Neuromuscular junction channelopathies: a brief overview.
The neuromuscular junction lacks the protection of the blood-nerve barrier and is vulnerable to antibody-mediated disorders. In myasthenia gravis (MG), 85% of patients have IgG antibodies to acetylcholine receptors (AChRs). About half the remaining patients have IgG antibodies to Muscle Specific Kinase (MuSK), an AChR-associated transmembrane post-synaptic protein concerned in AChR aggregation. Bulbar weakness is typically predominant in this form of MG, and females are more often affected. The Lambert-Eaton Myasthenic Syndrome (LEMS) can occur in a paraneoplastic form (P-LEMS) usually with small cell lung cancer, or in a non-paraneoplastic form (NP-LEMS). In both, IgG antibodies to nerve terminal voltage-gated calcium channels (VGCCs), detectable in over 90% of patients, lead to VGCC loss and impaired quantal release of transmitter and may be implicated in the occasionally associated cerebellar ataxia. Neuromyotonia (NMT) and Cramp-Fasciculation syndrome (C-FS) are manifestations of peripheral nerve hyperexcitability and share some clinical and electromyographic features. Antibodies to voltage-gated potassium channels (VGKCs) are present in about 40% of NMT patients, but less frequently in C-FS, and appear to cause loss of functional VGKCs. They may also be implicated in the Maladie de Morvan and limbic encephalitis that can associate with NMT: The antibodies described here provide valuable aids to diagnosis and management. The Congenital Myasthenic Syndromes are a group of genetically determined heterogeneous disorders, usually recessively inherited. The commonest mutation sites appear to be the acetylcholine receptor epsilon-subunit and rapsyn.
University of Oxford, Department of Clinical Neurology, Oxford, UK. john.newsomdavis@btinternet.com
John
J
Newsom-Davis
D000328:Adult; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020511:Neuromuscular Junction Diseases / Q000503:physiopathology*
D015220:Calcium Channels