Ischaemic stroke in South Asians: The BRAINS study.

BACKGROUND AND PURPOSE: Studies on stroke in South Asian populations are sparse. The aim of this study was to compare differences in age of onset of ischaemic stroke in South Asian patients living in the United Kingdom and South Asian patients living in India versus White British stroke patients. METHODS: We studied the UK and Indian arms of the ongoing BRAINS study, an international prospective hospital-based study of South Asian stroke patients. The BRAINS study includes 4038 South Asian and White British patients with first-ever ischaemic stroke, recruited from sites in the United Kingdom and India. RESULTS: Of the included patients, 1126 were South Asians living in India (ISA), while 1176 were British South Asian (BSA) and 1736 were White British (WB) UK residents. Patients in the ISA and BSA groups experienced stroke 19.5 years and 7.2 years earlier than their WB counterparts, respectively (mean [interquartile range] age: BSA 64.3 [22] years vs. ISA 52.0 [18] years vs. WB 71.5 [19] years; p < 0.001). Patients in the BSA group had higher rates of hypertension, diabetes mellitus and hypercholesterolaemia than those in the ISA and WB groups. After adjustment for traditional stroke risk factors, an earlier age of stroke onset of 18.9 years (p < 0.001) and 8.9 years (p < 0.001) was still observed in the ISA and BSA groups, respectively. In multivariable stepwise linear regression analysis, ethnicity accounted for 24.7% of the variance in early age onset. CONCLUSION: Patients in the BSA and ISA groups experienced ischaemic stroke approximately 9 and 19 years earlier, respectively, than their WB counterparts. Ethnicity is an independent predictor of early age of stroke onset. Our study has considerable implications for public health policymakers in countries with sizable South Asian populations.

Decompressive surgery in cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia.

BACKGROUND AND PURPOSE: Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is an adverse drug reaction occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. CVST-VITT patients often present with large intracerebral haemorrhages and a high proportion undergoes decompressive surgery. Clinical characteristics, therapeutic management and outcomes of CVST-VITT patients who underwent decompressive surgery are described and predictors of in-hospital mortality in these patients are explored. METHODS: Data from an ongoing international registry of patients who developed CVST within 28 days of SARS-CoV-2 vaccination, reported between 29 March 2021 and 10 May 2022, were used. Definite, probable and possible VITT cases, as defined by Pavord et al. (N Engl J Med 2021; 385: 1680-1689), were included. RESULTS: Decompressive surgery was performed in 34/128 (27%) patients with CVST-VITT. In-hospital mortality was 22/34 (65%) in the surgical and 27/94 (29%) in the non-surgical group (p < 0.001). In all surgical cases, the cause of death was brain herniation. The highest mortality rates were found amongst patients with preoperative coma (17/18, 94% vs. 4/14, 29% in the non-comatose; p < 0.001) and bilaterally absent pupillary reflexes (7/7, 100% vs. 6/9, 67% with unilaterally reactive pupil, and 4/11, 36% with bilaterally reactive pupils; p = 0.023). Postoperative imaging revealed worsening of index haemorrhagic lesion in 19 (70%) patients and new haemorrhagic lesions in 16 (59%) patients. At a median follow-up of 6 months, 8/10 of surgical CVST-VITT who survived admission were functionally independent. CONCLUSIONS: Almost two-thirds of surgical CVST-VITT patients died during hospital admission. Preoperative coma and bilateral absence of pupillary responses were associated with higher mortality rates. Survivors often achieved functional independence.

Association of 24 h Blood Pressure on Functional Outcome in Patients with Acute Ischemic Stroke Post Intravenous Thrombolysis.

