Gazulla J
Servicio de Neurología, Hospital Universitario Miguel Servet, Zaragoza, Spain.
Rev Neurol. 2007;45(1):31-41.
To review the available neurochemical data on the different cerebellar ataxias, and the therapeutic trials undertaken in the last twenty-five years.
The cerebellar ataxias have been classified according to the compromised structures in cortical cerebellar atrophies, olivopontocerebellar atrophies, spinocerebellar atrophies, and degenerations of the dentate nucleus and efferent tracts of the cerebellum. Episodic ataxias have been included, as they are eminently treatable. No nosological, nor genetic classification has been followed in this article. In each section, the (frequently fragmentary) neurochemical data is presented first, followed by the most relevant attempts at pharmacological therapy undertaken in the last twenty-five years. As can be observed from the reviewed data, neurochemical principles have rarely been applied in the majority of the analysed clinical trials. An outline of the physiological neurotransmission of the cerebellum is given at the beginning of this article.
A systematic search for treatable ataxias is emphasized, as a response to the severity of the degenerative conditions. The use of GABAergic drugs is proposed in ataxias associated with a deficiency of GABA in the brain, and that of glutamatergic agents, for ataxias associated with glutamate deficiency. The use of serotoninergic and cholinergic drugs is ruled out due to insufficient neurochemical evidence. It is proposed that research on remedies for the cerebellar ataxias should be based on either molecular data, or on neurochemical data, in its defect. To this end, the study of animal or experimental models of ataxia, the use of objective methods for the measurement of ataxia, and the recruitment of homogenous study populations, are all recommended.
回顾有关不同类型小脑性共济失调的现有神经化学数据,以及过去25年中进行的治疗试验。
小脑性共济失调已根据皮质小脑萎缩、橄榄桥脑小脑萎缩、脊髓小脑萎缩以及小脑齿状核和传出束的变性中受损的结构进行分类。发作性共济失调也被纳入其中,因为它们是可显著治疗的。本文未遵循疾病分类学或遗传学分类。在每个部分中,首先呈现(通常是不完整的)神经化学数据,然后是过去25年中最相关的药物治疗尝试。从所回顾的数据中可以看出,在大多数分析的临床试验中很少应用神经化学原理。本文开头给出了小脑生理神经传递的概述。
强调对可治疗的共济失调进行系统搜索,以应对退行性疾病的严重性。对于与大脑中γ-氨基丁酸(GABA)缺乏相关的共济失调,建议使用GABA能药物;对于与谷氨酸缺乏相关的共济失调,建议使用谷氨酸能药物。由于神经化学证据不足,排除使用5-羟色胺能和胆碱能药物。建议对小脑性共济失调治疗方法的研究应基于分子数据或其缺陷中的神经化学数据。为此,推荐研究共济失调的动物或实验模型,使用客观的共济失调测量方法,并招募同质的研究人群。