Showing papers in "Annals of Neurology in 1979"

Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-D-glucose: validation of method.

Abstract: Tracer techniques and quantitative autoradiographic and tissue counting models for measurement of metabolic rates were combined with positron computed tomography (PCT) and (F-18)2-fluoro-2-deoxy-D-glucose (FDG) for the measurement of local cerebral metabolic rate for glucose (LCMRGlc) in humans. A three-compartment model, which incorporates hydrolysis of FDG-6-PO4 to FDG, was developed for the measure of kinetic constants and calculation of LCMRGlc. Our model is an extension of that developed by Sokoloff et al. Although small, hydrolysis of FDG-6-PO4 was found to be significant. A PCT system, the ECAT, was used to determine the rate constants, lumped constant, and stability of the model in human beings. The data indicate that cerebral FDG-6-PO4 in humans increases for about 90 minutes, plateaus, and then slowly decreases. After 10 minutes, cerebral blood FDG activity levels were found to be a minor fraction of tissue activity. Precursor pool turnover rate, distribution volumes, and red blood cell-plasma concentration ratios were determined. Reproducibility (precision) of LCMRGlc measurements (approximate 2 cm2 regions) was +/- 5.5% over a 5-hour period. The replacement of arterial blood sampling with venous sampling was validated.

Mechanisms underlying hemispatial neglect

Abstract: If patients with left-sided hemispatial neglect bisect lines incorrectly because hemianopia or sensory hemiinattention prevents them from seeing how far the line extends to the left, a strategy that ensures their seeing the left side of the line in their normal field should improve performance. If patients have hemispatial hypokinesia, moving the line toward the normal half of body space should improve performance. Six patients with left-sided neglect from right hemisphere infarctions were required to identify a letter at either the right or the left end of a line before bisecting that line. The task was given with the lines placed at either the right, the center, or the left of the body midline. Performance in trials when subjects were required to look to the left before bisecting a line did not differ from when they were required to look right. Performance was significantly better when the line was placed to the right side of the body than to the left. These observations support the hypothesis that patients with hemispatial neglect have hemispatial hypokinesia. An alternative hypothesis is that these subjects had a hemispatial memory defect. Although they saw the left side of the line in their normal field, they were incapable of forming a stable trace and performed as if they did not see the left side of the line.

Creutzfeldt‐Jakob disease: Patterns of worldwide occurrence and the significance of familial and sporadic clustering

Abstract: The worldwide epidemiology of Creutzfeldt-Jakob disease (CJD) is presented from an analysis of 1,435 patients. In the United States, the average annual mortality rate is at least 0.26 deaths per million. Temporal-spatial clustering of cases was not found in the United States, but reports from other countries indicate that such clustering does occur. Fifteen percent of the cases were of the familial type, suggesting a genetic susceptibility to infection. Iatrogenic transmission by corneal transplantation and neurosurgical operations has occurred, and the possibility is raised that previous surgery or preexisting neurological operations has occurred, and the possibility is raised that previous surgery or preexisting neurological disease may be associated with an increased risk of developing CJD. It remains to be determined whether the virus of CJD is maintained only by patient-to-patient transmission, has a zoonotic reservoir such as scrapie, or causes widespread latent infection of man that is occasionally activated.

Cytoarchitectonic abnormalities in developmental dyslexia: A case study

Abstract: A patient is reported who had a well-documented history of developmental dyslexia. Reading difficulties were present in other male members of the immediate family. Gross anatomical and cytoarchitectonic analysis of the brain in serial sections showed a consistently wider left cerebral hemisphere, an area of polymicrogyria in the left temporal speech region, and mild cortical dysplasias in limbic, primary, and association cortices of the left hemisphere . Galaburda AM, Kemper TL: Cytoarchitectonic abnormalities in developmental dyslexia: a case study. Ann Neurol 6:94-100, 1979 Despite the fact that developmental dyslexia has been recognized for nearly 100 years, the structural basis for the disability has not been established. Only one brief report of the neuropathological findings has appeared [S]. Abnormal gyri were said to exist in the parietal regions, with accompanying thinning of related areas of the corpus callosum, and ectopic neurons were present in the subcortical white matter. An intriguing finding described recently by Hier and colleagues [ 151 in a computerized brain tomographic study in patients with developmental dyslexia is the presence of a disproportionately large number of brains with a wider right than left parietooccipital region, a reversal of the more common pattern of asymmetry in this area 1191. In the present study we report the results of a systematic survey of wholebrain serial sections in a well-documented case of developmental dyslexia. Case Report The patient was born at term after a normal gestation and delivery. There were no neonatal complications, and his early developmental milestones were judged to be normal. The only abnormality noted in early childhood was that the patient was clumsier than his siblings. Speech in full sentences was delayed until after the age of 3 years. Difficulties with reading and spelling were noted soon after entrance into elementary school, and he repeated the first grade. At that time the diagnosis of specific developmental dyslexia was first made. A routine neurological evaluation disclosed no abnormal findings, and the Stanford-Binet intelligence score was 105. The patient's difficulties persisted despite special tutoring, and at age 13 years he was given a battery of tests of intelligence and achievement, with repeat testing at ages 14, 15, and 19 years. The test results, which are summarized in the Table, showed that in spite

