Shifting Perceptions of Risk and Reward: Use of Anticoagulation in Patients With Acute Brain Ischemia and Atrial Fibrillation: Nine-Year Data From a National Acute Stroke Registry (National Acute Stroke Israeli Survey [NASIS]).

BACKGROUND AND PURPOSE: Despite overwhelming evidence for the benefits of anticoagulation in patients with brain ischemia and atrial fibrillation, vast underuse has been reported. METHODS: Use of anticoagulation for secondary stroke prevention was assessed in the National Acute Stroke Israeli Survey registry (NASIS) of hospitalized patients with atrial fibrillation and acute brain ischemia. Logistic regression analysis was performed to evaluate the effects of clinical covariates on anticoagulation therapy at discharge, and anticoagulation use over time was assessed in subgroups of patients with identified barriers to anticoagulation utilization. RESULTS: There were 1254 survivors of acute brain ischemia with atrial fibrillation (mean age 77.2±10.6 years; 57.7% female). Between 2004 and 2013, the proportion of patients discharged on anticoagulation increased from 55% to 76.2%, and among those without perceived contraindications from 70% to 96% (P<0.0001). Older age, greater stroke severity, earlier registry period, and presence of contraindications were independent predictors of withholding therapy. Increased anticoagulation use over the years was observed even in patients with barriers to anticoagulation use, including patients with potential contraindications (P<0.001). CONCLUSIONS: In survivors of acute brain ischemia with atrial fibrillation, we observed a substantial increase in anticoagulation utilization within less than a decade. This change was mainly driven by greater utilization of anticoagulation in subgroups with traditional clinical barriers to anticoagulation use, indicating a shift in physicians' perceptions of the risk-benefit ratio of anticoagulation.

Costeff syndrome: clinical features and natural history.

Costeff syndrome (CS) is a rare autosomal-recessive neurological disorder, which is known almost exclusively in patients of Iraqi Jewish descent, manifesting in childhood with optic atrophy, ataxia, chorea and spastic paraparesis. Our aim was to study the clinical spectrum of CS and natural history using a cross-sectional study design. Consecutive patients with CS were recruited to the study. Patients were diagnosed based on clinical features, along with elevated urinary levels of methylglutaconic and methylglutaric acid, and by identification of the disease-causing mutation in the OPA3 gene in most. All patients were examined by a neurologist and signs and symptoms were rated. 28 patients with CS (16 males, 21 families, age at last observation 28.6 ± 16.1 years, range 0.5-68 years) were included. First signs of neurological deficit appeared in infancy or early childhood, with delayed motor milestones, choreiform movements, ataxia and visual disturbances. Ataxia and chorea were the dominant motor features in childhood, but varied in severity among patients and did not seem to worsen with age. Pyramidal dysfunction appeared later and progressed with age (r = 0.71, p < 0.001) leading to spastic paraparesis and marked gait impairment. The course of neurological deterioration was slow and the majority of patients could still walk beyond the fifth decade. While visual acuity seemed to deteriorate, it did not correlate with age. CS is a rare neurogenetic disorder that causes serious disability and worsens with age. Spasticity significantly increases over the years and is the most crucial determinant of neurological dysfunction.

Burden and outcome of prevalent ischemic brain disease in a national acute stroke registry.

BACKGROUND AND PURPOSE: Previous overt stroke and subclinical stroke are frequent in patients with stroke; yet, their clinical significance and effects on stroke outcome are not clear. We studied the burden and outcome after acute ischemic stroke by prevalent ischemic brain disease in a national registry of hospitalized patients with acute stroke. METHODS: Patients with ischemic stroke in the National Acute Stroke Israeli prospective hospital-based registry (February to March 2004, March to April 2007, and April to May 2010) with information on previous overt stroke and subclinical stroke per computed tomography/MRI (n=3757) were included. Of them, a subsample (n=787) was followed up at 3 months. Logistic regression models were computed for outcomes in patients with prior overt stroke or subclinical stroke, compared with patients with first stroke, adjusting for age, sex, vascular risk factors, stroke severity, and clinical classification. RESULTS: Two-thirds of patients had a prior overt stroke or subclinical stroke. Death rates were similar for patients with and without prior stroke. Adjusted odds ratios (OR; 95% confidence interval [CI]) for disability were increased for patients with prior overt stroke (OR, 1.31; 95% CI, 1.03-1.66) and subclinical stroke (OR, 1.45; 95% CI, 1.16-1.82). Relative odds of Barthel Index≤60 for patients with prior overt stroke (OR, 2.04; 95% CI, 1.14-3.68) and with prior subclinical stroke (OR, 2.04; 95% CI, 1.15-3.64) were twice higher than for patients with a first stroke. ORs for dependency were significantly increased for patients with prior overt stroke (OR, 1.95; 95% CI, 1.19-3.20) but not for those with subclinical stroke (OR, 1.36; 95% CI, 0.84-2.19). CONCLUSIONS: In our national cohort of patients with acute ischemic stroke, nearly two thirds had a prior overt stroke or subclinical stroke. Risk of poor functional outcomes was increased for patients with prior stroke, both overt and subclinical.

