IMPETUS Stroke: Assessment of hospital infrastructure and workflow for implementation of uniform stroke care pathway in India.

BACKGROUND: India accounts for 13.3% of global disability-adjusted life years (DALYs) lost due to stroke with a relatively younger age of onset compared to the Western population. In India's public healthcare system, many stroke patients seek care at tertiary-level government-funded medical colleges where an optimal level of stroke care is expected. However, there are no studies from India that have assessed the quality of stroke care, including infrastructure, imaging facilities, or the availability of stroke care units in medical colleges. AIM: This study aimed to understand the existing protocols and management of acute stroke care across 22 medical colleges in India, as part of the baseline assessment of the ongoing IMPETUS stroke study. METHODS: A semi-structured quantitative pre-tested questionnaire, developed based on review of literature and expert discussion, was mailed to 22 participating sites of the IMPETUS stroke study. The questionnaire assessed comprehensively all components of stroke care, including human resources, emergency system, in-hospital care, and secondary prevention. A descriptive analysis of their status was undertaken. RESULTS: In the emergency services, limited stroke helpline numbers, 3/22 (14%); prenotification system, 5/22 (23%); and stroke-trained physicians were available, 6/22 (27%). One-third of hospitals did not have on-call neurologists. Although non-contrast computed tomography (NCCT) was always available, 39% of hospitals were not doing computed tomography (CT) angiography and 13/22 (59%) were not doing magnetic resonance imaging (MRI) after routine working hours. Intravenous thrombolysis was being done in 20/22 (91%) hospitals, but 36% of hospitals did not provide it free of cost. Endovascular therapy was available only in 6/22 (27%) hospitals. The study highlighted the scarcity of multidisciplinary stroke teams, 8/22 (36%), and stroke units, 7/22 (32%). Lifesaving surgeries like hematoma evacuation, 11/22 (50%), and decompressive craniectomy, 9/22 (41%), were performed in limited numbers. The availability of occupational therapists, speech therapists, and cognitive rehabilitation was minimal. CONCLUSION: This study highlighted the current status of acute stroke management in publicly funded tertiary care hospitals. Lack of prenotification, limited number of stroke-trained physicians and neurosurgeons, relatively lesser provision of free thrombolytic agents, limited stroke units, and lack of rehabilitation services are areas needing urgent attention by policymakers and creation of sustainable education models for uniform stroke care by medical professionals across the country.

Parent's Perspective of Problems Faced during the COVID-19 Pandemic Lockdown on the Care of Children with Epilepsy: A Qualitative Study.

Background: COVID-19 has significantly impacted the care of children with chronic illness. There is a paucity of data on issues faced by parents of children with epilepsy (CWE) in an Indian setup. Objectives: The objective was to describe the parental perspective of the problems faced by them on the care of their CWE during the first wave of the COVID-19 pandemic. Materials and Methods: Parents of CWE who physically visited the clinic for their follow-up visit were asked to narrate their experiences about the problems they faced during the first lockdown due to COVID-19. The narratives were audio recorded, and transcripts were analyzed using thematic analysis to arrive at broad themes. Results: Four broad themes were identified: transport-related issues, medication-related issues, issues related to doctor consultation, and diagnostic delay. Limited transportation facilities, lack of appropriate social distancing norms in public transport and outpatient units, rigorous frisking by personnel during travel, fear of viral transmission during outpatient visits, nonavailability of antiseizure medications (ASMs) in local markets, lack of discounts by pharmacy, change of brands of ASM, and inability to undergo scheduled diagnostic investigations were some of the major issues raised by parents of CWE. Conclusion: Parents of CWE had trouble in transport to the hospital, inadequate access to ASMs, difficulties in doctor consultation, and delays in diagnostic investigations during the first COVID-19 pandemic lockdown.

The Distribution of Lifestyle Risk Factors Among Patients with Stroke in the Indian Setting: Systematic Review and Meta-Analysis.

