Differential activation on fMRI of monozygotic twins discordant for AD.

This is the first report of fMRI in monozygotic twins discordant for AD. FMRI brain activation patterns were examined during visuospatial and verbal working memory tasks. The affected twin had greater parietal involvement bilaterally during both working memory tasks and reduced left dorsolateral prefrontal cortex activity on the visuospatial memory task. Thus, fMRI may identify additional brain regions recruited in patients with AD to perform a given cognitive task.

Occipital brain perfusion deficits in children with major depressive disorder.

UNLABELLED: Occipital lobe perfusion defects have been identified on regional cerebral blood flow (rCBF) SPECT scans of adolescent children and young adults with major depressive disorder (MDD). We reinvestigated a series of rCBF SPECT scans obtained several years ago on drug-naive children with a clinical diagnosis of MDD and on healthy children. METHODS: To test whether visually apparent abnormalities in rCBF constitute statistically significant differences between patients, given the relatively small sample sizes, we applied the technique of statistical parametric mapping (SPM). RESULTS: Two groups of patients were identified: 8 with significant posterior flow deficits in the occipital cortex (Brodmann's areas 18 and 19), usually symmetric, and best visualized on paramedian sagittal sections, and 13 without obvious occipital perfusion deficits but with anterior rCBF deficits in a pattern often described in the literature, attaining statistical significance in the right frontal region. Other localizations in the left frontal and bilateral prefrontal regions did not attain significance, but each localization contained statistically significant maxima (z scores). The scan findings of all 18 healthy children were normal. CONCLUSION: With the aid of SPM, 2 groups of children with significantly different rCBF behavior were identified. The reason for this difference is not known but should be investigated to determine its possible significance to patients with MDD.

Familial dementia due to adult polyglucosan body disease.

BACKGROUND: Adult polyglucosan body disease (APBD) is a rare disorder, presenting with varying combinations and severity of upper and lower motor neuron dysfunction, sensory deficits, dementia, and urinary incontinence. Onset is in the 40s or 50s. The diagnosis is made by finding polyglucosan bodies (PB) in histologic sections of brain or spinal cord, peripheral nerve, or dermal sweat glands. Although 2 pairs of the 22 previously reported cases were siblings, the familial nature of the disease has not been emphasized. METHODS: We report 2 adult siblings, a male and a female, each of whom had the clinical diagnosis of vascular dementia. Both were confirmed at autopsy to have APBD. We characterized the lesions in autopsy tissues using a battery of histological stains, lectin histochemistry, and electron microscopy. RESULTS: Innumerable PB were distributed throughout brain, heart, skeletal muscle, liver, and dermal sweat glands. PB were highlighted by periodic acid Schiff stain and concanavalin A lectin. Ultrastructurally, PB were composed of aggregates of filaments within axons and astrocytic processes, and lying free in the neuropil, but not within neuronal perikarya. CONCLUSIONS: It is important to consider APBD in cases of familial dementia of unknown etiology. Ante-mortem biopsy of axillary skin may be diagnostic.

Brain blood flow in the dementias: SPECT with histopathologic correlation in 54 patients.

PURPOSE: To evaluate single photon emission computed tomographic (SPECT) imaging of regional cerebral blood flow in the diagnosis of Alzheimer disease (AD) and the differential diagnosis of the dementias. MATERIALS AND METHODS: Regional cerebral blood flow SPECT was performed with inhaled xenon-133 in 261 patients and with injected technetium-99m hexamethyl-propyleneamine oxime (HMPAO) in 162 patients with possible dementia. In 16 patients, both agents were used in 1 day. SPECT images obtained in elderly healthy control subjects (with Xe-133 in 15, with Tc-99m HMPAO in 14) were available. In each patient without AD, further classification of disease was attempted. Histopathologic correlation was available in 54 patients (with autopsy in 51, with biopsy in three). RESULTS: SPECT diagnoses were true-positive in 37, true-negative in eight, false-positive in three, and false-negative in six patients. Sensitivity was 86% (37 of 43; 95% confidence limits = .72, .95); specificity, 73% (eight of 11; confidence limits = .39, .94); positive predictive value, 92% (37 of 40; confidence limits = .80, .98); and negative predictive value, 57% (eight of 14; confidence limits = .29, .82). CONCLUSION: Regional cerebral blood flow SPECT may assist in the early and late diagnoses of AD and in the differential-diagnosis of the dementias when there is a complicated or confusing clinical picture.

Evaluation of neurologic function in Gulf War veterans. A blinded case-control study.

