Development of an online calculator for the prediction of seizure freedom following pediatric hemispherectomy using the Hemispherectomy Outcome Prediction Scale (HOPS).

OBJECTIVES: Although hemispheric surgeries are among the most effective procedures for drug-resistant epilepsy (DRE) in the pediatric population, there is a large variability in seizure outcomes at the group level. A recently developed HOPS score provides individualized estimation of likelihood of seizure freedom to complement clinical judgement. The objective of this study was to develop a freely accessible online calculator that accurately predicts the probability of seizure freedom for any patient at 1-, 2-, and 5-years post-hemispherectomy. METHODS: Retrospective data of all pediatric patients with DRE and seizure outcome data from the original Hemispherectomy Outcome Prediction Scale (HOPS) study were included. The primary outcome of interest was time-to-seizure recurrence. A multivariate Cox proportional-hazards regression model was developed to predict the likelihood of post-hemispheric surgery seizure freedom at three time points (1-, 2- and 5- years) based on a combination of variables identified by clinical judgment and inferential statistics predictive of the primary outcome. The final model from this study was encoded in a publicly accessible online calculator on the International Network for Epilepsy Surgery and Treatment (iNEST) website (https://hops-calculator.com/). RESULTS: The selected variables for inclusion in the final model included the five original HOPS variables (age at seizure onset, etiologic substrate, seizure semiology, prior non-hemispheric resective surgery, and contralateral fluorodeoxyglucose-positron emission tomography [FDG-PET] hypometabolism) and three additional variables (age at surgery, history of infantile spasms, and magnetic resonance imaging [MRI] lesion). Predictors of shorter time-to-seizure recurrence included younger age at seizure onset, prior resective surgery, generalized seizure semiology, FDG-PET hypometabolism contralateral to the side of surgery, contralateral MRI lesion, non-lesional MRI, non-stroke etiologies, and a history of infantile spasms. The area under the curve (AUC) of the final model was 73.0%. SIGNIFICANCE: Online calculators are useful, cost-free tools that can assist physicians in risk estimation and inform joint decision-making processes with patients and families, potentially leading to greater satisfaction. Although the HOPS data was validated in the original analysis, the authors encourage external validation of this new calculator.

Defining benchmark outcomes for mesial temporal lobe epilepsy surgery: A global multicenter analysis of 1119 cases.

OBJECTIVE: Benchmarking has been proposed to reflect surgical quality and represents the highest standard reference values for desirable results. We sought to determine benchmark outcomes in patients after surgery for drug-resistant mesial temporal lobe epilepsy (MTLE). METHODS: This retrospective multicenter study included patients who underwent MTLE surgery at 19 expert centers on five continents. Benchmarks were defined for 15 endpoints covering surgery and epilepsy outcome at discharge, 1 year after surgery, and the last available follow-up. Patients were risk-stratified by applying outcome-relevant comorbidities, and benchmarks were calculated for low-risk ("benchmark") cases. Respective measures were derived from the median value at each center, and the 75th percentile was considered the benchmark cutoff. RESULTS: A total of 1119 patients with a mean age (range) of 36.7 (1-74) years and a male-to-female ratio of 1:1.1 were included. Most patients (59.2%) underwent anterior temporal lobe resection with amygdalohippocampectomy. The overall rate of complications or neurological deficits was 14.4%, with no in-hospital death. After risk stratification, 377 (33.7%) benchmark cases of 1119 patients were identified, representing 13.6%-72.9% of cases per center and leaving 742 patients in the high-risk cohort. Benchmark cutoffs for any complication, clinically apparent stroke, and reoperation rate at discharge were ≤24.6%, ≤.5%, and ≤3.9%, respectively. A favorable seizure outcome (defined as International League Against Epilepsy class I and II) was reached in 83.6% at 1 year and 79.0% at the last follow-up in benchmark cases, leading to benchmark cutoffs of ≥75.2% (1-year follow-up) and ≥69.5% (mean follow-up of 39.0 months). SIGNIFICANCE: This study presents internationally applicable benchmark outcomes for the efficacy and safety of MTLE surgery. It may allow for comparison between centers, patient registries, and novel surgical and interventional techniques.

Physical fitness in Indian women with epilepsy on anti-seizure medications and its association with reproductive status, quality of life and stigma: A cross-sectional study.

