Multiple versus fewer antiplatelet agents for preventing early recurrence after ischaemic stroke or transient ischaemic attack.

BACKGROUND: Stroke is a leading cause of morbidity and mortality worldwide. Antiplatelet agents are considered to be the cornerstone for secondary prevention of stroke, but the role of using multiple antiplatelet agents early after stroke or transient ischaemic attack (TIA) to improve outcomes has not been established. OBJECTIVES: To determine the effectiveness and safety of initiating, within 72 hours after an ischaemic stroke or TIA, multiple antiplatelet agents versus fewer antiplatelet agents to prevent stroke recurrence. The analysis explores the evidence for different drug combinations. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last searched 6 July 2020), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 7 of 12, 2020) (last searched 6 July 2020), MEDLINE Ovid (from 1946 to 6 July 2020), Embase (1980 to 6 July 2020), ClinicalTrials.gov, and the WHO ICTRP. We also searched the reference lists of identified studies and reviews and used the Science Citation Index Cited Reference search for forward tracking of included studies. SELECTION CRITERIA: We selected all randomised controlled trials (RCTs) that compared the use of multiple versus fewer antiplatelet agents initiated within 72 hours after stroke or TIA. DATA COLLECTION AND ANALYSIS: We extracted data from eligible studies for the primary outcomes of stroke recurrence and vascular death, and secondary outcomes of myocardial infarction; composite outcome of stroke, myocardial infarction, and vascular death; intracranial haemorrhage; extracranial haemorrhage; ischaemic stroke; death from all causes; and haemorrhagic stroke. We computed an estimate of treatment effect and performed a test for heterogeneity between trials. We analysed data on an intention-to-treat basis and assessed bias for all studies. We rated the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 15 RCTs with a total of 17,091 participants. Compared with fewer antiplatelet agents, multiple antiplatelet agents were associated with a significantly lower risk of stroke recurrence (5.78% versus 7.84%, risk ratio (RR) 0.73, 95% confidence interval (CI) 0.66 to 0.82; P < 0.001; moderate-certainty evidence) with no significant difference in vascular death (0.60% versus 0.66%, RR 0.98, 95% CI 0.66 to 1.45; P = 0.94; moderate-certainty evidence). There was a higher risk of intracranial haemorrhage (0.42% versus 0.21%, RR 1.92, 95% CI 1.05 to 3.50; P = 0.03; low-certainty evidence) and extracranial haemorrhage (6.38% versus 2.81%, RR 2.25, 95% CI 1.88 to 2.70; P < 0.001; high-certainty evidence) with multiple antiplatelet agents. On secondary analysis of dual versus single antiplatelet agent therapy, benefit for stroke recurrence (5.73% versus 8.06%, RR 0.71, 95% CI 0.62 to 0.80; P < 0.001; moderate-certainty evidence) was maintained as well as risk of extracranial haemorrhage (1.24% versus 0.40%, RR 3.08, 95% CI 1.74 to 5.46; P < 0.001; high-certainty evidence). The composite outcome of stroke, myocardial infarction, and vascular death (6.37% versus 8.77%, RR 0.72, 95% CI 0.64 to 0.82; P < 0.001; moderate-certainty evidence) and ischaemic stroke (6.30% versus 8.94%, RR 0.70, 95% CI 0.61 to 0.81; P < 0.001; high-certainty evidence) were significantly in favour of dual antiplatelet therapy, whilst the risk of intracranial haemorrhage became less significant (0.34% versus 0.21%, RR 1.53, 95% CI 0.76 to 3.06; P = 0.23; low-certainty evidence). AUTHORS' CONCLUSIONS: Multiple antiplatelet agents are more effective in reducing stroke recurrence but increase the risk of haemorrhage compared to one antiplatelet agent. The benefit in reduction of stroke recurrence seems to outweigh the harm for dual antiplatelet agents initiated in the acute setting and continued for one month. There is lack of evidence regarding multiple versus multiple antiplatelet agents. Further studies are required in different populations to establish comprehensive safety profiles and long-term outcomes to establish duration of therapy.

