Declining Rate and Severity of Hospitalized Stroke From 2004 to 2013: The National Acute Stroke Israeli Registry.

BACKGROUND AND PURPOSE: Stroke is a leading cause of morbidity and disability. We assessed trends in rates of hospitalized stroke and stroke severity on admission in a prospective national registry of stroke from 2004 to 2013. METHODS: All 6693 acute ischemic strokes and intracerebral hemorrhage in the National Acute Stroke Israeli participants ≥20 years old were included. Data were prospectively collected in 2004 (February-March), 2007 (March-April), 2010 (April-May), and 2013 (March-April). Rates of hospitalized stroke from 2004 to 2013 were studied using generalized linear models assuming a quasi-Poisson error distribution with a log link. Stroke severity on admission was determined using the National Institutes of Health Stroke Scale score and trends were studied. Analysis was performed for stroke overall and by sex and age-group as well as by stroke type. RESULTS: Estimated average annual rates of hospitalized stroke decreased from 24.9/10 000 in 2004 to 19.5/10 000 in 2013. The age and sex-adjusted rates ratio (95% confidence interval) for hospitalized stroke overall was 0.82 (0.76-0.89) for 2007, 0.71 (0.65-0.77) for 2010, and 0.72 (0.66-0.78) for 2013 compared with 2004. Severity on admission decreased over time: rates (95% confidence interval) of severe stroke (National Institutes of Health Stroke Scale score of ≥11) decreased from 27% (25%-29%) in 2004 to 19% (17%-21%) in 2013, whereas rates (95% confidence interval) of minor stroke (National Institutes of Health Stroke Scale score of ≤5) increased from 46% (44%-49%) in 2004 to 60% (57%-62%) in 2013 (P<0.0001). Findings were consistent by sex, age-group, and stroke type. CONCLUSIONS: Based on our national data, rates of hospitalized stroke and severity of stroke on admission have decreased from 2004 to 2013 overall and by stroke type, in men and women. Despite the observed declines in rates and severity, stroke continues to place a considerable burden to the Israeli health system.

Is CT perfusion helpful in the treatment allocation of patients with acute ischemic stroke? An expert-opinion analysis.

BACKGROUND: Intravenous tPA is the standard treatment for acute ischemic stroke within 4.5 hours of symptom onset. Neuroradiological selection is currently based upon non-contrast- brain CT scan (NCCT). AIMS: To verify, in an "expert-opinion setting", the possible usefulness of CT perfusion (CTP) in decision-making toward i.v. thrombolysis. PATIENTS AND METHOD: One hundred and three consecutive patients with acute ischemic stroke who underwent NCCT and CTP were re-evaluated by an expert in cerebrovascular disease, to verify if adding CTP information would have changed expert's opinion. RESULTS: After CTP, a definitive decision was made for 20 more patients, changing the proportion of patients candidate to i.v. tPA from 44% to 51%, and reducing uncertainty from 29% to 10%. CTP results were useful inmilder stroke (p = 0.01). CONCLUSIONS: In a "real world" setting, CT perfusion could be useful for clinical decision, in particular for milder stroke.

Is the evaluation and treatment of transient ischemic attack performed according to current knowledge? A nationwide Israeli registry.

BACKGROUND: Patients with transient ischemic attack (TIA) at a high risk of stroke can be identified and should be managed urgently. OBJECTIVES: To investigate whether recognized recommendations are being implemented in Israel. METHODS: An Israeli nationwide registry (NASIS) on patients admitted with stroke and TIA was conducted in all acute care hospitals within 2 successive months during 2004, 2007 and 2010. A revised ABCD2 score was applied retrospectively. Patients with TIA were divided into a low risk group (LRG, 0-3 points) and a high risk group (HRG, 4-6 points) and were compared to patients with minor ischemic strokes (MIS, NIHSS score < or = 5 points). RESULTS: A total of 3336 patients were included (1023 with TIA: LRG 484, HRG 539, and MIS 2313). LRG patients were younger and had lower rates of most traditional risk factors as compared with HRG and MIS patients. Brain imaging was performed in almost all the patients. Ancillary tests (vascular and cardiac) were overall underused, yet were performed more in LRG (53.2% and 26.9% respectively) than in HRG patients (41.6%, 18.9%). Between periods there was no change in usage of ancillary tests for the LRG and a modest increase in both HRG and MIS patients. For performance of vascular investigations overall, the odds ratio was 1.69 (95% confidence interval 1.42-2.00) comparing 2010 with 2004, but 0.7 (95% CI 0.5-0.9) comparing HRG with LRG. Between periods an increase in statin usage was observed in all groups (OR 2.69, 95% CI 2.25-3.21) but was more marked in MIS patients (OR 3.06, 95% CI 2.47-3.8). CONCLUSIONS: The approach to TIA risk stratification and management in Israeli hospitals does not follow standards set by current guidelines. Standardized protocols for TIA should be used to assure effective management.