Background: The burden of stroke is increasing in India, but there is limited understanding of the distribution of reported risk factors in the Indian setting. It is vital to generate robust data on these modifiable risk factors to scale up appropriate strategies for the prevention of cerebrovascular diseases in this setting. Summary: The objective of this study is to estimate the overall proportion of life style risk factors of patients with stroke in the Indian setting. We searched PubMed and Google Scholar and relevant studies published till February 2022 were included. The risk of bias assessment was considered for the study selection criterion in the meta-analysis. The publication bias was evaluated by funnel plots and Egger's test. We identified 61 studies in the systematic review and after quality assessment, 36 studies were included for meta-analysis. Random effect model was used due to the significant inconsistency among the included studies (I2 > 97%). The mean age of the participants was 53.84±9.3 years and patients with stroke were predominantly males (64%). Hypertension (56.69%; 95% CI: - 48.45 - 64.58), obesity (36.61%; 95% CI: - 19.31 - 58.23), dyslipidemia (30.6%; 95% CI: - 22 - 40.81) and diabetes mellitus (23.8%; 95% CI: - 18.79 - 29.83) are the leading intermediate conditions associated with stroke. The Physical inactivity - 29.9% (95% CI: - 22.9 - 37.1), history of tobacco use (28.59 %; 95% CI: - 22.22 - 32.94) and alcohol use (28.15 %; 95% CI: - 20.49 - 37.33) were reported as the behavioral risk factors for stroke in this setting. Key Messages: The current meta-analysis provides robust estimates of the life style related risk-factor of stroke in India based on the observational studies conducted from 1994 to 2019. Estimating the pooled analysis of stroke risk factors is crucial to predict the imposed burden of the illness and ascertain the treatment and prevention strategies for controlling the modifiable risk factors in this setting.

Modified Atkins Diet vs. Ketogenic Diet in the Management of Children with Epileptic Spasms Refractory to First Line Treatment: An Open Labelled, Randomized Controlled Trial.

OBJECTIVE: To compare the efficacy and tolerability of modified Atkins diet (mAD) and ketogenic diet (KD) among children aged 9 mo to 3 y with epileptic spasms refractory to the first line treatment. METHODS: An open labelled, randomized controlled trial with parallel group assignment was conducted among children aged 9 mo to 3 y with epileptic spasms refractory to the first line treatment. They were randomized to either receive the mAD along with conventional anti-seizure medications (n = 20) or KD with conventional anti-seizure medications (n = 20). Primary outcome measure was proportion of children who achieved "spasm freedom" at 4 wk and 12 wk. Secondary outcome measures were proportion of children who achieved >50% and >90% reduction in spasms at 4 wk and 12 wk, nature and proportion of the adverse effects as per parental reports. RESULTS: Proportion of children achieving spasm freedom [mAD {4 (20%)} vs. KD {3 (15%)}: OR (95% CI) 1.42 (0.27-7.34); P = 0.67], >50% spasm reduction [mAD {3 (15%)} vs. KD {5 (25%)}: OR (95% CI) 0.53 (0.11-2.59); P = 0.63] and >90% spasm reduction [mAD {4 (20%)} vs. KD {2 (10%)}: OR (95% CI) 2.25 (0.36-13.97); P = 0.41] was comparable between the two groups at 12 wk. The diet was well tolerated in both the groups with vomiting and constipation being the most common reported adverse effect. CONCLUSIONS: mAD is an effective alternative to KD in the management of children with epileptic spasms refractory to first line treatment. However, further studies with adequately powered sample size and longer follow-up are required. TRIAL REGISTRATION: CTRI/2020/03/023791.

Gabapentin as Add-on Therapy to Trihexyphenidyl in Children with Dyskinetic Cerebral Palsy: A Randomized, Controlled Trial.

