Off-hours admission for acute stroke is not associated with worse outcome--a nationwide Israeli stroke project.

BACKGROUND AND PURPOSE: Several studies reported worse outcome for stroke patients arriving on weekends. We compared working hours to off-work hours throughout the week as there is lack of experienced staff and special services during off-hours. METHODS: A nationwide stroke survey project on acute stroke was carried out in all acute care hospitals in Israel during 2004, 2007 and 2010 (2-month each). 'On-hours' were defined as regular Israel working hours and the rest, including holidays, were defined as 'off-hours'. The modified Rankin scale (mRS) at discharge was used for the main analysis on outcome. RESULTS: A total of 4827 acute strokes patients were analyzed (2139 arrived on-hours and 2688 during off-hours). 'Off-hours' patients were 1 year younger (mean 70 vs. 71 years in 'on-hours') had lower rates of prior cardiac interventions, but had higher admission blood pressure levels and had more intracerebral hemorrhages (ICH) (11% vs. 8% in 'on-hours' patients, P < 0.001). Death during hospitalization was recorded in 9% of 'off-hours' vs. 6% of 'on-hours' patient (P = 0.004). Controlling for age, blood pressure, stroke type, pre-stroke mRS, admission NIHSS, and thrombolysis, the relative odds of poor outcome (i.e. mRS ≥ 2) amongst 'off-hours' admissions compared to on-hours was 1.09 (95% CI: 0.92-1.30). Odds ratio amongst ischaemic stroke patients was 1.08 (95% CI: 0.88-1.33). CONCLUSIONS: Off-hours stroke admissions were associated with higher short-term mortality rate, probably due to a higher rate of ICH. After controlling for the latter and other potential confounders, 'off-hours' admissions were not different from 'on-hours' with respect to poor outcome.

Cerebrovascular events in patients with significant stenosis of the carotid artery are associated with hyperhomocysteinemia and platelet antigen-1 (Leu33Pro) polymorphism.

BACKGROUND AND PURPOSE: Although risk factors for carotid artery stenosis caused by atherosclerosis are known, it is unclear what triggers "activation" of the atherosclerotic plaques and the ensuing thromboembolic cerebral events. The aim of this study was to evaluate whether thrombophilic factors, platelet glycoprotein (GP) polymorphisms, and homocysteine are associated with a risk of ischemic events in patients with significant carotid stenosis. METHODS: Consecutive patients with >/=50% carotid stenosis, whether symptomatic (with ipsilateral ischemic events) or asymptomatic, who were evaluated and followed in a neurovascular clinic were tested for plasma levels of homocysteine, C677T mutation in methylenetetrahydrofolate reductase, G20210A mutation of factor II, factor V Leiden, antiphospholipid antibodies, and polymorphisms of platelet membrane GP: human platelet antigen (HPA)-1, GP Ia (C807T), and GP Ib (variable number of tandem repeats, Kozak, and HPA-2). RESULTS: Eighty-six asymptomatic and 67 symptomatic patients were evaluated. The former group was older (73.7+/-6.9 versus 69.5+/-9.1 years, P=0.02). Major risk factors for stroke were similar in both groups. In symptomatic patients versus asymptomatic patients, hyperhomocysteinemia was 3-fold more frequent (34.3% versus 12.8%, respectively; P=0.002) and HPA-1a/b was almost 2-fold more common (38.8% versus 20.9%, respectively; P=0.01). All other thrombophilic factors and platelet polymorphisms studied did not differ significantly between the 2 groups. Multivariate analysis revealed that hyperhomocysteinemia and the HPA-1a/b genotype conferred a significant risk of cerebral ischemic events, with odds ratios (95% CI) of 4.07 (1.7 to 9.7) and 3.4 (1.5 to 7.8), respectively. CONCLUSIONS: Hyperhomocysteinemia and HPA-1a/b are independent risk factors for ischemic events in patients with significant carotid stenosis.

The risk of stroke in patients with first-ever retinal vs hemispheric transient ischemic attacks and high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial.