Asymptomatic carotid stenosis: intervention or just stick to medical therapy--the case for medical therapy.

Asymptomatic significant (≥50%) carotid stenosis (ASCS) is a frequent finding in the aging population. The prevalence of moderate stenosis (50-70%) increases from 3.6% for those <70 years to 9.3% in those ≥70 years. The (additional) prevalence of severe (70-99%) stenosis is 1.7%. The natural history of ASCS is quite benign. The overall risk of stroke is around 2% per year and within the group higher degrees of stenosis are associated with higher risks. Yet this stroke risk also includes "unrelated" strokes (i.e., lacunar and cardioembolic), and similarly, it is more of a marker for identifying high-risk group of patients at risk of cardiovascular morbidity and mortality (as revealed by many studies)! Carotid endarterectomy (CEA) has been evaluated in several studies; mainly ACAS and ACST. An overall modest benefit of about 1% risk reduction (per year) was found for CEA (with a peri-operative risk of <3%) versus medical treatment, over a 5-year period. Basically these two studies recruited similar patients with ≥60% stenosis based on carotid duplex. However, the similar favorable results differ: while ACAS (published in 1995) found the risk for ipsilateral stroke in the medical group to be 11% over a 5-year period, the 11.8% risk observed in ACST (published in 2004) was for any strokes--showing a better "natural history" for patients with ASCS in the recent study. This observation adds to other reports suggesting a better outcome for patients with ASCS in the recent years, probably because of better medical treatment, mainly due to the significant increase in the use of statins. The suggested guideline that results from the above-mentioned studies is that CEA should be considered in every patient with significant (≥60%?, ≥70%?) stenosis who has a life expectancy of more than 5 years (and is <75 years?). Taking this advice as such, would mean that we should screen for ASCS and operate on all appropriate candidates. This will result in a surge of CEA's! Such a recommendation is not in place, because the observed benefit of CEA by numbers needed to treat (NNT) per year to prevent any stroke is more than one hundred! (for symptomatic patients NNT is <10). This high-figure (i.e., low yield) results from failure of these studies to identify specific risk-factors (including the degree of stenosis within the wide range [60-99%] allowed in the studies) in patients with ASCS. Some studies are underway. Therefore, at present, it seems that for most patients, best (intensive) medical treatment is the best option. Alternately, they should join studies that will help to identify patients with the highest risk--those who will clearly benefit from carotid intervention.

Impact of previous stroke on outcome after thrombectomy in patients with large vessel occlusion.

BACKGROUND: Many patients with large vessel occlusion (LVO) who are otherwise candidates for endovascular treatment (EVT) have had previous strokes. We aimed to examine the effect of previous stroke on outcome after EVT. METHODS: Consecutive patients with LVO were prospectively entered into a National Acute Stroke registry of patients undergoing EVT. Patients treated with EVT were divided into those with and without previous strokes. The rates of favorable reperfusion status, mortality, and excellent outcome at 90 days post-stroke as well as symptomatic intracranial hemorrhage (sICH) were evaluated. RESULTS: A total of 390 underwent EVT and 35 had previous strokes. Patients with previous strokes were significantly older; more frequently had a history of prior myocardial infarction and more often had pre-existing functional disability. Favorable target vessel recanalization was less frequently achieved in patients with previous strokes (60% vs. 82%; p = 0.005) and ordinal regression analysis for functional outcome revealed higher frequency of deterioration at three months in patients with previous strokes. Nevertheless, 9% of these patients maintained their previous disability state and sICH rates did not differ between the groups. Mortality rates at one year post stroke were significantly higher in patients with previous strokes (37% vs. 16%; p = 0.005). CONCLUSIONS: Previous strokes are associated with higher likelihoods of mortality and unfavorable outcome in patients with LVO undergoing EVT. However, because some of these patients maintain their previous disability state, the presence of previous stroke should not be used as an exclusion criterion from EVT.