PURPOSE: To determine the status of physical fitness, reproductive abnormalities, QOL and epilepsy associated stigma in women with epilepsy (WWE) and their association with ASM therapy and seizure frequency. METHODS: This cross-sectional study included WWE of reproductive age (18-50 years) on antiseizure medications (ASMs) for at least three months before enrolment. Physical fitness was assessed using International Physical Activity Questionnaires (IPAQ) and Body composition analysis. Subjects were interviewed for menstrual abnormalities [menstrual disturbance or Polycystic Ovary Syndrome (PCOS)/hirsutism]. Validated questionnaires were used for assessment of, QOL (QOLIE-10) and Stigma in epilepsy (Epilepsy Stigma Scale). Sub-group analysis was done to compare the above parameters on the basis of a) type of therapy (mono or polytherapy), b) type of ASMs treatment (conventional, newer, or conventional + newer ASMs), and c) seizure type and (d) seizure frequency. Correlation and regression analysis were done to find out the association among different variables with physical fitness. RESULTS: The overall prevalence of poor physical fitness, reproductive abnormalities, worsened QOL and stigma in the enrolled WWE (n = 203) were 21.18 %, 20.19 %, 52.7 %, and 21.67 %, respectively. Sub-group analysis revealed that WWE on monotherapy (n = 99) had higher median IPAQ score (p = 0.002), comparatively less reproductive abnormalities (24.03 %, p = 0.008), and higher stigma (24.03 %, p = 0.04) than polytherapy group. WWE on conventional ASMs had significantly higher IPAQ scores compared to newer and conventional + newer ASMs groups (p = 0.02). The prevalence of poor physical fitness and stigma was significantly higher in WWE with higher number of seizures (p = 0.007, <0.001, respectively). No significant difference in QOL was observed on the basis of ASM type and therapy; however, WWE with generalized onset seizures had worsened QOL compared to those with focal onset seizures (p = 0.04). A significant negative correlation was found among seizure frequency and IPAQ score in WWE (p = 0.04). CONCLUSION: WWE on polytherapy were physically less active, higher occurrence of reproductive abnormalities, and stigma compared to the monotherapy group. WWE with higher seizure frequency had poor physical fitness, and higher stigma compared to those with lesser number of seizures. These findings may aid value in optimization of ASM treatment in WWE of reproductive age.

Neuropsychological Rehabilitation for Epilepsy in India: Looking Beyond the Basics.

BACKGROUND: Neuropsychological Rehabilitation (NR) helps manage cognitive deficits in epilepsy. As internationally developed programs have limited applicability to resource-limited countries, we developed a program to bridge this gap. This 6-week caregiver-assisted, culturally suitable program has components of (1) psychoeducation, (2) compensatory training, and, (3) cognitive retraining and is called EMPOWER (Indigenized Home Based Attention and Memory Rehabilitation Program for Adult Patients with Drug Refractory Epilepsy). Its efficacy needs to be determined. METHODS: We carried out an open-label parallel randomized controlled trial. Adults aged 18-45 years with Drug Refractory Epilepsy (DRE), fluency in Hindi and or English, with impaired attention or memory (n = 28) were randomized to Intervention Group (IG) and Control Group (CG). The primary outcomes were objective memory (Auditory Verbal Learning Test), patient and caregiver reported everyday memory difficulties (Everyday Memory Questionnaire-Revised), number of memory aids in use, depression (Hamilton Depression Rating Scale), anxiety (Hamilton Anxiety Rating Scale) and quality of life (Quality of Life in Epilepsy-31). Intention to treat was carried out for group analysis. In the absence of norms necessary for computing Reliable Change Indices (RCIs), a cut-off of +1.0 Standard Deviation (SD) was utilized to identify clinically meaningful changes in the individual analysis of objective memory. A cut-off of 11.8 points was used for quality of life. Feedback and program evaluation responses were noted. RESULTS: The majority of the sample comprised DRE patients with temporal lobe epilepsy who had undergone epilepsy surgery. Group analysis indicated improved learning (p = 0.013), immediate recall (p = 0.001), delayed recall (p < 0.001), long-term retention (p = 0.031), patient-reported everyday memory (p < 0.001), caregiver-reported everyday memory (p < 0.001), anxiety (p = 0.039) and total quality of life (p < 0.001). Individual analysis showed improvement in 50 %, 64 %, 71 %, 57 %, and 64 % of patients on learning, immediate recall, delayed recall, long-term retention, and total quality of life respectively. Despite improvements, themes indicative of a lack of awareness and understanding of cognitive deficits were identified. Overall, the program was rated favorably by patients and caregivers alike. CONCLUSION: NR shows promise for patients with DRE, however larger studies are warranted. The role of cognition in epilepsy needs to be introduced at the time of diagnosis to help lay the foundation for education and acceptance.

Development of sensitive magnetic nanoparticle assisted rapid sandwich assay(s-MARSA) to monitor Parkinson's disease and Schizophrenia pharmacotherapy.