OBJECTIVE: To compare the efficacy of gabapentin as add-on therapy to trihexyphenidyl in the treatment of children with dyskinetic cerebral palsy (CP). METHODS: An open-labelled, randomized, controlled trial was conducted among children aged 3-9 y with dyskinetic CP [Gross Motor Functional Classification System (GMFCS) 4-5]. Participants were assigned into two groups: gabapentin with trihexyphenidyl (n = 30) and trihexyphenidyl alone (n = 30). Dyskinesia Impairment Scale (DIS), Dystonia Severity Assessment Plan (DSAP), and International Classification of Functioning, Disability, and Health-Children and Youth Version (ICF-CY) were measured at baseline, 4 and 12 wk. RESULTS: There was significant reduction in baseline dystonia in both the groups (DIS: p < 0.001; DSAP: p = 0.007; ICF-CY: p < 0.001) but when data were compared between the groups, there was no significant difference in the severity of dystonia at 4 wk and at 12 wk (DIS: p = 0.09; DSAP: p = 0.49; ICF-CY: p = 0.25). Constipation was the commonest side effect observed in both the groups [3 (11.5%) vs. 4 (14.3%)]. CONCLUSION: Trihexyphenidyl alone is as effective as combination of gabapentin with trihexyphenidyl in decreasing the severity of dystonia at 12 wk. Hence, there is no added benefit of gabapentin as add-on therapy for dystonia among children with dyskinetic CP. TRIAL REGISTRATION: CTRI/2019/04/018603.

Fourteen Days vs 28 Days of Albendazole Therapy for Neurocysticercosis in Children: An Open Label Randomized Controlled Trial.

BACKGROUND: There is a paucity of literature to support 14-days albendazole therapy for neurocysticercosis (NCC). OBJECTIVE: To compare the efficacy of 14-day and 28-day albendazole therapy in the management of children with newly diagnosed active NCC. STUDY DESIGN: Open-labelled randomized controlled trial. PARTICIPANTS: Children aged 1-14 years with newly diagnosed active neurocysticercosis. INTERVENTION: Albendazole (15 mg/kg/day) for either 14 days or 28 days. OUTCOME: The primary outcome measure was proportion of children with radiological resolution of active lesion at 6-month follow up. Secondary outcome measures were proportion of children with seizure recurrence, duration to seizure recurrence and calcification on follow up imaging. RESULTS: 65 children with newly diagnosed NCC were rando-mized to receive albendazole therapy for 14 days (n=32) or 28 days (n=33). The proportion of children with complete resolution was comparable between the two groups [6 (18.8%) vs. 9 (27.3%); OR (95%CI):0.61 (0.19 to 1.98); P=0.56]. Similarly, proportion of children with seizure recurrence [5(15.6%) vs 2(6.1%); OR (95%CI): 2.87(0.51-16.0); P=0.26] and proportion of children with calcification on follow-up imaging [26(81.2%) vs 23(69.7%); OR (95%CI): 1.88 (0.59-5.99); P=0.39] were also comparable. There were no major side-effects noted during the study. CONCLUSION: 14-day treatment with albendazole therapy is as effective as 28-day treatment in achieving radiological resolution at six-month follow up. However, high rate of calcification in both the groups indicates need for further evaluation with an adequately powered study and longer follow up.

Spinocerebellar Ataxia 12 Patients have better Quality of Life than Spinocerebellar Ataxia 1 and 2.

