Large subcortical hemispheric infarctions. Presentation and prognosis.

A specific form of large subcortical hemispheric infarction on computed tomography was identified in 24 of 2198 (1%) stroke registry patients. Combined with 13 cases from earlier literature reports, a characteristic neurologic picture developed. Severe face plus arm plus leg weakness at onset (76%), corticallike features of aphasia and/or contralateral neglect (68%), and premonitory transient ischemic attacks (24%) were frequent. Twenty-two patients (59%) had large vessel arterial occlusive disease. Eight patients (22%) had primary embolic occlusion in the middle cerebral artery territory. During an average follow-up of 16 months, five patients (14%) suffered recurrent stroke or death. The clinical presentation and prognostic features of this distinct stroke subtype are described.

Evidence for transhemispheric diaschisis in unilateral stroke.

Nineteen patients with strictly unilateral ischemic stroke as determined by clinical examination, computed tomography, magnetic resonance imaging, and standard angiography underwent cerebral blood flow (CBF) analysis using fluorine 18 fluoromethane and positron emission tomography. Mean flow values for averaged hemispheric, infarct, and homologous contralateral regions of interest (ROIs) were determined. All patient CBF values were significantly below comparable CBF ROIs in neurologically normal controls using Wilcoxon's two-sample rank testing. Multiple regression analysis disclosed a significant correlation between contralateral CBF are both localized CBF in the infarct ROI and patient age. Correlations between contralateral CBF and dependency score or severity of neurologic deficit at time of positron emission tomography, expired PCO2, mean arterial blood pressure, serum glucose or hematocrit, risk factor score, and number of days studied after stroke were not statistically significant. Although we did not identify the biologic mechanisms involved, we conclude that CBF reduction contralateral to a strictly unilateral ischemic infarction is due to a combination of aging and transhemispheric diaschisis.

Chronic progressive leukoencephalopathy in adult celiac disease.

Progressive leukoencephalopathy developed in a patient with adult celiac disease. Neurologic abnormalities appeared 4 years after the gastrointestinal manifestations despite a gluten-free diet and replacement of vitamins. Brain MRI showed marked confluent white matter abnormalities, and stereotactic brain biopsy revealed chronic leukoencephalopathy. Treatment with I.V. steroids and immunoglobulins did not stop disease progression. Celiac disease should be considered in the differential diagnosis of the leukoencephalopathies.

Delayed immune response in chorea-amyotrophy with spherocytosis.

Progressive CSF lymphocytic pleocytosis and intrathecal IgG-synthesis occurred late in familial amyotrophy, neuropathy, chorea, and dementia with spherocytosis. Immunoblotting showed a serum and CSF antibody apparently directed against glial fibrillary acidic protein. A secondary autoimmune response was probably triggered during the evolution of the neurodegenerative process.

Cerebral vasocapacitance and TIAs.

We report the vasocapacitance of the cerebral circulation, as determined by cerebral blood flow reactivity to induced hypercapnia using fluoromethane positron emission tomography, in 32 patients with unilateral anterior circulation transient ischemic attacks. A hemodynamic subset of eight patients, defined based on exertional, positional, orthostatic, or cardiac dysrhythmic induction of symptomatology, is characterized by multiple (median, 4.5 attacks per patient), brief (median, 2.5 minutes per attack), continued episodes of hemispheric ischemia including focal limb shaking. Symptomatic middle cerebral artery flow territories show significantly lower (p less than 0.04) and more asymmetric (p = 0.036) vasodilatory responses in the hemodynamic subset. Although ipsilateral internal carotid artery occlusion is more prevalent in the hemodynamic subset, the features of age, mean arterial blood pressure, carbon dioxide values, serum glucose, serum hematocrit, and number or type of risk factors do not differ significantly between groups. These studies of vasocapacitance help validate clinical criteria for cerebral hemodynamic events with an objective physiologic measurement.

Functional cortical interaction patterns in visual perception and visuospatial problem solving.

To explore the integration of functional neuronal interactions in human higher cortical functions, we applied multivariate mathematical techniques to regional cerebral blood flow (rCBF) increases induced by mental activity. rCBF was measured using the intravenous xenon-133 clearance technique with 32 bihemispheric detectors in 84 normal volunteers at rest and during both a visuoperceptual accuracy task and a visuospatial problem solving task. Both paradigms activated rCBF in bilateral premotor, motor and postcentral regions. Bilateral prefrontal activation occurred during problem solving but not during the perceptual accuracy task. Partial correlations coefficients and factor analysis identified significant interactions between numerous cortex regions in both tasks. There were highly ordered and integrated patterns of functional interaction patterns between cortex areas subserving elementary subfunctions of complex behavior. Cortical interaction analysis by such techniques is a useful tool to describe the functional anatomy of large-scale neurocognitive networks in the intact human brain. Imaging functional interactions between active cortex areas are complementary to other experimental neurophysiologic methods to explore brain-behavior relationships in health and disease.

