Multicenter, Open-Label, Prospective Study Shows Safety and Therapeutic Benefits of a Defined Ginkgo Biloba Extract for Adults with Major Neurocognitive Disorder.

INTRODUCTION: The safety and therapeutic effects of Gingko biloba extract EGb 761® to treat cognitive decline have been demonstrated in numerous clinical trials. However, trials in Indian populations have been lacking. METHODS: This open-label, multicenter, single-arm, phase IV trial enrolled 150 patients aged ≥50 years with major neurocognitive disorder due to Alzheimer's disease, major vascular neurocognitive disorder, or mixed forms of both according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria and a Mini-Mental State Examination (MMSE) score of 12-24. Patients took 120 mg EGb 761® twice daily for 18 weeks. Therapeutic effects were assessed by CERAD constructional praxis and recall of constructional praxis (CERAD CP, CERAD recall of CP), Trail-Making Test (TMT), Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD), Clinical Global Impressions (CGI) scale, and 11-point box scales for tinnitus and vertigo. Safety assessment was based on the occurrence of adverse events as well as changes in clinical, laboratory, and functional parameters. RESULTS: After 18 weeks, significant improvements compared to baseline were found in constructional praxis (CERAD CP, p < 0.0001), memory (CERAD recall of CP, p < 0.0001), speed and executive functioning (TMT A, p < 0.0001; TMT B, p < 0.0001), and behavioral symptoms (BEHAVE-AD, p < 0.0001). Forty-five adverse events were reported in 33 (22.0%) patients in total, including ten presumed adverse drug reactions in 9 (6.0%) patients. Headache and diarrhea of mild-to-moderate severity were the most frequent events. Two serious adverse events, both considered unrelated to the study drug, occurred in 2 (1.3%) patients. CONCLUSION: This study confirmed the favorable safety profile and suggested therapeutic benefits of EGb 761® in Indian patients with major neurocognitive disorder.

Coordination, cooperation, competition, crowding and congestion of molecular motors: Theoretical models and computer simulations.

Cytoskeletal motor proteins are biological nanomachines that convert chemical energy into mechanical work to carry out various functions such as cell division, cell motility, cargo transport, muscle contraction, beating of cilia and flagella, and ciliogenesis. Most of these processes are driven by the collective operation of several motors in the crowded viscous intracellular environment. Imaging and manipulation of the motors with powerful experimental probes have been complemented by mathematical analysis and computer simulations of the corresponding theoretical models. In this article, we illustrate some of the key theoretical approaches used to understand how coordination, cooperation and competition of multiple motors in the crowded intra-cellular environment drive the processes that are essential for biological function of a cell. In spite of the focus on theory, experimentalists will also find this article as an useful summary of the progress made so far in understanding multiple motor systems.

Headache prevalence and demographic associations in the Delhi and National Capital Region of India: estimates from a cross-sectional nationwide population-based study.

BACKGROUND: India is a large and populous country where reliable data on headache disorders are relatively scarce. This study in northern India (Delhi and National Capital Territory Region [NCR], including surrounding districts in the States of Haryana, Uttar Pradesh and Rajasthan) continues the series of population-based studies within the Global Campaign against Headache and follows an earlier study, using the same protocol and questionnaire, in the southern State of Karnataka. METHODS: This cross-sectional study used the Global Campaign's established methodology. Biologically unrelated Indian nationals aged 18-65 years were included through multistage random sampling in both urban and rural areas of NCR. Interviews at unannounced household visits followed the structured Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire in its original English version or in the validated Hindi version. Demographic enquiry was followed by a neutral headache screening question and diagnostic questions based on the International Classification of Headache Disorders edition 3 (ICHD-3), which focused on each respondent's most bothersome headache. Questions about headache yesterday (HY) enabled estimation of 1-day prevalence. A diagnostic algorithm first identified participants reporting headache on ≥ 15 days/month (H15+), diagnosing probable medication-overuse headache (pMOH) in those also reporting acute medication use on ≥ 15 days/month, and "other H15+" in those not. To all others, the algorithm applied ICHD-3 criteria in the order definite migraine, definite tension-type headache (TTH), probable migraine, probable TTH. Definite and probable diagnoses were combined. RESULTS: Adjusted for age, gender and habitation, 1-year prevalences were 26.3% for migraine, 34.1% for TTH, 3.0% for pMOH and 4.5% for other H15+. Female preponderance was seen in all headache types except TTH: migraine 35.7% vs. 15.1% (aOR = 3.3; p < 0.001); pMOH 4.3% vs. 0.7% (aOR = 5.1; p < 0.001); other H15 + 5.9% vs. 2.3% (aOR = 2.5; p = 0.08). One-day prevalence of (any) headache was 12.0%, based on reported HY. One-day prevalence predicted from 1-year prevalence and mean recalled headache frequency over 3 months was slightly lower (10.5%). CONCLUSIONS: The prevalences of migraine and TTH in Delhi and NCR substantially exceed global means. They closely match those in the Karnataka study: migraine 25.2%, TTH 35.1%. We argue that these estimates can reasonably be extrapolated to all India.

