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Background: Progressive myoclonus epilepsy (PME) is a neurodegenerative disorder marked by recurrent seizures and progressive myoclonus. To date, based on the phenotypes and causal genes, more than 40 subtypes of PMEs have been identified, and more remain to be characterized. Our study is aimed at identifying the aberrant gene(s) possibly associated with PMEs in two siblings born to asymptomatic parents, in the absence of known genetic mutations. Methods: Clinical assessments and molecular analyses, such as the repeat expansion test for CSTB ; SCA1, 2, 3, 6, and 7; whole exome sequencing (WES); and mitochondrial genome sequencing coupled with computational analysis, were performed. Results: A family-based segregation analysis of WES data was performed to identify novel genes associated with PMEs. The potassium channel, KCNH8 [c.298T>C; (p.Tyr100His)], a DNA repair gene, regulator of telomere elongation helicase 1 ( RTEL1 ) [c.691G>T; (p.Asp231Tyr)] and long noncoding RNA, RTEL1-TNFRSF6B [chr20:62298898_G>T; NR_037882.1, hg19] were among the candidate genes that were found to be associated with PMEs. These homozygous variations in siblings belong to genes with a loss-of-function intolerant (pLI) score of ≤ 0.86, expected to be detrimental by multiple computational analyses, and were heterozygous in parents. Additionally, computational analysis and the expression of RTEL1 and RTEL1-TNFRSF6B revealed that RTEL1-TNFRSF6B may modulate RTEL1 via hsa-miR-3529-3p. In the patient with the severe phenotype, a further deleterious mutation in SLC22A17 was identified. No de novo variants specific to these probands were identified in the mitochondrial genome. Conclusions: Our study is the first to report variants in KCNH8 , RTEL1 , and RTEL1-TNFRSF6B among PME cases. These genes when characterized fully may shed light on pathogenicity and have the potential to be used in the diagnosis of PME., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Sima Chaudhari et al.)

Background: Cerebral venous sinus thrombosis (CVST) presents with a wide variety of neurological symptoms in various combinations and has a high mortality rate of up to 50%. Recent advances in neuroimaging and therapeutic interventions have brought it down to 10%-20%. The study aims to identify critical prognostic factors associated with poor outcomes in patients with CVST., Materials and Methods: All cases of CVST aged >18 years from July 2015 to July 2020 who were not terminally ill and bedridden before the illness were evaluated at the entry point for various risk factors and after 30 days for outcome assessment with the modified Rankin scale (mRS). The outcome was dichotomized, applying mRS <3 as a good outcome, and analyzed with the Chi-square test or the Fischer's exact test in a bivariate analysis to identify associated variables., Results: A total of 149 subjects were studied. Glasgow Comma Scale (GCS) <9 ( P <0.001), focal neurological deficits ( P = 0.05), the presence of a mass effect ( P <0.001), and the need for decompressive hemicraniectomy ( P <0.001) were associated with poor outcomes. Age, gender, diagnostic delay, seizures at onset, papilledema, parenchymal lesions, deep sinus involvement, and multiple sinus thrombosis were not associated with a poor outcome., Conclusion: In our study, early diagnosis and treatment of CVST is associated with an overall favorable outcome even in the presence of traditional poor prognostic factors such as age, seizures at onset, deep sinus involvement, and multiple sinus involvement in the face of conventional risk factors. A large country-wide prospective study might help in elucidating the poor prognostic factors., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Annals of Indian Academy of Neurology.)

Objectives: Recent advancement in understanding neurological disorders has revealed the involvement of dysbiosis of the gut microbiota in the pathophysiology of Parkinson's disease (PD). We sequenced microbial DNA using fecal samples collected from PD cases and healthy controls (HCs) to evaluate the role of gut microbiota., Methods: Full-length bacterial 16S rRNA gene sequencing of fecal samples was performed using amplified polymerase chain reaction (PCR) products on the GridION Nanopore sequencer. Sequenced data were analyzed using web-based tools BugSeq and MicrobiomeAnalyst., Results: We found that certain bacterial families like Clostridia UCG 014, Cristensenellaceae, and Oscillospiraceae are higher in abundance, and Lachinospiracea, Coriobacteriaceae and genera associated with short-chain fatty acid production, Faecalibacterium , Fusicatenibacter , Roseburia and Blautia , are lower in abundance among PD cases when compared with the HC. Genus Akkermansia , Dialister , Bacteroides , and Lachnospiraceae NK4A136 group positively correlated with constipation in PD., Conclusion: Observations from this study support the other global research on the PD gut microbiome background and provide fresh insight into the gut microbial composition of PD patients from a south Indian population. We report a higher abundance of Clostridia UCG 014 group, previously not linked to PD., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Annals of Indian Academy of Neurology.)

