Intravenous immunoglobulin for multifocal motor neuropathy (Cochrane Review)

Background: Multifocal motor neuropathy is a rare, probably immune mediated disorder characterised by slowly progressive, asymmetric, distal weakness of one or more limbs with no objective loss of sensation. It may cause prolonged periods of disability. The treatment options for multifocal motor neuropathy are sparse. Patients with multifocal motor neuropathy do not usually respond to steroids or plasma exchange, and may even worsen with these treatments. Many uncontrolled studies have suggested a beneficial effect of intravenous immunoglobulin.

Objectives: To review systematically the evidence from randomised controlled trials concerning the efficacy and safety of intravenous immunoglobulin in multifocal motor neuropathy.

Search strategy: We used the search strategy of the Cochrane Neuromuscular Disease Review Group to search the Disease Group register (searched September 2003), MEDLINE (January 1990 to September 2003), EMBASE (January 1990 to September 2003) and ISI (January 1990 to September 2003) databases for randomised controlled trials.

Selection criteria: Randomised controlled studies examining the effects of any dose of intravenous immunoglobulin versus placebo in patients with definite or probable multifocal motor neuropathy.Outcome measures had to include one of the following: disability, strength, or conduction block. Studies which reported the frequency of adverse effects were used to assess safety.

Data collection and analysis: Two authors reviewed literature searches to identify potentially relevant trials, scored their quality and extracted data independently. For dichotomous data, we calculated relative risks, and for continuous data, effect sizes and weighted pooled effect sizes. Statistical uncertainty was expressed with 95% confidence intervals.

Main results: Four randomised controlled trials including a total of 34 patients were suitable for this systematic review. Strength improved in 78% of patients treated with intravenous immunoglobulin and only 4% of placebo-treated patients. Disability improved in 39% of patients after intravenous immunoglobulin treatment and in 11% after placebo (statistically not significantly different). Mild, transient side effects were reported in 71% of intravenous immunoglobulin treated patients. Serious side effects were not encountered.

Authors' conclusions: Limited evidence from randomised controlled trials shows that intravenous immunoglobulin has a beneficial effect on strength. There was a non-significant trend towards improvement in disability. More research is needed to discover whether intravenous immunoglobulin improves disability and is cost-effective.

Citation: van Schaik IN, van den Berg LH, de Haan R, Vermeulen M. Intravenous immunoglobulin for multifocal motor neuropathy. The Cochrane Database of Systematic Reviews 2005, Issue 2.

Antioxidant treatment for amyotrophic lateral sclerosis / motor neuron disease (Cochrane Review)

Orrell RW, Lane RJM, Ross M

Background: Free radical accumulation and oxidative stress have been proposed as contributing to the progression of amyotrophic lateral sclerosis (or motor neuron disease). A range of antioxidant medications are available, and have been studied.

Objectives: To examine the effects of antioxidant medication in the treatment of people with amyotrophic lateral sclerosis.

Search strategy: We searched the Cochrane Neuromuscular Disease Group trials register (July 2003), MEDLINE (from January 1966 to July 2003), EMBASE (from January 1980 to July 2003) and other sources.
Selection criteria: All randomized or quasi-randomized controlled trials of antioxidant treatment for amyotrophic lateral sclerosis.

Data collection and analysis: The reviewers independently applied the selection criteria, assessed study quality and two reviewers performed independent data extraction.

Main results: The search identified 21 studies for consideration but only eight studies met the inclusion criteria. Only two studies used our predetermined primary outcome measure, (survival at 12 months treatment). Sufficient data were available from three studies to allow analysis of the primary outcome measure, and a meta-analysis was performed. In the individual studies no significant effect was observed of vitamin E 500 mg twice daily; acetylcysteine 50 mg/kg daily subcutaneous infusion; or a combination of L-methionine 2 g, vitamin E 400 International Units, and selenium 3 x 10-5g three times daily (Alsemet). No significant effect on the primary outcome measure was observed in a meta-analysis of antioxidants in general when combining the results. No significant differences were demonstrated in secondary outcome measures.

Authors' conclusions: There is insufficient evidence of efficacy of individual antioxidants, or antioxidants in general, in the treatment of people with amyotrophic lateral sclerosis. One study reported a mild positive effect, but this was not supported by the analysis we used. Generally the studies were poorly designed, and underpowered, with low numbers of participants and of short duration. Further well-designed trials of medications such as vitamin C and E are unlikely to be performed. If future trials of antioxidant medications are performed, careful attention should be given to sample size, outcome measures, and duration of the trial. The high tolerance and safety, and relatively low cost of vitamins C and E, and other considerations related to the lack of other effective treatments for amyotrophic lateral sclerosis, explain the continuing use of these vitamins by physicians and patients. While there is no substantial clinical trial evidence to support their clinical use, there is no clear contraindication.

Citation: Orrell RW, Lane RJM, Ross M. Antioxidant treatment for amyotrophic lateral sclerosis / motor neuron disease. The Cochrane Database of Systematic Reviews 2005, Issue 1. Art. No.: CD002829.pub3. DOI: 10.1002/14651858.CD002829.pub3.

Cigarette smoking and the progression of multiple sclerosis

An increased risk of multiple sclerosis among smokers has been found in several prospective epidemiological studies. The association between smoking and progression of multiple sclerosis has not been examined. We identified patients who had a first multiple sclerosis diagnosis recorded in the General Practice Research Database (GPRD) between January 1993 and December 2000. Their diagnosis and date of first symptoms were confirmed through examination of medical records. Smoking status was obtained from the computer records.

To assess the association between smoking and risk of multiple sclerosis, we conducted a case–control study nested in the GPRD. Up to 10 controls per case were randomly selected, matched on age, sex, practice, date of joining the practice and availability of smoking data. To assess the association between smoking and progression of multiple sclerosis, we conducted a cohort study of multiple sclerosis cases with a relapsing–remitting onset. Our nested case–control study included 201 cases of multiple sclerosis and 1913 controls. The odds ratio [95% confidence interval (CI)] of multiple sclerosis was 1.3 (1.0–1.7) for ever smokers compared with never smokers. Our cohort study included 179 cases with a mean (median) length of follow-up of 5.3 (5.3) years. The hazard ratio of secondary progression was 3.6 (95% CI 1.3–9.9) for ever smokers compared with never smokers. These results support the hypothesis that cigarette smoking is associated with an increased risk of multiple sclerosis, and suggest that smoking may be a risk factor for transforming a relapsing–remitting clinical course into a secondary progressive course.

From Brain 2005 128(6):1461-1465