Ischemic strokes in Pakistan: observations from the national acute ischemic stroke database.

BACKGROUND: The objective of this study was to establish a multicenter ischemic stroke registry, first of its kind in Pakistan, to provide insight into the epidemiology, subtypes, and risk factors of ischemic strokes in this country. METHODS: Four academic centers (3 urban and 1 rural) participated in this project. The inclusion criteria for subjects included adults (>14 years) with acute neurologic deficit, consistent with clinical diagnosis of ischemic stroke and supported by neuroimaging. RESULTS: Data were available for 874 subjects. Mean age of the subjects was 59.7 years, 60.5% were males, and 18% were young. Large vessel strokes were the most common subtype found in 31.7% subjects, followed by small vessel disease (25.7%) and cardioembolic strokes (10.4%). Almost 32% subjects had ill-defined etiology for their ischemic stroke. Dyslipidemia was a most common risk factor present in 83% patients. Data related to in-hospital complications were available for 808 subjects, of which 233 complications were recorded. Pneumonia was the most common of these seen in 105 (13%) subjects, followed by urinary tract infection (7.2%). Outcome at discharge was recorded for 697 subjects. Ninety-two had died during their hospital stay (13.2%). Only 36% subjects had a favorable outcome at discharge defined as a modified Rankin Scale (mRS) score of 2 or less. A total of 446 of 697 subjects had poor outcome at discharge (defined as an mRS score≥3). CONCLUSIONS: Hypertension and dyslipidemia were the most common risk factors and large vessel atherosclerosis was the most common stroke etiology. Elderly patients were significantly more likely to have in-hospital complications, die during their hospital stay, and have a higher mRS score at discharge.

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.

Frequency and outcome of carotid atheromatous disease in patients with stroke in Pakistan.

BACKGROUND AND PURPOSE: Limited data exist on the frequency and outcome of carotid artery disease in Pakistan. Such information would help guide the usefulness of screening for the condition in this low-middle income health care setting. METHODS: A prospective, descriptive study was conducted among 3 large teaching hospitals in Karachi, Pakistan. Patients referred for carotid Doppler ultrasound examination were included if they had experienced a stroke or TIA within the previous month. The severity and morphology of carotid disease were characterized by trained technicians using standardized criteria. Demographic and risk factor data were collected at baseline, and the outcome of patients was assessed at least 6 months later. RESULTS: A total of 672 patients underwent bilateral carotid Doppler ultrasound (1344 carotid examinations). The findings revealed 0% to 50% stenosis in 526 (78%), 51% to 69% stenosis in 57 (8%), 70% to 99% stenosis in 82 (12%), and total occlusion in 7 patients (1%). Potentially surgically correctable disease, defined as 70% to 99% carotid artery stenosis, was present in only 79 (12%) patients, of whom 47 (60%) were ipsilateral symptomatic, 15 (20%) asymptomatic, and 17 (20%) had status unknown. Outcome information at >or=6 months follow-up was available for 36 of the 47 (76%) surgically correctable and only 4 of these patients (12%) had undergone surgical or radiological intervention (carotid endarterectomy in 3 patients and carotid stenting in 1 patient). CONCLUSIONS: The frequency of carotid artery disease of at least moderate severity is very low in patients with recent stroke or TIA and there is low utilization of high-cost, carotid intervention procedures in Pakistan. These data raise questions regarding the applicability and cost-effectiveness of routine carotid ultrasound screening in our country and similar population in Asia. The local socio-economic and clinical data do not support routine carotid Doppler ultrasound in every patient with stroke and TIA in Pakistan. Studies are warranted to determine predictors of significant carotid artery stenosis in stroke/TIA patients of our country to develop reliable stroke guidelines appropriate for local population.

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.

Post stroke seizures: descriptive study from a tertiary care centre in Pakistan.

OBJECTIVE: To determine the frequency, mode of onset and outcome of post stroke seizures in a local setting. METHODS: The retrospective (Aug 1999 to July 2001) and prospective (August 2001 to July 2002) data of patients aged 14 years and above, with post stroke seizures was collected from a tertiary care centre in a metropolitan city. The demographic, clinical, radiological, laboratory, neurophysiologic and outcome data was recorded and analyzed. RESULTS: During the three year period 1548 patients with stroke were admitted to the hospital. Four hundred thirty one (28%) had intracerebral haemorrhage (ICH) and 1117 (72%) had ischaemic stroke. One hundred seventeen (8%) of the 1548 had seizures. Their mean age was 63 +/- 12 (range; 15-70) years. Fifty-nine (50%) were men and 58 (50%) were women. Twenty of 431(5%) patients with ICH and 97/1117 (9%) with ischaemic stroke, developed seizures. Nine of 117 (8%) developed a seizure within 14 days of stroke and 108/117 (92%) developed seizures after 14 days of stroke. Twenty-six (22%) had partial and 91 (78%) had generalized seizures. Two patients expired early in the course. Twenty four (21%) of these continued to have seizures at one year follow up. Fifteen of 37 (40%) patients who had systemic infections early in the course continued to have seizures at one year as compared to 9/80 (11%) who did not (p = 0.001). CONCLUSIONS: Frequency of post stroke seizures is the same as reported in western literature. Post stroke seizures are more common in patients with ischaemic stroke. Generalized seizures are more common than partial seizures. Systemic infections early in the course are associated with recurrence of seizures at one year.

