Biological markers in the diagnosis and treatment of ALS

被引:28
作者
Kalra, S
Arnold, DL
Cashman, NR
机构
[1] Univ Toronto, Ctr Res Neurodegenerat Dis, Dept Med Neurol, Toronto, ON M5S 3H2, Canada
[2] McGill Univ, Montreal Neurol Hosp & Inst, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada
关键词
amyotrophic lateral sclerosis; survival; positron emission tomography;
D O I
10.1016/S0022-510X(99)00023-4
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
The care of patients with amyotrophic lateral sclerosis (ALS), which has classically focused on treatment of symptomatology, has now entered an encouraging new era of therapy targeted at the pathophysiology of the disease. However, an objective measure of disease progression and therapeutic response is sorely needed. Quantitative neuromuscular examinations, measurement of pulmonary function, disability scales, and even survival, are limited by variability due to a number of poorly controlled factors. Quantitative electromyography, positron emission tomography scanning, and magnetic cortical stimulation, provide potential objective indicators of disease progression, but require a large number of patients and a long observation period for adequate statistical power. We have examined the role of magnetic resonance spectroscopic imaging in detecting acute changes in motor cortical metabolism in response to riluzole therapy. N-acetylaspartate (NAA), the most prominent signal in proton spectra of normal brain, is a neuron-specific molecule. ALS patients were found to experience a significant increase in the NAA/creatine ratio within 3 weeks of initiation of riluzole therapy. As glutamate can trigger the generation of reactive oxygen species in neurons, we speculate that acute changes in NAA levels may reflect oxidative injury to mitochondria where NAA is synthesised. The advent of a useful test for upper motor neuron metabolic compromise may provide an objective, non-invasive, short duration measure with which to screen the efficacy of potential therapeutic agents for ALS. (C) 1999 Published by Elsevier Science B.V. All rights reserved.
引用
收藏
页码:S27 / S32
页数:6
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