Interictal Dysfunctions of Attention, Vigilance, and Executive Functions in Migraine and Their Reversal by Preventive Treatment: A longitudinal Controlled Study.

OBJECTIVE: To assess attention, vigilance, and executive functions in migraine patients during headache-free (interictal) periods and in healthy controls without migraine and to study the impact of migraine preventive treatment on these cognitive functions. METHODS: Preventive drug-naive migraine patients, aged ≥18 years, without a history of medication overuse were studied and compared to non-migraine controls. Psychiatric comorbidity was screened by Patient Health Questionnaire-9, and those who screened positive were evaluated further by specific scales. The Epworth Sleepiness Scale assessed subjective complaints of sleep quality. Cognitive functions were assessed by Mini-Mental State Examination (MMSE), digit span forward and backward (DS-F, DS-B), trail-making tests (TMT-A and B) and Stroop word (SW), Stroop color (SC), and Stroop interference (SI) tests. Cognitive test scores at the end of 6 months following treatment were compared to baseline scores. RESULTS: One hundred and fifty migraine patients and controls each were studied. Compared to controls, migraine patients performed significantly worse in DS-B ( P < 0.0001), TMT-A ( P = 0.00004), TMT-B ( P < 0.0001), SW ( P < 0.0001), SC ( P < 0.0001), and SI ( P = 0.0221). MMSE scores did not differ between patients and the controls ( P = 0.3224). Compared to the patients without psychiatric comorbidity, migraine patients with psychiatric comorbidity showed no significant differences in the cognitive test scores. Significant improvement in all cognitive test scores ( P < 0.001) was observed after 6 months of treatment. CONCLUSION: Migraine patients, compared to non-migraine controls, showed deficits in attention, vigilance, and executive functions during the interictal period, which improved with successful preventive treatment. Psychiatric comorbidities did not have a significant impact on cognitive dysfunctions.

The burden of headache disorders in North India: methodology, and validation of a Hindi version of the HARDSHIP questionnaire, for a community-based survey in Delhi and national capital territory region.

BACKGROUND: Knowledge of the prevalence and attributable burden of headache disorders in India is sparse, with only two recent population-based studies from South and East India. These produced conflicting results. A study in North India is needed. We report the methodology of such a study using, and validating, a Hindi translation of the Headache-Attributed Restriction, Disability, Social Handicap, and Impaired Participation (HARDSHIP) questionnaire developed by Lifting The Burden (LTB). Almost half of the Indian population speak Hindi or one of its dialects. METHODS: The study adopted LTB's standardized protocol for population-based studies in a cross-sectional survey using multistage random sampling conducted in urban Delhi and a surrounding rural area. Trained interviewers visited households unannounced, randomly selected one adult member from each and applied the Hindi version of HARDSHIP in face-to-face interviews. The most bothersome headache reported by participants was classified algorithmically into headache on ≥ 15 days/month (H15 +), migraine (including definite and probable) or tension-type headache (including definite and probable). These diagnoses were mutually exclusive. All participants diagnosed with H15 + and a 10% subsample of all others were additionally assessed by headache specialists and classified as above. We estimated the sensitivity and specificity of HARDSHIP diagnoses by comparison with the specialists' diagnoses. RESULTS: From 3,040 eligible households, 2,066 participants were interviewed. The participating proportions were 98.3% in rural areas but 52.9% in urban Delhi. In the validation subsample of 291 participants (149 rural, 142 urban), 61 did not report any headache (seven of those assessed by HARDSHIP, eight by headache specialists and 46 by both) [kappa = 0.83; 95% CI: 0.74-0.91]. In the remaining 230 participants who reported headache in the preceding year, sensitivity, specificity and kappa with (95% CI) were 0.73 (0.65-0.79), 0.80 (0.67-0.90) and 0.43 (0.34-0.58) for migraine; 0.71 (0.56-0.83), 0.80 (0.730.85) and 0.43 (0.37-0.62) for TTH and 0.75 (0.47-0.94), 0.93 (0.89-0.96) and 0.46 (0.34-0.58) for H15 + respectively. CONCLUSION: This study validates the Hindi version of HARDSHIP, finding its performance similar to those of other versions. It can be used to conduct population surveys in other Hindi-speaking regions of India.

