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Genetic advances over the past decade have enhanced our understanding of the genetic landscape of childhood epilepsy. However a major challenge for clinicians ha been understanding the rationale and systematic approach towards interpretation of the clinical significance of variant(s) detected in their patients. As the clinical paradigm evolves from gene panels to whole exome or whole genome testing including rapid genome sequencing, the number of patients tested and variants identified per patient will only increase. Each step in the process of variant interpretation has limitations and there is no single criterion which enables the clinician to draw reliable conclusions on a causal relationship between the variant and disease without robust clinical phenotyping. Although many automated online analysis software tools are available, these carry a risk of misinterpretation. This guideline provides a pragmatic, real-world approach to variant interpretation for the child neurologist. The focus will be on ascertaining aspects such as variant frequency, subtype, inheritance pattern, structural and functional consequence with regard to genotype-phenotype correlations, while refraining from mere interpretation of the classification provided in a genetic test report. It will not replace the expert advice of colleagues in clinical genetics, however as genomic investigations become a first-line test for epilepsy, it is vital that neurologists and epileptologists are equipped to navigate this landscape., Competing Interests: Conflicts of interest None, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: A paucity of literature exists on genotype- phenotype correlates of 'unknown-etiology' infantile-onset developmental-epileptic encephalopathies (DEE) from India. The primary objective was to explore the yield of genetic testing in identifying potential disease causing variants in electro-clinical phenotypes of DEE METHODS: An observational hospital-based study was undertaken on children with unexplained refractory seizure-onset ≤12 months age and developmental delay, whose families consented and underwent genetic testing during a three year time period (2016-2018) by next-generation sequencing (NGS) or multiplex ligand protein amplification. Yield was considered based on demonstration of pathogenic/likely pathogenic variants only and variants of unknown significance (VUS) were documented., Results: Pathogenic/likely pathogenic variants were identified in 26 (31.7 %) out of 82 children with DEE. These included those variants responsible for primarily DEE- 21(76.7 %); neuro-metabolic disorders- 3(18.6 %) and chromosomal deletions- 2(4.7 %). Of these patients, early-infantile epilepsy onset ≤ 6 months age was noted in 22(84.6 %). The DEE studied included Ohtahara syndrome associated with STXBP1 and SCN8A variants with yield of 50 % (2/4 tested); early myoclonic encephalopathy (no yield in 2); West syndrome with CDKL5, yield of 13.3 % (2/15 tested); epilepsy of infancy with migrating partial seizures due to CACNA1A and KCNT1 variants, yield of 67 % (2/3 tested); DEE-unclassified with KCNQ2, AP3B2, ZEB2, metabolic variants (SUOX, ALDH7A1, GLDC) and chromosome deletions (chr 1p36, chr2q24.3); yield of 32 % (8/25 tested). Patients with Dravet syndrome/Dravet-like phenotypes (N = 33) had variants in SCN1A (N = 10), SCN1B, CHD2; yield of 36.4 % (12/33 tested; 57.1 % from NGS). Eighteen patients with potential variants (SCN1A, SCN2A, SCN8A, KCNQ2, ALDH7A1 which also included VUS) could be offered targeted therapy., Conclusions: Our study confirms a good yield of genetic testing in neonatal and infantile-onset DEE provided robust phenotyping of infants is attempted with prognostic and therapeutic implications, particularly relevant to centres with resource constraints., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: The success of epilepsy surgery lies in identifying the ictal onset zone accurately. The significance of auras has little been explored on surgical outcome in drug-resistant epilepsy. This study focuses on the clinicopathological correlation of aura(s) and its role in predicting surgical outcome in drug-resistant temporal lobe epilepsy (TLE). We compared surgical outcome in TLE between patients with and without aura and identified the clinico-pathological, radiological and surgical differences between the two groups., Methods: Consecutive patients who underwent presurgical evaluation from January 2009 to December 2014 for drug-resistant TLE who underwent anterior temporal lobectomy (ATL) were included. Patients were followed up at 3months, 12 months and then annually., Results: Among 456 patients, 344(75%) had aura. Multivariate logistic regression showed that prototype EEG pattern at ictal onset (OR 2.12, 95% CI 