Parkinson's disease and Schizophrenia fall under low dopamine neurodegenerative and high dopamine psychiatric disorders respectively. Pharmacological interventions to correct mid-brain dopamine concentrations sometimes overshoots the physiological dopamine levels leading to psychosis in Parkinson's disease patients and, extra-pyramidal symptoms in schizophrenia patients. Currently no validated method is available to monitor side effects in such patients, Apolipoprotein E is one of the CSF biomarkers identified in the recent past that shows an inverse relation to mid-brain dopamine concentration. In this study, we have developed s-MARSA for the detection of Apolipoprotein E from ultra-small volume (2 µL) of CSF. s-MARSA exhibits a broad detection range (5 fg mL-1 to 4 µg mL-1) with a better detection limit and could be performed within an hour utilizing only a small volume of CSF sample. The values measured by s-MARSA strongly correlates with the values measured by ELISA. Our method has advantages over ELISA in having a lower detection limit, a broader linear detection range, shorter analysis time, and requiring a low volume of CSF samples. The developed s-MARSA method holds promise for the detection of Apolipoprotein E with clinical utility for monitoring pharmacotherapy of Parkinson's and Schizophrenia patients.

Added value of corpus callosotomy following vagus nerve stimulation in children with Lennox-Gastaut syndrome: A multicenter, multinational study.

OBJECTIVE: Lennox-Gastaut syndrome (LGS) is a severe form of epileptic encephalopathy, presenting during the first years of life, and is very resistant to treatment. Once medical therapy has failed, palliative surgeries such as vagus nerve stimulation (VNS) or corpus callosotomy (CC) are considered. Although CC is more effective than VNS as the primary neurosurgical treatment for LGS-associated drop attacks, there are limited data regarding the added value of CC following VNS. This study aimed to assess the effectiveness of CC preceded by VNS. METHODS: This multinational, multicenter retrospective study focuses on LGS children who underwent CC before the age of 18 years, following prior VNS, which failed to achieve satisfactory seizure control. Collected data included epilepsy characteristics, surgical details, epilepsy outcomes, and complications. The primary outcome of this study was a 50% reduction in drop attacks. RESULTS: A total of 127 cases were reviewed (80 males). The median age at epilepsy onset was 6 months (interquartile range [IQR] = 3.12-22.75). The median age at VNS surgery was 7 years (IQR = 4-10), and CC was performed at a median age of 11 years (IQR = 8.76-15). The dominant seizure type was drop attacks (tonic or atonic) in 102 patients. Eighty-six patients underwent a single-stage complete CC, and 41 an anterior callosotomy. Ten patients who did not initially have a complete CC underwent a second surgery for completion of CC due to seizure persistence. Overall, there was at least a 50% reduction in drop attacks and other seizures in 83% and 60%, respectively. Permanent morbidity occurred in 1.5%, with no mortality. SIGNIFICANCE: CC is vital in seizure control in children with LGS in whom VNS has failed. Surgical risks are low. A complete CC has a tendency toward better effectiveness than anterior CC for some seizure types.

VE-MMODE - A randomized controlled trial of Venlafaxine versus Escitalopram for treatment of mild to moderate depression in persons with epilepsy.

OBJECTIVES: Depression in persons with epilepsy (PWE) goes undiagnosed and untreated. Despite being common, there are no direct efficacy comparisons of available antidepressants in PWE. Our aim was to compare the effectiveness of Venlafaxine (VEN) and Escitalopram (ESCIT) in comorbid depression in PWE. METHODS: In a single-center, prospective, double-blinded randomized controlled trial (RCT) 90 PWE (age ≥18 years) with mild to moderate depression, were randomized in a 1:1 ratio to receive ESCIT (5-20 mg/day) or VEN (37.5-150 mg/day) for 8 weeks. The primary outcome was to study differences in the efficacy, based on the change in scores of the Hamilton depression rating scale (HAM-D) at 8 weeks. Seizure frequency, QOLIE-31, adverse event profile, and medication adherence were secondary outcome measures. RESULTS: Using the NDDI-E scale, we screened 350 PWE, 90 were enrolled. ITT analysis included all participants and the PP analysis included 40 participants to VEN group and 42 to ESCIT group. Baseline mean (±SD) HAM-D scores for both groups were similar (13.53 ± 3.27; 13.02 ± 3.57). The mean difference (95%CI) on HAM-D scores at 8 weeks was found to be significant within both groups (ITT/PP- VEN: 7.75(6.75, 8.79)/7.92 (7.06, 8.78); p < 0.001, ESCIT: 8.21 (7.39, 9.03)/8.23(7.43, 9.04); p < 0.001). However, there was no significant difference in the efficacy of VEN versus ESCIT at 8 weeks. A significant improvement in QOLIE-31 index and seizure frequency was observed from baseline in both the groups. 90% of those on VEN and 92.9% of those using ESCITadhered to the treatment at week 8. Adverse events were more in VEN group than the ESCIT group. CONCLUSIONS: This study found that HAMD scores improved significantly in the ESCIT and VEN groups, despite the fact that there was no clinically meaningful difference observed between the two groups. Trials with a larger sample size and longer duration are required to establish whether ESCIT or VEN is superior.