INTRODUCTION: Elevated admission blood pressure (BP) and BP variability have been shown to be associated with poor outcomes in most studies, while few studies have not found such an association. We investigated the association of various BP parameters with 3-month functional outcomes, mortality, and symptomatic intracerebral hemorrhage (sICH) in patients with acute ischemic stroke (AIS) receiving intravenous thrombolysis (IVT). METHODS: Patients with AIS who received IVT between January 2012 and March 2020 were analyzed. Admission BP, 24 h mean BP, and BP variability were noted for all patients. Outcomes assessed were 3-month modified Rankin Scale (mRS), mortality, and sICH. RESULTS: Of the 237 patients, 161 were males. The mean admission systolic BP (SBP), 24 h mean SBP, and BP variability were 158.1 mm Hg (SD 30.25), 138 mm Hg (SD 16.78), 19.42 (SD 12.79), respectively. At 3 months, 147 (62%) patients had a good outcome (mRS 0-2). Multivariate analysis showed prior stroke, NIHSS >15, mean SBP ≥160 mm Hg, and SBP variability >45 to be significant predictors of poor outcome (mRS > 2) at 3 months. Eleven patients (4.6%) developed sICH. Age more than 60 years, presence of atrial fibrillation, admission blood sugar ≥180 mg/Dl, and SBP variability >45 predicted sICH. None of the above factors were predictive of 3-month mortality. CONCLUSION: An elevated mean SBP and greater SBP variability were predictive of poor functional outcomes, whereas a high SBP variability predicted sICH. Our study emphasizes the need for BP control and minimizing large fluctuations to achieve good poststroke outcomes.

Risk of Stroke and Cardiac Events in Medically Treated Asymptomatic Carotid Stenosis.

BACKGROUND: The risk of stroke in patients with 50% or more asymptomatic carotid stenosis (ACS) on intensive medical treatment is low. Hence, the optimal treatment of ACS remains controversial at this point of time. AIM: We assessed the risk of stroke/transient ischemic attack (TIA) and cardiac events in patients with 50% or more ACS on intensive medical treatment. METHODS: All patients with TIA/minor stroke (National Institutes of Health Stroke Scale score ≤5) who had undergone vessel imaging as part of their evaluation and patients with coronary artery disease who had undergone vessel imaging before cardiac intervention were screened for the presence of asymptomatic carotid stenosis. The risk of TIA/stroke, cardiac events, and vascular deaths were evaluated. RESULTS: Of 1,800 patients, 92 patients (.05%) had ACS having 50% to 99% stenosis; 63 had TIA/minor stroke, and 29 had coronary artery disease, of whom 7 patients had bilateral ACS, thus constituting 99 study units of ACS. The mean follow-up was 34.7 months (range 3-120 months). Two patients developed ischemic events on the side ipsilateral to the ACS and 9 patients developed cardiac events during the follow-up. The average annual event rate for cerebral ischemic events was .93% (95% confidence interval [CI], .11-3.37), 4.21% (95% CI, 1.92-7.98) for cardiac events, and 3.27% (95% CI, 1.31-6.74) for death. CONCLUSIONS: Although the risk of stroke in patients with ACS is low, acute coronary events and vascular deaths were significant. This highlights the importance of intensive risk factor modification to reduce adverse cardiovascular events in ACS rather than revascularization of the carotid stenosis.

Imaging and clinical predictors of unfavorable outcome in medically treated symptomatic intracranial atherosclerotic disease.

