Comparison of PET, MRI, and CT with pathology in a proven case of Alzheimer's disease

Positron emission tomography (PET) with fluorodeoxyglucose (FDG), magnetic resonance imaging (MRI), and CT were carried out in a patient with Alzheimer's disease 16 months before he died. At autopsy, the gross appearance of the brain correlated with MRI and CT, which showed some regional atrophy. These were much less revealing than PET, which correlated with microscopic findings of neuronal loss and proliferation of glia. In areas of moderately impaired local cerebral metabolic rate of glucose, as revealed by reduced FDG uptake, there was some gliosis, primarily around the numerous senile plaques. In areas of severe metabolic impairment, there was a profound loss of neurons, extensive gliosis, and a diminished appearance of plaques. PET-FDG is a better measure of the severity of Alzheimer's disease than MRI or CT, because it reflects the degree of neuronal pathology.     

In situ hybridization analysis for herpes simplex virus nucleic acids in Alzheimer disease

Histological sections of brain from patients showing evidence of advanced pathology of Alzheimer disease (AD) were examined for the presence of herpes simplex type-1 (HSV-1) nucleic acids by a sensitive in-situ hybridization technique. Samples from neurologically normal patients were examined in parallel. Sensitivity of the assay was verified by the detection of HSV-1 nucleic acids in neurons of trigeminal ganglia taken from cases of AD and normal controls. This indicated that the hybridization reaction was sufficiently sensitive to detect latent HSV-1 infections. Positive hybridization in the brain was only detected in a confirmed case of herpes simplex virus encephalitis. These results appear to confirm previous reports that HSV-1 infection is not directly involved in the pathology associated with AD.     

Immunohistochemical localization of vitronectin, its receptor and beta-3 integrin in Alzheimer brain tissue.

The vitronectin receptor (VNR) is an integrin which consists of an alpha-subunit which can associate with multiple beta-subunits. A polyclonal antibody to this integrin weakly stained resting microglia in white matter of control brain and strongly stained reactive microglia in both gray and white matter of Alzheimer brain. This antibody, as well as a monoclonal antibody to beta 3, stained some platelets in capillaries of both control and Alzheimer tissue. When the antiserum was immunoabsorbed with a preparation enriched in the alpha-chain of the vitronectin receptor, it failed to stain microglial cells, but continued to stain platelets. When it was immunoabsorbed with a peripheral blood platelet preparation, all immunostaining was abolished. These results indicate that the vitronectin receptor of microglia is associated with a beta-chain different from beta 3, but that beta 3 is expressed by some platelets in brain capillaries. An antibody to vitronectin itself stained senile plaques and neurofibrillary tangles in Alzheimer entorhinal cortex, but only residual plasma in control tissue. Senile plaques positive for vitronectin had microglial cores strongly positive for the vitronectin receptor. The high levels of vitronectin receptor on reactive microglia in areas containing extracellular vitronectin suggest the possibility that vitronectin is serving an opsonizing function for microglial phagocytosis.     

Loss of insulin receptor immunoreactivity from the substantia nigra pars compacta neurons in Parkinson's disease

Immunohistochemistry using both a newly developed polyclonal, and a commercially available monoclonal, anti-insulin receptor antibody was done on the midbrain from cases of idiopathic Parkinson's disease (PD), Alzheimer's disease, amyotrophic lateral sclerosis, vascular parkinsonism and non-neurological controls. Both antibodies gave indentical patterns of neuronal staining. The neurons of the oculomotor nucleus were immunopositive in all the brains. However, the neurons in the pars compacta of the substantia nigra, paranigral nucleus, parabrachial pigmental nucleus, tegmental pedunculopontine nucleus, supratrocheal nucleus, cuneiform nucleus, subcuneiform nucleus and lemniscus medialis, which were positive in other diseases and in non-neurological controls, were not stained by these antibodies in PD brains. These results suggest that, in PD, a dysfunction of the insulin/insulin receptor system may precede death of the dopaminergic neurons.The work in the Kinsmen Laboratory was supported by the MRC of Canada and the Parkinson Society of Canada     

Appearance of paired nucleated, Tau-positive glia in patients with progressive supranuclear palsy brain tissue.

Many Tau-positive glia with paired nuclei and astrocyte type morphology were identified in three brains from patients with progressive supranuclear palsy (PSP). They were positive by Bielschowsky's and Bodian's silver staining as well as by immunostaining with Tau-2, Alz-50, anti-GFAP and anti-paired helical filament antibodies, but not with anti-ubiquitin antibody. They were predominantly localized in the striatum, thalamus and frontal cortex but were not seen in white matter and were not plentiful in areas of heavy neuronal degeneration. Electron microscopy clearly showed the nuclear pairing and localized the Tau protein to bundles suggestive of microtubules in the cytoplasm and proximal processes. Such glial cells were rarely seen in cases of other neurodegenerative diseases or neurologically normal controls. These data suggest that there is an unusual gliotic reaction in PSP in brain areas which show relatively little neuronal loss.     

