Masazumi Adachi

Spongy degeneration of the central nervous system (van Bogaert and Bertrand type; Canavan's disease). A review.

Abstract The clinical, genetic, morphological, and biochemical aspects of spongydegeneration of the central nervous system in infancy, including our own seven cases, are reviewed. Although the pathogenesis is still obscure, recent ultrastructural and biochemical studies have demonstrated unique features that are consistent, with the accumulation of excessive fluid mainly within the astrocytic cytoplasm and myelin lamellae. The primary cause of fluid aggregation is unknown. However, ultrastructural and histochemical studies suggested that spongy degeneration is primarily due to a metabolic disturbance of abnormal astrocytic mitochondria. Further studies of these organelles therefore may provide a better understanding of this disease.

PRENATAL DIAGNOSIS OF TAY-SACHS DISEASE

Abstract Uncultured cells and fluid collected by amniocentesis during the second trimester from a mother of a child with Tay-Sachs disease were shown to have trace amounts of hexosaminidase-A activity. Accordingly the pregnancy was terminated. Biochemical and morphological studies of the aborted fetal tissue confirmed the prenatal diagnosis of Tay-Sachs disease.

Fine Structure of Spongy Degeneration of the Central Nervous System (van Bogaert and Bertrand Type)

The present study describes the fine structure of cortex and white matter of a one year old Jewish boy afflicted with spongy degeneration of the brain. The most characteristic clinical and pathologic feature of this disease is megalencephaly which is due to increased intracellular water content in the brain, mainly in the subcortical white matter. The light microscopic picture was similar to that previously reported. Electron microscopically, multiple vacuoles in the subcortical white matter and deep cortical lamina (fusiform layer) were due to separation of the lamellae of myelin. The vacuoles were present between the major dense lines of the myelin membranes, and it is conjectured that the obscured intraperiod lines might be the origin of these vacuoles. The extracellular spaces in the subcortical white matter were widened due to the rupture of the myelin lamellae and astrocytic cell membranes. It is hypothesized that a secondarily increased extracellular water content in the white matter might have accelerated further degeneration in the white matter at the advanced stage. There were smaller vacuoles present in the cortex, especially in the ganglionic layer which were the result of marked enlargement of astrocytes and their processes, although no increased extracellular spaces or ruptured cell membranes were present. The large and pale astrocytic nuclei described as Alzheimer type II by light microscopy appeared ultramicroscopically also enlarged and were seen to contain sparse nucleoplasmic granules, loss of chromatin and distinct nucleoli with preserved nucleolonema. Marked changes in size, and frequently in appearance, of mitochondria were observed in the processes of the astrocytes in the cortex, especially in the ganglionic layer. Histochemical studies showed that the activity of ATPase within these mitochondria was decreased when compared with that of normal brain tissue. The fine structure of the neurons, oligodendroglia and blood vessels was not altered.

The AB-variant of GM2-gangliosidosis

SummaryClinical, neuropathological, and biochemical studies are reported in two children with the aB-variant of GM2-gangliosidosis. One patient had become symptomatic by 1–1.5 years, initially showing cerebellar signs, and then progressive psychomotor retardation, with hypotonia, spasticity, dementia, and macular cherry red spots, until death at the age of 4.5 years. The second patient showed an earlier onset of retardation and a more rapidly progressive course. At postmortem, the brains were of normal or near normal weights and displayed grossly only mild cerebral cortical and cerebellar atrophy, and mild pallor or attenuation of the white matter. Neuronal storage was widespread throughout the CNS, and both neurons and glia contained a variety of abnormal, membranous inclusions. Visceral organs were not involved. Ganglioside sialic acid was increased several fold in gray matter, with GM2 the predominant ganglioside species. N-acetyl-β-glucosaminidase activities in serum, leukocytes, fibroblasts, and postmortem gray matter, assayed with an artificial, fluorogenic substrate, were normal, as were activities of other lysosomal hydrolases.

Congenital failure of myelinization: Pelizaeus‐Merzbacher disease?