BACKGROUND: Patients with symptomatic intracranial atherosclerotic disease (sICAD) have an increased risk of stroke and vascular death. The aim of the study was to evaluate the natural history and outcome of patients with sICAD treated medically. METHODS: The study population was first-ever transient ischemic attack (TIA) or stroke patients presenting to our institute who on vascular imaging had isolated intracranial atherosclerosis as cause of their symptoms and have a follow-up of 90 days. Unfavorable outcome was defined as occurrence of TIA, stroke, acute coronary event, and/or vascular death. RESULTS: Fifty-three (11.8%) of the 449 ischemic stroke patients had sICAD. The risk of stroke in sICAD was 8.9%, 11.1%, 13.3%, and 15.6% in first 7 days, 30 days, 90 days, and 1 year, respectively. Five (11.1%) had cardiovascular events and accounted for 50% of mortality. The predictors of unfavorable outcome were presented as limb weakness (85.7% versus 58.8%, hazard ratio 1.5; 95% confidence interval [CI], .05-.9; P = .04), National Institutes of Health Stroke Scale (NIHSS) score 8 at admission (50% versus 5.9%, hazard ratio 8.5; 95% CI, .007-.5; P = .02), magnetic resonance imaging (MRI) with multiple diffusion-weighted imaging (DWI) lesions (65.4% versus 26.7%; 95% CI, .04-.7; P = .01), and angiography suggestive of diffuse atherosclerosis (50% versus 11.8%; 95% CI, odds ratio .02-.7; P = .009). On stepwise multiple regression, variables for unfavorable outcome were NIHSS score of 8 or more at admission (P = .001), multiple DWI lesion on MRI (P = .04), and diffuse atherosclerosis on angiography (P = .006). CONCLUSION: The patients with sICAD have a high risk of stroke and cardiac events even on aggressive medical treatment. Clinical and imaging features can identify this high-risk group.

Position statement from the Indian Society of Gastroenterology, Cardiological Society of India, Indian Academy of Neurology and Vascular Society of India on gastrointestinal bleeding and endoscopic procedures in patients on antiplatelet and/or anticoagulant therapy.

Antiplatelet and/or anticoagulant agents (collectively known as antithrombotic agents) are used to reduce the risk of thromboembolic events in patients with conditions such as atrial fibrillation, acute coronary syndrome, recurrent stroke prevention, deep vein thrombosis, hypercoagulable states and endoprostheses. Antithrombotic-associated gastrointestinal (GI) bleeding is an increasing burden due to the growing population of advanced age with multiple comorbidities and the expanding indications for the use of antiplatelet agents and anticoagulants. GI bleeding in antithrombotic users is associated with an increase in short-term and long-term mortality. In addition, in recent decades, there has been an exponential increase in the use of diagnostic and therapeutic GI endoscopic procedures. Since endoscopic procedures hold an inherent risk of bleeding that depends on the type of endoscopy and patients' comorbidities, in patients already on antithrombotic therapies, the risk of procedure-related bleeding is further increased. Interrupting or modifying doses of these agents prior to any invasive procedures put these patients at increased risk of thromboembolic events. Although many international GI societies have published guidelines for the management of antithrombotic agents during an event of GI bleeding and during urgent and elective endoscopic procedures, no Indian guidelines exist that cater to Indian gastroenterologists and their patients. In this regard, the Indian Society of Gastroenterology (ISG), in association with the Cardiological Society of India (CSI), Indian Academy of Neurology (IAN) and Vascular Society of India (VSI), have developed a "Guidance Document" for the management of antithrombotic agents during an event of GI bleeding and during urgent and elective endoscopic procedures.

Carotid endarterectomy for symptomatic carotid stenosis: differences in patient profile in a Low-Middle Income Country.

INTRODUCTION: Carotid Endarterectomy (CEA) is the standard treatment for patients with symptomatic carotid stenosis. Data from Low- and Middle-Income Countries (LMIC) is sparse on CEA and its outcomes. We aimed to describe the profile of our patients, and factors associated with periprocedural cerebral ischemic events in patients with symptomatic carotid stenosis who underwent CEA in our institute. METHODS: Retrospective review of patients with symptomatic carotid stenosis(50-99%) who underwent CEA between January 2011 and December 2021 was done. Clinical and imaging parameters and their influence on periprocedural cerebral ischemic events were analysed. RESULTS: Of the 319 patients (77% males) with a mean age of 64 years (SD ±8.6), 207 (65%) presented only after a stroke. Majority (85%) had high grade stenosis (70%) of the symptomatic carotid. The mean time to CEA was 50 days (SD ±36), however only 26 patients (8.2%) underwent surgery within 2 weeks. Minor strokes and TIA occurred in 2.2%, while major strokes and death occurred in 4.1% patients. None of the clinical or imaging parameters predicted the periprocedural cerebral ischemic events. The presence of co-existing significant (50%) tandem intracranial atherosclerosis (n=77, 24%) or contralateral occlusion (n=24, 7.5%) did not influence the periprocedural stroke risk. CONCLUSION: There is a delay in patients undergoing CEA for symptomatic carotid stenosis. Majority have high grade stenosis and present late only after a stroke reflecting a lack of awareness. CEA can be performed safely even in patients with significant intracranial tandem stenosis and contralateral carotid occlusion.

