Critical Prognostic Factors in Cerebral Venous Sinus Thrombosis: An Observational Study.

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.

Effects of Serum Cholesterol on Severity of Stroke and Dosage of Statins on Functional Outcome in Acute Ischemic Stroke.

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.

Prognosticating Acute Ischemic Stroke and Estimating the Feasibility of Mapping Stroke Volume to the Functional Outcomes Using Diffusion-Weighted Images: A Systematic Review Protocol.

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).

Alzheimer's Disease: Treatment Today and Tomorrow.

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.

Step Ladder Expansive Cranioplasty: A Novel Perspective in Cranial Volume Augmentation Surgery.

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.

Exome sequencing of choreoacanthocytosis reveals novel mutations in VPS13A and co-mutation in modifier gene(s).

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.

Dysbiosis of the Beneficial Gut Bacteria in Patients with Parkinson's Disease from India.

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.

Prevalence of Cognitive Impairment and Dementia After Intracerebral Hemorrhage.

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.

Relevance of Geographical and Biochemical Factors in Causation of Cerebral Venous Sinus Thrombosis: An Observational Analytical Study.

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.

Identification of factors affecting outcomes in patients with Guillain Barre syndrome.

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.

Exploring the multifactorial aspects of Gut Microbiome in Parkinson's Disease.

Advanced research in health science has broadened our view in approaching and understanding the pathophysiology of diseases and has also revolutionised diagnosis and treatment. Ever since the establishment of Braak's hypothesis in the propagation of alpha-synuclein from the distant olfactory and enteric nervous system towards the brain in Parkinson's Disease (PD), studies have explored and revealed the involvement of altered gut microbiota in PD. This review recapitulates the gut microbiome associated with PD severity, duration, motor and non-motor symptoms, and antiparkinsonian treatment from recent literature. Gut microbial signatures in PD are potential predictors of the disease and are speculated to be used in early diagnosis and treatment. In brief, the review also emphasises on implications of the prebiotic, probiotic, faecal microbiota transplantation, and dietary interventions as alternative treatments in modulating the disease symptoms in PD.

Predicting post-stroke motor recovery of upper extremity using clinical variables and performance assays: A prospective cohort study protocol.

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.

Apurinic/Apyrimidinic Endonuclease 2 (APE2): An ancillary enzyme for contextual base excision repair mechanisms to preserve genome stability.

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.

INSTRuCT: Protocol, Infrastructure, and Governance.

Background and Purpose: Very few large scale multicentric stroke clinical trials have been done in India. The Indian Council of Medical Research funded INSTRuCT (Indian Stroke Clinical Trial Network) as a task force project with the objectives to establish a state-of-the-art stroke clinical trial network and to conduct pharmacological and nonpharmacological stroke clinical trials relevant to the nation and globally. The purpose of the article is to enumerate the structure of multicentric stroke network, with emphasis on its scope, challenges and expectations in India. Methods: Multiple expert group meetings were conducted by Indian Council of Medical Research to understand the scope of network to perform stroke clinical trials in the country. Established stroke centers with annual volume of 200 patients with stroke with prior experience of conducting clinical trials were included. Central coordinating center, standard operating procedures, data and safety monitoring board were formed. Discussion: In first phase, 2 trials were initiated namely, SPRINT (Secondary Prevention by Structured Semi-Interactive Stroke Prevention Package in India) and Ayurveda treatment in the rehabilitation of patients with ischemic stroke in India (RESTORE [Rehabilitation of Ischemic stroke Patients in India: A Randomized controlled trial]). In second phase, 4 trials have been approved. SPRINT trial was the first to be initiated. SPRINT trial randomized first patient on April 28, 2018; recruited 3048 patients with an average of 128.5 per month so far. The first follow-up was completed on May 27, 2019. RESTORE trial randomized first patient on May 22, 2019; recruited 49 patients with an average of 3.7 per month so far. The first follow-up was completed on August 30, 2019. Conclusions: In next 5 years, INSTRuCT will be able to complete high-quality large scale stroke trials which are relevant globally. REGISTRATION: URL: http://www.ctri.nic.in/; Unique Identifier: CTRI/2017/05/008507.

Association of SUMOylation Pathway Genes With Stroke in a Genome-Wide Association Study in India.

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.

Systematic review protocol to assess artificial intelligence diagnostic accuracy performance in detecting acute ischaemic stroke and large-vessel occlusions on CT and MR medical imaging.

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.

Socioeconomic consequences of drug-resistant epilepsy in an adult cohort from southern India.

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.

Effectiveness of a multifactorial context-enhancing functional therapy to promote functional arm use and recovery of stroke survivors: study protocol for a clinical trial.

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.