Treatment in the emergency department.

As a common headache disorder, migraine is also a common cause for emergency department (ED) visiting, which leads to tremendous medical and economic burden. The goals of migraine management in ED are resolving headache and migraine-related most bothersome symptoms rapidly, preventing ED revisiting due to headache relapse, and referring patients at risk, e.g., patients with chronic migraine and/or medication-overuse headache, to specialists. In this chapter, we elucidated the algorithm which was particularly adapted to ED settings for the diagnosis and treatment of migraine. We reviewed a plentiful amount of high-quality clinical trials, especially those conducted in populations derived from ED, to provide readers insights into the optimized treatment options for migraine in ED.

Clinical Profile and Quality of Life in Myasthenia Gravis Using MGQOL15 R(Hindi): An Indian Perspective.

Background: Myasthenia Gravis (MG) is a chronic fluctuating illness, due to the dysfunction of neuromuscular junction which is autoimmune in nature. The disease severely affects the Quality Of Life (QOL). Objective: The primary objective of our study was to assess the QOL in patients with MG using Short Form 36 (SF 36) and MGQOL 15 R (Hindi translated). The secondary objective was to assess the correlation of age, sex, illness duration, clinical characteristics, severity, and treatment with the QOL in MG patients. Methodology: A cross sectional study of 55 MG patients was done to analyse and evaluate the clinical status using Hybrid Myasthenia Gravis Foundation of America (HMGFA), Myasthenia gravis composite score (MGCS) and The Myasthenia Gravis Activities of Daily Living (MG - ADL). QOL was assessed by SF 36 and Hindi version of Myasthenia Gravis Quality of Life 15 - Revised (MG-QOL15R) score. Results: 78.2% patients had generalized MG. The mean MGC and MG-ADL scores were 5.27 and 3.29 (95% CI: 2.24 -4.34) respectively. The mean MGQOL15R score was 6.52 ± 7.7 and the score correlated with the symptoms. The SF 36 scores were the best and the worst in the bodily pain (93.72 ± 13.52) and general health subset (61.81 ± 39.64) respectively. Except for steroid dose, there was no significant correlation between SF36 and other factors. Conclusion: QOL in MG was found to be affected due to the disease. The MGQOL 15 R scores correlated with the clinical features, remission or active status, steroid use and thymectomy. No Significant association was observed between MG QOL scores and various lab parameters and repetitive nerve stimulation (RNS) test results. Higher dose of steroid was associated with poor QOL, while thymectomy was associated with better QOL scores. MGQOL15R (Hindi) is a quick and simple tool to assess the QOL in MG patients.

Galcanezumab in patients with episodic migraine: results from the open-label period of the phase 3 PERSIST study.