Remyelination in multiple sclerosis

Abstract: Chronic plaques in central nervous system tissue fixed by in situ perfusion for electron microscopy were examined for evidence of remyelination in 2 patients with multiple sclerosis (MS). Fibers with abnormal central myelin sheaths of several types were found at the margins of most of the plaques studied. The most common of these were: (1) the presence of bare stretches of axon between contiguous internodes, (2) the presence of thin paranodes, (3) internodes which changed markedly in thickness along their length due to premature termination of superficial or deep myelin lamellae that ended as hypertrophic lateral loops, and (4) abnormally thin internodes which were of uniform thickness along their length, which were shorter than normal, and which terminated in the form of normal nodal complexes. The finding of internodes of the last type at the edges of many plaques indicates that remyelination by oligodendrocytes can occur in the adult human CNS and that it is common in some cases of MS, although limited in its extent.

Brain electrical activity mapping (BEAM): a method for extending the clinical utility of EEG and evoked potential data.

Abstract: The difficulties inherent in extracting clinically useful information by visual inspection alone from the massive amounts of data contained in multichannel polygraphic recordings have placed limits on the accuracy and range of utility of electroencephalography and evoked potentials. A method for condensing and summarizing the spatiotemporal information contained in recordings from multiple scalp electrodes is described. Data dimensionality is reduced and visibility increased by computer-controlled topographic mapping and display of data as color television images. Examples are given in which such brain electrical activity mapping (BEAM) (1) localizes tumors in patients with normal or nondiagnostic EEGs, (2) adds additional information to that visible on computerized axial tomography, and (3) demonstrates electrophysiological abnormalities in patients with functional lesions but normal CT scans. A sensitivity to the functional component of a neurological lesion suggests that BEAM may provide complementary information to the anatomical definition provided by the CT scan.

Dementia in Parkinson Disease.

Abstract: In 520 patients with parkinsonism seen over eight years, 168 (32%) had moderate to marked dementia. Although the demented patients were older than the nondemented patients (70.4 versus 65.5 years), the incidence of dementia in Parkinson's disease (PD) was tenfold higher than among controls (similarly aged spouses of PD patients), and dementia is held to be related more to the disease than to age. Demented patients, in addition to being older, developed PD later, were more severely involved in a shorter time, and responded less well to levodopa. It is suggested that PD with dementia may represent a different disorder from PD without dementia.

Dorsal thalamic lesion in a noted case of human memory dysfunction

Abstract: The extensively studies patient N. A. has had a severe verbal memory deficit since 1960, when he sustained a stab wound to the brain with a miniature fencing foil. His amnesia occurs in the absence of any other know cognitive defect. Recent CT scans have localized a lesion in the left dorsal thalamus of this patient in a position corresponding to the dorsomedial nucleus; there is no radiographic evidence of other damage in the diencephalon or cerebral cortex. The dorsomedial thalamus may be critical in the neuropathology of diencephalic amnesia and, in humans, may be required for normal functions.

Alzheimer neurofibrillary tangles in diseases other than senile and presenile dementia.

Abstract: A brief description is given of neurofibrillary changes of the paired helical filament type in a variety of chronic neurological diseases. These include subacute sclerosing panencephalitis, lead encephalopathy, tuberous sclerosis, Down syndrome, Hallervorden-Spatz disease, and lipofuscinosis. In these conditions, with the exception of Hallervorden-Spatz disease neurofibrillary changes were previously recognized but paired helical filaments were identified only in some cases. Moreover, in the present series, the age of patients at death was often younger than in previously recorded cases.

