Nerve conduction velocity in CMT1A: what else can we tell?

BACKGROUND AND PURPOSE: Charcot-Marie-Tooth disease (CMT) type 1A is characterized by uniformly reduced nerve conduction velocity (NCV) that is fully penetrant since the first years of life, remains fairly stable through the life and does not correlate with disability whereas compound muscular action potential (CMAP) amplitude does. The aim of the present study was to analyze the large amount of electrophysiological data collected in the ascorbic acid trial in Italy and the UK (CMT-TRIAAL/CMT-TRAUK) and to use these data to gain insights into the pathophysiology of NCV in CMT1A. METHODS: Baseline electrophysiological data from 271 patients were analysed. Electrophysiological recordings were taken from the motor ulnar, median and peroneal nerves and the sensory ulnar nerve. Distal motor latency (DML), motor (MNCV) and sensory (SNCV) nerve conduction velocity, and amplitudes of CMAPs and sensory action potentials were assessed. Electrophysiological findings were correlated with age of patients at examination and the Charcot-Marie-Tooth Examination Score (CMTES). RESULTS: NCV was markedly and uniformly reduced. CMAP amplitudes were overall reduced but more severely in lower limbs. DML decreased and MNCV and SNCV increased with age of the patients, whereas CMAP amplitudes worsened with age and also correlated with CMTES. CONCLUSIONS: This is the largest sample of electrophysiological data obtained so far from CMT1A patients. Axonal degeneration as assessed by means of CMAP amplitude reflected clinical impairment and was consistent with a slowly progressive length-dependent neuropathy. All patients typically had markedly slowed NCV that did, however, slightly increase with age of the patients. The improvement of NCV might depend on myelin thickness remodelling that occurs during the adult life of CMT1A patients.

Regarding the past, what is the trial you have always been dreaming of in CIDP?

Chronic inflammatory demyelinating polyradiculoneuropathy is an orphan disease of poorly understood cause. While first line treatments with corticosteroids, intravenous immunoglobulin and plasma exchange have at least short-term efficacy, no trial has shown that immunosuppressants work. In our dream, we will take advantage of the recently improved EU regulations to launch a Europe wide trial which will investigate the cause of the disease. It will compare three parallel groups, the anti-B cell agent rituximab, the anti-T cell agent abatacept and usual care. The trial will not be blinded and the design will be very simple. The primary outcome measure will be improvement from baseline of the overall neuropathy limitations scale (ONLS) score by 1 or more grades at 12 weeks without increase in concomitant corticosteroids or IVIg or use of plasma exchange. There will be an option to substitute improvement in the Rasch-built overall disability scale depending on future experience with that scale as the primary outcome measure. The trial will require 3 groups of 60 participants to detect an increase from 20% in the usual care group to 30% with one of the other agents with a power of 90% and P-value of 5%. It will be larger than any trial of an immunosuppressant agent so far performed in CIDP. However, recruitment will be easier because inclusion criteria will be broad and allow randomisation of any patient in whom their neurologist wishes to introduce an immunosuppressant. Avoidance of blinding and use of simple monitoring with facetime will simplify running the trial and reduce expense. The trial will follow participants and measure outcomes at 12 months. Other outcomes will consist only of grip strength, time to walk 10 m and Euroqol, the last allowing us to estimate the cost per QALY of rituximab or abatacept. Even including central analysis of key biomarkers, the trial will only cost 3 million euros, a fraction of the cost of the usual phase III pharmaceutical company trial.

Responsiveness of clinical outcome measures in Charcot-Marie-Tooth disease.

BACKGROUND AND PURPOSE: Charcot-Marie-Tooth disease (CMT) is a very slowly progressive neuropathy which makes it difficult to detect disease progression over time and to assess intervention efficacy. Experience from completed clinical trials with ascorbic acid and natural history studies confirm difficulties in detecting such changes. Consequently, sensitive-to-change outcome measures (OMs) are urgently needed. METHODS: The relative responsiveness of clinical scales of the Italian-UK ascorbic acid trial (placebo arm) were assessed by using the standardized response mean (SRM), which is the ratio of the paired scores mean change over time to the standard deviation of the score change (0 is worst responsiveness). RESULTS: Little worsening of OM scores was found over 2 years. In detail, the primary OM of the trial, the CMT Neuropathy Score version 1 (CMTNSv1), showed low responsiveness (SRM 0.13). Some CMTNS items showed slightly greater responsiveness (CMT Examination Score 0.17; CMTNS Signs 0.19). Myometric assessments of handgrip and foot dorsiflexion strength were the most responsive (SRM -0.31 and -0.38, respectively). Amongst the other measures, the nine-hole peg test, which assesses upper limb functioning, showed the best sensitivity to change (SRM 0.28). CONCLUSIONS: Overall these OMs showed low or negligible responsiveness, confirming the need to improve current OMs and to develop novel ones for prognostic and interventional studies. However, handgrip and foot dorsiflexion myometry are worth retaining for future trials as they were the most responsive and are likely to be clinically relevant for patients.

