RESEARCH PAPER Is overwork weakness relevant in Charcot–Marie–Tooth disease? G Piscosquito, 1 M M Reilly, 2 A Schenone, 3 G M Fabrizi, 4 T Cavallaro, 4 L Santoro, 5 G Vita, 6 A Quattrone, 7 L Padua, 8 F Gemignani, 9 F Visioli, 10,11 M Laurà, 2 D Calabrese, 1 R A C Hughes, 2 D Radice, 12 A Solari, 1 D Pareyson, 1 for the CMT-TRIAAL & CMT-TRAUK Group For numbered affiliations see end of article. Correspondence to Dr Davide Pareyson, Clinic of Central and Peripheral Degenerative Neuropathies Unit, Department of Clinical Neurosciences—IRCCS Foundation, C. Besta Neurological Institute, via Celoria 11, Milan 20133, Italy; davide.pareyson@istituto-besta. it Received 10 January 2014 Revised 25 February 2014 Accepted 26 February 2014 Published Online First 21 March 2014 ▸ http://dx.doi.org/10.1136/ jnnp-2014-307924 To cite: Piscosquito G, Reilly MM, Schenone A, et al. J Neurol Neurosurg Psychiatry 2014;85: 1354–1358. ABSTRACT Background In overwork weakness (OW), muscles are increasingly weakened by exercise, work or daily activities. Although it is a well-established phenomenon in several neuromuscular disorders, it is debated whether it occurs in Charcot–Marie–Tooth disease (CMT). Dominant limb muscles undergo a heavier overload than non-dominant and therefore if OW occurs we would expect them to become weaker. Four previous studies, comparing dominant and non-dominant hand strength in CMT series employing manual testing or myometry, gave contradictory results. Moreover, none of them examined the behaviour of lower limb muscles. Methods We tested the OW hypothesis in 271 CMT1A adult patients by comparing bilateral intrinsic hand and leg muscle strength with manual testing as well as manual dexterity. Results We found no significant difference between sides for the strength of first dorsal interosseous, abductor pollicis brevis, anterior tibialis and triceps surae. Dominant side muscles did not become weaker than non-dominant with increasing age and disease severity (assessed with the CMT Neuropathy Score); in fact, the dominant triceps surae was slightly stronger than the non-dominant with increasing age and disease severity. Discussion Our data does not support the OW hypothesis and the consequent harmful effect of exercise in patients with CMT1A. Physical activity should be encouraged, and rehabilitation remains the most effective treatment for CMT patients. INTRODUCTION Overwork weakness (OW) is characterised by a progressive muscular weakening due to exercise, work or daily activities. It has been demonstrated in several neuromuscular diseases including post- polio syndrome, 1 facio-scapulo-humeral and Duchenne muscular dystrophies, 2 3 and amyo- trophic lateral sclerosis. 4 In these disorders, muscle overload increases disease progression. It is matter for debate whether OW plays a role also in Charcot–Marie–Tooth disease (CMT). The answer is of utmost importance because it will greatly influence the advice to perform physical activity and rehabilitation rather than to spare involved muscles for fear of further worsening. If OW plays a relevant role in CMT, we would expect a signifi- cant difference in hand strength (HS) in favour of the non-dominant hand (NDH), because dominant hand (DH) muscles undergo a heavier overload. Vinci and coauthors found the DH muscles to be weaker in about 66% of evaluated muscles in a series of 106 patients with different types of CMT (80 demyelinating CMT1 and 26 axonal CMT2 forms) by evaluating muscle research council scores on a 14-point scale. Therefore, they con- cluded that OW produces additional weakness and may be a cause of disease progression. 5 By con- trast, Van Pomeren et al tested a series of 28 CMT patients (13 CMT1 and 15 CMT2) by using the conventional 6-point MRC scale and also the Rotterdam Intrinsic Hand Myometer, which allows measuring intrinsic hand muscle strength. There was no finding in favour of the OW hypothesis; rather, in CMT2 patients the key-grip test showed the DH to be stronger than the NDH. 6 By using a digital handgrip dynamometer, Videler and colleagues found no significant differ- ences between sides for grip, 2-point, tripod and lateral pinch strength in a series of 49 patients with CMT type 1A (the most common CMT type). However, in the more severely affected sub- group (22 patients), pinch strength was signifi- cantly lower in the DH, which might fit the OW hypothesis. 7 Similarly, Arthur-Farraj and coauthors evaluated a series of 43 patients with the X-linked CMT type (CMTX1) and found that in patients with MRC grade less than 4-, the abductor pollicis brevis (APB) and first dorsal interosseous (FDI) muscles of the NDH were stronger than that of the DH, a finding which again might be in favour of OW. They also showed a relative reduction of the amplitude of the median nerve compound muscle action potential (CMAP) in the DH as compared with the NDH, whereas no differences between sides were found for median and ulnar motor nerve conduction velocities and ulnar nerve CMAP amplitude. 8 None of the previous studies tested the lower limbs, where the effect of domin- ance is still debated. 9 In order to verify the OW hypothesis in our population of 271 adult CMT1A patients enrolled in the ascorbic acid trial, we compared intrinsic hand and leg muscle strength in search of possible strength differences between sides. 10 We also tested manual dexterity because Videler and coauthors have shown that tripod pinch and thumb opposition strength are major determinants of manual dexterity in 1354 Piscosquito G, et al. J Neurol Neurosurg Psychiatry 2014;85:1354–1358. doi:10.1136/jnnp-2014-307598 Neuromuscular group.bmj.com on November 17, 2014 - Published by http://jnnp.bmj.com/ Downloaded from