Amyloid deposition in adults with drug-resistant temporal lobe epilepsy.

IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Epilepsia Pub Date : 2024-10-15 DOI:10.1111/epi.18142
Elena Fonseca, Sofía Lallana, Gemma Ortega, Amanda Cano, Silvana Sarria-Estrada, Deborah Pareto, Manuel Quintana, Carles Lorenzo-Bosquet, Samuel López-Maza, Ariadna Gifreu, Daniel Campos-Fernández, Laura Abraira, Estevo Santamarina, Adelina Orellana, Laura Montrreal, Raquel Puerta, Núria Aguilera, Maribel Ramis, Itziar de Rojas, Agustín Ruiz, Lluis Tárraga, Àlex Rovira, Marta Marquié, Mercè Boada, Manuel Toledo
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Abstract

Objective: Pathological amyloid-β (Aβ) accumulation and hyperphosphorylated tau proteins have been described in resected temporal lobe specimens of epilepsy patients. We aimed to determine cerebrospinal fluid (CSF) Aβ1-42 and p181-tau levels and cerebral Aβ deposits on positron emission tomography (Aβ PET) and correlate these findings with cognitive performance in adults with drug-resistant temporal lobe epilepsy (TLE).

Methods: In this cross-sectional study, we enrolled individuals with drug-resistant TLE who were 25-55 years old. Each participant underwent 18F-flutemetamol PET, determination of CSF Aβ1-42, p181-tau, and total tau, and a comprehensive neuropsychological assessment. We evaluated normalized standard uptake value ratios (SUVRs) for different brain regions on Aβ PET.

Results: Thirty patients (mean age = 41.9 ± SD 8.1 years, 57% men) were included. The median disease duration was 9.5 (interquartile range = 4-24) years. Twenty-six patients (87%) had a clinically significant cognitive impairment on neuropsychological evaluation, 18 (69%) of the amnesic type. On Aβ PET, high uptake was observed in both mesial temporal regions (ipsilateral: SUVR z-score = .90, 95% confidence interval [CI] = .60-1.20; contralateral: SUVR z-score = .92, 95% CI = .57-1.27; p < .001), which was higher when compared to SUVR z-scores in all the remaining regions (p < .001) and in the ipsilateral anterior cingulate (SUVR z-score = .27, 95% CI = .04-.49, p = .020). No significant deposition was observed in other regions. Seven patients (23%) had low Aβ1-42 levels, and two (7%) had elevated p181-tau levels in CSF. Higher p181-tau levels correlated with poorer verbal fluency (R = -.427, p = .044).

Significance: Our findings reveal a considerable Aβ deposition in mesial temporal regions and ipsilateral anterior cingulate among adults with drug-resistant TLE. Additionally, abnormal CSF Aβ1-42 levels were observed in a significant proportion of patients, and p181-tau levels were associated with verbal fluency. These results suggest that markers of neuronal damage can be observed in adults with TLE, warranting further investigation.

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成人耐药性颞叶癫痫患者体内的淀粉样蛋白沉积。
目的:在癫痫患者切除的颞叶标本中发现了病理性淀粉样蛋白-β(Aβ)堆积和高磷酸化tau蛋白。我们的目的是测定脑脊液(CSF)中Aβ1-42和p181-tau的水平以及正电子发射断层扫描(Aβ PET)显示的脑Aβ沉积物,并将这些结果与成人耐药性颞叶癫痫(TLE)患者的认知能力相关联:在这项横断面研究中,我们招募了 25-55 岁的耐药性颞叶癫痫患者。每位受试者都接受了18F-氟替美托咪醇正电子发射计算机断层扫描、脑脊液Aβ1-42、p181-tau和总tau测定以及全面的神经心理学评估。我们评估了 Aβ PET 不同脑区的归一化标准摄取值比(SUVR):共纳入 30 名患者(平均年龄 = 41.9 ± SD 8.1 岁,57% 为男性)。中位病程为 9.5 年(四分位数间距 = 4-24)。26名患者(87%)在神经心理评估中出现了明显的临床认知障碍,其中18名患者(69%)属于失忆类型。在 Aβ PET 上,两个颞中叶区域都观察到了高摄取(同侧:同侧:SUVR z-score = .90,95% 置信区间 [CI] = .60-1.20;对侧:SUVR z-score = .90,95% 置信区间 [CI] = .60-1.20:同侧:SUVR z 评分 = .90,95% 置信区间 [CI] = .60-1.20;对侧:SUVR z 评分 = .92,95% 置信区间 = .57-1.27;P 显著性:我们的研究结果表明,在耐药性TLE成人患者中,颞中叶区域和同侧扣带回前部存在大量Aβ沉积。此外,在相当一部分患者中观察到脑脊液 Aβ1-42 水平异常,p181-tau 水平与言语流畅性相关。这些结果表明,在成人TLE患者中可以观察到神经元损伤的标志物,值得进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Epilepsia
Epilepsia 医学-临床神经学
CiteScore
10.90
自引率
10.70%
发文量
319
审稿时长
2-4 weeks
期刊介绍: Epilepsia is the leading, authoritative source for innovative clinical and basic science research for all aspects of epilepsy and seizures. In addition, Epilepsia publishes critical reviews, opinion pieces, and guidelines that foster understanding and aim to improve the diagnosis and treatment of people with seizures and epilepsy.
期刊最新文献
Automatic responsiveness testing in epilepsy with wearable technology: The ARTiE Watch. WONOEP appraisal: Targeted therapy development for early onset epilepsies. Issue Information Association of cognitive and structural correlates of brain aging and incident epilepsy. The Framingham Heart Study. Epilepsia – November 2024 Announcements
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