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Background: Recent evidence from thrombolysis trials indicates the noninferiority of intravenous tenecteplase to intravenous alteplase with respect to good functional outcomes in patients with acute stroke. We examined whether the health-related quality of life (HRQOL) of patients with acute stroke differs by the type of thrombolysis treatment received. In addition, we examined the association between the modified Rankin Scale score 0 to 1 and HRQOL and patient-reported return to prebaseline stroke functioning at 90 days., Methods: Data were from all patients included in the AcT trial (Alteplase Compared to Tenecteplase), a pragmatic, registry-linked randomized trial comparing tenecteplase with alteplase. HRQOL at 90-day post-randomization was assessed using the 5-item EuroQOL questionnaire (EQ5D), which consists of 5 items and a visual analog scale (VAS). EQ5D index values were estimated from the EQ5D items using the time tradeoff approach based on Canadian norms. Tobit regression and quantile regression models were used to evaluate the adjusted effect of tenecteplase versus alteplase treatment on the EQ5D index values and VAS score, respectively. The association between return to prebaseline stroke functioning and the modified Rankin Scale score 0 to 1 and HRQOL was quantified using correlation coefficient ( r ) with 95% CI., Results: Of 1577 included in the intention-to-treat analysis patients, 1503 (95.3%) had complete data on the EQ5D. Of this, 769 (51.2%) were administered tenecteplase and 717 (47.7%) were female. The mean EQ5D VAS score and EQ5D index values were not significantly higher for those who received intravenous tenecteplase compared with those who received intravenous alteplase ( P =0.10). Older age ( P <0.01), more severe stroke assessed using the National Institutes of Health Stroke Scale ( P <0.01), and longer stroke onset-to-needle time ( P =0.004) were associated with lower EQ5D index and VAS scores. There was a strong association ( r , 0.85 [95% CI, 0.81-0.89]) between patient-reported return to prebaseline functioning and modified Rankin Scale score 0 to 1 Similarly, there was a moderate association between return to prebaseline functioning and EQ5D index ( r , 0.45 [95% CI, 0.40-0.49]) and EQ5D VAS scores ( r , 0.42 [95% CI, 0.37-0.46])., Conclusions: Although there is no differential effect of thrombolysis type on patient-reported global HRQOL and EQ 5D-5L index values in patients with acute stroke, sex- and age-related differences in HRQOL were noted in this study., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249., Competing Interests: Disclosures Dr Menon reports stock in Circle NVI and patents for systems of triage in acute stroke. Dr Sajobi reports consulting fees received from Circle NVI and employment at the University of Calgary. Dr Almekhlafi reports to be on the medical advisory board of Palmera Medical, Inc. Dr Deschaintre reports being part of the Association des neurologues du Québec, the Société des Sciences Vasculaires du Québec, and the Université de Montréal. Dr Coutts reports that Boehringer Ingelheim provided a study drug (tenecteplase) for the TEMPO-2 trial. Dr Catanese reports employment with Hamilton Health Sciences and McMaster University, consulting fees from Hoffmann-La Roche Ltd, and a grant/contract from Servier Pharmaceuticals LLC. Dr Field reports consulting fees from AstraZeneca Canada, Bayer, HLS Therapeutics, and Roche; stock and being a fiduciary officer (board member) in Destine Health; grants/contracts from Boehringer Ingelheim and Bayer; and being an expert witness for the Canadian Medical Protective Association. Dr Siddiqui reports a grant/contract from Allergan and other interests from Bayer and Boehringer Ingelheim. Dr Demchuk reports stock in Circle NVI and patents for stroke imaging software; consulting fees from Servier Pharmaceuticals LLC, NovaSignal, Boehringer Ingelheim, HLS Therapeutics, Inc, Hoffmann-La Roche Ltd, and Medtronic; data and safety monitoring with Philips; and other interests from AstraZeneca Canada, Novo Nordisk AS, and Pfizer Canada, Inc. Dr Hill reports employment with the University of Calgary; consulting fees from Brainsgate Ltd; grants/contracts from Biogen, Inc, Boehringer Ingelheim, the Canadian Institutes of Health Research, Medtronic, MicroVention, Inc, and NoNO, Inc; being part of the end point review committee at Merck; stock in Circle NVI; and patents for systems of triage in acute stroke. Dr Poppe reports grant funding from the Fondation Brain Canada and the Heart and Stroke Foundation of Canada and research funding from Stryker. Dr Swartz reports stock in FollowMD, Inc, and grants/contracts from the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, the National Institutes of Health, the Ontario Brain Institute, and the Sunnybrook Research Institute. The other authors report no conflicts.