BACKGROUND: The prognosis of amaurosis fugax has been considered to be favorable compared with that of hemispheric transient ischemic attacks. However, this has remained uncertain for patients with significant carotid stenosis as the assessment of progression of the disease has been confounded when patients undergo carotid endarterectomy. In the North American Symptomatic Carotid Endarterectomy Trial, patients with high-grade (70% to 99%) carotid stenosis were randomized to receive either medical or surgical treatment, thus making an unconfounded analysis possible. METHOD: We identified 129 medically treated patients with high-grade carotid stenosis who had their first-ever transient ischemic attack as the entry event into the trial. Fifty-nine patients with retinal transient ischemic attacks (RTIAs) were compared with 70 patients with hemispheric transient ischemic attacks (HTIAs). RESULTS: Patients with HTIAs were older, with a higher prevalence of most risk factors for stroke. Average time of delay from the onset of transient ischemic attacks to medical treatment was longer for patients with RTIAs than for patients with HTIAs (48.5 vs 15.2 days). Kaplan-Meier estimates of the risk of ipsilateral stroke at 2 years were 16.6% +/- 5.6% for patients with RTIAs and 43.5% +/- 6.7% for patients with HTIAs (P = .002 for the difference in risk between RTIAs and HTIAs). From corresponding Cox's proportional hazards regression analyses, the risk of ipsilateral stroke ranged from 11.2% to 28.9% for patients with RTIAs and from 37.4% to 96.3% for patients with HTIAs across stenoses, spanning 75% to 95%. Overall, the relative risk of ipsilateral stroke (HTIAs compared with RTIAs) was 3.23 (95% confidence interval, 1.47 to 7.12), regardless of the degree of high-grade stenosis. CONCLUSION: To our knowledge, this study is the first report on the expected outcome for medically treated patients with high-grade (70% to 99%) carotid stenosis in whom the first-ever event was either an RTIA or HTIA. The presence of RTIAs carries a considerable risk of ipsilateral strokes, particularly at higher degrees of stenosis. However, in comparison with HTIAs, patients with RTIAs still have a better prognosis.

Lack of relationship between leukoaraiosis and carotid artery disease. The North American Symptomatic Carotid Endarterectomy Trial.

OBJECTIVE: Leukoaraiosis (LA) (white matter changes) is frequently observed on computed tomographic scans of the brain of elderly patients at risk of stroke. A localized vascular-ischemic cause has been suggested for its underlying mechanism. Our aim was to assess whether high-grade carotid stenosis is associated with LA. DESIGN/SETTING: Patients enrolled in the North American Symptomatic Carotid Endareterectomy Trial (also known as NASCET) were evaluated for LA using a recently proposed grading scale. Ordinal regression analysis was used to assess the association between the severity of carotid artery stenosis and the extent of LA observed on computed tomographic scans. The patients' brain hemisphere was selected as the unit of analysis. RESULTS: Of the 2394 brain hemispheres contributed to the analyses, 352 (14.7%) had signs of LA. After controlling for known stroke risk factors in the ordinal regression analysis, only the history of stroke and increasing age were significantly related to LA. Severity of stenosis was observed to be unrelated (odds ratio [severe vs mild stenosis] = 1.08; 95% confidence interval, 0.73-1.62; P = .952) as were a history of hypertension and a history of myocardial infarction. CONCLUSION: Leukoaraiosis is not associated with severe carotid artery stenosis.

Brain imaging in late-onset GM2 gangliosidosis.

We describe brain CT and MRI characteristics of 10 patients with late-onset GM2 gangliosidosis. Cerebellar atrophy, particularly of the vermis, was a prominent feature in all patients with normal-appearing cerebral hemispheres. The severity of these findings did not correlate with the age of onset, disease duration, severity of neurologic impairment, or mode and distribution of the various clinical presentations. In particular, no cerebral abnormality was found by neuroimaging in seven patients with intellectual decline and in six patients with recurrent psychosis, while prominent cerebellar atrophy was present in the only patient who was free of cerebellar signs.

Ptosis in patients with hemispheric strokes.

BACKGROUND: Cerebral ptosis is considered rare; it has been reported with unilateral, usually right hemispheric lesions. However, the frequency of cerebral ptosis in patients with strokes has not received systematic study. OBJECTIVE: To determine the frequency of ptosis in patients with acute hemispheric stroke and to identify stroke features associated with ptosis. METHODS: Eyelid function was studied in 64 consecutive patients with acute hemispheric stroke and 40 age-matched subjects with no known neurologic disease. All underwent comprehensive neuro-ophthalmologic and general neurologic examination within 48 hours of admission, including measurement of palpebral fissures, marginal reflex distance, and range of upper lid movement. Only patients who could cooperate with eyelid testing were included. Brain CT scans were obtained for all patients who had had strokes. RESULTS: Twenty-four (37.5%) of the patients with strokes had neurogenic ptosis, which was bilateral in 10 and unilateral in 14. None of the control subjects had neurogenic ptosis. All patients with strokes with ptosis had a hemiparesis. Rightward gaze deviation and upgaze paresis were more common (p < 0.05) in the patients with ptosis compared with others who had had strokes. CT evidence of right-sided hemispheric cortical infarction was more common in patients with strokes with ptosis (p < 0.05). In five patients with large hemispheric infarction, complete bilateral or asymmetric ptosis was the first sign of imminent herniation, preceding pupillary dilation and ocular motor deficits. CONCLUSIONS: Ptosis occurs frequently in patients with hemispheric strokes, especially in association with right hemispheric lesions. Complete bilateral ptosis is usually caused by large infarctions and may be a premonitory sign of an impending herniation.