BACKGROUND: The phase 3 randomized PERSIST study demonstrated the efficacy and tolerability of galcanezumab, a humanized anti-calcitonin gene-related peptide (CGRP) monoclonal antibody for prevention of episodic migraines. We present findings from the open-label extension (OLE) of PERSIST, which evaluated the long-term efficacy and safety of galcanezumab in patients from China, India, and Russia. METHODS: Patients completing the 3-month double-blind period of PERSIST were eligible for the 3-month OLE. Patients previously randomized to galcanezumab (GMB/GMB group) continued to receive galcanezumab 120 mg at all three visits during the OLE whereas patients randomized to placebo received a 240 mg loading dose of galcanezumab and then two 120 mg doses (PBO/GMB group). The primary outcome was the mean change (from double-blind baseline) in the number of monthly migraine headache days (MHDs) to month 6. Other endpoints included percent reduction in monthly MHDs from double-blind baseline to month 6, functional outcomes, safety and tolerability. RESULTS: Overall, 99% of patients completing the double-blind period entered the OLE, and 96% completed through month 6. Patients in the GMB/GMB group achieved continued improvements in efficacy, with the reduction from baseline in the mean number of monthly MHDs, and slightly increasing from 4.01 days at the end of the double-blind period to 4.62 at the end of the OLE. Of patients who were ≥ 50% responders to galcanezumab at month 3, 66% maintained this response through to month 6. Patients in the PBO/GMB group experienced a rapid reduction in the number of monthly MHDs after initiation of galcanezumab, with a mean reduction from baseline of 4.56 days by month 6. The long-term benefits of galcanezumab were also supported by improvements in other efficacy and functional endpoints. All safety findings were consistent with the known long-term safety profile of galcanezumab; no patients experienced a treatment-related serious adverse event. CONCLUSIONS: Galcanezumab was efficacious and well-tolerated in patients with episodic migraine from China, India and Russia, for up to 6 months. TRIAL REGISTRATION: ClinicalTrisABSTRACT_pals.gov NCT03963232, registered May 24, 2019.

Anti-N-methyl D-aspartate Receptor Encephalitis in India: A Literature Review.

Anti N-methyl D-aspartate receptor encephalitis (NMDAR-E) though rare, is currently considered as the commonest antibody mediated encephalitis in the world. No review on perspectives of NMDAR-E from India is available. The aim of the study was to review all the cases of NMDAR-E reported from India until June 2021 in terms of clinical features, diagnosis, and treatment, and perform a comparison of adult and paediatric cases. A literature review of NMDAR-E case reports/case series published from India till June 2021 was done. Demography, clinical profile, triggers, electroencephalography (EEG), neuroimaging, treatment details and outcomes were analysed. Sixteen case series and 35 case reports with a total of 249 cases were analysed. 82% of cases were from paediatric age group. The female to male ratio was 3:1. Psychiatric deficits, movement disorders, seizures, and language abnormalities were the most common clinical features. MRI brain abnormalities were seen in 45% patients. Electroencephalographic abnormalities were seen in 85% of patients. Infective triggers (herpes simplex virus and various other agents) were reported in 11% of the cases. Pediatric patients as compared with adults had more encephalopathy, autonomic dysfunctions, and normal imaging whereas the latter had more cognitive dysfunctions and delta brush pattern in electroencephalography (p<0.005). Therefore, to conclude, this literature review suggests that overall, the clinical spectrum of Indian cases is like cases described from other parts of the world. However, most reported cases from India belonged to paediatric age group who had more encephalopathy, autonomic dysfunctions, and normal brain imaging compared to adults. A few novel infectious agents as triggers were described from India.

Greater occipital nerve blockade for the preventive treatment of chronic migraine: A randomized double-blind placebo-controlled study.

BACKGROUND: Greater occipital nerve blockade for the prevention of chronic migraine has a limited evidence base. A robust randomized double-blind, placebo-controlled trial is needed. METHODS: This double-blind, placebo-controlled, parallel-group trial, following a baseline period of four weeks, randomly assigned patients of chronic migraine 1:1 to receive four-weekly bilateral greater occipital nerve blockade with either 2 ml of 2% (40 mg) lidocaine (active group) or 2 ml of 0.9% saline (placebo) injections for 12 weeks. The primary and key secondary efficacy endpoints were a change from the baseline in the mean number of headache and migraine days and the achievement of ≥50% reduction in headache days from baseline across the weeks 9-12 respectively. Safety evaluations included the documentation and reporting of serious and other adverse events. RESULTS: Twenty-two patients each were randomly allocated to the active and placebo group. Baseline demography and clinical characteristics were similar between the two groups. Mean headache and migraine days at baseline (±SD) were 23.4 ± 4.4 and 15.6 ± 5.7 days in the active group and 22.6 ± 5.0 and 14.6 ± 4.6 days in the placebo group respectively. The active group compared to the placebo had a significantly greater least-squares mean reduction in the number of headache and migraine days (-4.2 days [95% CI: -7.5 to -0.8; p = 0.018] and -4.7 days [95%CI: -7.7 to -1.7; p = 0.003] respectively). 40.9% of patients in the active group achieved ≥50% reduction in headache days as compared with 9.1% of patients receiving a placebo (p = 0.024). Overall, 64 mild and transient adverse events were reported by 16 patients in the active group and 15 in the placebo. No death or serious adverse events were reported. CONCLUSION: Four-weekly greater occipital nerve blockade with 2% lidocaine for 12 weeks was superior to placebo in decreasing the average number of headache and migraine days in patients with chronic migraine with a good tolerability profile.Clinical trial.gov no. CTRI 2020/07/026709.