Stroke in Pakistan.

Stroke is the most common cause of disability and a leading cause of mortality world wide. Though the incidence is falling in West but probably is rising in Asia. The burden of stroke risk factors in Pakistan is enormous e.g. by 2020 Pakistan will be 4th most populous country in terms of diabetic patients. Similarly every 3rd person above age of 45 years has hypertension. Ironically a great majority of these patients are unaware of their diagnosis. This is further complicated by the fact that most of diagnosed patients have uncontrolled hypertension, as a result of poor compliance on patients part and poor updated knowledge on physicians part. Data on stroke incidence and prevalence from Pakistan is scarce, however, there are several reported case series in literature highlighting significant differences in terms of stroke epidemiology, risk factors and stroke subtypes/patterns. Considering a high population, absolute number of stroke in our country would be in millions. Its consequences are myriad ranging form physical disability to death, to psychologic, social and economic consequences. These consequences do not only affect the individual or his/her family but also society as a whole. We reviewed available literature on stroke and its risk factors from Pakistan.

Hypotension at presentation is an indicator of poor prognosis in acute intracerebral haemorrhage.

OBJECTIVE: To identify frequency of hypotension in a large cohort of patients with intracerebral haemorrhage and its prognostic significance. METHODS: We retrospectively reviewed medical records of 920 patients with spontaneous intracerebral haemorrhage (ICH). Patients were divided in three groups based on Diastolic blood pressure (DBP); hypotensive group (DBP < 70 mmHg), normotensive group (DBP; 71-90 mmHg) and hypertensive group (DBP > 90 mmHg). RESULTS: Of the total patients with ICH, 7% (64) presented with hypotension, 13% (120) were normotensive and 80% (736) were hypertensive. In the hypotensive group, 37% (24) patients died as compared to 25%(30) in normotensive group and 25% (182) in hypertensive group (p = 0.03). Hypotension at presentation, thalamic and lobar haemorrhages were predictors of poor outcome. Patients with diastolic BP of less than 70 were significantly more likely to die than with DBP 71-90 (OR = 1.9, 95% CI; 1.1-2.9, p = 0.03). This relationship was still significant after adjusting for age, sex, history of presentation, coma at presentation and location of haemorrhage (OR = 1.45, 95% CI; 1.0-2.2, p = 0.045). CONCLUSION: Our findings suggest that hypotension at presentation is a predictor of poor outcome in patients with ICH. Patients with diastolic blood pressure less than 70 are more likely to have a fatal outcome as compared to those with normal blood pressure.

Post-infarct cerebellar cognitive affective syndrome: a case report.

Post Infarct cerebellar cognitive affective syndrome is a rare disorder, characterized by cognitive impairment in the domains of memory, language, visuo-spatial functioning and affect after cerebellar stroke. We report a case of young female who developed mood alteration and cognitive disturbance following isolated cerebellar infarct. We, therefore, advocate a potential role of cerebellum in regulation of cognition and behaviour in humans.

A non-randomized study of safety and efficacy of heparin for DVT prophylaxis in intracerebral haemorrhage.

OBJECTIVE: To evaluate the safety and efficacy of subcutaneous heparin for deep venous thrombosis (DVT) prophylaxis in patients with intracerebral haemorrhage (ICH) during acute phase in comparison to elastic stockings. METHODS: The diagnosis of ICH was based on imaging (CT or MRI) and DVT was based on Doppler ultrasound. RESULTS: A total of 458 patients were identified over a period of 5 years (1997-2001). Median age was 59 years (range:12-99 years). Two hundred (44%) patients received heparin (heparin group) in addition to elastic stockings and 258 (56%) patients were only given elastic stockings (stockings group). These two groups were not randomized. Heparin was administered subcutaneously (SQ) in doses of 2500-5000 international units twice daily. Two groups were matched for age (p = 0.5), sex (p = 0.28), presence of diabetes mellitus (p = 0.14), cigarette smoking (p = 0.045) and presence of hydrocephalus or midline shift on CT/MRI (p= 0.87). One patient developed DVT in control group while none developed DVT in heparin group (p = 0.18). One patient had worsening of ICH on repeat CT scan in Heparin group. This worsening was non fatal. Systemic haemorrhagic complications (non fatal) were seen in 7 (14%) patients receiving heparin. Twenty five patients (12%) in heparin group and 52 (20%) in control group died (p = 0.02). CONCLUSION: Subcutaneous heparin in doses of 2500-5000 units twice daily during acute phase in patients with ICH may be safe for DVT prophylaxis. It was not superior to elastic stockings in a non-randomized comparison to prevent DVT.

