The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3): an international, stepped wedge cluster randomised controlled trial.

BACKGROUND: Early control of elevated blood pressure is the most promising treatment for acute intracerebral haemorrhage. We aimed to establish whether implementing a goal-directed care bundle incorporating protocols for early intensive blood pressure lowering and management algorithms for hyperglycaemia, pyrexia, and abnormal anticoagulation, implemented in a hospital setting, could improve outcomes for patients with acute spontaneous intracerebral haemorrhage. METHODS: We performed a pragmatic, international, multicentre, blinded endpoint, stepped wedge cluster randomised controlled trial at hospitals in nine low-income and middle-income countries (Brazil, China, India, Mexico, Nigeria, Pakistan, Peru, Sri Lanka, and Viet Nam) and one high-income country (Chile). Hospitals were eligible if they had no or inconsistent relevant, disease-specific protocols, and were willing to implement the care bundle to consecutive patients (aged ≥18 years) with imaging-confirmed spontaneous intracerebral haemorrhage presenting within 6 h of the onset of symptoms, had a local champion, and could provide the required study data. Hospitals were centrally randomly allocated using permuted blocks to three sequences of implementation, stratified by country and the projected number of patients to be recruited over the 12 months of the study period. These sequences had four periods that dictated the order in which the hospitals were to switch from the control usual care procedure to the intervention implementation of the care bundle procedure to different clusters of patients in a stepped manner. To avoid contamination, details of the intervention, sequence, and allocation periods were concealed from sites until they had completed the usual care control periods. The care bundle protocol included the early intensive lowering of systolic blood pressure (target <140 mm Hg), strict glucose control (target 6·1-7·8 mmol/L in those without diabetes and 7·8-10·0 mmol/L in those with diabetes), antipyrexia treatment (target body temperature ≤37·5°C), and rapid reversal of warfarin-related anticoagulation (target international normalised ratio <1·5) within 1 h of treatment, in patients where these variables were abnormal. Analyses were performed according to a modified intention-to-treat population with available outcome data (ie, excluding sites that withdrew during the study). The primary outcome was functional recovery, measured with the modified Rankin scale (mRS; range 0 [no symptoms] to 6 [death]) at 6 months by masked research staff, analysed using proportional ordinal logistic regression to assess the distribution in scores on the mRS, with adjustments for cluster (hospital site), group assignment of cluster per period, and time (6-month periods from Dec 12, 2017). This trial is registered at Clinicaltrials.gov (NCT03209258) and the Chinese Clinical Trial Registry (ChiCTR-IOC-17011787) and is completed. FINDINGS: Between May 27, 2017, and July 8, 2021, 206 hospitals were assessed for eligibility, of which 144 hospitals in ten countries agreed to join and were randomly assigned in the trial, but 22 hospitals withdrew before starting to enrol patients and another hospital was withdrawn and their data on enrolled patients was deleted because regulatory approval was not obtained. Between Dec 12, 2017, and Dec 31, 2021, 10 857 patients were screened but 3821 were excluded. Overall, the modified intention-to-treat population included 7036 patients enrolled at 121 hospitals, with 3221 assigned to the care bundle group and 3815 to the usual care group, with primary outcome data available in 2892 patients in the care bundle group and 3363 patients in the usual care group. The likelihood of a poor functional outcome was lower in the care bundle group (common odds ratio 0·86; 95% CI 0·76-0·97; p=0·015). The favourable shift in mRS scores in the care bundle group was generally consistent across a range of sensitivity analyses that included additional adjustments for country and patient variables (0·84; 0·73-0·97; p=0·017), and with different approaches to the use of multiple imputations for missing data. Patients in the care bundle group had fewer serious adverse events than those in the usual care group (16·0% vs 20·1%; p=0·0098). INTERPRETATION: Implementation of a care bundle protocol for intensive blood pressure lowering and other management algorithms for physiological control within several hours of the onset of symptoms resulted in improved functional outcome for patients with acute intracerebral haemorrhage. Hospitals should incorporate this approach into clinical practice as part of active management for this serious condition. FUNDING: Joint Global Health Trials scheme from the Department of Health and Social Care, the Foreign, Commonwealth & Development Office, and the Medical Research Council and Wellcome Trust; West China Hospital; the National Health and Medical Research Council of Australia; Sichuan Credit Pharmaceutic and Takeda China.