Is overwork weakness relevant in Charcot-Marie-Tooth disease?

BACKGROUND: In overwork weakness (OW), muscles are increasingly weakened by exercise, work or daily activities. Although it is a well-established phenomenon in several neuromuscular disorders, it is debated whether it occurs in Charcot-Marie-Tooth disease (CMT). Dominant limb muscles undergo a heavier overload than non-dominant and therefore if OW occurs we would expect them to become weaker. Four previous studies, comparing dominant and non-dominant hand strength in CMT series employing manual testing or myometry, gave contradictory results. Moreover, none of them examined the behaviour of lower limb muscles. METHODS: We tested the OW hypothesis in 271 CMT1A adult patients by comparing bilateral intrinsic hand and leg muscle strength with manual testing as well as manual dexterity. RESULTS: We found no significant difference between sides for the strength of first dorsal interosseous, abductor pollicis brevis, anterior tibialis and triceps surae. Dominant side muscles did not become weaker than non-dominant with increasing age and disease severity (assessed with the CMT Neuropathy Score); in fact, the dominant triceps surae was slightly stronger than the non-dominant with increasing age and disease severity. DISCUSSION: Our data does not support the OW hypothesis and the consequent harmful effect of exercise in patients with CMT1A. Physical activity should be encouraged, and rehabilitation remains the most effective treatment for CMT patients.

Epidemiology of chronic inflammatory neuropathies in southeast England.

BACKGROUND AND PURPOSE: There is little information about the prevalence and disease burden of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN) and paraproteinaemic demyelinating neuropathy (PDN). METHODS: Multiple sources were used to study the prevalence and clinical features of these diseases in a southeast England population of 3,557,352 people. RESULTS: The crude prevalences were as follows: CIDP, 2.84 (95% CI 2.31-3.45); MMN, 0.53 (95% CI 0.32-0.83); and PDN, 1.04 (95% CI 0.73-1.43) per 100,000 population. All three diseases were more common in men than in women. The peak decade of onset was older in those with CIDP (70-79 years) and PDN (70-79 years) than in those with MMN (50-59 years). Disability was greater in CIDP and PDN, with median (range) overall neuropathy limitations scores of 4 (0-8) and 4 (1-6), respectively, than in MMN, with a score of 2 (1-5). CONCLUSION: The common forms of chronic inflammatory neuropathy cause a considerable disease burden in the community.

Economic costs and quality of life in chronic inflammatory neuropathies in southeast England.

BACKGROUND AND PURPOSE: Cost-of-illness studies and health-related quality of life (HRQoL) measurements are needed to assess the effects of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN) and paraproteinaemic demyelinating neuropathy (PDN) on society. METHODS: This study was conducted in 2008 in a southeast England population of 3,557,352 people. Data on service use and treatment were collected with a client service receipt inventory and service costs were calculated by combining these data with national unit costs. The EuroQol was used to calculate utility scores, a measurement of HRQoL. RESULTS: The total annual cost-of-illness per patient was £22,085 for CIDP, £22,812 for MMN and £7566 for PDN. The annual total cost per patient was £49,430 for individuals on intravenous immunoglobulin (IVIg) and £9046 for those not on IVIg (P < 0.01). The mean (SD) utility scores were 0.62 (0.23) for CIDP, 0.63 (0.22) for PDN and 0.72 (0.14) for MMN (P = 0.52). The mean (SD) utility score for those on IVIg was 0.65 (0.16) and those not on IVIg 0.63 (0.23) (P = 0.77). CONCLUSION: The use of IVIg was the most important determinant of cost in all three diseases and the higher frequency of its use in CIDP and MMN accounted for the much greater average cost per patient in these diseases. There was no significant difference in HRQoL amongst the three diseases or between those receiving or not receiving IVIg.

