MR SPECTROSCOPY STUDIES OF ALCOHOL INDUCED BRAIN DAMAGE

描述：慢性酒精依赖患者有显着减少 脑容量和伴随的神经行为缺陷， 在禁欲期间 然而，这些有据可查的病理生理学 调查结果仍有待澄清。 质子磁共振 波谱[MRS]，允许在脑的体内进行非侵入性定量 在解剖学局部感兴趣体积[VOI]内的代谢物，我们有 发现随着戒断时间的延长， 相对于神经元标记物可见的含胆碱[Cho]的化合物， N-乙酰天冬氨酸[NAA]，在酒精中毒的小脑中线内 患者 我们的初步数据表明，Cho/NAA的比例可能是 与临床变量相关，特别是与脑损伤的严重程度相关， 功能障碍 我们建议描述这些的纵向过程， 大脑中被认为是敏感的区域的代谢变化 酒精引起的损伤（小脑蚓部、额叶皮质和额叶白色区） 事项）。 酒精依赖患者将使用质子MRS进行研究， 急性酒精戒断症状已减轻（在其发生后3至5天内）。 最后一次饮酒），在住院监测3周后 禁欲，出院后9周。 高分辨率MR 将同时采集图像，以确定对 灰质、白色物质和脑脊液的颅内体积， 小脑的体积和每个VOI的组织组成。 还有， 认知（注意力、心理速度和记忆）和小脑 （姿势摇摆）功能将被评估。 健康对照组也将 与酗酒者在相同的时间间隔进行研究， 潜在的MRS/MRI重新定位错误和学习效应 神经行为测试 经过3周的监测禁欲， 将进行全面的神经心理测试， 确定患者是否具有持久的、有临床意义的认知功能， 功能障碍 纵向进展和相互关系 脑VOI的代谢特征，体积变化， 认知/小脑功能以及相关临床变量将 分析了 如果我们的假设被证实，那就意味着白色物质 酒精性脑损伤的病理生理学损伤，以及 在CNS功能恢复中增加含Cho化合物 以禁欲的方式观察。 在未来，也许可以通过化学方法 通过使用尸体解剖的体外研究确定涉及的确切化合物， 人脑组织或使用可用的临床前动物模型， 对预防、鉴别诊断和 治疗与酒精中毒有关的器质性精神障碍。

DESCRIPTION: Chronic alcohol depended patients have a significant reduction in brain volume and concomitant neurobehavioral deficits which may recover during abstinence. However, the pathophysiology of these well-documented findings remains to be elucidated. Using proton magnetic resonance spectroscopy [MRS], which allows noninvasive quantitation in vivo of brain metabolites within anatomically localized volumes of interest [VOI], we have found an increase with duration of abstinence in the concentration of MR visible choline [Cho]- containing compounds relative to the neuronal marker, n-acetylaspartate [NAA], within the midline cerebellum of alcoholic patients. Our preliminary data suggest that the ratio Cho/NAA may be related to clinical variables, particularly to the severity of brain dysfunction. We propose to characterize the longitudinal course of these metabolic changes in regions of the brain recognized to be sensitive to alcohol-induced damage (cerebellar vermis, frontal cortex, and frontal white matter). Alcohol dependent patients will be studied using proton MRS when signs of acute alcohol withdrawal have abated (within 3 to 5 days of their last consumption of alcohol), after 3 weeks of inpatient monitored abstinence, and 9 weeks after discharge from hospital. High resolution MR images will be acquired concurrently to determine the contributions to the intracranial volume of gray matter, white matter, and cerebrospinal fluid, the volume of the cerebellum, and the tissue composition of each VOI. Also, cognitive (attention, psychomotor speed, and memory) and cerebellar (postural sway) functions will be evaluated. Healthy controls will also be studied at the same time intervals as the alcoholics to account for potential MRS/MRI repositioning error and learning effects of neurobehavioral testing. After 3 weeks of monitored abstinence, a comprehensive neuropsychological test battery will be administered to determine whether patients have enduring, clinically meaningful cognitive dysfunction. The longitudinal progression and interrelationships among metabolic characteristics of brain VOIs, volumetric changes, cognitive/cerebellar functions, and relevant clinical variables will be analyzed. If our hypotheses are confirmed, it would implicate white matter injury in the pathophysiology of alcohol-induced brain damage, and an increase in Cho-containing compounds in the recovery of CNS functions observed with abstinence. In the future, it may be possible to chemically identify the exact compounds involved by in vitro studies using autopsied human brain tissue or using available preclinical animal models, with significant implica-tions for prevention, differential diagnosis, and treatment of organic mental disorders associated with alcoholism.