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We studied the relation of serum glucose level measured in the first 12 hours of symptoms to the clinical findings, results of computed tomography (CT), and patterns of cerebral metabolism in 39 patients who had acute ischemic cerebral infarction. Structural damage was assessed by CT. Metabolic disruption was assessed using 18F-fluorodeoxyglucose and positron emission tomography (PET). Median initial serum glucose concentration was 155 mg/dl (6.7 mM). Clinical recovery was significantly poorer in patients with initial serum glucose levels higher than the median (p less than 0.05, chi square). PET tended to show normal results or minor abnormalities in patients with initial glucose levels less than the median, as opposed to lobar or multilobe abnormalities in patients with levels that were higher than the median (p less than 0.05, Kendall's Tau b). The severity of hypometabolism in the ischemic region, expressed as the percent asymmetry of local cerebral glucose metabolism between homologous brain regions, was greater in patients with initial glycemia concentrations higher than the median (p less than 0.001, t test). Relationships of serum glucose level with metabolic derangement and structural damage, but not outcome, held true in patients without a history of diabetes mellitus.

We used x-ray computed tomographic (XCT) scans to measure the degree of cerebral atrophy in brain regions defined by a region of interest (ROI) anatomy atlas. The same atlas was employed for quantitation of local cerebral glucose metabolic rates (LCMRglc) by PET. PET data were obtained from 9 young controls, 7 healthy elderly controls, and 10 patients with dementia. Cerebrospinal fluid (CSF) in atrophic brain regions was assumed to be metabolically inert, and LCMRglc measurements were corrected for the degree of atrophy. Significantly greater atrophy was seen for 7 of 8 regions in comparisons between demented patients and age-matched controls. This atrophy was most pronounced in superior parietal (SP) regions. Decreases in parietal LCMRglc in dementia patients and SP LCMRglc in old controls were no longer significant after correction for atrophy. These results emphasize the need to consider focal atrophy effects in regional quantitative analyses of emission tomographic data.

To the Editor. —In an imaging study of Alzheimer's disease and normal aging, Leys et al, 1 using our rating scale, 2 found no difference in magnetic resonance imaging white matter hyperintensities between the two groups, and only a trend toward increased periventricular hyperintensity in patients with Alzheimer's disease. This is in contrast to our initial observation of a hyperintense "halo" in six of 12 cases of Alzheimer's disease. 2 We would like to emphasize, however, that a part of us (F.F., R.S., H.O.) could not replicate this finding in a subsequent study performed under similar conditions. There still remains a trend toward more signal abnormalities in Alzheimer's disease, however. The Table summarizes the current data from subjects without cerebrovascular risk factors in this ongoing project. 3 A disproportionately higher number of patients with more marked ventricular enlargement in our first study appears to be the likeliest explanation for these

We studied the patterns of cerebral blood flow (CBF), over time, in patients with systemic lupus erythematosus and varying neurologic manifestations including headache, stroke, psychosis, and encephalopathy. For 20 paired xenon-133 CBF measurements, CBF was normal during CNS remissions, regardless of the symptoms. CBF was significantly depressed during CNS exacerbations. The magnitude of change in CBF varied with the neurologic syndrome. CBF was least affected in patients with nonspecific symptoms such as headache or malaise, whereas patients with encephalopathy or psychosis exhibited the greatest reductions in CBF. In 1 patient with affective psychosis, without clinical or CT evidence of cerebral ischemia, serial SPECT studies showed resolution of multifocal cerebral perfusion defects which paralleled clinical recovery.