Blood pressure variability in acute stroke: Risk factors and association with functional outcomes at 1 month.

BACKGROUND AND PURPOSE: Blood pressure variability, in acute stroke, may be an important modifiable determinant of functional outcome after stroke. In a large international cohort of participants with acute stroke, it was sought to determine the association of blood pressure variability (in the early period of admission) and functional outcomes, and to explore risk factors for increased blood pressure variability. PATIENTS AND METHODS: INTERSTROKE is an international case-control study of risk factors for first acute stroke. Blood pressure was recorded at the time of admission, the morning after admission and the time of interview in cases (median time from admission 36.7 h). Multivariable ordinal regression analysis was employed to determine the association of blood pressure variability (standard deviation [SD] and coefficient of variance) with modified Rankin score at 1-month follow-up, and logistic regression was used to identify risk factors for blood pressure variability. RESULTS: Amongst 13,206 participants, the mean age was 62.19 ± 13.58 years. When measured by SD, both systolic blood pressure variability (odds ratio 1.13; 95% confidence interval 1.03-1.24 for SD ≥20 mmHg) and diastolic blood pressure variability (odds ratio 1.15; 95% confidence interval 1.04-1.26 for SD ≥10 mmHg) were associated with a significant increase in the odds of poor functional outcome. The highest coefficient of variance category was not associated with a significant increase in risk of higher modified Rankin score at 1 month. Increasing age, female sex, high body mass index, history of hypertension, alcohol use, and high urinary potassium and low urinary sodium excretion were associated with increased blood pressure variability. CONCLUSION: Increased blood pressure variability in acute stroke, measured by SD, is associated with an increased risk of poor functional outcome at 1 month. Potentially modifiable risk factors for increased blood pressure variability include low urinary sodium excretion.

Risk Factors for Stroke in the Young (18-45 Years): A Case-Control Analysis of INTERSTROKE Data from 32 Countries.

BACKGROUND: It is not clear whether conventional vascular risk factors are responsible for most strokes in patients younger than 45 years of age. Our objective was to evaluate the association of common risk factors with stroke in individuals under 45 years. METHODS: INTERSTROKE was a case-control study carried out in 32 countries between 2007 and 2015. Patients presenting within 5 days of symptom onset of a first stroke were enrolled as cases. Controls were age and sex matched to cases and had no history of stroke. Cases and controls underwent similar evaluations. Odds ratios (ORs) and population attributable risks (PARs) were calculated to determine the association of various risk factors with all stroke, ischemic stroke, and intracranial hemorrhage, for patients 45 years of age or younger. FINDINGS: 1,582 case-control pairs were included in this analysis. The mean age of this cohort was 38.5 years (SD 6.32). Overall, 71% strokes were ischemic. Cardiac causes {OR: 8.42 (95% confidence interval [CI]: 3.01-23.5)}; binge drinking of alcohol (OR: 5.44 [95% CI: 1.81-16.4]); hypertension (OR: 5.41 [95% CI: 3.40-8.58]); ApoB/ApoA1 ratio (OR: 2.74 [95% CI: 1.69-4.46]); psychosocial stress (OR: 2.33 [95% CI: 1.01-5.41]); smoking (OR: 1.85 [95% CI: 1.17-2.94]); and increased waist-to-hip ratio (OR: 1.69 [95% CI: 1.04-2.75]) were the most important risk factors for ischemic stroke in these young cases. For intracerebral hemorrhage, only hypertension (OR: 9.08 [95% CI: 5.46-15.1]) and binge drinking (OR: 4.06 [95% CI: 1.27-13.0]) were significant risk factors. The strength of association and population attributable risk (PAR) for hypertension increased with age (PAR 23.3% in those <35 years of age, 50.7% in 35-45 years of age). INTERPRETATION: Conventional risk factors such as hypertension, smoking, binge drinking of alcohol, central obesity, cardiac causes, dyslipidemia, and psychosocial stress are important risk factors for stroke in those younger than 45 years of age. Hypertension is the most significant risk factor in all age groups and across all regions and both stroke subtypes. These risk factors should be identified and modified in early adulthood to prevent strokes in young individuals.

Predictors of Mortality and Functional Outcome in Pregnancy and Puerperium-Related Cerebral Venous Thrombosis.

