Brain Advance Access first published online on October 20, 2009
This version published online on November 5, 2009
Brain, doi:10.1093/brain/awp251
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The natural history of Charcot–Marie-Tooth type 1A in adults: a 5-year follow-up study
1 Department of Neurology and Clinical Neurophysiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands 2 Department of Clinical Epidemiology and Biostatistics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
Correspondence to:
Camiel Verhamme, Department of Neurology and Clinical Neurophysiology, H2-222, Academic Medical Centre, University of Amsterdam, PO box 22660, 1100 DD Amsterdam, The Netherlands E-mail: c.verhamme{at}amc.uva.nl
Charcot–Marie-Tooth type 1A is the most prevalent hereditary demyelinating polyneuropathy. The aim of this study was to investigate the natural history of the disease in adults during a 5-year follow-up and to compare the changes over time with those found in normal ageing. In a cohort of 46 adult Charcot–Marie-Tooth type 1A patients, impairments and physical disability were scored at baseline and at 1, 3 and 5 years. Standardized nerve conduction studies and electromyography were performed at baseline and at 5 years. Twenty-six healthy age- and sex-matched controls were evaluated at baseline and at 5 years. Forty-four of 46 Charcot–Marie-Tooth type 1A patients (range 17–69 years) and 26 controls (range 25–65 years) completed the 5-year follow-up. The decrease in muscle strength and in compound muscle action potential amplitudes was similar for patients and controls alike. However, in contrast to the control group, physical disability increased over time in the patient group. In patients, muscle strength and physical disability after 5 years were closely related to these parameters at baseline. None of the other assessed baseline characteristics, i.e. age, gender, compound muscle action potential amplitude and motor nerve conduction velocity, predicted the extent of deterioration of muscle strength or physical disability. In adult Charcot–Marie-Tooth type 1A patients, the decline in axonal function and in muscle strength may reflect, to a considerable extent, a process of normal ageing. The slow increase in physical disability in adulthood may well be explained by decreased reserves and compensatory mechanisms together with progression of skeletal deformations due to muscle weakness.
Key Words: Peripheral neuropathies; Charcot–Marie-Tooth Disease; Charcot–Marie-Tooth Disease type 1A; Hereditary motor and sensory neuropathies; Hereditary motor and sensory neuropathy type Ia; Natural history; Axonal dysfunction
Abbreviations: ABP, abductor pollicis brevis; ADQ, abductor digiti quinti; AHB, abductor hallucis brevis; ANCOVA, analysis of covariance; AT, anterior tibial; CMT1A, Charcot–Marie-Tooth disease type 1A; CMTNS, Charcot–Marie-tooth neuropathy score; CMAP, compound muscle action potential; EDB, extensor digitorum brevis; ISS, INCAT sensory sum score; MNCV, motor nerve conduction velocity; MRC, Medical Research Council; rpb, point biserial correlation coefficient
Received February 27, 2009. Revised August 10, 2009. Accepted August 21, 2009.