Validation of the Recent Life Changes Questionnaire (RLCQ) for stress measurement among adults residing in urban communities in Pakistan.

BACKGROUND: Recent Life Changes Questionnaire (RLCQ) developed by Richard Rahe has enabled quantification of stress by analyzing life events. The overall aim of the study was to create a reliable version of the Rahe's RLCQ for measuring stress in individuals living in developing countries and assess its validity. This paper discusses criterion validation of the adapted RLCQ in urban communities in Pakistan. METHODS: This is a criterion validation study. Four urban communities of Karachi, Pakistan were selected for the study in which households were randomly chosen. Two data collectors were assigned to administer the adapted RLCQ to eligible participants after obtaining written informed consent. Following this interaction, two psychologists interviewed the same participants with a diagnostic gold standard of Mini International Neuropsychiatric Interview (MINI) which is utilized in usual practice within Pakistan to confirm the presence of stress related mental disorders such as Depression, Anxiety, Dysthymia, Suicide, Phobia, OCD, Panic Disorder, PTSD, Drug abuse and dependence, Alcohol abuse and dependence, Eating Disorders and Antisocial Personality Disorder to validate the accuracy of the adapted RLCQ. We generated the ROC curves for the adapted RLCQ with suggested cut-offs, and analyzed the sensitivity and specificity of the adapted RLCQ. RESULTS: The area under the receiver operating characteristic curve (ROC) of common mental disorders such as depression and anxiety was 0.64, where sensitivity was 66%, specificity was 56% and the corresponding cut off from the adapted RLCQ was 750. Individuals scoring ≥750 were classified as high stress and vice versa. In contrast, the area under the ROC curve for serious mental disorder and adverse outcomes such as suicide, bipolar and dysthymia was 0.75, where sensitivity was 72% and specificity was 60% at the cut off of 800 on the adapted RLCQ. Individuals scoring ≥800 were classified as high stress and vice versa. The rate of agreement between the two psychologists was 94.32% (Kappa = 0.84). CONCLUSION: The adapted and validated RLCQ characterizes common mental disorders such as depression and anxiety with moderate accuracy and severe mental disorders such as suicide, bipolar and dysthymia with high accuracy. TRIAL REGISTRATION: Clinicaltrials.gov NCT02356263 . Registered January 28, 2015. (Observational Study Only).

Adaptation of the Recent Life Changes Questionnaire (RLCQ) to measure stressful life events in adults residing in an urban megapolis in Pakistan.

BACKGROUND: Contextually relevant stressful life events are integral to the quantification of stress. None such measures have been adapted for the Pakistani population. METHODS: The RLCQ developed by Richard Rahe measures stress of an individual through recording the experience of life changing events. We used qualitative methodology in order to identify contextually relevant stressors in an open ended format, using serial in-depth interviews until thematic saturation of reported stressful life events was achieved. In our next phase of adaptation, our objective was to scale each item on the questionnaire, so as to weigh each of these identified events, in terms of severity of stress. This scaling exercise was performed on 200 random participants residing in the four communities of Karachi namely Kharadar, Dhorajee, Gulshan and Garden. For analysis of the scaled tool, exploratory factor analysis was used to inform structuring. Finally, to complete the process of adaption, content and face validity exercises were performed. Content validity by subject expert review and face validity was performed by translation and back translation of the adapted RLCQ. This yielded our final adapted tool. RESULTS: Stressful life events emerging from the qualitative phase of the study reflect daily life stressors arising from the unstable socio-political environment. Some such events were public harassment, robbery/theft, missed life opportunities due to nepotism, extortion and threats, being a victim of state sponsored brutality, lack of electricity, water, sanitation, fuel, destruction due to natural disasters and direct or media based exposure to suicide bombing in the city. Personal or societal based relevant stressors included male child preference, having an unmarried middle aged daughter, lack of empowerment and respect reported by females. The finally adapted RLCQ incorporated "Environmental Stress" as a new category. CONCLUSION: The processes of qualitative methodology, in depth interview, community based scaling and face and content validity yielded an adapted RLCQ that represents contextually relevant life stress for adults residing in urban Pakistan. TRIAL REGISTRATION: Clinicaltrials.gov NCT02356263 . Registered January 28, 2015. (Observational Study Only).