Background: Early reperfusion has the best likelihood for a favorable outcome in acute ischemic stroke (AIS) with large vessel occlusion (LVO). Our experience with mobile stroke unit (MSU) for direct to angiosuite (DTAS) transfer in AIS patients with suspected LVO is presented., Methods: Retrospective review of prospectively collected data from November 2019 to August 2022, of patients evaluated and transferred by the University of Alberta Hospital MSU and moved to angiosuite for endovascular thrombectomy (EVT)., Result: A total of 41 cases were included. Nine were chosen for DTAS and 32 were shifted to angiosuite after stopping for computed tomography (CT) angiography of the head and neck (no-DTAS). Stroke severity measured by NIHSS (median with interquartile range (IQR)) was higher in patients of DTAS, 22 (14-24) vs 14.5 (5-25) in no-DTAS ( p = 0.001). The non-contrast CT head in MSU showed hyperdense vessels in 8 (88.88%) DTAS vs 11 (34.35%) no-DTAS patients ( p = 0.003). The EVT timelines (median with IQR, 90 th percentile) including "door to artery puncture time" were 31 (23-50, 49.2) vs 79 (39-264, 112.8) minutes, and "door to recanalization time" was 69 (49-110, 93.2) vs 105.5 (52-178, 159.5) minutes in DTAS vs no-DTAS group, respectively. The workflow times were significantly shorter in the DTAS group ( p < 0.001). Eight (88.88%) out of 9 DTAS patients had LVO and underwent thrombectomy., Conclusions: MSU for DTAS in patients with high NIHSS scores, cortical signs, and CT showing hyperdense vessel is an effective strategy to reduce the EVT workflow time.

Objective: To test the hypothesis that an Accredited social health activist (ASHA), a community health volunteer in a task-sharing model can help in sustained control of systolic blood pressure (BP) in rural people with Stroke and hypertension at 6 months follow up., Methods: In this randomized trial two rural areas (Pakhowal and Sidhwan bet) with 70 and 94 villages respectively were screened for people with stroke and hypertension. They were assigned to either ASHA-assisted BP control in addition to standard-of-care (Pakhowal-intervention Group) or standard-of-care alone (Sidhwan bet- Control Group). Assessors blinded to intervention conducted the baseline and 6 months follow-up visits to measure risk factors in both the rural areas., Results: A total of 140 people with stroke with mean age of 63.7 ± 11.5 years and 44.3% females were randomised. The baseline systolic BP was higher in the intervention group (n = 65,173.5 ± 22.9 mmHg) compared to the control group (n = 75,163 ± 18.7 mmHg, p = 0.004). The follow-up systolic BP was lower in the intervention group compared to the control group 145 ± 17.2 mmHg and 166.6 ± 25.7 mmHg respectively (p < 0.0001). According to the intention-to-treat analysis a total of 69.2% of patients in the intervention group achieved systolic BP control compared to 18.9% in the control group patients (OR 9, 95% CI 3.9-20.3; p < 0.0001)., Conclusion: Task sharing with ASHA a community health volunteer can improve BP control in rural people with stroke and hypertension. They can also help in the adoption of healthy behaviour., Clinical Trial Registration Number: ctri.nic.in, CTRI/2018/09/015709., Competing Interests: Declaration of Competing Interest The Authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In patients with ischemic stroke, motor and sensory impairments are common and are associated with functional disability. Conventional physiotherapy (CP) is the primary modality of rehabilitation for post-stroke sensorimotor dysfunction. Ayurveda is a commonly practiced alternative system of medicine that offers unique rehabilitative measures for post-stroke recovery. We hypothesize that Ayurvedic rehabilitative treatment (ART) is superior to similar duration CP in improving the sensorimotor recovery of patients with ischemic stroke at 90 days after enrollment. AyuRvedic TrEatment in the Rehabilitation of Ischemic STrOke Patients in India: A Randomized controllEd trial (RESTORE) is an investigator-initiated, multicenter, prospective, randomized, controlled, parallel-arm, blinded outcome assessment trial being conducted under the Indian Stroke Clinical Trial (INSTRuCT) Network across the four comprehensive stroke centers in India. Consecutive hemodynamically stable adult patients with their first acute ischemic stroke between 1 and 3 months from stroke onset are being randomized (1:1) into two treatment groups to receive either 1 month of ART or 1 month of CP. The primary outcome measure is the Fugl Meyer Assessment-upper extremity for physical performance at 90 days. The secondary outcomes are the modified Rankin Scale, Barthel Index, Berg Balance, and SF-36 at 90 days. The safety outcomes include a composite of irreversible morbidity and mortality. A sample size of 140 (70 in each group) patients with ischemic stroke will allow us to detect a minimal clinical important difference of 9.4 (standard deviation) with superiority margin of 5, an attrition rate of 10%, alpha of 5%, and power of 80%. This randomized trial will systematically assess the efficacy and safety of traditional ART compared to CP. The trial has been registered in the Clinical Trial Registry India (CTRI/2018/04/013379)., (© 2023 S. Karger AG, Basel.)

Background: Uncertainty prevails regarding the patterns of autonomic dysfunction in patients with idiopathic Parkinson's disease (IPD). This study was undertaken with the aim of assessing the complete spectrum of cardiovascular autonomic function tests (CAFTs) and blood pressure variability patterns in IPD patients while comparing the same with age-matched controls., Methods: Patients with IPD presenting to the Christian Medical College and Hospital from December 2016 to November 2018 along with age-matched controls were prospectively evaluated using CAFTs. The IPD patients also underwent ambulatory blood pressure (BP) monitoring (ABPM), and the diurnal systolic BP differences were used to classify into dippers (10-20%), non-dippers (0-10%), reverse dippers (<0%), and extreme dippers (>20%)., Results: Autonomic dysfunction (AD) was prevalent in 41 (68.3%) IPD patients even in early disease (median (inter-quartile range) symptom duration 2 (1-4) years, mean Hoehn and Yahr (H&Y) stage 2 (1.5-2.8). Both sympathetic and parasympathetic parameters were impaired among IPD patients when compared to healthy controls. (E: I ratio 1.17 ± 0.12 vs 1.26 ± 0.14 ( P < 0.001), Valsalva ratio (VR) 1.33 ± 0.27 vs 1.55 ± 0.25 ( P < 0.001), PRT 100 9.6 ± 8.0 vs 3.1 ± 1.8 ( P < 0.001), tilt-up SBP Avg change 8.8 (4.2-13.8) vs 1.8 (-2.9-6.1) ( P < 0.001), tilt-up HR Avg change 4.8 (2.2-8.2) vs 1.9 (-0.7-5.1) ( P < 0.001). BP variability was demonstrated in 47 (79.7%) of IPD patients, with reverse dipping pattern in 28 (47.5%) seen more frequently in this cohort., Conclusions: Timely detection of AD may be helpful not only in recognizing IPD in its pre-motor stages but also in optimizing management for this population of patients. BP variability and abnormal dipping patterns on ABPM can be a potential marker of dysautonomia., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Annals of Indian Academy of Neurology.)

