Angeline R. Mastri

Dementia lacking distinctive histologie features A common non‐Alzheimer degenerative dementia

From a series of 460 dementia patients referred to a regional brain bank, 14 (3%) patients had a pathologic diagnosis of primary degeneration of the brain involving multiple sites (frontoparietal cortex, striatum, medial thalamus, substantia nigra, and hypoglossal nucleus), with cell loss and astrocytosis. There were no neuronal inclusions and essentially no senile plaques. This entity, which we have termed “dementia lacking distinctive histology” (DLDH), presented with memory loss and personality changes, and led to death, usually within 2 to 7 years. Dysarthria and dysphagia were prominent in the later phases of the illness in most patients. The psychometric findings of some of the patients were consistent with a “frontal” lobe dementia. A few patients had prominent caudate atrophy on CT as well as neuropathologically. Eight of our patients had positive family histories for neurologic disease, mainly dementia. DLDH, in addition to Picks disease, is a major member of the frontal-lobe dementia group. In patients under age 70 years, the frontal lobe dementias represent an important diagnostic consideration.

Pick's disease versus Alzheimer's disease A comparison of clinical characteristics

The clinical recognition of Picks disease depends on its differentiation from Alzheimers disease (AD). To identify distinguishing clinical features, we reviewed the clinical records of 21 patients with pathologically confirmed Picks disease and matched them by sex, age of onset, and duration of dementia with 42 patients having pathologically confirmed AD. In the absence of temporal or frontal lobar atrophy on CTs, all the Pick patients and none of the AD patients had three of five clinical features: presenile onset (before age 66), an initial personality change, hyperorality, disinhibition, and roaming behavior. In addition, the Pick patients had a tendency toward reiterative and other speech disturbances. These findings suggest that Pick patients are potentially distinguishable from AD patients on the basis of clinical manifestations.

Clinically diagnosed Alzheimer disease : neuropathologic findings in 650 cases

Summary:Despite the introduction of formal clinical criteria for Alzheimer disease (AD), the clinical diagnosis of AD remains one of exclusion of other dementias. To determine the accuracy of a clinical diagnosis of AD as made by practicing physicians, we reviewed the clinicopathologic records of a dementia brain bank and summarized the literature. Of 650 demented patients diagnosed during life as having AD, at autopsy 505 (78%) had AD with or without other neuropathologic conditions; only 390 (60%) of these had AD as the only neuropathologic condition. Of the remaining 145 (22%) patients with no neuropathologic evidence of AD, 39 had the nigrostriatal changes of Parkinson disease (PD), 25 had nonspecific degenerations, 15 had Pick disease, 14 had multiple infarcts, and 11 lacked any neuropathologic abnormality. Although the overall clinical accuracy for AD was lower than that summarized from the literature, clinical accuracy improved significantly between 1986 and 1990. In our broad sample of practitioners, accuracy of clinical diagnosis of AD may be improving, but continues to be hampered by difficulty in distinguishing the dementia of AD from certain dementing conditions and from AD mixed with other neuropathologic conditions.

Pathology of Shy-Drager Syndrome

In four patients with the Shy-Drager syndrome, detailed pathological findings in the central nervous system are described. All four patients had striatonigral degeneration, olivopontocerebellar atrophy, pyramidal tract degeneration and ventral horn cell loss. Along with the multisystem degeneration, there was widespread loss of thoracolumbar autonomic neurons, which was demonstrated by comparative cell counts of the intermediolateral horns in two of the four patients. In all four patients, autonomic nuclei of the sacral cord, particularly the Onufs and intermediolateral nuclei, were severely affected and diffuse cell loss in the nuclei seems to account for disordered bladder, rectal and sexual functions in Shy-Drager syndrome.

Axonal dystrophy in the gracile nucleus in congenital biliary atresia and cystic fibrosis (mucoviscidosis): beneficial effect of vitamin E therapy.

In 63 patients with malabsorption syndromes, 16 with congenital biliary atresia (BA) and 47 with cystic fibrosis (CF), axonal dystrophy in the gracile nucleus (ADG) was studied. Of the 16 patients with BA, ADG of considerable severity was observed in all 10 over one year of age. Of the 47 patients with CF, it was observed in 32, 61, and 80% of the cases in the first, second, and third decades, respectively. Evidence is presented that there has been a substantial decrease in the incidence of ADG in CF patients in recent years and that the decreased incidence is attributable to vitamin E (Aquasol E) therapy. The beneficial effect of vitamin E supplementation in CF patients is proffered as strong evidence that ADG in BA and CF is related to vitamin E deficiency. The present study indicates that BA and CF patients require vitamin E supplementation to maintain a normal integrity of axons related to the gracile and perhaps other sensory nuclei. Critical neurological evaluation for possible dysfunction of the sensory nuclei in these patients with malabsorption syndromes is advised.