[Guideliness for the management of stroke--2008 invasive measures for prevention of ischemic stroke].

Stroke is a major cause of morbidity and mortality in Israel and the main cause for neurological disability among adults. Continued efforts for its prevention and treatment began a long time ago and currently persist. During the last decade, these efforts have resulted in a number of significant breakthroughs. Consequently, several new guidelines and consensus statements from Europe and North America have been published. In Israel, up to date, guidelines have been published only for acute stroke treatment, as well as for its prevention by medical means. The present guideline is supplemental to the previous papers and focuses on the invasive options to treat specific risk factors and conditions, when appropriate, for primary and secondary stroke prevention.

Direct Thrombectomy versus Bridging for Patients with Emergent Large-Vessel Occlusions.

BACKGROUND AND AIMS: Patients with emergent large-vessel occlusion (ELVO) that present earlier than 4 h from onset are usually treated with bridging systemic thrombolysis followed by endovascular thrombectomy (EVT). Whether direct EVT (dEVT) could improve the chances of favorable outcome remains unknown. METHODS: Consecutively, prospectively enrolled patients with ELVO presenting within 4 h of onset were entered into a National Acute Stroke Registry of patients undergoing revascularization. Patients treated with bridging were compared to those treated with dEVT. Excellent outcome was defined as having a modified Rankin Scale score ≤1 at 90 days following stroke. RESULTS: Out of 392 patients that underwent thrombectomy, 270 (68%) presented within 4 h and were included. Of those, 159 (59%) underwent bridging and 111 (41%) underwent dEVT. Atrial fibrillation and congestive heart failure were more common in the dEVT group (43 vs. 30%, p = 0.04 and 20 vs. 8%, p = 0.009, respectively), but other risk factors, demographics, stroke severity and subtypes as well as baseline vessel patency state and time metrics did not differ. Excellent target vessel recanalization defined as TICI 3 (thrombolysis in cerebral infarction score) was more common in the dEVT group (75 vs. 61%, p = 0.03), but in-hospital mortality, discharge destinations, short- and long-term excellent outcome rates did not differ. On multivariate regression analysis, treatment modality did not significantly modify the chances of excellent outcome at discharge (OR 0.7; 95% CI 0.3-1.5) or at 3 months (OR 0.78 95% CI 0.4-1.4). CONCLUSIONS: The chances of attaining excellent functional outcomes are similar in ELVO patients undergoing dEVT or bridging.

[Guidelines for the management of stroke--2007 prevention of ischemic stroke--general approach and medical treatment].

Stroke is a major cause of morbidity and mortality in Israel, the third most common cause of death and the main cause for neurological disability among adults. During the last decade several significant breakthroughs have occurred in the management of stroke and consequently several new guidelines and consensus statements from Europe and North America have been published. The new data necessitate a reappraisal of our approach to the management of stroke as well as to its primary prevention. The present guidelines focus on primary and secondary stroke prevention by medical means and provide detailed, updated, clinical guidelines for most specific risk factors and conditions, ways to investigate the underlying stroke mechanism and its preferred medical treatment. Invasive (surgical, stent insertion, correction of cardiac anomalies etc.) will be dealt with separately.

Stroke in congenital heart disease and patent foramen ovale.

Congenital heart disease is usually regarded as an esoteric field of medicine, dealt with primarily by dedicated specialists. However, over the last two decades, increased attention has been given by the medical profession, the media and the general public to the possible association between a minor and common congenital heart defect, namely patent foramen ovale, and stroke. In recent months, unusual and unfortunate circumstances have made this topic one of the most fiercely debated medical issues in Israel. It is the belief of the authors of this paper that the association of PFO and stroke can be better understood if the PFO is viewed as part of the broader context of congenital heart disease, and as such it will be presented. Paradoxical embolism is a mechanism of stroke unique to congenital heart disease. The direction and volume of shunted blood in various conditions have a central role in determining the risk of stroke, as will be explained. With this basic knowledge in mind, we shall critically assess the potential role of PFO in stroke patients, suggesting that each case be evaluated individually using the above-mentioned principles. Conditions that enhance the formation of clot or other embolic material will be discussed briefly. The review will conclude with the various treatment options and our center's own experience with this challenging topic.

