Neurological dysfunction and axonal degeneration in Charcot-Marie-Tooth disease type 1A

K. M KRAJEWSKI; Richard A Lewis; D. R FUERST; C TURANSKY; S. R HINDERER; J GARBERN; J KAMHOLZ; M. E SHY

doi:10.1093/brain/123.7.1516

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Neurological dysfunction and axonal degeneration in Charcot-Marie-Tooth disease type 1A

Journal article

Open access

Peer reviewed

Neurological dysfunction and axonal degeneration in Charcot-Marie-Tooth disease type 1A

K. M KRAJEWSKI, Richard A Lewis, D. R FUERST, C TURANSKY, S. R HINDERER, J GARBERN, J KAMHOLZ and M. E SHY

Brain (London, England : 1878), Vol.123(7), pp.1516-1527

2000

DOI: 10.1093/brain/123.7.1516

PMID: 10869062

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Abstract

Charcot-Marie-Tooth disease type 1A (CMT1A), the most frequent form of CMT, is caused by a 1.5 Mb duplication on the short arm of chromosome 17. Patients with CMT1A typically have slowed nerve conduction velocities (NCVs), reduced compound motor and sensory nerve action potentials (CMAPs and SNAPs), distal weakness, sensory loss and decreased reflexes. In order to understand further the molecular pathogenesis of CMT1A, as well as to determine which features correlate with neurological dysfunction and might thus be amenable to treatment, we evaluated the clinical and electrophysiological phenotype in 42 patients with CMT1A. In these patients, muscle weakness, CMAP amplitudes and motor unit number estimates correlated with clinical disability, while motor NCV did not. In addition, loss of joint position sense and reduction in SNAP amplitudes also correlated with clinical disability, while sensory NCV did not. Taken together, these data strongly support the hypothesis that neurological dysfunction and clinical disability in CMT1A are caused by loss or damage to large calibre motor and sensory axons. Therapeutic approaches to ameliorate disability in CMT1A, as in amyotrophic lateral sclerosis and other neurodegenerative diseases, should thus be directed towards preventing axonal degeneration and/or promoting axonal regeneration.

Neurology

Biological and medical sciences

Medical sciences

Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases

Details

Title: Subtitle: Neurological dysfunction and axonal degeneration in Charcot-Marie-Tooth disease type 1A
Creators: K. M KRAJEWSKI - Department of Neurology, Wayne State University School of Medicine, Wayne State University, Detroit, Michigan, United States
Richard A Lewis - Department of Neurology, Wayne State University School of Medicine, Wayne State University, Detroit, Michigan, United States
D. R FUERST - Department of Psychiatry and Behavioral Sciences, Wayne State University School of Medicine, Wayne State University, Detroit, Michigan, United States
C TURANSKY - Department of Neurology, Wayne State University School of Medicine, Wayne State University, Detroit, Michigan, United States
S. R HINDERER - Rehabilitation Institute of Michigan, Wayne State University, Detroit, Michigan, United States
J GARBERN - Department of Neurology, Wayne State University School of Medicine, Wayne State University, Detroit, Michigan, United States
J KAMHOLZ - Department of Neurology, Wayne State University School of Medicine, Wayne State University, Detroit, Michigan, United States
M. E SHY - Department of Neurology, Wayne State University School of Medicine, Wayne State University, Detroit, Michigan, United States
Resource Type: Journal article
Publication Details: Brain (London, England : 1878), Vol.123(7), pp.1516-1527
DOI: 10.1093/brain/123.7.1516
PMID: 10869062
NLM abbreviation: Brain
ISSN: 0006-8950
eISSN: 1460-2156
Publisher: Oxford University Press; Oxford
Language: English
Date published: 2000
Academic Unit: Neurology; Molecular Physiology and Biophysics; Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
Record Identifier: 9984020772602771

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