OBJECTIVE: To determine whether Gulf War-related illnesses are associated with central or peripheral nervous system dysfunction. DESIGN: Nested case-control study. PARTICIPANTS: Twenty-three veterans with factor analysis-derived syndromes (the cases), 10 well veterans deployed to the Gulf War (the deployed controls), and 10 well veterans not deployed to the Gulf War (the nondeployed controls). METHOD: With investigators blinded to group identities, participants underwent objective neurophysiological, audiovestibular, neuroradiological, neuropsychological, and blood tests. MAIN OUTCOME MEASURES: Evidence of neurologic dysfunction. RESULTS: Compared with the 20 controls, the 23 cases had significantly more neuropsychological evidence of brain dysfunction on the Halstead Impairment Index (P=.01), greater interside asymmetry of the wave I to wave III interpeak latency of brain stem auditory evoked potentials (P=.02), greater interocular asymmetry of nystagmic velocity on rotational testing, increased asymmetry of saccadic velocity (P=.04), more prolonged interpeak latency of the lumbar-to-cerebral peaks on posterior tibial somatosensory evoked potentials (on right side, P=.03, and on the left side, P=.005), and diminished nystagmic velocity after caloric stimulation bilaterally (P values range from .02 to .04). Cases (n=5) with syndrome 1 ("impaired cognition") were the most impaired on brain stem auditory evoked potentials (P=.005); those (n=13) with syndrome 2 ("confusion-ataxia") were the most impaired on the Halstead Impairment Index (P=.006), rotational testing (P=.01), asymmetry of saccadic velocity (P=.03), and somatosensory evoked potentials (P< or =.01); and those (n=5) with syndrome 3 ("arthro-myo-neuropathy") were the most impaired on caloric stimulation (P< or =.01). CONCLUSIONS: The 3 factor-derived syndromes identified among Gulf War veterans appear to represent variants of a generalized injury to the nervous system.

High-voltage electric injury: assessment of muscle viability with MR imaging and Tc-99m pyrophosphate scintigraphy.

PURPOSE: To evaluate use of magnetic resonance (MR) imaging and technetium-99m pyrophosphate (PYP) scintigraphy in preoperative assessment of muscle viability after high-voltage electric injury. MATERIALS AND METHODS: Twelve injured limbs were studied. Immediate, equilibrium, and delayed Tc-99m PYP scintigrams and gadolinium-enhanced and unenhanced MR images were obtained. Imaging results were compared with clinical findings. RESULTS: Scintigraphy demonstrated nonperfusion in four limbs that were subsequently amputated, but MR imaging had poor sensitivity in nonperfused regions owing to lack of edema. Tc-99m PYP uptake increased at transition zones between normal and nonperfused regions. MR imaging allowed further characterization of these zones by demonstrating edema as enhancing (perfused) or nonenhancing (nonperfused). In all nonamputated limbs, edema showed enhancement. CONCLUSION: In high-voltage electric injury, gadolinium-enhanced MR imaging appears able to demonstrate zones of potential viability within radionuclide-avid tissue but has poor perfusion sensitivity when used alone.

Cognitive deficits in asymptomatic first-degree relatives of Alzheimer's disease patients.

The present study was designed to determine whether neuropsychological deficits exist in asymptomatic first-degree relatives of Alzheimer's disease (AD) patients. The neuropsychological performances of 20 first-degree asymptomatic relatives of NINCDS-ADRDA diagnosed AD patients were compared to 20 normal controls without family history of AD. Cognitive functions assessed included intelligence, memory, overall brain function, verbal learning, and language and constructional abilities. Significant statistical differences were found between the groups across several cognitive areas indicating lower functioning in the first-degree relatives of AD patients. Fifty percent of the first-degree subjects but only 20% of controls showed a pattern of significant neuropsychological deficit. The results demonstrate neuropsychological deficits in asymptomatic first-degree relatives of AD patients, suggesting that preclinical markers for AD may be present long before the clinical manifestation of the disease.

Brain blood flow SPECT in temporary balloon occlusion of carotid and intracerebral arteries.

It is important to determine preoperatively which patients can tolerate permanent occlusion of a cervical internal carotid or cerebral artery when such a procedure may be necessary to treat cerebrovascular or neoplastic lesions. Here we report our experience in combining temporary intra-arterial balloon occlusion with concomitant cerebral blood flow imaging in preoperative evaluation of such patients. Forty-two patients with a variety of cerebrovascular and neoplastic lesions underwent trial balloon occlusion of an internal carotid or intracerebral artery. Eight patients developed both neurologic symptoms as well as brain perfusion defects during trial occlusion. Nine others developed only perfusion defects. The remainder were asymptomatic and had negative scans. Brain blood flow imaging during intra-arterial balloon occlusion identified 17 patients potentially at risk for developing postsurgical ischemic deficits. Treatment alternatives to acute arterial sacrifice were developed for these patients.