Neurological outcome in cerebrotendinous xanthomatosis treated with chenodeoxycholic acid: early versus late diagnosis.

OBJECTIVE: To present the long-term neurological outcome of Jewish Israeli patients with cerebrotendinous xanthomatosis (CTX) after several years of chenodeoxycholic acid (CDCA) treatment. METHODS: A cross sectional observational study of all patients with a diagnosis of CTX followed in a referral outpatient clinic during the years 2003-2012. RESULTS: Eighteen patients (10 men) from 11 families were enrolled. Sixteen patients were included in the analysis (2 patients had low compliance for treatment). The mean ± SD age at last evaluation was 35.0 ± 9.2 years (range, 16-45 years). After their diagnosis, at age 22.6 ± 10.8 years, all patients were treated with CDCA. Patients who started treatment after the age of 25 years had worse outcome and were significantly more limited in ambulation (P = 0.004) and more cognitively impaired (P = 0.047). Five patients who started treatment after 25 years of age continued to deteriorate despite CDCA treatment. CONCLUSIONS: Beginning CDCA treatment as early as possible is crucial to preventing neurological damage and deterioration in CTX. After significant neurological pathology is established, the effect of treatment is limited and deterioration may continue.

Trends in management and outcome of hospitalized patients with acute stroke and transient ischemic attack: the National Acute Stroke Israeli (NASIS) registry.

BACKGROUND AND PURPOSE: Improving stroke management, guideline adherence, and outcome is a global priority. Our aim was to examine trends in nationwide use of reperfusion therapy, stroke in-hospital management, and outcome. METHODS: Data were based on the triennial 2-month period of the National Acute Stroke Israeli registry (February to March 2004, March to April 2007, April to May 2010). The registry includes unselected patients admitted to all hospitals nationwide. There were in total 6279 patients: ischemic stroke, 4452 (70.9%); intracerebral hemorrhage, 485 (7.7%); undetermined stroke, 97 (1.6%); and transient ischemic attacks, 1245 (19.8%). RESULTS: Overall use of reperfusion therapy for acute ischemic stroke increased from 0.4% in 2004% to 5.9% in 2010 (P<0.001; adjusted OR, 17.0; 95% CI, 7.5-38.7). Use of CT or MR angiography for ischemic events increased from 2.1% in 2004% to 16.6% in 2010 (P<0.001; adjusted OR, 9.7; 95% CI, 6.8-13.9). Overall use of antithrombotics and anticoagulation for atrial fibrillation did not differ between periods, whereas clopidogrel use increased nearly 3-fold to 41% and statin use nearly 2-fold to 68%. The relative odds of providing reperfusion therapy, using CT or MR angiography, and prescribing anticoagulants for atrial fibrillation were higher among hospitals with large as compared with small stroke patient volumes. In-hospital mortality after acute ischemic stroke decreased from 7.2% in 2004 to 3.9% in 2010 (P<0.001; adjusted OR, 0.7; 95% CI, 0.4-1.0), whereas there was no significant change in odds of poor functional outcome. CONCLUSIONS: Based on a nationwide stroke registry, use of reperfusion therapy, vascular imaging, and statins is steadily increasing, whereas in-hospital mortality is decreasing.

Chronic kidney disease in patients with acute intracerebral hemorrhage: association with large hematoma volume and poor outcome.