A hypothetical explanation of saccadic oscillations.

Abstract: Eye movements in a patient with saccadic oscillations (ocular flutter) were recorded and analyzed. Findings were related to recent microelectrode studies in the monkey pontine reticular formation which have identified three types of premotor neurons related to saccadic eye movements: burst, tonic, and pause cells. We incorporated these cell types into a hypothetical circuit that generates saccades by rapidly driving the eye to a designated orbital position rather than preprogramming a distance for movement. Physiological measurements suggest that this neural network is unstable and that the burst neurons must be tonically inhibited to prevent saccadic oscillations during periods of fixation. Pause cells, which discharge tonically except during saccades, when they pause, appear to inhibit burst cells and prevent such saccadic oscillations. Analysis of our patient's behavior indicates that many types of saccadic oscillations can be explained and classified by assuming an abnormality of pause cell control over saccadic burst neurons.

Precise characterization and quantification of infantile spasms.

Abstract: With the use of a time-synchronized video and polygraphic recording system, 5,042 infantile spasms were monitored and analyzed in 24 infants aged 1 to 43 months. Of these, 33.9% were flexor, 22.5% extensor, and 42.0% mixed flexor-extensor. Sometimes the spasms were followed by a period of akinesia and diminished responsiveness lasting up to 90 seconds, and rarely (1.0%) this "arrest" effect constituted the entire seizures. More than one type of seizure occurred in 21 of the 24 infants. In the same number, 78.3% of the seizures occurred in clusters, and the intensity and frequency of the spasms in each cluster often increased to a peak, then progressively decreased until they stopped. Predominantly, the clusters occurred soon after arousal from sleep. The number of seizures occurring at night (55.2%) was similar to the diurnal number (44.8%). The electroencephalographic seizure pattern was variable, but a marked generalized attenuation of electrical activity was a feature of 71.7% of the attacks. Attenuation episodes of similar degree and duration occurred with no evidence of a seizure.

Suppressor cell function in multiple sclerosis: Correlation with clinical disease activity

Abstract: Concanavalin A (Con A)-activated suppressor cell activity was determined in multiple sclerosis (MS) patients who had been assigned to one of three subgroups, those with active disease, those recovering from a flare-up, and those with stable disease. The level of suppression induced by the Con A-activated suppressor cells on the mitogenic response of autologous peripheral blood lymphocytes was reduced in patients with active disease (3 +/- 8%) compared with stable patients (30 +/- 8%), patients recovering from a flare-up (62 +/- 5%), and controls (40 +/- 5%). As a measure of the actual amounts of suppressor factors released, the effect of supernatants from the Con A-activated cells on the proliferative activity of a dividing cell line (L cells) was determined concurrently. The inhibitory effect of supernatants from activated cells was reduced in active and stable MS patients (7 +/- 3%) compared to controls (21 +/- 4%). Three of 4 with active MS showed mildly elevated immune complex levels as measured by the Raji cell technique; each of these patients had low suppressor activity. Levamisole (1 microgram per milliliter) failed to alter suppressor cell activity in our in vitro system.

Multiple sclerosis in the faroe islands: I. Clinical and epidemiological features

Abstract: Intensive search over the past five years for all cases of multiple sclerosis (MS) on the Faroe Island since about 1920 has revealed 25 cases among native-born resident Faroese up to 1977. All but 1 patient had clinical onset of MS between 1943 and 1960; 1 case began in 1970. Four cases of MS in Faroese with prolonged foreign residence and 5 among Danish-born Faroese were excluded. The 24 included cases with onset between 1943 and 1960 meet all criteria for a point-source epidemic. The median year of onset was 1949. The cumulative risk of MS for Faroese in 1940 was 8.7 per 10,000. All 14 early-onset cases (1943 to 1949) were in patients 11 to 45 years old in 1940; all but 2 late-onset cases (1952 to 1960) were in persons aged up to 10 years old in 1940. British troops occupied the Faroese in large numbers for five years beginning in April, 1940. During the war, all but 3 patients resided in locations where the troops were stationed, and these 3 also had direct contact with the British. We conclude that there was an epidemic of MS on the Faroes and that the disease was probably introduced by the British troops (or their baggage). If so, then MS on the Faroes is a transmissible disease, most likely infectious; but only about 1 in 500 of the exposed individuals were clinically affected.

