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Purpose: Ring chromosome 20 {r(20)}--manifests as a refractory epilepsy syndrome with complex partial seizures (CPS), nocturnal frontal lobe seizures and non-convulsive status epilepticus (NCSE) in the majority of cases. r20 lacks a specific phenotypic expression or dysmorphic features. Psychomotor development may be normal, making the diagnosis difficult unless there is a high index of suspicion. This description of further cases is intended to improve recognition of this syndrome.Methods: Karyotyping for r20 was done in patients presenting with cryptogenic refractory epilepsy suggestive of r20 from August 2008 to September 2010. We identified three patients with r20 associated with refractory epilepsy. All were investigated with long-term video EEG. Their unique electro clinical features; epilepsy syndrome and outcome are discussed and compared to the available literature.Results: Karyotyping revealed ring 20 in 6-40% of lymphocytes. All manifested with seizures beginning at 2-10years of age. All had CPS; two had NCSE and one a seizure disorder resembling Lennox-Gastaut syndrome. The interictal EEG showed epileptiform abnormalities predominantly over the frontotemporal regions. Two patients had NCSE with generalized, frontally dominant theta and spike and wave discharges. None had facial dysmorphism or imaging abnormalities. They remained resistant to antiepileptic drugs.Conclusions: The use of routine karyotyping can easily pick up r(20); this information is especially useful in resource-poor countries. We have evolved an algorithm stating the indications to attempt r(20) karyotyping in a given patient in the light of the results of the present study and the existing literature. [ABSTRACT FROM AUTHOR]

Objective: To identify the rate of successful antiseizure medication (ASM) withdrawal after resective surgery in patients with long-term epilepsy-associated tumors (LEATs)., Methods: A retrospective analysis (from our prospectively archived data) on the post-operative ASM profile of 123 consecutive patients who completed a minimum of 2 years after resection of LEATs for ASM-resistant epilepsy. A comparison between recurred and non-recurred groups in terms of seizure recurrence was used to identify the potential predictors of seizure recurrence whose attributes were further analyzed using univariate and multiple logistic regression analysis. Kaplan-Meier survival curves were used to study the probability of ASM freedom following surgery., Results: We attempted ASM withdrawal in 102 (82.9 %) patients. Forty-eight (47.1 %) had seizure recurrence while reducing ASM, of which 22 (21.6 %) continued to have seizures even after ASM optimisation. On univariate analysis, presence of pre-operative secondary generalized seizure(s) was the only factor associated with seizure recurrence. At a mean follow-up of 6.1 years, 72 (58.5 %) patients were seizure-free and aura-free at terminal follow-up (53 patients were off any ASM). The cumulative probability of achieving complete ASM-free status was 29 % at fourth year, 42 % at sixth year, 55 % at eighth year, and 59 % at 10th year after surgery., Conclusions: Following resective surgery for LEATs, ASM(s) could be successfully discontinued in half of the patients. About one-third of the patients may have recurrent seizures on follow-up. Presence of secondary generalized seizure(s) prior to surgery predicts seizure recurrence, whereas MRI defined completeness of resection will not. This information will help in rationalising decisions on ASM management post-resection., Competing Interests: Declaration of Competing Interest All co-authors have seen and agreed with the contents of the manuscript, the ICMJE requirements for authorship have been met. Each author certifies that the manuscript represents honest work and that the submission including the abstract is not under review in any other publication. There is no competing interest/conflict of interest. No funding sources were involved in its completion. The authors report no disclosures relevant to the manuscript. As the corresponding author, I confirm that I have full access to all the data in the study and had final responsibility for the decision to submit for publication. No medical writer or editor was involved in the creation of your manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest withrespect to the research, authorship, and/or publication of thisarticle.

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.)

Objectives: The utility of intraoperative electrocorticography (ECoG)-guided resective surgery for pediatric long-term epilepsy-associated tumors (LEATs) with antiseizure medication (ASM) resistant epilepsy is not supported by robust evidence. As epilepsy networks and their ramifications are different in children from those in adults, the impact of intraoperative ECoG-based tailored resections in predicting prognosis and influencing outcomes may also differ. We evaluated this hypothesis by comparing the outcomes of resections with and without the use of ECoG in children and adults by a randomized study., Methods: From June 2020 to January 2022, 42 patients (17 children and 25 adults) with LEATs and antiseizure medication (ASM)-resistant epilepsy were randomly assigned to one of the 2 groups (ECoG or no ECoG), prior to surgical resection. The 'no ECoG' arm underwent gross total lesion resection (GTR) without ECoG guidance and the ECoG arm underwent GTR with ECoG guidance and further additional tailored resections, as necessary. Factors evaluated were tumor location, size, lateralization, seizure duration, preoperative antiepileptic drug therapy, pre- and postresection ECoG patterns and tumor histology. Postoperative Engel score and adverse event rates were compared in the pediatric and adult groups of both arms. Eloquent cortex lesions and re-explorations were excluded to avoid confounders., Results: Forty-two patients were included in the study of which 17 patients were in the pediatric cohort (age < 18 years) and 25 in the adult cohort. The mean age in the pediatric group was 11.11 years (SD 4.72) and in the adult group was 29.56 years (SD 9.29). The mean duration of epilepsy was 9.7 years (SD 4.8) in the pediatric group and 10.96 (SD 8.8) in the adult group. The ECoG arm of LEAT resections had 23 patients (9 children and 14 adults) and the non-ECoG arm had 19 patients (8 children and 11 adults). Three children and 3 adults from the ECoG group further underwent ECoG-guided tailored resections (average 1.33 additional tailored resections/per patient.).The histology of the tailored resection specimen was unremarkable in 3/6 (50%).Overall, the commonest histology in both groups was ganglioglioma and the temporal lobe, the commonest site of the lesion. 88.23% of pediatric cases (n = 15/17) had an excellent outcome (Engel Ia) following resection, compared to 84% of adult cases (n = 21/25) at a mean duration of follow-up of 25.76 months in children and 26.72 months in adults (p = 0.405).There was no significant difference in seizure outcomes between the ECoG and no ECoG groups both in children and adults, respectively (p > 0.05). Additional tailored resection did not offer any seizure outcome benefit when compared to the non-tailored resections., Conclusions: The use of intraoperative electrocorticography in LEATs did not contribute to postoperative seizure outcome benefit in children and adults. No additional advantage or utility was offered by ECoG in children when compared to its use in adults. ECoG-guided additional tailored resections did not offer any additional seizure outcome benefit both in children and adults., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: KCTD7-related progressive myoclonic epilepsy (PME) is a rare autosomal-recessive disorder. This study aimed to describe the clinical details and genetic variants in a large international cohort., Methods: Families with molecularly confirmed diagnoses of KCTD7-related PME were identified through international collaboration. Furthermore, a systematic review was done to identify previously reported cases. Salient demographic, epilepsy, treatment, genetic testing, electroencephalographic (EEG), and imaging-related variables were collected and summarized., Results: Forty-two patients (36 families) were included. The median age at first seizure was 14 months (interquartile range = 11.75-22.5). Myoclonic seizures were frequently the first seizure type noted (n = 18, 43.9%). EEG and brain magnetic resonance imaging findings were variable. Many patients exhibited delayed development with subsequent progressive regression (n = 16, 38.1%). Twenty-one cases with genetic testing available (55%) had previously reported variants in KCTD7, and 17 cases (45%) had novel variants in KCTD7 gene. Six patients died in the cohort (age range = 1.5-21 years). The systematic review identified 23 eligible studies and further identified 59 previously reported cases of KCTD7-related disorders from the literature. The phenotype for the majority of the reported cases was consistent with a PME (n = 52, 88%). Other reported phenotypes in the literature included opsoclonus myoclonus ataxia syndrome (n = 2), myoclonus dystonia (n = 2), and neuronal ceroid lipofuscinosis (n = 3). Eight published cases died over time (14%, age range = 3-18 years)., Significance: This study cohort and systematic review consolidated the phenotypic spectrum and natural history of KCTD7-related disorders. Early onset drug-resistant epilepsy, relentless neuroregression, and severe neurological sequalae were common. Better understanding of the natural history may help future clinical trials., (© 2024 International League Against Epilepsy.)