Early versus Late initiation of direct oral Anticoagulants in post-ischaemic stroke patients with atrial fibrillatioN (ELAN): Protocol for an international, multicentre, randomised-controlled, two-arm, open, assessor-blinded trial.

Rationale: Direct oral anticoagulants (DOAC) are highly effective in preventing ischaemic strokes in people with atrial fibrillation (AF). However, it is unclear how soon they should be started after acute ischaemic stroke (AIS). Early initiation may reduce early risk of recurrence but might increase the risk of haemorrhagic complications. Aim: To estimate the safety and efficacy of early initiation of DOACs compared to late guideline-based initiation in people with AIS related to AF. Methods and design: An international, multicentre, randomised (1:1) controlled, two-arm, open, assessor-blinded trial is being conducted. Early treatment is defined as DOAC initiation within 48 h of a minor or moderate stroke, or at day 6-7 following major stroke. Late treatment is defined as DOAC initiation after day 3-4 following minor stroke, after day 6-7 following moderate stroke and after day 12-14 following major stroke. Severity of stroke is defined according to imaging assessment of infarct size. Sample size: ELAN will randomise 2000 participants 1:1 to early versus late initiation of DOACs. This assumes a risk difference of 0.5% favouring the early arm, allowing an upper limit of the 95% confidence interval up to 1.5% based on the Miettinen & Nurminen formula. Outcomes: The primary outcome is a composite of symptomatic intracranial haemorrhage, major extracranial bleeding, recurrent ischaemic stroke, systemic embolism or vascular death at 30 ± 3 days after randomisation. Secondary outcomes include the individual components of the primary outcome at 30 ± 3 and 90 ± 7 days and functional status at 90 ± 7 days. Discussion: ELAN will estimate whether there is a clinically important difference in safety and efficacy outcomes following early anticoagulation with a DOAC compared to late guideline-based treatment in neuroimaging-selected people with an AIS due to AF.

Women and Stroke: Different, yet Similar.

BACKGROUND: The impact of gender on acute ischemic stroke, in terms of presentation, severity, etiology, and outcome, is increasingly getting recognized. Here, we analyzed the gender-related differences in etiology and outcome of ischemic stroke in South India. METHODS: Patients with first ever ischemic stroke within 1 week of onset presenting to the Comprehensive Stroke Care Centre, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India, were included in our study. Clinical and risk factor profile was documented. The stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) at onset, and stroke subtype classification was done using Trial of Org 10172 in Acute Ischemic Stroke criteria. The 3-month functional outcome was assessed using the modified Rankin Scale (mRS) with excellent outcome defined as an mRS ≤2. RESULTS: Of the 742 patients, 250 (33.7%) were females. The age, clinical profile, and rate of reperfusion therapies did not differ between the genders. Women suffered more severe strokes (mean NIHSS 9.5 vs. 8.4, p = 0.03). While large artery atherosclerosis was more common in men (21.3% vs. 14.8%, p = 0.03), cardioembolic strokes secondary to rheumatic heart disease were more common in women (27.2% vs. 19.7%, p = 0.02). Men had a better 3-month functional outcome compared to women (68.6% vs. 61.2%, p = 0.04), but was not statistically significant after adjusting for confounders. CONCLUSION: Our data, from a single comprehensive stroke unit from South India, suggest that stroke in women are different, yet similar in many ways to men. Guideline-based treatment can result in comparable short-term outcomes, irrespective of admission stroke severity.