Clinical and radiological spectrum of anti-myelin oligodendrocyte glycoprotein (MOG) antibody encephalitis: single-center observational study.

OBJECTIVE: The objective was to describe the clinical presentations, radiologic features, and outcomes of patients with autoimmune encephalitis associated with myelin oligodendrocyte glycoprotein antibody (MOG). BACKGROUND: During the past decade, the spectrum of the myelin oligodendrocyte glycoprotein antibody-associated diseases (MOGAD) has expanded. Recently, patients with MOG antibody encephalitis (MOG-E) who do not fulfill the criteria for ADEM have been reported. In this study, we aimed to describe the spectrum of MOG-E. METHODS: Sixty-four patients with MOGAD were screened for encephalitis-like presentation. We collected the clinical, radiological, laboratory, and outcome data of the patients who presented with encephalitis and compared it with the non-encephalitis group. RESULTS: We identified sixteen patients (nine males and seven females) with MOG-E. The median age of the encephalitis population was significantly lower than the non-encephalitis group (14.5 years (11.75-18) vs. 28 years (19.75-42), p = 0.0004). Twelve out of sixteen patients (75%) had fever at the time of encephalitis. Headache and seizure were present in 9/16 (56.2%) and 7/16 (43.75%) patients, respectively. FLAIR cortical hyperintensity was present in 10/16 (62.5%) patients. Supratentorial deep gray nuclei were involved in 10/16 (62.5%) patients. Three patients had tumefactive demyelination, and one patient had a leukodystrophy-like lesion. Twelve of 16 (75%) patients had a good clinical outcome. Patient with leukodystrophy pattern and other with generalized CNS atrophy showed a chronic progressive course. CONCLUSION: MOG-E can have heterogeneous radiological presentations. FLAIR cortical hyperintensity, tumefactive demyelination, and leukodystrophy-like presentations are novel radiological presentations associated with MOGAD. Though majority of MOG-E have a good clinical outcome, few patients can have chronic progressive disease even on immunosuppressive therapy.

Prevalence and determinants of post-stroke sleep disorders: a cross-sectional hospital-based study.

INTRODUCTION: Post-stroke sleep disorders (PSSD) are an important part of post-stroke disability. PSSD is neglected as a part of stroke rehabilitation. We aimed to study the prevalence and determinants of PSSD in a hospital based, single center setting. METHODS: In a cross-sectional study, adult patients (≥ 18 years) with stroke (one month to one year after the onset), were enrolled in the study. Demographic, clinical, radiological, and motor and functional disabilities were assessed. Sleep quality was assessed with Pittsburg Sleep Quality Index (PSQI) and STOP BANG questionnaire (for obstructive sleep apnea [OSA]). Patients with poor sleep quality (PSQI > 5) were analyzed for risk factors. RESULTS: A total of 103 patients were recruited in the study period (January 2021 to June 2022). The self-reported prevalence of PSSD was 16% which increased to 72% when the PSQI was administered. High risk of OSA was present in 33%. In bivariate analysis, factors associated with PSQI > 5 were involvement of ≥ 2 lobes, lower body mass index (BMI), worse modified Rankin Scale (mRS), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A) and Stroke Specific Quality of Life (SSQoL). In multivariate analysis, only depression was associated with PSQI > 5 (OR: 1.3 (1.0; 1.7); p-value = 0.03). CONCLUSION: PSSD had a prevalence of 72%. In multivariate analysis, the factor associated with PSQI > 5 was worse HAM-D score.

Association of obstructive sleep apnea and sleep quality with cognitive function: a study of middle-aged and elderly persons in India.

INTRODUCTION: Symptoms of obstructive sleep apnea (OSA) and poor sleep quality affect around one in ten people in India. We aimed to determine if OSA symptoms and poor sleep quality are independently associated with cognition in middle-aged and elderly urban Indian populations. METHODS: We studied the cross-sectional association between OSA symptoms (by Berlin Questionnaire), poor sleep quality (by Pittsburgh Sleep Quality Index), and cognitive function in adults ≥ 50 years. Using a standard neuropsychological battery for cognitive function, a G-factor was derived as the first rotated principal component assessing domains of information processing, memory, and executive function. The associations of exposures with cognitive measures were modeled using linear regression, adjusted for metabolic risk factors, lifestyle factors, and psychosocial problems, followed by stratified analysis by decadal age group. RESULTS: A total of 7505 adults were enrolled. Excluding those with MMSE < 26 (n 710), of 6795 individuals (49.2% women), mean (SD) age 64.2 (9.0) years, 38.3% had high risk of OSA symptoms, and 15.9% had poor sleep quality. OSA symptoms were negatively associated with cognitive domains of information processing (adjusted beta coefficient of z-score - 0.02, p-value 0.006), memory (- 0.03, 0.014), and G-factor (- 0.11, 0.014) in full-model. Stratified analysis by age group showed significant adverse effects of OSA symptoms on cognition for middle-aged people (50-60 years) (- 0.26, 0.001), but not in later age groups. Poor sleep quality was also associated with lower cognitive scores for G-factor (- 0.48, < 0.001), memory (- 0.08, 0.005), and executive domains (- 0.12, < 0.001), but not with information domain. CONCLUSION: The findings suggest that both symptoms of OSA and poor sleep quality have a direct adverse impact on cognition in an Indian setting. A modest effect of age on the relationship of OSA and cognition was also observed.