Using Mobile Health (mHealth) Technology in the Management of Diabetes Mellitus, Physical Inactivity, and Smoking.

PURPOSE OF REVIEW: Cardiovascular mortality remains high due to insufficient progress made in managing cardiovascular risk factors such as diabetes mellitus, physical inactivity, and smoking. Healthy lifestyle choices play an important role in the management of these modifiable risk factors. Mobile health or mHealth is defined as the use of mobile computing and communication technologies (i.e., mobile phones, wearable sensors) for the delivery of health services and health-related information. In this review, we examine some recent studies that utilized mHealth tools to improve management of these risk factors, with examples from developing countries where available. RECENT FINDINGS: The mHealth intervention used depends on the availability of resources. While developing countries are often restricted to text messages, more resourceful settings are shifting towards mobile phone applications and wearable technology. Diabetes mellitus has been extensively studied in different settings, and results have been encouraging. Tools utilized to increase physical activity are expensive, and studies have been limited to resource-abundant areas and have shown mixed results. Smoking cessation has had promising initial results with the use of technology, but mHealth's ability to recruit participants beyond those actively seeking to quit has not been established. mHealth interventions appear to be a potential tool in improving control of cardiovascular risk factors that rely on individuals making healthy lifestyle choices. Data related to clinical impact, if any, of commercially available tools is lacking. More studies are needed to assess interventions that target multiple cardiovascular risk factors and their impact on hard cardiovascular outcomes.

Mobile Health (mHealth) Technology for the Management of Hypertension and Hyperlipidemia: Slow Start but Loads of Potential.

PURPOSE OF REVIEW: Hypertension and hyperlipidemia represent two major risk factors for atherosclerotic cardiovascular disease. Mobile health or mHealth is defined as the use of mobile phone and wireless technologies to support the achievement of health objectives. Management of hypertension, and to some extent hyperlipidemia, has often employed mHealth interventions given lower cost and greater patient engagement compared to traditional methods. These interventions include the use of text messaging, wireless devices, and mobile phone applications. This review considers recent studies evaluating the effectiveness of mHealth interventions in the management of hypertension and hyperlipidemia. RECENT FINDINGS: Numerous studies have evaluated the role of mHealth interventions in the management of hypertension, while very few have evaluated their role in hyperlipidemia. Text messaging has been used most frequently. However, the trend is shifting towards the use of mobile phone applications and wireless devices. Interventions in developing countries have been modified for greater applicability to local settings. mHealth interventions were found to be frequently effective. However, studies comparing the relative efficacy of various mHealth strategies are scarce. Long-term cardiovascular outcomes data and analyses relating to cost effectiveness are also lacking. mHealth interventions may be effective in improving hypertension management. More studies are needed to evaluate the role of mHealth strategies in hyperlipidemia management, particularly in identifying high-risk individuals and improving medication adherence. Studies assessing the long-term impact of these interventions, comparing different interventions and analyzing their relative cost effectiveness, are also needed. Following recently published guidelines on reporting results of mHealth interventions will provide a more meaningful context for interpreting these promising early studies.

Adherence to cardiovascular medications in the South Asian population: A systematic review of current evidence and future directions.

