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.

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.

Opsoclonus in organophosphate poisoning.

Transient opsoclonus was observed in a patient who attempted suicide with the organophosphate insecticide Malathion (diethyl[dimethoxyphosphinothioyl]thiobutanedioate). Several toxins can cause opsoclonus, and these must be considered in its differential diagnosis. Eye movement disorders are one of the more common manifestations of organophosphate intoxication, and opsoclonus should now be included among these. Acetylcholine may be a neurotransmitter in the ocular motor pathway.

The lesion causing continuous facial myokymia in multiple sclerosis.

OBJECTIVE: To attempt to identify the site of the lesion causing continuous facial myokymia (CFM) in multiple sclerosis (MS) through the use of magnetic resonance imaging (MRI). DESIGN: A case series was employed. SETTING: The Baird Multiple Sclerosis Center, Millard Fillmore Hospital, and the Neurology Department, Buffalo General Hospital, Buffalo, NY. PARTICIPANTS AND MEASURES: Twelve patients with MS and CFM were examined by MRI of the brain while the CFM was present. The MRI examinations were also performed before the CFM had developed and after it had ceased in eight of the patients. Another 57 patients with MS who never had CFM but who had similar disabilities to those who did were also examined by MRI. RESULTS: In 11 of the 12 patients with MS and CFM, the causative lesion was demonstrated to involve the postnuclear, postgenu portion of the facial nerve intraaxially in the dorsolateral pontine tegmentum ipsilateral to the CFM. In the majority of patients who were studied after the CFM had stopped clinically, the lesion was observed to resolve on MRI. Seventeen percent of the patients with MS but without CFM were found to have the typical pontine tegmental lesion. CONCLUSIONS: Continuous facial myokymia in MS is caused by a pontine tegmental lesion involving the postnuclear, postgenu portion of the facial nerve. The lesion is identified by MRI in approximately 90% of patients with MS who have CFM clinically. The typical MRI lesion may also be found in a minority of patients with MS who do not have CFM clinically.

Neuroimaging criteria for vascular dementia.

OBJECTIVE: To examine published imaging criteria that separate cranial computed tomographic (CT) scans into grades of increasing support for a diagnosis of vascular dementia (VaD). DESIGN: Patients were divided into 4 grades of increasing extent of vascular lesions on CT. The frequency of VaD was compared between these grades. SETTING: A university department of neurology. PATIENTS: Forty-two consecutive patients who underwent neuropsychological assessment for possible dementia and who had a CT scan performed within 6 months following any stroke causing dementia. Patients with delirium, severe aphasia, and motor and/or sensory deficits that impaired neuropsychological testing and patients with mass lesions or nonvascular white matter disease shown on CT were excluded. MAIN OUTCOME MEASURE: The National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria for probable VaD. RESULTS: The frequency of VaD was greater in patients with grade 1 (7 [50%] of 14, P = .01), grade 2 (2[50%] of 4, P = .2), and grade 3(7[78%] of 9, P = .002) scans than the frequency of VaD with grade O scans (1[7%] of 15). There was a linear association of the frequencies of VaD between imaging grades (P = .0008). In a subgroup of patients with neuropsychological deficits caused by cerebrovascular disease, there was a linear association of the severity of the deficits between imaging grades (P = .007). CONCLUSIONS: We conclude that our criteria can separate CTs into increasing levels of support for a diagnosis of VaD. The extent of vascular lesions on CT reflects the severity of associated neuropsychological deficts.

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.

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.

Small deep infarcts diagnosed on computed tomography.

The clinical and angiographic correlations of small deep infarcts seen on computed tomography (CT) scan were studied in 297 consecutive patients. Some of these showed the features described by Fisher as part of the lacunar syndrome. In a large number, a source of emboli from either a cardiac or a carotid source was highly probable; in a smaller number, other vascular diseases were present. The finding of a small deep infarct on CT does not exclude the need for further investigation of a possible embolic source in selected patients.

"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.

Inter- and intrarater scoring agreement using grades 1.0 to 3.5 of the Kurtzke Expanded Disability Status Scale (EDSS). Multiple Sclerosis Collaborative Research Group.

