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Amyloid deposition in adults with drug-resistant temporal lobe epilepsy

  • 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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)3664-3675
Number of pages12
JournalEpilepsia
Volume65
Issue number12
DOIs
StatePublished - Dec 2024
Externally publishedYes

Keywords

  • amyloid positron emission tomography
  • cognitive impairment
  • temporal lobe epilepsy

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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