Noninvasive testing of cerebral perfusion reserve prior to coronary artery bypass graft surgery.

Cerebral perfusion reserve testing using fluorine-18-fluoromethane and positron emission tomographic brain scanning to define cerebral blood flow abnormalities was performed in 5 patients being considered for combined coronary and carotid reconstructive surgery. Blood flow testing during normocapnia and following hypercapnia was utilized in these patients to determine the hemodynamic significance of known extracranial carotid artery occlusive lesions. Reserve diminution in 2 of these patients prompted combined surgery, whereas normal reserve values in the other 3 prompted coronary surgery alone. Results obtained in this preliminary series show how preoperative noninvasive testing of cerebral perfusion reserve adds to the diagnostic evaluation of patients with widespread vascular disease.

Pitfalls of regional cerebral blood flow analysis in cerebrovascular disease.

In 20 patients with unilateral cerebrovascular disease, regional cerebral blood flow (rCBF) was measured by F-18-fluoromethane inhalation and positron emission tomography (PET). The purpose was to study various strategies of rCBF data analysis that are currently used in SPECT and PET. Methods of quantitative data analysis standardize rCBF values relative to an intraindividual reference, and thus create ratios as estimators of rCBF in the ischemic regions-of-interest (ROI). These ratios were compared as well as the absolute rCBF values in the ischemic ROI graphically and by Spearman's rank correlation coefficient (r). The results demonstrated that previously reported methods of data analysis failed to represent rCBF in the ischemic ROI; r values were 0.467, -0.406, -0.453, and 0.329, respectively (N.S.). This failure was due to a more widespread reduction of rCBF even in patients with minimal ischemic deficits. In conclusion, previously reported strategies of rCBF analysis based on intraindividual standardization should not be used in patients with cerebrovascular disease since they may produce misleading results.

Treatment of multiple sclerosis with 15 +/- deoxyspergualin. Design of a controlled study with close MRI-monitoring.

The rationale and design of a prospective randomized double blind study of 15 +/- Deoxyspergualin in the treatment of Multiple Sclerosis are presented. The study was started in autumn 1992 and will include more than 200 patients who will be randomized either to DSG low dose or DSG high dose or placebo. Average number of contrast enhancing lesions in monthly cranial MRIs during the first six months of treatment and change in EDSS at the end of the two-year study period will be the main efficacy parameters.

Quantitative positron emission tomography and single photon emission computed tomography measurements of human cerebral blood flow.

Current methods using emission tomography to quantitate human regional cerebral blood flow (rCBF) are reviewed. The sensitivity and spatial resolution of single photon emission tomography are too low to correlate reliably rCBF with known anatomic landmarks in the brain. However, even if the superior imaging qualities of positron emission tomography are employed, the radiotracers of rCBF frequently do not fully meet the requirements of the models of tracer kinetics that are employed. Therefore, the methodology of reported rCBF studies using emission tomography to measure quantitatively human rCBF needs to be carefully evaluated.

Data analysis in behavioral cerebral blood flow activation studies using xenon-133 clearance.

BACKGROUND AND PURPOSE: Three mainstream strategies exist to detect the responses of regional cerebral blood flow to functional activation. We tested the significance of changes in raw regional cerebral blood flow data, regional cerebral blood flow data normalized by division by global cerebral blood flow (dependent model of the regional-to-global cerebral blood flow relation), and regional cerebral blood flow data treating global cerebral blood flow as a covariate (independent model). Both latter models attempt to enhance regional sensitivity by removing global effects. We examined the sensitivity and pitfalls of these three strategies in behavioral activation studies. METHODS: These three strategies of data analysis were applied to changes in regional cerebral blood flow induced by a visuospatial problem-solving task in 38 healthy subjects as measured by the intravenous xenon-133 method with 32 stationary detectors. RESULTS: Mental activation increased blood flow in all regions of interest. Raw data were most sensitive and reliable to detect responses to mental stimulation. Both the independent and dependent models to remove global effects were less sensitive and falsely indicated deactivation in regions that were clearly stimulated. CONCLUSIONS: In behavioral activation paradigms, safe data analysis should be restricted to using raw regional cerebral blood flow increases without normalization or separation of global from regional effects. Studies using complex stimulation tasks should be scrutinized for global cerebral blood flow effects confounding regional responses.

Abnormalities of interictal cerebral perfusion in classic but not common migraine.

Regional cerebral blood flow (rCBF) was measured as gray matter blood flow using the 133Xe inhalation technique in 50 pain-free headache patients: Eight patients having classic migraine with normal computed tomograms were matched to patients having common migraine and to normal controls. Interictal rCBF was determined at least 6 days after the last migraine attack and more than 24 hours before the next one. There were no between-group differences for age, PCO2, mean hemispheric blood flow, interindividual and intraindividual variabilities, hyperfrontality, or rCBF symmetry. However, when subjects were classified as to overall abnormal perfusion, a significant number (n = 4, p less than 0.04) of patients with classic migraine had rCBF abnormalities, whereas only one such patient was seen in the group with common migraine. Patients with classic migraine had abnormal mean hemispheric blood flows or disturbed intrahemispheric rCBF patterns. Oligemic and hyperemic regions topographically corresponded to the clinical symptoms in one patient. We conclude that during migraine attacks and interictally there is an instability of rCBF control in patients with classic but not common migraine.