Comparison of Serum Holotranscobalamin with Serum Vitamin B12 in Population Prone to Megaloblastic Anemia and their Correlation with Nerve Conduction Study.

Early detection of megaloblastic anemia and associated neurological complications is crucial for management. This study was conducted to compare serum holotranscobalamin level with serum vitamin B12 level as early biomarker in people prone to megaloblastic anemia and to evaluate co-relation between these biomarkers and nerve conduction study in study patients. 83 adult patients (Hb > 12 gm/dl) prone to megaloblastic anemia were studied for basic haematological investigations, random blood sugar, thyroid function test, liver function test, kidney function test, serum vitamin B12, serum holotranscobalamin and serum folic acid levels. 45 patients among them underwent nerve conduction studies. All study patients were classified in 6 groups on the basis of risk factors for megaloblastic anemia. 29 patients (34.9%) were on antiepileptic drugs, 26 (31.3%) were chronic alcoholic, 10 patients (12%) each, had malabsorption and ileal tuberculosis, 6 (7.22%) had chronic pancreatitis and 2 (2.4%) had ileal resection. 30 patients (36.14%) had low serum holotranscobalamin, including 7 patients (8.43%) with low serum vitamin B12 level also, unmasking vitamin B12 deficiency in 23 patients (27.7%). 7 patients (8.43%) had mean corpuscular volume (MCV) > 100fL and 8 patients (9.63%) had vitamin B12 deficiency related changes on peripheral smear. Serum vitamin B12 and holotranscobalamin levels were significantly low in patients with peripheral smear changes, with p value 0.039 and 0.041 respectively, while no such association seen with MCV. Subclinical peripheral neuropathy was detected in 18 (40%) out of 45 patients on nerve conduction study. Serum holotranscobalamin levels were significantly lower (p = 0.031) than serum vitamin B12 levels (p = 0.2) in patients with neuropathic changes. Rest investigations and serum folic acid levels were normal in all patients. Holotranscobalamin levels can be considered early and reliable marker for vitamin B12 deficiency and deficiency associated peripheral neuropathy, even in patients who are prone to megaloblastic anemia, and not yet anemic or symptomatic for neuropathy.

Efficacy and Tolerability of Erenumab for Prevention of Episodic Migraine in India.

Background: EMPOwER, a 12-week, double-blind (DB), randomized, placebo-controlled study evaluated the efficacy and safety of erenumab in adult patients with episodic migraine (EM) from Asia, the Middle East, and Latin America. This study analyzes the Indian experience for the use of erunumab for prevention of episodic migraine. Objective: The study aimed to evaluate the efficacy and tolerability of erenumab (70 mg and 140 mg) in EM patients from India. Methods: Randomized patients received monthly subcutaneous injections of placebo and erenumab 70 mg or 140 mg for 3 months. The primary endpoint was a change from the baseline in monthly migraine days (MMDs) at month 3. Other endpoints included achievement of ≥50%, ≥75%, and 100% reduction in MMD; a change in monthly acute migraine-specific medication treatment days; a change in patient-reported outcomes; and safety assessment. Results: Of the 539 patients screened, 351 patients were randomized (erenumab, 70 mg: n = 133 and 140 mg: n = 94; placebo: n = 124). The mean (±SD) age, disease duration, and MMD were 35.1 (±8.6) years, 6.77 (±6.01) years, and 7.82 (±2.89) days, respectively. The placebo-adjusted difference in mean MMD for erenumab 70 mg was -0.88 (95% CI, -2.16, 0.39; P = 0.174) days, and that for erenumab 140 mg was -1.01 (-2.42, 0.41; P = 0.164) days versus placebo. Secondary and exploratory endpoints demonstrated consistently better results in both erenumab dosage groups versus placebo. Treatment-emergent adverse events were comparable across groups (erenumab, 70 mg: 22.7% and 140 mg: 24.5%; placebo: 25.2%). Conclusion: Both doses of erenumab showed numerical improvement for efficacy endpoints and were well-tolerated in the Indian population. No new safety signals were reported.

