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Neuropathy progression in Charcot-Marie-Tooth disease type 1A

From the Department of Neurology (M.E.S., E.R.S., R.T., K.M.K., R.A.L.) and Center for Molecular Medicine and Genetics (M.E.S.), Wayne State University, Detroit, MI; and Departments of Biostatistics and Computational Biology (L.C., M.P.M.) and Neurology (D.H., M.D.M.), University of Rochester, NY.

Address correspondence and reprint requests to Dr. Michael E. Shy, Wayne State University, Department of Neurology, 421 Ea Canfield, Detroit, MI 48201 m.shy{at}wayne.edu.

Objective: To determine the rate of disease progression in Charcot-Marie-Tooth disease type 1A (CMT1A).

Background: CMT1A is the most common inherited peripheral neuropathy, affecting approximately 1:5,000 people irrespective of ethnic background or gender. There is no cure for CMT1A. Clinical trials are being initiated that use the CMT Neuropathy Score (CMTNS), a composite score based on patient symptoms, signs, and neurophysiologic abnormalities, as the primary outcome variable. The sensitivity of the CMTNS or any other score to change over time, as a measure of CMT1A progression, has yet to be determined.

Methods: We determined the CMTNS as well as the Neuropathy Impairment Score (NIS) on 72 patients followed for up to 8 years. The rate of disease progression was evaluated for the CMTNS and NIS using mixed effects linear regression models, adjusting for age and gender.

Results: Both CMTNS and NIS showed changes over time. The CMTNS increased an average of 0.686 points per year (95% CI 0.461 to 0.911, p 0.0001). The NIS increased 1.368 points per year on average (95% CI 0.616 to 2.121, p = 0.0005). There was a suggestion that the rate of progression increased with age.

Conclusion: Progression of CMT1A can be detected by both the CMT Neuropathy Score (CMTNS) and the Neuropathy Impairment Score (NIS). This supports the feasibility of clinical trials to detect a slowing of disease progression using either or both of these scales as outcome measures. Since the CMTNS combines symptoms, signs, and electrophysiology and the NIS is based solely on the neurologic examination, the two scales may be complementary.

Abbreviations: AI = ambulation index; CMAP = compound muscle action potentials; CMT1A = Charcot-Marie-Tooth disease type 1A; CMTNS = CMT Neuropathy Score; MNCV = motor nerve conduction velocities; NCS = nerve conduction studies; NIS = Neuropathy Impairment Score; SNAP = sensory nerve action potential; SNCV = sensory nerve conduction velocities.

Supported by grants from the Muscular Dystrophy Association and the Charcot-Marie-Tooth Association.

Disclosure: The authors report no conflicts of interest.

Received May 23, 2007. Accepted in final form July 23, 2007.