Beaumont A, Clarke M, Whittle I R
Department of Clinical Neurosciences, Western General Hospital, Edinburgh, U.K.
Acta Neurochir (Wien). 1996;138(4):370-81. doi: 10.1007/BF01420298.
Generalised or partial seizures are a common problem with many supratentorial gliomas. Their underlying pathophysiological mechanisms are poorly understood. To investigate this problem clinical and EEG seizure thresholds were investigated in experimental rodent gliomas using the epileptogenic drug pentylenetetrazole (PTZ). Mixed C6/A15A5 malignant gliomas were grown in adult Wistar rats after unilateral stereotactic implantation of a 50:50 cell mix into the caudoputaminal region. Eleven to 14 days later EEG (raw and spectrally analysed) was recorded bilaterally from the frontal and parietal regions under mixed alpha-chloralose and urethane anaesthesia. Baseline EEG (15 minutes), EEG during and after (30 minutes) PTZ infusion (100 microliters/min) and the time to appearance of seizure manifestations after starting PTZ were recorded. Fourteen animals were studied (5 normal, 5 with tumours, 4 sham implants) and mean BP, PaCO2, PaO2 and temperature were similar in the three groups. Baseline raw EEG showed predominate slow wave activity with lower amplitude and less spontaneous activity overlying tumours. Following PTZ infusion a sequence of vibrissal twitching (following a mean of 14.5 mg/kg PTZ in control and sham animals); jaw/nasal twitches (17.5 mg/kg); fore and hind limb jerking (46 mg/kg); myoclonic jerking (47 mg/kg); and status (77.5 mg/kg) was observed. The seizure thresholds for all PTZ induced seizure phenomena were, except for status epilepticus, highest in the tumour bearing animals. The time to 70% seizure activity on the EEG was also significantly longer in the tumour bearing animals. Spectral analysis of the EEG, although showing increased alpha and theta activity after PTZ infusion, did not discriminate between the three experimental groups either before or after PTZ activation. These studies have confirmed that experimental gliomas alter baseline EEG and both the EEG and behavioural response to PTZ. The reasons for the raised seizure threshold in the glioma bearing animals and the relevance of this experimental paradigm to human tumour associated epilepsy are discussed.
全身性或部分性癫痫发作是许多幕上胶质瘤常见的问题。其潜在的病理生理机制尚不清楚。为了研究这个问题，我们使用致痫药物戊四氮（PTZ）在实验性啮齿动物胶质瘤中研究了临床和脑电图癫痫阈值。将50:50的细胞混合物单侧立体定向植入成年Wistar大鼠的尾壳核区域，培养混合的C6/A15A5恶性胶质瘤。11至14天后，在混合α-氯醛糖和乌拉坦麻醉下，从额叶和顶叶区域双侧记录脑电图（原始和频谱分析）。记录基线脑电图（15分钟）、PTZ输注期间和之后（30分钟）的脑电图（100微升/分钟）以及开始PTZ后癫痫发作表现出现的时间。研究了14只动物（5只正常、5只患有肿瘤、4只假植入），三组动物的平均血压、动脉血二氧化碳分压、动脉血氧分压和体温相似。基线原始脑电图显示主要为慢波活动，肿瘤上方的振幅较低且自发活动较少。PTZ输注后，观察到一系列抽搐现象：触须抽搐（对照和假植入动物平均在14.5毫克/千克PTZ后出现）；颌/鼻抽搐（17.5毫克/千克）；前肢和后肢抽搐（46毫克/千克）；肌阵挛抽搐（47毫克/千克）；以及癫痫持续状态（77.5毫克/千克）。除癫痫持续状态外，所有PTZ诱导的癫痫发作现象的癫痫阈值在荷瘤动物中最高。脑电图上出现70%癫痫活动的时间在荷瘤动物中也明显更长。脑电图的频谱分析虽然显示PTZ输注后α和θ活动增加，但在PTZ激活前后均未区分三个实验组。这些研究证实，实验性胶质瘤会改变基线脑电图以及脑电图和对PTZ的行为反应。讨论了荷瘤动物癫痫阈值升高的原因以及该实验范式与人类肿瘤相关性癫痫的相关性。