Objective: To study the prevalence of cognitive impairment in survivors of intracerebral hemorrhage (ICH)., Methods: Survivors of spontaneous ICH were followed up in the neurology outpatient department when they reported for follow-up after 6 months. Neuroimaging records at the onset and at follow-up visits are studied for the location of ICH, volume of ICH, intraventricular extension, and hydrocephalus. The volume of ICH is calculated by ABC/2 method on a CT scan. All patients underwent cognitive assessment with Addenbrooke's cognitive examination ACE III and were categorized as patients having cognitive impairment (or) no cognitive impairment., Results: A total of 120 patients were studied, out of which 77 (64%) are males and 43 (36%) are females with age groups ranging from 26 to 75 years. In the study population, the mean age was found to be 62.3 years. Specifically, the mean age for males was 56.9 years, while for females it was 63.4 years. Cognitive impairment was noted in 34 of 120 patients (28%) during 6 to 12 months of examination, of which 11 of 19 were in lobar location, 21 of 94 were in sub-cortical location, and 2 of 7 were in infratentorial location., Conclusion: It was found that 28% of survivors of ICH were cognitively impaired. Hence, it is essential to assess cognition in post-ICH patients during follow-up, so that suitable adjustments can be made in their employment, and also in educating family members in providing a good quality of life., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Annals of Indian Academy of Neurology.)

Background: A high dose of statin is used to obtain an intensive lipid-lowering in stroke patients, even in patients with normal lipid levels. There are limited data on effect of dosage of statins and functional outcome in stroke patients., Objectives: To compare serum cholesterol levels with severity of stroke measured by infarct volume. To compare functional outcome measured by mRS at day 90 with the dose of statin., Materials and Methods: This retrospective observational study was conducted in KMC Hospital Manipal, India between 2016 and 2018., Result: A total of 100 consecutive patients were included in the study, out of which 60 (60.0%) were males. Hyperlipidemia was present in 65 (65.0%) patients. On comparing the serum cholesterol levels with infarct volume using MRI, patients with low volume of ≤70 ml had higher mean serum total cholesterol concentration (223.83 mg/dl), whereas patients with high volume of >70 ml had low mean cholesterol level (218.70 mg/dl). The patients were divided into those who received low dose (≤20 mg) versus high dose (≥40 mg equivalent) of Atorvastatin. On comparing the mRS values at baseline and on day 90 with the dose of statins, patients who received a higher dosage had a statistically significant fall in mRS (p-0.045) at day 90., Conclusion: It was found that serum cholesterol levels were inversely related to the stroke severity. However, a higher the dose of statins resulted in better functional outcome and survival in post-stroke patients, possibly due to its neuroprotective effect., Competing Interests: None

Introduction: Diffusion-weighted image or DWI is commonly used to provide valuable and diverse information on acute stroke in tertiary care hospitals. DWI is a sensitive and accurate method for identifying the infarct core and can expose the area of cerebral infarction within a few hours of onset. This systematic review is planned to evaluate the measurement of stroke volume on DWI and correlate it with functional outcomes (modified ranking scale)., Method: We have adhered to the PRISMA-P checklist to report this systematic review protocol. PubMed, Web of Science, Scopus, and TRIP (Turning Research into Practice) databases will be searched. Two independent reviewers will screen the records, extract data, and critically appraise the studies. A checklist for critical appraisal will be applied for data abstraction, and data extraction will be done using predictive modeling for systematic reviews. The risk of bias will be measured by the Prediction Model Risk of Bias Assessment Tool (PROBAST). The meta-analysis will be considered only if included studies have adequate data, and STATA statistical package version 13.1 will be used for performing a meta-analysis. A narrative synthesis will be performed if meta-analysis is not possible., Ethics and Dissemination: As this review will focus on secondary information, there is no ethical consideration required. We will disseminate our findings by publishing our analysis in a peer-reviewed journal., Protocol Registration: In Prospective Register of Systematic Reviews (CRD42019141840)., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Annals of Indian Academy of Neurology.)

Choreoacanthocytosis, one of the forms of neuroacanthocytosis, is caused by mutations in vacuolar protein sorting-associated protein A (VPS13A), and is often misdiagnosed with other form of neuroacanthocytosis with discrete genetic defects. The phenotypic variations among the patients with VPS13A mutations significantly obfuscates the understanding of the disease and treatment strategies. In this study, two unrelated cases were identified, exhibiting the core phenotype of neuroacanthocytosis but with considerable clinical heterogeneity. Case 1 presented with an additional Parkinsonism phenotype, whereas seizures were evident in case 2. To decipher the genetic basis, whole exome sequencing followed by validation with Sanger sequencing was performed. A known homozygous pathogenic nonsense mutation (c.799C > T; p.R267X) in exon 11 of the VPS13A gene was identified in case 1 that resulted in a truncated protein. A novel missense mutation (c.9263T > G; p.M3088R) in exon 69 of VPS13A identified in case 2 was predicted as pathogenic. In silico analysis of the p.M3088R mutation at the C-terminus of VPS13A suggests a loss of interaction with TOMM40 and may disrupt mitochondrial localization. We also observed an increase in mitochondrial DNA copy numbers in case 2. Mutation analysis revealed benign heterozygous variants in interacting partners of VPS13A such as VAPA in case 1. Our study confirmed the cases as ChAc and identified the novel homozygous variant of VPS13A (c.9263T > G; p.M3088R) within the mutation spectrum of VPS13A-associated ChAc. Furthermore, mutations in VPS13A and co-mutations in its potential interacting partner(s) might contribute to the diverse clinical manifestations of ChAc, which requires further study., (© 2023. The Author(s).)

