Transient, Recurrent Central Nervous System Clinical Manifestations of X-Linked Charcot-Marie-Tooth Disease Presenting with Very Long Latency Periods between Episodes: Is Prolonged Sun Exposure a Provoking Factor?

Abstract

Charcot-Marie-Tooth disease is one of the most common inherited neurological disorders affecting the peripheral nervous system. The common clinical manifestations of the disease are distal muscle weakness and atrophy, often associated with a characteristic steppage gait and foot deformities. Transient acute and recurrent or chronic central nervous system manifestations, predominantly, dysarthria, dysphagia, motor weakness, and ataxia, have been recognized as a feature of the X-linked type 1 of CMT (CMTX1). The CNS symptoms occur typically in young age and often precede the clinical manifestation of the polyneuropathy. Several predisposing factors such as exercise, fever, and returning from areas of high altitude have been described as triggers of the CNS symptoms; however, in many cases, a substantial cause remains undetermined. In this report, we describe a patient with three attacks of transient CNS deficits at the ages of 11, 21, and 38 years, respectively, which were also accompanied by transient white matter abnormalities on MRI. Two of the attacks occurred after prolonged exposure to sunlight. In our knowledge, this is the first documented case with such long latency periods between CNS attacks as well as the only report describing intense sun exposure as a possible provoking factor.

Systematic review of CMTX1 patients with episodic neurological dysfunction

“…Finally, we identified 47 cases from 38 articles that met the criteria of our systematic review. 11‐48 The gradual selection and exclusion process of the studies is shown in Figure 1.…”

Clinical and electrophysiological characteristics of women with X‐linked Charcot–Marie–Tooth disease

“…We identified three women with a stroke‐like syndrome. However, in the previous cohort, stroke‐like attacks were more frequently reported in men [11–16] than in women. These central symptoms should prompt a discussion of differential diagnoses [34, 35].…”

“…Clinically there is usually a distal motor deficit of the lower and upper limbs, associated with muscle atrophy and bone deformities. In addition to peripheral neuropathy, CMTX1 is also characterized by acute episodic dysfunctions in the central nervous system [11][12][13][14][15][16][17][18]. Nerve conduction studies show in male patients intermediate slowing of conduction and distal axonal loss [19].…”

Caractéristiques cliniques et électrophysiologiques des femmes atteintes de la maladie de Charcot-Marie-Tooth liée à l’X

“…Clinically there is usually a distal motor deficit of the lower and upper limbs, associated with muscle atrophy and orthopedic deformities. In addition to peripheral neuropathy, acute episodic central nervous system dysfunctions are referred to as characteristics of CMTX1 (50)(51)(52)(53)57,58,68,69). Nerve conduction studies show in male patients intermediate slowing of conduction and distal axonal loss (49).…”

“…La Cx32 est également exprimée par les oligodendrocytes, les couplant aux astrocytes(67). du CMTX1(50)(51)(52)(53)57,58,68,69). Les études des vitesses de conduction montrent un ralentissement intermédiaire chez l'homme, et une perte axonale distale(49).…”