Recurrent stereotyped episodes in cerebral amyloid angiopathy: response to migraine prophylaxis in two patients.

BACKGROUND: Cerebral amyloid angiopathy (CAA) typically presents with cognitive decline or symptomatic intracerebral hemorrhage, but episodes of recurrent stereotyped limb attacks have also been reported. METHODS: Retrospective review of the medical records of 4 patients referred to the general neurology services and a specialist stroke center with clinically probable CAA. RESULTS: Four subjects, all Caucasian, mean age 74 years, were followed up over a mean duration of 20 months. They all experienced recurrent prolonged stereotyped attacks of sensory symptoms, lasting 5-30 min, that resolved completely between attacks. Three subjects developed intracerebral hemorrhage, and 2 had an irreversible rapid cognitive decline. Two patients experienced symptomatic improvement with migraine prophylaxis (verapamil or topiramate). CONCLUSIONS: Recurrent stereotyped prolonged attacks with sensory and motor elements can predate the development of intracerebral hemorrhage in individuals with clinically probable CAA. When evaluating patients with such attacks, neurologists need to consider CAA as a possible mimic of transient ischemic attacks. We suggest a trial of migraine prophylaxis for symptomatic management.

Oral anticoagulation in patients with cardiomyopathy or heart failure in sinus rhythm.

BACKGROUND: Despite many prospective randomized studies defining the benefits of anticoagulation in atrial fibrillation (AF), there have been no adequate studies in cardiomyopathy (CM) in sinus rhythm. METHODS: We review the current knowledge of the risk of stroke in CM, left ventricular systolic dysfunction and heart failure as well as the indications for antithrombotic agents and compare this with AF. RESULTS: The current knowledge of risk factors for stroke and indications for antithrombotic agents in CM is similar to that of AF prior to the treatment studies of the 1980s-1990s. CONCLUSION: Prospective randomized trial data are urgently needed to determine the role of antithrombotic drugs in CM.

"Economy class" stroke syndrome?

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.

Deep cerebral infarcts extending to the subinsular region.

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.

A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke.

BACKGROUND: Despite the use of antiplatelet agents, usually aspirin, in patients who have had an ischemic stroke, there is still a substantial rate of recurrence. Therefore, we investigated whether warfarin, which is effective and superior to aspirin in the prevention of cardiogenic embolism, would also prove superior in the prevention of recurrent ischemic stroke in patients with a prior noncardioembolic ischemic stroke. METHODS: In a multicenter, double-blind, randomized trial, we compared the effect of warfarin (at a dose adjusted to produce an international normalized ratio of 1.4 to 2.8) and that of aspirin (325 mg per day) on the combined primary end point of recurrent ischemic stroke or death from any cause within two years. RESULTS: The two randomized study groups were similar with respect to base-line risk factors. In the intention-to-treat analysis, no significant differences were found between the treatment groups in any of the outcomes measured. The primary end point of death or recurrent ischemic stroke was reached by 196 of 1103 patients assigned to warfarin (17.8 percent) and 176 of 1103 assigned to aspirin (16.0 percent; P=0.25; hazard ratio comparing warfarin with aspirin, 1.13; 95 percent confidence interval, 0.92 to 1.38). The rates of major hemorrhage were low (2.22 per 100 patient-years in the warfarin group and 1.49 per 100 patient-years in the aspirin group). Also, there were no significant treatment-related differences in the frequency of or time to the primary end point or major hemorrhage according to the cause of the initial stroke (1237 patients had had previous small-vessel or lacunar infarcts, 576 had had cryptogenic infarcts, and 259 had had infarcts designated as due to severe stenosis or occlusion of a large artery). CONCLUSIONS: Over two years, we found no difference between aspirin and warfarin in the prevention of recurrent ischemic stroke or death or in the rate of major hemorrhage. Consequently, we regard both warfarin and aspirin as reasonable therapeutic alternatives.