The type, frequency, and extent of MR signal abnormalities in Alzheimer's disease and normal aging are a subject of controversy. With a 1.5-MR unit we studied 12 Alzheimer patients, four subjects suffering from multiinfarct dementia and nine age-matched controls. Punctate or early confluent high-signal abnormalities in the deep white matter, noted in 60% of both Alzheimer patients and controls, were unrelated to the presence of hypertension or other vascular risk factors. A significant number of Alzheimer patients exhibited a more extensive smooth "halo" of periventricular hyperintensity when compared with controls (p = .024). Widespread deep white-matter hyperintensity (two patients) and extensive, irregular periventricular hyperintensity (three patients) were seen in multiinfarct dementia. Areas of high signal intensity affecting hippocampal and sylvian cortex were also present in five Alzheimer and two multiinfarct dementia patients, but absent in controls. Discrete, small foci of deep white-matter hyperintensity are not characteristic of Alzheimer's disease nor do they appear to imply a vascular cause for the dementing illness. The frequently observed "halo" of periventricular hyperintensity in Alzheimer's disease may be of diagnostic importance. High-signal abnormalities in specific cortical regions are likely to reflect disease processes localized to those structures.

The (F-18) fluorodeoxyglucose (FDG) technique to measure local cerebral metabolic rate for glucose (LCMRglu) is well accepted and widely used by many institutions around the world. A large number of studies has been carried out in normal volunteers and patients with a variety of CNS disorders. Several investigators have noted that no significant age-related changes in cerebral glucose use occur with normal aging. Some important and interesting findings have been revealed following sensory, motor, visual, and auditory stimulations. Functional imaging with FDG in certain neurologic disorders has dramatically improved our understanding of their underlying pathophysiologic phenomena. Some abnormalities detected on the positron emission tomography (PET) images have no corresponding changes on either x-ray computed tomograms (XCT) or magnetic resonance images (MRI). In patients with Alzheimer's disease, primary sensorimotor, visual, and cerebellar metabolic activity appears relatively preserved. In contrast, parietal, temporal, and to some degree, frontal glucose metabolism is significantly diminished even in the early stages of the disease. Patients with Huntington's disease and those at risk of developing this disorder have a typical pattern of diminished CMRglu in the caudate nuclei and putamen. In patients with stroke, PET images with FDG have demonstrated abnormal findings earlier than either XCT or MRI and with a wider topographic distribution. FDG scans have revealed interictal zones of decreased LCMRglu in approximately 70% of patients with partial epilepsy. The location of the area of hypometabolism corresponds to the site of the epileptic focus as determined by electroencephalography and microscopic examination of the resected tissue. Ictal scans during partial seizures demonstrate areas of hypermetabolism corresponding to the sites of seizure onset and spread. Several investigators have reported relative hypofrontal CMRglu in patients with schizophrenia. In our center, FDG scans from patients with schizophrenia were successfully differentiated from those obtained in normal controls. Finally, our preliminary data (using PET, XCT, and MRI) in patients with CNS disorders indicate that MRI provides excellent delineation of the structural abnormalities. It may prove to be superior to XCT in the evaluation of certain diseases such as cerebral ischemia and infarcts, head injury, tumors, and white matter lesions. Metabolic imaging with FDG provides functional information not obtainable with either MRI or NMR spectroscopy. Therefore, PET studies will play a complementary role to the anatomic imaging in the management of patients with CNS disorders.

Positron emission tomography (PET) studies have been performed using 18-F-fluorodeoxyglucose in 29 adult subjects with primary brain tumors. Seventy-two percent of the patients were treated previously. The glucose metabolic state in the lesions was increased in 16 patients, and was normal or decreased in 13 patients. The hypermetabolic tumors tended to behave in a more malignant fashion. Patients with hypermetabolic tumors had a median survival of 7 months after PET scan, compared to 33 months for those with hypometabolic lesions. Among the high-grade glioma patients, the PET results separated them into a good prognosis group (hypometabolic, with 78% 1-year survival) and a poor prognosis group (hypermetabolic, with a 29% 1-year survival after PET). These results suggest that glucose metabolic studies may provide an independent measure of the aggressiveness of a brain tumor, and may supplement pathologic grading.

