PHYSIOLOGIC AND PHARMACOLOGIC STUDIES IN EPILEPSY

癫痫是最常见的神经系统疾病之一，癫痫发作不受控制的患者会遭受许多不良影响。本研究的目的是研究癫痫对大脑结构和功能的影响，并在现有方法无法控制癫痫发作时测试创新的治疗方法。方法：对患者进行视频脑电图监测，确定癫痫发作类型和病灶定位。正电子发射断层扫描（PET）和磁共振成像（MRI）用于研究脑代谢、血流和结构。测定抗癫痫药物血药浓度。最近的发现：与对照组相比，癫痫患者同侧的海马体积明显小于癫痫区。此外，癫痫患者的同侧丘脑、尾状体和双侧透镜体的平均体积明显小于对照组。外侧颞新皮层也出现萎缩。这些研究表明，医学上难治性颞叶癫痫与可能涉及的海马体以外的脑结构的体积损失有关。体积损失可能反映了这些结构在反复发作活动中所造成的损害。我们还发现癫痫持续时间与同侧海马形成（HF）体积和同侧/对侧比值有显著关系。有长时间复杂发热性惊厥（FS）病史的患者同侧HF体积和同侧/对侧比值小于无FS病史的患者。发病年龄或扫描的影响不显著。与无FS病史的患者相比，有FS病史的患者癫痫发作年龄并不早，病程也不长。FS病史可以预测患者HF萎缩的严重程度。我们的研究表明，在最初的损伤后，持续癫痫发作的患者可能会出现进行性心衰损害。目前的研究：我们正在进行一项双盲安慰剂对照研究，研究低频（1/秒）经颅磁刺激（TMS）对复杂部分性癫痫发作频率的影响。动物实验表明，低频经颅磁刺激可引起神经元兴奋性的长期抑制。这些患者的癫痫发作不能被现有的抗癫痫药物控制，并且通过视频脑电图监测定位癫痫发作病灶。在安慰剂条件下，磁线圈被引导远离癫痫发作的焦点。我们已经开始了对颞叶癫痫患者血清素受体的PET研究。

Epilepsy is one of the most common neurological disorders, and patients whose seizures are not controlled suffer from many adverse effects. The goal of this study is to investigate the effects of epilepsy on brain structure and function, and to test innovative approaches to treatment when seizures cannot be controlled by currently available approaches. Methods: Patients undergo video-EEG monitoring to determine seizure type and focus localization. Positron emission tomography (PET) and magnetic resonance imaging (MRI) are used to study cerebral metabolism, blood flow, and structure. Antiepileptic drug blood levels are obtained. Recent findings: hippocampal volumes ipsilateral to the epileptogenic zone were significantly smaller in the patients with epilepsy as compared to controls. In addition, mean ipsilateral thalamic, caudate and bilateral lenticular volumes were significantly smaller in the patients with epilepsy as compared to controls. Lateral temporal neocortex shows atrophy as well. These studies revealed that medically intractable temporal lobe epilepsy is associated with volume loss in brain structures outside the presumably involved hippocampus. Volume loss may reflect damage due to the involvement of these structures in recurrent seizure activity. We also found that epilepsy duration had a significant relation to ipsilateral hippocampal formation (HF) volume and ipsilateral/contralateral ratio. Patients with a history of prolonged complex febrile seizures (FS) had smaller ipsilateral HF volume and ipsilateral/contralateral ratio than patients without a history of FS. The effect of age at onset or scan was not significant. Patients with a history of FS did not have earlier age at epilepsy onset or longer duration than those without a history of FS. A history of FS predicted the severity of HF atrophy in our patients. Our study suggests that, after an initial insult, progressive HF damage may occur in patients with persistent seizures. Current Studies: We are conducting a double-blind placebo controlled study of the effect of low-frequency (1/second) transcranial magnetic stimulation (TMS) on the frequency of complex partial seizures. Animal studies suggest that low frequency TMS may induce long-term depression of neuronal excitability. Patients whose seizures are not controlled by currently available anti-epileptic drugs, and have a seizure focus localized by video-EEG monitoring are being enrolled. In the placebo condition, the magnetic coil is directed away from the seizure focus. We have begun a PET study of serotonin receptors in patients with temporal lobe epilepsy.