Effect of flunarizine on regional cerebral blood flow in common and complicated migraine. Pilot study.

Alterations of regional cerebral blood flow (rCBF) are at least epiphenomena of common and complicated migraine, but may lead to serious clinical complications. Since flunarizine seems to be effective in migraine prevention it may exert a beneficial influence on rCBF in migraine as well. rCBF was assessed using the 133Xe inhalation method in 5 patients with common and 8 patients with complicated migraine. Measurements were done interictally prior and after therapy with 15 mg flunarizine p.o. daily over a period of 4 weeks. Major abnormalities of grey matter flow were observed even interictally. Significant improvement of rCBF in initially hypoemic regions may be attributed to flunarizine therapy. These preliminary data suggest that calcium entry blockers may prevent the ischemic complications of migraine.

Specific recognition of arteriovenous malformations using Xenon-133 RCBF technique.

With respect to the methodology of the atraumatic Xenon-133 technique the problem whether or not the proposed and introduced arterial artifact (AA) truely represents radiation from intravascular volume and to what extent it affects regional cerebral blood flow (rCBF) calculation is unresolved. We performed rCBF measurements in 22 patients with angiomas to clarify this issue in those patients known to have pathologically enlarged intracranial vessels. P4--the parameter suggested to represent the AA--as well as the conventional blood flow parameter for gray matter (F1) were compared to those of 50 volunteers using four criteria of abnormality: 1. intrahemispheric distribution, 2. interhemispheric differences of homologous detector pairs, 3. differences of mean hemispheric values, 4. visual evaluation of CBF maps. 19 of the 22 patients with angioma fulfilled at least two of the four criteria of abnormality, in comparison to 1 of 50 volunteers. P4's sensitivity for detecting angiomas proved to be higher (86%) than the perfusion parameters of gray matter. Focal increase of P4 proved to be highly specific for the presence of arteriovenous malformation (AVM, specifity 98%). A true arterial artifact exists in most instances in the presence of an AVM. Disregarding AA in the algorithm for calculation rCBF leads to an artificial overestimation of tissue flow in the region of the AVM.

Isolated supraclinoid occlusive disease of the internal carotid artery.

Isolated supraclinoid occlusive disease of the internal carotid artery is a rare cause of cerebral ischemia. The authors of the only review of this subject concluded that it is caused predominantly by factors other than atherosclerosis. We examined 6 patients with isolated supraclinoid occlusive lesions. Five of them had one or more risk factors for atherosclerosis. Thus, the isolated stenosis of that part of the internal carotid artery does not seem to represent a particular pathologic entity.

Cerebral perfusion reserve indexes determined by fluoromethane positron emission scanning.

An index of cerebral perfusion reserve (RES%), defined as the percent change of regional cerebral blood flow over baseline per mm Hg of end-tidal CO2 tension, was determined for each middle cerebral artery (MCA) territory in patients with unilateral carotid distribution transient ischemic attacks or minor cerebrovascular accidents and was compared with that of age-matched, neurologically normal volunteers. Vasodilator responses to induced hypercapnia were tested during inhalation of 5% CO2 in 95% O2 while regional cerebral blood flow was measured by fluoromethane inhalation positron emission tomography. Mean RES% for 24 normal MCA territories was 5.2 +/- 0.8%. Mean RES% for 15 patient nonischemic MCA territories was 3.8 +/- 1.3% and for 15 ischemic MCA territories was 2.8 +/- 1.9% (both p less than 0.001). Individual RES% values and symmetry ratios between ischemic and nonischemic regions were also determined and compared with angiographic data. Areas of diminished, asymmetric, or paradoxical (two patients) CO2 reactivity appear to correspond to areas of compensatory vasodilation. We found this technique to be a safe and reproducible method for defining and recording localized areas of cerebral tissue at apparent risk for hemodynamically related damage.

Contralateral flow reduction in unilateral stroke: evidence for transhemispheric diaschisis.

Using clinical presentation, angiography, computed tomography, and nuclear magnetic resonance imaging, 7 patients were identified who had strictly unilateral hemispheric infarction and unilateral cerebrovascular disease. In 6, cerebral blood flow measured by fluorine-18-fluoromethane inhalation and positron emission tomography was reduced in the contralateral hemisphere (p less than 0.05). Multiple regression analysis demonstrated a high correlation between contralateral flow reduction and the degree of flow impairment in the infarcted area (r = 0.941, p = 0.0014) but not with age, risk factor profile, blood pressure, PCO2, hematocrit, or duration of stroke. We conclude that transhemispheric diaschisis best explains the contralateral flow reduction seen in supratentorial ischemic stroke.