Recurrent Guillain-Barré syndrome.

BACKGROUND: Guillain-Barré syndrome (GBS) is generally considered to be monophasic, but recurrences do occur in a presently undefined subgroup of patients. OBJECTIVES: To determine which subgroup of patients develops a recurrence and to establish whether preceding infections and neurological symptoms are similar in subsequent episodes. METHODS: A recurrence was defined as two or more episodes that fulfilled the NINCDS criteria for GBS, with a minimum time between episodes of 2 months (when fully recovered in between) or 4 months (when only partially recovered). Patients with a treatment-related fluctuation or chronic inflammatory demyelinating polyneuropathy with acute onset were excluded. The clinical characteristics of recurrent GBS patients were compared with those of 476 non-recurrent patients. RESULTS: 32 recurrent GBS patients, who had a total of 81 episodes, were identified. The clinical symptoms in a first episode were similar to the following episodes in individual patients, being GBS or its variant Miller Fisher syndrome (MFS) but never both. While neurological symptoms in subsequent episodes were often similar, the severity of the symptoms and the nature of the preceding infections varied. Recurrent patients (mean age 34.2 years) were younger than non-recurrent patients (mean age 46.9; p = 0.001) and more often had MFS (p = 0.049) or milder symptoms (p = 0.011). CONCLUSIONS: Genetic or immunological host factors may play an important role in recurrent GBS, since these patients can develop similar symptoms after different preceding infections. Recurrences occur more frequently in patients under 30, with milder symptoms and in MFS.

Residual fatigue is independent of antecedent events and disease severity in Guillain-Barré syndrome.

The occurrence of severe fatigue after Guillain-Barré syndrome (GBS), and its relation with disease course, clinical characteristics, and antecedent infections was studied in 100 GBS patients. Severe fatigue, expressed as a mean Fatigue Severity Scale (FSS) score of 5.0 or more, was present in 60% of all patients. It was more frequently present in females and in patients over 50 years (p < 0.01). There was no significant relationship between fatigue severity and the level of functional disability at nadir, antecedent events or infections, clinical variables, and time to follow-up after GBS.

Corticosteroids for Guillain-Barré syndrome.

BACKGROUND: The cause of Guillain-Barré syndrome is inflammation of the peripheral nerves, which corticosteroids would be expected to benefit. OBJECTIVES: To examine the ability of corticosteroids to hasten recovery and reduce the long-term morbidity from Guillain-Barré syndrome. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Register (May 2005), MEDLINE (January 2000 to May 2005) and EMBASE (January 1980 to May 2005) and contacted trial authors and other experts. SELECTION CRITERIA: We included quasi-randomised or randomised controlled trials of people of all ages and all degrees of severity of Guillain-Barré syndrome who were treated with any form of corticosteroid or adrenocorticotrophic hormone. Our primary outcome measure was change in disability grade on a commonly used, validated seven-point scale at four weeks after randomisation. Secondary outcome measures were: time from randomisation until recovery of unaided walking, time from randomisation until discontinuation of ventilation (for those ventilated), mortality, proportion of participants dead or disabled (unable to walk without aid) after 12 months, improvement in disability grade after six and 12 months, relapse, and adverse events related to corticosteroid treatment. DATA COLLECTION AND ANALYSIS: Two authors extracted the data. MAIN RESULTS: Six trials with 587 participants provided data for our primary outcome measure . The overall evidence showed no significant difference between the corticosteroid and non-corticosteroid treated patients in disability grade. In four trials of oral corticosteroids with 120 participants in total, there was significantly less improvement after four weeks with corticosteroids than without corticosteroids (weighted mean difference of 0.82 of a disability grade less improvement, 95% confidence intervals 0.17 to 1.47). In two trials with a combined total of 467 participants, there was a trend towards more benefit from intravenous corticosteroids which was not quite significant, weighted mean difference 0.17 (95% confidence intervals -0.06 to 0.39) of a disability grade more improvement after four weeks than with placebo. There were no important significant differences between the corticosteroid-treated participants and the control group in any of the secondary outcome measures. Diabetes was significantly more common and hypertension much less common in the corticosteroid-treated participants. AUTHORS' CONCLUSIONS: Limited evidence shows that oral corticosteroids significantly slow recovery from Guillain-Barré syndrome. Substantial evidence shows that intravenous methylprednisolone alone does not produce significant benefit or harm. In combination with intravenous immunoglobulin, intravenous methylprednisolone may hasten recovery but does not significantly affect the long-term outcome. More research is needed and more effective treatments for Guillain-Barré syndrome should be sought.