We determined inter- and intrarater Kurtzke Expanded Disability Status Scale (EDSS) scoring agreement for four trained examining physicians who evaluated 10 clinically stable multiple sclerosis patients. These patients had previously been determined to have EDSS scores of 1.0 to 3.5 and were scheduled to participate in a funded clinical trial of intramuscular recombinant interferon-beta. Intrarater reliability was greater than interrater reliability for scoring the EDSS and all of its component functional systems scores (FSS). Specifically, individual examiners were able to reproduce three serial examination scores on the same patient on the same day (intrarater agreement) within 1.0 EDSS or 2.0 individual FSS points. Reproducible scoring across examiners (interrater agreement), however, could only be accomplished within 1.5 EDSS or 3.0 individual FSS points. Additionally, the interrater scoring variability in our patients is greater than that previously reported for patients with higher EDSS scores. We conclude that clinical trials that employ the EDSS as an outcome measure of treatment efficacy should include inter- and intrarater agreement data for all examining physicians. Most importantly, studies using a single examining physician to evaluate individual patients throughout the course of a clinical trial will require less change in the EDSS to reliably measure disease activity than will studies using more than one examining physician to evaluate individual patients throughout the trial.

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.

Cystic intracranial tumours. Cyst fluid, biochemical changes and computerised tomographic findings.

The concentrations of five biochemical substances were studied in cyst fluid from 49 cystic intracranial tumours and the findings were compared with the computerised tomographic (CT) scan and histological appearances of the tumours. The attenuation of the cyst wall on unenhanced CT was found to be related to cyst fluid alkaline phosphatase levels. Enhancement of the cyst wall with contrast medium was associated with higher levels of protein, cholesterol, alkaline phosphatase, phosphohexose isomerase (PHI) and lactate dehydrogenase (LDH) in the cyst fluid. Lesions of high grade malignancy had higher levels of protein, cholesterol, alkaline phosphatase, LDH and PHI than lesion of low grade malignancy and also higher levels of alkaline phosphatase, LDH and PHI than benign lesions. Oedema around a lesion was associated with increased malignancy.

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.

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.

Interrater agreement of computed tomography infarct measurement.

To determine the reliability of infarct measurements on hard-copy computed tomography (CT) images the in vivo (IV) infarct volumes of 20 CT-detected infarcts were estimated and divided into four size groups with 5 infarcts in each group: Group A, less than 0.5 ml; Group B, 0.5 to 5.0 ml; Group C, 5 to 50 ml; and Group D, more than 50 ml. Seventeen infarcts were measured once and 3 infarcts three times to the nearest 0.5 mm by each of two neurologists and two neuroradiologists using a ruler on hard-copy CT images. The longest diameter (designated AP), the greatest diameter at right angles to AP (designated LAT), and the number of slices showing the infarct were recorded and multiplied by the hard-copy minification factor to give IV dimensions. Volume (VOL) was calculated according to a previously published method. Interrater intraclass correlation coefficients for all infarcts combined were 0.98 (AP), 0.91 (LAT), and 0.97 (VOL). Using all raters' measurements for any single infarct, the difference between the largest and the smallest measurement of AP and LAT was smallest (< 6 mm IV) for Group A and largest (< 31 mm IV) for Group D. This difference was largest relative to the dimension being measured in Groups A and B, where it reached 101% of the mean of the four raters' measurements for the AP dimension being measured in Group B, and 70% of the dimension being measured in Group A. With all raters' measurements for any single infarct, the difference between the largest and smallest measurement of VOL was smallest (< 0.5 ml) for Group A and largest (< 260 ml) for Group D. This difference was largest relative to the mean volume of the infarct being measured in Group B, where it reached 153% of the mean of the four raters' measurements for VOL and reached 115% of the mean of the four raters' measurements for VOL in Group A. The authors conclude that infarcts can be measured on hard-copy images with good interrater agreement. When infarcts with a volume smaller than 5 ml are measured, differences between raters' measurements may exceed the size of the dimensions being measured.

Feasibility of SPECT for studies of brain perfusion during cardiopulmonary bypass.

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.

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.

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.

[Cerebellar hemorrhage and unilateral asterixis]. / Hémorragie cérébelleuse et astérixis unilatéral.

A hypertensive woman presented with asterixis ipsilateral to a cerebellar hemorrhage. Asterixis has not previously been described in association with a cerebellar lesion. The presence of asterixis in this patient may have been due to a reduction of afferent information through the loss of the dentato-thalamo-cortical input. Unilateral asterixis denotes a dysfunction of the mechanism underlying sustained muscular contraction and not a precise cerebral localisation.

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.