Background: Intravenous thrombolysis with alteplase bolus followed by infusion is a global standard of care for patients with acute ischaemic stroke. We aimed to determine whether tenecteplase given as a single bolus might increase reperfusion compared with this standard of care., Methods: In this multicentre, open-label, parallel-group, registry-linked, randomised, controlled trial (AcT), patients were enrolled from 22 primary and comprehensive stroke centres across Canada. Patients were eligible for inclusion if they were aged 18 years or older, with a diagnosis of ischaemic stroke causing disabling neurological deficit, presenting within 4·5 h of symptom onset, and eligible for thrombolysis per Canadian guidelines. Eligible patients were randomly assigned (1:1), using a previously validated minimal sufficient balance algorithm to balance allocation by site and a secure real-time web-based server, to either intravenous tenecteplase (0·25 mg/kg to a maximum of 25 mg) or alteplase (0·9 mg/kg to a maximum of 90mg; 0·09 mg/kg as a bolus and then a 60 min infusion of the remaining 0·81 mg/kg). The primary outcome was the proportion of patients who had a modified Rankin Scale (mRS) score of 0-1 at 90-120 days after treatment, assessed via blinded review in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment who did not withdraw consent). Non-inferiority was met if the lower 95% CI of the difference in the proportion of patients who met the primary outcome between the tenecteplase and alteplase groups was more than -5%. Safety was assessed in all patients who received any of either thrombolytic agent and who were reported as treated. The trial is registered with ClinicalTrials.gov, NCT03889249, and is closed to accrual., Findings: Between Dec 10, 2019, and Jan 25, 2022, 1600 patients were enrolled and randomly assigned to tenecteplase (n=816) or alteplase (n=784), of whom 1577 were included in the ITT population (n=806 tenecteplase; n=771 alteplase). The median age was 74 years (IQR 63-83), 755 (47·9%) of 1577 patients were female and 822 (52·1%) were male. As of data cutoff (Jan 21, 2022), 296 (36·9%) of 802 patients in the tenecteplase group and 266 (34·8%) of 765 in the alteplase group had an mRS score of 0-1 at 90-120 days (unadjusted risk difference 2·1% [95% CI - 2·6 to 6·9], meeting the prespecified non-inferiority threshold). In safety analyses, 27 (3·4%) of 800 patients in the tenecteplase group and 24 (3·2%) of 763 in the alteplase group had 24 h symptomatic intracerebral haemorrhage and 122 (15·3%) of 796 and 117 (15·4%) of 763 died within 90 days of starting treatment INTERPRETATION: Intravenous tenecteplase (0·25 mg/kg) is a reasonable alternative to alteplase for all patients presenting with acute ischaemic stroke who meet standard criteria for thrombolysis., Funding: Canadian Institutes of Health Research, Alberta Strategy for Patient Oriented Research Support Unit., Competing Interests: Declaration of interests BKM has stock options in Circle NVI and has consulted for Biogen and Boehringer Ingelheim. SBC is principal investigator of the TEMPO-2 trial, for which Boehringer Ingelheim provides the study drug (tenecteplase). LC has received payments by Servier and consulting fees from Ischaemavie RAPID, Circle NV, and Canadian Medical Protective Association. JS has a grant from Medtronic to the University of Manitoba. AMD has received consulting fees from Medtronic and honoraria from Boehringer Ingelheim. LCG is on advisory boards for AstraZeneca and Servier and has stock options in AstraZenca. ASh has received consulting fees from Bayer, Servier Canada, Daiichi Sanyko Compan, AstraZeneca, VarmX, and Takeda; honoraria from Bayer and Daiichi Sankyo; is on an advisory board for Bayer; and has stock options in Ensho. MDH has received consulting fees from Sun Pharma and Brainsgate and has stock options in Circle NVI. DJG has received consulting fees from HSL Therapeutics. APo has received a project research grant from Stryker and honoraria from BMS-Pfizer. TTS has received consulting fees from Circle NVI. RHS has stock options in FollowMD and receives salary support for research from the Heart & Stroke Foundation of Canada, Sandra Black Centre for Brain Resilience & Recovery, and Ontario Brain Institute. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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.