Purpose: Drug-resistant epilepsy is seen in patients with inborn errors of metabolism and metabolic dysfunction in neurons is crucial to brain disorders associated with psychomotor impairment. Diagnostic rates of metabolic causes of developmental and epileptic encephalopathy (DEE) using next generation sequencing have been rarely studied in literature., Methods: A prospective hospital study was carried out in 384 children with DEE, who underwent genetic testing. Metabolic disorders were evaluated with biochemical blood/urine assays and when required CSF estimations performed., Results: A total of 154 pathogenic/likely pathogenic variants in 384 children were identified. Out of 384 children, 89 were clinically suspected to have probable or possible metabolic disorders. Pathogenic/likely pathogenic variants in metabolic genes were identified in 39 out of 89 (43.8 %) and promising VUS in 28 (31.4 %). These included variants for progressive myoclonus epilepsies (21; 53.8 %), DEE with focal/multifocal seizures (8; 20.5 %), generalized epilepsy (5;12.8 %), early myoclonic encephalopathy (2; 5.1 %), LGS (1; 2.6 %) and West syndrome (2; 5.1 %)., Conclusion: Our cohort demonstrates for the first time from the Indian subcontinent that identification of metabolic variants can guide investigations and has therapeutic implications in patients with variable DEE phenotypes. A high utility is noted with regard to diagnosis and prognostication, given the low yield of available biochemical tests, indicating cost-effectiveness of this approach., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2023 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: We aimed to compare the electroclinical correlates of truncating and missense variants of SCN1A variants in children with Dravet syndrome (DS) and to determine phenotypic features in relation to variants identified and seizure outcomes., Methods: A single center prospective study was carried out on a South Indian cohort. Patients below 18 years of age who met the clinical criteria for DS who had undergone genetic testing and completed a minimum of one year follow up were included. We compared the differences in clinical profile, seizure outcome, developmental characteristics and anti-seizure medication (ASM) responsiveness profiles between patients with missense and truncating variants., Results: Out of a total of 3967 children with drug-resistant epilepsy during the period 2015-2021, 49 patients who fulfilled the inclusion criteria were studied. Thirty-seven had positive genetic tests, out of which 29 were SCN1A variants and 9 were other novel variants. The proportion of missense (14; 48.3%) and truncating SCN1A variants (15; 51.7%) was similar. A significant trend for developing multiple seizure types was noted among children with truncating variants (p = 0.035) and seizure freedom was more likely among children with missense variants (p = 0.042). All patients with truncating variants had ASM resistant epilepsy (p = 0.020). Developmental outcomes did not differ between the variant subtypes., Conclusion: Our results show that children harbouring missense variants demonstrated a significantly lower propensity for multiple seizure subtypes and a higher proportion with seizure freedom. However developmental implications appear to be independent of variant subtype., Competing Interests: Declaration of competing interest Nil., (Copyright © 2024 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Introduction It is important to establish criteria to define vascular cognitive impairment (VCI) in India as VCI is an image-based diagnosis and magnetic resonance imaging (MRI) changes resulting from age with prevalent vascular risk factors may confound MRI interpretation. The objective of this study was to establish normative community data for MRI volumetry including white matter hyperintensity volume (WMHV), correlated with age-stratified cognitive scores and vascular risk factors (VRFs), in adults aged 40 years and above.  Methods We screened 2651 individuals without known neurological morbidity, living in Mumbai and nearby rural areas, using validated Marathi translations of Kolkata Cognitive Battery (KCB) and geriatric depression score (GDS). We stratified 1961 persons with GDS ≤9 by age and cognitive score, and randomly selected 10% from each subgroup for MRI brain volumetry. Crude volumes were standardized to reflect percentage of intracranial volume.  Results MRI volumetry studies were done in 199 individuals (F/M = 90/109; 73 with body mass index (BMI) ≥25; 44 hypertensives; 29 diabetics; mean cognitive score 76.3). Both grey and white matter volumes decreased with increasing age. WMHV increased with age and hypertension. Grey matter volume (GMV) decreased with increasing WMHV. Positive predictors of cognition included standardized hippocampal volume (HCV), urban living, education, and BMI, while WMHV and age were negative predictors. Urban dwellers had higher cognitive scores than rural, and, paradoxically, smaller HCV.  Conclusion In this study of MRI volumetry correlated with age, cognitive scores and VRFs, increasing age and WMHV predicted lower cognitive scores, whereas urban living and hippocampal volume predicted higher scores. Age and WMHV also correlated with decreasing GMV. Further study is warranted into sociodemographic and biological factors that mutually influence cognition and brain volumes, including nutritional and endocrine factors, especially at lower cognitive score bands. In this study, at the lower KCB score bins, the lack of laboratory data pertaining to nutritional and endocrine deficiencies is a drawback that reflects the logistical limitations of screening large populations at the community level. Our volumetric data which is age and cognition stratified, and takes into account the vascular risk factors associated, nevertheless constitutes important baseline data for the Indian population. Our findings could possibly contribute to the formulation of baseline criteria for defining VCI in India and could help in early diagnosis and control of cognitive decline and its key risk factors., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Sundar et al.)

Chromosomal microarray is recommended as the first line of investigation in neurodevelopmental disorders (NDDs). However, advances in next-generation sequencing have unraveled more than 900 genes associated with NDDs, thus improving the genetic diagnosis. Therefore, this study was conducted to explore the utility of clinical exome sequencing (CES) in NDDs from a tertiary care centre in India. A retrospective observational analysis of 78 children with NDDs for whom CES was performed between 2017 and 2021 was conducted. The American College of Medical Genetics and Genomics (ACMG) criteria were used to classify the variants. The mean age was 5.8 ± 3.6 y, and 42 (53%) were male. Pathogenic, likely pathogenic, and variants of uncertain significance (VUS) were observed in 22 (28.2%), 10 (12.8%), and 26 (33.3%) patients, respectively, which included five copy number variants. The diagnostic yield for pathogenic and likely pathogenic variants in NDDs by CES was 41%, which was reasonably high., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Arginase deficiency, which leads to hyperargininaemia is a rare urea cycle disorder caused by a mutation in the ARG1 gene. It is an under-recognized cause of pediatric developmental epileptic encephalopathy, with the key coexistent clinical features being developmental delay or regression and spasticity. Detection of ARG1 gene mutation on genetic testing is the confirmatory diagnostic test. However, elevated levels of plasma arginine and low plasma arginase level can be considered as biochemical markers for diagnosis. We present two cases of arginase deficiency with genetically confirmed ARG1 mutation in one and biochemical confirmation in both. As the spectrum of epilepsy in arginase deficiency has been less explored, we attempted to elucidate the novel electroclinical features and syndromic presentations in these patients. Informed consent was obtained from families of patients. Electroclinical diagnosis was consistent with Lennox Gastaut syndrome (LGS) in the first patient while the second patient had refractory atonic seizures with electrophysiological features consistent with developmental and epileptic encephalopathy. Though primary hyperammonaemia is not a consistent feature, secondary hyperammonaemia in the setting of infectious triggers and drugs like valproate (valproate sensitivity) has been well described as also observed in our patient. In the absence of an overt antecedent in a child with spasticity and seizure disorder, with a progressive course consistent with a developmental epileptic encephalopathy, arginase deficiency merits consideration. Diagnosis often has important therapeutic implications with respect to dietary management and choice of the appropriate antiseizure medications., (© 2023 International League Against Epilepsy.)

