Granulovacuolar Degeneration Research Articles

Amyotrophic lateral sclerosis with diffuse neurofibrillary changes. Report of a case.

A 41-year-old male former boxer had amyotrophic lateral sclerosis (ALS) for about eight years prior to his death from bronchopneumonia. Neuropathologic examination revealed, in addition to the classical changes of ALS, numerous neurofibrillary changes (tangles) of the neurons in the cerebrum and brain stem. The tangles were most prominent in Ammon horn, amygdaloid nuclei, and locus caeruleus. Other findings included a moderate degree of neuronal loss and gliosis of the substantia nigra. Granulovacuolar degeneration and Hirano bodies were seen in the neurons of Ammon horn. Senile plaques were not found. The distribution of the tangles resembled that reported in Guamanian ALS. Ultrastructurally, the intracytoplasmic fibrils had a twisted configuration and were similar to those described in Alzheimer disease and Guamanian ALS. The presence and distribution of the neurofibrillary changes in a patient with ALS could well be coincidental; however, the occurrence of the Guamanian type of ALS in the northeastern population of the United States is worth reporting in view of the etiologic and epidemiologic considerations of this form of ALS.

Neurotoxic effects of 6-aminonicotinamide on cultures of central nervous tissue.

Well myelinated cultures of chick embryo spinal cord were exposed to medium containing 6-aminonicotinamide in a concentration of 0.5 mmol for up to 48 h. By 24–48 h of exposure to the antivitamin, neurons showed a granulovacuolar degeneration which later led to the formation of large vacuoles in the neuronal perikarya. Myelin degeneration was also observed in this period in the form of swelling, beading and ballooning. Electron microscopy revealed moderately swollen mitochondria and dilated endoplasmic reticulum as the earliest neuronal change. Later, neurons became pyknotic and the cytoplasmic organelles disintegrated. Presynaptic endings and glial cells, however, was spared any degenerative change. Intermittent and irregular splitting of myelin lamellae were also observed along the intraperiod lines. Biochemical assay of the glucose-6-phosphate dehydrogenase activity in the experimental cultures showed that 45% of the enzyme activity was lost during the 30-h period. It is concluded that the formation of 6-aminonicotinamide analogues of NAD and NADP coenzymes leads to the impairment of the pentose phosphate pathway and the glucose turnover, and thus produces neurotoxic effects in the central nervous system.

Morphologic study of a neuromyopathy caused by prolonged chloroquine treatment.

Two muscle biopsies were made in a case of chloroquine neuromyopathy in a 57-year-old woman with discoid lupus erythematosus. Histological study demonstrates widespread granulovacuolar degeneration and alterations of terminal innervation. Ultrastructural changes include formation of myelin figures and autophagic vacuoles. Of particular interest is the amount and mode of recovery from such alterations 2 months after cessation of the treatment.

Early Pick's disease. A light and ultrastructural study.

A case of asymptomatic Pick's disease is reported. The pathologic findings were limited to the amygdala, Ammon's horns, hippocampal gyri and right fusiform gyrus. Numerous Pick bodies, Hirano bodies and granulovacuolar degeneration of neurons were found. Pick bodies ultrastructurally were composed of randomly arranged short osmiophilic filaments of 125 to 200 A diameter which did not contain definite lumen.