[Guidelines for the management of acute stroke--2005].

Stroke is a major cause for morbidity and mortality in Israel, the third most common cause of death and the main cause for neurological disability among adults. Several significant breakthroughs occurred over recent years in the management of stroke, and acute stroke has increasingly been recognized as a medical emergency--a "brain attack" comparable to a "heart attack". Several new scientific publications, guidelines and consensus statements from Europe and North America necessitate a paradigm shift in the management of acute stroke. The guidelines focus on a number of issues: acute stroke as a medical emergency, dedicated stroke units, early reperfusion therapy for acute ischemic stroke, emergency management and general stroke treatment, use of diagnostic tests in the acute phase, and the prevention and treatment of complications.

Ten-year risk of stroke in patients with previous cerebral infarction and the impact of carotid surgery in the Asymptomatic Carotid Surgery Trial.

BACKGROUND: Silent brain infarcts are common in patients at increased risk of stroke and are associated with a poor prognosis. In patients with asymptomatic carotid stenosis, similar adverse associations were claimed, but the impact of previous infarction or symptoms on the beneficial effects of carotid endarterectomy is not clear. Our aim was to evaluate the impact of prior cerebral infarction in patients enrolled in the Asymptomatic Carotid Surgery Trial, a large trial with 10-year follow-up in which participants whose carotid stenosis had not caused symptoms for at least six months were randomly allocated either immediate or deferred carotid endarterectomy. METHODS: The first Asymptomatic Carotid Surgery Trial included 3120 patients. Of these, 2333 patients with baseline brain imaging were identified and divided into two groups irrespective of treatment assignment, 1331 with evidence of previous cerebral infarction, defined as a history of ischemic stroke or transient ischemic attack > 6 months prior to randomization or radiological evidence of an asymptomatic infarct (group 1) and 1002 with normal imaging and no prior stroke or transient ischemic attack (group 2). Stroke and vascular deaths were compared during follow-up, and the impact of carotid endarterectomy was observed in both groups. RESULTS: Baseline characteristics of patients with and without baseline brain imaging were broadly similar. Of those included in the present report, male gender and hypertension were more common in group 1, while mean ipsilateral stenosis was slightly greater in group 2. At 10 years follow-up, stroke was more common among participants with cerebral infarction before randomization (absolute risk increase 5.8% (1.8-9.8), p = 0.004), and the risk of stroke and vascular death was also higher in this group (absolute risk increase 6.9% (1.9-12.0), p = 0.007). On multivariate analysis, prior cerebral infarction was associated with a greater risk of stroke (hazard ratio = 1.51, 95% confidence interval: 1.17-1.95, p = 0.002) and of stroke or other vascular death (hazard ratio = 1.30, 95% confidence interval: 1.11-1.52, p = 0.001). At 10 years, greater absolute benefits from immediate carotid endarterectomy were seen in those patients with prior cerebral infarction (6.7% strokes immediate carotid endarterectomy vs. 14.7% delayed carotid endarterectomy; hazard ratio 0.47 (0.34-0.65), p = 0.003), compared to those lower risk patients without prior cerebral infarction (6.0% vs. 9.9%, respectively; hazard ratio 0.61 (0.39-0.94), p = 0.005), though it must be emphasized that the first Asymptomatic Carotid Surgery Trial was not designed to test this retrospective and non-randomized comparison. CONCLUSIONS: Asymptomatic carotid stenosis patients with prior cerebral infarction have a higher stroke risk during long-term follow-up than those without prior cerebral infarction. Evidence of prior ischemic events might help identify patients in whom carotid intervention is particularly beneficial.

Serum uric acid and subsequent cognitive performance in patients with pre-existing cardiovascular disease.

