种系遗传变异会影响耐药性癫痫的手术效果吗？

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research Pub Date : 2024-08-06 DOI:10.1016/j.eplepsyres.2024.107425

Paula Marques , Patrick B. Moloney , Caihong Ji , Quratulain Zulfiqar Ali , Archana Ramesh , David B. Goldstein , Karen Barboza , Ilakkiah Chandran , Marlene Rong , Arunan Selvarajah , Farah Qaiser , Victor S.T. Lira , Taufik A. Valiante , Carl W. Bazil , Hyunmi Choi , Orrin Devinsky , Chantal Depondt , Terence O’Brien , Piero Perucca , Arjune Sen , Danielle M. Andrade

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引用次数: 0

摘要

目的我们对之前接受过手术前评估的耐药性癫痫（DRE）患者进行了回顾性研究，以确定手术结果与癫痫基因中致病变异之间的相关性。方法通过国际合作，我们对接受过手术候选筛查的成年 DRE 患者进行了评估。无论基因诊断是在手术前评估之前还是之后做出的，与癫痫相关的基因中存在致病性（P）或可能致病性（LP）种系变异的患者都被包括在内。患者分为两组：切除性手术候选者（RS）和非切除性手术候选者（NRSC），后者又分为：姑息性手术（迷走神经刺激、脑深部刺激、反应性神经刺激或胼胝体切开术）和不手术。我们比较了不同基因异常患者的手术候选评估和术后结果。经过术前评估，36 名患者接受了 RS 手术，106 名患者接受了 NRSC 手术。与 RS 组（14%）相比，NRSC 组（48%）中离子通道和突触传递基因变异的患者更为常见（p<0.001）。RS 组的大多数患者患有结节性硬化综合症。在 RS 组中，几乎一半（17/36，47%）的患者有恩格尔分级 I 级或 II 级结果。与 mTOR 病变患者相比，通道病变患者接受外科手术的可能性较低，但在被认为适合切除的情况下，手术效果较好（恩格尔 I/II 级为 71% ，恩格尔 I/II 级为 41%）。在NRSC组中，有40人接受了姑息手术，其中26/40（65%）人在平均随访11年后癫痫发作减少了≥50%。包括通道病诊断在内的基因组学发现不应排除手术前评估或癫痫手术，经过适当选择的病例可能会获得良好的手术效果。对接受癫痫手术的单基因癫痫患者进行前瞻性登记可为了解手术效果提供更多信息。

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Do germline genetic variants influence surgical outcomes in drug-resistant epilepsy?

Objective

We retrospectively explored patients with drug-resistant epilepsy (DRE) who previously underwent presurgical evaluation to identify correlations between surgical outcomes and pathogenic variants in epilepsy genes.

Methods

Through an international collaboration, we evaluated adult DRE patients who were screened for surgical candidacy. Patients with pathogenic (P) or likely pathogenic (LP) germline variants in genes relevant to their epilepsy were included, regardless of whether the genetic diagnosis was made before or after the presurgical evaluation. Patients were divided into two groups: resective surgery (RS) and non-resective surgery candidates (NRSC), with the latter group further divided into: palliative surgery (vagus nerve stimulation, deep brain stimulation, responsive neurostimulation or corpus callosotomy) and no surgery. We compared surgical candidacy evaluations and postsurgical outcomes in patients with different genetic abnormalities.

Results

We identified 142 patients with P/LP variants. After presurgical evaluation, 36 patients underwent RS, while 106 patients were NRSC. Patients with variants in ion channel and synaptic transmission genes were more common in the NRSC group (48 %), compared with the RS group (14 %) (p<0.001). Most patients in the RS group had tuberous sclerosis complex. Almost half (17/36, 47 %) in the RS group had Engel class I or II outcomes. Patients with channelopathies were less likely to undergo a surgical procedure than patients with mTORopathies, but when deemed suitable for resection had better surgical outcomes (71 % versus 41 % with Engel I/II). Within the NRSC group, 40 underwent palliative surgery, with 26/40 (65 %) having ≥50 % seizure reduction after mean follow-up of 11 years. Favourable palliative surgery outcomes were observed across a diverse range of genetic epilepsies.

Significance

Genomic findings, including a channelopathy diagnosis, should not preclude presurgical evaluation or epilepsy surgery, and appropriately selected cases may have good surgical outcomes. Prospective registries of patients with monogenic epilepsies who undergo epilepsy surgery can provide additional insights on outcomes.

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来源期刊

Epilepsy Research 医学-临床神经学

CiteScore

0.10

自引率

4.50%

发文量

143

审稿时长

62 days

期刊介绍： Epilepsy Research provides for publication of high quality articles in both basic and clinical epilepsy research, with a special emphasis on translational research that ultimately relates to epilepsy as a human condition. The journal is intended to provide a forum for reporting the best and most rigorous epilepsy research from all disciplines ranging from biophysics and molecular biology to epidemiological and psychosocial research. As such the journal will publish original papers relevant to epilepsy from any scientific discipline and also studies of a multidisciplinary nature. Clinical and experimental research papers adopting fresh conceptual approaches to the study of epilepsy and its treatment are encouraged. The overriding criteria for publication are novelty, significant clinical or experimental relevance, and interest to a multidisciplinary audience in the broad arena of epilepsy. Review articles focused on any topic of epilepsy research will also be considered, but only if they present an exceptionally clear synthesis of current knowledge and future directions of a research area, based on a critical assessment of the available data or on hypotheses that are likely to stimulate more critical thinking and further advances in an area of epilepsy research.