Background: Spinocerebellar ataxia is a neurodegenerative disease. Information on comparative assessment of quality of life (QoL) among SCAs, particularly SCA 12, is scarce. We aimed to compare health-related QoL in SCA 1, 2 and 12. Methods: We conducted a cross-sectional study among individuals with genetically-confirmed SCAs. Ataxia severity was assessed using Brief Ataxia Rating Scale (BARS), independence in activities of daily living (ADL) using Katz index (Katz ADL) and depression using Beck's Depression Inventory-II (BDI-II). QoL was assessed via Short Form Health Survey version 2.0 (SF-36). Results: We enrolled 89 individuals (SCA1 = 17, SCA2 = 43, SCA12 = 29; 56% males). Mean age at onset (41.0 ± 11.6 for SCA12 versus 24.9 + 7.0 for SCA1 and 28.8 ± 9.8 years for SCA2) was significantly higher among SCA12. SCA12 had lower BARS (mean score 4.1 ± 4.5 versus 10.6 ± 4.6 for SCA1 and 12.5 ± 4.5 for SCA2). SCA12 scored better on all SF-36 subdomains including Physical (PCS) and Mental Component Summary (MCS) scores. PCS score amongst SCA12 was 44.4 ± 9.0 versus 30.4 ± 9.1 for SCA1 and 33.3 ± 8.9 for SCA2. MCS score for SCA12 was 51.4 ± 11.4 versus 41.8 ± 11.5 for SCA1 and 41.8 ± 11.2 for SCA2. SCA12 had lower mean BDI scores (5.0 ± 6.0) versus SCA1 (9.5 ± 11.6) and SCA2 (10.9 ± 10.3). BARS and BDI emerged as significant predictors of most SF-36 subdomains. Conclusions: Our study suggests that despite older age and comparable disease duration, SCA12 patients experience better QoL, less severe depression and ataxia versus SCA1 and SCA2. Severity of ataxia and depression are significant predictors of QoL among the three SCA types.

The Quality of Life of Stroke Survivors in the Indian Setting: A Systematic Review and Meta-Analysis.

Background: The significant burden of stroke on the mortality rates of developing countries, including India, is well-documented in the literature. However, robust data regarding the aggregates of evidence on the quality of life (QOL) of stroke survivors is limited. Objective: To gather relevant information for policymakers on the QOL of stroke survivors based on observational studies conducted in the Indian setting. Methods: We searched PubMed, Scopus, and Google Scholar for studies conducted in the Indian setting. The methodological quality of each study was scored, and data were extracted from the published reports. The risk of bias assessment was conducted based on the JBI Critical Appraisal Checklist criteria. The relevant data regarding QOL were analyzed by a random effects model using R software. Results: 16 studies were included in the systematic review in which the majority of the studies recruited study participants in the hospital-based setting with an average duration of 3-6 months following the stroke episode. Our findings suggest that the pooled mean quality of life in the four dimensions of the World Health Organization Quality of Life instrument (WHOQOL-BREF) were ranged from 46.86 to 61.37 and the overall Stroke Specific Quality of Life scale (SS-QOL) mean score was 157.16. There was a significant inconsistency among the included studies as heterogeneity was high (I2 >97%). Conclusion: Assessment of the quality of life among stroke survivors is a crucial step to predict the illness' imposed burden and ascertain the effectiveness of the treatment. The present meta-analysis elucidates the aggregate estimates of quality of life and contributes to the research on the quality of life following a stroke in an Indian context.

Psychiatric comorbidity and quality of life in patients with epilepsy on anti-epileptic monotherapy and polytherapy.

Objective: The bio-psycho-social factors affecting the quality of life in patients with epilepsy can be numerous but are often overlooked. The behavioral side effects of anti-seizure medications can be one such potential factor. The aim of the study is to address the effect of the number of anti-seizure medications on the development of psychiatric comorbidity and quality of life in patients with adequate seizure control. Materials and Methods: The study recruited 100 participants with generalized tonic-clonic seizures from a tertiary care center in North India, who were seizure-free from the last 1 month. The study participants were divided into two groups based on whether they were on monotherapy or polytherapy. The two groups were matched for their socio-demographic and clinical profile. We assessed for psychiatric comorbidity in each group using Mini International Neuropsychiatric Interview. All the study participants were given Hindi translated version of quality of life in the epilepsy-31 questionnaire for objective assessment of the quality of life. Results: The patients receiving anti-epileptic polytherapy had significantly higher prevalence of psychiatric comorbidity than patients on monotherapy. Furthermore, the patients on polytherapy scored significantly less on the cognitive domain of quality of life as well as the overall quality of life domain in the epilepsy-31 questionnaire. Conclusion: The patients with epilepsy must be evaluated for psychiatric comorbidity and side effect profile of anti-seizure medications to improve the quality of life. This is particularly more important for patients who are on anti-epileptic polytherapy even if the seizure control is adequate.