Slowly progressive aphasia without generalized dementia is a degenerative syndrome selectively affecting dominant hemisphere language areas. We report changes in regional glucose metabolism measured by positron emission tomography in two patients with this condition. Striking abnormalities of glucose utilization in the left cerebral cortex were demonstrated in both patients. The findings of other neurodiagnostic studies were relatively unremarkable. The first patient had a 3-year history of progressive anomia and impaired auditory verbal recall. An electroencephalogram was normal, and computed tomography showed mild left perisylvian atrophy. Positron emission tomography revealed profound hypometabolism in the left temporal regions. The second patient also had a 3-year history of progressive anomia. Electroencephalography, computed tomography, and magnetic resonance imaging scans were normal. Positron emission tomography showed a major reduction in left parietal glucose utilization, with a lesser decrement in left temporal metabolism. Neither patient demonstrated significant contralateral or global abnormalities such as those reported in positron emission tomographic studies of Alzheimer's disease with or without focal clinical features. These observations support the concept of adult-onset progressive aphasia without dementia as a clinical syndrome distinct from Alzheimer's disease.

The authors examined eight patients with dementia of the Alzheimer's type (DAT), five with prominent visual symptoms early in the illness (VS) and three with no visual symptoms (NVS). Results of neuro-ophthalmologic examinations on VS patients showed relatively consistent abnormalities in figure copying, color vision tested by isochromatic plates, and stereopsis. Cerebral glucose metabolism determined by 18F-fluoro-2-deoxyglucose positron emission tomography (PET) was unchanged in primary visual cortex of VS and NVS patients compared with 12 normal volunteers of similar age and sex. Glucose metabolism in VS patients was decreased by 45 and 34% in left and right visual association cortex (P less than 0.01 and P less than 0.05, respectively) and 34 and 37% in left and right inferior parietal cortex (P less than 0.05) compared with controls; NVS patients had no significant metabolic alteration in these areas. Symptoms, physical examination, and metabolic imaging imply that these patients are a heterogenous but distinct clinical subgroup of DAT often with mild dementia who have visual symptoms due primarily to visual agnosia.

We report resolving metabolic abnormalities corresponding to clinical improvement in a patient with pure alexia secondary to acute cerebral infarction. Local cerebral glucose metabolism (lCMRgl) was measured with positron emission tomography (PET) using 18 F-fluorodeoxyglucose ( 18 F-FDG) close to ictus and 4 1 / 2 months later. Serial CTs and a subsequent MRI demonstrated small, unchanging left-hemispheric lesions involving the area of the lateral geniculate body and the splenium of the corpus callosum. PET demonstrated the evolution of the metabolic abnormality resulting from intrahemispheric (lateral geniculate) and interhemispheric (splenium) disconnection in the absence of occipital lobe infarction. This case illustrates that cerebral disconnection can result in the syndrome of pure alexia. The factors accounting for focal hypometabolism in the absence of cerebral infarction are discussed.

We used [18F]fluoro-2-deoxyglucose positron emission tomography (PET) to study serial changes in the local cerebral metabolic rate of glucose in 5 patients with ischemic lesions of the posterior afferent visual system causing homonymous visual field defects. All 5 patients had striking impairment of glucose metabolism in the striate cortex shortly after ictus. In 2 patients, visual field defects abated, and repeat PET scans showed reduced size of the metabolic lesion and improvement of striate metabolism. Three patients did not recover vision, and repeat PET scans did not show improvement. Patients who recovered vision had ischemic lesions outside the occipital lobe, while those who did not experience improvement had primary damage to the occipital lobe itself.

We studied cerebellar metabolism in 118 subjects including young and elderly controls and patients suffering from stroke, supratentorial brain tumor and Alzheimer's disease using fluorine-18 fluorodeoxyglucose ([18F]FDG) and position emission tomography (PET). Alzheimer's disease and normal aging did not alter mean cerebellar metabolism. In stroke and tumor mean cerebellar metabolism was lower in the hemisphere contralateral to the supratentorial lesion. In tumor bilaterally significant reductions in absolute cerebellar metabolism also were noted, unlike stroke. Primary sensory stimulation did not alter absolute or relative cerebellar metabolism. These results show that absolute and relative values for cerebellar metabolism vary depending on the process under study. Thus analysis schemes employing normalization of regional metabolic data to cerebellar values may be subject to error.

