Abstracts

Rationale: Patients with drug-resistant temporal lobe epilepsy (TLE) commonly exhibit cognitive impairment. It may result from recurrent seizures and pathological changes in the temporal lobe structures. It has been hypothesized that amyloid-ß (Aß) plaques and hyperphosphorylated tau (pTau) might play a pathological role in the cognitive deficits in patients with TLE. We investigated the prevalence of Aß plaques and pTau in TLE patients who underwent resective surgery and correlated their presence with pre-operative psychometric test scores and clinical factors.

Methods: Eligible patients were retrospectively selected from the epilepsy surgery register of the Royal Melbourne Hospital, Melbourne, Australia. Patients with histologically confirmed hippocampal sclerosis (HS) or without identified pathology, and who had pre-surgical psychometric testing, were included. Patients without available paraffin blocks containing the brain tissue, or results of the specified psychometric tests, or who had a diagnosis of Alzheimer’s disease, were excluded. Sections from the resected hippocampus and temporal lobe tissues were immunostained for Aß plaques (using primary antibody 1E8) and pTau (using primary antibody AT8). Sections were assessed semi-quantitatively with scores of none, sparse ( < 3 plaques/100x microscopic field), moderate (3-6 plaques) or frequent ( >6 plaques). Their presence and severity were correlated with clinical characteristics and pre-operative verbal and visual learning functions as measured by the Verbal Pair Associates Test (VPA) and Rey Complex Figure Test (RCFT).

Results: 56 patients (55% female) aged 20 to 68 years (median 34 years) at surgery were included. Most (n=51) had histologically confirmed HS. Aß plaques were present in 4 patients (7%) (temporal cortex section in 3 patients and both temporal cortex and hippocampus in 1), all at the moderate level. Of these, 2 were under 50 years old. There was no difference in duration, age of onset of epilepsy or side of resection between patients with and without Aß plaques. Very occasional pTau tangles were found in only 2 patients (3.5%). Both had moderate Aß plaques and were over 50 years of age (Figure 1). Patients with Aß plaques had a lower median score for the VPA hard assessment compared to those without (0 vs. 4; p=0.02). There was otherwise no correlation between the pre-surgical psychometric testing scores and the presence of Aß plaques and pTau (Figure 2).

Conclusions: Aß plaques and pTau tangles were uncommon in patients undergoing temporal lobectomy for drug-resistant epilepsy and overall did not correlate with clinical characteristics of epilepsy or pre-operative psychometric test scores, except for a lower VPA score in patients with Aß plaques. Extended follow up is necessary to assess the potential association of such pathology on long-term cognitive function after epilepsy surgery. Considering the low incidence of Aß plaques and pTau tangles herein observed, cognitive impairment in TLE may not be driven by the same mechanisms as in Alzheimer’s disease.

Funding: Please list any funding that was received in support of this abstract.: Melbourne International Fee Remission Scholarship and Melbourne International Research Scholarship, both awarded by the University of Melbourne.