Efficacy and tolerability of combination treatment of topiramate and greater occipital nerve block versus topiramate monotherapy for the preventive treatment of chronic migraine: A randomized controlled trial.

OBJECTIVE: To compare the efficacy and tolerability of combination treatment of topiramate and greater occipital nerve block to topiramate monotherapy in adult chronic migraine patients. BACKGROUND: Options for the preventive treatment of chronic migraine are limited and costly. Combination treatments do not have an evidence base yet. METHODS: This was a parallel group, 3 arms with 1:1:1 allocation ratio randomized controlled study in consecutive adult chronic migraine patients attending Headache Clinic in a tertiary care hospital. Patients received either topiramate monotherapy 100 mg/day (group A), or topiramate plus greater occipital nerve block with 40 mg lidocaine (2%) and 80mg (2 ml) methylprednisolone as the first injection followed by monthly injections of lidocaine for the next 2 months (group B) or topiramate plus greater occipital nerve block with 40 mg lidocaine (2%) injections monthly for 3 months (group C). The primary endpoint was the mean change in monthly migraine days at Month 3. Multiple secondary endpoints were assessed that included among others, achievement of ≥50% reduction in mean monthly headache days compared to baseline at Month 3 and assessment for any adverse events. RESULTS: One hundred and twenty-five patients were randomized; 41 to group A, 44 to group B, and 40 to group C. Efficacy assessments were done for 121 patients. Patients receiving combination treatment of topiramate and greater occipital nerve block with steroids and lidocaine and greater occipital nerve block with only lidocaine compared to topiramate monotherapy showed greater reductions in monthly migraine days at Month 3 (-9.6 vs -7.3 days; p = 0.003) and (-10.1 vs -7.3 days; p < 0.001) respectively. Greater proportion of patients in both the combination treatment groups (added greater occipital nerve block with and without steroid) achieved ≥50% reduction in mean monthly headache days [71.4% vs 39%; OR (95% CI) 3.9(1.6-9.8); p = 0.004] and [62.4% vs 39%; OR (95% CI) 2.7(1.1-6.7); p = 0.034] respectively, compared to those receiving topiramate monotherapy. Adverse effects between the groups were comparable although patients receiving combination treatment with added greater occipital nerve block reported transient adverse effects like post-injection dizziness, local site swelling, and pain. No serious adverse event was reported. CONCLUSION: Combination treatments of topiramate with monthly injections of greater occipital nerve block were more effective in reducing monthly migraine days in chronic migraine than topiramate monotherapy at Month 3. Combination treatments were well tolerated.

TOP-PRO study: A randomized double-blind controlled trial of topiramate versus propranolol for prevention of chronic migraine.

OBJECTIVE: The aim of the TOP-PRO-study, a double-blind randomized controlled trial, was to assess the efficacy (non-inferiority) and tolerability of propranolol compared to topiramate for the prevention of chronic migraine. BACKGROUND: Except for topiramate, oral preventive treatment for chronic migraine lacks credible evidence. METHODS: Chronic migraine patients aged above 18 years and less than 65 years of age, not on any preventive treatment were randomly allocated to receive topiramate (100 mg/day) or propranolol (160 mg/day). The primary efficacy outcome was the mean change in migraine days per 28 days at the end of 24 weeks from baseline. A mean difference of 1.5 days per four weeks was chosen as the cut-off delta value. Multiple secondary efficacy outcomes and treatment emergent adverse events were also assessed. RESULTS: As against the planned sample size of 244, only 175 patients could be enrolled before the spread of the corona virus disease-2019 pandemic and enforcement of lockdown in India. Of the 175 randomized patients, 95 (topiramate 46 and propranolol 49) completed the trial. The mean change in migraine days was -5.3 ± 1.2 vs -7.3 ± 1.1 days (p = 0.226) for topiramate and propranolol groups respectively. Propranolol was found to be non-inferior and not superior to topiramate (point estimate of -1.99 with a 95% confidence interval of -5.23 to 1.25 days). Multiple secondary outcomes also did not differ between the two groups. Intention to treat analysis of 175 patients and per-protocol analysis of 95 patients yielded concordant results. There was no significant difference in the incidence of adverse events between the two groups. CONCLUSION: Propranolol (160mg/day) was non-inferior, non-superior to topiramate (100mg/day) for the preventive treatment of chronic migraine and had a comparable tolerability profile.Trial Registration: Clinical Trials Registry-India CTRI/2019/05/018997).