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.

Modified Atkins Diet vs Low Glycemic Index Treatment for Drug-Resistant Epilepsy in Children: An Open Label, Randomized Controlled Trial.

OBJECTIVE: To compare the efficacy of the modified Atkins diet (mAD) and low glycemic index treatment (LGIT) among children with drug-resistant epilepsy. DESIGN: Randomized, open labelled, controlled clinical trial. SETTING: Tertiary care referral center. PARTICIPANTS: Children aged 6 months to 14 years with drug-resistant epilepsy. INTERVENTION: mAD (n=30) or LGIT (n=30) as an add-on to the ongoing antiseizure drugs. MAIN OUTCOME MEASURES: Proportion of children who achieved seizure freedom as defined by complete cessation of seizure at 12 weeks as primary outcome measure. Secondary outcome measures were proportion of children who achieved >50% and >90% seizure reduction at 12 weeks, and adverse effects of the two therapies. RESULTS: Of the 60 recruited children, 3 in the mAD group, and 3 in LGIT group were lost to follow-up. The proportion of children with seizure freedom [16.6% vs 6.6%; relative risk reduction (RRR) (95% CI), 1.5 (-10.9, 0.5); P=0.42] and >90% seizure reduction [30% vs 13.3%; RRR, -1.2 (-5.5, 0.2); P=0.21] was comparable between the mAD and LGIT group at 12 weeks. The proportion of children with >50% seizure reduction was significantly higher at 12 weeks among those who received LGIT as compared to the mADgroup [73.3% vs 43.3%; RRR (95% CI) 0.4 (0.1-0.6); P=0.03] although the effect size was small. The diet was well tolerated with lethargy being the most common adverse effect in children in mAD (53.3%) and LGIT (66.7%) groups. CONCLUSIONS: The present study with limited sample size shows that seizure freedom at 12 weeks was comparable between mAD and LGIT for the treatment of drug-resistant epilepsy.

Predictors of Seizure-Related Injuries in an Epilepsy Cohort from North India.

BACKGROUND AND PURPOSE: To identify predictors of seizure-related injury (SRI) and death in people with epilepsy (PWE) in a North Indian cohort. METHODS: This ambispective cohort study included PWE registered in an epilepsy clinic in Delhi between May 2010 and December 2011. Five hundred twenty-six patients were enrolled and followed for 25 months. Patients were categorized into two groups based on SRI/no SRI during the study period. We analyzed various factors to identify predictors of SRI and death. RESULTS: Of 526 patients, 355 (67.5%) reported having no SRIs and 171 (32.5%) had sustained an SRI. Among patients with SRI, 72.5% were male; 62% of those with no SRI were male. The injury type included soft tissue (60%), head trauma (20%), dental trauma (10%), orthopedic (10%), and burns (5%). On univariate analysis, factors predicting SRI occurrence were male gender, abnormal birth history (p < 0.01), abnormal mental status (p < 0.01), seizure duration (p < 0.04), daytime seizures (p < 0.05), dependence on a caregiver (p < 0.008), and uncontrolled seizures (p < 0.001), history of cluster seizures or status epilepticus (p < 0.001), occurrence of generalized tonic-clonic seizures (GTCS), and use of >3 antiepileptic drugs (p < 0.008). On multiple logistic regression analysis, male gender, uncontrolled seizures, history of cluster seizures or status epilepticus, and GTCS were significant risk factors. Sixteen deaths occurred in our cohort, and 13 fit the definition of probable sudden unexpected death in epilepsy (SUDEP). Most patients with SUDEP had an unwitnessed event (69.2%). The only significant factor in predicting death was uncontrolled seizures. CONCLUSIONS: Male gender, occurrence of GTCS, uncontrolled seizures, and history of cluster seizures or status epilepticus predicted SRI occurrence in PWE. Precautions should be taken by caregivers of patients with these risk factors, to prevent injury.