MERZBACHER disease was restricted to a unique and characteristic combination of clinical and pathological criteria.182 Merzbacher conceived the disorder to be the result of a congenital aplasia of myelin sheaths.2 The original criteria have been gradually expanded and modified to accommodate an ever-increasing number of cases, and consequently the eponymic designation has lost much ef its original clinical value.3 The nosologic cohfusion has been compounded by speculative concepts of pathogenesis.3-7 The present case offers biochemical and morphological support for the concept of congenital arrest or aplasia of myelin sheaths. Furthermore, there is circumstantial evidence relating this case to Pelizaeus-Merzbacher disease, and thus the pathogenesis of PelizaeusMerzbacher disease may be associated with a failure of myelination.

Electron microscopic and enzyme histochemical studies of cerebellum, ocular and skeletal muscles in chronic progressive ophthalmoplegia with cerebellar ataxia

SummaryElectron microscopic and enzyme histochemical studies were performed on the cerebellum and the ocular and deltoid muscles from a 38 year old woman who developed bilateral ptosis at the age of nine years. Histologically the cerebellum appeared normal. The biopsies of three ocular muscles showed varying sizes of muscle fibers which were rounded and contained increased numbers of subsarcolemmal nuclei. The deltoid muscle stained by hematoxylin and eosin appeared normal, but the trichrome stain showed increased numbers of red granules within the sarcolemma corresponding ultrastructurally to increased numbers of abnormal mitochondria. These abnormal mitochondria displayed increased reaction products with LDH, NADH and SDH preparations, while the muscle gave normal reaction in phosphorylase, PAS and myosin ATP preparations. Chemical studies on the cerebellum showed normal proteolipids, glycolipids and phospholipids. Ultrastructurally, the cerebellum, the myofibers of three ocular muscles and the deltoid muscle exhibited abnormal mitochondria which showed peculiarly arranged circular cristae. They frequently contained paracrystalline structures which consisted of individual tubules arranged in a helical pattern. Frequently, the abnormal mitochondria were replaced by dense rectangular inclusions and occasionally showed complete transition to crystalline structures.

Electron miscroscopic and enzyme histochemical studies of the cerebellum in spongy degeneration

SummaryElectron microscopic and enzyme histochemical studies were performed on the cerebellum from a 9 month old Jewish boy with spongy degeneration. Histologically, the main pathological changes were noted in the Purkinje cell layer, the deeper areas of the granular cell layers and the subcortical white matter. Ultrastructurally, multiple vacuoles were present within the swollen cytoplasm and processes of protoplasmic astrocytes in the cortex, while in the subcortical white matter vacuoles were observed within splitting myelin lamellae as well as within astrocytes. There were also abnormal mitochondria within swollen protoplasmic astrocytic cytoplasm and processes which in ATPase preparations showed little or no reaction product. However, the fibrillary astrocytes were not swollen and contained intact mitochondria which showed normal reaction product in ATPase preparations. Since the myelin changes are known to be nonspecific and secondary to abnormal fluid accumulation, the characteristic distribution of the multiple vacuoles in the central nervous system in this disorder seems primarily to be related to swelling of the protoplasmic astrocytes.

Effects of sodium deprivation on pituitary and plasma prolactin, growth hormone, and thyrotropin levels in the rat.

An experiment was performed to determine the effectof sodium deprivation on pituitary and plasma radioimmunoassayable proiactin, growth hormone and thyrotropin, aldosterone and total corticosteroid se

Clinical and ultrastructural correlation in congenital and acquired ptosis.

The levator superioris muscle has been studied with the light microscope and the electron microscope in congenital and acquired ptosis. Ultrastructural finding correlated closely with the clinical entities. Congenital ptosis appears to be on a myogenic basis. Acquired ptosis ultrastructurally indicates a regenerative process.

Enzyme replacement treatment for Tay-Sachs disease brain cells in culture utilizing Concanavalin A-mediated hexosaminidase A uptake: Biochemical and morphological evidence of GM2 mobilization

SummaryWhen Concanavalin A (Con A) is bound to the cell membrane, it functions as an artificial enzyme receptor, mediating the binding and intracellular incorporation of significant amounts of exogenous hexosaminidase A (Hex A) into Tay-Sachs disease (TSD) glial cells. The treated cells retained almost 50% of incorporated Hex A activity after 3 days incubation in Hex A free medium. Hex A was released from Con A within the cell and was available as free enzyme. Biochemical analysis of gangliosides in Con A and Hex A treated cells depicted a greater than 50% reduction in stored GM2 ganglioside and a fourfold reduction in GM2label (14C) when compared to controls. Ultrastructural evidence of GM2 breakdown is presented which supports the biochemical and labeling studies.