Wandschneider Britta, Burdett Jane, Townsend Lucy, Hill Andrea, Thompson Pamela J, Duncan John S, Koepp Matthias J
From the Department of Clinical and Experimental Epilepsy (B.W., J.B., A.H., P.J.T., J.S.D., M.J.K.), UCL Institute of Neurology, London; and MRI Unit (B.W., J.B., L.T., A.H., P.J.T., J.S.D., M.J.K.), Epilepsy Society, Chalfont St. Peter, UK.
Neurology. 2017 Mar 21;88(12):1165-1171. doi: 10.1212/WNL.0000000000003736. Epub 2017 Feb 17.
To investigate the effects of topiramate (TPM), zonisamide (ZNS), and levetiracetam (LEV) on cognitive network activations in patients with focal epilepsy using an fMRI language task.
In a retrospective, cross-sectional study, we identified patients from our clinical database of verbal fluency fMRI studies who were treated with either TPM (n = 32) or ZNS (n = 51). We matched 62 patients for clinical measures who took LEV but not TPM or ZNS. We entered antiepileptic comedications as nuisance variables and compared out-of-scanner psychometric measures for verbal fluency and working memory between groups.
Out-of-scanner psychometric data showed overall poorer performance for TPM compared to ZNS and LEV and poorer working memory performance in ZNS-treated patients compared to LEV-treated patients. We found common fMRI effects in patients taking ZNS and TPM, with decreased activations in cognitive frontal and parietal lobe networks compared to those taking LEV. Impaired deactivation was seen only with TPM.
Our findings suggest that TPM and ZNS are associated with similar dysfunctions of frontal and parietal cognitive networks, which are associated with impaired performance. TPM is also associated with impaired attenuation of language-associated deactivation. These studies imply medication-specific effects on the functional neuroanatomy of language and working memory networks.
This study provides Class III evidence that in patients with focal epilepsy, TPM and ZNS compared to LEV lead to disruption of language and working memory networks.
使用功能磁共振成像（fMRI）语言任务，研究托吡酯（TPM）、唑尼沙胺（ZNS）和左乙拉西坦（LEV）对局灶性癫痫患者认知网络激活的影响。
在一项回顾性横断面研究中，我们从言语流畅性fMRI研究的临床数据库中识别出接受TPM治疗（n = 32）或ZNS治疗（n = 51）的患者。我们为62名服用LEV但未服用TPM或ZNS的患者匹配了临床测量指标。我们将抗癫痫药物作为干扰变量输入，并比较了各组之间扫描仪外言语流畅性和工作记忆的心理测量指标。
扫描仪外心理测量数据显示，与ZNS和LEV相比，TPM的总体表现较差；与接受LEV治疗的患者相比，接受ZNS治疗的患者工作记忆表现较差。我们发现服用ZNS和TPM的患者有共同的fMRI效应，与服用LEV的患者相比，认知额叶和顶叶网络的激活减少。仅在TPM治疗时观察到失活受损。
我们的研究结果表明，TPM和ZNS与额叶和顶叶认知网络的类似功能障碍有关，这些功能障碍与表现受损有关。TPM还与语言相关失活的减弱受损有关。这些研究暗示了药物对语言和工作记忆网络功能神经解剖学的特异性影响。
本研究提供了III类证据，即在局灶性癫痫患者中，与LEV相比，TPM和ZNS会导致语言和工作记忆网络的破坏。