High serum uric acid (UA) levels are associated with numerous vascular risk factors, and vascular disease, that predispose patients to cognitive impairment, yet UA is also a major natural antioxidant and higher levels have been linked to slower progression of several neurodegenerative disease. In-order to test the association between UA and subsequent cognitive performance among patients that carry a high vascular burden, UA levels were determined by calorimetric enzymatic tests in a sub-cohort of patients with chronic cardiovascular disease who previously participating in a secondary prevention trial. After an average of 9.8±1.7 years, we assessed cognitive performance (Neurotrax Computerized Cognitive Battery) as well as cerebrovascular reactivity (CVR) and common carotid intima-media thickness (IMT). Among 446 men (mean age 62.3±6.4 yrs) mean UA levels were 5.8±1.1 mg/dL. Adjusted linear regression models revealed that low UA levels (bottom quintile) were associated with poorer cognitive performance. Adjusted differences between the bottom quintile and grouped top UA quintiles were (B coefficient±SE) -4.23±1.28 for global cognitive scores (p = 0.001), -4.69±1.81 for memory scores (p = 0.010), -3.32±1.43 for executive scores (p = 0.020) and -3.43±1.97 for visual spatial scores (p = 0.082). Significant difference was also found for attention scores (p = 0.015). Additional adjustment for impaired CVR and high common carotid IMT slightly attenuated the relationship. Stronger UA effect on cognitive performance was found for older (age>65) patients with significant age interaction for global cognitive score (p = 0.016) and for executive (p = 0.018) and attention domains (p<0.001). In conclusion, we demonstrate that low UA levels in patients with preexisting cardiovascular disease are associated with poorer cognitive function a decade later. These findings lend support to the hypothesis that oxidative stress may be involved in the pathogenesis of age-associated cognitive impairment.

Development and progression of leukoaraiosis in patients with brain ischemia and carotid artery disease.

BACKGROUND AND PURPOSE: Leukoaraiosis (LA) or the presence of white matter changes, a frequent finding on brain CT scans of elderly individuals, is a risk factor for stroke and vascular death. The aim of the study was to seek development and progression of LA and associated risk factors in patients with symptomatic carotid artery disease. METHODS: Presence and extent of LA were determined on entry and follow-up CT scans from 685 patients in the North American Symptomatic Carotid Endarterectomy Trial. RESULTS: Among 596 patients without LA at entry, 107 (18.0%) developed restricted LA and 18 (3.0%) developed widespread LA during a mean follow-up of 6.1 years (range, 3.0 to 9.6 years). Older age was associated significantly with LA development (P<0.001). History of hypertension, diabetes mellitus, ischemic heart disease, and intermittent claudication had weak associations with LA development. During follow-up, 36.0% of patients who developed LA had 1 or more strokes, particularly of the lacunar type, in comparison to 23.5% of patients who did not develop LA (P=0.01). In patients who developed LA, the percentage with small deep infarcts (diameter < or =1.5 cm) increased from 34.4% on entry to 45.6% on follow-up CT scans compared with no increase (20.4% and 20.4%, respectively) in patients who did not develop LA. Among 89 patients who had restricted LA at entry, 28 (31.5%) progressed to widespread LA. Progression was associated with occurrence of strokes. CONCLUSIONS: LA is common in elderly patients with symptomatic cerebrovascular disease. Its development and progression are associated with higher occurrence of strokes, mainly of the lacunar type.

Prognostic importance of leukoaraiosis in patients with symptomatic internal carotid artery stenosis.