Genetics of Ataxias in Indian Population: A Collative Insight from a Common Genetic Screening Tool.

Cerebellar ataxias (CAs) represent a group of autosomal dominant and recessive neurodegenerative disorders affecting cerebellum with or without spinal cord. Overall, CAs have preponderance for tandem nucleotide repeat expansions as an etiological factor (10 TREs explain nearly 30-40% of ataxia cohort globally). The experience of 10 years of common genetic ataxia subtypes for ≈5600 patients' referrals (Pan-India) received at a single center is shared herein. Frequencies (in %, n) of SCA types and FRDA in the sample cohort are observed as follows: SCA12 (8.6%, 490); SCA2 (8.5%, 482); SCA1 (4.8%, 272); SCA3 (2%, 113); SCA7 (0.5%, 28); SCA6 (0.1%, 05); SCA17 (0.1%, 05), and FRDA (2.2%, 127). A significant amount of variability in TRE lengths at each locus is observed, we noted presence of biallelic expansion, co-occurrence of SCA-subtypes, and the presence of premutable normal alleles. The frequency of mutated GAA-FRDA allele in healthy controls is 1/158 (0.63%), thus an expected FRDA prevalence of 1:100 000 persons. The data of this study are relevant not only for clinical decision making but also for guidance in direction of genetic investigations, transancestral comparison of genotypes, and lastly provide insight for policy decision for the consideration of SCAs under rare disease category.

Game-environment feedback dynamics in growing population: Effect of finite carrying capacity.

The tragedy of the commons (TOC) is an unfortunate situation where a shared resource is exhausted due to uncontrolled exploitation by the selfish individuals of a population. Recently, the paradigmatic replicator equation has been used in conjunction with a phenomenological equation for the state of the shared resource to gain insight into the influence of the games on the TOC. The replicator equation, by construction, models a fixed infinite population undergoing microevolution. Thus, it is unable to capture any effect of the population growth and the carrying capacity of the population although the TOC is expected to be dependent on the size of the population. Therefore, in this paper, we present a mathematical framework that incorporates the density dependent payoffs and the logistic growth of the population in the eco-evolutionary dynamics modeling the game-resource feedback. We discover a bistability in the dynamics: a finite carrying capacity can either avert or cause the TOC depending on the initial states of the resource and the initial fraction of cooperators. In fact, depending on the type of strategic game-theoretic interaction, a finite carrying capacity can either avert or cause the TOC when it is exactly the opposite for the corresponding case with infinite carrying capacity.

An Internet-based study on the impact of COVID-19 pandemic-related lockdown on migraine in India.

OBJECTIVES: To assess the impact of lockdown during the COVID-19 pandemic on migraine patients in India on disease activity, healthcare accessibility, and quality of life (QoL). MATERIALS & METHODS: This internet-based survey study using a structured questionnaire was conducted from 27th April to 31st July 2020. Previous physician-diagnosed migraine patients or those fulfilling any two of three clinical features (limitation of activities for >1 day, associated nausea or vomiting, and photophobia or phonophobia) were diagnosed as migraine patients. QoL was captured using a Likert scale and determinants of poor QoL were identified by logistic regression. RESULTS: A total of 4078 persons completed the full survey out of which 984 (24.1%) had migraine (mean age 35.3 ±11.2). Compared to pre-lockdown, 51.3% of migraineurs reported worsening of their headaches in terms of increased attack frequency (95.6%), increased headache days (95%), increased attack duration (89.9%) and increased headache severity (88.1%). The worsening was attributed to anxiety due to the pandemic (79.7%), inability or difficulty to access healthcare (48.4%) and migraine medicines (48.9%), and financial worries (60.9%). 26.8% of migraineurs reported poor QoL compared to 7.37% of non-migraineurs [p<0.0001]. Migraine affected QoL in 61.4% of migraineurs. The predictors of poor QoL on logistic regression included worsening migraine during the lockdown (AOR 4.150; CI 2.704- 6.369) and difficulty accessing migraine medicines (AOR 4.549; CI 3.041- 6.805). Employment as an essential COVID-19 worker (AOR 0.623; CI 0.409- 0.950) protected against poor QoL. CONCLUSIONS: COVID-19 pandemic-related lockdown greatly impacted migraine patients in India which significantly reduced their QoL.

