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

Amyloid deposition in adults with drug-resistant temporal lobe epilepsy

Elena Fonseca  1   2 , Sofía Lallana  1   2 , Gemma Ortega  3   4 , Amanda Cano  3   4 , Silvana Sarria-Estrada  5 , Deborah Pareto  5 , Manuel Quintana  1   2 , Carles Lorenzo-Bosquet  6 , Samuel López-Maza  1   2 , Ariadna Gifreu  1   2 , Daniel Campos-Fernández  1   2 , Laura Abraira  1   2 , Estevo Santamarina  1   2 , Adelina Orellana  3   4 , Laura Montrreal  3 , Raquel Puerta  3 , Núria Aguilera  3 , Maribel Ramis  3 , Itziar de Rojas  3   4 , Agustín Ruiz  3   4 , Lluis Tárraga  3   4 , Àlex Rovira  5 , Marta Marquié  3   4 , Mercè Boada  3   4 , Manuel Toledo  1   2
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Amyloid deposition in adults with drug-resistant temporal lobe epilepsy

Elena Fonseca et al. Epilepsia. 2024 Dec.

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.

Keywords: amyloid positron emission tomography; cognitive impairment; temporal lobe epilepsy.

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