INTRODUCTION: Cerebral venous thrombosis (CVT) associated with pregnancy and puerperium has long been recognized, with poor information in terms of functional outcomes. Our objective was to analyze risk factors, clinical, imaging, and laboratory variables to predict functional outcome and death in this population. METHODS: CVT registries from three referral centers from Pakistan, Turkey, and Mexico, recruiting prospective cases, were combined for CVT associated with pregnancy or puerperium. Datasets and variables were standardized. Demographic characteristics, presentation, risk factors, and functional outcomes in pregnancy/puerperium-related CVT were analyzed. Binary logistic regression was used to assess predictors of outcome. The main outcome was modified Rankin score >2 at 30 days and mortality at 30 days. RESULTS: Five hundred fifty-three cases (median age 28 years [IQR 23-34]) of CVT associated with pregnancy and puerperium were included; 439 cases (79.4%) happened in the puerperium and 20.6% during pregnancy (53.5% occurred during the first trimester). Anemia (36.7%) and dehydration (22.9%) were the commonest obstetric risk factors identified. Predictors of poor outcome (mRS >2) were encephalopathy (OR 12.8, p < 0.001), cases from Mexican origin (OR 3.1, p = 0.004), fever/puerperal infection (OR 2.7, p = 0.02), and anemia (OR 2.2, p = 0.01). Cases from Mexican origin (OR 12.0, p = 0.003) and Encephalopathy (OR 7.7, p < 0.001), presented with the highest mortality association in the final adjusted model. DISCUSSION/CONCLUSION: In CVT associated with pregnancy and puerperium, encephalopathy, fever/puerperal infection, and anemia are associated with bad functional outcomes, meanwhile encephalopathy and cases from Mexican origin with higher mortality in the acute (30-days) of CVT onset. Anemia and infection are potential reversible predictors of poor outcome that clinicians should be aware of in order to prevent poor outcomes in these patients.

COVID-19 independently predicts poor outcomes in Acute Ischemic Stroke- Insights from a multicenter study from Pakistan and United Arab Emirates.

BACKGROUND: Ischemic stroke associated with coronavirus 2019 (COVID-19) has been well recognized by now. Few studies have compared COVID related versus unrelated strokes. We intend to report on a large group of Asian patients from two countries and compare COVID with non-COVID strokes admitted during the same time period. METHODS: Consecutive cases of acute ischemic stroke either presenting or developing, between March 2020 and December 2021 in four tertiary care hospitals (1 in Dubai, UAE and 3 in Karachi, Pakistan) and testing positive for COVID-19 were included in the study. Patients admitted with ischemic stroke during the same time period and who tested negative for COVID-19 were also randomly selected from the four hospitals. All data was collected from the medical records of the patients and recorded on a standard questionnaire before it was entered in SPSS version 21 for analysis. RESULTS: There were 139 COVID positive and 271 COVID negative patients with acute ischemic stroke included in the current study. There were significantly more males (80.6% vs 64.9%, p=0.001) and more large vessel strokes in the COVID positive group (41% vs 21.8%, p<0.001). Being COVID positive was an independent predictor of poor outcome at discharge, defined as a modified Rankin score of 3-6 (OR 3.87, 95% CI 2.21-6.77) after adjusting for country, age, sex, vascular comorbid conditions and stroke subtype. CONCLUSIONS: In this largest series of patients with COVID related strokes from Asia, COVID-19 was an independent predictor of poor outcomes at discharge after adjusting for other variables.

First Report of Cerebral Venous Thrombosis Following Inactivated-Virus Covid Vaccination (Sinopharm and Sinovac).

Cerebral venous thrombosis (CVT) is an uncommon cerebrovascular disease, which has been reported with covid infection as well as covid vaccines, particularly AstraZeneca and Janssen vaccines. We present four consecutive cases of CVT after receiving either Sinopharm or Sinovac vaccine, both of which are composed of an inactivated-virus. All the patients recovered well with anticoagulation and discharged with a good functional outcome. This is the first case series reporting CVT following the administration of these vaccines.