Hypoperfusion-related cerebral ischemia and cardiac left ventricular systolic dysfunction.

BACKGROUND: Cardiomyopathy and low ejection fraction (EF) are associated with cardiac thrombi and cardiogenic embolism but may also be risk factors for hypoperfusion-related cerebral ischemia (HRCI). Current stroke subtype criteria do not include an HRCI category. METHOD: To look for evidence of HRCI, we compared mean infarct volume between serial patients with EF < or =35% and high-grade (> or = 70%) carotid stenosis and serial patients with normal EF and high-grade carotid stenosis. We matched serial stroke patients with EF < or =35% with stroke patients with normal EF and compared the number and type of ischemic lesion (symptomatic or asymptomatic) and mean infarct volume on magnetic resonance imaging. We blindly compared stroke subtype in these groups using modified Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria, including an HRCI category. RESULTS: In patients with carotid stenosis, ipsilateral infarct volume was greater with EF < or = 35% (74.7 mL, 95% CI, 17.3-132.1 mL) than in controls (17.1 mL, 95% Cl, 9.4-24.8 mL) (P<.05). There was no difference in the mean number of HRCI-compatible infarcts on computed tomography scan between patients with low EF and controls. Symptomatic HRCI occurred in 4 of 15 patients with low EF and in 0 of 15 controls. CONCLUSIONS: Symptomatic HRCI occurs in patients with low EF. Severe arterial stenosis may interact with left ventricular systolic dysfunction to cause cerebral hypoperfusion. Modification of the TOAST criteria to include an HRCI subtype is feasible and HRCI should be included as a stroke subtype.

Effect of citicoline on ischemic lesions as measured by diffusion-weighted magnetic resonance imaging. Citicoline 010 Investigators.

We examined the effect of the neuroprotective and neuroreparative agent citicoline on the growth of cerebral ischemic lesions in a double-blind placebo-controlled study involving patients with acute ischemic stroke using diffusion-weighted magnetic resonance imaging (DWI). Patients with acute ischemic stroke symptom onset 24 hours or less before the start of treatment, National Institutes of Health Stroke Scale (NIHSS) scores of 5 or higher, and lesions of 1 to 120 cc in cerebral gray matter by DWI were enrolled. DWI, T2-weighted magnetic resonance imaging (MRI), perfusion-weighted MRI, and magnetic resonance angiography were obtained at baseline, week 1, and week 12. Citicoline (500 mg/day) was administered orally for 6 weeks, and patients were followed for 12 weeks. The primary assessment was progression of ischemic lesion volume from baseline to 12 weeks as measured by MRI. A total of 100 patients entered the study. The primary MRI analysis included 40 placebo-treated patients and 41 citicoline-treated patients with both baseline and week 12 MRI data and failed to demonstrate a significant difference in lesion volume change from baseline to week 12. From baseline to week 12, ischemic lesion volume [all values mean (SE)] expanded by 180% (107) among placebo-treated patients compared with 34% (19) among citicoline-treated patients. In a secondary analysis, lesion volume decreased from week 1 to week 12 by 6.9 cc (2.8) on placebo versus 17.2 cc (2.6) on citicoline. Baseline variables that were predictors of change in lesion size over 12 weeks were the volume of hypoperfusion (strongest association), baseline NIHSS score, lesion volume on DWI, arterial lesion by magnetic resonance angiography, and categorized elapsed time (< or =12 or >12 hours) from stroke onset to first dose. A marked association between lesion volume reduction and improvement of NIHSS score by seven or more points was observed. Significant correlations between lesion volumes and clinical measures were found, replicating values reported in the literature for smaller case series. We observed a reduction in lesion volume growth from baseline to week 12 with citicoline treatment, with a significantly greater reduction in volume from week 1 to week 12 with citicoline. We found a significant inverse relationship between lesion volume change over 12 weeks as measured by MRI and clinical outcome for ischemic stroke. This relationship supports the role of DWI as a surrogate marker of clinically meaningful lesion progression in stroke clinical trials. The hypothesis that citicoline reduces lesion growth and improves clinical outcome will be tested further.

