An African American family with early-onset Alzheimer disease and an APP (T714I) mutation.

The occurrence of an APP T174I mutation is described in a large American family of African descent with Alzheimer disease. The clinical characteristics were an unusually early onset of disease (early 30s), similar to a previously reported age at onset of this mutation in an Austrian family. Distinct from that family, seizures and myoclonus were prominent features of the disease in this kindred.

Quantitative electroencephalographic correlates of psychosis in Alzheimer disease.

OBJECTIVE: We hypothesized that the distinctive neurobiology of Alzheimer disease (AD) with psychosis would be reflected in more severe abnormalities in frontal and temporal regions on quantitative electroencephalography (QEEG). BACKGROUND: Patients with AD and psychosis have more rapid cognitive decline and greater pathologic involvement of frontal and temporal cortex than AD patients without psychotic features. METHOD: We evaluated brain function using QEEG in a group of 44 patients who had a diagnosis of probable or possible AD. All patients were administered the Mini-Mental State Examination and the Neuropsychiatric Inventory to assess psychiatric symptoms, including the presence of hallucinations and delusions. Absolute and relative power in patients with and without psychosis were compared to determine if there were regional or global QEEG differences in these two groups. RESULTS: Patients with psychosis showed greater overall absolute and relative delta power but no regional predominance of slowing compared with those without psychosis. Those with psychosis had a concomitant decrease in relative alpha power. These differences remained after adjustment for different dementia severity in the two groups. CONCLUSIONS: This finding suggests more severe brain dysfunction in patients with psychosis than in those with similar levels of cognitive impairment but without psychosis. The QEEG abnormalities were not regionally specific and involved all areas assessed.

Fulminant demyelinating encephalomyelitis associated with productive HHV-6 infection in an immunocompetent adult.

Human herpesvirus 6 (HHV-6), the etiologic agent of roseola in young children, has been reported to be detectable in the brain of many neurologically normal adults, although regional localization to plaques of multiple sclerosis has also been demonstrated. Large amounts of this virus were present in multifocal demyelinating white matter lesions of fulminant encephalomyelitis with seizures in a 21-year-old woman with normal immune parameters. Brain biopsy after 3 weeks of neurologic deterioration revealed a viral etiology by light and electron microscopy; the virus was identified as HHV-6 by immunohistochemistry and by polymerase chain reaction (PCR) amplification in biopsy and autopsy specimens.

The temporal variant of frontotemporal dementia.

Frontotemporal dementia is a dementia syndrome with diverse clinical characteristics. Based upon clinical parameters and single photon emission computed tomography, we identified 47 frontotemporal dementia subjects. In 10 of these 47 the primary site of brain dysfunction was anterior temporal and orbital-frontal with other frontal regions relatively spared. In this temporal lobe variant (TLV) of frontotemporal dementia, five of the subjects had more severe left-sided, and five had more right-sided, hypoperfusion. The clinical, neuropsychological and neuropsychiatric features of predominantly left-sided (LTLV) and right-sided (RTLV) TLV subjects are discussed and contrasted with more frontal presentations of frontotemporal dementia. In LTLV, aphasia was usually the first and most severe clinical abnormality RTLV patients presented with behavioural disorders characterized by irritability, impulsiveness, bizarre alterations in dress, limited and fixed ideas, decreased facial expression and increased visual alertness. These findings suggest that: (i) frontotemporal dementia is clinically heterogeneous with bitemporal and inferior frontal lobe dysfunction contributing to the clinical presentation; (ii) behavioural disturbance and aphasia are the most prominent features of predominantly temporal subtypes of frontotemporal dementia; (iii) the right and left anterior temporal regions may mediate different behavioural functions. The results of this study suggests that TLV offers a valuable source of information concerning the behavioural disorders seen with combined anterior temporal and inferior frontal lobe dysfunction.

Congenital insensitivity to pain and anhidrosis with mitochondrial and axonal abnormalities.

Hereditary sensory and autonomic neuropathy type IV, or congenital insensitivity to pain with anhidrosis (CIPA), is a rare clinical disorder with only 32 cases reported in the literature. There has been no consistent pathophysiologic defect of the sensory nerve detected by light microscopic examination, but a frequent finding of decreased small myelinated fibers and a uniform finding of decreased unmyelinated fibers by ultrastructural analysis has been reported. Muscle biopsy in a 2-year-old boy with congenital insensitivity to pain with anhidrosis indicated lipid droplet accumulation and reduced cytochrome C oxidase histochemically on light microscopy. Electron microscopic study showed almost absent small unmyelinated nerve axons within the muscle, increased microfilaments, and decreased microtubules in axons, some abnormally enlarged mitochondria, and normal-appearing motor endplates. Biochemical analysis of muscle mitochondrial enzyme function revealed cytochrome c oxidase function to be reduced to 35% of normal, with normal function of the other mitochondrial enzymes.