Corpora amylacea and glymphatic system in temporal lobe epilepsy patients: Clinicopathological correlation

Corpora amylacea (CA), now called wasteosomes, are basophilic inclusions associated with aging, neurodegeneration, and impaired glymphatic waste clearance. Their presence is well described in temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) and related to hippocampal neuronal loss and longer epilepsy duration. Here, we assessed CA deposition in TLE patients submitted to epilepsy surgery with any histological diagnosis and explored its relationship with clinical and neuropsychological variables. Histological signs of the glymphatic system were evaluated.

Qualitative and quantitative evaluation of CA was performed on neocortical and hippocampal surgical specimens and correlated with age at onset, duration of epilepsy, type of seizure at surgery, antecedents, psychiatric symptoms, and seizure outcome. Podoplanin (PDPN) expression was assessed in a subgroup of patients with high and low CA presence as a histological marker of lymphatic elements. Comparison with nonepileptic tissues was also performed.

Fifty consecutive patients were included with the following histological diagnosis: 18 patients with HS only, 10 patients with HS and associated focal cortical dysplasia (type IIIa), seven patients with encephalocele, five cryptogenic patients with no abnormalities on resected brain specimens (no lesion), and 10 patients with other histological findings. Patients with HS were vulnerable to CA accumulation compared to other etiologies. There was a significant association between CA density and duration of epilepsy, independent of age at surgery or other clinical parameters, and the presence of CA was associated with a worse preoperative cognitive profile. Preliminary histological observations from a few cases suggested enlarged perivascular spaces and altered PDPN vascular expression in patients with higher deposition of CA.

These findings provide evidence that CA accumulation correlates with epilepsy duration and suggest a contribution of altered brain clearance mediated by the glymphatic system to cortical dysfunction and cognitive deficits. Future research on glymphatic alterations and their therapeutic modulation may improve management of TLE and other epileptic or neurodegenerative conditions.