AIM: To review methods of assessing adherence and strategies to improve adherence to cardiovascular disease (CVD) medications, among South Asian CVD patients. METHODS: We conducted a systematic review of English language studies that examined CVD medication adherence in South Asian populations from 1966 to April 1, 2015 in SCOPUS and PubMed. Working in duplicate, we identified 61 studies. After exclusions, 26 studies were selected for full text review. Of these, 17 studies were included in the final review. We abstracted data on several factors including study design, study population, method of assessing adherence and adherence rate. RESULTS: These studies were conducted in India (n = 11), Pakistan (n = 3), Bangladesh (n = 1), Nepal (n = 1) and Sri Lanka (n = 1). Adherence rates ranged from 32%-95% across studies. Of the 17 total publications included, 10 focused on assessing adherence to CVD medications and 7 focused on assessing the impact of interventions on medication adherence. The validated Morisky Medication Adherence Scale (MMAS) was used as the primary method of assessing adherence in five studies. Three studies used validated questionnaires similar to the MMAS, and one study utilized Medication Event Monitoring System caps, with the remainder of the studies utilizing pill count and self-report measures. As expected, studies using non-validated self-report measures described higher rates of adherence than studies using validated scale measurements and pill count. The included intervention studies examined the use of polypill therapy, provider education and patient counseling to improve medication adherence. CONCLUSION: The overall medication adherence rates were low in the region, which suggest a growing need for future interventions to improve adherence.

Frequency and determinants of intracranial atherosclerotic stroke in urban Pakistan.

BACKGROUND: Intracranial atherosclerosis (ICAD) is a frequent underlying mechanism of ischemic stroke. There is little direct evidence on its frequency and determinants from regions of high prevalence. This study explores the conventional and socioeconomic risk factors of ICAD in a South Asian population. METHODS: The Karachi Intracranial Stenosis Study is a case-control study of 313 cases of ischemic stroke secondary to ICAD and 331 controls enrolled from 4 major hospitals in Karachi, Pakistan. Stroke subtype was verified by a vascular neurologist using the Trial of Org 10172 in Acute Stroke Treatment classification. Relationships of conventional and socioeconomic risk factors with ICAD-related strokes are reported by calculating odds ratios (ORs) and their 95% confidence intervals (CIs). RESULTS: ICAD was the cause of stroke in 81.1% cases with large-artery atherosclerosis and 19.5% of all stroke events. Along with risk factors like history of hypertension (OR, 3.33; CI, 2.31-4.78), history of diabetes (OR, 2.29; CI, 1.56-3.35), use of tobacco (OR, 1.49; CI, 1.03-2.16), waist-to-hip ratio (OR, 1.58; CI, 1.04-2.41), and family history of stroke (OR, 1.89; CI, 1.21-2.95), other significant social determinants of ICAD strokes were monthly income (OR, 1.59; CI, 1.01-2.51), unemployment (OR, 2.15; CI, 1.21-3.83), and chronic stress (OR, 3.67; CI, 2.13-6.34). These social determinants were independent predictors of the risk of ICAD, in addition to those described in other world populations. CONCLUSIONS: ICAD accounted for one fifth of all strokes making it the most common ischemic stroke mechanism. In addition to aggressive risk factor control, data also indicated broader holistic efforts on ameliorating inequity, unemployment, and stress reduction to reduce stroke because of ICAD.

Distribution, Severity and Radiologic Features of Intracranial Stenosis in Asymptomatic Pakistanis.

BACKGROUND: Intracranial atherosclerotic disease (ICAD) is the most common ischemic stroke subtype globally. It accounts for 30-50% of all ischemic strokes in Asians. AIMS: The aim of the study is to report the frequency of asymptomatic ICAD and its associated Magnetic Resonance Imaging (MRI) findings. METHODS: 200 adult participants were recruited from the Radiology Departments of two major diagnostic centers in Karachi. Eligible participants were confirmed for the absence of stroke symptoms via the Questionnaire for Verifying Stroke Free Status (QVSFS). QVSFS negative subjects underwent MRI on a 1.5 Tesla scanner. Images were centrally reviewed on Di com Viewer 3.0 with electronic calipers to calculate the degree of ICAD. RESULTS: Mean age of subjects was 37.1 years (S.D 15.1) with 50.5% men (n=101) and 49.5% women (n=99). Asymptomatic ICAD was found in 34.5% (n=69) subjects. Of the 3800 intracranial arteries studied, 2.2% (n=88) had biological disease. 20.5% (n=18) of these vessels had atherosclerotic irregularities, 43.2% (n=38) had mild stenos is, 11.4% (n=10) had moderate stenos is, 5.7% (n=5) had severe stenos is while 19.3% (n=17) were completely occluded. The posterior cerebral artery (42% of stenosed arteries, n=37) was most affected. 23.5% (n=47) of subjects had peri-ventricular lucencies, 10.5% (n=21) had brain atrophy while 3.5% (n=7) had silent brain infarcts. There was a significant association between asymptomatic ICAD and peri ventricular lucencies (PR 1.59; 95% CI 1.35-1.99). CONCLUSION: Asymptomatic ICAD is common in young Pakistanis, with no gender predilection; it preferentially affects the posterior circulation. Silent infarcts are rare compared to peri ventricular lucencies and atrophy.

