Central Nervous System Demyelination in a Charcot-Marie-Tooth Type 1A Patient

Introduction. Central nervous system involvement, either clinical or subclinical, has been reported mainly in X-linked Charcot-Marie-Tooth (CMT-X) patients. Case Presentation. We present the case of a 31-year-old man with a genetically confirmed history of CMT1A who developed CNS involvement mimicking multiple sclerosis (MS). Clinical, imaging, and laboratory findings suggested an autoimmune CNS demyelination. Discussion. Although the simultaneous existence of CMT1A and MS could be coincidental we postulate that overexpression of PMP22, the target protein in CMT1A, might influence the immunological self-tolerance to CNS proteins via molecular mimicry, leading to a CNS autoimmune demyelinating disorder. 1. Introduction Charcot-Marie-Tooth (CMT) disease represents a heterogeneous group of inherited neuropathies characterized by distal limb weakness and atrophy, sensory loss, and decreased or absent tendon reflexes. Despite the fact that the core symptoms of CMT involve the peripheral nervous system (PNS), central nervous system (CNS) involvement either in the form of clinical symptoms or magnetic resonance imaging (MRI) white matter lesions has been occasionally reported, mainly for the X-linked type of CMT [1, 2]. 2. Case Presentation Herein, we present the case of a 31-year-old man with a history of CMT1A who developed CNS involvement mimicking multiple sclerosis. During his army duty, five years before presentation, he complained of gait disorder. Bilateral atrophy of the distal lower extremities was observed. Electrophysiological investigation revealed slow motor and sensory nerve conduction velocities in upper and lower limbs indicative of a predominantly demyelinating polyneuropathy with secondary axonal loss (Table 1). The CMT1A diagnosis was confirmed, by means of molecular evaluation [peripheral myelin protein 22 gene (PMP22) duplication]. However, his family history was negative. Table 1: Comparative motor and sensory conduction studies of the patient at diagnosis of CMT and during present evaluation. The patient was initially referred to us because of a 3-day history of diplopia, present in horizontal gaze positions. He also reported an episode of right hemibody dysesthesias two weeks earlier, with spontaneous remission within three days. Clinical examination revealed distal muscle weakness and atrophy more pronounced in the lower limbs, pes cavus, galloping gait, absent tendon reflexes, distal hypoesthesia in the lower limbs, and decreased sensation to vibration in the toes. There was no evidence of nerve hypertrophy or fasciculations.