Mobile Stroke Unit (MSU) expedites the delivery of intravenous thrombolysis in acute stroke patients. We further evaluated the functional outcome of patients shipped to a tertiary care centre or repatriated to local hospitals after triage by MSU in acute stroke syndrome in rural northern Alberta. Consecutive patients with suspected acute stroke syndrome were included. On the basis of neurology consultation and, Computed Tomography findings, patients, who were thrombolysed or needed advanced care were transported to the Comprehensive stroke center (CSC) (Triage to CSC group). Other patients were repatriated to local hospital care (Triage to LHC group). A total of 156 patients were assessed in MSU, 73 (46.8%) were female and the mean age was 66.6 ± 15 years. One hundred and eight (69.2%) patients, including 41 (26.3%) treated with thrombolysis were transported to the CSC (Triage to CSC group) and 48 (30.8%) were repatriated to local hospital care. The diagnosis made in MSU and final diagnosis were matching in 88% (95) and 91.7% (44, p = 0.39) in Triage to CSC and Triage to LHC groups respectively. Prehospital triage by MSU of acute stroke syndrome can reliably repatriate patients to the home hospital. The proposed model has the potential to triage patients according to their medical needs by enabling treatment in home hospitals whenever reasonable.

Purpose: Aging and increased burden of cardiovascular risk factors are associated with severity of white matter hyperintensity (WMH). We assessed the burden and risk factor profile of WMHs in South Asian patients with transient ischemic attack (TIA) and minor stroke., Methods: Patients with acute ischemic stroke with the National Institute of Health stroke scale (NIHSS) score ≤ 5 who underwent MRI were included. The severity of WMHs was assessed based on age-related white matter change (ARWMC) scale (0-30). A score of > 8 or more was considered moderate-severe involvement. Logistic regression analysis was performed to assess the association with risk factors., Results: A total of 424 patients with a mean ± SD age of 57.4 ± 14.5 years [females, 108 (25.5%)] were analyzed. Fifty-four (12.7%) patients had moderate or severe WMHs (ARWMC score > 8). Age (OR 1.03, 95% CI 1.01-1.06; p = 0.004), hypertension (OR 2.3, 95% CI 1.1-5.1; p = 0.03) and smoking tobacco (OR 2.8, 95% CI 1.4-5.6; p = 0.003) were independently associated with ARWMC score > 8. The median (IQR) regional score in patients with ARWMC score > 8 was maximum in frontal areas 4 (4-6, p < 0.0001) and parietooccipital areas 4.5(4-6, p < 0.0001). The presence of microbleeds (OR 6.3, 95% CI 3.1-12.7; p < 0.0001) was independently associated with ARWMC score > 8., Conclusion: South Asian patients with TIA and minor stroke are relatively young, and few patients have moderate and severe WMHs. Hypertension and tobacco smoking increases the risk of WMH. Targeting modifiable risk factors may reduce the burden of WMHs and vascular dementia.

Background: Lack of compliance to medication and uncontrolled risk factors are associated with increased risk of recurrent stroke and acute coronary syndrome in patients with recent stroke. Multimodal patient education may be a strategy to improve the compliance to medication and early adoption of nonpharmacological measures to reduce the vascular risk factor burden in patients with stroke. We thus aim to develop multilingual short messaging services (SMS), print, and audio-visual secondary stroke prevention patient education package. The efficacy of the package will be tested in a randomized control trial to prevent major cardiovascular and cerebrovascular events., Methods: In the formative stage, intervention materials (SMS, video, and workbook) were developed. In the acceptability stage, the package was independently assessed and modified by the stakeholders involved in the stroke patient care and local language experts. The modified stroke prevention package was tested for implementation issues ( implementation stage)., Results: Sixty-nine SMS, six videos, and workbook with 11 chapters with 15 activities were developed in English language with a mean ± SD SMOG index of 9.1 ± 0.4. A total of 355 stakeholders including patients (24.8%), caregivers (24.8%), doctors (10.4%), nurses (14.1%), local language experts (2.8%), physiotherapists (13.2%), and research coordinators (9.8%) participated in 10 acceptability stage meetings. The mean Patient Education Material Assessment Tool understandability score in all languages for SMS, video scripts, and workbook was 95.2 ± 2.6%, 95.2 ± 4.4%, and 95.3 ± 3.6%, respectively. The patients [ n = 20, mean age of 70.3 ± 10.6 years and median interquartile range (IQR) baseline NIHSS 1 (0-3)] or the research coordinators ( n = 2) noted no implementation issues at the end of 1 month., Conclusion: An implementable complex multilingual patient education material could be developed in a stepwise manner. The efficacy of the package to prevent major adverse cardiovascular events is being tested in the SPRINT INDIA study., Competing Interests: There are no conflicts of interest., (Copyright: © 2006 - 2020 Annals of Indian Academy of Neurology.)

