The extracellular matrix (ECM) is an important regulator of excitability and synaptic plasticity, especially in its highly condensed form, the perineuronal nets (PNN). In patients with drug-resistant mesial temporal lobe epilepsy (MTLE), hippocampal sclerosis type 1 (HS1) is the most common histopathological finding. This study aimed to evaluate the ECM profile of HS1 in surgically treated drug-resistant patients with MTLE in correlation to clinical findings. Hippocampal sections were immunohistochemically stained for aggrecan, neurocan, versican, chondroitin-sulfate (CS56), fibronectin, Wisteria floribunda agglutinin (WFA), a nuclear neuronal marker (NeuN), parvalbumin (PV), and glial-fibrillary-acidic-protein (GFAP). In HS1, besides the reduced number of neurons and astrogliosis, we found a significantly changed expression pattern of versican, neurocan, aggrecan, WFA-specific glycosylation, and a reduced number of PNNs. Patients with a lower number of epileptic episodes had a less intense diffuse WFA staining in Cornu Ammonis (CA) fields. Our findings suggest that PNN reduction, changed ECM protein, and glycosylation expression pattern in HS1 might be involved in the pathogenesis and persistence of drug-resistant MTLE by contributing to the increase of CA pyramidal neurons’ excitability. This research corroborates the validity of ECM molecules and their modulators as a potential target for the development of new therapeutic approaches to drug-resistant epilepsy.
Coronavirus disease 2019 (COVID-19) vaccines have been reported as possible triggers of the production of antibodies pathogenic to the peripheral nerve and neuromuscular junction. We report on a patient who experienced vertical diplopia three weeks after the booster dose of the Pfizer-BioNTech vaccine (Comirnaty®). The diagnosis of myasthenia gravis (MG) was established based on highly positive antibodies to the nicotinic acetylcholine receptor (nAChR). Treatment with pyridostigmine and prednisone was started with gradually raising doses. On a follow-up exam two months after treatment initiation, clinical improvement was noted with an almost normal bulbomotor examination. The occurrence of diplopia following COVID-19 vaccination should raise suspicion of new-onset ocular MG and testing for anti-nAChR antibodies is advised.
26 October 2022 in Journal of the Neurological Sciences