Cilostazol versus aspirin for secondary prevention of vascular events after stroke of arterial origin.

BACKGROUND: Aspirin is widely used for secondary prevention after stroke. Cilostazol has shown promise as an alternative to aspirin in Asian people with stroke. OBJECTIVES: To determine the relative effectiveness and safety of cilostazol compared directly with aspirin in the prevention of stroke and other serious vascular events in patients at high vascular risk for subsequent stroke, those with previous transient ischaemic attack (TIA) or ischaemic stroke of arterial origin. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched September 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 4), MEDLINE (1950 to May 2010) and EMBASE (1980 to May 2010). In an effort to identify further published, ongoing and unpublished studies we searched journals, conference proceedings and ongoing trial registers, scanned reference lists from relevant studies and contacted trialists and Otsuka Pharmaceutical Co Ltd. SELECTION CRITERIA: We selected all randomised controlled trials (RCTs) comparing cilostazol with aspirin where participants were treated for at least one month and followed systematically for development of vascular events. DATA COLLECTION AND ANALYSIS: Data extracted from eligible studies included: (1) a composite outcome of vascular events (stroke, myocardial infarction or vascular death) during follow up (primary outcome); (2) separate outcomes of stroke (ischaemic or haemorrhagic, fatal or non-fatal), myocardial infarction (MI) (fatal or non-fatal), vascular death and death from all causes; and (3) main outcomes of safety including any intracranial, extracranial or gastrointestinal (GI) haemorrhage and other outcomes during treatment follow up (secondary outcomes). We computed an estimate of treatment effect and performed a test for heterogeneity between trials. We analysed data on an intention-to-treat basis and assessed bias for all included studies. MAIN RESULTS: We included two RCTs with 3477 Asian participants. Compared with aspirin, cilostazol was associated with a significantly lower risk of composite outcome of vascular events (6.77% versus 9.39%, risk ratio (RR) 0.72, 95% confidence interval (CI) 0.57 to 0.91), and lower risk of haemorrhagic stroke (0.53% versus 2.01%, RR 0.26, 95% CI 0.13 to 0.55). In terms of outcome of safety compared with aspirin, cilostazol was significantly associated with minor adverse effects (8.22% versus 4.95%, RR 1.66, 95% CI 1.51 to 1.83). AUTHORS' CONCLUSIONS: Cilostazol is more effective than aspirin in the prevention of vascular events secondary to stroke. Cilostazol has more minor adverse effects, although there is evidence of fewer bleeds.

Utilization and outcome of thrombolytic therapy for acute stroke in Pakistan.

Our objective was to identify the outcome of patients treated with tissue plasminogen activator (r-tPa) in Pakistan and compare these data to available regional and international data. The charts of all patients treated with r-tPa for acute stroke at two centers in Pakistan (Aga Khan University, Karachi and Liaquat National hospital, Karachi) were retrospectively reviewed. We identified 21 patients. The utilization of tPa at Aga Khan Hospital was 18/1,185 patients (1.5%) from 2005 to 2007 while at Liaquat National Hospital was 3/575 patients (0.52%) over 1 year (2007). Mean time interval between stroke onset and start of r-tPa infusion was 169 min. Three patients (14%) developed fatal hemorrhage and two (10%) developed non-fatal hemorrhage. Four patients (19%) died. We identified protocol violations in seven patients (33%). In conclusion, the utilization of thrombolytic therapy is low and complication rate is high. Interventions for training physicians are needed.

