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The authors report three cases of ischemic stroke in young adults that occurred during or after an airplane flight. Workup was negative for any cause of stroke other than the presence of a patent foramen ovale (PFO). There is an increasing awareness of deep vein thrombosis and pulmonary embolism occurring in relation to long flights. Individuals with a PFO under these circumstances may be vulnerable to stroke from paradoxic embolism. "Economy class" stroke syndrome may be underdiagnosed and is an eminently preventable cause of stroke.

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BACKGROUND AND PURPOSE: We sought to determine the clinical and radiological features and pathogenesis of deep cerebral infarcts extending to the subinsular region (DCIs). METHODS: - We defined DCIs as subcortical infarcts extending between the lateral ventricle and the subinsular region with a paraventricular extent >1.5 cm and a subinsular extent of at least one third of the anteroposterior extent of the insula. We identified patients by review of imaging records and noted the clinical information, risk factors, and investigations. We compared risk factors and clinical features between DCIs and "internal border zone" infarcts restricted to the paraventricular region. RESULTS: - Eight patients were studied. The typical clinical features of DCIs were hemiparesis, aphasia, dysarthria, and dysphagia. Aphasia was seen in 3 of 5 patients with left-sided infarcts. Six of 8 patients (75%) had hypoperfusion as a possible pathogenetic factor (carotid occlusion in 4, surgical clipping of MCA in 1, low ejection fraction in 1), and 3 patients (38%) had cardioembolism as a possible pathogenetic factor (atrial fibrillation in 2, low ejection fraction in 1). One patient (12%) had no cause for stroke. Clinical features were similar to those for paraventricular infarcts. Carotid occlusion was more frequent (P=0.04), and there was a trend toward a higher frequency of hypertension (P<0.1) and smoking with DCIs than with paraventricular infarcts. DCIs were located in a deep vascular border zone. CONCLUSIONS: - The clinical features and pathogenesis of DCIs overlap with those of internal border zone paraventricular infarcts. Hypoperfusion may give rise to DCIs since large-artery occlusion is their main risk factor. The larger size of DCIs compared with paraventricular infarcts may relate to a poorer collateral blood supply.

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A 61-year-old man presented with coma and left hemiparesis. He was found to have tonic downward and inward deviation of the right eye, and a right lateral gaze palsy. He also had occasional downward bobbing movements of the right eye, and a partial bilateral upgaze paresis. CT showed a right pontine tegmental hemorrhage extending to the ipsilateral midbrain. Tonic ocular downward and inward deviation associated with pontine tegmental hemorrhage may be due to irritation of mesencephalic downgaze and convergence centers by rostral extension of the hematoma. Although 'eyes seeming to peer at the tip of the nose' is characteristic of thalamic hemorrhage, it may also be seen secondary to pontine tegmental hemorrhage.

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BACKGROUND: Cardiac failure is associated with both stroke of presumed cardioembolic origin and a high mortality rate. Warfarin is used frequently in patients with reduced cardiac left ventricular ejection fraction (EF), although no randomized trials have confirmed that anticoagulation benefits these patients. METHODS: A literature review was performed pertaining to the frequency of stroke and mortality, and the effect of antithrombotic agents on stroke and mortality rates, in patients with cardiac failure or reduced cardiac EF. We also reviewed the main features of two new proposed studies (Warfarin and Antiplatelet Therapy in Chronic Heart Failure [WATCH] and Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction [WARCEF]) comparing warfarin and antiplatelet agents in patients with low EF. RESULTS: The risk of stroke increases with decreasing EF and the risk of mortality increases with the clinical severity of cardiac failure (New York Heart Association class). Data from heart failure treatment studies suggest that warfarin may reduce stroke and mortality in patients with reduced EF, but definitive answers are lacking. The stroke rate alone is too low to be used as a primary endpoint, but an endpoint combining stroke and death (as WARCEF and WATCH propose) should allow an assessment of the effect of antithrombotics in cardiac failure. Amalgamating the data on stroke from these two trials should yield enough statistical power to compare the effects of warfarin and aspirin on stroke as an independent secondary endpoint. CONCLUSION: Whether warfarin is superior to aspirin in reducing stroke and mortality in patients with low ejection fraction is an important clinical issue that warrants prospective evaluation.