In this study, we classify the seizure types using feature extraction and machine learning algorithms. Initially, we pre-processed the electroencephalogram (EEG) of focal non-specific seizure (FNSZ), generalized seizure (GNSZ), tonic-clonic seizure (TCSZ), complex partial seizure (CPSZ) and absence seizure (ABSZ). Further, 21 features from time (9) and frequency (12) domain were computed from the EEG signals of different seizure types. XGBoost classifier model was built for individual domain features and combination of time and frequency features and validated the results using 10-fold cross-validation. Our results revealed that the classifier model with combination of time and frequency features performed well followed by the time and frequency domain features. We obtained a highest multi-class accuracy of 79.72% for the classification of five types of seizure while using all the 21 features. The band power between 11-13 Hz was found to be the top feature in our study. The proposed study can be used for the seizure type classification in clinical applications.

We present a deep network-based model of the associative memory functions of the hippocampus. The proposed network architecture has two key modules: (1) an autoencoder module which represents the forward and backward projections of the cortico-hippocampal projections and (2) a module that computes familiarity of the stimulus and implements hill-climbing over the familiarity which represents the dynamics of the loops within the hippocampus. The proposed network is used in two simulation studies. In the first part of the study, the network is used to simulate image pattern completion by autoassociation under normal conditions. In the second part of the study, the proposed network is extended to a heteroassociative memory and is used to simulate picture naming task in normal and Alzheimer's disease (AD) conditions. The network is trained on pictures and names of digits from 0 to 9. The encoder layer of the network is partly damaged to simulate AD conditions. As in case of AD patients, under moderate damage condition, the network recalls superordinate words ("odd" instead of "nine"). Under severe damage conditions, the network shows a null response ("I don't know"). Neurobiological plausibility of the model is extensively discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kanagamani, Chakravarthy, Ravindran and Menon.)

Epilepsy is a neurological disorder characterized by recurrent seizures. Automated prediction of epileptic seizures is essential in monitoring the health of an epileptic individual to avoid cognitive problems, accidental injuries, and even fatality. In this study, scalp electroencephalogram (EEG) recordings of epileptic individuals were used to predict seizures using a configurable Extreme Gradient Boosting (XGBoost) machine learning algorithm. Initially, the EEG data was preprocessed using a standard pipeline. We investigated 36 minutes before the onset of the seizure to classify between the pre-ictal and inter-ictal states. Further, temporal and frequency domain features were extracted from the different intervals of the pre-ictal and inter-ictal periods. Then, the XGBoost classification model was utilized to optimize the best interval for the pre-ictal state to predict the seizure by applying Leave one patient out cross-validation. Our results suggest that the proposed model could predict seizures 10.17 minutes before the onset. The highest classification accuracy achieved was 83.33 %. Thus, the suggested framework can be optimized further to select the best features and prediction interval for more accurate seizure forecasting.

A 14-year-old girl presented with subacute onset headache, fever, and vomiting and was managed initially with antibiotics for suspected bacterial meningitis. Her symptoms further evolved over the next few weeks with systemic signs and symptoms favoring chronic meningitis with raised intracranial pressure. After the etiologic workup was unrevealing, she was started on empirical antituberculous therapy. After a period of partial improvement, symptoms recurred with a new-onset focal seizure. Her imaging findings evolved from features suggestive of focal leptomeningitis to multifocal heterogeneous enhancing cortical and subcortical lesions with hemorrhagic foci, leading to brain biopsy that confirmed diagnosis. Our case highlights the utility of diagnostic biopsy in patients with "chronic meningitis" in uncertain cases rather than confining the approach to the law of parsimony. The decision to initiate empirical therapy in chronic meningitis should be considered on a case-by-case basis and take into account factors, such as clinical examination findings, immune status, recent exposures, and potential risks of treatment. Atypical MRI features should lower the threshold for meningocortical biopsy when indicated., (© 2023 American Academy of Neurology.)

Purpose: Telemedicine gained popularity in the setting of the COVID-19 pandemic. We aimed to study the satisfaction levels of persons with epilepsy (PWE) with online video consultation (OVC) and physical consultation (PC)., Methods: This was a cross-sectional questionnaire-based study conducted in a tertiary referral care center for epilepsy in India. All PWE who had availed of both OVC and PC were included. Those who did not give consent to a questionnaire were excluded. A questionnaire was given to assess patients' satisfaction regarding OVC and PC. Scores for each question for both OVC and PC were compared., Results: One hundred and forty-one patients who had PC earlier and later availed of OVC from December 2020 to July 2021 formed the cohort. Seventy one patients who responded to the questionnaire were included. 49% and 51% of the patients belonged to urban and rural regions respectively. 8.5% of the patients were off anti-seizure medications (ASM), while 5.6% and 85.9% were on single and multiple ASMs respectively. There were no differences between PC and OVC regarding ease of getting the appointment, privacy during a consultation, patients' perceived chances of missing consultations, and overall comfort and experience on either type of consultation. Physical consultation scored more than OVC in patients' satisfaction with the time doctor spent with them, an opportunity to communicate their queries well, clarifications received from the doctor, and the likelihood of patients recommending the particular type of consultation to others(p < 0.05)., Conclusions: Online video consultation can be a satisfactory alternative to PC and can improve patient satisfaction if some of the issues in OVC are addressed properly., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Multivoxel pattern analysis (MVPA) has emerged as a powerful unbiased approach for generating seed regions of interest (ROIs) in resting-state functional connectivity (RSFC) analysis in a data-driven manner. Studies exploring RSFC in multiple sclerosis have produced diverse and often incongruent results. Objectives: The aim of the present study was to investigate RSFC differences between people with relapsing-remitting multiple sclerosis (RRMS) and healthy controls (HC). Methods: We performed a whole-brain connectome-wide MVPA in 50 RRMS patients with expanded disability status scale ≤4 and 50 age and gender-matched HCs. Results: Significant group differences were noted in RSFC in three clusters distributed in the following regions: anterior cingulate gyrus, right middle frontal gyrus, and frontal medial cortex. Whole-brain seed-to-voxel RSFC characterization of these clusters as seed ROIs revealed network-specific abnormalities, specifically in the anterior cingulate cortex and the default mode network. Conclusions: The network-wide RSFC abnormalities we report agree with the previous findings in RRMS, the cognitive and clinical implications of which are discussed herein. Impact statement This study investigated resting-state functional connectivity (RSFC) in relapsing-remitting multiple sclerosis (RRMS) people with mild disability (expanded disability status scale ≤4). Whole-brain connectome-wide multivoxel pattern analysis was used for assessing RSFC. Compared with healthy controls, we were able to identify three regions of interest for significant differences in connectivity patterns, which were then extracted as a mask for whole-brain seed-to-voxel analysis. A reduced connectivity was noted in the RRMS group, particularly in the anterior cingulate cortex and the default mode network regions, providing insights into the RSFC abnormalities in RRMS.

