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.

Ocular pathology in NeuroAIDS - An autopsy study.

The central nervous system (CNS) and the eye are involved in Human immunodeficiency virus related disease. Although, optic nerve is considered an extension of the CNS, it has not been systematically evaluated to determine if infections of brain can extend into the eye or vice versa. The brain and posterior compartment of eyeball retrieved at autopsy of patients succumbing to NeuroAIDS, were evaluated with Hematoxylin & Eosin, special stains and immunohistochemistry for infective pathogens. Multiplex PCR was performed in vitreous, CSF and serum for simultaneous detection of bacterial, viral, and protozoal opportunistic infections. Ocular involvement in NeuroAIDS was seen in 93.7% (15/16) with opportunistic infection being the most common 62.5% (10/16); with toxoplasma optic neuropathy in 5 (50%), Cryptococcal optic neuritis in 3 (30%), and Cytomegalovirus chorioretinitis in 2 (20%). Concordance between ocular and CNS pathology was seen in 50% of cases. CSF PCR was more sensitive than PCR in vitreous for detecting ocular infections in posterior compartment of eye.

Surgical outcome in patients with mesial temporal sclerosis, with and without associated temporal lobe pathology: A clinicopathological study

Objective: Mesial temporal sclerosis with associated extra hippocampal pathology is considered ‘dual pathology’ that could influence the progression and clinical outcome of complex partial seizures. This study is undertaken to evaluate and compare the clinical outcome and pathology of the temporal lobe and hippocampus in cases of mesial temporal sclerosis (MTS) alone and MTS with associated pathological changes in the extrahippocampal temporal lobe (dual pathology). Methods: The clinical and presurgical evaluation data and post surgical follow up (2 years) were reviewed retrospectively from medical records of 15 cases with MTS alone and 11 cases having dual pathology. Specific pathological changes were recorded after reviewing the material from hippocampus and temporal lobe and immunostaining with antibodies to synaptophysin, and neurofilament to delineate dystrophic neurons and synaptic pathology and S-100 protein for glial elements. Results: Among the 11 patients with dual pathology, 2 patients had mild cortical dysplasia (MCD) and 9 had focal cortical dysplasia (FCD) in the adjacent temporal cortex, as described by Palmini et al. High resolution MRI (1.5 Tesla) did not detect the presence of the second pathology reported in this series. Thirteen of the 15 patients with MTS alone and 6 of the 11 patients with dual pathology had good post surgical outcome. Six (2 MTS + 4 dual pathology) out of 7 patients who failed to show good clinical outcome had significant loss of neurons in CA3 sub-field of Ammon’s horn, whereas only 12 out of 19 patients who had good outcome had CA3 neuronal loss. Various types of cytoskeletal and synaptic pathology are found in the dysplastic neurons in the zones of cortical dysplasia. Conclusion: Two types of structural lesions underlie complex partial seizures, MTS with or without associated extrahippocampal lesions of neuronal cytoarchitectural abnormality may influence the prognosis. Neuronal loss in CA3 subfield of Ammon’s horn seems to have a role in negative clinical outcome, though this feature needs to be further validated.