The natural history of Charcot-Marie-Tooth type 1A in adults: a 5-year follow-up study

Abstract

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.

Afferent control of walking: Are there distinct deficits associated to loss of fibres of different diameter?

“…Further, duration of the double support was much longer in DNP than in CMT1A and HS. The performance of the CMT1A patients was also abnormal, as also shown by Verhamme et al (2009) and Guillebastre et al (2011). However, our CMT1A patients did not differ significantly from HS as far as cadence, duration of the single and double support phase, and foot yaw angle are concerned.…”

Clinical progression in Charcot–Marie-Tooth disease type 1A duplication: clinico-electrophysiological and MRI longitudinal study of a family

“…Similarly, in crosssectional studies of CMT1A, abnormal spontaneous muscle activity indicating denervation of TA muscle is reported in 11% of CMT1A patients [31]. It is worth noting that the presence of abnormal spontaneous muscle activity in TA occurs in more severely affected CMT1A patients, but is not an indication of a faster rate of clinical decline [32].…”

“…Despite all clinical examinations being either performed or supervised by one of the authors (JB), we have to admit that a limitation for detecting subtle changes of clinical signs is that we used conventional neurological examination just complemented with the CMTNS and FDS [3,29]. Analysis of physical disability, evaluated by scores of the physical dimension of the generic sickness impact profile and by timed physical activities, and use of handheld dynamometry and INCAT sensory sum score would allow detection of minimal variations indicative of disease progression [32]. However, such planning work would be very difficult, if not impossible, to apply to a longitudinal study initiated almost three decades ago.…”

“…Shy et al [30] reported disease progression over time, 2-3 years on average, measured using the CMT Neuropathy Score (CMTNS) and Neuropathy Impairment Score. Conversely, in a 5-year follow-up study comparing CMT1A patients and a control group, Verhamme et al [32] found that patients and controls had a similar decline of strength and of CMAP amplitudes, this finding suggesting that in the disease the decline in adulthood may, to a considerable extent, reflect a process of normal ageing rather than on-going active disease.…”

“…With regard to the disease course in adult CMT1A patients, cross-sectional studies indicate that clinical disability at the impairment and severity level is related to axonal dysfunction [23,31]. Because of the cross-sectional design, these studies cannot answer the question of whether and to what extent there is clinically and electrophysiologically disease progression in adult patients [32]. Two recent longitudinal clinico-electrophysiological studies in adult CMT1A patients have shown divergent results.…”