Introduction: The study aimed to explore longitudinal cognitive outcomes and to ascertain predictors of conversion to dementia in a hospital-based mild cognitive impairment (MCI) cohort classified according to the neuropsychological phenotype at baseline., Materials and Methods: Subjects aged &gt;55 years who had a clinical diagnosis of MCI at initial visit between 2010 and 2018, with at least one formal neuropsychological assessment at baseline and follow-up of a minimum of 2 years were included. The prospective study was completed based on evaluation at last follow-up to gauge conversion to dementia, quantification of performance on activities of daily living and when available, longitudinal neuropsychological test scores., Results: Ninety-five patients with MCI met the inclusion criteria with a mean age of 68.4 ± 6.4 years at baseline and a mean duration of follow-up for 6.4 ± 3.2 years. The cumulative conversion rate to dementia was 22.2% (21/95) and the annualized conversion rate was 3.3% per year of follow-up. The majority of subjects who had converted had multidomain MCI (66%). Only white matter changes on MRI brain revealed correlation with baseline neuropsychology tests. The multivariate logistic regression analysis revealed the utility of lower baseline list recognition (adjusted odds ratio: 0.735 [95% confidence interval: 0.589-0.916]; p 0.006), lower immediate logical memory (0.885 [0.790-0.990]; p 0.03), and high perseverative error scores on set shifting (3.116 [1.425-6.817]; p 0.004) as predictors of conversion. A model score of +2.615 could predict conversion with sensitivity of 72% and specificity of 98% over 6.4 years follow-up., Conclusion: There was a higher risk of conversion associated with multidomain MCI. Logistic regression-based estimations of dementia risk utilizing domain-based neuropsychology test scores in MCI have high specificity for diagnosis at baseline., (© 2023 S. Karger AG, Basel.)

Objective: To explore novel word learning via fast mapping (FM) and explicit encoding (EE) in temporal lobe epilepsy (TLE)., Methods: 16 right and 16 left temporal lobe epilepsy (RTLE and LTLE) patients along with 32 normal controls (NC) underwent learning of 24 novel object name pairs through standard FM and EE techniques. Their learning was assessed via a three-choice alternate delayed recognition task on the day of learning and on the following day. Recognition scores were compared using nonparametric statistics across the groups with P value set at <.05., Results: RTLE and NC performed similarly, while LTLE and NC differed significantly in novel word learning irrespective of the method of encoding. LTLE and RTLE differed in EE-based novel word learning alone. Further, with respect to encoding techniques, all groups performed better on EE compared to FM. The novel word associations learned via FM showed a lesser decline compared to EE following overnight integration in RTLE and NC., Conclusion: Novel word learning via FM did not facilitate learning above EE in TLE patients or NC. But FM-based words could better overcome forgetting following overnight integration in RTLE and NC. Hence, it is possible that FM has the potential to improve retention of novel information following overnight integration in RTLE as in NC. However, its efficacy in improving retention in LTLE needs further evidence., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Annals of Indian Academy of Neurology.)

Robotic right live donor hepatectomy (r-LDRH) has been reported with reduced morbidity compared to open donor right hepatectomy (o-LDRH) in few recent series. Nevertheless, its routine use is debated. We present a large series comparing pure r-LDRH with o-LDRH. Consecutive r-LDRH performed from June 2018 to June 2020 (n = 102) were compared with consecutive donors undergoing o-LDRH (n = 152) from February 2016 to February 2018, a period when r-LDRH was not available at this center. Propensity score matched (PSM) analysis of 89 case-control pairs was additionally performed. Primary endpoints were length of high dependency unit (HDU) and hospital stay and Clavien-Dindo graded complications among donors. Although r-LDRH took longer to perform (540 vs. 462 min, P < .001), the postoperative peak transaminases levels (P < .001), the length of HDU (3 vs. 4 days, P < .001), and hospital stay (8 vs. 9 days, P < .001) were lower in in donors undergoing r-LDRH. Clavien-Dindo graded complications were similar (16.67% in r-LDRH and 13.16% in o-LDRH). The rates of early allograft dysfunction (1.6% vs. 3.3%), bile leak (14.7% vs. 10.7%), and 1-year mortality (13.7% vs. 11.8%) were comparable between r-LDRH and o-LDRH recipients. PSM analysis yielded similar results between the groups. These data support the safety and feasibility of r-LDRH in select donors., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Competing Interests: There are no conflicts of interest.

SHANK- associated RH domain-interacting protein (SHARPIN) is a multifunctional protein associated with numerous physiological functions and many diseases. The primary role of the protein as a LUBAC-dependent component in regulating the activation of the transcription factor NF-κB accounts to its role in inflammation and antiapoptosis. Hence, an alteration of SHARPIN expression or genetic mutations or polymorphisms leads to the alteration of the above-mentioned primary physiological functions contributing to inflammation-associated diseases and cancer, respectively. However, there are complications of targeting SHARPIN as a therapeutic approach, which arises from the wide-range of LUBAC-independent functions and yet unknown roles of SHARPIN including neuronal functions. The identification of SHARPIN as a postsynaptic protein and the emerging studies indicating its role in several neurodegenerative diseases including Alzheimer's disease suggests a strong role of SHARPIN in neuronal functioning. This review summarizes the functional roles of SHARPIN in normal physiology and disease pathogenesis and strongly suggests a need for concentrating more studies on identifying the unknown neuronal functions of SHARPIN and hence its role in neurodegenerative diseases., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Purpose: To study if one can conceptualize the scalp ictal onset pattern through analysis of interictal spike domain analysis in temporal lobe epilepsy (TLE)., Methods: Seventy-four patients with unilateral mesial temporal sclerosis (MTS) were categorized into "type A" interictal epileptiform discharges (IEDs) with negativity over infero-lateral scalp electrodes over temporal region and contralateral central region showing positivity; all IEDs other than type A were categorized as type B. The ictal electrographic patterns was termed "focal" when confined to side of MTS, was "regional" when lateralized to the ipsilateral hemisphere; "diffuse" if nonlateralized/localized; and ictal onset contralateral to MTS termed as "discordant.", Results: A total of 377 seizures and 5,476 spikes were studied. These were divided into four types: (1) type A IEDs ipsilateral to MTS (44 patients), (2) type A IEDs bitemporally (16 patients), (3) type A IEDs contralaterally (7 patients) and type B IEDs ipsilaterally, and (4) bilateral type B IEDs (7 patients). The ictal pattern was either focal or regional in 51 of 60 patients (85%) with type A IEDs; it was "diffuse" in 9 patients (15%). Diffuse ictal onset was seen in 12 of 14 (86%) with either ipsilateral/bitemporal type B IEDs. Ictal onset on the opposite hemisphere was noted in 2 (14%)., Conclusions: Type A IEDs signify a focal ictal onset and type B IEDs suggest a diffuse ictal onset in patients with MTS on one side., Significance: Interictal spike domain analysis helps predicting ictal patterns in temporal lobe epilepsy., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 by the American Clinical Neurophysiology Society.)

