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Combined Ex Vivo 9.4T MRI and Quantitative Histopathological Study in Normal and Pathological Neocortical Resections in Focal Epilepsy.

ABSTRACT: High-resolution magnetic resonance imaging (MRI) may improve the preoperative diagnosis of focal cortical dysplasia (FCD) in epilepsy. Quantitative 9.4T MRI was carried out (T1, T2, T2* and magnetization transfer ratio) on 13 cortical resections, representing pathologically confirmed FCD (five cases) and normal cortex. Quantitative immunohistochemistry for myelination (myelin basic protein/SMI94), neuronal populations [microtubule-associated protein 2 (MAP2), neurofilament (SMI31, SMI32), synaptophysin, NeuN, calbindin], reactive glia (GFAP), microglia (CD68) and blood-brain barrier permeability (albumin) was carried out in 43 regions of interest (ROI) from normal and abnormal white matter and cortex. MRI was spatially aligned and quantitative analysis carried out on corresponding ROI. Line profile analysis (LPA) of intensity gradients through the cortex was carried out on MRI and immunostained sections. An inverse correlation was noted between myelin/SMI94 and T1, T2 (P < 0.005) and T2* (P < 0.05; Spearman's correlation) and a positive correlation between neuronal MAP2 and T1 (P < 0.005) and T2* (P < 0.05) over all ROI. Similar pathology-MRI correlations were observed for histologically unremarkable white matter ROI only. LPA showed altered gradient contours in regions of FCD, reflecting abnormal cortical lamination and myelo-architecture, including a preoperatively undetected FCD case. This study demonstrates the ability of quantitative 9.4T MRI to detect subtle differences in neuronal numbers and myelination in histologically normal appearing white matter and LPA in the evaluation of cortical dyslamination. These methods may be translatable to the in vivo detection of mild cortical malformations.

SUBMITTER: Reeves C

PROVIDER: S-EPMC4950048 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveTo characterize seizure and cognitive outcomes of sparing vs removing an magnetic resonance imaging (MRI)-normal hippocampus in patients with temporal lobe epilepsy.MethodsIn this retrospective cohort study, we reviewed clinical, imaging, surgical, and histopathological data on 152 individuals with temporal lobe epilepsy and nonlesional hippocampi categorized into hippocampus-spared (n = 74) or hippocampus-resected (n = 78). Extra-hippocampal lesions were allowed. Pre- and postoperative cognitive data were available on 86 patients. Predictors of seizure and cognitive outcomes were identified using Cox-proportional hazard modeling followed by treatment-specific model reduction according to Akaike information criterion, and built into an online risk calculator.ResultsSeizures recurred in 40% within one postoperative year, and in 63% within six postoperative years. Male gender (P = .03), longer epilepsy duration (P < .01), normal MRI (P = .04), invasive evaluation (P = .02), and acute postoperative seizures (P < .01) were associated with a higher risk of recurrence. We found no significant difference in postoperative seizure freedom rates at 5 years between those whose hippocampus was spared and those whose hippocampus was resected (P = .17). Seizure outcome models built with pre- and postoperative data had bootstrap validated concordance indices of 0.65 and 0.72. The dominant hippocampus-spared group had lower rates of decline in verbal memory (39% vs 70%; P = .03) and naming (41% vs 79%; P = .01) compared to the hippocampus-resected group. Partial hippocampus sparing had the same risk of verbal memory decline as for complete removal.SignificanceSparing or removing an MRI-normal hippocampus yielded similar long-term seizure outcome. A more conservative approach, sparing the hippocampus, only partially shields patients from postoperative cognitive deficits. Risk calculators are provided to facilitate clinical counseling.

Project description:ObjectiveSeizure outcomes after brain surgery for drug-resistant epilepsy (DRE) are very heterogeneous and difficult to predict with models utilizing the current clinical, imaging, and electrophysiological variables. In this pilot study, we investigated whether genetic and molecular biomarkers (e.g., genomic, transcriptomic) can provide additional insight into differential response to surgery.MethodsPost-operative seizure-outcomes were collected at last follow-up (>6 months) for 201 adult patients with DRE who underwent surgery between 2004 and 2020. Resected tissue was sent for miRNA sequencing (n = 132) and mRNA sequencing (n = 135). Following the selection of 10 genes (SCN1A, NBEA, PTEN, GABRA1, LGL1, DEPDC5, IL1A, ABCB1, C3, CALHM1), we investigated SNPs in those 10 genes from previously acquired exome sequencing data (n = 106). Logistic regression was performed to test for associations between individual features (mRNAs, miRNAs, and SNPs) and post-operative seizure-outcome with an exploratory FDR P < 0.25 as the threshold for significance. Post-operative time-to-seizure analyses were performed for each SNP using a Cox proportional hazards model.ResultsThe majority of patients (83%) had temporal lobe epilepsy. Mean age at surgery was 38.3 years, and 56% were female. Three SNPs (rs10276036, rs11975994, rs1128503) in multi-drug resistance gene, ABCB1, were associated with post-operative seizure outcomes. Patients with alternate alleles in ABCB1 were more likely to be seizure-free at last follow-up (52-56% reduction in seizure recurrence; FDR P = 0.24). All three SNPs were in linkage disequilibrium and highly correlated with each other. Median post-operative time-to-seizure was 63 months for patients with 2 alternate alleles, 24-33 months with 1 alternate allele, and 10-11 months with 0 alternate alleles. These SNPs improved outcome prediction beyond MRI and sex alone. No independent miRNAs or mRNAs were significantly associated with seizure-outcome (P > 0.05). However, pathway analysis identified "cancer drug resistance by drug efflux" (mir-154 and mir-379) as enriched (P = 0.02), supporting the role of drug response genes in post-operative seizure recurrence.SignificanceABCB1 may have a role in epileptogenesis and surgery outcomes independent of its drug efflux activity necessitating further investigation. SNPs in ABCB1 may serve as independent predictors of post-operative outcome.

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Combined Ex Vivo 9.4T MRI and Quantitative Histopathological Study in Normal and Pathological Neocortical Resections in Focal Epilepsy.

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