Steroids in the Guillain-Barré syndrome: is there a therapeutic window?

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HLA class II alleles are not a general susceptibility factor in Guillain-Barré syndrome.

OBJECTIVE: To assess whether human leukocyte antigen (HLA)-DRB1 and HLA-DQB1 alleles confer susceptibility to Guillain-Barre syndrome (GBS) or are related to specific clinical or serologic subgroups of GBS. METHODS: The HLA-DRB1 and HLA-DQB1 loci were genotyped by PCR amplification with sequence-specific primers in 164 well-documented Dutch patients with GBS and 207 healthy Dutch control subjects. Patients with GBS were divided into subgroups based on clinical features, severity of disease, antecedent infection, and anti-ganglioside antibodies. Data were compared with those of all case-control HLA studies in GBS performed previously. RESULTS: In this case-control study, HLA-DRB1 and HLA-DQB1 alleles did not differ between GBS patients and control subjects. The frequency of HLA-DRB1*01 was increased in patients who needed mechanical ventilation (odds ratio 4.2; 95% CI 1.9 to 9.6; p(c) = 0.02). Multivariate logistic regression analysis showed that this association was independent of the severity of paresis and the presence of cranial nerve involvement (all p < 0.05). There was a tendency toward an association between certain HLA alleles and several anti-ganglioside antibodies. CONCLUSIONS: Human leukocyte antigen (HLA) class II antigens are not a general susceptibility factor in Guillain-Barre syndrome (GBS). However, HLA class II alleles may be a determinant in distinct subgroups of GBS, indicating the need for further exploration in large-scale studies.

Effect of methylprednisolone when added to standard treatment with intravenous immunoglobulin for Guillain-Barré syndrome: randomised trial.

BACKGROUND: Despite available treatment with intravenous immunoglobulin (IVIg), morbidity and mortality are considerable in patients with Guillain-Barré syndrome (GBS). Our aim was to assess whether methylprednisolone, when taken with IVIg, improves outcome when compared with IVIg alone. METHODS: We did a double-blind, placebo-controlled, multicentre, randomised study, to which we enrolled patients who were unable to walk independently and who had been treated within 14 days after onset of weakness with IVIg (0.4 g/kg bodyweight per day) for 5 days. We assigned 233 individuals to receive either intravenous methylprednisolone (500 mg per day; n=116) or placebo (n=117) for 5 days within 48 h of administration of first dose of IVIg. Because age is an important prognostic factor, we split treatment groups into two age-groups-ie, younger than age 50 years, or 50 years and older. Our primary outcome was an improvement from baseline in GBS disability score of one or more grades 4 weeks after randomisation. Analysis was by intention to treat. FINDINGS: We analysed 225 patients. GBS disability scores increased by one grade or more in 68% (76 of 112) of patients in the methylprednisolone group and in 56% (63 of 113) of controls (odds ratio [OR] 1.68, 95% CI 0.97-2.88; p=0.06). After adjustment for age and degree of disability at entry, treatment OR was 1.89 (95% CI 1.07-3.35; p=0.03). Side-effects did not differ greatly between groups. INTERPRETATION: We noted no significant difference between treatment with methylprednisolone and IVIg and IVIg alone. Because of the relevance of prognostic factors and the limited side-effects of methylprednisolone, the potential importance of combination treatment with the drug and IVIg, however, warrants further investigation.

Cross-reactive anti-galactocerebroside antibodies and Mycoplasma pneumoniae infections in Guillain-Barré syndrome.