Obstetric cerebral venous thrombosis.

Pregnancy and puerperium are most prevalent prothrombotic states leading to cerebral venous thrombosis. Likelihood of stroke to be of venous origin is greater in stroke associated with pregnancy compared to stroke unrelated to pregnancy. Pregnancy induces several changes in coagulation system, which persists at least during early puerperium, rendering it a prothrombotic state. Hypercoaguability worsens further after delivery as a result of volume depletion and trauma. During puerperium additional risk factors include infection and instrumental delivery or Caesarean section. The management follows general rules as for the venous thrombosis unrelated to pregnancy, however the prognosis is different.

Autonomic nervous system dysfunction predicts poor prognosis in patients with mild to moderate tetanus.

BACKGROUND: Autonomic nervous system (ANS) dysfunction is present in up to one third of patients with tetanus. The prognostic value of ANS dysfunction is known in severe tetanus but its value is not well established in mild to moderate tetanus. METHODS: Medical records of all patients admitted with tetanus at two academic tertiary care centers in Karachi, Pakistan were reviewed. The demographic, clinical and laboratory data was recorded and analyzed. ANS dysfunction was defined as presence of labile or persistent hypertension or hypotension and sinus tachycardia, tachyarrythmia or bradycardia on EKG. Patients were divided into two groups based on presence of ANS dysfunction (ANS group and non ANS group). Tetanus severity was classified on the basis of Ablett criteria. RESULTS: Ninety six (64 males; 32 females) patients were admitted with the diagnosis over a period of 10 years. ANS group had 31 (32%) patients while non ANS group comprised of 65 (68%) patients. Both groups matched for age, gender, symptom severity, use of tetanus immunoglobulin and antibiotics. Twelve patients in ANS group had mild to moderate tetanus (Ablett I and II) and 19 patients had severe/very severe tetanus (Ablett III and IV). Fifteen (50%) patients in ANS group required ventilation as compared to 28 (45%) in non-ANS group (p = 0.09). Fourteen (47%) patients died in ANS group as compared to 10 (15%) in non ANS group (p= 0.002). Out of those 14 patients died in ANS group, six patients had mild to moderate tetanus and eight patients had severe/very severe tetanus. Major cause of death was cardiac arrhythmias (13/14; 93%) in ANS group and respiratory arrest (7/10; 70%) in non ANS group. Ten (33%) patients had complete recovery in ANS group while in non ANS group 35(48%) patients had complete recovery (p= 0.05). CONCLUSIONS: ANS dysfunction was present in one third of our tetanus population. 40% patients with ANS dysfunction had only mild to moderate tetanus. ANS dysfunction, irrespective of the need of mechanical ventilation or severity of tetanus, predicted poor outcome.

Kleine-Levin syndrome.

Kleine-Levin Syndrome (KLS) is a rare disorder of uncertain etiology, characterized by recurring episodes of undue sleepiness lasting for days. We report a case of young female presenting with episodes of undue sleep along with hypersexuality and excessive food intake, who improved significantly on lithium and valproate. KLS should be considered in young patients, who present with episodes of undue somnolence.

Predictors of ischemic versus hemorrhagic strokes in hypertensive patients.

OBJECTIVE: To identify the factors that predispose to ischemic versus hemorrhagic stroke in hypertensive patients. DESIGN: Cohort study. PLACE AND DURATION OF STUDY: The study was conducted at the Aga Khan University Hospital (AKUH), Karachi, from August 1999 to May 2001. MATERIALS AND METHODS: All the hypertensive patients, who were registered in AKUH acute stroke outcome data base, over a period of 22 months, were identified and from this cohort the patients with first ever stroke were selected. The data regarding demographics, stroke type (ischemic vs. hemorrhagic), pre-existing medical problems, laboratory and radiological investigations was recorded and analyzed. RESULTS: Five hundred and nineteen patients with either ischemic stroke or parenchymal hemorrhage were registered over a period of 22 months. Three hundred and forty-eight patients (67%) had hypertension and of these, 250 had first ever stroke at the time of admission. Presence of diabetes mellitus (OR: 3.76; CI:1.67-8.46) and ischemic heart disease (OR: 6.97; CI:1.57-30.98) were found to be independent predictors of ischemic strokes. CONCLUSION: Presence of diabetes mellitus and ischemic heart disease predict ischemic stroke in a patient with hypertension.