Background and Aims: The scope of treatment in Alzheimer's Disease has widened in recent times with FDA approval of new drugs. This review looks at established treatments in AD as well as critically analyses the newer drugs available., Methods: Data in this review was gathered from PubMed; Google Scholar and MEDLINE from January-March 2023. Search words used were 'Alzheimer's Disease treatment' and 'Dementia treatment'., Results: Older time tested drugs like Acetyl Choline Receptor Inhibitors and NMDA Receptor antagonists remain the mainstay of pharmacological treatment in AD. Despite a lot of excitement about newer FDA approved drugs; we have to be cautious in their use. Aducanumab showed good reduction in CSF amyloid levels (biomarker of AD); but this did not necessarily translate into better clinical outcomes of patients., Conclusion: Despite the recent advances and approval of drugs in treatment of AD, we have to exhibit caution while prescribing these drugs. Even with a sound mechanism of action, these drugs do not always show improvement in clinical outcomes. More clinical trials are required for development of drugs in treatment of AD which explore various different mechanisms of action., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Annals of Indian Academy of Neurology.)

Background  In face of a refractory raised intracranial pressure (ICP), surgeons most commonly resort to decompressive craniectomy (DC). Procedure leaves an unprotected brain underlying the craniectomy defect and Monro-Kellie doctrine: disrupted. Different variants of hinge craniotomies (HC) have been used with clinical outcomes comparable to DC as single stage alternatives. However, both DC and every variant of HC have a limit to the achievable volume augmentation and all invariably cause a compression of the cerebral cortex and its vasculature at the craniotomy site. We believe both these limitations adversely affect the outcome. Methods  A team of neuroscientists in Indian Armed Forces Medical Services has been working for the last 9 years toward developing a novel surgical technique that can mitigate both these drawbacks. Desired procedure should take the centripetal pressure exerted by the combination of the tensile strength of the scalp (with or, without an underlying bone flap) and atmospheric pressure off the brain surface while achieving an assured augmentation of intracranial volume that can be optimized on a case-to-case basis. We call it a "step ladder expansive cranioplasty." Results  The distance of the parietal eminence was found to have increased by 10.2 mm on the operated side after expansive cranioplasty. Conclusion  From drawing board to bedside, we have made some progress toward our goal, but it is still far away from completion. More studies are required to fill in the gaps in our knowledge necessary to optimize the various parameters of the surgery. Procedure has promise to be of special role in in war and disaster scenarios., Competing Interests: Conflict of Interest None declared., (Asian Congress of Neurological Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: Guillain Barre syndrome (GBS) is a rare autoimmune neurological disorder resulting in variable clinical course and outcome. Various factors such as age, symptoms and disease form that influence the outcome of GBS have been previously studied., Aim: This study aimed at identifying factors affecting the outcomes in patients with GBS., Methods: A retrospective observational study was conducted on GBS (ICD-G61.0) patients admitted to the hospital between 2014 and 2019. Patient information on demographics, medical and medication history, laboratory parameters, electrophysiological data, type of GBS and therapy received were retrieved from medical records. Univariate and multivariate analysis were conducted to identify factors associated with outcome (improved and not improved) and calculate odds ratio (OR)., Results: A total of 212 GBS patients were included in the study, of which 67% were males and the mean age was 39.9±20.1 years. 168 (79%) patients showed improvement whereas the remaining 44(21%) did not show improvement. Patients with hypertension (OR=4.512; CI=1.309-15.556, p=0.017), alcoholics (OR=5.148; CI=1.234-21.472, p=0.025), sepsis (OR= 9.139; CI=1.102-75.760, p=0.040) and cardiac arrest (OR=17.495; CI=1.249-245.027, p=0.034) were associated with risk of no improvement. Whereas those treated with IVIgG plus Physiotherapy/Occupational therapy (OR=0.062; CI=0.016-0.242, p=0.001) and Plasmapheresis plus Physiotherapy/Occupational therapy (OR=0.007; CI=0.000-0.147, p=0.001) were associated with improvement., Conclusion: Understanding these factors help to further give a more directed and focused management to improve the condition in patients who are at risk of poor outcome. Further follow-up studies could be done to determine and manage the residual disabilities associated with GBS to improve patient's quality of life.

Competing Interests: There are no conflicts of interest.

Objectives: There is a higher prevalence of cerebral venous sinus thrombosis (CVST) in more recent times, owing to increased awareness, clinical diagnostic skills, and advancements in neuroimaging modalities. This study aimed to identify and characterize the geographical, clinical, and etiological profiles of patients with CVST that may be relevant to planning appropriate diagnostic and therapeutic strategies to improve functional recovery., Methods and Results: A retrospective observational study was carried out at a tertiary care hospital between March 2014 and October 2018. The demographics and clinical profile of the hospitalized patients were extracted from the Medical Record Division. Choropleth maps were created to present the geographic distribution of the patients with CVST admitted to our hospital. A total of 145 patients with CVST were included in the study. Etiological factors revealed striking abnormalities in red blood cells counts and serum homocysteine. Analyzing the geographical distribution of the patients with CVST showed most of the patients hailed from Central Karnataka Plateau 106 (73%). Polycythemia was most commonly seen in patients residing in the Central Karnataka Plateau 21 (62%)., Conclusion: It is inferred that large scale community-based studies to identify a genetic abnormality like a mutant erythropoietin gene should be undertaken to plan effective diagnostic, therapeutic, and preventive measures., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Annals of Indian Academy of Neurology.)