Brain blood flow in the dementias: SPECT with histopathologic correlation.

Single photon emission computed tomography (SPECT) of regional cerebral blood flow (RCBF) has been employed experimentally in the assessment of patients with dementia. The standard with which the SPECT diagnosis has been compared previously has been the initial clinical diagnosis. Recognizing that histopathologic diagnosis would be a more reliable standard, the authors compared SPECT diagnoses and clinical diagnoses with histopathologic diagnoses in a series of 18 patients who had been referred by the Alzheimer Disease Research Center. SPECT RCBF studies were carried out prospectively in 15 patients with an inhaled xenon-133 SPECT technique and in three patients with technetium-99m hexamethyl-propylene-amine oxime and triple-camera-scanner SPECT. When compared with histopathologic diagnosis, clinical diagnosis was correct in 15 of 18 patients; visual scanning diagnosis, in 13 of 18; and Xe-133-SPECT diagnosis based on quantitative ratios in regions of interest, in 14 of 15 (13 of 13 with Alzheimer disease).

Xenon-133 SPECT-determined regional cerebral blood flow in Alzheimer's disease: what is typical?

A study of 76 consecutive xenon-133 SPECT studies of regional cerebral blood flow was undertaken to determine the frequency of various patterns of blood flow in cases of clinically diagnosed probable and possible Alzheimer's disease. The reference tomographic section was a slice 6 cm above and parallel to the canthomeatal line. With the use of this technique, the "classic" finding of bilateral temporoparietal (TP) flow reductions as the sole abnormality occurred in only 28% of cases. Bilateral TP reductions accompanied by bilateral or unilateral frontal flow reductions were nearly as common (24%), and other patterns accounted for the other 48% of cases.

Temporary balloon occlusion of the carotid artery combined with brain blood flow imaging as a test to predict tolerance prior to permanent carotid sacrifice.

PURPOSE: To describe the technique of using SPECT brain blood flow imaging to identify patients at risk for having strokes after balloon or surgical ligation of an internal carotid artery. PATIENTS AND METHODS: 29 patients underwent temporary balloon occlusion of the internal carotid artery and blood flow imaging studies were obtained prior to sacrifice of the vessel; 11 internal carotid arteries were indeed sacrificed and form the basis of our study. Follow-up of these patients ranged from 3 to 65 days. RESULTS: Three groups emerged: group I, patients with symptoms during occlusion and an abnormal blood flow study (one patient); group II, patients with no symptoms during the occlusion but with an unequivocally abnormal blood flow study (two patients); group III, patients without symptoms during occlusion and a normal or slightly abnormal blood flow study (eight patients). CONCLUSION: Carotid sacrifice without initial and temporary balloon occlusion is unnecessarily risky. Imaging of blood flow in the brains of these patients can further improve the safety of occlusion procedures in the internal carotid artery.

The skeleton in congenital, generalized lipodystrophy: evaluation using whole-body radiographic surveys, magnetic resonance imaging and technetium-99m bone scintigraphy.

Congenital generalized lipodystrophy (CGL) is a rare genetic disease characterized by the absence of body fat from birth. Focal bone lesions have also been reported, but their pathophysiology is poorly understood. To characterize skeletal abnormalities further in 3 patients with CGL, we employed whole-body radiographic skeletal surveys, magnetic resonance imaging (MRI, including gadolinium enhancement), and triple phase technetium-99m methylene diphosphonate bone scintigraphy. Radiographs showed numerous focal lesions within the long bones, as described in other reports. MRI showed that the entire marrow space of the long bones was abnormal and was characterized, at least in part, by the absence of marrow fat. Prolonged T1 and T2 times and marked gadolinium enhancement were observed in radiographically normal-appearing long bone. Radiographically lytic lesions occasionally demonstrated fluid-fluid levels on MRI and enhanced peripherally after gadolinium infusion. Bone scintigraphy findings such as periarticular hyperemia were relative subtle. We conclude that the appendicular skeleton of patients with CGL is diffusely abnormal and is predisposed to focal osteolysis and cyst formation.

Differential diagnosis of bacterial myositis in AIDS: evaluation with MR imaging.

