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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The term Morvan's disease, first coined in 1890, is still in use, although the generic term neuromyotonia--which is not exempt from criticism--has largely superseded it. Symptoms and signs are variable, ranging from benign painful fasciculations, pseudomyotonic cases, rigid forms, cases in which central nervous system features are also present (with, in addition to nerve hyperexcitability, agitation, confusion, delirium, insomnia, hyperhidrosis and tachycardia). A distal peripheral motor nerve is the origin of nerve hyperexcitability. There is growing evidence that autoimmunity is involved in the pathogenesis of many cases. Antibodies to voltage-gated potassium channels are detected in the serum of many patients with peripheral nerve hyperexcitability. Other cases are probably genetic. Inherited disorders are related to episodic dominant ataxia type 1, with the same mutation of a gene coding for potassium channel subunit Kv 1-1. Many inappropriate or non specific names are used to refer to peripheral nerve hyperexcitability. Isaacs syndrome, voltage-gated potassium channelopathy, or Morvan's syndrome are suggested.
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PMID:[From Morvan's disease to potassium channelopathies]. 1550 15

The episodic ataxias are autosomal dominant disorders usually beginning in the first two decades of life. Episodic ataxia type 1 (EA1) is characterized by brief episodes of ataxia, typically lasting seconds, and interictal myokymia, while episodic ataxia type 2 (EA2) is manifested by longer episodes of ataxia (hours) with interictal nystagmus. The EA1 gene (KCNA1) codes for the six transmembrane segments (S1 to S6) of the Kv1.1 potassium channel subunit and the EA2 gene (CACNA1A) encodes for the Ca(v)2.1 subunit of the P/Q calcium channel complex. EA1 mutations are always missense while most EA2 mutations disrupt the reading frame. Studies of the biophysical properties of the mutant Kv1.1 and Ca(v)2.1 channels in Xenopus oocytes and mammalian cell lines demonstrate clear physiologic consequences of the genetic mutations although no consistent pattern for genotype-phenotype correlation has emerged. Genetic testing for EA1 and EA2 is available, but since no single mutation is prominent for either KCNA1 or CACNA1A, all of the coding regions of the genes need to be screened for mutations. Acetazolamide can be dramatic in controlling episodes of ataxia with EA2 but is typically less beneficial with EA1.
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PMID:Episodic ataxias 1 and 2. 2182 20

The voltage-dependent potassium channel subunit Kv3.3 is expressed at high levels in cerebellar Purkinje cells, in auditory brainstem nuclei and in many other neurons capable of firing at high rates. In the cerebellum, it helps to shape the very characteristic complex spike of Purkinje cells. Kv3.3 differs from other closely related channels in that human mutations in the gene encoding Kv3.3 (KCNC3) result in a unique neurodegenerative disease termed spinocerebellar ataxia type 13 (SCA13). This primarily affects the cerebellum, but also results in extracerebellar symptoms. Different mutations produce either early onset SCA13, associated with delayed motor and impaired cognitive skill acquisition, or late onset SCA13, which typically produces cerebellar degeneration in middle age. This review covers the localization and physiological function of Kv3.3 in the central nervous system and how the normal function of the channel is altered by the disease-causing mutations. It also describes experimental approaches that are being used to understand how Kv3.3 mutations are linked to neuronal survival, and to develop strategies for treatment.
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PMID:Kv3.3 potassium channels and spinocerebellar ataxia. 2644 72