Prognostic indicators in patients with primary intraventricular haemorrhage.

OBJECTIVES: Primary intraventricular haemorrhage (PIVH) is a rare clinical entity. We sought to evaluate risk factors, clinical and radiological features, and outcome of patients with PIVH. MATERIALS AND METHODS: Cases of PIVH were identified from cohort of patients with non traumatic intracerebral haemorrhage (ICH) by reviewing the radiological data. Their charts were reviewed and demographic, clinical, radiological and laboratory data was recorded and analyzed. Chi square and t test were used to determine predictors of poor outcome. RESULTS: Fifteen of 677 (2%) patients with ICH had PIVH. Nine (60%) were men. Median age was 56 years. Predisposing factors included hypertension in twelve (80%), coagulopathy in five (33%) and vascular malformations in two (13%) patients. Eleven (73%) patients developed hydrocephalus. Two patients died. Univariate analysis identified diabetes mellitus, blood in all ventricles and coagulopathy as predictors of death during initial hospital stay and hydrocephalus as predictor of poor outcome (death and disability combined) (p < 0.05). CONCLUSION: Hypertension is most common associated risk factor for primary intraventricular haemorrhage followed by coagulopathy. Hydrocephalus is a common complication, associated with poor outcome. Diabetes mellitus, coagulopathy and panventricular blood predict early mortality.

Guillain-Barré syndrome (demyelinating) six weeks after bariatric surgery: A case report and literature review.

Obesity is a major health problem worldwide. Bariatric surgery has been increasingly used to manage obesity. Many acute as well as chronic neurological complications have been reported after bariatric surgery including Guillain-Barré syndrome (GBS). An autoimmune process has been postulated as the underlying pathophysiology. Most of the reported cases of GBS after bariatric surgery are of the axonal variety. Here, we report a case of a demyelinating variety of GBS in a young woman who presented with acute onset of progressive weakness and paresthesia of all limbs within six weeks after bariatric surgery. She was treated with intravenous immunoglobulin (IVIG) and rehabilitation. She had complete recovery on follow-up. We believe that onset of acute inflammatory demyelinating polyradiculoneuropathy (AIDP), which is demyelinating variety of GBS, is associated with changes in immune system after bariatric surgery.

Predictors of restless legs syndrome in pregnancy: a hospital based cross sectional survey from Pakistan.

Restless legs syndrome (RLS) is more common in pregnant women. The objective of our study was to determine frequency of RLS in pregnant women and predictors of RLS in pregnancy in Pakistan. All pregnant women admitted at The Aga Khan University Hospital for delivery from June to July 2005 were enrolled. Eighty-one of 271 (30%) interviewed women fulfilled the diagnostic criteria of RLS. One hundred seventeen (43%) of the subjects dropped their haemoglobin during the pregnancy. No significant difference in haemoglobin drop was noted between the RLS group and healthy group. On multivariate analysis family history of RLS (OR: 8.43, CI: 2.32-30.57, p value<0.001), history of RLS in prior pregnancy (OR: 53.74, CI: 6.72-429.8, p value<0. 001), history of RLS in past even when non-pregnant (OR: 12.91, CI: 3.34-49.87, p value<0.001) and haemoglobin of 11g/dL or less (OR: 2.05, CI: 1.04-4.04, p value 0.036) were found to be independent predictors of RLS during pregnancy. Subgroup analysis revealed that family history of RLS (OR: 3.06, CI: 1.2-7.83, p value 0.019) and anemia (OR: 1.89, CI: 0.96-3.71, p value 0.06) were associated with de novo RLS, and family history of RLS (OR: 12.39, CI: 4.45-35.54, p value<0.001) and multiparity (OR: 6.84, CI: 2.15-21.71, p value 0.001) were predictors of pre-existing RLS.

The burden of stroke in Pakistan.

Epidemiologic literature on stroke burden, patterns of stroke is almost non existent from Pakistan. However, several hospital-based case series on the subject are available, mainly published in local medical journals. Despite the fact that true stroke incidence and prevalence of stroke in Pakistan is not known, the burden is assumed to be high because of highly prevalent stroke risk factors (hypertension, diabetes mellitus, coronary artery disease, dyslipidemia and smoking) in the community. High burden of these conventional stroke risk factors is further compounded by lack of awareness, poor compliance hence poor control, and inappropriate management/treatment practices. In addition certain risk factors like rheumatic valvular heart disease may be more prevalent in Pakistan. We reviewed the existing literature on stroke risk factors in community, the risk factor prevalence among stroke patients, patterns of stroke, out come of stroke, availability of diagnostic services/facilities related to stroke and resources for stroke care in Pakistan.