Associations have been described between task difficulty and autonomic arousal. This study addresses task difficulty effects on regional cerebral blood flow (rCBF), a measure of cortical activity. Earlier work suggested that in contrast to a positive association between anxiety and autonomic arousal, there is a curvilinear, inverted-U relationship between anxiety and cortical activity. A sample of 26 normal volunteers (14 men, 12 women) was administered the 133-Xenon inhalation technique for measuring rCBF. Measurements were taken under three conditions: Resting baseline, and Easy and Hard verbal analogy tasks. Subjects were grouped into three anxiety levels on the basis of their average score on a self-report measure. The rCBF was higher during task performance than at rest, but did not differ between the two difficulty conditions. There were Task × Hemisphere interactions showing the expected asymmetry of activation, with higher left hemispheric increase for the verbal task. Anxiety had an inverted-U relationship with both performance and rCBF, which were themselves positively related. These results with measures of central nervous system activity differ from those reported for autonomic responses. They indicate that anxiety effects on cortical activity may mediate the relation between anxiety and performance.

The extracranial carotid systems of 105 patients with retinal ischemia were examined using B-mode ultrasonography with integrated pulsed Doppler. Sixty-four patients had amaurosis fugax (AF), 17 central retinal artery occlusions (CRAO), and 21 branch retinal artery occlusions (BRAO). The prevalence of carotid stenosis (greater than or equal to 60%) ipsilateral to the symptomatic eye was low (16%). Eighty-six percent of AF patients had either no plaque causing less than a 60% stenosis. A significant proportion of subjects with normal duplex scans had alternative explanations for their retinal ischemia (eg, migraine, cardiac embolus). Patients with Hollenhorst plaques were more likely to have stenotic or ulcerated plaque (p = 0.04). The degree of carotid stenosis correlated significantly with the number of vascular risk factors identified in individual patients (p = 0.02). The presence of risk factors was more common in CRAO and BRAO patients compared with the AF group. Combined ultrasound-Doppler investigations of the carotid bifurcation are valuable noninvasive tools for the screening of patients with retinal ischemia.

Previous reports of emission tomography studies in acute stroke mainly have been concerned with cerebral perfusion and metabolism within the ischemic lesion. Measurements have been made of regional cerebral blood flow (rCBF) and regional cerebral oxygen consumption (rCMRO2) and have allowed the definition of the regional oxygen extraction ratio (rOER) in ischemic areas [1, 4, 12].

We measured mean cerebral blood flow (CBF) in 25 lupus patients using the xenon-133 method. The CBF was normal in lupus patients without cerebral disease and also in CNS lupus patients in remission. The CBF was lower than normal during bouts of cerebral lupus (p less than 0.001). Repeat studies showed a stereotyped pattern consisting of depressed CBF during exacerbation of CNS disease and normalization of CBF during remission (p less than 0.01). These results show that CBF is a sensitive indicator of activity of CNS disease and that the direction of change in CBF reflects the clinical course of CNS lupus.

Positron emission tomography is a noninvasive tomographic technique for measuring regional tissue concentrations of labeled radionuclides in man. Detection of two photons emitted from the annihilation of a positron and an electron is used to reconstruct the distribution of a positron-emitting isotope within an organ. PET provides the capacity to measure quantitatively the local tissue distribution of a variety of radionuclides that are attached to compounds that distribute according to function. Commonly measured functions include local cerebral metabolism using 18F-fluorodeoxyglucose or 11C-deoxyglucose, cerebral blood flow, cerebral oxygen utilization, and cerebral blood volume. Clinical applications of PET are multiple, involving normal and disease states. By demonstrating the metabolic alterations, PET adds another dimension to our understanding of the brain, which up until recently has been based on the structural changes seen on CT and MRI.

Positron emission tomography (PET) studies have been performed using 18-F-fluorodeoxyglucose in 29 adult subjects with primary brain tumors. Seventy-two percent of the patients were treated previously. The glucose metabolic state in the lesions was increased in 16 patients, and was normal or decreased in 13 patients. The hypermetabolic tumors tended to behave in a more malignant fashion. Patients with hypermetabolic tumors had a median survival of 7 months after PET scan, compared to 33 months for those with hypometabolic lesions. Among the high-grade glioma patients, the PET results separated them into a good prognosis group (hypometabolic, with 78% 1-year survival) and a poor prognosis group (hypermetabolic, with a 29% 1-year survival after PET). These results suggest that glucose metabolic studies may provide an independent measure of the aggressiveness of a brain tumor, and may supplement pathologic grading.