Anti-galactocerebroside (GalC) antibodies are reported to be present in GBS patients with preceding Mycoplasma pneumoniae (MP) infection. We investigated the presence of anti-GalC reactivity in serum of a large group of GBS patients using ELISA and compared this with healthy controls and individuals with an uncomplicated MP infection. Anti-GalC antibody reactivity was present in 12% of the GBS patients. Furthermore, anti-GalC antibodies were associated with MP infections, a relatively mild form of the disease and demyelinating features. Anti-GalC antibodies cross-reacted with MP antigen. In conclusion, anti-GalC antibodies in GBS patients may be induced by molecular mimicry with MP.

Infections and course of disease in mild forms of Guillain-Barré syndrome.

OBJECTIVE: Twenty-eight percent of patients with the Guillain-Barré syndrome remain able to walk unaided. Studying patients with the mild form of Guillain-Barré syndrome can further contribute to knowledge of the spectrum of the syndrome and explore whether this subgroup may need treatment with IV immunoglobulin. METHODS: Patients fulfilling the National Institute of Neurologic and Communicative Disorders and Stroke criteria for Guillain--Barré syndrome were included in a nationwide survey over a 2-year period. Clinical characteristics and serum samples were collected prospectively. In addition, a questionnaire was completed concerning the course and outcome of the disease. RESULTS: A total of 139 patients were included. Nineteen of the patients (14%) included were mildly affected, and 120 (86%) were severely affected. Infections with Epstein-Barr virus were found more frequently in mildly affected patients (p = 0.02). Antiganglioside antibodies were less frequently found in the mildly affected patients (p = 0.03). The degree of severity of the disease between mildly and severely affected patients was different on the day of admission (p < 0.01). Thereafter, the groups showed a remarkably similar rate of progression. Thirty-eight percent of mildly affected patients report problems in hand function and an inability to run at 3 and 6 months (all women, p = 0.02). CONCLUSION: The difference in severity of Guillain--Barré syndrome seems to be determined in an early phase of the disease. Preceding infections and antiganglioside antibodies may influence the initial immune attack, determining the severity of the disease. The presence of residual signs in patients with mild disease may advocate the use of early treatment in mildly affected patients.

Gastroenteritis-associated Guillain-Barré syndrome on the Caribbean island Curaçao.

BACKGROUND: The number of patients with Guillain-Barré syndrome (GBS) who have been observed in Curaçao, the Netherlands Antilles, may be increasing. METHODS: Clinical and serologic data were obtained from records of patients admitted between 1987 and 1999 and fulfilling National Institute of Neurological and Communicative Disorders and Stroke criteria for GBS. When possible, serum and stool samples were collected. The results were compared with a large Dutch epidemiologic study. RESULTS: The authors identified 49 patients, an overall crude incidence rate (IR) in Curaçao of 2.53/100,000 inhabitants (95% CI 1.87 to 3.35) (Dutch study 1.18, rate ratio (RR) of 2.14, p < 0.001). The IR in Curaçao increased from 1.62 in 1987 to 1991 to 3.10 in 1992 to 1999, RR 5.22 (95% CI 2.48 to 10.2, p = 0.02). The IR showed a curvilinear shape within a year. In comparison with the Dutch group, patients from Curaçao had a more severe course of the disease, with a mortality rate of 23% (3.4% in the Dutch group, p < 0.001), a higher percentage of preceding gastroenteritis (p < 0.001), and less sensory involvement (p < 0.001). In 8 of 10 serum samples, evidence was found for a recent infection with Campylobacter jejuni. CONCLUSIONS: The authors found a steady increase in incidence of GBS over the years in association with a more pronounced seasonal preponderance and a more severe course. The clinical characteristics suggest a role for C jejuni.

Changes in referral pattern and its effect on outcome in patients with Guillain-Barré syndrome.