BACKGROUND AND PURPOSE: Leukoaraiosis (LA) is a frequent finding on brain CT scans. This study examined patients with LA and symptomatic internal carotid artery disease. METHODS: Patients in the North American Symptomatic Carotid Endarterectomy Trial were evaluated for the extent of LA. Long-term prognosis and perioperative risk associated with carotid endarterectomy were assessed. RESULTS: Among 2618 patients, 493 had LA: 354 restricted and 139 widespread. Patients with LA were older, had a history of hypertension, had more hemispheric ischemic events (particularly stroke), and had small, deep brain infarcts. The 3-year risks of stroke for medically treated patients were 20.2% (no LA), 27.3% (restricted LA), and 37.2% (widespread LA) (P=0.01). For surgically treated patients, the risks were 14.2%, 25.4%, and 33.6%, respectively (P<0.001). With widespread LA, occurrence of disabling strokes doubled in medical patients and tripled in surgical patients. The 30-day perioperative risks of any stroke or death for surgical patients with 50% to 99% internal carotid artery stenosis were 5.3% (no LA), 10.6% (restricted LA), and 13.9% (widespread LA). Despite higher perioperative risk, endarterectomy reduced the absolute 3-year risk of stroke ipsilateral to the symptomatic 50% to 99% stenosed artery by 11.6% (P=0.46) for patients with widespread LA, 7.6% (P=0.39) with those with restricted LA, and 10.9% (P<0.001) for those with no LA. CONCLUSIONS: In patients with a transient ischemic attack or nondisabling stroke associated with internal carotid artery disease, presence of LA was associated with an increased risk of any stroke and of disabling or fatal stroke. Patients with widespread LA had the worst prognosis. Despite the higher perioperative risk, endarterectomy reduced the risk of stroke.

Melatonin rhythms in stroke patients.

Very little is known regarding melatonin's circadian rhythm in stroke patients. We compared urinary-sulfatoxymelatonin (6-SMT), its major metabolite, in 11 extensive cortical and seven deep or lacunar stroke patients on day 3 or 4 and day 10 post-stroke. Urinary 6-SMT and creatinine measured every 4 h for 24 h starting at 06:00 h significantly fluctuated during the day in both types of stroke and did not differ between day 3 or 4 and day 10 post-stroke. However, in extensive cortical lesions, a delay in the 6-SMT excretion was observed in the first post-stroke days compared to day 10. We conclude that circadian oscillator is preserved in extensive cortical as well as in deep and lacunar strokes. Extensive cortical stroke might delay the melatonin surge during the first post-stroke days.

[Hyperperfusion syndrome].

Hyperperfusion syndrome (HPS) is a neurological syndrome, which consists of a triad of unilateral headache, seizures and focal neurological deficits. In its extreme form it can present as an intracerebral hemorrhage. Originally HPS was described in patients undergoing carotid endarterectomies for severe carotid stenosis but, more recently, it was also described following other means of cerebral revascularization such as stent-assisted angioplasty. It is believed to result from hyperperfusion of blood into an unprotected or damaged brain parenchyma. HPS is considered to be a rare complication of carotid endarterectomy, yet this may not be precise as the full picture of the syndrome usually develops after several days, following the patient's discharge from hospital. Physicians who are unfamiliar with this syndrome are called to treat these patients and thus it may be misdiagnosed. For invasive vascular procedures the hospitalization time is even shorter and therefore, this scenario may become more common. Nowadays, HPS may be diagnosed fairly easily, even before its typical clinical presentation has developed, with the use of transcranial doppler intra- or postoperatively. Meticulous blood pressure monitoring can prevent its appearance in most cases.

Connective tissue disorders: systemic lupus erythematosus, Sjögren's syndrome, and scleroderma.

Connective tissue disorders are systemic, autoimmune, multiorgan diseases in which the central and peripheral nervous systems are frequently involved. The objective of this chapter is to describe the neurological manifestations of three of the most common systemic autoimmune disorders: systemic lupus erythematosus (SLE), scleroderma, and Sjögren's syndrome (SS). In SLE the neuropsychiatric manifestations involve mainly the central nervous system (CNS), including cognitive dysfunction, headache, psychosis and mood changes, seizures, cerebrovascular disease, and myelopathy. Peripheral nervous system (PNS) manifestations are less common and include polyneuropathies as well as mononeuropathies and acute inflammatory demyelinating polyneuropathy. Antiphospholipid syndrome (APLS) is relatively common and should be searched for whenever focal neurological symptoms occur. In scleroderma the PNS is more commonly involved; symptoms include polyneuropathies, entrapment neuropathies, and mononeuropathies (mostly cranial neuropathies or mononeuritis multiplex). Additionally autonomic involvement occurs and myopathies are relatively common. In SS the PNS is similarly involved with several types of polyneuropathies, mononeuropathies, and autonomic dysfunction. Also common are myelopathies and aseptic meningitides. These and other, less common manifestations, as well as the diagnostic procedures and the therapeutic approaches, will be dealt with in this chapter.