Prognosis for patients following a transient ischemic attack with and without a cerebral infarction on brain CT. North American Symptomatic Carotid Endarterectomy Trial (NASCET) Group.

BACKGROUND: Although cerebral infarctions are commonly observed on brain CTs of patients with TIAs, their prognostic importance is unknown. METHOD: The association between appropriately sited brain infarctions (ie, lesions located in the anterior circulation of the brain and ipsilateral to the symptomatic stenosed carotid artery) visualized on CT and the risk of subsequent stroke was assessed by Cox proportional hazards regression in 164 patients presenting with TIA (and no history of previous stroke) and severe angiographically defined carotid stenosis (70 to 99%) from the North American Symptomatic Carotid Endarterectomy Trial. RESULTS: Patients with a TIA and CT-verified brain lesions were older and were more likely to have higher degrees of carotid stenosis and carotid plaque ulceration, a longer duration of symptoms, and a history of hypertension. With regard to prognosis, after adjusting for all known risk factors (patient characteristics) in a regression analysis, the presence of ischemic lesions observed on CT was not associated with an increased risk of ipsilateral stroke at 2 years (adjusted hazard ratio = 1.00; 95% CI: 0.39 to 2.58; p value = 0.99). CONCLUSION: Considered in combination with other patient characteristics, the mere presence of an appropriately sited cerebral infarction on CT does not alter the prognosis (risk of ipsilateral strokes) of severely stenosed patients with TIA. Therefore, there is no clinical rationale in differentiating patients with TIA on the basis of CT findings alone.

Muscle computed tomography features of motor neuron disease in late-onset GM2 gangliosidosis.

Late-onset GM2 gangliosidosis, a rare inherited neuronal storage disease, is characterized by a variety of clinical manifestations. The common clinical picture comprises neuromuscular, spinocerebellar, extrapyramidal, cognitive, and psychiatric abnormalities. Details of the extent of muscle involvement have never been reported. Eight patients with this syndrome were evaluated for the existence and extent of motor neuron disease using routine electrodiagnosis and systematic evaluation of skeletal musculature by computed tomography. Motor neuron disease was present in each and every patient regardless of the clinical manifestations and to a degree beyond that suspected on neurological examination. Muscle imaging disclosed a diffuse wasting and fatty replacement of muscles with predilection of pelvic and thigh muscles, and especially the quadriceps group. It seems that progressive motor disability in this syndrome is mainly due to motor neuron disease, as manifested by muscle atrophy, which can be easily demonstrated by muscle computed tomography.

Cardiogenic cerebral emboli: diagnosis and treatment.

New technology has made it possible to identify cardiogenic cerebral emboli more easily and reliably. In recent years echocardiography, and in particular transesophageal echocardiography, has become the gold standard for the identification of cardiogenic sources of emboli, whereas transcranial Doppler is an important technique for the detection of cerebral emboli. Treatment strategies are better established and more accurate, if more complex, since the completion of large randomized trials. For primary prevention of stroke in elderly patients with nonvalvular atrial fibrillation, warfarin is generally indicated, yet in patients aged 60-75 years with no risk factors, aspirin may be sufficient. Warfarin is hazardous in older high-risk patients even at the 'low intensity' of the anticoagulation regimen; even lower doses are therefore being tested. Heparin and aspirin are indicated for short-term treatment of acute myocardial infarction, whereas for long-term treatment aspirin is still the drug of choice. However, if mobile left ventricular thrombi are present, warfarin is superior and new studies have shown its effectiveness for all myocardial infarction survivors. Combined treatment of warfarin and aspirin appears to be most effective in patients with mechanical prosthetic valves.

Factors associated with the time of presentation of acute stroke patients in an Israeli community hospital.

Recently it has been shown that effective treatment for acute stroke must be initiated within 3-6 h from onset. In order to determine whether this is feasible and the reasons for delayed presentation, a prospective study was conducted in a community hospital in Israel. Of the 216 patients enrolled, 18% arrived at the hospital within 90 min of stroke onset and 54% presented within 6 h. Important factors associated with early presentation included major stroke (as compared to mild stroke) and time of day of onset (afternoon as compared with nighttime). Further efforts must be made to shorten the delay in hospital arrival of acute stroke patients.

