J. Meulstee

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.

High-dose intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyneuropathy: a double-blind, placebo-controlled, crossover study

We discontinued high-dose intravenous immunoglobulin treatment (IVIg) in 7 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) who seemed to have responded to IVIg. After discontinuation of treatment, all 7 patients deteriorated. We then randomized the patients to IVIg or placebo (albumin) treatment in a double-blind crossover study. The clinical condition of all patients improved after IVIg and did not improve after placebo treatment. The mean time lapse from the end of the trial treatment to the occurrence of deterioration was 6.4 weeks after treatment with IVIg and 1.3 weeks after treatment with placebo. This selected group of patients with CIDP had a beneficial response to IVIg.

Treatment of Guillain-Barré syndrome with high-dose gammaglobulin

Intravenous gammaglobulin (IVGG) can improve the clinical course of several immune-mediated diseases. We report the first results of such treatment in eight patients with severe Guillain-Barré syndrome (GBS). We observed that IVGG was beneficial in at least some of the patients with severe GBS. These results should be confirmed in a randomized trial.

Cytomegalovirus infection and Guillain-Barre syndrome The clinical, electrophysiologic, and prognostic features

Guillain-Barre syndrome (GBS) is usually preceded by infections, in particular cytomegalovirus (CMV) and Campylobacter jejuni infection. We studied the clinical and electrophysiologic features of 20 CMV-associated GBS patients and compared the findings with earlier established data of C. jejuni-related GBS patients (n = 43) and of GBS patients without these infections (n = 71). The patients all participated in the Dutch GBS trial in which we compared the effect of intravenous immune globulins and plasma exchange. We demonstrate that CMV-related GBS patients have a different clinical pattern in comparison with the other two GBS groups. They are significantly younger, initially have a severe course indicated by a high frequency of respiratory insufficiency, and often develop cranial nerve involvement and severe sensory loss. This is in contrast to C. jejuni infection, which is associated with motor GBS. Both infections are associated with delayed recovery compared with the GBS patients without these infections. NEUROLOGY 1996;47: 668-673

Diagnostic and classification criteria for the Guillain-Barré syndrome

Background: Diagnostic criteria for the Guillain-Barré syndrome (GBS) have been available since 1978. Since then, several variants have been described. More recently, a distinction has been made between pure motor forms, severe sensory forms, primary axonal and primary demyelinating varieties. Associations of clinical characteristics, and specific infections and the presence of antiganglioside antibodies have been found. For further studies on GBS, it is therefore necessary to reconsider the available diagnostic criteria and add additional criteria for subclassification. Methods: A panel of (20) experts was formed. The literature representing the recent developments in GBS subclassification was reviewed. Following a consensus protocol, diagnostic and classification criteria were formulated. Results: The diagnosis of GBS can usually be made on clinical characteristics. A schedule for subclassification has been made to cover also the clinical variants in a systematic manner.

Prognostic factors of Guillain-Barré syndrome after intravenous immunoglobulin or plasma exchange

Objective: To determine the influence of clinical, laboratory, and electrodiagnostic factors on the prognosis of Guillain-Barré syndrome (GBS). Background: Identification of prognostic factors may lead to better selection of patients with a poor prognosis for new therapeutic trials. Methods: The authors studied 147 patients with GBS who participated in the Dutch GBS trial comparing the effect of IV immunoglobulins with plasma exchange (PE). Outcome was measured at 8 weeks because half of the patients had recovered independent locomotion by then and at 6 months, the endpoint of the study. Results: Multivariate logistic regression revealed the following factors predicting outcome (inability to walk independently) at 8 weeks: a preceding gastrointestinal illness (yes, no), age (≥50, <50 years), Medical Research Council sum score (<40, ≥40) at the start of treatment, and—described for the first time—a recent cytomegalovirus (CMV) infection (yes, no). At 6 months, the same clinical factors were found, but an initial rapid progression of weakness also appeared to be a prognostic factor. Analysis of treatment interactions revealed that the effect of diarrhea was more pronounced in the PE-treated group. Conclusions: The main predictors of outcome in GBS are clinical factors. Diarrhea is an important poor predictor of outcome, especially for the PE-treated group, and a recent CMV infection predicts delayed early recovery.

