Uwamie Tomiyasu

Amnesia with hippocampal lesions cardiopulmonary arrest

A patient developed an amnesic syndrome after cardiopulmonary arrest. Neuropathologic examination revealed pronounced anoxic injury to both hippocampi with little damage to other hemisphere structures. The clinical and pathologic findings suggest that lesions limited to the hippocampus can cause profound amnesia.

Dementia with Lewy bodies: Reliability and validity of clinical and pathologic criteria

Clinical criteria for dementia with Lewy bodies (DLB) have been proposed, but their formulation, reliability, and validity require further study.Pathologic criteria for DLB are also undergoing evolution. Two studies were conducted with the goal of identifying the components of these evolving criteria that may benefit from further refinement; one study evaluated the components of the clinical criteria and another study operationalized the pathologic criteria for DLB. Twenty-four patients with a premorbid diagnosis of probable or possible Alzheimers disease (AD) (n = 18), Parkinsons disease (PD) (n = 5), or progressive supranuclear palsy (PSP) (n = 1) were studied. Inter-rater reliability and validity of the clinical criteria were determined by a retrospective chart review, done by five neurologists, and a blinded pathologic evaluation. The Consortium on dementia with Lewy bodies (CDLB) pathologic criteria were operationalized to compare past criteria and test the validity of the evolving clinical criteria on the dementia patients. Three or more cortical fields (at 250x magnification) with many (four or more) Lewy bodies (LBs) on ubiquitin immunoreactive sections were required to meet the CDLB neocortical score of >6. Fifteen of the AD patients had at least one LB in a cortical section, four had many LBs, while three had no LBs; all patients with movement disorder had at least one LB in a cortical section. The sensitivity/specificity ratio of the CDLB probable DLB clinical criteria based upon many LBs being present was 75%/79%. Reformulated clinical criteria that require the presence of extrapyramidal signs significantly predicted those patients with many LBs versus those with few or no LBs (chi squared = 5.48, p = 0.02) and increased clinical specificity to 100%. This preliminary study identifies components of the evolving clinical and pathologic criteria for DLB that require further refinement. NEUROLOGY 1996;47: 1403-1409

Hippocampal pyramidal cell loss in human status epilepticus

Summary: A pilot case‐control quantitative study of the hippocampus in patients with severe status epilepticus was performed to identify specific patterns of pyramidal cell loss. Pyramidal cell densities from five patients who died following status epilepticus were compared with five normal controls and five controls matched for age, hypoxialischemia, previous epilepsy, and alcohol abuse. Neuronal densities were greatest in the normal control group and least in patients with status epilepticus. Significant reductions were identified in Sommers sector (prosubiculum and CA1) as well as in CA3 when compared to normal controls.

Dendritic organization of the anterior speech area.

Golgi studies revealed significant differences in dendritic patterns between neurons of the left and right opercular regions of the frontal lobe (Brocas speech area on the dominant side) and between cells of the left and right precentral areas (the orofacial motor zones) just behind. Although total dendritic length of the basilar dendritic array seemed characteristic of an area independent of side, a larger proportion of the length on the left (dominant) side was made up of higher order (4, 5, 6) dendrite branches, and lower order (1, 2, 3) segments predominated on the right. The pattern was partially reversed in non-right-handed patients. These findings can be interpreted as indicating an early preponderance of dendrite growth in the non-speech-gifted hemisphere followed by enhanced dendrite growth in the dominant hemisphere coincident with the beginning of conceptualization and speech function.

Dendritic sprouting in Alzheimer's presenile dementia

Abstract The use of Golgi techniques on brain tissue from aging and senescent human individuals has shown a series of progressive deteriorative changes in neurons at a number of sites in cortical structures. These include loss of dendritic spines, irregular swelling of cell body and dendrites, and progressive loss of the dendritic domain, culminating in cell death. These changes which characterize the senile dementias have now been seen also in two cases of Alzheimer presenile dementia. This material is additionally characterized by the presence of clusters of new dendritic growth, developing at one or more sites along the dendritic or somal surface. The dendritic branchlets are densely spine-covered at a time when the original dendritic systems of the neuron may be partially or totally devoid of their spine complements. Because these dendrite clusters appear haphazard in placement and orientation and do not coincide with any known presynaptic terminal fields, we provisionally refer to them as “lawless.” The mechanisms which trigger their development in presenile, but not senile, dementing disease are unknown at present.

