La Spezia area in Italy. A retrospective (from 1 January 2003 to 31 December 2011) followed by a prospective (from 1 January 2012 to 31 December 2015) analysis was carried out on patients admitted to La Spezia hospital who fulfilled the GBS diagnostic criteria. A total of 86 patients (58 men), mean age of 62.7 years (range 21‐90), were included. The mean annual incidence rate was 3/100 000 (range: 0.9/100 000‐5.37/100 000) significantly higher than the European incidence (P < 0.001). Forty‐seven percent were classified as acute inflammatory demyelinating polyradiculoneuropathy (AIDP), 35% as acute motor and motor‐sensory axonal neuropathy (AMAN‐AMSAN), 13% as variant forms, and 5% were not defined. AIDP was most common in “Golfo dei Poeti” (50%) and “Val di Magra” (63.2%), whereas AMAN/AMSAN prevailed in “Val di Vara” (63.6%) and “Riviera Spezzina” (62.5%) (P = 0.024). In La Spezia area GBS incidence (especially the AMAN subtype) is significantly higher than the incidence reported in Europe. AIDP predominates in the eastern area whereas AMAN/AMSAN in the western, with a significantly different incidence rate (P = 0.003). Prospective studies to assess possible predisposing environmental factors are needed.     

What's new in Guillain‐Barré syndrome in 2007–2008?*

The years 2007 and early 2008 have been an exciting time for Guillain‐Barré syndrome (GBS) research. Epidemiological studies have shown that the incidence of GBS remains stable at about 2/100,000 per year but that there have been changes in hospitalization use, likely due to the widespread availability of IVIg. Research into mechanisms has shown the importance of single amino acids in Campylobacter jejuni and the importance of ganglioside conformation. In a murine model of anti‐ganglioside antibody‐mediated neuropathy, Eculizumab was effective in reversing clinical disease and preventing pathology. This suggests trials of Eculizumab in GBS should be considered. Unfortunately, there are no new randomized controlled trials in GBS to report although the unmet need is great.     

The long‐term functional status in patients with Guillain‐Barré syndrome

Background and purpose: The purpose of this study was to analyse the long‐term impact of Guillain‐Barré syndrome (GBS) on quality of life, and the relationship between clinical variables at disease onset and symptoms at follow‐up to general health status. Methods: Forty‐two GBS patients were examined at median 6 years after disease onset and were compared with 50 healthy controls. The fatigue severity scale (FSS), visual analogue scale (VAS) for pain, disability rating index (DRI) and medical outcome study 36‐item short‐form health status scale (SF‐36) were applied. Variables at onset and symptoms at follow‐up were correlated with outcome measurements in GBS. Results: VAS [2.9 (SD 3.3) vs. 1.5 (SD 1.9); P = 0.01] and DRI [2.5 (SD 2.1) vs. 1.0 (SD 1.5); P < 0.001] were significantly higher in patients with GBS, compared with healthy controls. Decreased physical functioning and general health were found on SF‐36. Differences between GBS patients with shorter (<6 years) and longer (≥6 years) follow‐up after onset were not found. Conclusions: Relatively independent from various variables at onset, patients with GBS seem to have a reduced quality of life and functioning, and the distress seems to have become persistent after the first few years with improvement following the acute disease.     

Clinical and serological prognostic factors in childhood Guillain‐Barré syndrome: A prospective cohort study in Bangladesh

Guillain‐Barré syndrome (GBS) is the most common cause of acute flaccid paralysis in children. The objective of this study was to investigate the preceding infections, clinical, serological and electrophysiological characteristics and outcome of childhood GBS in Bangladesh. We included 174 patients with GBS aged <18 years from a prospective cohort in Bangladesh between 2010 and 2018. We performed multivariate logistic regression to determine the risk factors for poor outcome. Among 174 children with GBS, 74% (n = 129) were male. Around half of the patients (49%, n = 86) had severe muscle weakness, 65% (n = 113) were bedbound (GBS disability score 4) and 17% (n = 29) patients required mechanical ventilation at admission. Campylobacter jejuni serology and anti‐GM1 IgG antibody were positive in 66% and 21% of the patients respectively. One hundred and forty‐three (82%) patients did not receive standard treatment and half of them recovered fully or with minor deficits at 6‐month. Twenty patients (11%) died throughout the study period. At 3‐month of onset of weakness, complete recovery or recovery with minor deficit was significantly higher in demyelinating GBS patients compared to axonal GBS patients (86% vs 51%, P = .001). Cranial nerve palsy (OR = 4.00, 95%CI = 1.55‐10.30, P = .004) and severe muscle weakness (OR = 0.16, 95%CI = 0.06‐0.45, P = .001) were the important risk factors of poor outcome in children with GBS. Further large‐scale studies are required for better understanding of factors associated with mortality and morbidity in childhood GBS.     

