耐药性颞叶癫痫成人患者的淀粉样蛋白沉积

Fonseca Elena, Lallana Sofía, Ortega Gemma, Cano Amanda, Sarria-Estrada Silvana, Pareto Deborah, Quintana Manuel, Lorenzo-Bosquet Carles, López-Maza Samuel, Gifreu Ariadna, Campos-Fernández Daniel, Abraira Laura, Santamarina Estevo, Orellana Adelina, Montrreal Laura, Puerta Raquel, Aguilera Núria, Ramis Maribel, de Rojas Itziar, Ruiz Agustín, Tárraga Lluis, Rovira Àlex, Marquié Marta, Boada Mercè, Toledo Manuel

Epilepsy Unit, Neurology Department, Medicine Department, Universitat Autònoma de Barcelona, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.

Research Group on Status Epilepticus and Acute Seizures, Vall d'Hebron Research Institute, Vall d'Hebron University Hospital, Vall d'Hebron Hospital Campus, Barcelona, Spain.

Epilepsia. 2024 Dec;65(12):3664-3675. doi: 10.1111/epi.18142. Epub 2024 Oct 15.

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 F-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.

目的

在癫痫患者切除的颞叶标本中已发现病理性淀粉样β蛋白（Aβ）积聚和tau蛋白高度磷酸化。我们旨在测定耐药物性颞叶癫痫（TLE）成人患者的脑脊液（CSF）Aβ1-42和p181-tau水平以及正电子发射断层扫描（Aβ PET）上的脑Aβ沉积情况，并将这些结果与认知表现相关联。

方法

在这项横断面研究中，我们纳入了年龄在25至55岁之间的耐药物性TLE患者。每位参与者均接受了F-氟代甲磺酸美他莫尔PET检查、脑脊液Aβ1-42、p181-tau和总tau的测定，以及全面的神经心理学评估。我们评估了Aβ PET上不同脑区的标准化标准摄取值比率（SUVRs）。

结果

共纳入30例患者（平均年龄 = 41.9 ±标准差8.1岁，57%为男性）。疾病中位持续时间为9.5年（四分位间距 = 4 - 24年）。26例患者（87%）在神经心理学评估中存在具有临床意义的认知障碍，其中18例（69%）为遗忘型。在Aβ PET上，双侧内侧颞叶区域均观察到高摄取（同侧：SUVR z评分 =.90，95%置信区间[CI] =.60 - 1.20；对侧：SUVR z评分 =.92，95% CI =.57 - 1.27；p <.001），与所有其他区域的SUVR z评分相比更高（p <.001），且高于同侧前扣带回（SUVR z评分 =.27，95% CI =.04 -.49，p =.020）。在其他区域未观察到明显沉积。7例患者（23%）脑脊液Aβ1-42水平较低，2例（7%）脑脊液p181-tau水平升高。p181-tau水平越高，言语流畅性越差（R = -.427，p =.044）。