Abstracts

Rationale: Several studies utilizing post-mortem tissue and/or surgically resected tissue from the brains of people with medication-refractory epilepsy have demonstrated the presence of pathological tau aggregates, particularly in older adults.  Tau aggregation has previously been reported in the setting of hippocampal sclerosis, focal cortical dysplasias, cortical tubers, glioneuronal tumors, and vascular malformations.  Reduction of endogenous tau levels in various animal models of epilepsy has also been shown to be protective against seizures, raising the question of whether certain types of epilepsy should be considered “tauopathies.”  To further investigate the prevalence and type of tau pathology in adults with medication-refractory epilepsy, we evaluated a series of banked surgical specimens of cortical and/or hippocampal tissue from adults with medication-refractory epilepsy who previously underwent resective surgery for their epilepsy.  Methods: Epilepsy surgical specimens from 44 patients were examined for total tau protein by immunohistochemistry. At the time of surgery, the average patient age was 44.5 years old (ranging from 30 to 59 years old) and the average duration of epilepsy was 23.6 years (ranging from 1 to 51 years).  Histopathological diagnoses included hippocampal sclerosis (n=21), non-specific gliosis (n=5), cortical dysplasia (n=4), dysembryoplastic neuroepithelial tumour (n=4), vascular neoplasms/malformations (n=3), WHO grade II gliomas (n=3), among others (n=4).  Tissue from both the hippocampus and cortex was available in 32 patients, hippocampus only in 1 patient, and cortex only in 11 patients.  For immunohistochemistry, anti-human pan-Tau antibody (1:150; A0024, Dako) was used to stain 5 micron sections obtained from formalin-fixed, paraffin-embedded tissue.  Documented cases of Alzheimer’s disease were used as positive controls sections. Results: Only 1 out of 44 patients in the cohort demonstrated tau-related tangles by immunohistochemistry.  This patient was a 54 year old female with a history of epilepsy for 25 years. Tissue obtained from an anterior temporal lobectomy revealed hippocampal sclerosis with extensive loss of neurons and gliosis in the dentate fascia, CA1, CA2, CA4 and part of CA3.  On immunohistochemical staining, tau-related tangles were present in the entorhinal cortex (Braak & Braak stage I of VI).  The remaining 43 patients in the cohort were negative for definitive immunohistochemical staining of tau, with absent subpial band staining, neuropil threads, and neurofibrillary tangles. Conclusions: In our series of 44 surgical specimens from adults with medication-refractory epilepsy, we found little evidence of tau pathology.  This is in contrast to prior reports (Tai et al, Brain, 2016; Thom et al, Brain, 2011).  Our cohort was significantly younger than those in prior studies, which may have contributed to the absence of tau pathology.  Further studies are needed to better understand whether tau pathology plays a significant role in epilepsy. Funding: N/A