Role of Immuno-Polymerase Chain Reaction (I-PCR) in Resolving Diagnostic Dilemma Between Tuberculoma and Neurocysticercosis: A Case Report.

BACKGROUND Tuberculoma and neurocysticercosis (NCC) often show similar clinical and neuroimaging features. Differential diagnosis of these 2 diseases is imperative, as tuberculoma is an active infection that requires immediate anti-tubercular therapy (ATT). CASE REPORT We present the case of a 17-year-old Indian girl with fever, severe headache, and right 6th cranial nerve palsy. Brain magnetic resonance imaging (MRI) showed multiple tiny ring-enhancing lesions in bilateral cerebral parenchyma with mild perilesional edema, which were initially thought to be NCC, but subsequently were diagnosed as brain tuberculomas. Based on clinical findings, mildly increased choline/creatine ratio (1.35) with slight prominent lipid lactate peak and absence of alanine, succinate peak by magnetic resonance spectroscopy (MRS), and the detection of Mycobacterium tuberculosis (Mtb)-specific early-secreted antigenic target-6 (ESAT-6, Rv3875) protein from the cerebrospinal fluid (CSF) by indirect ELISA, as well as indirect immuno-PCR (I-PCR) assay, diagnosis of brain tuberculomas associated with tuberculous meningitis (TBM) was confirmed, which was followed by ATT. The patient responded well and the symptoms resolved. CONCLUSIONS In this case, multiple ring-enhancing lesions of the brain by MRI were diagnosed as tuberculomas associated with TBM by MRS and indirect ELISA/I-PCR method, thus resolving the diagnostic dilemma.

Cerebral Venous Sinus Thrombosis and Posterior Reversible Encephalopathy Syndrome Coexisting in a Woman: A Rare Coincidence.

Cerebral venous sinus thrombosis (CVST) and posterior reversible encephalopathy syndrome (PRES) are two rare diseases which may present with similar symptoms and signs. We report a case with coexisting PRES and CVST in a 34 years old postpartum female presented with multiple episodes of generalized seizures and bilateral vision loss after delivery. MRI brain and venography revealed left transverse sinus, sigmoid sinus and internal cerebral vein thrombosis with vasogenic edema in bilateral parieto-occipital, right temporal and left frontal area, which was suggestive of posterior reversible encephalopathy syndrome (PRES). She was treated with antihypertensive, low molecular weight heparin (LMWH), oral anticoagulant and responded well to the treatment.

Proteus Syndrome.

Proteus syndrome is an extremely rare disorder with a documentation of only 100 cases world over till date. This sporadic disorder involves the skeletal system, central nervous system, eyes, skin, soft tissues and vascular system. We report a case of Proteus syndrome in a 22 year male presenting with abnormally enlarged and hypertrophied feet resulting in marked physical constraints.

Epilepsia Partialis Continua as Presenting Manifestation of AIDS: A Rarity.

Seizures, most commonly generalized tonic-clonic, are common in known human immune deficiency virus (HIV) sero-positive patients, and they usually have a focal lesion on brain imaging. However, it is very unusual to see a patient with no premorbid illness presenting with epilepsia partialis continua (EPC) and then being detected HIV seropositive with an Acquired Immune Deficiency Syndrome (AIDS)-defining illness. We report the case of a teenaged boy with no past significant history or known high-risk behavior who presented with recurrent focal seizures of 5 days' duration, EPC, and encephalopathy. His electroencephalogram showed periodic lateralized epileptiform discharges (PLEDS), and magnetic resonance imaging (MRI) of the brain showed abnormal signal changes in the right parieto-occipital cortex and thalamus, both as yet unreported in cytomegalovirus (CMV) encephalitis, which was diagnosed by the cerebrospinal fluid (CSF) analysis.