Vigorimeter grip strength in CIDP: a responsive tool that rapidly measures the effect of IVIG--the ICE study.

BACKGROUND AND PURPOSE: In a recent trial in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), the ICE study, grip strength measurement captured significantly more improvement in patients receiving immune globulin (IGIV-C) intravenously than in those receiving placebo. METHODS: We conducted a systematic analysis to determine the sensitivity of grip strength as an indicator of meaningful clinical changes in CIDP. RESULTS: A randomized double-blind trial was undertaken in 117 CIDP patients who received IGIV-C or placebo every 3 weeks for up to 24 weeks. Grip strength and inflammatory neuropathy cause and treatment (INCAT) disability scores were assessed at each visit, and the responsiveness of each scale was compared. A minimum clinically important difference cut-off value for grip strength (>8 kPa) and INCAT score (>1 point) was applied to assess the proportion of responders to IGIV-C versus placebo. This analysis showed that grip strength demonstrated significant improvement earlier (as early as day 16) than the INCAT disability scale in patients receiving IGIV-C compared with placebo. A significantly higher proportion of improvers were seen in the IGIV-C group (37.5%-50.9%) than in the placebo group (21.1%-25.9%) for grip strength at day 16, week 3, week 6 and the end of the first period. Also, grip strength showed within the first 6 weeks in the placebo group significantly more patients with a clinically meaningful deterioration (>8 kPa), compared with the INCAT (>1-point deterioration) findings. CONCLUSIONS: Grip strength can be considered a sensitive tool for assessing clinically relevant changes in patients with CIDP. Its use in daily practice is suggested.

Confirming the efficacy of intravenous immunoglobulin in CIDP through minimum clinically important differences: shifting from statistical significance to clinical relevance.

BACKGROUND: The ICE trial demonstrated the efficacy of immune globulin intravenous (IGIV-C) over placebo in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). However, improving the interpretability of the results by analysing the minimum clinically important difference (MCID) had not been considered. OBJECTIVES: To identify MCID thresholds of various outcome measures using different methods and to test treatment differences (IGIV-C vs placebo) using these thresholds. METHODS: One anchor-based (Short Form-36 question 2) and three distribution-based (½ SD, 1 SE of measurement, and effect size) techniques were employed to identify MCID cut-offs for various impairments (electromyographic parameters, Medical Research Council (MRC) sum score, grip strength, inflammatory neuropathy cause and treatment (INCAT) sensory sum score), disability (INCAT scale score, Rotterdam handicap scale (RHS) score) and quality of life (SF-36). IGIV-C or placebo was administered every 3 weeks for up to 24 weeks to 117 CIDP patients. Patients who did not improve by ≥1 point on the INCAT scale received alternate treatment. The proportion of patients with results exceeding identified MCID thresholds was compared. Results MCID cut-offs for outcomes were determined using each method. For the INCAT disability scale (primary ICE-trial outcome), all MCID methods identified significantly more responders with IGIV-C than placebo. Significant differences favouring IGIV-C were also demonstrated for various nerve conduction parameters, MRC sum score, grip strength, RHS score and SF-36 physical component summary score. CONCLUSION: In addition to being statistically significant, all MCID analyses showed that CIDP improvements with IGIV-C are clinically meaningful. Consideration of MCID is recommended in future therapeutic trials. Trial Registration Number NCT00220740 (http://ClinicalTrials.gov).

Clinical applications of intravenous immunoglobulins in neurology.

Intravenous immunoglobulin (IVIg) is used increasingly in the management of patients with neurological conditions. The efficacy and safety of IVIg treatment in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Guillain-Barré syndrome (GBS) have been established clearly in randomized controlled trials and summarized in Cochrane systematic reviews. However, questions remain regarding the dose, timing and duration of IVIg treatment in both disorders. Reports about successful IVIg treatment in other neurological conditions exist, but its use remains investigational. IVIg has been shown to be efficacious as second-line therapy in patients with dermatomyositis and suggested to be of benefit in some patients with polymyositis. In patients with inclusion body myositis, IVIg was not shown to be effective. IVIg is also a treatment option in exacerbations of myasthenia gravis. Studies with IVIg in patients with Alzheimer's disease have reported increased plasma anti-Abeta antibody titres associated with decreased Abeta peptide levels in the cerebrospinal fluid following IVIg treatment. These changes at the molecular level were accompanied by improved cognitive function, and large-scale randomized trials are under way.