Background and Purpose: Measurement of movement quality is essential to distinguish motor recovery patterns and optimize rehabilitation strategies post-stroke. Recently, the Stroke Recovery and Rehabilitation Roundtable Taskforce (SRRR) recommended four kinetic and kinematic performance assays to measure upper extremity (UE) movements and distinguish behavioral restitution and compensation mechanisms early post-stroke. The purpose of this study is to develop and validate a prediction model to analyze the added prognostic value of performance assays over clinical variables assessed up to 1-month post stroke for predicting recovery of UE motor impairment, capacity and quality of movement (QoM) measured at 3 months post-stroke onset., Methods: In this prospective cohort study, 120 stroke survivors will be recruited within seven days post-stroke. Candidate predictors such as baseline characteristics, demographics and performance assays as per SRRR recommendations along with tonic stretch reflex threshold will be measured up to 1-month post-stroke. Upper extremity motor recovery will be evaluated in terms of motor impairment (Fugl-Meyer assessment for UE), UE capacity measured with Action Research Arm Test (ARAT) and QoM (movement smoothness in the form of peak metrics [PM]) assessed with a reach-to-grasp-to-mouth task (mimicking a drinking task) at 3 months post-stroke. Three multivariable linear regression models will be developed to predict factors responsible for the outcomes of Fugl-Meyer assessment for upper extremity (FM-UE), ARAT and movement quality. The developed models will be internally validated using a split-sample method., Discussion: This study will provide a validated prediction model inclusive of clinical and performance assays that may assist in prediction of UE motor recovery. Predicting the amount of recovery and differentiating between behavioral restitution and compensation (as reflected by the FM-UE, QoM and ARAT) would enable us in realistic goal formation and planning rehabilitation. It would also help in encouraging patients to partake in early post-stroke rehabilitation thus improving the recovery potential., (© 2022 John Wiley & Sons Ltd.)

The genome of living organisms frequently undergoes various types of modifications which are recognized and repaired by the relevant repair mechanisms. These repair pathways are increasingly being deciphered to understand the mechanisms. Base excision repair (BER) is indispensable to maintain genome stability. One of the enigmatic repair proteins of BER, Apurinic/Apyrimidinic Endonuclease 2 (APE2), like APE1, is truly multifunctional and demonstrates the independent and non-redundant function in maintaining the genome integrity. APE2 is involved in ATR-Chk1 mediated DNA damage response. It also resolves topoisomerase1 mediated cleavage complex intermediate which is formed while repairing misincorporated ribonucleotides in the absence of functional RNase H2 mediated excision repair pathway. BER participates in the demethylation pathway and the role of Arabidopsis thaliana APE2 is demonstrated in this process. Moreover, APE2 is synthetically lethal to BRCA1, BRCA2, and RNase H2, and its homolog, APE1 fails to complement the function. Hence, the role of APE2 is not just an alternate to the repair mechanisms but has implications in diverse functional pathways related to the maintenance of genome integrity. This review analyses genomic features of APE2 and delineates its enzyme function as error-prone as well as efficient and accurate repair protein based on the studies on mammalian or its homolog proteins from model systems such as Arabidopsis thaliana, Schizosaccharomyces pombe, Trypanosoma curzi, Xenopus laevis, Danio rerio, Mus musculus, and Homo sapiens., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2021 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Frontotemporal dementia (FTD) is an entity that includes a group of neurodegenerative disease with symptoms predominantly pertaining to deficits in behavior, executive function (or) language. FTD is one of the most common type of dementia before 65 years of age and is one of the most underdiagnosed dementia as most often the symptoms overlap with psychiatric manifestations. Based on the clinical features, FTD is further subdivided into behavioral variant FTD (Bv-FTD) and primary progressive dementia (PPA). We searched PubMed, MEDLINE, and Google Scholar for articles about FTD disease published in English between January 1, 1975 till 2018. We used the search terms "frontotemporal dementia," "Fronto temporal dementia-motor neuron disease," "dementia," "cognition," "behavioral variant," and "primary progressive aphasia., Competing Interests: None

Objective: To undertake a genome-wide association study (GWAS) to identify genetic variants for stroke in an Indian population., Methods: In a hospital-based case-control study, 8 teaching hospitals in India recruited 4,088 participants, including 1,609 stroke cases. Imputed genetic variants were tested for association with stroke subtypes using both single-marker and gene-based tests. Association with vascular risk factors was performed with logistic regression. Various databases were searched for replication, functional annotation, and association with related traits. Status of candidate genes previously reported in the Indian population was also checked., Results: Associations of vascular risk factors with stroke were similar to previous reports and show modifiable risk factors such as hypertension, smoking, and alcohol consumption as having the highest effect. Single-marker-based association revealed 2 loci for cardioembolic stroke (1p21 and 16q24), 2 for small vessel disease stroke (3p26 and 16p13), and 4 for hemorrhagic stroke (3q24, 5q33, 6q13, and 19q13) at p < 5 × 10 -8 . The index single nucleotide polymorphism of 1p21 is an expression quantitative trait locus ( p lowest = 1.74 × 10 -58 ) for RWDD3 involved in SUMOylation and is associated with platelet distribution width (1.15 × 10 -9 ) and 18-carbon fatty acid metabolism ( p = 7.36 × 10 -12 ). In gene-based analysis, we identified 3 genes ( SLC17A2 , FAM73A , and OR52L1 ) at p < 2.7 × 10 -6 . Eleven of 32 candidate gene loci studied in an Indian population replicated ( p < 0.05), and 21 of 32 loci identified through previous GWAS replicated according to directionality of effect., Conclusions: This GWAS of stroke in an Indian population identified novel loci and replicated previously known loci. Genetic variants in the SUMOylation pathway, which has been implicated in brain ischemia, were identified for association with stroke., (© 2021 American Academy of Neurology.)

