Department of Neurology, University of Campinas, Campinas, Brazil.
Epilepsy Res. 2013 Jul;105(1-2):250-5. doi: 10.1016/j.eplepsyres.2012.12.007. Epub 2013 Jan 17.
Topiramate (TPM) is known to cause language impairment in healthy volunteers and patients with epilepsy. We assessed the effects of TPM on functional language networks in both patients with focal epilepsies and healthy controls using functional magnetic resonance imaging (fMRI).
We obtained fMRI data in 24 controls and 35 patients with frontal lobe epilepsy using a simple verbal fluency (VF) paradigm. Eight of the 35 patients were treated with TPM in polytherapy. We compared cognitive task related activations and de-activations in patients taking TPM with patients taking other AEDs and healthy controls. In a longitudinal pilot study with VF-fMRI paradigm, we studied two patients with focal epilepsies twice, prior to starting and on stable doses of TPM, two patients twice, before and after tapering TPM completely and two healthy controls twice, before and after single doses of 200mg TPM.
Cross sectional analyses of VF-fMRI showed a reduction in the task-related deactivation of the default mode network (DMN) in patients taking TPM. The longitudinal study corroborated these findings as both chronic administration and a single dose of TPM were associated with impaired categorical verbal fluency and disruption of task-related deactivations.
Similar neuropsychological and fMRI findings in patients and healthy controls indicate a specific effect of TPM in default mode network areas that may be essential components of the language network. Our preliminary data suggest a mechanism by which TPM impairs cognitive processing during language function and highlights the sensitivity of fMRI to detect the effects of AEDs on cognitive brain networks.
已知托吡酯（TPM）可引起健康志愿者和癫痫患者的语言障碍。我们使用功能磁共振成像（fMRI）评估了 TPM 对局灶性癫痫患者和健康对照者功能性语言网络的影响。
我们使用简单的言语流畅性（VF）范式从 24 名对照者和 35 名额叶癫痫患者中获得了 fMRI 数据。35 名患者中有 8 名接受了 TPM 的多药治疗。我们比较了服用 TPM 的患者、服用其他抗癫痫药的患者和健康对照者的认知任务相关激活和去激活情况。在一项使用 VF-fMRI 范式的纵向初步研究中，我们两次研究了两名局灶性癫痫患者，一次是在开始 TPM 治疗之前，一次是在 TPM 稳定剂量时；两次研究了两名患者，一次是在完全停用 TPM 之前，一次是在 TPM 完全停用之后；两次研究了两名健康对照者，一次是在服用 200mg TPM 之前，一次是在服用之后。
VF-fMRI 的横断面分析显示，服用 TPM 的患者默认模式网络（DMN）的任务相关去激活减少。纵向研究证实了这些发现，因为慢性给药和单次 TPM 剂量均与类别言语流畅性受损和任务相关去激活中断有关。
患者和健康对照者的类似神经心理学和 fMRI 发现表明 TPM 对默认模式网络区域的特定影响，这可能是语言网络的重要组成部分。我们的初步数据表明 TPM 损害语言功能期间认知加工的一种机制，并强调了 fMRI 检测抗癫痫药对认知脑网络影响的敏感性。