BACKGROUND: Chronic kidney disease (CKD) is associated with both a risk of adverse vascular outcome and a risk of bleeding. We have tested the hypothesis that in the setting of an acute intracerebral hemorrhage (ICH), CKD is associated with poor outcome and with larger hematoma volume. METHODS: We examined the association between CKD and ICH characteristics and outcome within a prospective cohort study of consecutive patients hospitalized with an acute stroke and followed for 1 year. CKD was categorized by the estimated baseline glomerular filtration rate into moderate/severe impairment (<45), mild impairment (45-60) and no impairment (>60 ml/min/1.73 m(2)). RESULTS: Among 128 patients with an ICH (mean age = 71.7 ± 12.3 years, 41.4% women) 46.1% had CKD (23.4% mild and 22.7% moderate/severe). Patients with moderate/severe impairment had >4-fold adjusted hazard ratio for mortality over 1 year (4.29; 95% CI = 1.69-10.90) compared to patients with no impairment. The hematoma volumes [median (25-75%)] were 15.3 ml (5.4-37.5) in patients with no impairment, 16.6 (6.8-36.9) in mild impairment and 50.2 (10.4-109.1) in moderate/severe impairment (p = 0.009). The location of the hematoma was lobar in 12% with no impairment, 17% with mild impairment and 39% with moderate/severe impairment (p = 0.02). Patients with moderate/severe impairment exhibited a 2.3-fold higher hematoma volume (p = 0.04) and a >6-fold higher odds of lobar location (95% CI = 1.59-24.02) as compared to no impairment. Further adjustment for antiplatelet use and for presence of leukoaraiosis attenuated the association with hematoma volume (p = 0.15), while moderate/severe impairment was associated with an adjusted OR of 5.35 (95% CI = 1.18-24.14) for lobar location. CONCLUSIONS: Presence of moderate/severe CKD among patients with ICH is associated with larger, lobar hematomas and with poor outcome.

Anemia status, hemoglobin concentration and outcome after acute stroke: a cohort study.

BACKGROUND: In the setting of an acute stroke, anemia has the potential to worsen brain ischemia, however, the relationship between the entire range of hemoglobin to long-term outcome is not well understood. METHODS: We examined the association between World Health Organization-defined admission anemia status (hemoglobin<13 in males, <12 g/dl in women) and hemoglobin concentration and 1-year outcome among 859 consecutive patients with acute stroke (ischemic or intracerebral hemorrhage). RESULTS: The mean baseline hemoglobin concentration was 13.8 +/- 1.7 g/dl (range 8.1 - 18.7). WHO-defined anemia was present in 19% of patients among both women and men. After adjustment for differences in baseline characteristics, patients with admission anemia had an adjusted OR for all-cause death at 1-month of 1.90 (95% CI, 1.05 to 3.43) and at 1-year of 1.72 (95% CI, 1.00 to 2.93) and for the combined end-point of disability, nursing facility care or death of 2.09 (95% CI, 1.13 to 3.84) and 1.83 (95% CI, 1.02 to 3.27) respectively. The relationship between hemoglobin quartiles and all-cause death revealed a non-linear association with increased risk at extremes of both low and high concentrations. In logistic regression models developed to estimate the linear and quadratic relation between hemoglobin and outcomes of interest, each unit increment in hemoglobin squared was associated with increased adjusted odds of all-cause death [at 1-month 1.06 (1.01 to 1.12; p = 0.03); at 1-year 1.09 (1.04 to 1.15; p < 0.01)], confirming that extremes of both low and high levels of hemoglobin were associated with increased mortality. CONCLUSIONS: WHO-defined anemia was common in both men and women among patients with acute stroke and predicted poor outcome. Moreover, the association between admission hemoglobin and mortality was not linear; risk for death increased at both extremes of hemoglobin.

Relation of effective anticoagulation in patients with atrial fibrillation to stroke severity and survival (from the National Acute Stroke Israeli Survey [NASIS]).