Introduction: The use of artificial intelligence (AI) to support the diagnosis of acute ischaemic stroke (AIS) could improve patient outcomes and facilitate accurate tissue and vessel assessment. However, the evidence in published AI studies is inadequate and difficult to interpret which reduces the accountability of the diagnostic results in clinical settings. This study protocol describes a rigorous systematic review of the accuracy of AI in the diagnosis of AIS and detection of large-vessel occlusions (LVOs)., Methods and Analysis: We will perform a systematic review and meta-analysis of the performance of AI models for diagnosing AIS and detecting LVOs. We will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols guidelines. Literature searches will be conducted in eight databases. For data screening and extraction, two reviewers will use a modified Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies checklist. We will assess the included studies using the Quality Assessment of Diagnostic Accuracy Studies guidelines. We will conduct a meta-analysis if sufficient data are available. We will use hierarchical summary receiver operating characteristic curves to estimate the summary operating points, including the pooled sensitivity and specificity, with 95% CIs, if pooling is appropriate. Furthermore, if sufficient data are available, we will use Grading of Recommendations, Assessment, Development and Evaluations profiler software to summarise the main findings of the systematic review, as a summary of results., Ethics and Dissemination: There are no ethical considerations associated with this study protocol, as the systematic review focuses on the examination of secondary data. The systematic review results will be used to report on the accuracy, completeness and standard procedures of the included studies. We will disseminate our findings by publishing our analysis in a peer-reviewed journal and, if required, we will communicate with the stakeholders of the studies and bibliographic databases., Prospero Registration Number: CRD42020179652., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The objective of this study was to describe the socioeconomic consequences of drug-resistant epilepsy (DRE)., Methods: This study comprised 132 (equal males and females) consecutive patients aged ≥18 years, who fulfilled the International League Against Epilepsy (ILAE) definition for DRE, prospectively seen in a tertiary care center in South India. We used a structured questionnaire to gather relevant information., Results: The mean age was 31 (range 18-70) years. Mean age of onset of epilepsy was 17 years and mean duration of epilepsy 14 years. The most common epilepsy type and etiology were focal epilepsy and gliotic lesions secondary to perinatal insults, respectively. The average out of the pocket expenditure on antiseizure drugs annually amounted to 19% of the gross national product (GNP)/capita, which was borne by family members in more than two-thirds of the subjects. Almost 60% reported epilepsy having affected their education, 40% their employment, and 90% their marital prospects. Female patients were less often employed outside their homes and had more marital problems compared with males., Conclusions: In addition to high seizure burden, DRE adversely affects the pursuit of higher education, employment, and marriage. Besides the direct cost of epilepsy, these issues augment both the patient and the caregiver's liability. Socioeconomic consequences of DRE are widely prevalent in developing countries, and this study highlights the need to address them., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: After a stroke, 55% of survivors do not regain the ability to completely use their arm in daily life functioning. Currently, evidence-based guidelines recommend functional training for improving the affected hand after stroke. However, promoting an optimal quantity and quality of functional training is influenced by personal and environmental contextual factors. Studies that comprehensively target multiple factors regulating arm use are limited. This study compares the effects of functional training to multifactorial context-enhancing functional training program for improving functional arm use and recovery after stroke., Methods and Analysis: This is a protocol for an observer-blinded, two parallel groups, randomised controlled trial. A total of 126 community-dwelling subacute and chronic stroke survivors will be included in the study. A tailor-made multifactorial context-enhancing intervention-incorporating education, environmental enrichment and behaviour change techniques to reinforce functional training will be provided to the experimental group. The functional training group will be provided with functional exercises. The intervention will be delivered for 2 months. The primary outcomes of functional arm use and recovery will be measured using Motor Activity Log, Goal Attainment Scale and Rating of Everyday Arm-use in the Community and Home scale. The secondary outcomes of arm motor impairment and function will be measured using Fugl-Meyer upper limb score, Action Research Arm Test, ABILHAND questionnaire and Stroke Impact Scale. These will be measured at three points in time: before, after 2 months and after 1-month follow-up. The outcome measures will be analysed using one-way analysis of variance and regression analysis will be performed to identify factors limiting optimal task practice., Ethics and Dissemination: The study has been approved by the Institutional Ethics Committee of Kasturba Hospital, Manipal, India. Participants will sign a written informed consent prior to participation. The results will be published on completion of the trial and communicated to community-dwelling stroke survivors., Trial Registration Number: CTRI/2017/10/010108., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: There are no conflicts of interest.