Positron emission tomography (PET) studies with 18F deoxyglucose were completed in 35 patients with acute ischemic strokes. Twelve cases were studied within 72 h, 23 between 4 and 14 days. Results indicate the functional and prognostic significance of early tomography studies of metabolism, and anticipate possible use of metabolic imaging in the evaluation of treatment.

The authors examined eight patients with dementia of the Alzheimer's type (DAT), five with prominent visual symptoms early in the illness (VS) and three with no visual symptoms (NVS). Results of neuro-ophthalmologic examinations on VS patients showed relatively consistent abnormalities in figure copying, color vision tested by isochromatic plates, and stereopsis. Cerebral glucose metabolism determined by 18F-fluoro-2-deoxyglucose positron emission tomography (PET) was unchanged in primary visual cortex of VS and NVS patients compared with 12 normal volunteers of similar age and sex. Glucose metabolism in VS patients was decreased by 45 and 34% in left and right visual association cortex (P less than 0.01 and P less than 0.05, respectively) and 34 and 37% in left and right inferior parietal cortex (P less than 0.05) compared with controls; NVS patients had no significant metabolic alteration in these areas. Symptoms, physical examination, and metabolic imaging imply that these patients are a heterogenous but distinct clinical subgroup of DAT often with mild dementia who have visual symptoms due primarily to visual agnosia.

Positron emission tomographic exploration of local cerebral metabolism in acute cerebrovascular diseases have concentrated mostly on the use of 150.

Dementia is a progressive clinical state characterized by the deterioration of intellect, memory, judgment, and abstract thinking (Diagnostic and Statistical Manual III 1980). The syndrome has many etiologies and is a leading cause of disability among the elderly in the U.S. and Europe. A prevalence of as high as 5% in people over 65 years has been estimated in recent surveys (Katzman 1976; Terry 1976). By far the most common cause of dementia in the world today is Alzheimer’s disease, or dementia of the Alzheimer type (DAT), a primary degenerative process identifiable pathologically by its classic microscopic findings of amyloid plaques and neurofibrillary tangles (Blackwood and Corsellis 1976). DAT produces a highly variable spectrum of symptoms and it progresses at an equally variable rate. It is a clinical diagnosis of exclusion unless a brain biopsy is done, but as many as 80% of all demented people are probable victims of DAT (Wells 1978; Maisden and Harrison 1972). The other principal cause of dementia is atherosclerotic cerebrovascular disease, as diagnosed by history and X-ray computed tomography (XCT) scan, which has been labeled multi-infarct dementia (MID) by Hachinski et al. (1974).

A 56-year-old man with chronic lymphocytic leukemia, progressive multifocal leukoencephalopathy, and a dense left homonymous hemianopia had 18F-fluorodeoxyglucose positron emission tomography. Cortical glucose metabolism was decreased in the right cerebral hemisphere and the left cerebellar hemisphere. To our knowledge, this is the first demonstration of cerebral and cerebellar hypometabolism due solely to white matter disease.

• Local cerebral glucose metabolism was determined with 18-F-fluorodeoxyglucose using positron emission tomography in a sample of 12 unmedicated schizophrenics and 12 matched normal controls. The data were analyzed for absolute metabolic rates and region/whole-brain ratios using the cortical-subcortical, antero-posterior, and laterality dimensions. Lobar areas within cortical regions were also compared. Across groups, subcortical metabolism was higher than cortical metabolism. Patients had lower metabolism, cortically and subcortically, and a steeper subcortical to cortical gradient. Patients with higher scores on the Brief Psychiatric Rating Scale had higher absolute metabolism and higher left relative to right hemispheric metabolism than did patients with lesser severity. The results did not show "hypofrontality" in schizophrenia. These findings provide some support for cerebral dysfunction in schizophrenia and indicate the need for further examination of the cortical-subcortical dimension.