Prediction of disease progression in Miller Fisher and overlap syndromes.

Patients with Miller Fisher syndrome (MFS) may have a relatively mild clinical course or progress to Guillain-Barré syndrome (GBS) with limb weakness (MFS-GBS overlap syndrome). Other variants in this spectrum are GBS with ophthalmoparesis and Bickerstaff's Brainstem encephalitis (BBE). To compare the clinical course of MFS and overlap syndromes and to identify predictors of disease progression. In a prospective study of 170 patients with GBS and variant forms, 37 (22%) had a MFS, MFS-GBS overlap syndrome, ophthalmoplegic GBS or BBE. The clinical, serological, and electrophysiological features were compared. Twenty-three patients presented with MFS, of which 10 (43%) developed limb weakness (MFS-GBS overlap syndrome). All these transitions occurred in the first week after onset of symptoms. There were no differences in the clinical, electrophysiological and serological features at entry between MFS and MFS-GBS. Twelve patients had ophthalmoplegic GBS and the disease severity at nadir and outcome was worse than in the patients with a MFS-GBS overlap syndrome. No early predictors for progression from MFS to MFS-GBS overlap syndrome were found. All transitions occurred in the first week. This finding implicates that all patients with MFS need careful monitoring for at least 1 week.

Prediction of respiratory insufficiency in Guillain-Barré syndrome.

OBJECTIVE: Respiratory insufficiency is a frequent and serious complication of the Guillain-Barré syndrome (GBS). We aimed to develop a simple but accurate model to predict the chance of respiratory insufficiency in the acute stage of the disease based on clinical characteristics available at hospital admission. METHODS: Mechanical ventilation (MV) in the first week of admission was used as an indicator of acute stage respiratory insufficiency. Prospectively collected data from a derivation cohort of 397 GBS patients were used to identify predictors of MV. A multivariate logistic regression model was validated in a separate cohort of 191 GBS patients. Model performance criteria comprised discrimination (area under receiver operating curve [AUC]) and calibration (graphically). A scoring system for clinical practice was constructed from the regression coefficients of the model in the combined cohorts. RESULTS: In the derivation cohort, 22% needed MV in the first week of admission. Days between onset of weakness and admission, Medical Research Council sum score, and presence of facial and/or bulbar weakness were the main predictors of MV. The prognostic model had a good discriminative ability (AUC, 0.84). In the validation cohort, 14% needed MV in the first week of admission, and both calibration and discriminative ability of the model were good (AUC, 0.82). The scoring system ranged from 0 to 7, with corresponding chances of respiratory insufficiency from 1 to 91%. INTERPRETATION: This model accurately predicts development of respiratory insufficiency within 1 week in patients with GBS, using clinical characteristics available at admission. After further validation, the model may assist in clinical decision making, for example, on patient transfer to an intensive care unit.

IVIG treatment and prognosis in Guillain-Barré syndrome.

INTRODUCTION: Guillain-Barré syndrome (GBS) is an acute, immune-mediated polyneuropathy that often leads to severe weakness. Intravenous immunoglobulin (IVIG) is a proven effective treatment for GBS (class 1 evidence). However, about 25% of patients need artificial ventilation and 20% are still unable to walk unaided after 6 months. Important clinical factors associated with poor outcome are age, presence of preceding diarrhea and the severity of disability in the early course of disease. These clinical factors were combined in a clinical prognostic scoring scale, the Erasmus GBS Outcome Scale (EGOS). MATERIALS AND METHODS: GBS patients being unable to walk unaided are currently treated with a standard single IVIg dose (0.4 g/kg bodyweight for 5 days). A recent retrospective study in 174 GBS patients enrolled in one of our randomized controlled clinical trials showed that patients with a minor increase of serum IgG level after standard single IVIg dose recovered significantly slower. Additionally, fewer patients reached the ability to walk unaided at six months after correction for the known clinical prognostic factors (multivariate analysis; P < 0.022). DISCUSSION: It is yet unknown why some GBS patients only have a minor increase after standard IVIg treatment. By using the EGOS it is possible to select GBS patients with a poor prognosis. These patients potentially may benefit from a second IVIg dose. CONCLUSION: A standard dose of IVIG is not sufficiently effective in many GBS patients. Whether these patients might benefit from a second IVIg dose needs further investigation.