Background: Sleep apnea is increasingly being recognized as 1 of the important, modifiable risk factors of stroke and cardiovascular diseases. Sleep apnea is thought to impair the functional recovery following stroke. Hence, we evaluated the patients with acute ischemic stroke for prevalence of sleep apnea and compared the functional outcomes of patients with and without sleep apnea, at 3rd month of acute ischemic stroke., Method: This study was conducted in Kasturba Medical College (KMC) hospital, Manipal, India, between May 2015 and August 2016. We included 102 consecutive patients of acute ischemic stroke with hemiplegic upper limb power of Medical Research Council (MRC) 3 or less. Sleep apnea was diagnosed in these patients using the sleep disordered Questionnaire, Berlin Questionnaire, and Epworth sleepiness scale. Functional outcome was measured using Barthel score on day 7 and at 3rd month following the onset of stroke., Result: Out of 102 patients, sleep apnea was present in 31 (30.6%) patients, more in males (67.7%) and elderly. Hypertension was present in 66.6% of patients with sleep apnea. NIHSS score at admission did not differ between the 2 groups. At 3rd month, the Barthel score calculated was better among patient with no apnea, but this was not statistically significant (P = .119). When mean Barthel score at baseline and 3rd month was calculated using repeated measure Analysis of Variance (ANOVA) between the 2 groups, gain in functional independence in no apnea group was statistically significant (P < .001)., Conclusion: Sleep-disordered breathing is an independent risk factor for stroke, and sleep apnea is also associated with other known stroke risk factors like hypertension. In acute ischemic stroke, sleep apnea has a negative impact on functional recovery. Sleep apnea is amenable to treatment and should be considered in patients with acute ischemic stroke to improve the chance of recovery, and to reduce the risk of recurrence., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

WHAT IS THE ROLE OF DUAL ANTIPLATELET THERAPY AFTER HIGH RISK TRANSIENT ISCHAEMIC ATTACK OR MINOR STROKE? SPECIFICALLY, DOES DUAL ANTIPLATELET THERAPY WITH A COMBINATION OF ASPIRIN AND CLOPIDOGREL LEAD TO A GREATER REDUCTION IN RECURRENT STROKE AND DEATH OVER THE USE OF ASPIRIN ALONE WHEN GIVEN IN THE FIRST 24 HOURS AFTER A HIGH RISK TRANSIENT ISCHAEMIC ATTACK OR MINOR ISCHAEMIC STROKE? AN EXPERT PANEL PRODUCED A STRONG RECOMMENDATION FOR INITIATING DUAL ANTIPLATELET THERAPY WITHIN 24 HOURS OF THE ONSET OF SYMPTOMS, AND FOR CONTINUING IT FOR 10-21 DAYS CURRENT PRACTICE IS TYPICALLY TO USE A SINGLE DRUG., Competing Interests: Competing interests: All authors have completed the BMJ Rapid Recommendations interests disclosure form, and a description of all disclosures is reported in appendix 1 on bmj.com. As with all BMJ Rapid Recommendations, the executive team and The BMJ judged that no panel member had any financial conflict of interest. Professional and academic interests are minimised as much as possible, while maintaining necessary expertise on the panel to make fully informed decisions., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: The inability to propel a bolus of food successfully from the posterior part of the oral cavity to the oropharynx is defined as transfer dysphagia. The present case series describes the varied presentation of transfer dysphagia due to focal dystonia and highlights the importance of early detection by following up on strong suspicions., Methods: We describe seven cases of transfer dysphagia due to focal dystonia. Transfer dysphagia as a form of focal dystonia may appear as the sole presenting complaint or may present with other forms of focal dystonia., Results: Four out of seven patients had pure transfer dysphagia and had previously been treated for functional dysphagia. A high index of suspicion, barium swallow including videofluoroscopy, associated dystonia in other parts of the body and response to drug therapy with trihexyphenidyl/tetrabenazine helped to confirm the diagnosis., Conclusion: Awareness of these clinical presentations among neurologists and non-neurologists can facilitate an early diagnosis and prevent unnecessary investigations.

Background: Haematoma expansion due to raised blood pressure in spontaneous intracerebral haemorrhage may determine outcome. The aim of this study was to determine safety and efficacy of lowering blood pressure in acute spontaneous intracerebral haemorrhage., Methods: This open label, multicentric trial randomized patients ≥18 years with spontaneous intracerebral haemorrhage with no secondary cause within 72 h of onset to tight BP control arm where treatment was initiated if mean arterial pressure (MAP) was ≥115 mm of Hg and conventional BP control arm where treatment was initiated if MAP was ≥130 mm of Hg. The MAP was maintained in the respective arm for another 72 h after which both arms had MAP below 115 mm of Hg. Primary outcome was modified Rankin Scale at 90 days., Results: 118 patients, 59 in each arm were included. Follow up was available for all. Baseline characteristics were similar. At 90 days there was no significant difference between median mRS between the two arms. Odds Ratio for "poor outcome" (mRS 3-6) in the tight control arm (safety of the intervention) against "good outcome" (mRS 0-2) was not significant (OR 0.70 [95% CI 0.34-1.47] p  = 0.35). Efficacy of the intervention in the form of Odds Ratio for "good outcome" in the tight control arm was not significant (OR 1.43 [95% CI 0.68-2.99], p  = 0.35)., Conclusion: In patients with spontaneous intracerebral haemorrhage who present within 72 h of the onset of symptoms, MAP can be safely lowered if it crosses 115 mm of Hg but it does not improve clinical outcome.