An Unusual Degenerative Disorder of Neurons Associated with a Novel Intranuclear Hyaline Inclusion (Neuronal Intranuclear Hyaline Inclusion Disease)A Clinicopathological Study of a Case

A 21-year-old woman with an unusual, progressive, degenerative neurological disorder is described. The disorder is characterized clinically by behavioral abnormality, peculiar involuntary movements, and ataxia starting in early childhood and subsequent development of dementia, choreoathetosis, rectal and bladder incontinence, bulbar and spinal muscular weakness, pes cavus, kyphoscoliosis, and generalized seizures. The clinical manifestations are correlated, with widespread pathological changes affecting almost all neuronal systems. The pathological changes are discussed in relation to the wide spectrum of “multisystem atrophies.” Particular attention is directed to the ubiquitous occurrence of a novel intranuclear, eosinophilic, hyaline inclusion in almost all types of central, peripheral, and autonomic neurons. The ubiquitous neuronal involvement seems to explain the diffuse multiple system degeneration. The pathogenesis of the neuronal inclusions is unknown, but it is speculated that the disorder may represent a metabolic abnormality affecting the nuclear protein of neurons, rather than a viral infection. The pathological features, consisting of the neuronal intranuclear hyaline inclusions associated with multiple system atrophy, have not hitherto been described, and “neuronal intranuclear hyaline inclusion disease” is proposed as a name for the disorder. Rectal biopsy demonstrating the intranuclear hyaline inclusions in ganglion cells of the myenteric plexuses may serve as a diagnostic procedure for the disorder.

Tuberous sclerosis: a review for the neurosurgeon.

&NA; The clinical. radiological, and pathological characteristics of tuberous sclerosis are reviewed. Neurosurgical intervention in the syndrome is discussed in light of two recently treated cases and a literature review. (Neurosurgery 14:93‐98. 1984)

Dementia without Alzheimer pathology

We studied five demented patients who, on neuropathologic examination, had cell loss and Lewy bodies in substantia nigra and locus ceruleus and few Alzheimer-type changes. The nucleus basalis had minimal cell loss in three patients and was not available in two. The lesions in the substantia nigra and locus ceruleus were unlikely to account for the dementia, and other structural or biochemical derangements, probably cortical but possibly subcortical, must also have been present but not visible at the light microscopic level.

Ineffectiveness of Dexamethasone for Treatment of Experimental Cerebral Infarction

Ischemic cerebral edema occurring with cerebral infarction may cause increases of intracranial pressure and neurological deficits or death. Certain other types of cerebral edema are influenced by adrenal glucocorticoids; there is conflicting evidence about effects on ischemic edema, largely due to differences in experimental models and dosages. Therefore, dexamethasone in large doses was studied in 15 cats with experimental cerebral ischemia and infarction produced by transorbital occlusion of one middle cerebral artery (MCA). Five cats received dexamethasone, 4 mg per kilogram intramuscularly, twice daily for two weeks before and two weeks after MCA occlusion; five received dexamethasone for two weeks after occlusion; and five received no dexamethasone. There were no apparent differences among the three groups in the neurological deficits resulting from MCA occlusion, and no statistically significant differences in the sizes of cerebral infarcts. Dexamethasone is ineffective for the treatment of experimental cerebral ischemia produced by MCA occlusion.

Spinal autonomic neurons in Werdnig-Hoffmann disease, mannosidosis, and Hurler's syndrome: distribution of autonomic neurons in the sacral spinal cord.

In Werdnig-Hoffmann disease, mannosidosis, and Hurlers syndrome, two groups of neurons (the Onuf s and intermediomedial nuclei) in the ventral horn of the mid-sacral region are found to share common selective sparing or vulnerability with the intermediolateral nuclei of the thoracolumbar and sacral regions of the spinal cord. This finding confirms the previous observations on the characteristic involvement or sparing in Fabrys disease (14), Shy-Drager syndrome (17), amyotrophic lateral sclerosis, anterior poliomyelitis, and neuronal intranuclear hyaline inclusion disease (15), and supports the assumption that the Onuf s and intermediomedial nuclei in the ventral horn represent autonomic neurons much as the thoracolumbar and sacral intermediolateral nuclei.