The correlation between the hypotensive effect of increasing single doses of nifedipine tablets with its plasma concentration in patients with essential hypertension.

The hypotensive effect and the plasma concentration following 20, 40, 60 and 80 mg single doses of nifedipine (NIF) tablets were monitored during the first 3 hours and again after 12, 24 and 48 hours in six hypertensive patients. The maximal hypotensive effect was observed at 3 hours. Following the 40 mg NIF dose, systolic blood pressure (SBP) fell from a mean value (+/- s.e.m.) of 181 +/- 5.7 mmHg to 151 +/- 6.4 mmHg (p less than 0.001) and the diastolic blood pressure (DBP) from a mean of 111 +/- 3.8 mmHg to 91 +/- 3.0 mmHg (p less than 0.001). No significant further reduction was found with the 60 and 80 mg dose. At doses above 40 mg the hypotensive effect lasted up to 24 hours. A linear correlation was found between the dose given and the area under the NIF plasma concentration time curve, as well as with the peak plasma levels for each dose. Mean plasma levels were maximal at 3 hours for each dose. The overall correlation between the NIF plasma concentration and the drop in blood pressure was r = -0.388 for SBP and r = -0.421 for DBP (n = 141). Marked interindividual variation was found for the correlation between plasma levels and the change in blood pressure. Adverse effects were minimal.

The importance of brain infarct size and location in predicting outcome after stroke.

Fifty-six consecutive elderly ( > or = 65 years) patients, admitted for acute stroke to a geriatric department were included in the study and underwent CT scanning. Functional status was graded according to the modified Rankin scale. Three patients had primary intra-cerebral haemorrhage, 22 deep hemispheric infarct, 17 had anterior circulation cortical infarcts, five had posterior circulation infarcts and in nine the CT scan was normal. Stroke risk factors were equally distributed among the different CT scan groups, and all three larger groups had similar rates of non-neurological major complications including death (41%). However, independence in ADL (Rankin 0-2) was observed in 72% of deep infarct survivors, but only 15% of the cortical infarct group (p = 0.00018). For the normal scan group, functional recovery was intermediate. In the cortical infarct group patients with an infarct of > or = 50 mm mean diameter (five cases) should worse functional recovery than did eight patients with small infarcts. The mean difference between pre- and post-stroke Rankin score (DR) was 3.4 for the larger infarct patients and 1.9 for the smaller infarct group (p = 0.027). Pearson correlation revealed a direct relationship between the infarction size and DR (p = 0.039). Such a relationship was not observed for the deep hemispheric group.

Significance of plaque ulceration in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial.

BACKGROUND AND PURPOSE: The importance of carotid plaque ulceration as a cause of cerebral ischemic symptoms remains uncertain. Moreover, its prominence in symptomatic patients with severe carotid stenosis is unknown. METHODS: The association between angiographically defined plaque ulceration and risk of subsequent stroke was assessed using Cox proportional hazards regression in 659 patients with severe (70% to 99%) carotid stenosis from the North American Symptomatic Carotid Endarterectomy Trial. RESULTS: Treatment assignment (medical versus surgical) and degree of ipsilateral stenosis were identified as having a significant influence on the results. The risk of ipsilateral stroke at 24 months for medically treated patients with ulcerated plaques increased incrementally from 26.3% to 73.2% as the degree of stenosis increased from 75% to 95%. For patients with no ulcer, the risk of stroke remained constant at 21.3% for all degrees of stenosis. The net result yielded relative risks of stroke (ulcer versus no ulcer) ranging from 1.24 (95% confidence interval, 0.61 to 2.52) to 3.43 (95% confidence interval, 1.49 to 7.88). Conversely, for surgically treated patients with antecedent presence of an ulcerated plaque, the risk of stroke increased slightly at the highest degrees of stenosis. Overall, carotid endarterectomy reduced the risk of ipsilateral stroke at 24 months by at least 50%. Similar results were obtained for risk of major ipsilateral stroke and risk of all strokes and death. CONCLUSIONS: The presence of angiographically defined ulceration for medically treated symptomatic patients is associated with an increased risk of stroke. The risk of stroke more than doubles at higher degrees of stenosis. Carotid endarterectomy is beneficial in substantially reducing the risk of stroke, regardless of plaque ulceration and degree of severe carotid stenosis.

Prognosis after transient monocular blindness associated with carotid-artery stenosis.