Stroke Care during the COVID-19 Pandemic: International Expert Panel Review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has placed a tremendous strain on healthcare services. This study, prepared by a large international panel of stroke experts, assesses the rapidly growing research and personal experience with COVID-19 stroke and offers recommendations for stroke management in this challenging new setting: modifications needed for prehospital emergency rescue and hyperacute care; inpatient intensive or stroke units; posthospitalization rehabilitation; follow-up including at-risk family and community; and multispecialty departmental developments in the allied professions. SUMMARY: The severe acute respiratory syndrome coronavirus 2 uses spike proteins binding to tissue angiotensin-converting enzyme (ACE)-2 receptors, most often through the respiratory system by virus inhalation and thence to other susceptible organ systems, leading to COVID-19. Clinicians facing the many etiologies for stroke have been sobered by the unusual incidence of combined etiologies and presentations, prominent among them are vasculitis, cardiomyopathy, hypercoagulable state, and endothelial dysfunction. International standards of acute stroke management remain in force, but COVID-19 adds the burdens of personal protections for the patient, rescue, and hospital staff and for some even into the postdischarge phase. For pending COVID-19 determination and also for those shown to be COVID-19 affected, strict infection control is needed at all times to reduce spread of infection and to protect healthcare staff, using the wealth of well-described methods. For COVID-19 patients with stroke, thrombolysis and thrombectomy should be continued, and the usual early management of hypertension applies, save that recent work suggests continuing ACE inhibitors and ARBs. Prothrombotic states, some acute and severe, encourage prophylactic LMWH unless bleeding risk is high. COVID-19-related cardiomyopathy adds risk of cardioembolic stroke, where heparin or warfarin may be preferable, with experience accumulating with DOACs. As ever, arteritis can prove a difficult diagnosis, especially if not obvious on the acute angiogram done for clot extraction. This field is under rapid development and may generate management recommendations which are as yet unsettled, even undiscovered. Beyond the acute management phase, COVID-19-related stroke also forces rehabilitation services to use protective precautions. As with all stroke patients, health workers should be aware of symptoms of depression, anxiety, insomnia, and/or distress developing in their patients and caregivers. Postdischarge outpatient care currently includes continued secondary prevention measures. Although hoping a COVID-19 stroke patient can be considered cured of the virus, those concerned for contact safety can take comfort in the increasing use of telemedicine, which is itself a growing source of patient-physician contacts. Many online resources are available to patients and physicians. Like prior challenges, stroke care teams will also overcome this one. Key Messages: Evidence-based stroke management should continue to be provided throughout the patient care journey, while strict infection control measures are enforced.

Exploring the Relationship Between Air Quality and Ischemic Stroke Admissions During the COVID-19 Pandemic.

OBJECTIVES: Amongst all the global catastrophe due to Coronavirus disease 2019, a significant bright spot is a reduction in air pollution as countries undergo lockdowns to limit the spread of infection. Another reduction that has been reported is in the number of strokes presenting to hospitals, despite the virus implicated in causing a hypercoagulable state. Acute exposure to air pollution has been linked to increase in stroke incidence and the improvement in air quality may be responsible for the decrease in stroke presentations. MATERIALS AND METHODS: To explore this hypothesis, we compared the air quality index (AQI) of Karachi, the largest cosmopolitan city of Pakistan, during the lockdown period in 2020 to the same period in the previous year. RESULTS: We found a significant drop in AQI depicting an improvement in air quality. Simultaneously, we identified a drop in number of stroke admissions to less than half from 2019 to 2020 at one of the largest tertiary care hospitals of the city, during this period of interest. CONCLUSION: We hypothesize that one important reason for this drop in stroke admissions, may be an actual reduction in stroke incidence brought about by an improvement in air quality.

Neurological manifestations of COVID-19.

Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) has turned out to be a formidable pandemic. Upcoming evidence from confirmed cases of COVID-19 suggests an anticipated incursion of patients with neurological manifestations in the weeks to come. An expression of the angiotensin-converting enzyme 2 (ACE 2), the cellular receptor for SARS-CoV-2 over the glial cells and neurons have made the brain a potential target. Neurotoxicity may occur as a result of direct, indirect and post-infectious complications. Attention to neurological deficits in COVID-19 is fundamental to ensure appropriate, timely, beneficial management of the affected patients. Most common neurological manifestations seen include dizziness, headache, impaired consciousness, acute cerebrovascular disease, ataxia, and seizures. Anosmia and ageusia have recently been hinted as significant early symptoms in COVID-19. As cases with neurological deficits in COVID-19 emerge, the overall prognosis is yet unknown.

Practice patterns and outcomes after stroke across countries at different economic levels (INTERSTROKE): an international observational study.

