Salinsky Martin, Storzbach Daniel, Oken Barry, Spencer David
Oregon Health and Science University Epilepsy Center, 3181 SW Sam Jackson Park Road, CDW-3, Portland, OR 97201, USA.
Epilepsy Behav. 2007 May;10(3):463-9. doi: 10.1016/j.yebeh.2006.12.011. Epub 2007 Mar 6.
Previous quantitative EEG (QEEG) studies of carbamazepine (CBZ), oxcarbazepine (OXC), and phenytoin (PHT) revealed a pattern of EEG slowing and an increase in drowsiness on the awake maintenance task (AMT). EEG slowing has been shown to correlate with negative effects on cognitive tests. Topiramate (TPM) is a novel AED with relatively large negative effects on cognitive function. We tested the hypothesis that TPM would induce significant slowing of EEG background rhythms and an increase in AMT drowsiness.
Forty healthy volunteers were randomized to TPM, gabapentin (GBP), or placebo. Doses were escalated as tolerated to a maximum of 400mg/day for TPM or 3600 mg/day for GBP, over a 10-week period, followed by a minimum 2-week plateau period. Volunteers underwent an EEG, cognitive tests, and the AMT prior to starting an AED and again 12 weeks later. The EEG was captured using a structured recording protocol and quantified using the fast Fourier transform. Four target measures were derived from the averaged occipital electrodes (peak frequency of the dominant posterior rhythm, median frequency, percentage theta, and percentage delta). Test-retest changes for all measures were scored against similar test-retest distributions previously obtained from untreated healthy volunteers.
TPM produced no significant change in any of the four target EEG measures or on the AMT, even though several target cognitive tests revealed moderate or greater negative effects. There were also no significant changes in the placebo group. GBP slowed the peak and median frequency EEG measures and increased the percentage of theta and delta activity. Neither TPM, GBP, nor placebo caused a significant increase in drowsiness on the AMT.
TPM has a unique neurotoxicity profile. It has no effect on EEG background measures or on the AMT, but induces moderate to large negative changes in many cognitive test scores. This profile differs from those of CBZ, OXC, PHT, and GBP.
先前对卡马西平（CBZ）、奥卡西平（OXC）和苯妥英（PHT）进行的定量脑电图（QEEG）研究显示，在清醒维持任务（AMT）中存在脑电图减慢和嗜睡增加的模式。脑电图减慢已被证明与对认知测试的负面影响相关。托吡酯（TPM）是一种新型抗癫痫药物，对认知功能有相对较大的负面影响。我们检验了以下假设：TPM会导致脑电图背景节律显著减慢以及AMT嗜睡增加。
40名健康志愿者被随机分为TPM组、加巴喷丁（GBP）组或安慰剂组。在10周内，根据耐受情况逐渐增加剂量，TPM最大剂量为400mg/天，GBP最大剂量为3600mg/天，随后至少有2周的稳定期。志愿者在开始服用抗癫痫药物前以及12周后再次接受脑电图检查、认知测试和AMT。使用结构化记录协议采集脑电图，并使用快速傅里叶变换进行量化。从平均枕叶电极得出四个目标测量值（优势后节律的峰值频率、中位数频率、θ波百分比和δ波百分比）。所有测量值的重测变化根据先前从未经治疗的健康志愿者获得的类似重测分布进行评分。
TPM在四个目标脑电图测量值中的任何一个或AMT上均未产生显著变化，尽管几项目标认知测试显示出中度或更大的负面影响。安慰剂组也没有显著变化。GBP使脑电图的峰值和中位数频率测量值减慢，并增加了θ波和δ波活动的百分比。TPM、GBP和安慰剂均未导致AMT上的嗜睡显著增加。
TPM具有独特的神经毒性特征。它对脑电图背景测量值或AMT没有影响，但会在许多认知测试分数中引起中度至较大的负面变化。这种特征与CBZ、OXC、PHT和GBP不同。