The authors assessed the referral pattern and outcome in patients with Guillain-Barré syndrome (n = 266) after the introduction of intravenous immunoglobulin (IVIg). Fewer patients were transferred from small to large hospitals after the introduction of IVIg (p = 0.05). This did not result in a worse outcome in patients treated in small centers. The introduction of IVIg has led to a better use of different levels of health care facilities.

A case of Guillain-Barré syndrome following a family outbreak of Campylobacter jejuni enteritis.

We describe an outbreak of Campylobacter jejuni enteritis involving three family members of whom one developed Guillain-Barré syndrome (GBS). The patients' serum reacted strongly with several gangliosides and with the lipopolysaccharide (LPS) fractions from the C. jejuni strains isolated from his family members. Only low titer anti-ganglioside antibodies were found in his siblings. HLA-typing did not indicate a locus associated with auto-antibody production. Comparing the immune response in GBS patients and C. jejuni enteritis patients can be of great value in determining the additional factors that lead to post-Campylobacter GBS. Ganglioside mimicry alone is necessary but not sufficient for the induction of anti-ganglioside antibodies. Other susceptibility factors are required to induce an anti-neural immune response.

IgG receptor IIa alleles determine susceptibility and severity of Guillain-Barré syndrome.

OBJECTIVE: Guillain-Barré syndrome (GBS) is characterized by nerve infiltration of leukocytes and autoantibodies of the immunoglobulin G (IgG) isotype directed against nerve constituents. Leukocyte receptors for IgG (FcgammaR) constitute an important link between the humoral and cellular parts of the immune system and confer potent cellular effector functions to myelin-directed antibodies. Three FcgammaR subclasses exhibit genetically determined biallelic functional polymorphisms (FcgammaRIIa: R131 versus H131; FcgammaRIIIa: 158V versus 158F; FcgammaRIIIb: NA1 versus NA2) that determine efficacy of the cellular immune response. To study the relevance of these polymorphisms for susceptibility and severity of GBS, we compared FcgammaR genotype distributions in GBS patients with those in controls. METHODS: Genomic DNA was isolated from whole blood of 31 randomly selected patients with GBS and 187 healthy blood donors. Genotypes of the three polymorphic FcgammaR genes were determined by PCR. RESULTS: FcgammaRIIa-H131 homozygosity was significantly increased in patients as compared with healthy controls (OR 2.45; 95% CI 1.12 to 5.36; p = 0.037). Furthermore, FcgammaRIIa-H131 homozygous GBS patients had a higher risk for severe disease than did patients with other genotypes (OR 18.57; 95% CI 1.95 to 176.49; p = 0.007). CONCLUSION: FcgammaRIIa allotypes capable of initiating efficient cellular effector functions are associated with increased risk for GBS and a more severe disease course. FcgammaR alleles may constitute novel genetic risk markers for GBS.

Increasing the incidence of the Guillain-Barre syndrome in Curacao

OBJECTIVE: To confirm an observed increase in the occurrence of Guillain-Barre syndrome (GBS) in patients in Curacao. DESIGN AND METHODS: Between 1987 and 1999, medical records of all patients who fulfilled the National Institute of Neurological Communicative Disorders and Stroke (NINCDS) criteria for GBS were reviewed. RESULTS: Forty-nine patients were diagnosed as GBS resulting in an incidence rate (IR) of 2.53/100,000 inhabitants (95 percent CI 1.87-3.35). From 1987 to 1991, the IR remained stable, whereas from 1992 to 1999, there was a linear increase in the IR. There was a high IR in the colder months and a low IR in the warmer months. Patients showed a low percentage of sensory involvement (17 percent, generally 65 percent), rapid progression of the disease (83 percent, generally 30 percent), high percentage of artificial respiration (31 percent, generally 17 percent) and high mortality rate (23 percent, generally 3-5 percent). Fifty-five percent of the patients reported a preceding gastroenteritis (GE); 9/10 serum samples showed evidence of a recent Campylobacter jejuni infection. CONCLUSIONS: This is the first report of an increase in IR of GBS over a longer period, associated with low percentage of sensory involvement, a more severe course and a high mortality rate. The characteristics suggest a role for C jejuni. Prospective research is needed to show whether the increase in GBS is due to an overall increase in IR of C. jejuni infections on the island.(Au)

Mild forms of Guillain-Barré syndrome in an epidemiologic survey in The Netherlands.