Abnormal vergence with upper brainstem infarcts: pseudoabducens palsy.

BACKGROUND: Infarcts of the rostral brainstem often cause vertical gaze palsies but may also produce inappropriate convergence that manifests as pseudoabducens palsy and convergence-retraction nystagmus (CRN). Although the substrate for vergence has been defined in the monkey as lying dorsal and lateral to the oculomotor nucleus, the human homologue is unknown. METHOD: - The authors reviewed the clinical features, ocular findings, and CT or MR lesions in seven patients with pseudoabducens palsy and "top-of-the-basilar" infarction. They reviewed the literature for infarcts causing pseudoabducens palsy or CRN with precise autopsy localization. The authors then mapped the location of the infarcts on anatomic templates. RESULTS: The smallest MR infarct produced an ipsilateral pseudoabducens palsy and CRN, and was located just rostral to the oculomotor nucleus, near the midbrain-diencephalic junction. Two patients with only contralateral pseudoabducens palsy had both subthalamic and thalamic infarction. Four patients with bilateral pseudoabducens palsy had larger infarcts involving the midbrain. All patients with pseudoabducens palsy had upgaze palsy. Two patients with CRN from the literature had small infarcts near the midbrain-diencephalic junction at autopsy. CONCLUSIONS: Lesions near the midbrain-diencephalic junction are important for the development of pseudoabducens palsy. Pseudoabducens palsy and CRN are probably both manifestations of abnormal vergence activity. Inhibitory descending pathways for convergence may pass through the thalamus and decussate in the subthalamic region.

Tonic downward and inward ocular deviation ipsilateral to pontine tegmental hemorrhage.

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.

Spinal cord MRI hyperintensities in cervical spondylosis: an ischemic pathogenesis?

The pathophysiology of focal spinal cord MRI T2 hyperintensity (SCHI) in patients with cervical spondylosis is uncertain. This study was undertaken to determine the frequency and cause of SCHI. The authors reviewed serial cervical spine magnetic resonance imaging (MRI) reports and reviewed scans with spondylosis and cord compression or SCHI. The authors noted the location, shape, and extent of SCHI, and severity of spondylosis (expressed as a spondylosis score [SS]). The authors recorded the age and vascular risk factors for each patient. Nineteen of 273 scans (7%) with cervical spondylosis and 19 of 36 scans (53%) with cord compression had SCHI. The SCHI extended for one vertebral level from the compression in 12 patients and for three vertebral levels in 5 patients, and were distant from the compression in 2 patients. The SCHI had a focal, symmetrical, anterior spinal artery terminal zone location in 16 of 19 scans (84%). A rim isointense with normal cord separated all SCHI from the pial surface. Patients with SCHI were older (58.3 years +/- 12.8 years versus 46.8 +/- 8.1 years) (p = 0.007) and had a higher SS (5.7 +/- 2.4 versus 3.9 +/- 1.4) (p = 0.02) than patients without SCHI. The SCHI relates to the severity of cervical spondylosis. The anterior spinal artery territory location, the normal cord between SCHI and the compressive lesion, and the presence of SCHI at a distance from the compressive level all suggest an ischemic basis for SCHI.

Stroke in patients with heart failure and reduced left ventricular ejection fraction.

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.

Cranial magnetic resonance imaging findings in bacterial endocarditis: the neuroimaging spectrum of septic brain embolization demonstrated in twelve patients.

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.

Reversible impairment in cognition and midbrain hematoma.

A 78-year-old man presented with a 2-week history of cognitive decline. Computed tomography (CT) showed obstructive hydrocephalus due to a small midbrain hematoma. He regained premorbid neurological status after ventriculostomy. Spontaneous midbrain hemorrhage is a rare cause of cognitive decline that can be diagnosed by CT and treated by shunting.

Mass effect and death from severe acute stroke.

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.