Transcriptomic profiling of nonneoplastic cortical tissues reveals epileptogenic mechanisms in dysembryoplastic neuroepithelial tumors.

Low-grade dysembryoplastic neuroepithelial tumors (DNTs) are a frequent cause of drug-refractory epilepsy. Molecular mechanisms underlying seizure generation in these tumors are poorly understood. This study was conducted to identify altered genes in nonneoplastic epileptogenic cortical tissues (ECTs) resected from DNT patients during electrocorticography (ECoG)-guided surgery. RNA sequencing (RNAseq) was used to determine the differentially expressed genes (DEGs) in these high-spiking ECTs compared to non-epileptic controls. A total of 477 DEGs (180 upregulated; 297 downregulated) were observed in the ECTs compared to non-epileptic controls. Gene ontology analysis revealed enrichment of genes belonging to the following Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways: (i) glutamatergic synapse; (ii) nitrogen metabolism; (iii) transcriptional misregulation in cancer; and (iv) protein digestion and absorption. The glutamatergic synapse pathway was enriched by DEGs such as GRM4, SLC1A6, GRIN2C, GRM2, GRM5, GRIN3A, and GRIN2B. Enhanced glutamatergic activity was observed in the pyramidal neurons of ECTs, which could be attributed to altered synaptic transmission in these tissues compared to non-epileptic controls. Besides glutamatergic synapse, altered expression of other genes such as GABRB1 (synapse formation), SLIT2 (axonal growth), and PROKR2 (neuron migration) could be linked to epileptogenesis in ECTs. Also, upregulation of GABRA6 gene in ECTs could underlie benzodiazepine resistance in these patients. Neural cell-type-specific gene set enrichment analysis (GSEA) revealed transcriptome of ECTs to be predominantly contributed by microglia and neurons. This study provides first comprehensive gene expression profiling of nonneoplastic ECTs of DNT patients and identifies genes/pathways potentially linked to epileptogenesis.

Role of Altered Expression, Activity and Sub-cellular Distribution of Various Histone Deacetylases (HDACs) in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis.

Histone deacetylases (HDACs) have been described to have both neurotoxic and neuroprotective roles, and partly, depend on its sub-cellular distribution. HDAC inhibitors have a long history of use in the treatment of various neurological disorders including epilepsy. Key role of HDACs in GABAergic neurotransmission, synaptogenesis, synaptic plasticity and memory formation was demonstrated whereas very less is known about their role in drug-resistant epilepsy pathologies. The present study was aimed to investigate the changes in the expression of HDACs, activity and its sub-cellular distribution in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) patients. For this study, surgically resected hippocampal tissue specimens of 28 MTLE-HS patients and 20 hippocampus from post-mortem cases were obtained. Real-time PCR was done to analyse the mRNA expression. HDAC activity and the protein levels of HDACs in cytoplasm as well as nucleus were measured spectrophotometrically. Further, sub-cellular localization of HDACs was characterized by immunofluorescence. Significant upregulation of HDAC1, HDAC2, HDAC4, HDAC5, HDAC6, HDAC10 and HDAC11 mRNA were observed in MTLE-HS. Alterations in the mRNA expression of glutamate and gamma-aminobutyric acid (GABA) receptor subunits have been also demonstrated. We observed significant increase of HDAC activity and nuclear level of HDAC1, HDAC2, HDAC5 and HDAC11 in the hippocampal samples obtained from patients with MTLE-HS. Moreover, we found altered cytoplasmic level of HDAC4, HDAC6 and HDAC10 in the hippocampal sample obtained from patients with MTLE-HS. Alterations in the level of HDACs could potentially be part of a dynamic transcription regulation associated with MTLE-HS. Changes in cytoplasmic level of HDAC4, 6 and 10 suggest that cytoplasmic substrates may play a crucial role in the pathophysiology of MTLE-HS. Knowledge regarding expression pattern and sub-cellular distribution of HDACs may help to devise specific HDACi therapy for epilepsy.

