COVID-19 vaccine associated demyelination & its association with MOG antibody.

BACKGROUND: ChAdOx1-S (Covishield™/Vaxzervria, AstraZeneca) and BBV152 (Covaxin) SARS-CoV-2 vaccines are proven to be safe and effective, but rare complications have been reported. OBJECTIVE: To describe reports of central nervous system (CNS) demyelination following ChAdOx1-S and BBV152 vaccinations. METHODS & RESULTS: We report 29 (17 female; mean 38 years) cases of CNS demyelination; twenty-seven occurred in temporal association with ChAdOx1-S vaccine; two in association with BBV152 vaccine. Eleven patients had presentation with myelitis, six patients developed optic neuritis, five had acute demyelinating encephalomyelitis, three presented with brainstem demyelination, and four had multiaxial involvement. Myelin oligodendrocyte glycoprotein (MOG) antibodies were positive in ten patients. One patient with ADEM and tumefactive demyelinating lesions died after a prolonged intensive care unit stay and superimposed infection. As compared to the control group (87); the postvaccinial cases were found to have a significantly higher mean age, presence of encephalopathy (p value:0.0007), CSF pleocytosis (p value: 0.0094) and raised CSF protein (p value: 0.0062). CONCLUSIONS: It is difficult to establish a causal relationship between vaccination and neurological adverse events such as demyelination. The temporal association with the vaccination and the presence of MOG antibodies raises the possibility of an immunogenic process triggered by the vaccine in susceptible individuals.

Altered vascular permeability but not angiogenesis may play a role in the epileptogenesis of human hippocampal sclerosis.

OBJECTIVE: We investigated the role of angiogenesis and vascular permeability in the pathogenesis of human drug-resistant epilepsy due to hippocampal sclerosis. METHODS: Resected hippocampi from 30 histologically confirmed cases of hippocampal sclerosis and 30 age-matched post-mortem controls were examined by immunohistochemical quantitation of vascular endothelial markers, CD31 and CD105 (markers of newly formed vessels), and data were analysed relative to MR volumetry. The blood-brain barrier was evaluated based on immunohistochemistry for IgG, albumin, VEGF and AQP4. RESULTS: Mean vascular density in the hippocampus was 8.71/mm2 in hippocampal sclerosis samples compared to 7.94/mm2 in age-matched controls. No statistically significant increase in vascular density was found in hippocampal sclerosis samples. Although no neoangiogenesis was found in hippocampal sclerosis samples based on CD105, breakdown of the blood-brain barrier, enhanced neuronal expression of VEGF, and perivascular seepage of IgG and albumin with uptake within neurons and astrocytes were found. Redistribution of the water channel protein, AQP4, reflected by change from normal punctate labelling to intense diffuse staining in hippocampal sclerosis samples, indicated an altered glia-vascular interface, disrupting blood-brain barrier permeability. SIGNIFICANCE: Our data show no objective histological evidence of angiogenesis in hippocampal sclerosis samples. When controlled for the confounding variable of hippocampal area, there was no difference in vascular density between cases and controls. A leaky blood-brain barrier and redistribution of AQP4 were identified which may contribute to epileptogenesis. This constitutes the largest study in the published literature evaluating a role of vascular permeability and angiogenesis in human hippocampal sclerosis.

Dual/double pathology in neurocysticercosis causing drug resistant epilepsy - Chance association or causal?

INTRODUCTION: Neurocysticercosis (NCC) as cause of drug resistant epilepsy (DRE) is commonly reported from India. We reviewed the neuropathological findings in patients undergoing resective surgery for DRE due to NCC, to determine the pathomechanism of epileptogenesis. METHODS: Clinical, demographic and neuropathological findings of histologically confirmed cases of NCC causing DRE between 2005-2019 were reviewed. NeuN, GFAP, phosphorylated neurofilament, vimentin, CD34 for glial/ neuronal alterations, and Masson trichrome, Luxol Fast blue for evidence of fibrosis/ demyelination was used to determine cause of epileptogenesis. RESULTS: There were 12 cases of NCC associated with dual/ double pathology, which constituted 3.02 % (12/398) of all the operated DRE. [Age range: 17-37y, Male:Female = 1.4:1]. Seizure duration ranged from 3-32y, with seizure onset between 4-27y. On MRI, lesions were of variable signal intensity on T1 and isointense on T2 with blooming on GRE/ SWI, and CT revealed calcification. Majority (11/12) had associated hippocampal sclerosis (HS) type 1 (dual pathology), localised to the same side as cysticercal cyst, suggesting it may be involved in the pathogenesis of HS. Ten had single cysticercal lesion involving ipsilateral hippocampus in 6, parahippocampal gyrus in 2, amygdala and temporal lobe in 1 case each. One had multiple NCC located in bilateral frontal, parietal and ipsilateral hippocampus. Adjacent cortex around the NCC evaluated in 6 cases, revealed inflammation, gliosis, axonal disruption/ beading, and variable synaptic/ neuronal dystrophic changes. There was a single case of NCC with Focal cortical dysplasia (FCD) type IIb (double pathology). In 11/12 cases Engel's post-surgery outcome was available with all having class I outcome. CONCLUSION: HS was most common pathology associated with cysticercosis (Dual pathology), localised ipsilateral to the cysticercal cyst, suggesting that HS is a secondary/ epiphenomenon. Perilesional changes such as inflammation, gliosis, dystrophic synaptic and axonal pathology play a role in inducing or perpetuating the epileptiform activity. The association of FCD IIb with NCC in one case is likely to be a chance occurrence.