The Khachaturian criteria and the Consortium to Establish a Registry for Alzheimer Disease (CERAD) criteria for the neuropathological assessment of Alzheimer disease (AD) emphasize senile or neuritic plaques, age, and clinical history. A new scheme stressing topographic staging of neurofibrillary changes in addition to neuritic plaques has been proposed by the National Institute on Aging (NIA)-Reagan Institute Consensus Conference. This scheme assigns cases to high, intermediate, or low likelihood categories that the dementia is due to AD. We applied this method to 84 brains from subjects with clinical and neuropathological diagnoses of AD (n = 33), non-AD dementing illnesses (n = 34), including dementia with Lewy bodies (DLB) and progressive supranuclear palsy (PSP), and no neurological disease (n = 17). We also used Khachaturian and CERAD criteria. Neurofibrillary tangle and neuropil thread densities were assessed on 6-micrometer-thick modified Bielschowsky-stained paraffin sections from entorhinal-perirhinal cortex, CA1 of hippocampus, and neocortex including inferior temporal, visual association, and primary visual cortices. Each case was assigned a Braak and Braak stage. Using the NIA-Reagan criteria, we found excellent agreement between clinical history of AD dementia and brains assigned to the high likelihood category that dementia was due to AD. Among brains diagnosed neuropathologically with other degenerative diseases, NIA-Reagan criteria were more conservative than previous criteria, and these cases were likely to be categorized as intermediate or low likelihood that dementia was due to AD. All brains from nondemented subjects were assigned to the low (81%) or intermediate (19%) categories. In summary, we found good correlation between the NIA-Reagan criteria and clinical dementia, and there was generally good agreement between these criteria and existing neuropathological methods, Khachaturian and CERAD, in diagnosing AD. In studying several other neurodegenerative diseases, such as DLB, which shows neuropathological and clinical overlap with AD, the staging of neurofibrillary changes offered potential diagnostic refinement.

A 'syringomyelia-like' syndrome has been infrequently reported in neurological disorders such as Tangiers disease and lepromatous leprosy. This study reports a novel 'syringomyelia-like' syndrome in four adult male patients, which we have termed facial onset sensory and motor neuronopathy, or FOSMN syndrome, that appears to have a neurodegenerative aetiology. Clinical, neurophysiological and pathological data of four patients were reviewed, including the autopsy in one patient. Four male patients (mean age at onset 43), initially developed paraesthesiae and numbness in a trigeminal nerve distribution, which slowly progressed to involve the scalp, neck, upper trunk and upper limbs in sequential order. Motor manifestations, including cramps, fasciculations, dysphagia, dysarthria, muscle weakness and atrophy developed later in the course of the illness. Neurophysiological findings revealed a generalized sensory motor neuronopathy of caudally decreasing severity in all four patients. Autopsy in one patient disclosed loss of motoneurons in the hypoglossal nucleus and cervical anterior horns, along with loss of sensory neurons in the main trigeminal sensory nucleus and dorsal root ganglia. FOSMN syndrome appears to be a slowly progressive neurodegenerative disorder, whose pathogenesis remains to be determined.

The present studies investigated the expression of the two

We examined 11 subjects with inherited amyotrophic lateral sclerosis (familial amyotrophic lateral sclerosis, FALS) associated with the most common copper/zinc superoxide dismutase 1 (SOD1) mutation, an alanine for valine substitution in codon 4 (A4V). Autopsies were performed on 5 subjects. The clinical and pathological findings are described and compared with those of 9 sporadic ALS (SALS) subjects. There was no clinical evidence of upper motor neuron (UMN) involvement in 10 FALS A4V subjects. All subjects had lower motor neuron (LMN) signs and electrophysiological evidence of denervation in at least three limbs. All SALS subjects had signs of both UMN and LMN involvement. Pathological studies found severe abnormalities of LMNs in all FALS and SALS subjects. UMN involvement was either absent or mild in the A4V SOD1 FALS subjects and severe in the SALS subjects. Pathological abnormalities in systems other than the motor neurons were more frequent in the FALS A4V subjects. This information suggests that current diagnostic criteria for ALS, requiring dinical evidence for both upper and lower motor neuron involvement, should be modified; ie, the diagnosis should be deemed established when there is evidence of denervation in three or more limbs and a mutation in the gene for SOD1, even without dinical signs of UMN involvement.

The clinical features, pathologic findings and treatment courses of eight adults with central nervous system small-cell neuronal tumors were reviewed. Five patients had central neurocytomas, two patients central nervous system neuroblastomas, and one patient a neurocytoma-like spinal cord tumor. The neurocytomas were intraventricular, moderately cellular tumors with bland nuclei and perinuclear halos. Patients with neurocytoma were treated with surgery, radiation therapy, and/or chemotherapy, and have followed favorable clinical courses. The neuroblastomas were intraparenchymal, hypercellular tumors with necrosis and frequent mitoses. Patients with neuroblastomas were treated with surgery, radiation therapy and chemotherapy, with some clinical response, but overall poor survival. One of the two patients developed extracranial metastasis. The spinal cord tumor had histologic features of neurocytoma, and responded well to biopsy and radiation therapy. The cases are compared with the varieties of small-celled neuronal tumors described in the literature, and pathologic, histogenetic and treatment implications are discussed.

Dexamethasone ameliorates cerebral edema, but its effect on normal blood-brain barrier is unknown, as is the site of action. Sixteen normal mice were given dexamethasone, 3 mg/kg intramuscularly or 2 mg/kg intravenously. One to two hours later 10 mg of horseradish peroxidase (HRP) in 0.1 ml of saline was administered intravenously and allowed to circulate for 15 minutes. Brain slices were examined by light and electron microscopy. The number of HRP-permeable arteriolar segments per brain was less in dexamethasone-treated than in control mice (p less than 0.001). In addition, the number of small HRP-filled endothelial vesicles of capillaries and of HRP-permeable and -impermeable arterial segments was less in dexamethasone-treated mice than that for similar vessels in control mice (p less than 0.005, p less than 0.05, and p less than 0.01, respectively). The total number of small vesicles and the number of larger HRP-filled vesicles in arterioles was the same in treated and control mice. Dexamethasone therefore decreased the normal permeability of cerebral blood vessels to HRP. This decrease was accompanied by a decrease in the number of HRP-containing small endothelial vesicles. These data suggest that dexamethasone influences cerebral edema by decreasing the permeability of the cerebral vasculature for macromolecules.

Cholesterol emboli (CE) to the brain are an important but often unrecognized cause of stroke. The authors reviewed 29 cases of brain CE identified on autopsy. Most patients were elderly (mean age, 74 years) and presented with encephalopathy and acute renal failure. Ten patients developed symptoms spontaneously, 19 after a procedure involving manipulation of the aorta. Brain imaging revealed multiple, small ischemic lesions and border zone infarcts in 11 of 17 patients. Pathology in most patients demonstrated multiple CE mixed with emboli of other types.

A patient with a discrete metastasis in the ventral hypothalamus and optic chiasm is reported, who developed an abnormal daily rhythm of oral temperature without alteration of the 24-h mean temperature. This region, its afferents, and its efferents appear to be important in the neural regulation of human circadian rhythmicity.