Although the benefit of antithrombotic therapy for stroke prevention in atrial fibrillation (AF) is well recognized, its potential effect on stroke severity and outcome is less well established. Our objective was to examine the effect of preadmission antithrombotic therapy on stroke severity and outcome in patients with AF within a large comprehensive nationwide stroke survey. The data from consecutive patients with AF admitted with acute ischemic stroke or transient ischemic attack during a 2-month period were collected. The patients were categorized into 4 groups according to the use of preadmission antithrombotic therapy: no antithrombotic therapy, antiplatelet therapy, warfarin with an admission international normalized ratio (INR) <2 and INR of > or = 2. Of 1,938 patients presenting with acute brain ischemia, 329 (17%) had AF. The age-adjusted rate of more severe stroke (baseline National Institutes of Health stroke scale score >5) stratified by antithrombotic therapy use was 70% for no antithrombotic therapy use, 55% for antiplatelet therapy use, 59% for warfarin with an INR <2, and 38% for warfarin with an INR of > or = 2 (p = 0.01). Compared to warfarin therapy with an admission INR of > or = 2, the adjusted odds ratio for more severe strokes was 4.0 (95% confidence interval [CI] 1.7 to 10.0) for no antithrombotic therapy, 2.2 (95% CI 1.0 to 9.4) for antiplatelet therapy, and 2.7 (95% CI 1.1 to 6.7) for warfarin therapy with an INR of <2. Similarly, graded associations of antithrombotic medication were observed with severe disability (modified Rankin Scale score >3) or death at discharge, with corresponding adjusted odds ratios of 4.1 (95% CI 1.8 to 9.9), 2.1 (95% CI 1.0 to 4.6), and 1.5 (95% CI 0.6 to 3.5), and 1-year mortality, with corresponding adjusted ORs of 2.4 (95% CI 0.9 to 6.7), 1.9 (95% CI 0.8 to 5.0), and 2.2 (95% CI 0.8 to 6.2). In conclusion, in addition to its established benefit for stroke prevention, effective anticoagulation therapy is associated with decreased stroke severity and better functional outcome and survival in patients with AF presenting with acute brain ischemia.

Ischemic stroke due to acute basilar artery occlusion: proportion and outcomes.

BACKGROUND: Multiple case series, mostly highly selected, have demonstrated a very high mortality following acute basilar artery occlusion. The more widespread availability and use of non-invasive vascular imaging over recent years has increased the rate of ABAO diagnosis. OBJECTIVES: To estimate the proportion of diagnosed ABAO among all-cause ischemic stroke in an era of increasing use of non-invasive vascular imaging and to compare the characteristics and outcomes between these two groups. METHODS: We compared 27 consecutive cases of ABAO identified in a university hospital between 2003 and 2007 with 311 unselected cases of ischemic stroke from two 4 month surveys. RESULTS: ABAO diagnosis increased from 0.3% of all-cause ischemic stroke (2003-2004) to 1.1% (2007), reflecting the increased use of non-invasive vascular imaging. In comparison to all-cause ischemic stroke, ABAO patients were younger (mean age 60 vs. 71 years), were more likely to be male (89% vs. 60%), had less atrial fibrillation (7% vs. 26%), more severe strokes (baseline NIHSS over 20: 52% vs. 12%), higher admission white cell count (12,000 vs. 9000 cells/ mm3), lower admission systolic blood pressure (140 +/- 24 vs. 153 +/- 27 mmHg), higher in-hospital mortality rates (30% vs. 8%) and worse functional outcome (modified Rankin scale < or = 3, 22% vs. 56%) (P< 0.05 for all). Rates of reperfusion therapy for ABAO increased from 0 in 2003-2004 to 60% in 2007. CONCLUSIONS: In this study, ABAO patients represented approximately 1% of all-cause ischemic stroke and were about a decade younger than patients with all-cause ischemic stroke. We report a lower ABAO mortality compared to previous more selected case series; however, most survivors had a poor functional outcome. Given the marked clinical heterogeneity of ABAO, a low threshold for non-invasive vascular imaging with a view to definitive reperfusion treatment is needed.

Improved exercise capacity in patients after minor ischemic stroke undergoing a supervised exercise training program.