Magnetic resonance (MR) imaging was used to assess for the presence of bacterial myositis, rare outside the tropics, in 13 patients with either the acquired immunodeficiency syndrome (AIDS) (n = 11) or positive results of serologic tests for the human immunodeficiency virus but without other evidence of AIDS (n = 2). Bacterial myositis was diagnosed in six patients: in five it was caused by pyogenic bacteria, and in the other, by Mycobacterium tuberculosis; in each patient, little or no subcutaneous tissue alteration occurred. On T1-weighted images in three patients, muscle abscesses showed a rim of increased signal intensity corresponding to margins between drainable pus and edematous muscle. Subcutaneous tissues appeared normal in patients with bacterial myositis but was not in the others, in whom muscle abnormalities tended to be less prominent. The latter group included patients with lymphoma (n = 1), Kaposi sarcoma (n = 2), and carbunculosis (n = 1), and three patients in whom no diagnosis was made; lymphedema was presumed to account for imaging abnormalities in four of the latter group.

Single photon tomography in Alzheimer's disease and the dementias.

Measurements of brain blood flow has evolved over the past 50 years, and during the latter half of that time radionuclide techniques have been used to study this important function. Using Xenon 133 and scintillation multiprobe systems, several teams of investigators measured regional cerebral blood flow (rCBF), and noted that under many circumstances it could be equated with local brain physiological activity. The dementias were investigated using the scintillation multiprobe method, and posterior flow deficits were described in patients who were thought to have Alzheimer's disease. The multiprobe technique gave way first to planar, and then tomographic imaging, with initial favorable results achieved by positron emission tomography (PET). Soon investigators learned to measure rCBF with single-photon emission computed tomography (SPECT) using high-sensitivity systems and 133Xe as a tracer, or high-resolution systems with 123I-iodoamphetamine (IMP), and later, 99mTc-HMPAO. Three-dimensional tomographic imaging shows to advantage the flow patterns that characterize Alzheimer's disease, with rCBF reductions in temporal, parietal, and sometimes frontal areas, as opposed to randomly distributed deficits in multiinfarct dementia, reduced frontal flow in entities such as Pick's disease, and others. Herein we will review our own experience with high-sensitivity rCBF SPECT in 119 patients with dementia, and with high-resolution SPECT, using a new, three-camera scanner and 99mTc-HMPAO in an additional 39 patients. SPECT rCBF study of patients with dementia and Alzheimer's disease, will aid in separating patients with untreatable Alzheimer's from those patients who may have treatable causes of dementia, and will be useful in evaluating experimental drugs for the treatment of Alzheimer's disease.

Hypofrontality and cognitive impairment in schizophrenia: dynamic single-photon tomography and neuropsychological assessment of schizophrenic brain function.

Regional cerebral blood flow (rCBF) was assessed in 40 chronic male schizophrenic patients (20 medicated, 20 unmedicated) and 31 matched normal controls with Dynamic Single-photon Emission Computed Tomography (D-SPECT). Blind analyses of normalized color-coded tomograms revealed significant bifrontal and bitemporal rCBF deficits in the patient group. Frontal flow deficits were most prominent in paranoid patients (n = 21) and right temporal deficits were most prominent in nonparanoid patients (n = 19). These relative regional declines were observed within the context of significantly elevated hemispheric blood flow in schizophrenics compared with controls. Reduced left frontal rCBF was associated with neuropsychological impairment on the Wisconsin Card Sorting Test and Luria-Nebraska Battery. Increased hemispheric CBF was correlated with the presence of positive schizophrenic symptoms. Medication status was unrelated to rCBF. These findings demonstrate that hypofrontality has important implications for cognitive function in some schizophrenic individuals.

Cognitive function and regional cerebral blood flow in partial seizures.

Patients with partial seizures have cognitive function impairments that have been attributed to the toxic side effects of anticonvulsants and structural cerebral damage. However, even when these factors are absent, neuropsychological (NP) deficits have been demonstrated, although of milder degree than in structurally brain-damaged patients. Assessment of cerebral metabolism using positron emission tomography and cerebral blood flow with single photon emission computed tomography (SPECT) reveals focal physiologic deficits in structurally normal areas. Using both SPECT and NP assessment with the Halstead-Reitan Battery, we evaluated 50 patients with partial seizures. Comparison of the location of visually identified regional cerebral blood flow (rCBF) deficits in these patients with the location of the NP deficits revealed a significant correlation. Additional analyses indicated that rCBF quantification in visually identified areas of hypoperfusion was significantly lower than in "normal" areas and that quantified NP variables significantly discriminated patients with and without visual rCBF deficits in temporal and frontal brain regions.