Objective: 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) is widely used in presurgical assessment in patients with drug-resistant focal epilepsy (DRE) if magnetic resonance imaging (MRI) and scalp electroencephalography (EEG) do not localize the seizure onset zone or are discordant., Methods: In this multicenter, retrospective observational cohort study, we included consecutive patients with DRE who had undergone FDG-PET as part of their presurgical workup. We assessed the utility of FDG-PET, which was defined as contributing to the decision-making process to refer for resection or intracranial EEG (iEEG) or to conclude surgery was not feasible., Results: We included 951 patients in this study; 479 had temporal lobe epilepsy (TLE), 219 extratemporal epilepsy (ETLE), and 253 epilepsy of uncertain lobar origin. FDG-PET showed a distinct hypometabolism in 62% and was concordant with ictal EEG in 74% in TLE and in 56% in ETLE (p < .001). FDG-PET was useful in presurgical decision-making in 396 patients (47%) and most beneficial in TLE compared to ETLE (58% vs. 44%, p = .001). Overall, FDG-PET contributed to recommending resection in 78 cases (20%) and iEEG in 187 cases (47%); in 131 patients (33%), FDG-PET resulted in a conclusion that resection was not feasible. In TLE, seizure-freedom 1 year after surgery did not differ significantly (p = .48) between patients with negative MRI and EEG-PET concordance (n = 30, 65%) and those with positive MRI and concordant EEG (n = 46, 68%). In ETLE, half of patients with negative MRI and EEG-PET concordance and three quarters with positive MRI and concordant EEG were seizure-free postsurgery (n = 5 vs. n = 6, p = .28)., Significance: This is the largest reported cohort of patients with DRE who received presurgical FDG-PET, showing that FDG-PET is a useful diagnostic tool. MRI-negative and MRI-positive cases with concordant FDG-PET results (with either EEG or MRI) had a comparable outcome after surgery. These findings confirm the significance of FDG-PET in presurgical epilepsy diagnostics., (© 2022 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: Cognitive decline is a non-hemorrhagic, major complication of intracranial dural arteriovenous fistula (DAVF), thought to be primarily related to venous hypertension. However, imaging features to predict cognitive decline are scanty in the literature., Purpose: To evaluate functional connectivity (FC) changes of resting-state networks (RSNs) in DAVF before and after treatment and its relation to cognitive impairment., Study Type: Prospective., Subjects: DAVF subjects were screened for inclusion. Pre-embolization (N = 33, mean age 45.9 years, 29 males), 1 month post-embolization (N = 20, mean age 42.7 years, 19 males), and healthy controls (HC, N = 33, mean age 45.09 years, 27 males)., Field Strength/sequence: 3.0 T, resting-state functional magnetic resonance imaging (MRI), three-dimensional (3D) T1, T 2 fast spin echo (FSE), diffusion weighted imaging (DWI), susceptibility weighted imaging (SWI), fluid-attenuated inversion recovery, and time of flight., Assessment: Data quality assessment was performed. FC analysis was done using group independent component analysis (ICA) and seed to voxel analysis. Neuropsychology (NP) scores of patients were compared with HC and correlated with FC changes., Statistical Tests: Voxel-wise parametric T-statistics for F-test was executed in FC analysis (p-FDR corrected <0.05). NP scores between DAVF group and HC group were compared using one-way analysis of variance with post hoc Bonferroni correction (P < 0.05)., Results: Both RSNs analysis methods showed reduced FC at the precuneus-posterior cingulate cortex (PC-PCC) of default mode network (DMN), anterior cingulate cortex (ACC) of the salience network (SN), and possible compensatory increased connectivity at the frontoparietal (FPN) and dorsal attention (DAN) networks. DAVF with low NP scores showed reduced FC at DMN and SN and minimal to absent connectivity at FPN and DAN. At post-embolization 1-month follow-up, improvement in FC at PC-PCC of DMN and ACC of SN were noted., Data Conclusion: RS-fMRI in DAVF displayed FC changes that may be related to cognitive decline and its subsequent reversibility after treatment. FC changes at DMN, SN, FPN, and DAN were linked to cognitive decline and the corresponding NP scores., Level of Evidence: 2 TECHNICAL EFFICACY: Stage 2., (© 2021 International Society for Magnetic Resonance in Medicine.)

Background: Prediction of outcome of West syndrome (WS) in relation to etiology and electrophysiology remain pertinent challenges., Objective: This study aimed to compare electro-clinical and imaging characteristics between WS of "unknown-etiology"; "symptomatic"WS; to gauge the evolution and impact of electroencephalographic (EEG) patterns on seizure outcomes., Materials and Methods: Electro-clinico-radiological data of 76 children with WS who were followed up for atleast 1 year was collected for reviewing clinical, therapeutic and EEG profiles (sub-typed as typical and modified hypsarrhythmia [HA]). Quantified seizure scores were assessed., Results: Among 76 children included in this retrospective analysis, 31 (40.8%) were of unknown-etiology and 45 (59.2%) were "symptomatic" (structural cause/developmental-encephalopathy). Children with symptomatic WS (p = 0.037), specifically with gliosis on imaging (p = 0.05) and typical HA (including the multifocal subtype; P = 0.023) were more likely to have other seizure types before onset of spasms and exhibit prior delay or regression in milestones (p = 0.017). There was negative correlation between time to diagnosis and reduction in seizure scores (r = -0.32; p = 0.005).Significant reduction was noted in seizure scores with pharmacotherapy, irrespective of etiology (P < 0.001 in unknown-etiology and symptomatic subgroups). Seizure freedom rates did not differ between typical and modified HA groups (p = 0.215) with a higher proportion of children with meaningful reduction in seizure scores in the former sub-group (p = 0.030). Children who failed to achieve seizure remission were more likely to exhibit developmental impairment (p = 0.019)., Conclusions: Early diagnosis and initiation of optimal therapy is crucial towards improving outcome, irrespective of etiology (which impacts pre-spasm development) and HA subtypes., Competing Interests: None

Open reading frame variants which lack stop codons such as C12orf57 variants are known to cause Temtamy syndrome, an extremely rare disorder characterized by intellectual disability, seizures, facial dysmorphism and agenesis of corpus callosum. C12orf57 was initially reported to be required for human corpus callosum development. We report the first child who is of Indian origin with developmental and epileptic encephalopathy (DEE) with a unique phenotypic evolution as focal onset reflex seizures. We performed whole exome sequencing of genomic DNA isolated from peripheral blood samples of proband and his parents. Two pathogenic compound heterozygous variants, a start loss variant (Chr12:7053285:c.1A>G) and a premature stop gain variant (Chr12:7053327:c.43C>T), involving the C12orf57 gene were identified in the proband. Our case report which details genotyping in this rare syndromic developmental encephalopathy, with no prior cases reported from India, expands the ethnic spectrum of patients.