Humoral and cellular immune responses to myelin protein peptides in chronic inflammatory demyelinating polyradiculoneuropathy.

OBJECTIVES: Evidence that chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease was sought, by studying cellular and humoral immune responses to peripheral nerve myelin proteins. METHODS: 40 CIDP, 36 healthy control subjects (HC) and subjects with non-immune mediated neuropathies (other neuropathies, ON) for antibodies were studied by ELISA and cellular responses by cytokine ELISPOT (INF gamma, IL10) and ELISA (IL17) to synthetic peptides representing P0, P2 and PMP22. RESULTS: Antibodies to P0, P2 or PMP22 peptides were detected in only a minority of CIDP, both not treated (nT-CIDP) and treated (T-CIDP). IgG antibodies to P2(80-105) were significantly more frequent in CIDP than in HC (4/30 vs 0/32; p<0.05) but the difference from ON (1/25) was not significant. In ELISPOT assays, IFN gamma was detected at a low frequency in CIDP and did not differ from HC or ON. In contrast, IL10 responses against P2(1-85) were more frequent in nT and T-CIDP (7/24 and 3/16) than HC (0/36; p<0.001 and p<0.05, respectively). The production of IL17 in cell-culture supernatants was not increased. CONCLUSIONS: Antibodies to non-conformational antigenic epitopes of myelin proteins rarely occur in CIDP. None of the myelin protein peptides elicited IFN gamma responses, but P2 elicited IL10 responses significantly more often in CIDP patients than in controls. This reactivity may be part of an antigen-specific Th2 type pathogenetic or regulatory mechanism or represent a transitory epiphenomenon due to nerve damage. In our study, P2 was the protein antigen most likely to be involved in the aberrant immune responses in CIDP.

Derivation and validation of diagnostic criteria for chronic inflammatory demyelinating polyneuropathy.

To develop diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP), a retrospective series of patients' records diagnosed by sexpert consensus as CIDP or other chronic polyneuropathies were analyzed. Classification and regression tree analysis was applied to 150 patients to derive a classification rule. According to the rule, diagnosis of CIDP required that a patient have a chronic non-genetic polyneuropathy, progressive for at least eight weeks, without a serum paraprotein and either 1) recordable compound muscle action potentials in > or =75% of motor nerves and either abnormal distal latency in >50% of nerves or abnormal motor conduction velocity in >50% of nerves or abnormal F wave latency in >50% of nerves; or 2) symmetrical onset of motor symptoms, symmetrical weakness of four limbs, and proximal weakness in > or =1 limb. When validated in 117 patients, the rule had 83% sensitivity (95% confidence interval 69%-93%) and 97% specificity (95% confidence interval 89%-99%) and performed better than published criteria.

A prospective study of physiotherapist prescribed community based exercise in inflammatory peripheral neuropathy.

There is insufficient evidence to support the use of exercise in the management of chronic disablement in people with inflammatory peripheral neuropathy. Therefore, our study aimed to determine the feasibility and effectiveness of a physiotherapist prescribed community based exercise programme for reducing chronic disablement in patients with stable motor neuropathy. We assessed the effects of a 12 week unsupervised, community based strengthening, aerobic and functional exercise programme on activity limitation and other measures of functioning in 16 people with stable motor neuropathy and 10 healthy control subjects. Fourteen of 16 patients and 8 out of 10 healthy control subjects completed the study and exercised safely in the community with no adverse events. Significant improvements were seen in all measures of activity limitation and in wider measures of health including anxiety, depression and fatigue in the patient group. Improvements were sustained at six months after completion of the exercise programme, except for depression. Ten patients continued to exercise regularly at six months. These findings demonstrate that individually prescribed community based exercise is feasible and acceptable for people with stable motor neuropathy and participation in exercise may be successful in reducing chronic disablement. Future randomised controlled trials are needed to examine the efficacy of this complex community based intervention.

Immunosuppressive treatment for non-systemic vasculitic neuropathy.