OBJECTIVE: Assessment of incidence rates of Guillain-Barré syndrome (GBS) in the Netherlands over a 10-year period; investigation of a relationship between possible seasonality in GBS and the occurrence of preceding infections; and determination of distinctive characteristics in patients with GBS who are only mildly affected (able to walk unaided at nadir). METHOD: Records of patients with GBS admitted between 1987 and 1996 from all 45 hospitals in the southwest Netherlands were evaluated, covering a population of 4.2 million inhabitants. RESULTS: A total of 476 patients met National Institute for Neurological and Communicative Disorders and Stroke criteria for GBS. This resulted in a crude incidence rate (IR) of 1.18/100,000 inhabitants. This IR increased linearly with age (p < 0.001). Men were more frequently affected than women (p < 0.001). No seasonal preponderance for GBS, nor for any of the preceding infections, was found. Patients under 50 years of age (p < 0.001) and men (p = 0.01) were more frequently found in the mildly affected group. In both groups a preceding infection was reported in 70% of the cases. In the severely affected group, serologic evidence for infection with Campylobacter jejuni, cytomegalovirus, Epstein-Barr virus, or Mycoplasma pneumoniae was found more frequently than in the mildly affected group (41% versus 16%, p = 0.001). CONCLUSIONS: Overall IR in the Netherlands are similar to those found in other studies. The incidence increases linearly with age and men are more frequently affected than women. Distinctive characteristics for mildly and severely affected patients were found regarding age, sex, and preceding infections. This suggests that other infectious agents or host factors may be involved in mild forms of GBS.

Health burden in the Netherlands due to infection with thermophilic Campylobacter spp.

Infection with thermophilic Campylobacter spp. usually leads to an episode of acute gastroenteritis. Occasionally, more severe diseases may be induced, notably Guillain Barré syndrome and reactive arthritis. For some, the disease may be fatal. We have integrated available data in one public health measure, the Disability Adjusted Life Year (DALY). DALYs are the sum of Years of Life Lost by premature mortality and Years Lived with Disability, weighted with a factor between 0 and 1 for the severity of illness. The mean health burden of campylobacter-associated illness in the Dutch population in the period 1990-5 is estimated as 1400 (90% CI 900-2000) DALY per year. The main determinants of health burden are acute gastroenteritis (440 DALY), gastroenteritis related mortality (310 DALY) and residual symptoms of Guillain-Barré syndrome (340 DALY). Sensitivity analysis demonstrated that alternative model assumptions produced results in the above-mentioned range.

Measuring vibration threshold with a graduated tuning fork in normal aging and in patients with polyneuropathy. European Inflammatory Neuropathy Cause and Treatment (INCAT) group.

OBJECTIVE: To provide clinically useful vibration threshold normal values. METHODS: The graduated Rydel-Seiffer tuning fork was evaluated in 198 healthy controls and 59 patients with a polyneuropathy. The measures were done in triplicate at four locations: the distal interphalangeal joint of the index finger, ulnar styloid process, interphalangeal joint of the hallux, and internal malleolus. The values obtained with this tuning fork in healthy controls and patients with polyneuropathy were compared with the values of an electronic device, the Vibrameter. RESULTS: Vibration sense was better perceived in the arms compared with the legs. There was a significant age related decline of vibration sense at all locations. The values from the Rydel-Seiffer tuning fork and the Vibrameter were significantly correlated in both groups. The sensitivity of these two instruments for the four sites examined in the polyneuropathy group ranged from 29-76% and 31-73%, respectively and was the highest at the hallux for both instruments. CONCLUSION: This study provides clinical useful normal values of vibration threshold for the Rydel-Seiffer tuning fork. This is a simple and easily applicable instrument that assesses vibration sense semiquantitatively and should therefore have a place in routine neurological examination.