Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.
Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.
Neurosurgery. 2019 Jul 1;85(1):E4-E15. doi: 10.1093/neuros/nyy480.
Minimally invasive therapies for drug-resistant epilepsy (DRE) have been advocated. A study of convection-enhanced delivery (CED) of muscimol, a GABAA receptor agonist, was previously completed in non-human primates.
To investigate the safety and anti-epileptic effects of intracerebral muscimol infusion into the epileptic focus of patients with DRE.
In this phase 1 clinical trial, 3 adult patients with DRE underwent CED into the seizure focus of artificial CSF vehicle followed by muscimol for 12 to 24 h each using a crossover design. Basic pathophysiology of the epileptic focus was examined by assessing the infusions' effects on seizure frequency, electroencephalogram (EEG) spike-wave activity, and power-spectral EEG frequency.
Inter-ictal neurological function remained normal in all patients. Pathological examination of resected specimens showed no infusion-related brain injuries. Seizure frequency decreased in 1 of 3 patients during muscimol infusion but was unchanged in all patients during vehicle infusion. Mean beta frequencies did not differ significantly before, during, or after infusion periods. Infused fluid provided insufficient MRI-signal to track infusate distribution. In the 2 yr after standard epilepsy surgery, 1 patient had temporary reduction in seizure frequency and 2 patients were seizure-free.
CED of muscimol into the epileptic focus of patients with DRE did not damage adjacent brain parenchyma or adversely affect seizure surgery outcome. This study did not confirm that intracerebral muscimol infusion effectively suppressed seizures. A surrogate tracer is recommended to track infusion distribution to the epileptic focus and surrounding structures in future studies using CED to suppress the seizure focus.
已经提倡采用微创疗法治疗耐药性癫痫（DRE）。此前，已在非人类灵长类动物中完成了关于 GABA 受体激动剂 muscimol 的经颅超声促渗给药（CED）的研究。
研究将 muscimol 脑内输注到 DRE 患者癫痫灶内的安全性和抗癫痫作用。
在这项 1 期临床试验中，3 例 DRE 成年患者采用交叉设计，先经 CED 将人工 CSF 载体输注到癫痫灶内，然后再输注 muscimol 持续 12 至 24 小时。通过评估输注对癫痫发作频率、脑电图（EEG）棘波活动和功率谱 EEG 频率的影响，检查癫痫灶的基本病理生理学。
所有患者的间发性神经功能均保持正常。切除标本的病理检查显示无与输注相关的脑损伤。在 muscimol 输注期间，3 例患者中有 1 例癫痫发作频率降低，但在载体输注期间所有患者均无变化。输注前后的平均β频率无显著差异。输注的液体提供的 MRI 信号不足以追踪输注物的分布。在标准癫痫手术后的 2 年内，1 例患者癫痫发作频率暂时降低，2 例患者无癫痫发作。
将 muscimol 脑内输注到 DRE 患者的癫痫灶内不会损害相邻的脑实质，也不会对癫痫手术结果产生不利影响。本研究并未证实脑内 muscimol 输注能有效抑制癫痫发作。建议在未来使用 CED 抑制癫痫灶的研究中，使用示踪剂来追踪输注物在癫痫灶及其周围结构中的分布。