Epilepsy-related stigma and attitudes: Systematic review of screening instruments and interventions - Report by the International League Against Epilepsy Task Force on Stigma in Epilepsy.

OBJECTIVE: This is a systematic review aimed at summarizing the evidence related to instruments that have been developed to measure stigma or attitudes toward epilepsy and on stigma-reducing interventions. METHODS: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. A broad literature search (1985-2019) was performed in 13 databases. Articles were included if they described the development and testing of psychometric properties of an epilepsy-related stigma or attitude scale or stigma-reducing interventions. Two reviewers independently screened abstracts, reviewed full-text articles, and extracted data. Basic descriptive statistics are reported. RESULTS: We identified 4234 abstracts, of which 893 were reviewed as full-text articles. Of these, 38 met inclusion criteria for an instrument development study and 30 as a stigma-reduction intervention study. Most instruments were initially developed using well-established methods and were tested in relatively large samples. Most intervention studies involved educational programs for adults with pre- and post-evaluations of attitudes toward people with epilepsy. Intervention studies often failed to use standardized instruments to quantify stigmatizing attitudes, were generally underpowered, and often found no evidence of benefit or the benefit was not sustained. Six intervention studies with stigma as the primary outcome had fewer design flaws and showed benefit. Very few or no instruments were validated for regional languages or culture, and there were very few interventions tested in some regions. SIGNIFICANCE: Investigators in regions without instruments should consider translating and further developing existing instruments rather than initiating the development of new instruments. Very few stigma-reduction intervention studies for epilepsy have been conducted, study methodology in general was poor, and standardized instruments were rarely used to measure outcomes. To accelerate the development of effective epilepsy stigma-reduction interventions, a paradigm shift from disease-specific, siloed trials to collaborative, cross-disciplinary platforms based upon unified theories of stigma transcending individual conditions will be needed.

Systematic review of frequency of felt and enacted stigma in epilepsy and determining factors and attitudes toward persons living with epilepsy-Report from the International League Against Epilepsy Task Force on Stigma in Epilepsy.

OBJECTIVE: To review the evidence of felt and enacted stigma and attitudes toward persons living with epilepsy, and their determining factors. METHODS: Thirteen databases were searched (1985-2019). Abstracts were reviewed in duplicate and data were independently extracted using a standardized form. Studies were characterized using descriptive analysis by whether they addressed "felt" or "enacted" stigma and "attitudes" toward persons living with epilepsy. RESULTS: Of 4234 abstracts, 132 met eligibility criteria and addressed either felt or enacted stigma and 210 attitudes toward epilepsy. Stigma frequency ranged broadly between regions. Factors associated with enacted stigma included low level of knowledge about epilepsy, lower educational level, lower socioeconomic status, rural areas living, and religious grouping. Negative stereotypes were often internalized by persons with epilepsy, who saw themselves as having an "undesirable difference" and so anticipated being treated differently. Felt stigma was associated with increased risk of psychological difficulties and impaired quality of life. Felt stigma was linked to higher seizure frequency, recency of seizures, younger age at epilepsy onset or longer duration, lower educational level, poorer knowledge about epilepsy, and younger age. An important finding was the potential contribution of epilepsy terminology to the production of stigma. Negative attitudes toward those with epilepsy were described in 100% of included studies, and originated in any population group (students, teachers, healthcare professionals, general public, and those living with epilepsy). Better attitudes were generally noted in those of younger age or higher educational status. SIGNIFICANCE: Whatever the specific beliefs about epilepsy, implications for felt and enacted stigma show considerable commonality worldwide. Although some studies show improvement in attitudes toward those living with epilepsy over time, much work remains to be done to improve attitudes and understand the true occurrence of discrimination against persons with epilepsy.

The Childhood and Adolescent Sleep Evaluation Questionnaire (CASEQ): Development and validation of an ICSD-3-based screening instrument, a community and hospital-based study.

Sleep disorders are common in children and adolescents. Polysomnography is the gold-standard diagnostic method; however, it is a tedious procedure. The objective of the study was to develop a screening questionnaire for sleep problems based on International Classification of Sleep Disorders-3 in children and adolescents, and validate it with clinical evaluation and polysomnography. A questionnaire was developed in English and Hindi with content validation by eight multidisciplinary experts. Respondents were parents of children and adolescents, aged 2-18 years, recruited from a public school and a tertiary care teaching hospital in north India. A subset of these children and adolescents underwent overnight polysomnography and detailed clinical evaluation within 4 weeks of applying the questionnaire. The questionnaire, named Childhood and Adolescent Sleep Evaluation Questionnaire, contains primary questions covering all subgroups of disorders under International Classification of Sleep Disorders-3, and secondary questions on sleep hygiene and comorbidities. The questionnaire was filled by 750 respondents, out of which 100 cases underwent polysomnography and clinical evaluation. The internal consistency in the form of Cronbach's α was 0.8 for the questionnaire. The sensitivity, specificity, positive and negative predictive values for the questionnaire in identifying those with sleep problems compared with detailed clinical and polysomnographic evaluations were 85%, 100%, 100% and 62.5%, respectively. For individual subgroups of disorders, the sensitivity, specificity, positive and negative predictive values varied between 72.7% and 100%, 88.9% and 100%, 62.5% and 100% and 81.6% and 100%, respectively. The Childhood and Adolescent Sleep Evaluation Questionnaire has good psychometric properties, moreover, its simplicity and translatability make it ideal for use at the community and hospital settings.