Observations on the brains of demented old people

The brains from 50 cases of proven dementia in old age were examined and various features objectively assessed, and compared with similar features in a group of non-demented (controls) old people. Statistically significant differences were found in the two groups in relation to cortical atrophy, ventricular dilatation, senile plaque formation, Alzheimer's neurofibrillary change, granulo-vacuolar degeneration and the quantity of cerebral softening. Seventy per cent of the cases showed more changes of senile or ischaemic type than any control, and in 90% the changes found were probably sufficient to allocate the cases to a specific diagnostic category. 50% were considered to be cases of senile dementia, showing the histological features of Alzheimer's disease, the majority with no or small ischaemic lesions. By contrast only 12% appeared to be definitely and solely produced by cerebral softening (arteriosclerotic dementia) although a further 5% were probably of this origin. Mixed cases, with the pathological features of senile and arteriosclerotic disease, accounted for 8% with certainty, and probably for a further 10%, though the evidence in these latter cases was less certain. One case of Wernicke's encephalopathy was seen and 1 was possibly of traumatic origin. Five cases (10%) were not classified on pathological grounds, but in only 2 of these were no significant lesions found and 1 of these may have been mentally subnormal from birth. Striking sex differences in the incidence of the major lesions was found in the series. Thus 15 of the 16 females were, on pathological grounds, cases of senile dementia, whereas only 10 of the 34 males showed only this type of pathology, and in the males, arteriosclerosis probably caused, or contributed to the dementia in 50%. The age incidence of the cases of arteriosclerotic dementia was significantly less than the cases of senile dementia, or the cases of mixed senile or arteriosclerotic dementia. Arteriosclerotic dementia is almost certainly over-diagnosed clinically.

Motor nuclear involvement in progressive supranuclear palsy.

IN 1964, Steele et al 1 focused attention upon distinct clinicopathological syndrome which they termed progressive supranuclear palsy. The disorder was characterized clinically by ophthalmoplegia, mainly affecting vertical, and particularly downward gaze, pseudobulbar palsy, dysarthria, dystonic rigidity of the neck and upper trunk, and by other less constant cerebellar and pyramidal signs. It was emphasized that intellectual impairment was mild. The pathologic picture was one of neuronal loss, gliosis, neurofibrillary tangles, granulovacuolar degeneration, and demyelination which they believed to represent a degenerative disease, affecting chiefly the brain stem, basal ganglia, and cerebellum. There have been subsequent reports of this disorder, some with minor variation from the complete picture described by Steele et al, 1 but always with striking ophthalmoplegia and tonic rigidity as the outstanding clinical features. The purpose of this report is to present the second case of a woman studied pathologically as well as clinically, and

Neurofibrillary changes, granulovacuolar bodies and argentophilic globules observed in tuberous sclerosis.

A lesion of tuberous sclerosis was observed in the parietal cortex of a 13-year old girl. Numerous giant neurons in the affected areas contained Alzheimer's neurofibrillary tangles, granulovacuolar degeneration and argentophilic globules. These findings in tuberous sclerosis, insofar as we know, are new in the literature.

Observations on the brains of non-demented old people

The pathological findings in the brains of 28 old people, established by careful examination shortly before death as being free of evidence of dementia, are reported. Brain weights and ventricular size were not greatly different from those reported in younger age groups, and evidence of cerebral atrophy was usually slight or absent. Many brains showed softening and changes of “senile” type (senile plaques, Alzheimer's neurofibrillary change and granulo-vacuolar degeneration) either alone or in combination. An attempt was made to estimate the quantity of cerebral softening and to count the senile plaques and the extent of these changes is described. Cases with functional psychosis and acute confusion did not show greater pathological changes than those dying with purely physical diseases. These findings must be borne in mind when interpreting the changes in the brains of demented old people, or in the investigation of any other central nervous system disorder in old age.

Clinicopathologic significance of granulovacuolar degeneration in Alzheimer's disease.

The observation of granulovacuoles in the hippocampal pyramidal neurons in cases of senile dementia was made at the turn of the century, but the extent to which the abnormality is specific and of diagnostic value in morphologic classification has not been clearly established. An analysis of the abnormality in a series of 200 unselected autopsies on patients with all forms of mental disease is presented. Granulovacuolar degeneration among the hippocampal neurons is a constant finding in Alzheimer's disease which lends itself to easy recognition and quantitation using routine staining methods. With approximate quantitation the abnormal feature has sufficient specificity to be of diagnostic value, and, in contrast to more commonly used morphologic criteria, granulovacuolar degeneration retains its specificity for the clinical manifestations of Alzheimer's disease throughout the “senile” age period.