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Motor axonal excitability properties are strong predictors for survival in amyotrophic lateral sclerosis.
MedLine Citation:
PMID:  22566594     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
ObjectiveThe aim of this study was to investigate whether axonal excitability indices are associated with survival in patients with amyotrophic lateral sclerosis (ALS). Previous nerve excitability studies suggested increased persistent sodium currents in motor axons of patients with ALS, which lead to axonal hyperexcitability and potentially enhance neuronal death.Methods112 patients with sporadic ALS were followed up until endpoint (death or tracheostomy). Multivariate analyses were performed using the Cox proportional hazard model. Threshold tracking was used to measure multiple axonal excitability indices in median motor axons, such as strength-duration time constant (SDTC; a measure of nodal persistent sodium current). Latent addition was also used to estimate the magnitude of persistent sodium currents.ResultsThe overall median tracheostomy-free survival from onset was 37 months. Prolonged SDTC was strongly associated with shorter survival (adjusted HR 4.07; 95% CI 1.7 to 9.8; p=0.0018) compared with older onset age (>60 years; HR=1.80) and bulbar onset (HR=1.80). Estimated median survival was 34 months in the longer SDTC group and 51 months in the shorter SDTC group. This index was highly statistically significant even after multiple testing adjustments with age and site of onset (bulbar or limb). Latent addition study results were consistent with these findings.ConclusionsAxonal persistent sodium currents, estimated by SDTC and latent addition, are strong and independent predictors for shorter survival in patients with ALS. Membrane hyperexcitability is possibly associated with motor neuronal death, and modulation of excessive sodium currents could be a novel therapeutic option for ALS.
Authors:
Kazuaki Kanai; Kazumoto Shibuya; Yasunori Sato; Sonoko Misawa; Saiko Nasu; Yukari Sekiguchi; Satsuki Mitsuma; Sagiri Isose; Yumi Fujimaki; Shigeki Ohmori; Shunsuke Koga; Satoshi Kuwabara
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-7
Journal Detail:
Title:  Journal of neurology, neurosurgery, and psychiatry     Volume:  -     ISSN:  1468-330X     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-5-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985191R     Medline TA:  J Neurol Neurosurg Psychiatry     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.
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