Effect of glucocorticoid receptor gene polymorphisms in Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is a postinfectious immune-mediated polyneuroradiculopathy in which host factors influence disease susceptibility and clinical course. Single-nucleotide polymorphisms (SNPs) in the glucocorticoid receptor (GR) gene influence the sensitivity to glucocorticoids and are related to both microbial colonization and susceptibility to develop auto-immune disease. This genetic variation may therefore also influence the chance to develop GBS. In this study, we genotyped 318 GBS patients and 210 control subjects for five known SNPs in the GR gene. We could distinguish six different GR haplotypes of which two carried the BclI polymorphism: haplotype 1, which consists of the minor allele of BclI in combination with the common variant of TthIIII and haplotype 2, which carries the minor allele of BclI as well as the minor allele of TthIIII. The GR haplotypes were not related to susceptibility to develop GBS. Carriers of haplotype 2 had more frequently preceding diarrhea, serum antibodies to GM1 and GD1a, and more severe muscle weakness at entry. Haplotype 1 carriers had a significantly better prognosis. In conclusion, GR haplotypes are not a susceptibility factor for GBS. However, haplotypes carrying the minor allele of the BclI polymorphism were related to the phenotype and outcome of GBS.

Clinical features, pathogenesis, and treatment of Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is an important cause of acute neuromuscular paralysis. Molecular mimicry and a cross-reactive immune response play a crucial part in its pathogenesis, at least in those cases with a preceding Campylobacter jejuni infection and with antibodies to gangliosides. The type of preceding infection and patient-related host factors seem to determine the form and severity of the disease. Intravenous immunoglobulin (IVIg) and plasma exchange are effective treatments in GBS; mainly for practical reasons, IVIg is the preferred treatment. Whether mildly affected patients or patients with Miller Fisher syndrome also benefit from IVIg is unclear. Despite medical treatment, GBS often remains a severe disease; 3-10% of patients die and 20% are still unable to walk after 6 months. In addition, many patients have pain and fatigue that can persist for months or years. Advances in prognostic modelling have resulted in the development of a new and simple prognostic outcome scale that might also help to guide new treatment options, particularly in patients with GBS who have a poor prognosis.

Determination of pain and response to methylprednisolone in Guillain-Barré syndrome.

UNLABELLED: Pain can be a serious problem in patients with Guillain-Barré syndrome (GBS). Different pain symptoms and the effect of methylprednisolone on pain are evaluated. METHODS: GBS patients were recruited from a randomized placebo-controlled study comparing intravenous immunoglobulin (IVIg) + methylprednisolone (500 mg for 5 days) versus IVIg + placebo. Presence and severity of pain were prospectively scored at randomization and after 4 weeks. Efficacy of methylprednisolone was evaluated using endpoints: percentage of patients with pain and percentage of patients improving in pain-severity level. Medical records of the subgroup of patients treated in the Erasmus MC were screened retrospectively for different pain symptoms and course. Pain was scored at different time intervals: within 4 weeks before randomization and 0-2, 2-4, 4-24, 24-52 weeks after randomization. RESULTS: 123 (55%) of 223 patients had pain at randomization. In 70%, pain already started before onset of weakness. Methylprednisolone did not show a positive effect on the presence and reduction of pain. In the subgroup of 39 patients, backache (33%), interscapular (28%), muscle (24%), radicular pain (18%) and painful par-/dysaesthesiae (18%) were most frequently present within the period of 4 weeks before randomization. Twenty-six percent had extreme pain 0-2 weeks after randomization. Most symptoms of pain decreased after this period, but painful par-/dysaesthesiae and muscle pain often remained present during at least 6 months. CONCLUSIONS: Pain frequently occurs, often starts before onset of weakness and may cause severe complaints. Especially painful par-/dysaesthesiae and muscle pain may persist for months. Methylprednisolone seems to have no significant effect on the presence and intensity of pain.

Unmyelinated and myelinated skin nerve damage in Guillain-Barré syndrome: correlation with pain and recovery.