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Infective endocarditis (IE) is an elusive systemic disorder that is often associated with neurologic complications. The contribution of brain magnetic resonance imaging (MRI) to the diagnosis of IE and the spectrum of such findings has been only sparsely described previously. The authors report cranial MRI findings in 12 patients with IE. Each of the patients had MRI evidence of cerebral embolization, with multiple brain lesions noted in most patients (n = 10). Cortical branch infarction was the most common lesion (n = 8), which usually involved the distal middle cerebral artery tree. The next most common finding (n = 7) was numerous small embolic lesions which typically lodged in the supratentorial gray-white junction, some of which were clinically silent and many of which enhanced (probable microabscesses). Brain hemorrhages were noted in four patients, most commonly subarachnoid hemorrhage (n = 3). Two patients developed multiple frank parenchymal macroabscesses/cerebritis lesions. A previously unreported finding in septic embolization, a stroke that became infected with abscess formation ("septic infarction"), was noted in two patients. MRI showed orbital cellulitis in two patients. Most patients studied with gadolinium showed enhancement of lesions (n = 5/8). The authors conclude that cranial MRI may be a valuable tool in the evaluation of patients with IE. The presence of characteristic cranial MRI lesions, especially of multiple types, may prompt early diagnosis and treatment.

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BACKGROUND: In severe acute stroke, the degree of midline cerebral displacement is related to level of consciousness but not to survival. Early identification of patients at high risk of death from mass effect would assist patient management decisions. METHODS: We measured lesion volume, horizontal pineal displacement (PD), and horizontal septum pellucidum displacement (SD) on axial CT of consecutive patients with severe (Canadian Neurological Scale score < or = 5) acute hemispheric stroke. We correlated CT measurements with the probability of 14-day survival. RESULTS: Forty-six (39%) of 118 patients died within 14 days and 72 (61%) died within 1 year following stroke. Crude risk factors for 14-day mortality were as follows: lesion volume > or = 400 ml, SD > or = 9 mm, PD > or = 4 mm, intraventricular hemorrhage, and coma on admission. Only SD (p = 0.001) and coma on admission (p = 0.019) remained significant in multivariate analysis, but PD was highly correlated with SD (r = 0.82). PD of > or = 4 mm on a scan performed within 48 hours of stroke onset identified patients with a low probability of 14-day survival (0.16; CI 0 to 0.32) with a specificity of 89% and a sensitivity of 46%. CONCLUSIONS: The degree of horizontal midline cerebral displacement correlates with the likelihood of death following stroke. Patients with > or = 4 mm PD on CT performed within 48 hours of stroke onset are at high risk for early death.

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Single-photon emission computed tomography (SPECT) and transcranial Doppler (TCD) ultrasonography were used to assess brain perfusion during cardiopulmonary bypass. Intravenous injections of technetium 99 m-hexamethylpropyleneamineoxime (99mTc-HMPAO) were administered before surgery and intraoperatively after the first 2 minutes in the first patient and at the end (42 minutes) of cardiopulmonary bypass in the second patient. The total middle cerebral artery territory counts were calculated using the region-of-interest method and compared to cerebellar regional counts. 99mTc-HMPAO uptake on SPECT scans was increased at the beginning and at the end of cardiopulmonary bypass, compared to baseline preoperative values (11-17%) in the presence of multiple microembolic signals on TCD (n1 = 35 and n2 = 42 for unilateral middle cerebral artery monitoring). These results indicate the feasibility of using HMPAO-SPECT to study brain perfusion changes during cardiac surgery. A combination of SPECT and TCD ultrasonography may be used to study the impact of microembolism during cardiac surgery with cardiopulmonary bypass.

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The accepted standard treatment of relapsing multiple sclerosis consists of medications for disease symptoms, including treatment for acute exacerbations. However, currently there is no therapy that alters the progression of physical disability associated with this disease. The purpose of this study was to determine whether interferon beta-1a could slow the progressive, irreversible, neurological disability of relapsing multiple sclerosis. Three hundred one patients with relapsing multiple sclerosis were randomized into a double-blinded, placebo-controlled, multicenter phase III trial of interferon beta-1a. Interferon beta-1a, 6.0 million units (30 micrograms¿, was administered by intramuscular injection weekly. The primary outcome variable was time to sustained disability progression of at least 1.0 point on the Kurtzke Expanded Disability Status Scale (EDSS). Interferon beta-1a treatment produced a significant delay in time to sustained EDSS progression (p = 0.02). The Kaplan-Meier estimate of the proportion of patients progressing by the end of 104 weeks was 34.9% in the placebo group and 21.9% in the interferon beta-1a-treated group. Patients treated with interferon beta-1a also had significantly fewer exacerbations (p = 0.03) and a significantly lower number and volume of gadolinium-enhanced brain lesions on magnetic resonance images (p-values ranging between 0.02 and 0.05). Over 2 years, the annual exacerbation rate was 0.90 in placebo-treated patients versus 0.61 in interferon beta-1a-treated patients. There were no major adverse events related to treatment. Interferon beta-1a had a significant beneficial impact in relapsing multiple sclerosis patients by reducing the accumulation of permanent physical disability, exacerbation frequency, and disease activity measured by gadolinium-enhanced lesions on brain magnetic resonance images. This treatment may alter the fundamental course of relapsing multiple sclerosis.