Telephonic Barthel Index (BI) assessment is less time-consuming and more feasible than a face-to-face interview. The aim of this study was to test the validity as well as reliability of the BI administered by telephone in comparison with face-to-face assessment in a multi-centric study. The study was conducted during the course of a randomized controlled trial in which 120 patients with subacute strokes from five teaching hospitals from different parts of India were recruited. Central telephonic follow-up and face-to-face assessment of BI and modified Rankin Scale (mRS) at 3 and 6 months were done by trained and certified blinded researchers. Kappa or weighted kappa (wK) was estimated. Sensitivity and specificity at various cutoff levels of telephonic BI were calculated. Concurrent validity of the telephonic BI was assessed by correlating it with the mRS and National Institutes of Health Stroke Scales (NIHSS) at 3 and 6 months. We observed high sensitivity and specificity at various cutoff levels of BI. Moderate to substantial agreement was observed between the two methods at 6 months wK 0.72 (95% CI 0.70-0.77). Item-wise and center-wise kappa also reflected substantial agreement. The study shows that telephonic assessment of activities of daily living with the BI in moderate to severely disabled stroke patients is valid and reliable compared to face-to-face assessment. Our study shows that telephonic assessment requires smaller sample size compared to face-to-face assessment of BI.

Background Patients with cerebral small vessel disease may suffer from varying levels of cognitive deficit and may progress on to vascular dementia. The extent of involvement, as seen on conventional magnetic resonance (MR) measures, correlates poorly with the level of cognitive decline. The purpose of this study was to investigate the utility of diffusion tensor imaging (DTI) as a marker for white matter damage in small vessel disease and to assess its correlation with cognitive function. Methods Thirty consecutive patients with cerebral small vessel disease underwent conventional MR imaging, DTI, and neuropsychological assessment. Results On tractographic analysis, fractional anisotropy was significantly reduced while mean diffusivity significantly increased in several white matter tracts. The alteration in DTI indices correlated well with cognitive function. No significant correlation was identified between T2 lesion load and cognitive performance. Conclusions Tractographic analysis of white matter integrity is a useful measure of disease severity and correlates well with cognitive function. It may have a significant potential in monitoring disease progression and may serve as a surrogate marker for treatment trials.

Aim: Neurocognitive dysfunction continues to be the bane of open heart surgery despite vast improvements in surgical, anesthetic, and postoperative management. This observational cohort study was carried out to evaluate the efficacy of intraoperative CO2 insufflation by the field flooding technique in reducing postoperative neurocognitive dysfunction., Methods: Three hundred randomly selected patients undergoing open heart surgery were observed: 150 (group A) were exposed to CO2 insufflation, and the other 150 (group B) were not exposed to CO2. Anesthetic, cardiopulmonary bypass, and myocardial protection techniques were standardized and similar in both groups. Neurocognitive function tests were performed preoperatively, 1 week postoperatively, and after 1 month., Results: The analysis revealed that neurocognitive dysfunction occurred in 8 of 150 patients in group A (incidence p1 = 0.053) and 27 of 150 in group B (incidence p2 = 0.18). The relative risk of neurocognitive dysfunction was 0.30 (p = 0.001, 95% confidence interval 0.14-0.63), implying that CO2 insufflation is protective against neurocognitive dysfunction. The risk difference was 0.13 (p2-p1); this implies that 13% of patients can be prevented from developing neurocognitive dysfunction if exposed to CO2., Conclusion: This study confirms the known advantage of the relatively underutilized practice of CO2 insufflation. We recommend that CO2 insufflation be performed in all open heart surgery cases to bring down the incidence of neurocognitive dysfunction. This technique is simple to use without any major paraphernalia or additional cost., (© The Author(s) 2015.)

Background: Several studies reported prognostic value of biomarker in intracerebral hemorrhagic (ICH) but they are either preliminary observation or inadequately powered to analyse independent contribution of biomarkers over and above clinical and neuroimaging data., Objective: To examine whether the biomarker can significantly add to the predictive accuracy of prognosis of ICH., Method/design: In a multi-centric prospective cohort study, 1020 patients with ICH within 72 hours of onset are being recruited. After obtaining written informed consent from patients/proxy, venous blood sample (10 ml) is being collected and analysed for C-reactive protein (CRP) level, S100B, Glial fibrillary acidic protein (GFAP), Troponin, change in leukocyte count and Copeptin levels. The patients are telephonically followed using stroke scales (Barthel Index and modified Rankin Scale) at 3, 6, 12 months and 2 years after the recruitment., Discussion: This protocol will aim at predicting the short term or long term prognosis with the use of clinical, neuroimaging and biomarkers in order to help clinician to stratify patients for early referral or intervention.