Background: Door to needle (DTN) time provides valuable insight into stroke care workflow and is a performance indicator of an acute stroke unit. The aim of the current study was to ascertain whether a door to needle time of less than 60 min can be achieved for intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) and maintained long term in a comprehensive stroke unit., Methods: Patients with AIS treated with IVT in the stroke unit formed the study group. Demographic and clinical characteristics including door to imaging (DTI) time, DTN time, and 3 month functional outcome were abstracted. Pairwise comparison was done of yearly median DTI and DTN times with Bonferroni correction., Results: Over a period of 6 years a total of 196 patients with mean age of 61.5 ± 13.1 years and median (IQR) NIHSS 11 (8-16) underwent IVT. The median DTI time and DTN time over the study period was 15 (12-21) minutes and 40 (30-50) minutes respectively. A total of 90.1%, 69.4% and 29.1% patients received IVT within 60 min, 45 min and 30 min respectively. On pairwise comparison of the median yearly DTN Year 2016 and 2017 were lower compared to most of the earlier years (p < 0.0001). Good functional outcome (mRS ≤ 2) was noted in 68.7% patients at 3 months follow-up., Conclusion: It is possible to sustainably reduce DTN time for IVT in AIS to well below the current 60 min benchmark with hospital system training and teamwork., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The effect of blood pressure (BP) reduction on cerebral blood flow (CBF) in acute ischemic stroke is unknown. We measured regional CBF with perfusion-weighted MRI before and after BP treatment in a three-armed non-randomized prospective controlled trial. Treatment arm assignment was based on acute mean arterial pressure (MAP). Patients with (MAP) >120 mmHg ( n  = 14) were treated with intravenous labetalol and sublingual (SL) nitroglycerin (labetalol group). Those with MAP 100-120 mmHg ( n  = 17) were treated with SL nitroglycerin (0.3 mg) ('NTG Group') and those with baseline MAP<100 mmHg ( n  = 18) were not treated with antihypertensive drugs (untreated group). Forty-nine patients (18 female, mean age 65.3 ± 12.9 years) were serially imaged. Labetalol reduced MAP by 12.5 (5.7-17.7) mmHg, p  = 0.0002. MAP remained stable in the NTG (6.0 (0.4-16, p  = 0.3) mmHg and untreated groups (-0.3 (-2.3-7.0, p  = 0.2) mmHg. The volume of total hypoperfused tissue (CBF<18 ml/100 g/min) did not increase after labetalol (-1.1 ((-6.5)-(-0.2)) ml, p  = 0.1), NTG (0 ((-1.5)-4.5) ml, p  = 0.72), or no treatment 0.25 ((-10.1)-4.5) ml, p  = 0.87). Antihypertensive therapy, based on presenting BP, in acute stroke patients was not associated with an increased volume of total hypoperfused tissue.

Background and Purpose- Cerebral perfusion in acute ischemic stroke patients is often assessed before endovascular thrombectomy (EVT), but rarely after. Perfusion data obtained following EVT may provide additional prognostic information. We developed a tool to quantitatively derive perfusion measurements from digital subtraction angiography (DSA) data and examined perfusion in patients following EVT. Methods- Source DSA images from acute anterior circulation stroke patients undergoing EVT were retrospectively assessed. Following deconvolution, maps of mean transit time (MTT) were generated from post-EVT DSA source data. Thrombolysis in Cerebral Infarction grades and MTT in patients with and without hemorrhagic transformation (HT) at 24 hours were compared. Receiver operating characteristic modeling was used to classify the presence/absence of HT at 24 hours by MTT. Results- Perfusion maps were generated in 50 patients using DSA acquisitions that were a median (interquartile range) of 9 (8-10) seconds in duration. The median post-EVT MTT within the affected territory was 2.6 (2.2-3.3) seconds. HT was observed on follow-up computed tomography in 16 (32%) patients. Thrombolysis in Cerebral Infarction grades did not differ in patients with HT from those without (P=0.575). Post-EVT MTT maps demonstrated focal areas of hyperperfusion (n=8) or persisting hypoperfusion (n=3) corresponding to the regions where HT later developed. The relationship between MTT and HT was U-shaped; HT occurred in patients at both the lowest and highest extremes of MTT. An MTT threshold <2 or >4 seconds was 81% sensitive and 94% specific for classifying the presence of HT at follow-up. Conclusions- Perfusion measurements can be obtained using DSA perfusion with minimal changes to current stroke protocols. Perfusion imaging post-recanalization may have additional clinical utility beyond visual assessment of source angiographic images alone.

