Update on the pharmacotherapy of cerebellar and central vestibular disorders.
Update on the pharmacotherapy of cerebellar and central vestibular disorders.
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DOI：
10.1007/s00415-015-7987-x
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发表时间：
2016-04
影响因子：
6
通讯作者：
Strupp M
中科院分区：
文献类型：
--
作者：
Kalla R;Teufel J;Feil K;Muth C;Strupp M
本文综述了目前中枢性前庭综合征的药物治疗，以及最常见的中枢性眼球震颤和小脑疾病。4-氨基吡啶（4-AP）被推荐用于治疗下搏性眼球震颤（一种常见的获得性持续注视性眼球震颤）和上搏性眼球震颤。动物研究表明，这种电压门控钾通道的非选择性阻断剂增加浦肯野细胞的兴奋性，并使不规则放电率正常化，从而恢复小脑皮质对前庭和小脑深部核的抑制作用。在一项随机对照试验中，4-AP对发作性共济失调2型的疗效得到了证实，发作性共济失调2型最常见的原因是PQ-钙通道突变。这也显示在一个动物模型（蹒跚小鼠）的发作性共济失调2型。在一个病例系列中，氯唑沙宗（一种小电导钙激活钾通道的非选择性激活剂）显示可减少DBN。乙酰-DL-亮氨酸作为小脑疾病的潜在新对症治疗的疗效已在三个病例系列中得到证实。正在进行的发作性共济失调2型随机对照试验（缓释形式的4-氨基吡啶vs.乙酰唑胺vs.安慰剂; EAT 2 TREAT），前庭性偏头痛与美托洛尔（PROVEMIG试验），小脑步态障碍（缓释形式的4-氨基吡啶与安慰剂; FACEG）和小脑共济失调（乙酰-DL-亮氨酸与安慰剂; ALCAT）将为小脑和中枢前庭疾病的药物治疗提供新的见解。
An overview of the current pharmacotherapy of central vestibular syndromes and the most common forms of central nystagmus as well as cerebellar disorders is given. 4-aminopyridine (4-AP) is recommended for the treatment of downbeat nystagmus, a frequent form of acquired persisting fixation nystagmus, and upbeat nystagmus. Animal studies showed that this non-selective blocker of voltage-gated potassium channels increases Purkinje cell excitability and normalizes the irregular firing rate, so that the inhibitory influence of the cerebellar cortex on vestibular and deep cerebellar nuclei is restored. The efficacy of 4-AP in episodic ataxia type 2, which is most often caused by mutations of the PQ-calcium channel, was demonstrated in a randomized controlled trial. It was also shown in an animal model (the tottering mouse) of episodic ataxia type 2. In a case series, chlorzoxazone, a non-selective activator of small-conductance calcium-activated potassium channels, was shown to reduce the DBN. The efficacy of acetyl-DL-leucine as a potential new symptomatic treatment for cerebellar diseases has been demonstrated in three case series. The ongoing randomized controlled trials on episodic ataxia type 2 (sustained-release form of 4-aminopyridine vs. acetazolamide vs. placebo; EAT2TREAT), vestibular migraine with metoprolol (PROVEMIG-trial), cerebellar gait disorders (sustained-release form of 4-aminopyridine vs. placebo; FACEG) and cerebellar ataxia (acetyl-DL-leucine vs. placebo; ALCAT) will provide new insights into the pharmacotherapy of cerebellar and central vestibular disorders.