BACKGROUND: Regular physical activity is known to have a beneficial impact on multiple cardiovascular risk factors, but there is no routine provision of exercise training programs for patients after ischemic stroke. OBJECTIVES: To assess the tolerability, safety and effect of an outpatient supervised exercise training program in patients after a non-disabling ischemic stroke. METHODS: Patients discharged home following a minor ischemic stroke (modified Rankin scale; mRS < or = 2) were referred to a 3 month outpatient supervised exercise training program, performed twice weekly as prescribed by a physiologist and supervised by physical therapy. Exercise capacity was evaluated by the 6 minute walk test and the modified Bruce exercise test. RESULTS: Of the 52 patients who met the selection criteria, 43 underwent supervised exercise training within 2 months of stroke onset and 9 did not (control group). The baseline characteristics were comparable between the two groups. Following the exercise training program, an improvement in exercise capacity was observed manifested by improvement in the 6 minute walk test (444 +/- 90 to 557 +/- 99 meters in the exercise group vs. 438 +/- 101 to 418 +/- 126 in the control group; P = 0.002 for the score changes) and in the exercise duration achieved in the modified Bruce test and the metabolic equivalents achieved [9.6 +/- 3.7 to 12.4 +/- 3.2 minutes and 6.2 +/- 2.8 to 8.5 +/- 3.4 respectively in the exercise group (n = 41) vs. 9.2 +/- 3.5 to 8.0 +/- 3.4 min and 5.8 +/- 1.8 to 5.8 +/- 2.8 in the control group (n = 7); P = 0.0009 and 0.01 for score changes, respectively]. CONCLUSIONS: An outpatient supervised exercise training program after a minor ischemic stroke is feasible, well tolerated and is associated with improvement in exercise capacity. We strongly recommend that an aerobic exercise program be offered to suitable patients after an ischemic stroke.

Hospital disposition after stroke in a national survey of acute cerebrovascular diseases in Israel.

OBJECTIVE: To investigate predictive factors for disposition after acute stroke. DESIGN: A nationwide survey (2004 National Acute Stroke Israeli Survey). SETTING: All 28 primary general medical centers operating in Israel. PARTICIPANTS: Acute stroke patients (n=1583) admitted during February and March 2004 and discharged from the primary hospital. INTERVENTIONS: Data collected on baseline characteristics, stroke presentation, type and severity, in-hospital investigation and complications, discharge disability, acute hospital disposition, and mortality follow-up. MAIN OUTCOME MEASURE: Hospital disposition to home, acute rehabilitation, or nursing facility. RESULTS: Among patients, 58.9% (n=932) were discharged home, 33.7% (n=534) to rehabilitation departments, and only 7.4% (n=117) to nursing facilities. Admission neurologic status was a good predictor of hospital disposition. Patients with severe strokes were mostly discharged to rehabilitation facilities. Patients with significant functional decline before the index stroke, resulting from a previous stroke or another cause, were sent to inpatient rehabilitation less frequently. Disability level at discharge from acute hospitalization had high predictive value in hospital disposition after stroke. In the northern region of Israel, a higher proportion of patients were sent home and a lower proportion to rehabilitation and nursing facilities, probably because of lower availability of rehabilitation care in this region of Israel. CONCLUSIONS: This nationwide survey shows that most stroke survivors in Israel are discharged home from the acute primary hospital. Good functional status before the index stroke is an important predictor for being sent to acute inpatient rehabilitation. Severity of neurologic impairment and level of disability after the stroke at discharge from the primary hospital are strong predictors for disposition after stroke in Israel. Our data may be useful in discharge planning for stroke patients by policy-makers and health care providers in Israel.

Trombolysis in acute stroke.

BACKGROUND: Rapid restoration of cerebral blood flow is the principle goal of acute ischemic stroke therapy. Intravenous recombinant tissue plasminogen activator is an effective therapy for acute ischemic stroke. It has been available in the United States for over a decade and was approved for use in Israel at the end of 2004. OBJECTIVES: To assess the implementation of intravenous rt-PA in routine clinical care at our center after its formal approval in Israel, and the therapeutic and logistic implications for reperfusion therapy for acute ischemic stroke in Israel. METHODS: Patients with acute ischemic stroke admitted between January 2005 and June 2006 who were treated with intravenous rt-PA or endovascular-based reperfusion were reviewed. Implementation, timing, safety and clinical outcomes were assessed. RESULTS: Forty-six patients received reperfusion therapy (37 with intravenous rt-PA and 9 with endovascular-based therapy), corresponding to 4.0% of ischemic stroke patients in 2005 and a projection of 6.2% in 2006. The mean age of intravenously treated patients was 67 years (range 22-85 years), median baseline NIHSS score was 14 (25-75%, 10-18) and the median 'onset to drug time' was 150 minutes (25-75%, 120-178). Symptomatic intracerebral hemorrhage and orolingual angioedema each occurred in one patient (2.7%). Significant clinical improvement occurred in 54% of treated patients, and 38% of patients were independent at hospital discharge. CONCLUSIONS: The use of reperfusion therapy for acute ischemic stroke has increased in our center after the formal approval of rt-PA therapy to over 5%, with 'onset to drug time', safety and outcome after intravenous rt-PA treatment comparing favorably with worldwide experience. A prerequisite for the implementation of effective reperfusion therapy and expansion of the proportion of patients treated nationwide is the establishment of a comprehensive infrastructure.