BACKGROUND: Stroke disproportionately affects people in low-income and middle-income countries. Although improvements in stroke care and outcomes have been reported in high-income countries, little is known about practice and outcomes in low and middle-income countries. We aimed to compare patterns of care available and their association with patient outcomes across countries at different economic levels. METHODS: We studied the patterns and effect of practice variations (ie, treatments used and access to services) among participants in the INTERSTROKE study, an international observational study that enrolled 13 447 stroke patients from 142 clinical sites in 32 countries between Jan 11, 2007, and Aug 8, 2015. We supplemented patient data with a questionnaire about health-care and stroke service facilities at all participating hospitals. Using univariate and multivariate regression analyses to account for patient casemix and service clustering, we estimated the association between services available, treatments given, and patient outcomes (death or dependency) at 1 month. FINDINGS: We obtained full information for 12 342 (92%) of 13 447 INTERSTROKE patients, from 108 hospitals in 28 countries; 2576 from 38 hospitals in ten high-income countries and 9766 from 70 hospitals in 18 low and middle-income countries. Patients in low-income and middle-income countries more often had severe strokes, intracerebral haemorrhage, poorer access to services, and used fewer investigations and treatments (p<0·0001) than those in high-income countries, although only differences in patient characteristics explained the poorer clinical outcomes in low and middle-income countries. However across all countries, irrespective of economic level, access to a stroke unit was associated with improved use of investigations and treatments, access to other rehabilitation services, and improved survival without severe dependency (odds ratio [OR] 1·29; 95% CI 1·14-1·44; all p<0·0001), which was independent of patient casemix characteristics and other measures of care. Use of acute antiplatelet treatment was associated with improved survival (1·39; 1·12-1·72) irrespective of other patient and service characteristics. INTERPRETATION: Evidence-based treatments, diagnostics, and stroke units were less commonly available or used in low and middle-income countries. Access to stroke units and appropriate use of antiplatelet treatment were associated with improved recovery. Improved care and facilities in low-income and middle-income countries are essential to improve outcomes. FUNDING: Chest, Heart and Stroke Scotland.

Cerebral Venous Thrombosis at High Altitude: Analysis of 28 Cases.

OBJECTIVE: An association between cerebral venous sinus thrombosis (CVST) and high altitude has been previously proposed, but limited published data exist to support this association. We investigated 28 cases of CVST occurring at high altitude and sought to describe patient demographics, altitude and acclimatization, hematological laboratory findings, neuroimaging, treatment, and prognosis in these cases. METHODS: Twenty-eight cases of symptomatic CVST occurring at high altitude were identified between the months of August 2017 and December 2018, in collaboration with Military Hospital, Rawalpindi and Combined Military Hospital, Skardu (Pakistan). Follow-up visits were performed at 1 and 6 months. RESULTS: Twenty-seven (96%) of the patients were males, and the mean age was 33 years. In total, 32.1% were smokers. The mean NIHSS score on presentation was 5.5. 85.7% of the cases occurred at altitude higher than 8,000 feet. On average 107.8 days were spent at a high altitude prior to CVST. Totally, 71.4% had acclimatized for >2 weeks. The mean hemoglobin (Hb) value was 16.7 g/dL and 50% had d-dimer levels higher than 1,000 ng/mL. On MRI, 25% showed signs of hemorrhage and 14.3% showed infarcts. Treatments provided include low-molecular-weight heparin and Rivaroxaban and were associated with good outcomes. CONCLUSION: CVST is not uncommon at high altitude (>8,000 feet). It is predominantly a male disease. Most patients have high Hb and high D-dimer levels. The overall outcome was good.

Spectrum of neurological disorders in neurology outpatients clinics in urban and rural Sindh, Pakistan: a cross sectional study.

