RYR1-related malignant hyperthermia with marked cerebellar involvement - a paradigm of heat-induced CNS injury?
Neuromuscul Disord
; 25(2): 138-40, 2015 Feb.
Article
em En
| MEDLINE
| ID: mdl-25466363
ABSTRACT
Heat-induced CNS injury has been recognized for more than 50 years but the biological basis for the marked selectivity of CNS damage is currently uncertain. We present clinical, imaging, autopsy and genetic findings of a 14-year-old male who developed fatal cerebellar swelling in the course of a malignant hyperthermia (MH) episode caused by triggering anaesthetics. Unaccustomed intense exercise in the days prior to general anaesthesia was a probable confounding factor for the MH reaction. Autopsy findings demonstrated pronounced degeneration of cerebellar Purkinje cells. Post mortem genetic analysis revealed a mutation (c.6502G>A; p.Val2168Met) in the skeletal muscle ryanodine receptor (RYR1) gene previously associated with the MH trait. RYR1 mutations appear to be associated with heat-induced CNS injury in a distribution compatible with known expression pattern of the RyR1 isoform in cerebellar Purkinje cells. Recent exercise in genetically predisposed individuals may prime abnormal muscle prior to general anaesthesia and contribute to the severity of MH reactions.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cerebelo
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Canal de Liberação de Cálcio do Receptor de Rianodina
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Febre
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Mutação
Limite:
Adolescent
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Humans
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Male
Idioma:
En
Revista:
Neuromuscul Disord
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Reino Unido