BACKGROUND: Transient monocular blindness associated with internal-carotid-artery stenosis is a risk factor for stroke. The effect of carotid endarterectomy in patients who present with transient monocular blindness has not been determined. METHODS: We compared the risk of stroke among patients presenting with transient monocular blindness with the risk among patients presenting with hemispheric transient ischemic attack. The effect of endarterectomy was assessed in patients with transient monocular blindness. The analyses were based on data from the North American Symptomatic Carotid Endarterectomy Trial. RESULTS: A total of 198 medically treated patients with transient monocular blindness had a three-year risk of ipsilateral stroke that was approximately half of that among 417 medically treated patients with hemispheric transient ischemic attack (adjusted hazard ratio, 0.53; 95 percent confidence interval, 0.30 to 0.94). Six factors were associated with a higher risk of stroke in patients with monocular blindness--an age of 75 years or more, male sex, a history of hemispheric transient ischemic attack or stroke, a history of intermittent claudication, stenosis of 80 to 94 percent of the luminal diameter, and the absence of collateral circulation. The three-year risk of stroke with medical treatment for patients with zero or one risk factor was 1.8 percent, with two risk factors 12.3 percent, and with three or more risk factors 24.2 percent (P=0.003). The three-year absolute reduction in the risk of stroke associated with endarterectomy was -2.2 percent (i.e., a 2.2 percent increase in risk) among patients with zero or one risk factor, 4.9 percent among those with two risk factors, and 14.3 percent among those with three or more risk factors (P=0.23 by a test for interaction). CONCLUSIONS: Among patients with internal-carotidartery stenosis, the prognosis was better for those presenting with transient monocular blindness than for those presenting with hemispheric transient ischemic attack. Among patients with transient monocular blindness, carotid endarterectomy may be beneficial when other risk factors for stroke are also present.

Internal borderzone infarction: a marker for severe stenosis in patients with symptomatic internal carotid artery disease. For the North American Symptomatic Carotid Endarterectomy (NASCET) Group.

BACKGROUND AND PURPOSE: Among subcortical infarctions, internal borderzone infarcts (IBI) are considered to be separate entities from perforating artery infarcts (PAI). The purpose of the present study is to examine the relationship between the presence of IBI and the degree of angiographically defined internal carotid artery (ICA) stenosis in symptomatic patients. METHODS: A review of 1253 brain CTs from patients recruited by the North American Symptomatic Carotid Endarterectomy Trial was performed, using templates for the identification of subcortical and cortical vascular territories. RESULTS: A total of 413 patients had visible ischemic lesions on the side ipsilateral to their symptomatic ICA. Of these, 138 had PAI, 108 had IBI, 122 had cortical infarcts, and 45 had a combination of different lesions. Mean (+/-SD) lesion diameter was larger for IBI (11.0+/-5.9 mm) than for PAI (7.1+/-4.7 mm) (P<0.001 for comparing 2 means). IBI was associated with higher degrees of ICA stenosis (P<0. 001). Sixty-three percent of the patients with IBI had severe (70% to 99%) ICA stenosis compared with 42% of patients with PAI; 18% of the IBI patients had stenosis of 90% or more compared with 8% of the patients with PAI. Multiple logistic regression did not identify any patient characteristics as confounders. CONCLUSIONS: Among subcortical infarctions, IBI are associated with higher degrees of ICA stenosis in symptomatic patients. Differentiating between internal borderzone and perforating artery infarcts is important, because each may arise from different mechanisms, namely, carotid disease and small-vessel disease, respectively.

Angiographic detection of carotid plaque ulceration. Comparison with surgical observations in a multicenter study. North American Symptomatic Carotid Endarterectomy Trial.

BACKGROUND AND PURPOSE: Carotid plaque ulceration is used as one of the determinants in deciding which patients should be submitted to carotid endarterectomy. Uncertainties about its importance persist. Its detection by angiography is an important consideration. METHODS: The detection of ulceration by angiography was compared with observations during endarterectomy in the first 500 patients recruited into the North American Symptomatic Carotid Endarterectomy Trial. This represents the first multicenter compilation of data on this subject and the largest series of patients with both arteriographic and direct surgical observation. RESULTS: Sensitivity and specificity of detecting ulcerated plaques were 45.9% and 74.1%, respectively. The positive predictive value of identifying an ulcer was 71.8%. These results remained unchanged with differing degrees of carotid stenosis and were confirmed by analyses based on receiver operating characteristic (ROC) methodology. The area under the ROC curve (Az) was estimated to be 0.61 (95% confidence interval, 0.55 to 0.67). CONCLUSIONS: These observations from a multicenter study confirm that little agreement exists between angiography and surgical observation in detecting carotid plaque ulceration.