Moyamoya disease: a clinical spectrum, literature review and case series from a tertiary care hospital in Pakistan.

BACKGROUND: Moyamoya is a rare cerebrovascular disease of unknown etiology. The data on moyamoya disease from Pakistan is sparse. We report a case series of 13 patients who presented with moyamoya disease to a tertiary care hospital in Pakistan with a national referral base. METHODS: We conducted a retrospective review of thirteen patients who presented to The Aga Khan University and diagnosed with "Moyamoya Disease" during the period 1988 - 2006. These patients were identified from existing hospital database via ICD-9 codes. A predesigned questionnaire containing information about clinical presentation, management and neuroimaging was administered to all identified patients. RESULTS: There were seven males and six females. Mean age at presentation was 16.5 years and a female predominance was found in the pediatric age group (n = 10, 71.4%). Stroke (n = 11, 84.2%) was the most common presentation with motor deficit being the universal cortical symptom. Fever was a common symptom in the lower age groups (n = 4, 51.7%). Cerebral Angiography and Magnetic Resonance Angiography showed bilateral involvement of the vessels in eleven patients while unilateral in two. Subarachnoid and interventricular haemorrhage appeared in 2(15.4%) adults. Twelve (92.3%) patients were discharged as independent with minor deficits regardless of therapeutic modality. Only three (23.0%) patients underwent surgery whereas the remaining were managed conservatively. CONCLUSION: Physicians when dealing with childhood strokes and characteristic deficits in adult population should consider Moyamoya disease.

Anticoagulants for acute ischaemic stroke.

BACKGROUND: Most ischaemic strokes are caused by blood clots blocking an artery in the brain. Clot prevention with anticoagulants might improve outcome if bleeding risks were low. This is an update of a Cochrane review first published in 1995, and previously updated in 2004. OBJECTIVES: To assess the effect of anticoagulant therapy versus control in the early treatment (less than 14 days) of patients with acute ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched 2 October 2007), and two Internet clinical trials registries for relevant ongoing studies (last searched October 2007). SELECTION CRITERIA: Randomised trials comparing early anticoagulant therapy (started within two weeks of stroke onset) with control in patients with acute presumed or confirmed ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, assessed trial quality, and extracted the data. MAIN RESULTS: Twenty-four trials involving 23,748 participants were included. The quality of the trials varied considerably. The anticoagulants tested were standard unfractionated heparin, low-molecular-weight heparins, heparinoids, oral anticoagulants, and thrombin inhibitors. Based on 11 trials (22,776 participants) there was no evidence that anticoagulant therapy reduced the odds of death from all causes (odds ratio (OR) 1.05; 95% confidence interval (CI) 0.98 to 1.12) at the end of follow up. Similarly, based on eight trials (22,125 participants), there was no evidence that anticoagulants reduced the odds of being dead or dependent at the end of follow up (OR 0.99; 95% CI 0.93 to 1.04). Although anticoagulant therapy was associated with fewer recurrent ischaemic strokes (OR 0.76; 95% CI 0.65 to 0.88), it was also associated with an increase in symptomatic intracranial haemorrhages (OR 2.55; 95% CI 1.95 to 3.33). Similarly, anticoagulants reduced the frequency of pulmonary emboli (OR 0.60; 95% CI 0.44 to 0.81), but this benefit was offset by an increase in extracranial haemorrhages (OR 2.99; 95% CI 2.24 to 3.99). AUTHORS' CONCLUSIONS: Since the last version of the review, neither of the two new relevant studies have provided additional information to change the conclusions. In patients with acute ischaemic stroke, immediate anticoagulant therapy is not associated with net short or long-term benefit. Treatment with anticoagulants reduced recurrent stroke, deep vein thrombosis and pulmonary embolism, but increased bleeding risk. The data do not support the routine use of any the currently available anticoagulants in acute ischaemic stroke.