BACKGROUND: Non-systemic vasculitic neuropathy is a rare disabling disease that usually has a subacute onset of progressive or relapsing-remitting sensory or sensorimotor deficits. Asymmetry, pain and weakness are key features. The diagnosis can only be made by exclusion of other causes, the absence of systemic vasculitis or other rheumatic diseases, and the demonstration of vasculitis in a nerve or a combined nerve and muscle biopsy. There is a need for efficacious therapy to prevent disease progression and to improve prognosis. OBJECTIVES: To assess if immunosuppressive treatment in non-systemic vasculitic neuropathy reduces disability, and ameliorates neurological symptoms, and if such therapy can be given safely. SEARCH STRATEGY: The Cochrane Neuromuscular Disease Group Trials Register (March 2006), The Cochrane Library (Issue 1, 2006), MEDLINE, EMBASE, LILACS, and ISI were searched from January 1980 until April 2006. In addition, the reference lists of relevant articles, reviews and textbooks were handsearched. SELECTION CRITERIA: All randomised or quasi-randomised trials that examined the efficacy of immunosuppressive treatment for non-systemic vasculitic neuropathy at least one year after the onset of therapy were sought. Participants had to fulfill the following criteria: absence of systemic or neurological disease, exclusion of any recognised cause of the neuropathy by appropriate clinical or laboratory investigations, electrophysiological studies in agreement with axonal neuropathy, confirmation of vasculitis in a nerve or a combined nerve and muscle biopsy. The primary outcome measure was to be improvement in disability. Secondary outcome measures were to be change in the mean disability score, change in muscle strength measured with the Medical Research Council sum score, change in pain or other positive sensory symptoms, number of relapses, and adverse events. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed and extracted details of all potentially relevant trials. For included studies pooled relative risks and pooled weighted standardised mean differences were to be calculated to assess treatment efficacy. MAIN RESULTS: Fifty-nine studies were identified and assessed for possible inclusion in the review, but all were excluded because of insufficient quality or lack of relevance. AUTHORS' CONCLUSIONS: No adequate randomised or quasi-randomised controlled clinical trials have been performed on which to base treatment for non-systemic vasculitic neuropathy. Randomised trials of corticosteroids and other immunosuppressive agents are needed.

A modified peripheral neuropathy scale: the Overall Neuropathy Limitations Scale.

A new peripheral neuropathy activities measure, the Overall Neuropathy Limitations Scale (ONLS), was derived by modifying the Overall Disability Sum Score (ODSS) slightly. Its inter-rater reliability was found to be high and its correlation with the ODSS (r = 0.97), 36-item Short Form Questionnaire Physical Component Summary Score, and participation and impairment measures was significant. Acceptable responsiveness (standardised response mean 0.76) was shown by the ONLS. The results obtained from the questionnaire agreed closely with those obtained from observation of the tasks on the ONLS, but were not equivalent. The simplicity of the ODSS is shared by the ONLS, but the ONLS has better content validity and less ceiling effect, which may make it more useful for clinical practice and research.

Clinimetric properties of a walking scale in peripheral neuropathy.

Difficulty in walking is seen in many people with peripheral neuropathies, but walking ability is not comprehensively measured by commonly used outcome measures. The clinimetric properties of the 12-Item Multiple Sclerosis Walking Scale (MSWS-12, renamed the Walk-12) were investigated in 65 patients with peripheral neuropathies. Owing to its excellent internal consistency and reliability, and strong correlation with measures of physical and social function (r>0.8), the Walk-12 is recommended for measuring walking ability in peripheral neuropathies.

European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of multifocal motor neuropathy.

Several diagnostic criteria for multifocal motor neuropathy have been proposed in recent years and a beneficial effect of intravenous immunoglobulin (IVIg) and various other immunomodulatory drugs has been suggested in several trials and uncontrolled studies. The objectives were to prepare consensus guidelines on the definition, investigation and treatment of multifocal motor neuropathy. Disease experts and a patient representative considered references retrieved from MEDLINE and the Cochrane Library in July 2004 and prepared statements which were agreed in an iterative fashion. The Task Force agreed good practice points to define clinical and electrophysiological diagnostic criteria for multifocal motor neuropathy and investigations to be considered. The principal recommendations and good practice points were: (i) IVIg (2 g/kg given over 2-5 days) should be considered as the first line treatment (level A recommendation) when disability is sufficiently severe to warrant treatment. (ii) Corticosteroids are not recommended (good practice point). (iii) If initial treatment with IVIg is effective, repeated IVIg treatment should be considered (level C recommendation). The frequency of IVIg maintenance therapy should be guided by the individual response (good practice point). Typical treatment regimens are 1 g/kg every 2-4 weeks or 2 g/kg every 4-8 weeks (good practice point). (iv) If IVIg is not or not sufficiently effective then immunosuppressive treatment may be considered. Cyclophosphamide, ciclosporin, azathioprine, interferon beta1a, or rituximab are possible agents (good practice point). (v) Toxicity makes cyclophosphamide a less desirable option (good practice point).