BACKGROUND: Neurological disorders are the most common cause of morbidity and mortality in developing countries. Available evidence on urban-rural differences on neurological diseases is scare in such countries. Our study objective was to determine the prevalence of neurological diseases in urban and rural tertiary care hospitals of Sindh, Pakistan. METHODS: This was a cross sectional study conducted in selected urban and rural region of tertiary care hospitals of Sindh, Pakistan. The outpatients medical records of adults (18 years and above) was obtained from January 1st, 2014 to December 31st, 2014. RESULTS: A total of 10,786 outpatients visit were recorded in this period. Mean age of the participants was 40.6 ± 15 years; majority was females 6104 (56.6%). About three-fourth of the patients were from rural hospital 7828 (72.6%). Common neurological diseases were headache disorders 3613 (33.4%), nerve and root lesion 2928 (27.1%), vascular diseases 1440 (13.3%), epilepsies 566 (5.2%), muscle disorders 424 (3.9%), psychiatric disorders 340 (3.1%) and CNS infection 303 (2.8%). Comparison between the urban and rural samples showed that ischaemic stroke (72.7% vs. 82%) and psychiatric disorders (2.1% vs. 3.5%) were more prevalent in rural area as compared to urban setting. CONCLUSION: Stroke, headache and nerve and root lesion are major causes of neurological disorders in urban and rural settings of Sindh, Pakistan. The policy and planning must be focus on primary care, preventive measures and the promotion of health.

Asian Study of Cerebral Venous Thrombosis.

BACKGROUND/OBJECTIVE: Most of the studies and registries related to cerebral venous thrombosis (CVT) are reported from European countries and the United States. The objective of the present study is to identify risk factors, presentation, and outcome of CVT in Asian patients. METHODS: Asian CVT registry is a prospective multinational observational study that included patients (aged > 16 years) with symptomatic CVT. RESULTS: Eight hundred and twelve patients (59% women) from 20 centers in 9 Asian countries were included. Mean age of the patients was 31 years. Motor weakness in limbs was present in 325 (40%) patients. One hundred and eighty (22.1%) patients had a normal Glasgow coma scale (GCS) at presentation, and another 529 patients (65%) had GCS between 11 and 14. The rest (103; 13%) had a GCS of less than 10 at presentation. Permanent risk factors were present in 264 (33%) patients, transient in 342 (42%) patients, both in 43 (5%) patients and no risk factors were found in 163 (20%) patients. Anemia was present in 51%, use of oral contraceptive pills (OCP) was present in 12% women and a hypercoaguable state was present in more than 40% of those tested. One hundred and forty-three cases (18%) were in women who were either pregnant (18; 2%) or in the puerperium (up to 6 weeks postpartum; N = 125; 15%). A total of 86 (10.5%) patients were diagnosed with infection in any part of the body. The most common MRI finding was local brain edema or ischemia (53.3%) followed by hemorrhage (26.7%). Twenty-seven patients (3.3%) died during hospital stay. The mRS score at discharge was available for 661 (81%) patients. Of these, 577 (87.3%) had good functional outcome at discharge. Motor weakness at presentation, GCS of 9 or less and mental status disorder were the strongest independent predictors of mortality at last follow-up among patients with CVT. CONCLUSIONS: Important differences were identified as compared to western data including younger age, high frequency of anemia, low use of OCP, and high frequency of hypercoaguable states. Functional outcome at discharge was good.

Utilization and outcomes with low dose tissue plasminogen activator as intravenous thrombolytic therapy for ischaemic stroke at Aga Khan University Hospital, Karachi: a retrospective analysis.

OBJECTIVE: To determine the utilisation of intravenous tissue plasminogen activator at a certain dose for ischaemic stroke thrombolysis and to compare the outcomes with those of a different dosage mentioned in literature. METHODS: The retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised medical records from January, 2007, to October, 2016, of all patients having received intravenous tissue plasminogen activator for ischaemic stroke thrombolysis. Primary safety outcome variables included symptomatic intracerebral haemorrhage after the start of treatment (0.6mg/kg) and death within three months as per the modified Rankin scale 6. Secondary efficacy outcome variable was functional independence as per modified Rankin scale 0-2 at three months. The outcomes were compared with those mentioned in literature with a dose of 0. 9mg/kg. RESULTS: Of the 79 patients, 52 (66%) were male and 27 (34 %) were female. Median pre-treatment tissue plasminogen activator score was 12 (interquartile range: 8-15). Overall utilisation of t-PA remained at 1.7%. Symptomatic intracerebral haemorrhage was not seen in our cohort while it was seen in 107 (1.7%) patients at the higher dose. Using another definition, it was seen in 3 (3.8%) patients versus 468 (7.3%) patients at the higher dose. Functional independence was seen in 40 (50.6%) patients at three months compared to 3362 (54.8%) patients at the higher dose. CONCLUSIONS: Low-dose intravenous thrombolytic therapy for ischaemic stroke patients was found to be safe and efficacious, and yielded comparable results with those obtained at a higher dose..