Background: Despite the use of validated prehospital stroke scales, stroke mimics are frequent among patients transported by Emergency Medical Services to the Emergency Department. We aimed to describe the frequency and characteristics of neurological and non-neurological mimics transported to a comprehensive stroke center for acute stroke evaluation., Methods: This was a retrospective analysis of a database consisting of all consecutive patients with suspected stroke transported to the Emergency Department of a comprehensive stroke center during an 18-month period. Hospital charts and neuroimaging were utilized to adjudicate the final diagnosis (acute stroke, stroke mimic, and specific underlying diagnoses)., Results: Nine hundred fifty patients were transported with suspected stroke, among whom 405 (42.6%) were stroke mimics (age 66.9 ± 17.1 years; 54% male). Neurological mimics were diagnosed in 223 (55.1%) patients and mimics were non-neurological in 182. The most common neurological diagnoses were seizures (19.7%), migraines (18.8%), and peripheral neuropathies (11.2%). Cardiovascular (14.6%) and psychiatric (11.9%) diagnoses were common non-neurological mimics. Patients with neurological mimics were younger (64.1 ± 17.3 years versus 70.5 ± 16.1 years, P < .001) and had less vascular risk factors than non-neurological mimics. The proportion of non-neurological mimics remained high (38%) despite the use of a prehospital stroke identification scale., Conclusions: Stroke mimics are common among patients transported by Emergency Medical Services to a comprehensive stroke center for suspected stroke, with a considerable proportion being non-neurological in origin. Studies refining triage and transport of suspected acute stroke may be warranted to minimize the number of mimics transported by to a comprehensive stroke center for acute stroke evaluation., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Intracerebral haemorrhage growth is associated with poor clinical outcome and is a therapeutic target for improving outcome. We aimed to determine the absolute risk and predictors of intracerebral haemorrhage growth, develop and validate prediction models, and evaluate the added value of CT angiography., Methods: In a systematic review of OVID MEDLINE-with additional hand-searching of relevant studies' bibliographies- from Jan 1, 1970, to Dec 31, 2015, we identified observational cohorts and randomised trials with repeat scanning protocols that included at least ten patients with acute intracerebral haemorrhage. We sought individual patient-level data from corresponding authors for patients aged 18 years or older with data available from brain imaging initially done 0·5-24 h and repeated fewer than 6 days after symptom onset, who had baseline intracerebral haemorrhage volume of less than 150 mL, and did not undergo acute treatment that might reduce intracerebral haemorrhage volume. We estimated the absolute risk and predictors of the primary outcome of intracerebral haemorrhage growth (defined as >6 mL increase in intracerebral haemorrhage volume on repeat imaging) using multivariable logistic regression models in development and validation cohorts in four subgroups of patients, using a hierarchical approach: patients not taking anticoagulant therapy at intracerebral haemorrhage onset (who constituted the largest subgroup), patients taking anticoagulant therapy at intracerebral haemorrhage onset, patients from cohorts that included at least some patients taking anticoagulant therapy at intracerebral haemorrhage onset, and patients for whom both information about anticoagulant therapy at intracerebral haemorrhage onset and spot sign on acute CT angiography were known., Findings: Of 4191 studies identified, 77 were eligible for inclusion. Overall, 36 (47%) cohorts provided data on 5435 eligible patients. 5076 of these patients were not taking anticoagulant therapy at symptom onset (median age 67 years, IQR 56-76), of whom 1009 (20%) had intracerebral haemorrhage growth. Multivariable models of patients with data on antiplatelet therapy use, data on anticoagulant therapy use, and assessment of CT angiography spot sign at symptom onset showed that time from symptom onset to baseline imaging (odds ratio 0·50, 95% CI 0·36-0·70; p<0·0001), intracerebral haemorrhage volume on baseline imaging (7·18, 4·46-11·60; p<0·0001), antiplatelet use (1·68, 1·06-2·66; p=0·026), and anticoagulant use (3·48, 1·96-6·16; p<0·0001) were independent predictors of intracerebral haemorrhage growth (C-index 0·78, 95% CI 0·75-0·82). Addition of CT angiography spot sign (odds ratio 4·46, 95% CI 2·95-6·75; p<0·0001) to the model increased the C-index by 0·05 (95% CI 0·03-0·07)., Interpretation: In this large patient-level meta-analysis, models using four or five predictors had acceptable to good discrimination. These models could inform the location and frequency of observations on patients in clinical practice, explain treatment effects in prior randomised trials, and guide the design of future trials., Funding: UK Medical Research Council and British Heart Foundation., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background and Purpose: Early anticoagulation after cardioembolic stroke remains controversial because of the potential for hemorrhagic transformation (HT). We tested the safety and feasibility of initiating rivaroxaban ≤14 days after cardioembolic stroke/transient ischemic attack., Methods: A prospective, open-label study of patients with atrial fibrillation treated with rivaroxaban ≤14 days of transient ischemic attack or ischemic stroke (National Institute of Health Stroke Scale <9). All patients underwent magnetic resonance imaging <24 hours of rivaroxaban initiation and day 7. The primary end point was symptomatic HT at day 7., Results: Sixty patients (mean±SD age 71±19 years, 82% stroke/18% transient ischemic attack) were enrolled. Median (interquartile range) time from onset to rivaroxaban was 3 (5) days. At treatment initiation, median National Institute of Health Stroke Scale was 2 (4), and median diffusion-weighted imaging volume was 7.9 (13.7) mL. At baseline, HT was present in 25 (42%) patients (hemorrhagic infarct [HI]1=19, HI2=6). On follow-up magnetic resonance imaging, no patients developed symptomatic HT. New asymptomatic HI1 developed in 3 patients, and asymptomatic progression from HI1 to HI2 occurred in 5 patients; otherwise, HT remained unchanged at day 7., Conclusions: These data support the safety of rivaroxaban initiation ≤14 days of mild-moderate cardioembolic stroke/transient ischemic attack. Magnetic resonance imaging evidence of petechial HT, which is common, does not appear to increase the risk of symptomatic HT., (© 2016 American Heart Association, Inc.)

Background and Purpose: Acute ischemic stroke patients are at risk of early recurrence. We tested the feasibility and safety of initiating dabigatran in patients, within 24 hours of minor stroke in patients without atrial fibrillation., Methods: Minor stroke patients (National Institutes of Health Stroke Scale score ≤3) without atrial fibrillation and evidence of acute infarction on magnetic resonance imaging were treated with dabigatran. Treatment began within 24 hours of onset and was continued for 30 days. The primary end point was symptomatic hemorrhagic transformation., Results: A total of 53 patients with median (interquartile range) age of 68 (57-77) years and National Institutes of Health Stroke Scale score of 1 (0-2) were enrolled. Baseline diffusion-weighted imaging volume was 0.8 (0.3-2.4) mL. No patients experienced symptomatic hemorrhagic transformation. Three patients had evidence of asymptomatic petechial hemorrhagic transformation on day 7, which remained stable at day 30, while continuing dabigatran., Conclusions: Dabigatran treatment within 24 hours of minor stroke is feasible. A larger randomized trial is required to confirm the safety and efficacy of this treatment approach., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT 01769703., (© 2015 American Heart Association, Inc.)