We performed a prospective study in 32 patients with Guillain-Barré syndrome (GBS) or its variants to correlate intraepidermal nerve fiber density (IENFD) at the distal leg and lumbar region with pain, autonomic dysfunction, and outcome. In the acute phase, IENFD was reduced in 60% and 61.9% of patients at the distal leg and lumbar region, respectively. In the acute phase, 43.7% of patients complained of neuropathic pain. Their IENFD at the distal leg was significantly lower than in patients without pain (P<.001) and correlated with pain intensity (r(s)=-0.51; P=.003). Intriguingly, also patients with the pure motor variant of GBS and pain had low IENFD. At 6-month follow-up, only 3 patients complained of persisting neuropathic pain, whereas 3 patients reported late-onset pain symptoms. IENFD in the acute phase did not predict presence or intensity of pain at 6-month follow-up. IENFD in the acute phase did not correlate with clinical dysautonomia or GBS severity at nadir. However, it correlated with poorer GBS disability score at 6 months (P=.04), GBS score at nadir (P=.03), and clinically probable dysautonomia (P=.004). At 6-month follow-up, median IENFD remained significantly low both at the distal leg (P=.024) and lumbar region (P=.005). Double and triple staining confocal microscope studies showed diffuse damage of myelinated dermal nerves along with axonal degeneration, and mononuclear cell infiltration. Unmyelinated and myelinated skin nerves are diffusely affected in GBS and its variants, including the pure motor form. IENFD declines early, remains low over time, correlates with pain severity in the acute phase, and may predict long-term disability.

Diagnostic value of anti-GQ1b antibodies in a patient with relapsing dysarthria and ataxia.

Serum antibodies to the ganglioside GQ1b are associated with immune-mediated ophthalmoplegia and ataxia in patients with Miller-Fisher syndrome (MFS) and Guillain-Barré syndrome. A patient with two clinically similar episodes of progressive bulbar signs, ophthalmoplegia and ataxia is reported here. During both episodes the patient required artificial ventilation. Serum anti-GQ1b antibodies were detected during the first episode compatible with MFS, but were absent during the second. Neuroradiological investigations during the second episode showed brain stem ischaemia and obstruction of the left posterior inferior cerebral artery. These findings illustrate that anti-GQ1b serology is a reliable and robust method that helped to distinguish between different causes of relapsing dysarthria and ataxia.

Distinguishing acute-onset CIDP from Guillain-Barré syndrome with treatment related fluctuations.

Guillain-Barré syndrome (GBS) patients may worsen after initial treatment (treatment-related fluctuation [TRF]). It is difficult to distinguish GBS-TRF from chronic inflammatory demyelinating polyneuropathy with acute onset (A-CIDP). The authors compared 13 patients with A-CIDP with 11 patients with GBS-TRF and concluded that A-CIDP should be suspected when a patient with GBS deteriorates after 9 weeks from onset or when deterioration occurs three times or more. Maintenance treatment should then be considered.

Treatment of chronic inflammatory demyelinating polyneuropathy.

PURPOSE OF REVIEW: Chronic inflammatory demyelinating poly(radiculo)neuropathy (CIDP) is a treatable disorder. There are three proven effective treatments available. Randomized controlled trials have only focused on short-term effects, but most patients need long-term therapy. The most up-to-date treatment options are discussed. Attention is also paid to the use of appropriate assessment scales and treatment of residual findings. RECENT FINDINGS: A Cochrane review is available indicating that intravenous immunoglobulin is an effective treatment. Equal efficacy of intravenous immunoglobulin and steroids was shown during a 6-week treatment period. New open studies indicated possible efficacy for mycophenolate, interferon-beta and etanercept. Combinations of treatment are scarcely studied yet. Some CIDP patients may have a more acute onset of disease since maximum severity is reached within 4-8 weeks, resulting in confusion about the diagnosis. It was shown that severe fatigue can be a major complaint in CIDP patients; a training regimen might partially resolve these problems. SUMMARY: CIDP is a treatable disorder, but most patients need long-term treatment. Intravenous immunoglobulin, steroids and plasma exchange are shown to be effective. It is suggested that other immunomodulatory agents can also be effective, but randomized trials are needed to confirm these benefits. General measures to rehabilitate patients and to manage symptoms like fatigue and other residual findings are important.