Effectiveness of establishing a dedicated acute stroke unit in routine clinical practice in Israel.

BACKGROUND: Clinical trials have demonstrated the superiority of managing acute stroke in a dedicated stroke unit over conventional treatment in general medical wards. Based on these findings, nationwide stroke unit care programs have been implemented in several countries. OBJECTIVE: To assess the effect of establishing a new dedicated acute stroke unit within a department of neurology on indicators of process of care and outcome of acute stroke in a routine clinical setting in Israel. METHODS: Stroke patients admitted to the Sheba Medical Center during the period March 2001 to June 2002 were included in a prospective study according to selection criteria. Data on demographics, risk factors, co-morbidities and stroke severity were collected. Indicators of process of care and outcome were assessed at hospital discharge and 30 days follow-up. Comparison between outcome variables by hospitalization ward was done using logistic regression analysis adjusting for confounders. RESULTS: Of 616 acute stroke patients (mean age 70 years, 61% men, 84% ischemic stroke), 353 (57%) were admitted to general wards and 263 (43%) to the stroke unit. Diagnostic procedures were performed more often and the infection rate was lower in the setting of the stroke unit. Poor outcome (modified Rankin scale > or = 3 or death) was present less often in patients managed in the stroke unit both at hospital discharge (adjusted odds ratio 0.5, 95% confidence interval 0.3-0.8) and at 30 day follow-up (adjusted OR 0.6, 95%CI 0.3-0.9). A Functional Independence Measure score < or = 90 or death at 30 day follow-up was less frequent among patients managed in the stroke unit than in general wards (adjusted OR 0.5, 95%CI 0.2-0.8). CONCLUSIONS: Improved outcomes and higher adherence to guidelines were observed in patients treated in a stroke unit within a department of neurology. The results suggest that patients with acute stroke should have access to treatment in a dedicated stroke unit.

Intravenous recombinant tissue plasminogen activator therapy for acute ischemic stroke: initial Israeli experience.

BACKGROUND: Intravenous recombinant tissue plasminogen activator therapy within 3 hours of stroke onset is a proven effective treatment for acute ischemic stroke. OBJECTIVE: To assess the feasibility and safety of rt-PA therapy for reperfusion in routine clinical practice in Israel, in the setting of a dedicated stroke unit. METHODS: Consecutive patients presenting within less than 3 hours of stroke onset were evaluated by an emergency physician and the neurology stroke team. After brain computerized tomography, eligible patients were treated with intravenous rt-PA (0.9 mg/kg, maximum dose 90 mg) according to an in-hospital protocol corresponding to recommended criteria. Patients were admitted to the acute stroke unit. Safety and clinical outcome were routinely assessed. Recanalization was assessed by serial transcranial Doppler. RESULTS: The study group comprised 16 patients, mean age 61 years (range 47-80 years), male to female ratio 10:6, whose median baseline National Institutes of Health stroke scale was 13 (range 6-24). They were treated within a mean door-to-CT time of 39 minutes (range 17-62 min), door-to-drug time 101 minutes (range 72-150), and stroke onset-to-drug time 151 minutes (range 90-180). There was an early improvement within 24 hours (of > or = 4 points in the NIHSS score) in 7 patients (44%) and no early deteriorations. There were no protocol deviations, no symptomatic intracranial hemorrhages, and no major systemic hemorrhage within 36 hours of rt-PA treatment. Three asymptomatic hemorrhagic transformations of the infarct were noted on routine follow-up brain CT associated with neurologic improvement. Outcome data were comparable to the National Institute of Neurological Disorders and Stroke rt-PA Stroke Study. CONCLUSION: Intravenous rt-PA treatment within 3 hours of stroke onset in routine clinical practice in Israel is feasible and appears safe in the setting of a neurology stroke unit and team. Careful implementation of rt-PA therapy for selected patients in Israel is encouraged.