Kockelmann Edgar, Elger Christian E, Helmstaedter Christoph
Department of Epileptology, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany.
Epilepsy Res. 2003 May;54(2-3):171-8. doi: 10.1016/s0920-1211(03)00078-0.
Topiramate (TPM) is a highly effective anticonvulsant drug, but a comparably high rate of cognitive adverse effects have been reported. In this study, we investigated changes in frontal lobe associated cognitive measures after TPM withdrawal in epilepsy patients hospitalized for presurgical evaluation.
Twenty epilepsy patients were administered a brief neuropsychological test battery before and after withdrawal of TPM. Neuropsychological evaluation included a verbal fluency task, verbal (Wechsler's digits) and spatial spans (Corsi block-tapping) and Trail Making Test (TMT, parts A and B). Median baseline dosage of TPM was 237.5mg/d, the median retest-interval was 8 days. Results were compared to a matched group of patients, who had been tested and retested before and after reduction of AEDs other than TPM at comparable time intervals.
After TPM withdrawal, group performance appeared significantly improved in five of six tests administered. The scores of the control patients remained largely unchanged after drug reduction. After withdrawal, the scores of the TPM group did not differ significantly from the results of the control group whereas pronounced differences had been observed before. Individual improvement became apparent in the majority of patients. Cognitive performance was not correlated to current daily dosages/current blood serum levels of TPM.
Withdrawal of TPM causes significant improvement in frontal lobe associated measures like verbal fluency and working memory. As withdrawal was part of the preoperative work-up, and not initiated because of patients' complaints or hints of intoxication, cognitive impairment due to TPM appears to be easily overlooked and underestimated.
托吡酯(TPM)是一种高效抗惊厥药物,但据报道其认知不良反应发生率相对较高。在本研究中,我们调查了因术前评估而住院的癫痫患者停用TPM后额叶相关认知指标的变化。
20例癫痫患者在停用TPM前后接受了简短的神经心理学测试。神经心理学评估包括言语流畅性任务、言语(韦氏数字)和空间广度(科西方块敲击)以及连线测验(TMT,A和B部分)。TPM的基线中位剂量为237.5mg/d,中位复测间隔为8天。将结果与一组匹配的患者进行比较,这些患者在可比的时间间隔内接受了除TPM之外的抗癫痫药物减量前后的测试和复测。
停用TPM后,在进行的六项测试中有五项测试中,该组的表现明显改善。对照组患者在药物减量后分数基本保持不变。停药后,TPM组的分数与对照组的结果无显著差异,而之前观察到有明显差异。大多数患者个体有明显改善。认知表现与TPM的当前每日剂量/当前血清水平无关。
停用TPM可使额叶相关指标如言语流畅性和工作记忆有显著改善。由于停药是术前检查的一部分,并非因患者主诉或中毒迹象而启动,TPM所致的认知损害似乎很容易被忽视和低估。