Does a defect of energy metabolism in the nerve fiber underlie axonal degeneration in polyneuropathies

Abstract: A number of chemically unrelated neurotoxic compounds and several types f metabolic abnormalities cause strikingly similar patterns of distal symmetrical polyneuropathy in humans and animals. Experimental studies with laboratory species have demonstrated that many toxic polyneuropathies are associated with distal and retrograde axonal degeneration occurring in vulnerable nerve fiber tracts in the central as well as the peripheral nervous system. This has been termed central-peripheral distal axonopathy. Recent observations from the authors' laboratories regarding (1) the spatial-temporal evolution of nerve fiber degeneration in experimental toxic neuropathies and (2) the inhibition of glycolytic enzymes by chemically unrelated neurotoxic compounds point to a common metabolic basis for many distal axonopathies. It is postulated that neurotoxic compounds deplete energy supplies in the axon by inhiniting nerve fiber enzymes required for the maintenance of energy synthesis. Resupply of enzymes from the neuronal soma fails to meet the increased demand for enzyme replacement in the axon, causing the concentration of enzymes to drop in distal regions. This leads to a local blockade of energy-dependent axonal transport, which produces a series of pathological changes culminating in distal nerve fiber degeneration. The idea provides a working hypothesis with which to study the cause of inherited and acquired human and animal polyneuropathies.

The decreasing incidence of primary intracerebral hemorrhage: a population study.

Abstract: This population study describes the experience with primary intracerebral hemorrhage (PIH) in residents of Rochester, MN, for the 32-year period from 1945 through 1976. The average annual age-adjusted incidence rate for PIH was 12.1 per 100,000 population, and the incidence for all cases of spontaneous intracerebral hemorrhage was 15.2 per 100,000. The PIH rates were higher for males than for females, and they increased steadily with age. When patients on long-term anticoagulant therapy were excluded, there was a steady decrease in the average annual age-adjusted incidence rate for PIH in each succeeding 8-year interval since 1945. Prehemorrhage hypertension, present overall in 89% of patients, was much more frequent and severe in the earlier years of the study. The frequency and severity of prehemorrhage hypertension also varied inversely with age in the population with PIH. The median age at the onset of PIH increased from 65 years for the period 1945 through 1952 to 71 years for 1969 through 1976.

Ocular tilt reaction with peripheral vestibular lesion

Abstract: Following inadvertent destruction of the left vestibular labyrinth during stapedectomy, a patient developed a transient abnormality of posture consisting of leftward ocular counterrolling, leftward had tilting, and a right-over-left skew deviation. This postural pattern, known as the "ocular tilt reaction," is the normal compensatory response of the dependent utricle to tilting. In this patient, the unopposed action of the intact right utricle was presumably responsible for the appearance of a normal leftward ocular tilt reaction.

Transmission of chronic spongiform encephalopathy with kuru plaques from humans to small rodents.

Abstract: An unusual case of spongiform encephalopathy was transmitted directly from a human to rats and mice. After serial passages, incubation periods were shortened to about six months in rats and four months in mice. Clinical symptoms were similar in rats and mice, including ruffled fur, arched back, bradykinesia, and hind limb paralysis. Pathologically, a spongy state, proliferation of astrocytes, and neuronal changes were observed. Electron microscopic observation of the parietal cortex of rats and mice disclosed many membrane-bound vacuoles in the neuropil, predominantly in dendrites. In the pons of mice, intramyelinic vacuoles and accumulation of extracellular fluid were prominent. The clinicopathological symptoms of the affected animals resembled those in other experimental spongiform encephalopathies, especially scrapie.

Effects of physostigmine and lecithin on memory in Alzheimer disease

Abstract: Because there is evidence that central cholinergic mechanisms are depleted in dementia, we studied the effects of central cholinergic augmentation on the memory of 5 patients with Alzheimer disease. Patients received placebo, lecithin, physostigmine, or lecithin plus physostigmine in a double-blind study using titrated doses of the acetylcholinesterase inhibitor physostigmine. Memory was evaluated with alternate forms of the selective reminding procedure. Compared with lecithin alone, the combination of physostigmine and lecithin consistently enhanced memory storage and retrieval; physostigmine without lecithin produced no memory facilitation. The strategy of combining a cholinergic agonist and precursor holds promise, although a larger clinical trial is needed.