Progressive dendritic changes in the aging human limbic system

Abstract The methods of Golgi have been used in histological evaluation of tissue from the limbic lobe of nine aged patients, six of whom showed clinical signs and symptoms of senility. Special attention was paid to the pes hippocampus and dentate gyrus as prototypic exampes of archicortex and to entorhinal cortex serving as an example of transitional cortex. Sequences of degenerative changes with aging and senescence were found in all the regions studied. Although there were general similarities among the pathological patterns, changes appeared idiosyncratic to the regions involved. The severity of pathological changes appeared to correlate more closely with the amount of antecedent psychomotor loss than with the chronologic age of the patient. Dendritic systems showed progressive deteriorative changes in all three regions. Entorhinal cortex also appeared characterized in at least three of the more severely affected patients by the appearance of spindle-shaped thickenings along the apical shafts, frequently clustered at specific distances throughout the depth of cortex. Some suggestions are made as to the possible significance of this type of dendritic lesion, and of the putative consequences of patchy lesions in pes hippocampus.

Progressive multifocal leukoencephalopathy in AIDS: a clinicopathologic study and review of the literature

We reviewed the clinical, radiographic, and pathologic features of 15 patients with the acquired immune deficiency syndrome (AIDS) and progressive multifocal leukoencephalopathy (PML). Brain tissue from 10 autopsy and 6 biopsy specimens was studied using: in situ hybridization (ISH) for JC virus (JCV), immunohistochemistry for human immunodeficiency virus (HIV) p24 antigen, and electron microscopy. Thirteen patients presented with focal neurologic deficits, while 2 presented with a rapid decline in mental status. PML was commonly the initial opportunistic infection of AIDS and produced hemiparesis, dementia, dysarthria, cerebellar abnormalities; and seizures. Magnetic resonance imaging was more sensitive than computed tomography in detecting lesions, and often showed multifocal areas of PML. CD4+ T-cell counts were uniformly low (mean 84/mm3), except in 1 patient who improved on 3′-azido-3′-deoxythymidine (AZT). PML involved the cerebral hemispheres, brain stem, cerebellum, and cervical spinal cord. The distribution of brain involvement was consistent with hematogenous dissemination of the virus. In 2 brain specimens, multiple HIV-type giant cells were present within the regions involved by PML. When co-infection by HIV and papovavirus was present, PML dominated the pathological picture. ISH for JCV showed virus in the nuclei of oligodendrocytes and astrocytes. Occasionally there was staining for JCV in the cytoplasm of glial cells and in the neuropil, the latter possibly a correlate of papovavirus spread between myelin sheaths, as seen by electron microscopy. ISH demonstrated more extensive foci of PML than did routine light microscopy.

Denervation microangiopathy in senile dementia, Alzheimer type.

Structural analysis of the capillary plexus in the brains of 5 patients with clinical and neuropathological diagnosis of Senile Dementia, Alzheimer Type, revealed a group of striking physical alterations compared with tissue specimens from 5 age-matched controls. Capillary walls were thickened with irregular lumpy, nodulated contours which appeared due, in part, to infiltration of the vascular wall with rounded cell-like bodies. In some cases, these resembled the perikarya of pericytes or monocytes, or their protoplasmic extensions, which were often filled with lipids. In each case, there was no trace of the perivascular neural plexus which regularly invests the microvasculature of the brain parenchyma. The loss of this neural plexus, believed to originate largely from locus ceruleus and the basal forebrain, may be related to the changes in capillary wall structure, and these, in turn, may lead to profound alterations in blood-brain barrier function. We suggest that this subcortically induced denervation microangiopathy may serve as a pathogenic factor in the development of SDAT.

Degeneration of the human Betz cell due to amyotrophic lateral sclerosis

Abstract The giant pyramidal cell of Betz is known to be partially affected in cases of amyotrophic lateral sclerosis (ALS). Though biochemical, physiologic, and histologic properties of the diseased Betz soma have been investigated, the morphologic status of the largest portion of cell membrane, that of its vast dendritic array, has not. Precentral cortex from six patients, ages 51 to 64 years, who had succumbed to the sequelae of ALS was examined using variants of the Golgi techniques. ALS is shown to be a degenerative disorder which causes a decline in the integrity of the Betz dendritic arbor as well as of the soma of origin. Dendritic fragmentation occurs and numerous irregularities appear, while the number of dendritic spines declines. Concomitantly, a reactive gliosis encroaches upon the soma and may extend onto initial dendritic segments. These observations are remarkably similar to those of the Betz cell in normal aging. The correlation of qualitative histologic data in these conditions is meaningful in light of suggestions that aging and ALS may be related processes. This could provide some clue as to the etiology of Betz cell degeneration and of motor neuron disease.

Altered Behavior Associated with Damage to the Ventromedial Hypothalamus: a Distinctive Syndrome

An adult manifested a tetrad of neurobehavioral findings consisting of episodic rage, emotional lability, hyperphagia with obesity, and memory impairment with intellectual decline following surgical removal of a craniopharyngioma. Post-mortem investigation of the topography of the lesion as well as review of previously reported cases suggest that this tetrad represents a specific neurobehavioral syndrome referable to damage to the ventromedial hypothalamus.