Treatment for Charcot-Marie-Tooth disease

Charcot-Marie-Tooth disease (CMT) comprises a large variety of different forms of motor and sensory neuropathies. The most frequent are demyelinating forms (CMT1) and axonal forms (CMT2). The molecular basis of several CMT forms has been clarified during the last 15 years. Since muscle wasting and sensory disturbance are the main features of these syndromes, treatments aim to improve motor impairment and sensory disturbances. Specific treatment trials are rare.

The objective was to review systematically all randomised and quasi-randomised studies of any treatment for CMT.

We searched the Cochrane Neuromuscular Disease Group Trials Register, MEDLINE (January 1966 to August 2007), EMBASE (January 1980 to August 2007), LILACS (January 1982 to August 2007) for randomised controlled trials of treatment for CMT.

We included randomised and quasi-randomised trials of any treatment for people with CMT. Where a study aimed to evaluate the treatment of general neuromuscular symptoms of people with peripheral neuropathy including CMT, we included the study if we were able to identify the effect of treatment in the CMT group. Observational studies and case reports on the treatment of people with CMT were not included.

Two review authors (PY and TBB) extracted the data, assessed study quality and performed data extraction independently.

Only one trial with only eight participants met all the inclusion criteria and provided the primary outcome measure for this review. In this trial, four participants treated with neurotrophin-3 had more improvement after six months on the Neuropathy Impairment Score, mean difference -9.50 (95% CI -13.77 to -5.23), than those four treated with placebo. Small trials of exercise training, creatine monohydrate, orthoses and purified bovine brain ganglioside injections (Cronassial) showed no significant benefit in people with genetically undefined CMT1 or CMT2.

Small trials of exercise, creatine, purified brain gangliosides, and orthoses have been performed. None showed significant benefit. A very small trial of neurotrophin-3 showed possible minor benefit which needs to be replicated in a larger trial. None of the two trials were large enough to detect moderate benefit or harm. Larger RCTs are needed for any form of pharmacological intervention as well as as for any form of physical intervention. Outcome measures should include a validated composite scale such as the Charcot-Marie-Tooth neuropathy scale.