Biogenic amine metabolism in tourette syndrome

Abstract: Biogenic amine metabolism in the central nervous system of 9 children with Tourette syndrome was evaluated by quantitation of their metabolites in cerebrospinal fluid by a gas chromatographic/mass spectrometric method. Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) were measured in CSF before and after oral administration of probenecid. Dopamine metabolism appeared defective, as both baseline and accumulated levels of HVA after probenecid were decreased. Serotonin metabolism also appeared defective in some patients with low baseline and low accumulated levels of 5-HIAA after probenecid. Taken together with other clinical features of this disease, the results suggest an underlying disorder of dopamine and serotonin metabolism in Tourette syndrome.

Language deficits after apparent clinical recovery from childhood aphasia

Abstract: Twenty-seven children with childhood injury to the left hemisphere were tested for language function and compared with appropriate controls Eleven children had incurred their lesions before the age of 1 year, 16 afterward The group with perinatal injury to the left hemisphere did not show a specific aphasic deficit even though they were mildly cognitively impaired The group of children with later injury to the left hemisphere showed aphasic deficits if the original injury had caused a language defect; otherwise the left hemisphere injury was not associated with specific disturbances in language function The average age at time of lesion in those children who had recovered from aphasia was 47 years We conclude that even when childhood aphasia results from a unilateral nonprogressive lesion, recovery of language is less complete than has been generally supposed

High-dose barbiturate therapy in humans: A clinical review of 60 patients

Abstract: Over the past three years, high-dose barbiturate therapy has been used in the treatment of 60 patients with head injury (N = 45), encephalitis (N = 8), acute focal cerebral ischemia (stroke, N = 4), and global anoxia secondary to drowning (N = 3). High-dose barbiturates appear to be useful adjuncts in the control of intracranial hypertension refractory to other methods of therapy. Administration of barbiturates to patients with this problem will often reduce the requirement for osmotic agents, thereby facilitating medical management by avoiding hyperosmolality and fluid and electrolyte depletion. In a carefully controlled intensive care setting the risk of barbiturate therapy is low, though the costs and demands on personnel are great. Survival appeared to be improved in aptients with ,head injury and encephalitis. Although the ultimate outcome was not altered in patients with stroke or near-drowning, intracranial hypertension did not occur until barbiturate therapy was withdrawn. This experience provides an ethical basis to justify further randomized studies for determining whether or not barbiturates materially improve the neurological outcome following cerebral ischemic and traumatic insults.

Cerebral infarcts with arterial occlusion in neonates.

Abstract: Among 592 infants examined at autopsy during a four-year period, 32 (5.4%) had cerebral infarcts. Excluded were cases of traumatic hemorrhages and softening, periventricular leukomalacia, venous lesions, and any mass, including encephaloceles, with arterial distortion and infarction. Histological abnormalities were similar to those of infarcts in adults. Relatively advanced histopathological changes in some infants living only a few hours indicated that some infarctions may have occured in utero. The most common cause of arterial occlusion was embolization, with sepsis and disseminated intravascular coagulation playing a major role. The brains of term neonates were more frequently involved than those of premature infants. Multiple small infarcts occurred more often in premature infants. In most cases autonomic dysfunction with prolonged apnea, episodic seizures, and metabolic acidosis were the major associated clinical features, rather than focal neurological deficits. Similar cerebral infarcts in infants who survive with less severe systemic complications may lead to porencephaly, hemiplegia, mental and motor retardation, and recurrent seizures.

Emery‐dreifuss muscular dystrophy

Abstract: A man had weakness of humeroperoneal distribution associated with limited range of motion of the cervical spine and elbows. At age 25 he developed permanent atrial paralysis, and a cardiac pacemaker was inserted. Although this case was sporadic, most others have been transmitted as an X-linked recessive trait. Mixed patterns in electromyography and muscle histology have caused nosological confusion, but the unique clinical signs seem to define a distinct form of muscular dystrophy, warranting the designation "emery-Dreifuss" type.

An explanation for the localization of herpes simplex encephalitis

Abstract: Herpes simplex virus encephalitis tends to localize to the temporal and orbitofrontal lobes, giving characteristic clinical and pathological findings. Since the virus remains latent in the trigeminal ganglia, we postulate that this localization may be explained by reactivated virus spreading along the fifth nerve fibers, which innervate basal meninges of the anterior and middle fossae.