Chronic motor neuropathies: response to interferon-beta1a after failure of conventional therapies

OBJECTIVES The effect of interferon-β1a (INF-β1a; Rebif®) was studied in patients with chronic motor neuropathies not improving after conventional treatments such as immunoglobulins, steroids, cyclophosphamide or plasma exchange. METHODS A prospective open study was performed with a duration of 6–12 months. Three patients with a multifocal motor neuropathy and one patient with a pure motor form of chronic inflammatory demyelinating polyneuropathy were enrolled. Three patients had anti-GM1 antibodies. Treatment consisted of subcutaneous injections of IBF-β1a (6 MIU), three times a week. Primary outcome was assessed at the level of disability using the nine hole peg test, the 10 metres walking test, and the modified Rankin scale. Secondary outcome was measured at the impairment level using a slightly modified MRC sumscore. RESULTS All patients showed a significant improvement on the modified MRC sumscore. The time required to walk 10 metres and to fulfil the nine hole peg test was also significantly reduced in the first 3 months in most patients. However, the translation of these results to functional improvement on the modified Rankin was only seen in two patients. There were no severe adverse events. Motor conduction blocks were partially restored in one patient only. Anti-GM1 antibody titres did not change. CONCLUSION These findings indicate that severely affected patients with chronic motor neuropathies not responding to conventional therapies may improve when treated with INF-β1a. From this study it is suggested that INF-β1a should be administered in patients with chronic motor neuropathies for a period of up to 3 months before deciding to cease treatment. A controlled trial is necessary to confirm these findings.

Electrodiagnostic criteria for polyneuropathy and demyelination: application in 135 patients with Guillain-Barré syndrome. Dutch Guillain-Barré Study Group.

Since the development of effective but expensive therapeutic strategies for the treatment of Guillain-Barré syndrome, early confirmation of the diagnosis has become very important. Electrodiagnostic criteria were developed for the discrimination of polyneuropathy and in particular for demyelination. The sensitivity and specificity of these criteria were determined in 135 patients with Guillain-Barré syndrome in an early stage of the disease, along with 45 healthy volunteers. The algorithms used to develop our criteria consisted of sets of selected electrodiagnostic variables, each of them relevant to the detection of polyneuropathy. Each set was applied on all of three consecutive electrodiagnostic examinations within one month of disease onset. Application of the best set resulted in 85% of patients with Guillain-Barré syndrome fulfilling the criteria for polyneuropathy at the first examination (mean time interval six days of disease onset), whereas none of the healthy volunteers fulfilled the criteria (sensitivity 85%, specificity 100%). The set of criteria for the detection of demyelination was fulfilled by 60% during the first examination (by 66% and 72% during the second and third examination). Application of criteria for demyelinating polyneuropathy as defined by others resulted in substantially lowered incidence (3%-46%). It is concluded that these criteria for the electrodiagnostic delineation of polyneuropathy are the most sensitive to date, with respect to the early confirmation of the diagnosis of Guillain-Barré syndrome.

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-Barré 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; pc = 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-Barré 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.

Guillain-Barré Syndrome: Multifactorial Mechanisms versus Defined Subgroups

The clinical spectrum of Guillain-Barré syndrome (GBS) is summarized in relation to antecedent infections and anti-ganglioside antibodies. Associations exist between a pure motor form of GBS, diarrhea, Campylobacter jejuni infection, and anti-GM1 antibodies; between cranial nerve involvement and Miller Fisher syndrome, C. jejuni infection, and anti-GQ1b antibodies; and between variants, such as severe sensory involvement and cytomegalovirus infection. These three clinical variants are suggested to form the extremes of a continuous spectrum; they are discussed in relation to the more pathologically defined patterns of acute motor axonal neuropathy and acute motor-sensory axonal neuropathy. In particular, patients with a clinically pure motor variant of GBS, diarrhea, anti-GM1 antibodies, or C. jejuni infection seem to respond better to early treatment with high-dose immunoglobulins than to plasma exchange.