Diabetes mellitus may affect short‐term outcome of Guillain‐Barré syndrome

We sought to determine influence of diabetes mellitus on Guillain‐Barré syndrome (GBS) course and short‐term prognosis. Among the 257 GBS patients included in this retrospective study, diabetes mellitus was present in 17%. The degree of disability at admission and on discharge was assessed according to the GBS Disability Scale (mild disability = 0–3, severe disability = 4–6). Even after correction for age, diabetes mellitus was significantly associated with more severe disability at nadir (odds ratio, OR = 3.4, p < 0.05) and on discharge (OR = 2.0, p < 0.05). Linear regression analysis with multiple factors included showed that age and presence of diabetes were significant predictors of severe disability at nadir (adjusted R² = 0.21, p < 0.05), and on discharge (adjusted R² = 0.19, p < 0.05). The presence of diabetes mellitus affects short‐term prognosis of GBS, independent of age.     

The 2016 Singapore Zika virus outbreak did not cause a surge in Guillain‐Barré syndrome

Although individuals with Zika virus (ZIKV) antibodies were reported in Malaya in mid‐1950s, entomological and human surveillance in Singapore did not identify autochthonous transmission until the outbreak of August‐November, 2016. A total of 455 cases from 15 separate clusters were identified. We asked if this ZIKV outbreak increased the incidence of Guillain‐Barré syndrome (GBS) and aimed to characterize these cases. Eleven GBS cases, consecutively enrolled into our prospective GBS database from onset to 4 weeks after outbreak, and six controls, comprising three GBS patients enrolled before outbreak and three non‐GBS patients, were examined for evidence of recent ZIKV infection. We performed serum, urine ZIKV RT‐PCR, ZIKV serology, and virus neutralization assays, accounting for cross‐reaction and co‐infection with dengue (DENV). We found five GBS cases with only serological evidence of recent ZIKV infection (including one ZIKV‐DENV co‐infection). A temporal relationship with ZIKV outbreak was unlikely as two cases were GBS controls enrolled 3 months before outbreak. None reported symptoms of ZIKV infection. In addition, compared to last 10 years the national number of GBS hospitalizations did not increase during and immediately after outbreak. We conclude the 2016 Singapore ZIKV outbreak did not cause a change in GBS epidemiology.     

Clinico‐electrophysiological findings and prognosis of Guillain‐Barré syndrome – 10 years’ experience

Soysal A, Aysal F, Calıskan B, Dogan Ak P, Mutluay B, Sakallı N, Baybas S, Arpacı B. Clinico‐electrophysiological findings and prognosis of Guillain‐Barré syndrome – 10 years’ experience.
Acta Neurol Scand: 2011: 123: 181–186.
© 2010 John Wiley & Sons A/S. Objective – To assess correlation between the prognosis and epidemiological, clinical, laboratory, electrophysiological findings in patients with Guillain‐Barré syndrome (GBS). Methods – We reviewed the medical records of 104 GBS patients who were hospitalized and followed up at our outpatient clinic during October 1997–November 2007. Results – Guillain‐Barré syndrome patients were followed up with a median period of 232 days. Full recovery or minor deficits were observed in 41% of patients in the first month, 71% in the third month, 86% in the sixth month and 92% in the first year. We found that there was a correlation between Medical Research Council (MRC) sum scores at admission, clinical subtypes, respiratory distress, interference pattern and prognosis. Conclusions – Demographic, clinical and electrophysiological findings of our GBS cases were highly similar to those of the previous reports. Two of our cases were presented with preceding tuberculosis infection, which was not reported before in the literature.     

Health‐related quality of life in Guillain‐Barré syndrome patients: a systematic review

Guillain‐Barré syndrome (GBS) encompasses a broad spectrum of health‐related quality of life (HRQL) determinants, including mobility, fatigue, pain, and depression. We systematically reviewed the literature on functional outcome domains in which GBS patients experience limitations in the short and long terms and evaluated determinants of HRQL in GBS patients. MEDLINE and EMBASE were systematically searched by two independent reviewers for articles covering HRQL data of GBS patients. Of 730 abstracts screened, 17 articles covering data of 14 studies matched the selection criteria. The included articles showed that many GBS patients experienced physical limitations, even years after the acute phase of the disease, while results were inconsistent for perceived levels of pain, fatigue, and general mental well‐being. Only three papers covered HRQL assessments at more than one time point, generally showing large improvements in HRQL in the first year after GBS onset, but not thereafter. We appraised the methodological quality of included studies using a 13‐item checklist; none of the articles fulfilled all items and only seven articles presented data on correlations between HRQL and determinants. In conclusion, the majority of studies on HRQL in GBS patients are cross‐sectional and of low methodological quality. This paper provides guidance for much needed high‐quality studies on patterns of patient‐perceived recovery after GBS onset.