Background: Although minimally invasive right donor hepatectomy (RDH) has been reported, this innovation is yet to be widely accepted by transplant community. Bleeding during transection, division of right hepatic duct (RHD), suturing of donor duct as well as retrieval with minimal warm ischemia are the primary concerns of most donor surgeons. We describe our simplified technique of robotic RDH evolved over 144 cases., Patients and Methods: Right lobe mobilization is performed in a clockwise manner from right triangular ligament over inferior vena cavae up to hepatocaval ligament. Transection is initiated using a combination of bipolar diathermy and monopolar shears controlled by console surgeon working in tandem with lap CUSA operated by assistant surgeon. With the guidance of indocyanine green cholangiography, RHD is divided with robotic endowrist scissors (Potts), and remnant duct is sutured with 6-0 PDS. Final posterior liver transection is completed caudocranial without hanging manoeuvre. Right lobe with intact vascular pedicle is placed in a bag, vascular structures then divided, and retrieved through Pfannenstiel incision., Conclusion: Our technique may be easy to adapt with the available robotic instruments. Further innovation of robotic platform with liver friendly devices could make robotic RDH the standard of care in future., Competing Interests: None

Background: In adult right lobe living donor liver transplantation (LDLT), venous drainage of the anterior sector is usually reconstructed on the bench to form a neo-middle hepatic vein (MHV). Reconstruction of the MHV for drainage of the anterior sector is crucial for optimal graft function. The conduits used for reconstruction include cryopreserved allografts, synthetic grafts, or the recipient portal vein. However, the ideal choice remains a matter of debate. This study compares the efficacy of the native recipient portal vein (RPV) with PTFE grafts for reconstruction of the neo-MHV., Methods: Patients in this equivalence-controlled, parallel-group trial were randomized to either RPV (62 patients) or PTFE (60 patients) for use in the reconstruction of the neo-MHV. Primary endpoint was neo-MHV patency at 14 days and 90 days. Secondary outcomes included 90-day mortality and post-transplant parameters as scored by predefined scoring systems., Results: There was no statistically significant difference in the incidence of neo-MHV thrombosis at 14 days (RPV 6.5 per cent versus PTFE 10 per cent; P = 0.701) and 90 days (RPV 14.5 per cent versus PTFE 18.3 per cent; P = 0.745) between the two groups. Irrespective of the type of graft used for reconstruction, 90-day all-cause and sepsis-specific mortality was significantly higher among patients who developed neo-MHV thrombosis. Neo-MHV thrombosis and sepsis were identified as risk factors for mortality on Cox proportional hazards analysis. No harms or unintended side effects were observed in either group., Conclusion: In adult LDLT using modified right lobe graft, use of either PTFE or RPV for neo-MHV reconstruction resulted in similar early patency rates. Irrespective of the type of conduit used for reconstruction, neo-MHV thrombosis is a significant risk factor for mortality., Registration Number: CTRI/2018/11/016315 (www.ctri.nic.in)., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Sporadic nonlesional intractable visual-sensitive epilepsies of childhood represent a challenging subset of epilepsies in terms of management and prognostication given a propensity to evolve as epileptic encephalopathy., Objective: To study the genetic heterogeneity of drug-resistant visual sensitive epilepsy of childhood., Methods: A retrospective chart review was conducted on patients in the pediatric age group between 2016 and 2018, with drug-resistant epilepsy (DRE) and video electro encephalography (VEEG) documented reflex photosensitivity, eye-condition sensitivity. Those patients who underwent genetic testing with targeted next-generation sequencing using an epilepsy gene panel were selected., Results: During the study period, out of 96 patients who underwent genetic testing, 4 patients (4.17%) with sporadic DRE presented with clinical phenotypes ranging from myoclonic-atonic epilepsy, generalized epilepsy with eyelid myoclonia as well as febrile and unprovoked seizures, along with visual sensitivity. Video EEG documented abnormalities ranged from occipital, posterior-cortex and generalized discharges with "eyes-closed state" triggered, self-induced "smart-phone" triggered, photosensitive focal-onset and generalized myoclonic seizures. Accompanying developmental impairment was noted. These patients who were investigated with clinical exome sequencing were detected to have mutations in not only SCN1A genes (pathogenic exonic and intronic variants) but also CHD2 (pathogenic) and CACNA1H genes (a familial febrile-seizure susceptibility variant of unknown significance)., Conclusions: The series highlights the complex genetics of drug-resistant visual-sensitive epilepsy of childhood. Such genotype-phenotype associations throw light on the role of ion-channel and non-ion channel genes on reflex epileptogenesis in this group of patients., Competing Interests: None

Objectives: The growing prevalence of dementia, especially in low- and middle-income countries (LMICs), has raised the need for a unified cognitive screening tool that can aid its early detection. The linguistically and educationally diverse population in India contributes to challenges in diagnosis. The present study aimed to assess the validity and diagnostic accuracy of the Indian Council of Medical Research-Neurocognitive Toolbox (ICMR-NCTB), a comprehensive neuropsychological test battery adapted in five languages, for the diagnosis of dementia. Methods: A multidisciplinary group of experts developed the ICMR-NCTB based on reviewing the existing tools and incorporation of culturally appropriate modifications. The finalized tests of the major cognitive domains of attention, executive functions, memory, language, and visuospatial skills were then adapted and translated into five Indian languages: Hindi, Bengali, Telugu, Kannada, and Malayalam. Three hundred fifty-four participants were recruited, including 222 controls and 132 dementia patients. The sensitivity and specificity of the adapted tests were established for the diagnosis of dementia. Results: A significant difference in the mean (median) performance scores between healthy controls and patients with dementia was observed on all tests of ICMR-NCTB. The area under the curve for majority of the tests included in the ICMR-NCTB ranged from 0.73 to 1.00, and the sensitivity and specificity of the ICMR-NCTB tests ranged from 70 to 100% and 70.7 to 100%, respectively, to identify dementia across all five languages. Conclusions: The ICMR-NCTB is a valid instrument to diagnose dementia across five Indian languages, with good diagnostic accuracy. The toolbox was effective in overcoming the challenge of linguistic diversity. The study has wide implications to address the problem of a high disease burden and low diagnostic rate of dementia in LMICs like India., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Verma, Tripathi, Nehra, Paplikar, Varghese, Alladi, Narayanan, Dhaliwal, Sharma, Saroja, Arshad, Divyaraj, Ghosh, Manae, Mekala, Menon, Hooda, Iyer, Sunitha, Kandukuri, Kaul, Khan, Mathew, Nandi, Padma, Pauranik, Ramakrishnan, Sarath, Shah, Sylaja, Varma and Vishwanath.)