Impact of exercise as a complementary management strategy in people with epilepsy: A randomized controlled trial.

OBJECTIVE: To measure the impact of 12 weeks of physical exercise as complementary management strategy on quality of life (QOL) in people with epilepsy (PWE). METHODS: In a parallel-group, randomized controlled study with blinded outcome assessment, PWE of 18-65 years old, smartphone users were randomized into two groups. The exercise group was advised minimum 150 min per week of moderate-intense aerobic activity, as per current WHO recommendation [1], in addition to standard medical care; the control group received only standard medical care. QOL was assessed using Quality of Life in Epilepsy (QOLIE-31) inventory [2,3]; physical activity, with Global Physical Activity Questionnaire version 2 (GPAQ), and Pedometer Step Counter (a smartphone-based activity tracker application), at baseline and after 12 weeks. Body weight, body mass index, seizure frequency, and stigma scores (Epilepsy Stigma Scale Austin and colleagues) [4] were also noted. RESULTS: One hundred and seventeen PWE were recruited (58 exercise, 59 control). Although there was an improvement in the physical activity correlates after 12 weeks compared to mean values at baseline, the differences were not significant between the groups. The total QOL mean scores at baseline in the exercise and control groups were 64.9 and 63.7 (p = 0.597) and after 12 weeks, 68.4 and 66.9 (p = 0.660), respectively. However, intragroup comparison of energy/fatigue score in the exercise group showed significant change with a p value of 0.009 and intragroup comparison of Overall QOL score in the control group showed a significant change with a p value of 0.003. Similar improvement was seen in stigma scores (p = 0.500) and seizure frequency (p = 0.388) at 12 weeks in exercise and control groups. After 12 weeks, mean values of METS ((metabolic equivalents) were 794.81 and 714.27 (p = 0.159), steps per day were 4018.32 and 3730.0 (p = 0.314), calories spent per day were 173.85 and 159.68 (p = 0.320 and distance walked per day in meters were 2576.52 and 2198.42 (p = 0.072), in the exercise and control groups, respectively. SIGNIFICANCE: Regular physical activity for at least 150 min per week, in the form of moderate-intense aerobic exercises resulted in positive yet non-significant improvement of QOL, seizure frequency, and stigma in PWE.

MoCA in five Indian languages: A brief screening tool to diagnose dementia and MCI in a linguistically diverse setting.

INTRODUCTION AND OBJECTIVES: Early dementia diagnosis in low and middle-income countries (LMIC) is challenging due to limited availability of brief, culturally appropriate, and psychometrically validated tests. Montreal Cognitive Assessment (MoCA) is one of the most widely used cognitive screening tests in primary and secondary care globally. In the current study, we adapted and validated MoCA in five Indian languages (Hindi, Bengali, Telugu, Kannada, and Malayalam) and determined the optimal cut-off points that correspond to screening for clinical diagnosis of dementia and MCI. METHODS: A systematic process of adaptation and modifications of MoCA was fulfilled. A total of 446 participants: 214 controls, 102 dementia, and 130 MCI were recruited across six centers. RESULTS: Across five languages, the area under the curve for diagnosis of dementia varied from 0.89 to 0.98 and MCI varied from 0.73 to 0.96. The sensitivity, specificity and optimum cut-off scores were established separately for five Indian languages. CONCLUSIONS: The Indian adapted MoCA is standardized and validated in five Indian languages for early diagnosis of dementia and MCI in a linguistically and culturally diverse population.

Spectrum of Movement Disorders of Late-Onset Niemann-Pick Disease Type C.

Niemann-Pick disease type C (NPC), is a rare lysosomal storage disorder, which has a variable presentation based on the age of onset. We describe five adult/adolescent-onset NPC cases presenting with a range of movement disorders along with vertical supranuclear gaze palsy as part of the clinical presentation. A diagnostic delay of 4-17 years from the symptom onset was found in this case series. A high index of clinical suspicion in adult/adolescent patients presenting with vertical supranuclear gaze palsy along with various movement disorder phenomenology can help in the early diagnosis of NPC.