Background and Purpose: Diffusion-weighted imaging (DWI) lesion volume on magnetic resonance imaging is increasingly being used as a surrogate outcome measure in clinical trials. We aimed to characterize the evolution of DWI lesion volumes within 30 days of symptom onset after minor stroke., Methods: Minor stroke patients with DWI lesions on magnetic resonance imaging within 48 hours of symptom onset were prospectively followed with magnetic resonance imaging brain scan at 7 and 30 days. Change in the lesion volume was defined as the difference between day 30 Fluid-Attenuated Inversion Recovery and baseline DWI lesion volumes., Results: Three patterns of infarct evolution were observed: reduction (72 [63%]), no change (26 [23%]), and growth (16 [14%]). Patients with infarct reduction at 30 days had larger baseline DWI lesion volumes (2.5 [0.9-8.5] mL) than those with stable infarcts (0.5 [0.3-0.9] mL; P=0.01). Complete DWI reversal at day 30, was seen in only 6 (5.3%) patients., Conclusions: The most common pattern of infarct evolution in patients with minor stroke is a reduction in volume, but complete resolution is uncommon., (© 2015 American Heart Association, Inc.)

Background and Purpose: Diffusion-weighted imaging (DWI) of tissue water is a sensitive and specific indicator of acute brain ischemia, where reductions of the diffusion of tissue water are observed acutely in the stroke lesion core. Although these diffusion changes have been long attributed to cell swelling, the precise nature of the biophysical mechanisms remains uncertain., Methods: The potential cause of diffusion reductions after stroke was investigated using an advanced DWI technique, oscillating gradient spin-echo DWI, that enables much shorter diffusion times and can improve specificity for alterations of structure at the micron level., Results: Diffusion measurements in the white matter lesions of patients with acute ischemic stroke were reduced by only 8% using oscillating gradient spin-echo DWI, in contrast to a 37% decrease using standard DWI. Neurite beading has recently been proposed as a mechanism for the diffusion changes after ischemic stroke with some ex vivo evidence. To explore whether beading could cause such differential results, simulations of beaded cylinders and axonal swelling were performed, yielding good agreement with experiment., Conclusions: Short diffusion times result in dramatically reduced diffusion contrast of human stroke. Simulations implicate a combination of neuronal beading and axonal swelling as the key structural changes leading to the reduced apparent diffusion coefficient after stroke., (© 2015 American Heart Association, Inc.)

Background: Acute ischemic stroke thrombolysis in patients taking dabigatran is controversial because of a presumed increased risk of symptomatic hemorrhagic transformation. Using data from our local hematopathology laboratory, we developed a thrombolysis protocol for acute ischemic stroke patients taking dabigatran., Methods: A local thrombin time (TT)-dabigatran concentration relationship was calculated using dabigatran calibrators. The effect of dabigatran on activated partial thromboplastin time (aPTT) and prothrombin time (PT) (international normalized ratio [INR]) was also measured. A protocol was developed, in which a dabigatran concentration less than 10 ng/mL (corresponding to a TT<38 seconds or a normal aPTT) was selected as the upper limit for thrombolysis. Consecutive patients presenting with acute stroke were then enrolled in this prospective study., Results: In the 8 months after development of the protocol, 13 potential thrombolysis candidates taking dabigatran were assessed at a median (interquartile range) time of 192 (143) minutes. The median National Institutes of Health Stroke Scale score was 18 (20). The mean time from arrival to TT, aPTT, and PT (INR) results were 39±4.1 minutes, 21±6.5 minutes, and 21±6.5 minutes, respectively. Based on TT/aPTT, 4 patients were ineligible for thrombolysis. Six patients were not treated because of minor or resolving symptoms and another presented with intracerebral hemorrhage. Two patients were treated with intravenous tissue plasminogen activator (tPA), without symptomatic hemorrhagic transformation in either case. In 3 patients (42.8%), aPTT was normal, despite a prolonged TT., Conclusions: Administration of intravenous tPA in dabigatran-treated patients is feasible. Although, the relationship between dabigatran concentrations and coagulation measures varies between laboratories, individual protocols, preferably based on TT, can be developed at acute stroke treatment centers., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Multimodal imaging in acute ischemic stroke defines the extent of arterial collaterals, resultant penumbra, and associated infarct core, yet limitations abound. We identified superficial and deep venous drainage patterns that predict outcomes in patients with a proximal arterial occlusion of the anterior circulation., Methods: An observational study that used computed tomography (CT) angiography to detail venous drainage in a consecutive series of patients with a proximal anterior circulation arterial occlusion. The principal veins that drain the cortex (superficial middle cerebral, vein of Trolard, vein of Labbé, and basal vein of Rosenthal) and deep structures were scored with a categorical scale on the basis of degree of contrast enhancement. The Prognostic Evaluation based on Cortical vein score difference In Stroke score encompassing the interhemispheric difference of the composite scores of the veins draining the cortices (superficial middle cerebral+vein of Trolard+vein of Labbé+basal vein of Rosenthal) was analyzed with respect to 90-day modified Rankin Scale outcomes., Results: Thirty-nine patients were included in the study. A Prognostic Evaluation based on Cortical vein score difference In Stroke score of 4 to 8 accurately predicted poor outcomes (modified Rankin Scale, 3-6; odds ratio, 20.53; P<0.001). On stepwise logistic regression analyses adjusted for CT Alberta stroke program early CT score, CT angiography collateral grading and National Institutes of Health Stroke Scale score, a Prognostic Evaluation based on Cortical vein score difference In Stroke score of 4 to 8 (odds ratio, 23.598; P=0.009) and an elevated admission National Institutes of Health Stroke Scale (odds ratio, 1.423; P=0.023) were independent predictors of poor outcome., Conclusions: The Prognostic Evaluation based on Cortical vein score difference In Stroke score, a novel measure of venous enhancement on CT angiography, accurately predicts clinical outcomes. Venous features on computed tomography angiography provide additional characterization of collateral perfusion and prognostication in acute ischemic stroke.