Background and Purpose: Pilot studies have suggested benefit from intravenous administration of bone marrow mononuclear stem cells (BMSCs) in stroke. We explored the efficacy and safety of autologous BMSCs in subacute ischemic stroke., Methods: This was a phase II, multicenter, parallel group, randomized trial with blinded outcome assessment that included 120 patients. Patients with subacute ischemic stroke were randomly assigned to the arm that received intravenous infusion of autologous BMSCs or to control arm. Coprimary clinical efficacy outcomes were Barthel Index score and modified Rankin scale at day 180. Secondary outcomes were change in infarct volume, National Institute of Health Stroke Scale (NIHSS) at day 90 and 180. Main safety outcomes were adverse events, any new area of (18)fluorodeoxyglucose positron emission tomography uptake in any body part over 365 days., Results: Fifty-eight patients received a mean of 280.75 million BMSCs at median of 18.5 days after stroke onset. There was no significant difference between BMSCs arm and control arm in the Barthel Index score (63.1 versus 63.6; P=0.92), modified Rankin scale shift analysis (P=0.53) or score >3 (47.5% versus 49.2%; P=0.85), NIHSS score (6.3 versus 7.0; P=0.53), change in infarct volume (-11.1 versus -7.36; P=0.63) at day 180. Adverse events were also similar in the 2 arms, and no patient showed any new area of (18)fluorodeoxyglucose uptake., Conclusions: With the methods used, results of this hitherto first randomized controlled trial indicate that intravenous infusion of BMSCs is safe, but there is no beneficial effect of treatment on stroke outcome., Clinical Trial Registration: URLs: http://ctri.nic.in/Clinicaltrials and http://www.clinicaltrials.gov. Unique identifiers: CTRI-ROVCTRI/2008/091/0004 and NCT0150177., (© 2014 American Heart Association, Inc.)

Stroke is a leading cause of death and disability in the world. Identifying the genes underlying stroke risk may help us to improve our understanding of the mechanisms that cause stroke and also identify novel therapeutic targets. To have sufficient power to disentangle the genetic component of stroke, large-scale highly phenotyped DNA repositories are necessary. The BRAINS (Bio-repository of DNA in stroke) study aims to recruit subjects with all subtypes of stroke as well as controls from UK, India, Sri Lanka and Qatar. BRAINS-UK will include 1500 stroke patients of European ancestry as well as British South Asians. BRAINS-South Asia aims to recruit 3000 stroke subjects and 3000 controls from across India and Sri Lanka. BRAINS-Middle East aims to enrol 1500 stroke patients from Qatar. The controls for BRAINS-Middle East will be recruited from a population-based Qatari Biobank. With the addition of new recruitment centres in India and Qatar, we present an updated version of the BRAINS study protocol. This is the first international DNA biobank for stroke patients and controls from the Middle East. By investigating the influence of genetic factors on stroke risk in European, South Asian and Middle Eastern populations, BRAINS has the potential to improve our understanding of genetic differences between these groups and may lead to new population-specific therapeutic targets.

Background: Guillain-Barré syndrome is the most common cause of acute neuromuscular paralysis and is considered a post-infectious disease., Methods: Twenty patients with Guillain-Barré syndrome admitted to the Neurosciences Centre at the All India Institute of Medical Sciences from November 1997 to August 1998 were investigated for evidence of antecedent infections. This case-control study included 2 controls for each patient, one a household control and the other an age- and sex-matched hospital control suffering from a neurological illness other than Guillain-Barré syndrome. Evidence of recent Campylobacter jejuni infection was investigated by culture and serology, and for Mycoplasma pneumoniae by serology., Results: There was evidence of recent C. jejuni infection in 35% of the patients compared with 25% of household controls and none of the hospital controls. M. pneumoniae infection was seen in 50% of patients compared with 25% of household controls and 15% of hospital controls. About one-third of the patients (30%) had evidence of both infections. The association of both infections in patients was found to be statistically significant as compared to hospital controls., Conclusion: C. jejuni and M. pneumoniae may be important antecedent illnesses in patients with Guillain-Barré syndrome in India.

A soldier presented in Jan 2002 with features of proximal myopathy and diplopia. Clinically he had features of myasthenia gravis, which was confirmed by significantly positive neostigmine test, decremental response on electrophysiological study and raised acetylcholine receptor antibody titres. He also tested positive for HIV during evaluation of a cervical lymph node detected incidentally. He responded well to neostigmine and has remained asymptomatic on follow up.

Purpose: To evaluate and delineate the characteristics of cerebral toxoplasmosis lesions using a combination of magnetic resonance (MR) spectroscopy, diffusion, and perfusion studies., Material and Methods: A total of 8 patients with 23 lesions were evaluated on a 1.5-T MR system. Diffusion-weighted imaging (DWI) was performed with three 'b' values of 50, 500, and 1000 s/mm2, and the apparent diffusion coefficient maps were calculated. The diffusion-weighted appearances and the T2-weighted MR appearances of the lesions were compared. MR spectroscopy was performed using the point-resolved single-voxel technique with two TE values of 135 ms and 270 ms. Perfusion studies were carried out using the dynamic contrast-enhanced technique, and the relative cerebral blood volume maps were qualitatively and quantitatively analyzed., Results: DWI revealed the majority of the lesions as having increased diffusion within their necrotic centers, with the ADC ranging from 0.5 to 3.01 (mean +/- SD: 1.49 +/- 0.7). All the lesions revealed a predominant lipid peak on MR spectroscopy and were extremely hypovascular on perfusion MR studies., Conclusion: MR diffusion, spectroscopy, and perfusion studies help in characterizing toxoplasmosis lesions and, in most cases, can be used in combination to help establish the diagnosis of toxoplasmosis.