Altered expression of activating transcription factor 3 in the hippocampus of patients with mesial temporal lobe epilepsy-hippocampal sclerosis (MTLE-HS).

Aim of the study: Activating Transforming factor 3 (ATF3) is a stress induced gene and closely associated with neuro-inflammation while Transforming growth Factor Beta (TGFß) signalling is also reported to be involved in neuro-inflammation and hyper-excitability associated with drug resistant epilepsy. Animal model studies indicate the involvement of ATF3 and TGFß receptors to promote epileptogenesis. Human studies also show that TGFß signalling is activated in MTLE-HS. However, lack of studies on ATF3 and TGFßRI expression in MTLE-HS patients exists. We hypothesize that ATF3 and TGFßRI might be expressed in hippocampi of patients with MTLE-HS and playing role in epileptogenesis.Materials & methods: Protein expression of ATF3 and TGFßRI was performed by western blotting. Localisation of ATF3 was performed by immunohistochemistry and immunoflorescence.Results: Protein expression of ATF3 and TGFßRI was significantly up-regulated in hippocampi of patients as compared to controls. Also ATF3 IR was significantly expressed in hippocampi of patients and ATF3 was expressed predominantly in cytoplasm as compared to nucleus. No correlation was found between ATF3 expression and epilepsy duration and seizure frequency.Conclusions: ATF3 and TGFßRI are both important players in neuro-inflammation and might potentiate epileptogenesis in these patients.

Picture-naming test for a linguistically diverse population with cognitive impairment and dementia.

BACKGROUND: Picture-naming tests (PNTs) evaluate linguistic impairment in dementia due to semantic memory impairment, impaired lexical retrieval or perceptual deficits. They also assess the decline in naming impairment at various stages of dementia and mild cognitive impairment (MCI) that occurs due to progressive cognitive impairment. With the increasing numbers of people with dementia globally, it is necessary to have validated naming tests and norms that are culturally and linguistically appropriate. AIMS: In this cross-sectional study we harmonized a set of 30 images applicable to the Indian context across five languages and investigated the picture-naming performance in patients with MCI and dementia. METHODS & PROCEDURES: A multidisciplinary expert group formed by the Indian Council of Medical Research (ICMR) collaborated towards developing and adapting a picture naming test (PNT) known as the ICMR-PNT in five Indian languages: Hindi, Bengali, Telugu, Kannada and Malayalam. Based on cross-cultural adaptation guidelines and item-wise factor analysis and correlations established separately across five languages, the final version of the ICMR-PNT test was developed. A total of 368 controls, 123 dementia and 128 MCI patients were recruited for the study. Psychometric properties of the adapted version of the ICMR-PNT were examined, and sensitivity and specificity were examined. OUTCOMES & RESULTS: The ICMR-PNT scores in all languages combined were higher in controls compared with patients with dementia and MCI (F2, 615 = 139.85; p < 0.001). Furthermore, PNT scores for MCI was higher in comparison with patients with dementia in all languages combined (p < 0.001). The area under the curve across the five languages ranged from 0.81 to 1.00 for detecting dementia. There was a negative correlation between Clinical Dementia Rating (CDR) and ICMR-PNT scores and a positive correlation between Addenbrooke's Cognitive Examination-III (ACE-III) and ICMR-PNT scores in control and patient groups. CONCLUSIONS & IMPLICATIONS: The ICMR-PNT was developed by following cross-cultural adaptation guidelines and establishing correlations using item-wise factor analysis across five languages. This adapted PNT was found to be a reliable tool when assessing naming abilities effectively in mild to moderate dementia in a linguistically diverse context. WHAT THIS PAPER ADDS: What is already known on this subject Picture-naming evaluates language impairment linked to naming difficulties due to semantic memory, lexical retrieval or perceptual disturbances. As a result, picture naming tests (PNTs) play an important role in the diagnosis of dementia. In a heterogeneous population such as India, there is a need for a common PNT that can be used across the wide range of languages. What this study adds to existing knowledge PNTs such as the Boston Naming Test (BNT) were developed for the educated, mostly English-speaking, Western populations and are not appropriate for use in an Indian context. To overcome this challenge, a PNT was harmonized in five Indian languages (Hindi, Bengali, Telugu, Kannada and Malayalam) and we report the patterns of naming difficulty in patients with MCI and dementia. The ICMR-PNT demonstrated good diagnostic accuracy when distinguishing patients with mild to moderate dementia from cognitively normal individuals. What are the potential or actual clinical implications of this work? With the growing number of persons suffering from Alzheimer's disease and other forms of dementia around the world, its critical to have culturally and linguistically relevant naming tests and diagnosis. This validated ICMR-PNT can be used widely as a clinical tool to diagnose dementia and harmonize research efforts across diverse populations.