Purpose: Emergent EEG (eEEG) is an EEG performed on a non-elective basis upon request from a clinician for a seemingly emergency indication. Little is known about the long-term prognosis of patients with emergent periodic lateralized epileptiform discharges (ePLEDs)., Methods: We analyzed the EEG and clinical records of patients with ePLEDs from January 2002 to December 2008., Results: Out of 1948 eEEGs, 79 (4%) patients had ePLEDs. Sixty-three patients had ePLEDs and 16 had eBiPLEDs (emergent bilateral periodic lateralized epileptiform discharges). The etiology of ePLEDs was CNS infection and inflammation (35.4%), stroke (32.9%), and metabolic encephalopathy (11.4%). Of the surviving 52 (65.8%) patients with ePLEDs, 34 (65.4%) had persistent seizures during a mean follow-up of 28 months (range 12-72 months). Seizure as the initial presentation was more commonly seen in children as compared to adults (64% versus 31%, p=0.005). CNS infection and inflammation were also seen more frequently in the pediatric age group (50% versus 27%, p=0.04). At follow-up, patients with eBiPLEDs had more seizures than patients with ePLEDs (87.5% versus 61.3%)., Conclusion: ePLEDs is associated with significant morbidity and mortality. However, the etiology of ePLEDs and brain dysfunction will influence the long-term outcome. This information is invaluable for prognostication and underscores the importance of rigorous management of patients with ePLEDs., (Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: To describe the clinical, radiological, and cerebrovascular fluid (CSF) findings and the outcome of microbiologically or histopathologically proven fungal infections of the central nervous system (CNS) in HIV-negative patients., Methodology and Results: We identified definite cases of CNS mycosis by screening the medical records of our institute for the period 2000-2008. The clinical and imaging details and the outcome were abstracted from the medical records and entered in a structured proforma. There were 12 patients with CNS mycosis (i.e., 2.7% of all CNS infections treated in this hospital); six (50%) had cryptococcal infection, three (25%) had mucormycosis, and two had unclassified fungal infection. Four (33%) of them had diabetes as a predisposing factor. The common presentations were meningoencephalitis (58%) and polycranial neuritis (41%). Magnetic resonance imaging revealed hydrocephalus in 41% and meningeal enhancement in 25%, as well as some unusual findings such as subdural hematoma in the bulbocervical region, carpeting lesion of the base of the skull, and enhancing lesion in the cerebellopontine angle. The CSF showed pleocytosis (66%), hypoglycorrhachia (83%), and elevated protein levels (100%). The diagnosis was confirmed by meningocortical biopsy (in three cases), paranasal sinus biopsy (in four cases), CSF culture (in three cases), India ink preparation (in four cases), or by cryptococcal polysaccharide antigen test (in three cases). Out of the ten patients for whom follow-up details were available, six patients recovered with antifungal medications (amphotericin B, 1 mg/kg/day for the minimum period of 6 weeks) and/or surgical treatment. Four patients expired (only one of them had received antifungal therapy)., Conclusions: Most patients with CNS mycosis recover with appropriate therapy, but the diagnosis and management of these rare infections remains a challenge to clinicians.

Background: Chronic infection with hepatitis B virus (HBV) causes a spectrum of diseases ranging from asymptomatic infective state to cirrhosis and hepato-cellular carcinoma. The asymptomatic state has highly variable characteristics., Methods: Sixty-one incidentally detected asymptomatic HBsAg-positive subjects (IDAHS), in whom HBsAg positivity persisted for > 6 months, were studied for liver biochemistry, HBeAg, anti HBe and HBV DNA levels (in HBeAg-negative subjects). Liver biopsy was done in 29 subjects and scored for histological activity index (HAI) and fibrosis using modified Knodell score., Results: Thirteen (21%) subjects were HBeAg positive. The remaining 48 (79%) were positive for anti HBe, with HBV DNA level of> 105 copies/mL in 15 (31.2%). Transaminase elevation was more frequent in HBeAg-positive subjects (69%; p< 0.05) and in HBV DNA-positive (93%) than in non-replicative (27%) infection. Seroconverted (anti HBe-positive) individuals were a decade older than HBeAg-positive ones and most (93.7%) of them were> 20 years of age. Fifteen of 29 (51.3%) had HAI> 3, more frequently in those with raised ALT (68.4%; p< 0.05) than with normal ALT (20%), but there was no difference in relation to HBeAg status., Conclusions: Seroconversion to anti HBe was noted in individuals aged 20 years or more. Ongoing liver disease was noted in approximately half of IDAHS, suggesting that a considerable proportion of IDAHS have active infection. In HBeAg-negative subjects, transaminase estimation may be sufficient in planning therapy.