Frequency and Impact of Cerebral Infarctions in Patients With Tuberculous Meningitis.

Background and Purpose- Cerebral infarctions complicate a variable proportion of tuberculous meningitis (TBM) cases and adversely affect outcomes. The objective of this study was to evaluate the predictors of cerebral infarcts in patients with TBM and to assess their impact on mortality. Methods- The study was based on a retrospective chart review of all patients with TBM admitted to a tertiary care hospital between 2002 and 2013. Data were collected on basic demographics, conventional vascular risk factors, radiological findings, severity of TBM, and neurological outcomes. Data were analyzed using SPSS version 19.0. Binary logistic regression was done to determine the factors predictive of cerebral infarcts and of mortality in patients with TBM. Results- A total of 559 patients were admitted with TBM during the study period. Mean age was 41.9 years (SD, 17.7 years), and 47% were women. A quarter of the patients had stage III disease. One hundred forty-four (25.8%) patients had cerebral infarcts on brain imaging of which 3 quarters were acute or subacute. Those with cerebral infarcts were more likely to be >40 years of age (adjusted odds ratio [AOR], 1.7; 95% CI, 1.1-2.7) and to have hypertension (AOR, 1.8; 95% CI, 1.1-2.8), dyslipidemia (AOR, 9.7; 95% CI, 3.8-24.8), and diabetes mellitus (AOR, 2.2; 95% CI, 1.3-3.6). Presence of cerebral infarction was an independent predictor of mortality among patients with TBM (AOR, 2.1; 95% CI, 1.22-3.5). Conclusions- Cerebral infarcts complicate a substantial proportion of TBM cases. Conventional vascular risk factors are the most important predictors of infarction, and future efforts need to focus on these high-risk patients with TBM to reduce morbidity and mortality.

Role of ADC values and ratios of MRI scan in differentiating typical from atypical/anaplastic meningiomas.

Atypical/anaplastic meningiomas are prone to aggressive behaviour which affects treatment planning and prognostication. Our aim was to assess the role of Apparent Diffusion Coefficient (ADC) values of MRI brain in differentiating typical from atypical/anaplastic meningioma. We reviewed 84 typical and 37 atypical/anaplastic meningiomas and compared mean ADC values and ADC ratios of their preoperative MRI brain. At 3 Tesla, mean ADC value for typical meningioma was1.03±0.10x10-3 and 0.63±0.05x10-3 for atypical/anaplastic meningioma. At 1.5 Tesla, mean ADC value for typical meningioma was 1.05±0.11x10-3 and atypical/ anaplastic meningioma was 0.70 ± 0.04x10-3. The mean ADC ratios were 1.08 ± 0.17 and 0.85 ± 0.15 for typical and atypical/anaplastic meningomas respectively. Mean ADC ratios and the mean ADC values of typical and atypical/anaplastic meningiomas were significantly different (p< 0.001). ADC values and ADC ratios have important role in differentiating typical from atypical/anaplastic meningioma and it must be part of the routine preoperative MRI reporting.

Evaluation of quality of warfarin therapy by assessing patient's time in therapeutic range at a tertiary care hospital in Pakistan.

OBJECTIVE: To assess the time in therapeutic range in patients on warfarin anti-coagulation therapy. METHODS: The retrospective chart review was conducted at Aga Khan University Hospital, Karachi, and comprised data of patients having undergone anti-coagulation with warfarin from January 2013 to April 2015. To determine the mean time in therapeutic range, Rosendaal method was used. Association of time in therapeutic range with the composite outcome, bleeding and thromboembolic events was also assessed. Percentage of patients with time in therapeutic range <60% was calculated. RESULTS: There were 92 patients whose median time in therapeutic range was 34.9% (interquartile range: 20.0- 55.7). Overall, 71(77.2%) patients had time in therapeutic range below 60% which had statistically significant correlation with the composite outcome (p<0.05). Number of comorbids was significant in predicting time in therapeutic range and patients with time in therapeutic range< 60% (p<0.05). CONCLUSION: Subjects had poor anti-coagulation quality. It might be prudent to move towards novel oral anticoagulant drugsas the first choice for therapeutic anti-coagulation.