Purpose: The functional changes concerning memory deficits in dural arteriovenous fistula (dAVF) brain are inadequately understood. This study aimed to understand the functional connectivity alterations of brain regions widely affirmed for explicit and implicit memory functions in dAVF patients (DP) and look into the frequency effects of the altered functional networks., Methods: Resting-state functional magnetic resonance imaging (rsfMRI) analysis was done in the memory-associated regions of 30 DP and 30 healthy controls (HC). Frequency decomposition was used to determine potential frequency-dependent functional connectivity changes. They underwent neuropsychological tests and were correlated with changes in memory networks compared with HC., Results: The results showed weaker functional connectivity among the medial temporal lobe and sub-regions in DP suggestive of dysfunction of explicit and implicit memory functions, which corroborated with the positive correlation between memory scores and hippocampal-parahippocampal connectivity of DP, along with a significant group difference of lower memory and cognitive performance in DP assessed by neuropsychological tests. A frequency-dependent study of the altered rsFC revealed lower functional connectivity strength and impaired neural coupling manifested at some sub-band frequencies indicative of disturbed cortical rhythm in DP., Conclusion: This pilot study gives insights into significant intrinsic functional connectivity changes in the memory regions of the dAVF brain. The results may have clinical implications in the choice of interventional management of dAVF and can impact clinical decision making for realizable prevention of progressive memory impairment and irreversible brain damage in such patients., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Locus of control (LOC) is the degree to which people believe that they have control over the outcome of events in their lives. A person's locus can be internal, external, or chance. A person with internal locus of control believes that one can control one's own life. A person with external locus of control believes that his life is controlled by external factors or people over which he has no influence. A person with chance locus of control believes that fate, chance, or luck controls his own life. The aim of the current study was to determine the health locus of control, anxiety, and depression levels in persons with epilepsy (PWE) and to assess whether locus of control has relation to anxiety, depression, and seizure control., Methods: Patients aged 18 years or older with a history of epilepsy for at least 1 year were recruited from the outpatient epilepsy clinic or from the inpatient epilepsy monitoring unit at SCTIMST, Trivandrum from January 2019 to May 2020. Patients filled the questionnaire form consisting of demographic data, age of onset of seizures, present seizure control, and the current antiepileptic drugs. The Hospital Anxiety and Depression (HAD) scale was used to estimate the level of anxiety and depression in these patients. The Form-C of the Multidimensional Health Locus of Control (MHLC) scale was used to evaluate the health locus of control. Healthy controls aged 18 years or older and free of any chronic disease or psychiatric illness were also recruited. They were asked to fill the questionnaire forms with basic demographic data. HAD scale was used to estimate the level of anxiety and depression and form-C of MHLC was used to evaluate the health locus of control in the healthy controls. The mean scores of anxiety, depression, and locus of control were compared between the two groups., Results: A total of 170 participants were recruited which consisted of 100 PWE and 70 healthy controls. The mean anxiety and depression scores were 8.13(SD = 4.23) and 5.85(SD = 3.66) in the PWE group and 6.75(SD = 3.39) and 4.14(SD = 2.96) in the control group, respectively. The mean internal, external, and chance LOC scores were 24.95(SD = 10.92), 26.94(SD = 4.96), and 24.41(SD = 6.46) in the PWE group; and 29.44(SD = 5.62), 26.53(SD = 5.79), and 19.9(SD = 7.13) in the control group, respectively. Persons with epilepsy had higher chance LOC scores and lower internal LOC scores compared to controls (p = 0.00003, p < 0.00001 respectively). There were no differences in the external LOC scores between the two groups (p = 0.620). Persons with epilepsy with some level of anxiety had lower internal LOC scores compared to patients with no anxiety (p = 0.04). PWE with poor seizure control had higher external LOC score and lower internal LOC scores which however did not reach statistical significance. Persons with epilepsy with poor seizure control had higher anxiety and depression scores., Conclusions: Persons with epilepsy had low perceptions of internal and strong perceptions of chance health locus of control. This means that PWE feel that luck plays an important role in their disease control. This information is important in the counseling of persons with epilepsy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: The objective of the study was to evaluate the frequency, clinical, and video-electroencephalographic (VEEG) predictors of convlusive status epilepticus (CSE) in the epilepsy-monitoring unit (EMU)., Methods: The data of all patients who had CSE in our EMU between 2008 and 2017 were reviewed. For each case, two age- and diagnosis-matched subjects who underwent VEEG and did not develop CSE were taken as internal controls. Electro-clinical data of both the groups were compared. Predictors of CSE were assessed using logistic regression analysis., Results: Out of 11,188 video-telemetries were conducted between 2008-17, forty-three events of CSE (0.38%) were recorded. On comparisons with 86 internal controls no differences were apparent on prevalence of cognitive impairment, structural lesion, number of baseline anti-seizure medications (ASM), ASM taper schedule, ictal patterns, and duration of VEEG monitoring. Inter-ictal rhythmic periodic patterns had significantly higher prevalence in cases (p = 0.028). Logistic regression analysis revealed that odds of CSE were higher with past history of SE [p = 0.008; adjusted odds ratio (OR) = 5.48 (confidence intervals {CI} 1.55-19.28)] and in presence of rhythmic spike and wave discharges [p = 0.016, OR = 33.518(CI = 1.93-581.4)]; the odds were lower if the first two seizures recorded did not evolve into CSE [p = 0.009, OR = 0.247 (CI = 0.08-0.70)] and if there was prior history of daily seizures [p = 0.02, OR = 0.250 (CI = 0.07-0.84)]., Conclusion: CSE is a rare yet important adverse event in EMU. Clinical predictors are more relevant in comparison to EEG variables. Extent of ASM withdrawal may not directly account for occurrence of CSE; factors inherent to a patient's epilepsy are deterministic., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Children with refractory focal to bilateral tonic-clonic seizures, despite normal high-resolution imaging, are often not subjected to genetic tests due to the costs involved and instead undergo multimodality presurgical evaluation targeted at delineating a focal onset. The objective of this study was to ascertain genotype-phenotype correlations in this group of patients., Method: An online hospital database search was conducted for children who presented in 2019 with drug-resistant epilepsy dominated by nonlateralizing focal-onset/rapid generalized (bilateral) tonic-clonic seizures (GTCS), subjected to presurgical evaluation and subsequent genetic testing due to absence of a clear focus hypothesis., Results: Phenotypic homogeneity was apparent in 3 children who had onset in infancy with drug-resistant GTCS (predominantly unprovoked and occasionally fever provoked) and subsequent delayed development. 3-Tesla magnetic resonance imaging (MRI) scans were negative and video EEG documented a homogeneous pattern of multifocal and/or generalized epileptiform discharges with phenomenology favoring probable focal-onset/generalized-onset bilateral tonic-clonic seizures. All 3 tested positive for SCN1A gene variants (heterozygous missense substitution variants in 2 children, one of which was novel and a novel duplication in one that led to frameshift and premature truncation of the protein), suggestive of SCN1A -mediated epilepsy. This electroclinical profile constituted 3 out of 25 patients with SCN1A -epilepsy phenotypes at our center., Conclusions: These cases suggest that children with early-onset drug-resistant "generalized" epilepsy are likely to have a genetic basis although the presentation may not be typical of Dravet syndrome. Hence, genetic testing for SCN1A variants is recommended in children with drug-resistant MRI negative focal-onset/generalized-onset bilateral tonic-clonic seizures before subjecting them to exhaustive presurgical workup and to guide appropriate treatment and prognostication.

Context: Cerebral blood flow (CBF) measurement using arterial spin labelling (ASL) MRI sequences has recently emerged as a prominent tool in dementia research., Aims: To establish association between quantified regional cerebral perfusion and gray matter (GM) volumes with cognitive measures in mild cognitive impairment (MCI) and early Alzheimer's Dementia (AD), using three dimensional fast spin echo pseudo-continuous ASL MRI sequences., Settings and Design: Hospital-based cross-sectional study., Methods and Material: Three age-matched groups, i.e., 21 cognitively normal healthy controls (HC), 20 MCI and 19 early AD patients diagnosed using neuropsychological tests and who consented for multimodality 3T MRI were recruited for the study., Statistical Analysis Used: Statistical parametric mapping and regions of interest (ROI) multivariate analysis of variance was used to ascertain differences between patients and controls on MRI-volumetry and ASL. Linear regression was used to assess relationship between CBF with GM atrophy and neuropsychological test measures., Results: Compared to HC, patients with MCI and AD had significantly lower quantified perfusion in posterior cingulate and lingual gyri, over hippocampus in MCI, with no differences noted between MCI and AD. Atrophy over the middle temporal gyrus and hippocampus differentiated AD from MCI. No significant positive correlations were noted between perfusion and GM volumes in ROI with the exception of temporal neocortex. Significantly positive coefficient b-value (p < 0.01) were apparent between global cognition with CBF in precuneus, temporal neocortex and precuneus volume, with negative b-values noted between medial temporal CBF for global cognition and recall scores., Conclusions: ROI-based CBF measurements differentiated MCI and AD from HC; volumetry of medial and neocortical temporal GM separates AD from MCI. Correlations between CBF and neuropsychology are variable and require further longitudinal studies to gauge its predictive utility on cognitive trajectory in MCI., Competing Interests: There are no conflicts of interest., (Copyright: © 2006 - 2021 Annals of Indian Academy of Neurology.)