Subacute motor neuronopathy: a remote effect of lymphoma.

Abstract: Ten patients developed a subacute lower motor neuron syndrome as a remote effect of Hodgkin's disease or other lymphoma. The illness usually followed a benign course independent of the activity of the underlying neoplasm. Seven of the patients improved spontaneously, and 3 became neurologically normal. Two patients died of intercurrent infections related to immunosuppression. Neuropathological examination of these 2 patients and 3 previously reported cases showed prominent neuronal degeneration restricted to the anterior horns of the spinal cord and mild posterior column demyelination. Demyelination was also present in the anterior roots of our autopsied patients and was accompanied by large, hyperchromatic Schwann cells. The cause of the illness is obscure, but both radiation therapy and opportunistic infection may be contributing factors. Attempts at virus isolation have been unsuccessful. The syndrome should be distinguished from the more common direct effects of lymphoma on the nervous system, since its identification spares the patient additional, potentially harmful therapy.

Agenesis of the corpus callosum: A study of the frequency of associated malformations

Abstract: Review of 11 cases of agenesis of the corpus callosum studied at our institution revealed a high incidence of associated anomalies. Nine patients had associated malformations of the central nervous system, 6 involving the pyramidal system. Eight cases were associated with malformations in the rest of the body. Review of completely examined cases from the literature yielded 47 examples of associated malformations. These were varied and without consistent pattern, with the possible exception of facial abnormalities.

The natural history of peripheral neuropathy in primary systemic amyloidosis

Abstract: The records of 31 patients with primary systemic amyloidosis and peripheral neuropathy seen during a 17-year period were analyzed to define the natural history of the neuropathy. Patients tended to be older men with a painful, distal, symmetrical sensorimotor neuropathy and prominent autonomic features. Loss of pain and temperature sensation was frequently more striking than loss of mechanoreception. Renal, cardiac, hematological, and gastrointestinal dysfunction often overshadowed the neuropathy. Clinical, neurophysiological, and histopathological studies pointed to axonal degeneration with predominant but not exclusive involvement of small myelinated and unmyelinated fibers. The neuropathy was progressive in all patients with or without treatment, but death was typically due to supervening medical complications.

Defective activation of the pyruvate dehydrogenase complex in subacute necrotizing encephalomyelopathy (leigh disease)

Abstract: Autopsy examination confirmed the diagnosis of subacute necrotizing encephalomyelopathy (SNE) in a 7-month-old male infant who underwent several metabolic studies before death. Intermittent lactic acidemia and fumaric aciduria, an extreme hyperglycemic response to an intravenous bolus of alanine, and an elevated total body flux rate of glucose (58.4 mumoles . kg-1 . min-1) suggested a disturbance in the oxidative decarboxylation of pyruvate. Enzymological studies of postmortem samples revealed low nonactivated pyruvate dehydrogenase activity in liver (19.4%) and brain (53.8%). The lowest brain pyruvate dehydrogenase activities were noted in the midbrain and pontine regions. Supramaximal activation of the hepatic pyruvate dehydrogenase complex (135% of control values) occurred in vitro. Spontaneous reactivation following in vitro inactivation of the complex with adenosine triphosphate was significantly less (p less than 0.02) in the patient's samples compared to controls. The biochemical defect was not apparent in fibroblasts. These enzymological observations point to an in vivo defect in the activation mechanism of the pyruvate dehydrogenase complex as the biochemical disturbance in SNE. The findings suggest that dichloroacetate may be beneficial in treating SNE.

Mechanisms of acute carotid stroke.

Abstract: In a three-year study, the clinical course and results of intracranial angiography were compared in patients having an acute stroke in the carotid artery territory combined with angiographic abnormalities indicating severe extracranial carotid stenosis or occlusion. Two major mechanisms of stroke were delineated. In one group, the angiographic intracranial abnormalities strongly suggested the presence of embolism in the cerebral vessels supplied by the stenotic or occluded carotid artery; many of these patients had no obvious transient ischemic attacks prior to their stroke and experienced a moderate to severe clinical deficit. In the other group, evidence of embolism was absent; many showed a widespread delay in cerebral arterial perfusion, experienced a greater frequency of transient ischemic attacks before their stroke, and had a milder stroke than did those with embolism.