Enlarged Perivascular Spaces in the Basal Ganglia Across Epilepsy Subtypes

IntroductionThe glymphatic system is thought to be the brains primary waste clearance system, responsible for eliminating soluble metabolites and proteins from the central nervous system. It consists of the cerebrospinal fluid, the interstitial fluid, and a conduit between the two, perivascular spaces (PVS), which are channels formed by astroglial cells surrounding the blood vessels. PVS can be observed on high-resolution T1-weighted MRI images. Small studies have implicated PVS and glymphatics in the pathophysiology of epilepsy, potentially via reduced clearance of excitotoxic substances. This study investigates enlarged PVS burden in a large patient group with various types of epilepsy. MethodsPeople with various types of epilepsy were recruited from the Hospital das Clinicas, Unicamp, Brazil. They were matched approximately in age and sex with healthy volunteers as controls. All participants were scanned with T1-weighted MRI on a 3T Phillips MRI scanner, resolution 1.0x1.0x1.0 mm3. A deep-learning algorithm, PINGU, was applied to segment PVS. The volumes of PVS in the White Matter (WM) and Basal Ganglia (BG) were calculated and divided by the respective volumes of WM and BG to derive the volume fractions (PVS-VF). These were used as dependent variables in a general linear model, with the diagnostic group as the independent variable of interest and age and sex included as nuisance covariates. ResultsWe recruited 467 people with epilepsy (median age 42 years, 41.5% male), of whom 267 had temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), 71 TLE with no MRI-visible lesions (TLE-NEG), 65 with focal extratemporal epilepsy (ETLE), and 64 with Idiopathic Generalized Epilepsy (IGE)). They were matched with 473 healthy controls (median age 35 years, 38.3% male). All epilepsy subtypes had higher PVS-VF in the BG compared to controls (101-140%, effect size=0.95-1.37, p<1.33x10-15). There was no difference in PVS-VF in the WM between the epilepsy group and healthy controls, or between different epilepsy subtypes. The TLE-HS group had an asymmetry in their PVS distribution, being larger on the contra-lateral side. This was not observed in the healthy controls or any other epilepsy subtypes. There was no association between PVS-VF and duration of illness (median duration 29 years). ConclusionVolume of PVS in the BG is enlarged in people with epilepsy. Longitudinal studies are needed to determine whether seizures have a detrimental effect on the brains glymphatic system, or whether impaired glymphatics contribute to the development of epilepsy.