Journal of neurosurgery. Spine
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Multicenter Study
Pharmacology of riluzole in acute spinal cord injury.
The aim of this paper was to characterize individual and population pharmacokinetics of enterally administered riluzole in a Phase 1 clinical trial of riluzole as a neuroprotective agent in adults 18-70 years old with acute spinal cord injury (SCI). ⋯ This is the first report of clinical pharmacokinetics of riluzole in patients with SCI. The C(max) and AUC(0-12) achieved in SCI patients were lower than those in ALS patients on the same dose basis, due to a higher clearance and larger volume of distribution in SCI patients. The finding in SCI patients of an increase in the clearance and distribution of riluzole between the 3rd and 14th days after SCI, with a lower plasma concentration of riluzole on the 14th day, stresses the importance of monitoring changes in drug metabolism after SCI in interpreting the safety and efficacy of therapeutic drugs that are used in clinical trials in SCI. Clinical trial registration no.: NCT00876889.
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The objective of this study was to identify commonly used physiological outcome measures and summarize evidence on the reliability and predictive validity of quantitative measures used in monitoring persons with spinal cord injury (SCI). ⋯ Evidence on the reliability and validity of the quantitative measures selected for this review is limited, and the overall quality of existing studies is poor. There is some evidence for the reliability of the EPT, dermatomal SSEPs, and the GRASSP to suggest that they may be useful in longitudinal studies of patients with SCI. There is a need for high quality studies of reliability, responsiveness, and validity for quantitative measures to monitor the level and degree of SCI.
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Multicenter Study
Riluzole for the treatment of acute traumatic spinal cord injury: rationale for and design of the NACTN Phase I clinical trial.
In the immediate period after traumatic spinal cord injury (SCI) a variety of secondary injury mechanisms combine to gradually expand the initial lesion size, potentially leading to diminished neurological outcomes at long-term follow-up. Riluzole, a benzothiazole drug, which has neuroprotective properties based on sodium channel blockade and mitigation of glutamatergic toxicity, is currently an approved drug that attenuates the extent of neuronal degeneration in patients with amyotrophic lateral sclerosis. Moreover, several preclinical SCI studies have associated riluzole administration with improved functional outcomes and increased neural tissue preservation. ⋯ Currently, a Phase I trial evaluating the safety and pharmacokinetic profile of riluzole in human SCI patients is being conducted by the North American Clinical Trials Network (NACTN) for Treatment of Spinal Cord Injury. The current review summarizes the existing preclinical and clinical literature on riluzole, provides a detailed description of the Phase I trial, and suggests potential opportunities for future investigation. Clinical trial registration no.: NCT00876889.
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The aim of this study was to identify the quality of life (QOL) measures commonly used to assess patients with spinal cord injury (SCI) and to summarize studies using common QOL measures that have been validated in SCI populations to compare scores in persons with SCI with those in a control population. ⋯ The SF-36 and WHOQOL-BREF are validated instruments that should be considered for use in SCI QOL studies. Future analysis of deficits in QOL among patients with SCI would benefit from the development of a QOL instrument specifically targeted to SCI. Longitudinal studies to assess the impact of injury level and injury completeness on SCI QOL are also needed.
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The object of this study was to identify, by means of a systematic review of the literature, the acute clinical predictors of neurological outcome, functional outcome, and survival after traumatic spinal cord injury (SCI). ⋯ On the basis on this review, the authors have identified a constellation of acute clinical features that may help to define an individual's profile for recovery and survival after SCI. This study will help to facilitate communication in the clinical realm and assist in classifying subsets of patients within future clinical studies.