Current management of transient ischemic attack.

Transient ischemic attack (TIA) is a precursor to ischemic stroke. At least half of patients with TIA have a new, small ischemic lesion demonstrable on magnetic resonance imaging using a diffusion weighted sequence. The risk of subsequent major stroke is 10-20% in the next 3 months with much of that risk front-loaded in the first week. Strategies to identify and treat high-risk patients need to be defined. The optimal treatment approach and the timing of interventions, both medical and surgical, remains unknown. In general, aspirin is the first line of treatment to prevent further stroke. Other antiplatelet agents such as clopidogrel alone or in combination with aspirin and the combination aspirin/extended-release dipyridamole may be administered. Endarterectomy or carotid stenting is of great benefit to patients with TIA secondary to stenosis in the extracranial carotid artery.

Persistent post-stroke dysphagia treated with cricopharyngeal myotomy.

Post-stroke dysphagia is a common problem after stroke. About 8-13% patients have persistent dysphagia and are unable to return to pre-stroke diet even after 6 months of stroke. Use of percutaneous endoscopic gastrostomy (PEG) may be required in these patients, which may be psychologically unacceptable and impair the quality of life. In those with cricopharyngeal dysfunction leading on to refractory post-stroke dysphagia, cricopharyngeal myotomy and injection of botulinum toxin are the treatment options. We present a case of vertebrobasilar stroke who had persistent dysphagia due to cricopharyngeal dysfunction with good recovery of swallowing function following cricopharyngeal myotomy 1.5 years after the stroke.

Multimodality imaging of carotid atherosclerotic plaque: Going beyond stenosis.

Apart from the degree of stenosis, the morphology of carotid atherosclerotic plaques and presence of neovascularization are important factors that may help to evaluate the risk and 'vulnerability' of plaques and may also influence the choice of treatment. In this article, we aim to describe the techniques and imaging findings on CTA, high resolution MRI and contrast enhanced ultrasound in the evaluation of carotid atherosclerotic plaques. We also discuss a few representative cases from our institute with the related clinical implications.

Employment concerns of people with epilepsy in Kerala, south India.

We examined current employment status, reasons for unemployment, and related psychosocial concerns of 202 persons with epilepsy from the south Indian state of Kerala. Compared with 19% of the general population, 58% of persons with epilepsy were unemployed. Seizure remission for > or = 2 years, monotherapy, better education, ability to travel alone, and ability to drive were significantly associated with being employed. More than three-fourths of the persons with epilepsy had disclosed their epilepsy to their employers and co-workers, which did not adversely affect employment for the majority. The unemployed perceived fear of having seizures and seizure-related falls in the workplace, inadequate education, and antiepileptic drug-induced fatigue as reasons for unemployment. We conclude that unemployment is a major concern of people with epilepsy in this developing region. In addition to optimum seizure control, persons with epilepsy need support in job seeking, in reducing fear of seizures and falls in the workplace, and in identifying their individual abilities and limitations.

Problems and pitfalls in developing countries.

Despite major challenges, in the last decade several epilepsy centers in the developing world have successfully implemented epilepsy surgery programs and produced results comparable to those from developed countries. If the program is to have a lasting impact, it would be essential to work with and educate the local professionals and public about the recent advances in the treatment of epilepsies. The epilepsy surgery centers in developing countries should initially restrict their surgical candidates to patients with mesial temporal lobe epilepsy and those with circumscribed potentially epileptogenic lesions in whom the epileptogenic zone can be unquestionably localized by using locally available relatively inexpensive and noninvasive technologies, and in whom an excellent postoperative outcome can be guaranteed. It is important for such epilepsy center to assess its capabilities and limitations regularly and adopt a stepwise progressive approach to increasing levels of complex presurgical evaluation and surgical treatment strategies.