Albert Bischoff

Oligodendroglial cell development in jimpy mice and controls. An electron-microscopic study in the optic nerve.

Glial development was studied in the optic nerve of 1- to 28-day-old Jimpy mice and controls. Abnormalities were found in oligodelopment and axons were not affected. These consisted in (a) Increased numbers of glioblastic cells containing lipids and increased occurrence of glial cell death in the premyelination stage; (b) Decreased numbers of maturing oligodendrocytes (i.e. young and active oligodendrocytes) in the period of early myelination; (c) An occurrence of abnormal oligodendroglial cells containing lipids and multimembranous tubes in the period of advanced myelination. The decreased number of maturing oligodendrocytes in the premyelination stage indicates that the lack of myelin in Jimpy mice may be secondary to a disturbance in the differentiation of the oligodendroglial cell line. The occurrence of abnormal, lipid-containing glioblasts and oligodendrocytes may be an expression of a defect in metabolism leading to an abnormality in the association of myelin proteins and myelin lipids.

Dysmyelination in 'jimpy' mouse. Electron microscopic study.

Abnormalities in oligodendroglial cells and nodal regions of the myelinated fibers in spinal cord and optic nerve of the mutant mouse Jimpy are described. Membranous tubes were found in the oligodendroglial cells which may have derived from abnormal membrane formation in these cells, thus representing dystopic myelin membrane formation. The rare myelin sheaths present in the Jimpy spinal cord were never found to extend over a distance greater than one internode. They terminated in halfnode structures which often showed abnormalities in the relation between axon and myelin sheath. These observations are interpreted to be further indications that the Jimpy defect consists of a dysmyelination due to oligodendroglial insufficiency.

Morphological and biochemical observations in the Jimpy spinal cord

SummaryThe cervical spinal cords from Jimpy and normal mice were examined by light and electron microscopy at 2 to 29 days after birth. By 2 days after birth the number of myelinated fibres present in the Jimpy spinal cord was significant less than the number present in normal spinal cords. This made it possible to identify the Jimpy mice before onset of the clinical symptoms. The paucity in myelin was also demonstrated by biochemical criteria. Astroglia cell sappeared normal in the Jimpy spinal cord but there was an apparent disturbance in the development of the oligodendroglial cell line, resulting in the appearance of abnormal cells containing voluminous lipid inclusions and/or membranous tubes. The probable significance of these observations and their relation to the myelin defect in the Jimpy mouse is discussed in the light of pathogenetic theories of human leukodystrophies.

Generalized giant axonal neuropathy

SummaryThe process of Giant Axonal Neuropathy (GAN) is not restricted to the peripheral nerves, but also involves the central nervous system. In a 25 year old man with normal hair, abundant axon swellings and spheroids were observed in the spinal cord, brain system, and cerebral cortex. The findings in the sural nerve have already been published by Boltshauser et al. (1977). Accumulations of filaments in the axons and in the perineural cells were accompanied by Rosenthal fibres. The ultrastructural pattern of GAN differs clearly from that of Neuroaxonal Dystrophies.

Sequence of morphological alterations in the nervous system of metachromatic leucodystrophy

SummaryLight and electronmicroscopic findings are reported in a case of metachromatic leukodystrophy diagnosed prenatally who died after iatrogenic abortion during the 23th week of gestation. The brain of this foetus was not yet myelinated while the spinal cord showed early, and the peripheral nerves advanced myelination. The onset and the degree of myelination were similar as in a normal foetus of the same age. Ultrastructurally there was evidence of sulphatide storage before the beginning of myelination. During myelination lysosomal storage material, staining metachromatically in acid cresyl violet preparations, appeared in oligodendrocytes and Schwann cells. Besides sulphatide storage material, prominent amounts of neutral lipids were found in oligodendrocytes. Myelin breakdown was encountered very seldom.

Morphological observations in the nervous system of prenatal mucopolysaccharidosis II (M. Hunter)

SummaryLight and electron microscopic findings in the nervous system of a 23-week-old fetus are reported, in which MPS II was diagnosed prenatally. The degrees of myelination and neuronal differentiation were similar as in a normal fetus of the same age. A storage of mucopolysaccharides in typical vacuolar inclusion bodies was present throughout the peripheral and central nervous system, mainly in cells of mesenchymal origin. “Zebra” bodies and granulo-membranous bodies, which are thought to represent secondary ganglioside accumulation were only found in the well developed neurons of the spinal cord and spinal ganglia, but not in the poorly developed neurons of the cerebellar and cerebral cortex. Mucopolysaccharide storage in endothelial cells of cerebral blood vessels precedes the appearance of lipid storage in cerebral neurons.