1.18-3.06, p = 0.012) and right sided epileptogenic zone (OR 1.82 95% CI 1.18-3.78, p = 0.007) were significantly associated with presence of aura. There was no difference in surgical outcome between those with and without aura. But patients with auditory aura (OR 7.28, CI 2.80-18.95, p = 0.0002) and vertiginous aura (OR 3.01, CI 1.55-7.85, p = 0.028) had a poor surgical outcome. Bivariate analysis showed that normal MRI (p = 0.028) and normal/indeterminate pathology (p = 0.001) were significantly more common with auditory/vertiginous auras., Conclusions: Mere presence of aura does not affect outcome after TLE surgery. However, auditory and vertiginous auras are predictors of poor surgical outcome. These patients require more extensive screening for an ictal onset zone beyond standard limits of ATL before surgery., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: To validate concurrent utility of within-scanner encoding and delayed recognition-memory paradigms to ascertain hippocampal activations during task-based memory fMRI., Methods: Memory paradigms were designed for faces, word-pairs and abstract designs. A deep-encoding task was designed comprising of a total of 9 cycles run within a 1.5T MRI scanner. A recall session was performed after 1 h within the scanner using an event-related design. Group analysis was done with 'correct-incorrect' responses applied as parametric modulators in Statistical Parametric Mapping version 8 using boot-strap method to enable estimation of laterality indices (LI) using custom anatomical masks involving the medio-basal temporal structures., Results: Twenty seven subjects with drug-resistant mesial temporal lobe epilepsy due to hippocampal sclerosis (MTLE-HS) [17 patients of left-MTLE and 10 patients of right-MTLE] and 21 right handed age-matched healthy controls (HC) were recruited. For the encoding paradigm blood oxygen level dependent (BOLD) responses in HC demonstrated right laterality for faces, left laterality for word pairs, and bilaterality for design encoding over the regions of interest. Both right and left MTLE-HS groups revealed left lateralisation for word-pair encoding, bilateral activation for face encoding, with design encoding in right MTLE-HS demonstrating a left shift. As opposed to lateralization shown in controls, group analysis of cued-recall BOLD signals acquired within scanner in left MTLE-HS demonstrated right lateralization for word-pairs with bilaterality for faces and designs. The right MTLE-HS group demonstrated bilateral activations for faces, word-pairs and designs., Conclusion: Recall-based fMRI paradigms indicate hippocampal plasticity in MTLE-HS, maximal for word-pair associate recall tasks., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Cavernomas are well-known congenital vascular lesions with presumably high epileptogenicity. We report two patients who developed cavernomas; both were in remission from childhood acute lymphoblastic leukemia following standard chemo-radiotherapy. They developed drug-resistant focal epilepsy secondary to cavernomas and were subjected to surgical/medical management. This report highlights the ictogenesis of radiation-induced "acquired" cavernous angiomatosis in the brain. Appropriate treatment, including resection of these lesions in selected cases, improves the quality of life in such patients., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Introduction: Failure to identify the association antiepileptic drug (AED)-resistant temporal lobe epilepsy (TLE) with idiopathic generalized epilepsy (IGE) can interfere with decision for anterior temporal lobectomy (ATL) and prediction of post-ATL seizure outcome., Methods: Out of the 664 consecutive patients who underwent ATL between March 1995 and December 2007, 12 (1.8%) had coexisting IGE. The decision for ATL was made after a thorough discussion in the multidisciplinary patient management conference based upon the concordance between the clinical, electroencephalographic and magnetic resonance imaging data. All of them underwent epilepsy surgery for AED-resistant TLE., Results: In seven of the 12 patients, IGE was not identified until post-ATL. During a median follow-up period of 8.5 years, 8 of our 12 patients were seizure-free; the remaining 4 patients only had infrequent myoclonus. In two them, AEDs were discontinued; others were on montherapy for IGE., Conclusions: Our study highlights the rare association of IGE with TLE, the most common AED-resistant focal epilepsy syndrome. As the seizure outcome following ATL is similar in AED-resistant TLE patients with and without IGE, their co-existence is not a contraindication for ATL. Future studies should explore the molecular genetic basis of the rare association between these two epilepsy syndromes., (Copyright © 2011 Elsevier B.V. All rights reserved.)