5. Electrophysiological features of peripheral and central nervous system in hereditary neuropathy Charcot Marie Tooth linked to X chromosome

Abstract

Background Hereditary neuropathy Charcot Marie Tooth linked to X chromosome (CMTX) is the second most frequent hereditary neuropathy (about 10% of all Charcot-Marie-Tooth neuropathies-CMT). CMTX is caused by mutations of gab junction β -1 (GJB1) gene coding connexin 32 protein. This protein is expressed by myelinating Schwann cells in the peripheral nerves and by oligodendrocytes in the central nervous system. We were interested in clinical features of GJB1 gene mutations in the peripheral nerves and central nervous system (acoustic, visual or vestibular pathways), which could be affected subclinically. We were also interested in differencies of electrophysiological results between CMTX males and females. Methods We report an electrophysiological study of 39 CMTX patients (18 M + 21 F) from 10 unrelated families with genetically proven diagnosis. We performed nerve conduction studies (NCS), evoked potentials (BAEP, VEP) and electronystagmography (ENG) to determine whether PNS, CNS or boths pathways were affected. Results The NCS were severly affected in CMTX males than in females. The conduction abnormalities in males fullfiled demyelinating pattern (MCV 32–33 m/s) in majority of them compare to females with intermediate slowing or normal (MCV 41–44 m/s) conduction velocity.The sensory fibers were more severe affected than motor fibers. Brainstem auditory evoked potentials (BAEP) were abnormal in 24 (13 M + 11 F) out of 29 patients (13 M + 16 F). BAEP were severly affected males than females. Visual evoked potentials (VEP) were abnormal in 5 (4 M + 1 F) out of 18 patients (10 M + 8 F), mainly prolonged latency and low amplitude of P100 wave. Electronystagmography (ENG) of 15 patients (7 M + 8 F) detected central abnormalities in 9 patients (4 M + 5 F). Conclusions Electrophysiological testing of peripheral nerves showed severe lesions in males compare to females and sensory fibers were more affected than motor fibers. The majority of CMTX males developed demyelinating type of conduction abnormity compare to normal results or mild axonopathy in CMTX females. BAEP are most sensitive method to detected subclinical lesion of CNS in CMTX patients. BAEP were abnormal in 82%, ENG in 43.7% and VEP in 25% of CMTX patients, mainly in males. The combination of the different modalities of evoked potentials increase the sensitivity of detection of central lesions in CMTX patients. Supported by MZ CR-RVO, FN Motol 00064203 and by IGA grant NT/14348.