Clinical profile and outcome of non-COVID strokes during pandemic and the pre pandemic period: COVID-Stroke Study Group (CSSG) India.

BACKGROUND: As the health systems around the world struggled to meet the challenges of COVID-19 pandemic, care of many non-COVID emergencies was affected. AIMS: The present study examined differences in the diagnosis, evaluation and management of stroke patients during a defined period in the ongoing pandemic in 2020 when compared to a similar epoch in year 2019. METHODS: The COVID stroke study group (CSSG) India, included 18 stroke centres spread across the country. Data was collected prospectively between February and July 2020 and retrospectively for the same period in 2019. Details of demographics, stroke evaluation, treatment, in-hospital and three months outcomes were collected and compared between these two time points. RESULTS: A total of 2549 patients were seen in both study periods; 1237 patients (48.53%) in 2019 and 1312 (51.47%) in 2020. Although the overall number of stroke patients and rates of thrombolysis were comparable, a significant decline was observed in the month of April 2020, during the initial period of the pandemic and lockdown. Endovascular treatment reduced significantly and longer door to needle and CT to needle times were observed in 2020. Although mortality was higher in 2020, proportion of patients with good outcome were similar in both the study periods. CONCLUSIONS: Although stroke admissions and rates of thrombolysis were comparable, some work flow metrics were delayed, endovascular stroke treatment rates declined and mortality was higher during the pandemic study period. Reorganization of stroke treatment pathways during the pandemic has likely improved the stroke care delivery across the globe.

Randomised, controlled trial of erenumab for the prevention of episodic migraine in patients from Asia, the Middle East, and Latin America: The EMPOwER study.

OBJECTIVE: EMPOwER, a double-blind, randomised, phase 3 study, evaluated the efficacy and safety of erenumab in adults with episodic migraine from Asia, the Middle East, and Latin America. METHODS: Randomised patients (N = 900) received monthly subcutaneous injections of placebo, erenumab 70 mg, or 140 mg (3:3:2) for 3 months. Primary endpoint was change from baseline in monthly migraine days at Month 3. Other endpoints included achievement of ≥50%, ≥75%, and 100% reduction in monthly migraine days, change in monthly acute migraine-specific medication treatment days, patient-reported outcomes, and safety assessment. RESULTS: At baseline, mean (standard deviation) age was 37.5 (9.9) years, 81.9% were women, and monthly migraine days was 8.2 (2.8). At Month 3, change from baseline in monthly migraine days (primary endpoint) was -3.1, -4.2, and -4.8 days for placebo, erenumab 70 mg, and erenumab 140 mg, respectively, with a statistically significant difference for erenumab versus placebo (P = 0.002 [70 mg], P < 0.001 [140 mg]). Both erenumab doses were also significantly superior to placebo on all secondary endpoints, including the proportion of patients achieving ≥50% reduction from baseline in monthly migraine days, change from baseline in monthly acute migraine-specific medication treatment days and change from baseline in the Headache Impact Test-6™ scores. The safety profile of erenumab was comparable with placebo; no new safety signals were observed. CONCLUSIONS: This study of erenumab in patients with episodic migraine from Asia, the Middle East, and Latin America met all primary and secondary endpoints. A consistent numerical benefit was observed with erenumab 140 mg versus erenumab 70 mg across all efficacy endpoints. These findings extend evidence of erenumab's efficacy and safety to patients under-represented in previous trials.ClinicalTrials.gov identifier: NCT03333109.