Background: Corticosteroids are an integral part of immunosuppression following solid organ transplantation, despite their metabolic complications. We conducted a randomized trial to evaluate the efficacy of steroid-free immunosuppression following live donor liver transplantation (LDLT)., Methods: We randomized 104 patients stratified based on pre-transplant diabetic status to either a steroid-free arm (SF-arm) (Basiliximab + Tacrolimus and Azathioprine,n = 52) or Steroid arm (S-Arm) (Steroid + Tacrolimus + Azathioprine,n = 52). The primary endpoint was the occurrence of metabolic complications (new-onset diabetes after transplant (NODAT), new-onset systemic hypertension after transplant (NOSHT), post-transplant dyslipidemia) within 6 months after transplant. Secondary endpoints included biopsy-proven acute rejection (BPAR) within six months, patient and graft survival at 6 months., Results: The incidence NODAT was significantly higher in S-arm at 3 months (64.5%vs. 28.1%,p-0.004) and 6 months (51.6% vs. 15.6%,p-0.006). Likewise, the incidence of NOSHT (27.8% vs. 4.8%,p-0.01) and hypertriglyceridemia (26.7% vs. 8%,p-0.03) at six months was significantly higher in S-arm. However, there were no differences in BPAR (19.2% vs. 21.2%, p-0.81), time to first rejection (58 vs. 53 days, p-0.78), patient and graft survival (610 vs. 554 days,p- 0.22)., Conclusion: Following LDLT, basiliximab induction with tacrolimus and azathioprine maintenance resulted in significantly lower metabolic complications compared to the triple-drug regimen of steroid, tacrolimus, and azathioprine., (Copyright © 2020 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Subacute sclerosing panencephalitis (SSPE) is a lethal slow viral disease of the central nervous system caused by a defective measles virus. The onset is mostly in childhood, manifesting clinically as decline in academic performance, behavioural changes, motor dysfunction and myoclonus. Adult-onset SSPE is rare and can present as rapidly progressive dementia. We present a young man of Indian origin with adult-onset SSPE with rapidly progressive dementia but no localising neurological signs. The diagnostic clues were parieto-occipital white matter changes on MR brain scan and history of childhood fever with rash. High titres of antimeasles antibody in cerebrospinal fluid confirmed the diagnosis. The long latency from primary measles virus infection to symptom onset can be misleading in adults. SSPE should be considered in adults with dementia, especially in tropical countries where vaccination coverage is suboptimal., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Perioral myoclonia with absences (POMA) is not recognized as a unique electro-clinical syndrome and studies suggest its inclusion under the genetic generalized epilepsy (GGE) spectrum. The aim of this study was to explore the prevalence and electro-clinical homogeneity of this disorder in an epilepsy monitoring unit. Between 2013 and 2019, among drug-resistant epilepsy patients who were referred for video-telemetry, those diagnosed with POMA based on the presence of documented absences with prominently observed peri-oral muscular contractions accompanied by generalized EEG features were included. Among 62 patients who were diagnosed with absence epilepsy, five finally met the criteria for POMA (8.1%) with late childhood or adolescent onset of epilepsy. Four (80%) had a referral diagnosis of focal epilepsy based on historical focal features with exacerbation of seizures on oxcarbazepine. All five patients demonstrated brief absences with orbicularis oris muscle contractions accompanied by subtle focal phenomenology. One patient had concurrent axial-appendicular myoclonic jerks precipitated by hyperventilation. While four patients had strikingly identical interictal and ictal characteristics of typical absence epilepsy, one patient demonstrated additional atypical generalized polyspike discharges without a "dart-dome" morphology. Therapeutic response to introduction of sodium valproate was noted in all five patients. Features that were not consistent with the diagnosis were apparent in one patient who was re-classified with combined focal and generalized epilepsy. Differentiating aspects in this patient included multifocal discharges, background slowing, fast-recruiting ictal rhythms and valproate resistance. This is one of the largest case series of POMA. This entity, which falls under the spectrum of GGE, remains under-diagnosed and its distinctive electro-clinical features need to be recorded in order to prevent misclassification as focal epilepsy of probable opercular origin. Background-slowing, atypical ictal rhythms and valproate unresponsiveness are not consistent with the diagnosis of this unique absence epilepsy. [Published with video sequences].

Competing Interests: There are no conflicts of interest.

Background: The role of N-acetylcysteine (NAC) in improving outcomes following live donor liver transplantation (LDLT) is not well established. We designed a randomized double-blind placebo-controlled trial to study the role of NAC infusion in recipients undergoing LDLT., Methods: We assigned 150 patients who underwent LDLT by computer-generated random sequence on 1:1 ratio to either NAC group or placebo group. Patients in the NAC group received NAC infusion which was started at beginning of graft implantation at an initial loading dose of 150 mg/kg/h over 1 h, followed by 12.5 mg/kg/h for 4 h and then at 6.25 mg/kg/h continued for 91 h. Placebo group received normal saline. The primary endpoint was composite occurrence of acute kidney injury (AKI) and early allograft dysfunction (EAD) in the recipient. Secondary endpoints included levels of bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, INR, primary graft non-function, intraoperative bleeding, post-transplant hospital stay and in-hospital mortality., Results: The composite endpoint did not show any significant difference between the NAC and placebo group (21.3% vs 29.3%, p = 0.35). Peak AST (425.65 IU/L vs 702.24 IU/L, p = 0.02) and peak ALT (406.65 IU/L vs 677.99 IU/L, p = 0.01) levels were significantly lower in the study group. Time to normalization of transaminases was also significantly low in the study group., Conclusions: Perioperative NAC infusion following LDLT resulted in significantly lower postoperative AST and ALT levels. Rapid normalization of transaminases was also observed. This, however, did not translate to improvement in AKI or EAD.

Purpose: This study aimed to investigate differences in functional connectivity (FC) among different resting state networks (RSN) in clinically non-progressive mild cognitive impairment (MCI) and Alzheimer's disease (AD)., Methods: Using 3T MRI acquired resting-state functional MRI (rs-fMRI), we attempted identification of different RSN using independent component analysis (ICA) in amnestic-MCI, convertors to early AD and age-matched cognitively normal healthy controls. Regions of interest (ROI) that showed significant differences in connectivity on group ICA were selected as seeds for seed-voxel analysis. Group differences in FC for each network-connectivity map were entered into a general linear model with age, gender and total intra-cranial volume (TIV) as covariates., Results: In this cross-sectional design 31 HC, 30 MCI and 30 MCI-convertors to early AD were evaluated. Seed-based analysis between AD and controls revealed reduced posterior connectivity within the default mode (DMN), dorsal attention (DAN) and antero-posterior connectivity with sensori-motor (SMN) networks. Reduced cerebellar connectivity of DMN and posterior connectivity within the frontal parietal network (FPN) separated AD from MCI. MCI-control comparisons revealed differences only on ICA. Positive correlation was observed between FC in DMN network clusters with verbal list-learning (r = 0.50) and recall scores (r = 0.51) in AD, the latter additionally demonstrating correlation with SMN clusters (r = 0.50)., Conclusions: Widespread network hypo-connectivity is apparent in AD as opposed to MCI non-convertors in comparison to controls, along with positive correlation with memory scores. Reduced connectivity involving DMN and FPN helps to differentiate between AD and MCI-nonconvertors to dementia. Longitudinal studies are required into utility of these measures., (Copyright © 2020 Elsevier B.V. All rights reserved.)