Cerebral glucose metabolism in Parkinson's disease with and without dementia.

Although cognitive impairment is commonly associated with Parkinson's disease, the relative importance of cortical and subcortical pathologic changes to the development of dementia is controversial. Characteristic abnormalities in cortical glucose metabolism have been reported previously in Alzheimer's disease, a disease in which cortical changes predominate. We measured cerebral glucose metabolism with positron emission tomography in 20 control subjects and in 14 patients with PD with mental status ranging from normal to severely demented to determine whether changes in cortical glucose metabolism occur in early PD and whether the degree and pattern of metabolic change relate to the severity of dementia. The patients were divided into demented and nondemented groups according to the results of neuropsychological assessment. Age-adjusted covariance analyses were performed, since the age distribution varied between groups. The nondemented patients with PD showed widespread cortical glucose hypometabolism without any selective temporoparietal defects. The pattern of glucose hypometabolism seen in the demented patients with PD resembled that described in patients with Alzheimer's disease; ie, there was a global decrease in glucose metabolism, with more severe abnormalities observed in the temporoparietal regions.     

Early diagnosis of SARS: lessons from the Toronto SARS outbreak

The clinical presentation of SARS is nonspecific and diagnostic tests do not provide accurate results early in the disease course. Initial diagnosis remains reliant on clinical assessment. To identify features of the clinical assessment that are useful in SARS diagnosis, the exposure status and the prevalence and timing of symptoms, signs, laboratory and radiographic findings were determined for all adult patients admitted with suspected SARS during the Toronto SARS outbreak. Findings were compared between patients with laboratory-confirmed SARS and those in whom SARS was excluded by laboratory or public health investigation. Of 364 cases, 273 (75%) had confirmed SARS, 30 (8%) were excluded, and 61 (17%) remained indeterminate. Among confirmed cases, exposure occurred in the healthcare environment (80%) or in the households of affected patients (17%); community or travel-related cases were rare (<3%). Fever occurred in 97% of patients by the time of admission. Respiratory findings including cough, dyspnea and pulmonary infiltrates evolved later and were present in only 59, 37 and 68% of patients, respectively, at admission. Direct exposure, fever on the first day of illness, and elevated temperature, pulmonary infiltrates, lymphopenia and thrombocytopenia at admission were associated with confirmed cases. Rhinorrhea, sore throat, and an elevated neutrophil count at admission were associated with excluded cases. In the absence of fever or significant exposure, SARS is unlikely. Other clinical, laboratory and radiographic findings further raise or lower the likelihood of SARS and provide a rational basis for estimating the likelihood of SARS and directing initial management.     

Senile plaques,amyloid β-protein,and acetylcholinesterase fibres: laminar distributions in Alzheimer's disease striate cortex

Summary The laminar distributions of senile plaques and amyloid -protein (AP) within the striate cortex of patients with Alzheimer's disease (AD) were studied with enhanced Bielschowsky (roughly equivalent to the Campbell technique) and immunohistochemical methods. The laminar distribution of acetylcholinesterase (AChE) fibres within the striate cortex of both AD patients and control patients was studied with an enzyme histochemical method. Quantification of Bielschowsky-stained plaque numbers along intersect lines drawn parallel to laminar boundaries revealed a significant aggregation of plaques at the interface of layers IVc and V. Lines drawn through layer VI intersected significantly fewer plaques than lines through other laminae. Immunoperoxidase staining for AP revealed a similar distribution fo senile plaques, and additional, prominent, diffuse deposits of AP within layers I and IVc. AChE fibres were markedly depleted in the striate cortex of AD cases. In control cases, AChE fibres were, like AP immunoreactivity, concentrated within layers I and IVc. The results indicate that enhanced silver methods may not reveal the complete distribution of AP. The codistribution of AP-immunoreactive diffuse amyloid deposits and AChE fibres to the same cortical laminae is consistent with the possibility that these deposits may be formed from degenerating cholinergic elements. The formation of a line of senile plaques at the interface of two cortical laminae within the striate cortex, in an anatomically analogous situation to a similar line of plaques within the dentate gyrus, suggests that formation of well-defined plaques may be accelerated by the interaction of specific neuronal systems.Supported by a Fellowship from the British Columbia Health Care Research Foundation to TGB. This work is part of the PhD. dissertation of Dr. Beach (University of British Columbia, 1991)     

Utilization review of the use of BACTEC PLUS high-volume blood culture bottles.

The BACTEC PLUS 26 (NR26) (Becton Dickinson, Towson, Md.) high-volume blood culture bottle replaced the less expensive smaller-volume NR6A bottle in our hospital. An audit carried out several months after their introduction revealed that only 17.5% of the NR26 bottles received the required blood volume. Several audits and educational programs were required in order to achieve a compliance rate of > 60%.