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BACKGROUND AND PURPOSE: The do-not-resuscitate (DNR) order is a mechanism of withholding cardiopulmonary resuscitation (CPR). The lack of DNR guidelines specific for acute stroke may result in many stroke patients receiving unnecessary and futile resuscitation and ventilator-assisted breathing. METHODS: A prospective multicenter evaluation of disease-specific criteria for DNR orders in acute stroke was initiated using a modified Delphi process. The participants were the Canadian and Western New York Stroke Consortium members who are closely involved in caring for acute stroke patients and conducting clinical trials at the academic centers. Previously published provisional criteria were reviewed by the participants. Modifications were made to the criteria until statistically significant agreement (P < .05, z score, or 67% similar answers) was achieved. RESULTS: Disease-specific criteria for DNR orders in acute stroke were discussed by 26 physicians in three rounds of the opinion survey. An agreement was reached that a "no resuscitation" decision is appropriate when any two of the following three clinical criteria are present (the degree of agreement is given in parentheses): severe stroke (88%, P = .00007), life-threatening brain damage (73%, P < .01), and significant comorbidities (92%, P = .00003). The poor prognosis implied by these criteria should be discussed whenever possible among physician(s), the patient, and family members before the decision to withhold CPR is made. Eighty-one percent of the participants agreed that these disease-specific criteria are appropriate for clinical use (P = .0008). CONCLUSIONS: Disease-specific criteria for DNR orders were developed to supplement general DNR policies for patients with hemispheric brain infarction and intracerebral hemorrhage during the first 2 weeks of stroke. A significant agreement was reached by a panel of physicians that patients with acute stroke should not be resuscitated if these disease-specific criteria are met.

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BACKGROUND AND PURPOSE: Single, oval lesions greater than 5 mm in diameter lying inferior to the lateral putamen (infraputaminal lacunes [IPLs]) seen on CT or MR images are commonly reported as lacunar infarcts. To determine the clinical relevance and underlying pathology of IPLs, we evaluated the imaging appearances, clinical features, vascular risk factors, and histopathology in patients with IPLs. METHODS: Consecutive MR scans were reviewed for the presence of IPLs. Serial patients seen in routine clinical practice with IPLs were also included. Vascular risk factors were obtained from a prescan questionnaire. Histology and microangiography were performed on postmortem material. A MEDLINE search for putaminal infarcts was performed to look for imaging lesions typical of IPLs. RESULTS: Three of 100 serial MR scans had IPLs (3%). Nine other patients with in vivo (7) or postmortem (2) MR scans had IPLs. No neurological symptoms could be related to the IPLs. There were no differences in age, hypertension, diabetes, or presence of cortical enlarged perivascular spaces (EPVSs) between patients with and without IPLs. Unlike infarcts, IPLs were isointense with the cerebrospinal fluid on proton density MR sequences. Histological correlation of three MR scans showed IPLs to be a single large EPVS, situated lateral to the anterior commissure. IPLs were located at a point where multiple lenticulostriates turn sharply dorsally. An IPL was the probable cause of the apparent infarct in six publications from peer-reviewed literature that linked different clinical signs to putaminal infarct. CONCLUSIONS: IPLs are EPVSs that can be differentiated from infarcts on proton density MR images.

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In the classical corneomandibular reflex (CMR), corneal stimulation elicits a bilateral eyelid blink and a brisk anterolateral jaw movement. We here describe 14 patients with a spontaneous palpebromandibular (eyelid-jaw) synkinesia (SPMS) in whom jaw movements, similar to those in CMR, regularly accompanied spontaneous eye blinks without an external corneal stimulus. Eleven of the patients with SPMS also had CMRs on corneal stimulation. Four patients had clinical and imaging evidence of brainstem lesions above the mid-pons, 5 patients had autopsy or imaging evidence of both bilateral cerebral and upper brainstem lesions, and 5 patients had clinical or imaging evidence of bilateral cerebral dysfunction. Topical corneal anesthesia administered to patients who had both CMR and SPMS blocked the CMR but had no effect on the SPMS. In patients with both SPMS and CMR, measurements of latency from onset of orbicularis oculi electromyographic activity to onset of lateral pterygoid EMG activity, and mandibular kinesiography of jaw velocity and direction showed that the eyelid-jaw synkinesias of CMR and SPMS had similar characteristics. We conclude that SPMS is pathophysiologically the same as the eyelid-jaw synkinesia of CMR and both synkinesias originate centrally, probably in the pons. In CMR, the jaw movement is primarily related to the blink rather than the corneal stimulus, but corneal stimulation may be necessary to overcome a higher threshold for expression of the synkinesia than in patients with SPMS. Like CMR, SPMS emerges in patients with upper brainstem or bilateral cerebral lesions and SPMS may therefore be a useful localizing clinical sign.

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