Dynamic aspects of peripheral nerve changes in progressive neural muscular atrophy

SummarySerial nerve biopsies were performed at an early, and at an advanced stage of the disease in 2 patients with progressive neural muscular atrophy. The early biopsy showed a complete loss of the large diameter and thickly myelinated fibres, as well as an expansion of the endoneurial interstitium in both cases. Myelinated and unmyelinated fibres exhibited axonal degeneration in all biopsies occasionally. “Onion bulb” formation, a typical feature of peripheral neuropathy in neural muscular atrophy, was found to be prominent only in the latter biopsies. As regards the formal pathogenesis of hypertrophic neuropathy in neural muscular atrophy, axonal dystrophy and interstitial changes of the endoneurium were regarded as primary phenomena, demyelination and “onion bulb” formation as secondary. A possible causal relation between axonal dystrophy and interstitial changes, observed in these cases, is discussed in the light of the present literature.ZusammenfassungBei 2 Patienten mit progressiver neuraler Muskelatrophie wurden Nervenbiopsien jeweils in einem frühen und in einem fortgeschrittenerem Stadium der Erkrankung entnommen und verglichen. In beiden Fällen zeigten bereits die frühen Biopsien ein völliges Fehlen der großkalibrigen, dickbemarkten Axone. Ebenfalls als frühe Veränderung wurde eine Erweiterung des endoneuralen Interstitiums festgestellt. Eine geringe Anzahl der vorhandenen bemarkten und unbemarkten Axone in allen Biopsien wies degenerative Veränderungen auf. Die für die progressive neurale Muskelatrophie typische Zwiebelschalenbildung der Schwannschen Zellen — möglicherweise eine Reaktion auf wiederholte De-und Remyelinisierungsvorgänge um dystrophische Axone — trat erst in den späteren Biopsien deutlicher hervor. Hinsichtlich der formalen Genese der hypertrophischen Neuropathie bei neuraler Muskelatrophie sind nach diesen Beobachtungen axonale Dystrophie und interstitielle Veränderungen des Endoneuriums als primäre Entmarkung und Zwiebelschalenbildung als sekundäre Phänomene zu betrachten. Die Möglichkeit einer kausalen Beziehung zwischen axonaler Dystrophie und interstitiellen Veränderungen wird an Hand der vorliegenden Befunde und Literatur diskutiert.

Focal mucoid degeneration of peripheral nerve. Light- and electronmicroscopic observation in a sural nerve biopsy of a case of progressive neural muscular atrophy (Charcot-Marie-Tooth).

Summary“Focal mucoid degeneration” was found in a N. suralis biopsy of a 8 year old child, diagnosed clinically and electrophysiologically as progressive muscular atrophy Charcot-Marie-Tooth.

Late infantile metachromatic leucodystrophy (MLD)

SummaryA typical case of late infantile MLD is presented with all available clinical, morphological and biochemical results. The diagnostical value of the different parameters is evaluated and the pathogenesis of the disorder discussed. In spite of successful experimental enzyme substitution in cultured MLD fibroblasts with restitution of function by added Arylsulfatase, the therapeutic possibilities for the fatal disease in the patients are extremely limited.ZusammenfassungAn einem typischen Fall von spätinfantiler metachromatischer Leukodystrophie (MLD) werden die klinischen und morphologischen Befunde sowie neuere biochemische Resultate dargestellt. Die Pathogenese der Krankheit wird aus dieser Sicht besprochen. Obwohl an gezüchteten Fibroblasten der Patienten mit MLD der Enzymdefekt und die metabolische Störung korrigiert werden können, sind die therapeutischen Möglichkeiten für diese letale Krankheit sehr beschränkt.

Niemann-Pick's disease

SummaryA diagnosis of Niemann-Pick disease type A was made in a 6-month-old boy on the grounds of progressive psychomotor retardation, hepatosplenomegaly, typical foam cells in the bone marrow and a deficiency of sphingomyelinase in a liver biopsy. Typical ultrastructural changes in lysosomes were found in hepatocytes and in Schwann cells. In spite of the absence of gross morphological changes in the axons and in the myelin sheath of the peripheral nerve biopsy, the nerve conduction velocity in the patient was greatly reduced. The ultrastructural aspect of the lysosomal inclusion suggested the storage of a phospholipid. Biochemical analysis of the liver biopsy demonstrated an increased content of total phospholipid of which sphingomyelin made up for more than 60%. The significance of these data are discussed.ZusammenfassungDas klinische, biochemische und ultrastrukturelle Bild einer Sphingolipidose vom Typ Niemann-Pick wurde an Hand eines Patienten mit der infantilen Form (A) dargestellt. Die Diagnose wurde klinisch auf Grund einer rasch progredienten psychomotorischen Retardation mit Hepatosplenomegalie sowie typischen Schaumzellen im Knochenmark gestellt und durch den Nachweis von exzessiver Speicherung von Sphingomyelin in einer Leberbiopsie und das Fehlen der Sphingomyelinase bestätigt. Ultrastrukturell konnte eine Anhäufung von präsumptiven Phospholipiden in den Lysosomen von Leber und peripherem Nerv festgestellt werden. Obwohl weder eine axonale Degeneration noch eine Demyelinisierung im biopsierten Nerv gefunden werden konnte, war die Nervenleitgeschwindigkeit in den peripheren Nerven beim Patienten schon bei der Diagnosestellung deutlich herabgesetzt. Die Bedeutung der Befunde wurde diskutiert.