Cerebral venous thrombosis: a descriptive multicenter study of patients in Pakistan and Middle East.

BACKGROUND AND PURPOSE: The natural history, causative factors, and outcomes of patients with cerebral venous thrombosis from Asia and Middle East have not been well described. This descriptive multicenter study describes the results for cerebral venous thrombosis patients in South Asia and the Middle East. METHODS: The retrospective and prospective data of patients with radiologically confirmed cerebral venous thrombosis were collected from 4 centers located in Pakistan and United Arab Emirates. The demographic, clinical, radiological, and outcome data were recorded and analyzed. Primary outcome was death or dependency (modified Rankin score >2) at the time of hospital discharge. RESULTS: This study included 109 patients with cerebral venous thrombosis; the presenting features most commonly being observed were headache (81%), focal motor deficits (45%), seizures (39%), and mental status changes (37%). Important predisposing factors included systemic and central nervous system infection (18%), postpartum state (17%), hyperhomocystinemia (9%), genetic thrombophilia (5%), and oral contraceptive pill use (3%). Ninety-six (67%) patients received therapeutic anticoagulation. Seven patients died and 43 had poor outcome at discharge. Focal motor deficits (OR, 2.93; 95% CI, 1.2-7.5; P=0.018) and hemorrhagic infarctions (OR, 2.81; 95% CI, 1.04-7.85; P=0.041) were independent predictors of unfavorable outcome at discharge. Hemorrhagic infarction was the most significant factor of long-term unfavorable outcome (OR, 5.87; 95% CI, 1.49-23.02; P=0.011). CONCLUSIONS: Infections and postpartum state were the most common predisposing factors for cerebral venous thrombosis in this cohort. Most patients (67%) were treated with anticoagulation therapy. Almost 50% of patients were dead or disabled at discharge.

Incidence and epidemiology of cerebral venous thrombosis.

Cerebral venous sinus thrombosis is a disorder whose epidemiology has changed over the past few decades. It is no longer regarded as a uniformly fatal disease. CVST is not a rare disorder. It may have a differential geographic distribution with a higher incidence in the Asian world. It is a disease of neonates, younger women and men, often a hypercoagulable state, either acquired (e.g., cancer) or a genetic prothrombotic condition may be present. Outcome is not uniformly dismal and prognostic criteria that detect patients with a poor outcome have become available from prospective studies. There is a paucity of well designed large scale epidemiologic studies focused on venous thrombosis from regions where it is relatively frequent (South Asia, Middle East). The newer epidemiologic data derived from a Caucasian database; suggest a better overall prognosis, younger age at distribution than arterial stroke.

Pathophysiology of cerebral venous thrombosis--an overview.

Cerebral venous sinus thrombosis is a disorder with a unique pathophysiology which needs to be described. A Medline search of all articles detailing pathophysiology of CVST was done, using keywords: cerebral venous thrombosis and pathophysiology. In addition, major texts were reviewed for additional references. The pathophysiology of CVST depends on two interconnected events, local signs due to venous infarct, e.g., hemiparesis and global signs due to raised ICP from an obstructed venous system--papilloedema and isolated intracranial hypertension being one of them. Pathophysiology of CVST is diverse and makes it easier to understand the diversity of clinical presentations.

Thrombolytic therapy in cerebral venous sinus thrombosis.

The use of thrombolytic agents to rapidly lyse the clot has emerged as a therapeutic modality, in concert with interventional neuroradiologic approaches to deliver the agent locally at the site of thrombosis. There are no randomized, double blind, placebo, controlled trials to support thrombolysis as a first line therapy in patients with cerebral venous sinus thrombosis compared to standard therapy using anticoagulation with weight based dose adjusted unfractionated Heparin. Numerous case reports and a single non randomized trial have shown that it is comparatively safe and may rescue patients who are deteriorating despite anticoagulation with unfractionated Heparin. Consideration must be given to the use of thrombolysis in this group. This is an approach that must be restricted to centers with considerable experience in neurointerventional therapy.