European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of paraproteinaemic demyelinating neuropathies: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society.

BACKGROUND: Paraprotein-associated neuropathies have heterogeneous clinical, neurophysiological, neuropathological and haematological features. Objectives. To prepare evidence-based and consensus guidelines on the clinical management of patients with both a demyelinating neuropathy and a paraprotein (paraproteinaemic demyelinating neuropathy, PDN). METHODS: Search of MEDLINE and the Cochrane library, review of evidence and consensus agreement of an expert panel. RECOMMENDATIONS: In the absence of adequate data, evidence based recommendations were not possible but the panel agreed the following good practice points: (1) Patients with PDN should be investigated for a malignant plasma cell dyscrasia. (2) The paraprotein is more likely to be causing the neuropathy if the paraprotein is immunoglobulin (Ig)M, antibodies are present in serum or on biopsy, or the clinical phenotype is chronic distal sensory neuropathy. (3) Patients with IgM PDN usually have predominantly distal and sensory impairment, with prolonged distal motor latencies, and often anti-myelin associated glycoprotein antibodies. (4) IgM PDN sometimes responds to immune therapies. Their potential benefit should be balanced against their possible side-effects and the usually slow disease progression. (5) IgG and IgA PDN may be indistinguishable from chronic inflammatory demyelinating polyradiculoneuropathy, clinically, electrophysiologically, and in response to treatment. (6) For POEMS syndrome, local irradiation or resection of an isolated plasmacytoma, or melphalan with or without corticosteroids, should be considered, with haemato-oncology advice.

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.

Intravenous immunoglobulin for Guillain-Barré syndrome.

BACKGROUND: Guillain-Barré syndrome is an acute, paralysing, inflammatory peripheral nerve disease. Intravenous immunoglobulin is beneficial in other autoimmune diseases. OBJECTIVES: We aimed to determine the efficacy of intravenous immunoglobulin for treating Guillain-Barré syndrome. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Trials Register (March 2005), MEDLINE (January 1966 to March 2005) and EMBASE (January 1980 to March 2005) using the terms 'Guillain-Barré syndrome' and 'acute polyradiculoneuritis'. SELECTION CRITERIA: We included all randomised and quasi-randomised trials. DATA COLLECTION AND ANALYSIS: Two authors independently selected papers, extracted data and assessed quality. MAIN RESULTS: Another Cochrane systematic review has shown that plasma exchange significantly hastens recovery. We found six randomised trials comparing intravenous immunoglobulin with plasma exchange. We undertook a meta-analysis of five trials involving 536, mostly adult participants who were unable to walk unaided and had been ill for less than two weeks. Our primary outcome measure was the change in a seven-grade disability scale four weeks after randomisation. The weighted mean difference of this measure was not statistically significant, being only -0.02 (95% confidence interval -0.25 to 0.20) of a disability grade more improvement in the intravenous immunoglobulin than the plasma exchange group. There were no statistically significant differences in other measures. One trial involving 249 participants compared plasma exchange followed by intravenous immunoglobulin with plasma exchange alone. Another involving 37 participants compared immunoabsorption followed by intravenous immunoglobulin with immunoabsorption alone. Neither revealed significant extra benefit from intravenous immunoglobulin. One study with 39 participants showed a trend towards more improvement with high-dose compared with low-dose intravenous immunoglobulin. Another trial with 51 children found no significant difference in outcome when the standard dose was given over two days rather than five days. Three studies including a total of 75 participants suggested that in children intravenous immunoglobulin significantly hastens recovery compared with supportive care. AUTHORS' CONCLUSIONS: In adults, there are no adequate comparisons with placebo. Randomised trials in severe disease show that intravenous immunoglobulin started within two weeks from onset hastens recovery as much as plasma exchange, which is known to be more effective than supportive care. Treatment with intravenous immunoglobulin is significantly more likely to be completed than plasma exchange. Giving intravenous immunoglobulin after plasma exchange did not confer significant extra benefit. In children, intravenous immunoglobulin probably hastens recovery compared with supportive care alone. More research is needed in mild disease and in treatment starting more than two weeks after onset of the condition. Dose-ranging studies are also needed.