A. P. Anzil

Neurovisceral lipidosis compatible with Niemann-Pick disease type C: morphological and biochemical studies of a late infantile case and enzyme and lipid assays in a prenatal case of the same family.

SummaryOne postnatal and one prenatal case (same family) of a neurovisceral lipidosis compatible with a diagnosis of Niemann-Pick disease type C were studied. The postnatal case, aged 4 and 6/12 at death, was characterized morphologically (foamy cells in the bone marrow; storage histiocytes in rectal submucosa and extraneural viscera and ballooned neurons, the two types of cells containing pleomorphic and oligomenbranous inclusion bodies, respectively; central demyelination) as well as biochemically (elevated spleen and liver content of sphingomyelin, cholesterol, glucosyl ceramide and lysobisphosphatidic acid). Sphingomyelinase activity (SM) was not significantly lowered and showed no greatly abnormal electrofocused pattern of activity; its extractability from brain, liver and spleen was distinctly hindered, a finding interpreted as expression of a reduced bioavailability of the enzyme. — The prenatal case was diagnosed by low SM in amniotic fluid. Diminished SM was confirmed in cultured amniotic cells and in tissues of the aborted fetus which, additionally, showed an elevated sphingomyelin and cholesterol content in the liver. A prenatal diagnosis of Niemann-Pick disease type C was made for the first time. The phenotypical variation of the disease may reflect genetic heterogeneity and, there-fore, a prenatally lowered SM need not be a constant finding. — The apparent normalization of SM in the postnatal case was accompanied by a decrease of visceromegaly raising the question of a causal relationship between the two phenomena.

Immunohistological evidence of perivascular localization of basic protein in early development of experimental allergic encephalomyelitis

SummaryThe early histological changes in the CNS, functional state of the blood-brain barrier, production of humoral anti-brain immunoglobulins and immunohistological changes in myelin sheaths have been studied in two groups of guinea pigs inoculated with encephalitogenic antigens (basic protein, homologous and heterologous brain) mixed with two different doses of adjuvant. All antigens mixed with a low dose of adjuvant induced histological changes in about 20% of the animals. The blood-brain barrier was not or only slight disturbed. Antigens mixed with a high dose of adjuvant provoked severe EAE in 95% of the animals. The blood-brain-barrier displayed multiple injuries with diffusion of anti-brain antibodies into the nervous tissue. Antibody production showed no significant dependence on the different antigens and the various doses of adjuvant. The immunohistological examination using antibasic protein serum revealed the abolition of fluorescence within areas of inflammatory infiltrates and/or within areas of diffusion of antibodies. The perivascular accumulation of basic protein occurs early preceding the formation of perivascular infiltrates. It is proposed that this probably endogenous basic protein represents the first target structure, which can easily be trapped by circulating sensitized lymphocytes and/or antibodies. In this way it acts as a trigger of early lesions in EAE.

Progressive supranuclear palsy case report with pathological findings

SummaryAn additional case of Steele-Richardson-Olszewski syndrome is reported, the 14th to be examined pathologically. Clinically, trismus had been a prominent sign. Pathologically, the subthalamic and the dentate nuclei were the most severely affected areas. Isolated glial nodules were also found.ZusammenfassungEin zusätzlicher Fall von Steele-Richardson-Olszewski-Syndrom wird berichtet, der 14., der pathologisch-anatomisch untersucht wurde. Klinisch war ein Trismus das hervorstechende Symptom. Pathologisch waren der N. subthalamicus und dentatus die am schwersten befallenen Gebiete. Es fanden sich auch vereinzelt Gliaknötchen.

Intraneuritic corpora amylacea

Within the framework of an Early Postmortem Brain Sampling Program we had the opportunity to make some light and electron microscopic observations on the orbital cortex of two elderly subjects known to have been free of neurologic and psychiatric disease. Filamentous deposits with the ultrastructural appearance of corpora amylacea were seen inside astrocytic and, more rarely, inside neuronal processes. The findings and their interpretation are discussed in the light of current views on cerebral corpora amylacea and Lafora bodies. It is concluded that todays views on this matter do not account satisfactorily for the present observation or for observations we have quoted from the literature.

Rod-shaped filamentous inclusions and other ultrastructural features in a cerebellar astrocytoma.

SummaryA biopsy specimen of a cerebellar astrocytoma from a 14-year-old girl was studied by light and electron microscopy. Histologically the tumor showed a mixture of loose and compact areas with numerous Rosenthal fibers. By electron microscopy most tumor cells contained, besides the usual organelles, large amounts of 70 to 100 Å thick filaments. Classical Rosenthal fibers were also identified. In addition, many cell bodies and processes were sprinkled with fragments of Rosenthal fiber material. Ordered filamentous arrays (so-called Hirano bodies) were seen in a number of tumor astrocytes. They are considered to be a nonspecific arrangement of filament units largely devoid of cytopathologic significance. Other ultrastructural features of some tumor cells were inchoate forms of the granulated bodies of conventional histology, paired cisternal elements of rough endoplasmic reticulum, and honeycomb-like profiles of transversely cut cylindrical units of smooth endoplasmic reticulum. Microtubular bodies were numerous in the endothelial cells of the tumor vessels.

Nucleolus-like inclusions in neuronal perikarya and processes: phase and electron microscope observations on the hypothalamus of the mouse.

SummaryThe ventromedial hypothalamic nuclei of goldthioglucose-treated and control mice were examined by phase and electron microscopy. Neuronal perikarya and processes contained nucleolus-resembling inclusion bodies detectable by phase and electron microscopy. The inclusions consisted of round unbounded masses of granular- or filamentous-appearing material of variable density. Elongated forms were occasionally seen. Even in damaged nerve cell bodies and processes the inclusions were recognizable as relatively well-preserved structures. The hypothesis is presented that they represent a storage or transit form of readily available material which is either piled up in the perikaryon or moved along its processes before being finally used and/or released.ZusammenfassungDie ventromedialen Hypothalamuskerne von Mäusen nach Goldthioglucose-Injektion und von Kontrollmäusen wurden phasenoptisch und elektronen-mikroskopisch untersucht. Die neuronalen Perikaryen und Fortsätze enthielten nucleolusähnliche, phasenkontrast- und elektronenmikroskopisch sichtbare Einschlußkörper. Diese bestanden aus rundlichen, nicht membranbegrenzten Anhäufungen eines granulär oder filamentär erscheinenden Materials von unterschiedlicher Dichte. Gelegentlich wurden auch längliche Formen beobachtet. Sogar in stark geschädigten Nervenzellen waren die Einschlüsse noch als relativ gut erhaltene Strukturen zu erkennen. Es wird die Hypothese aufgestellt, daβ die nucleolusähnlichen Körper eine Depot- oder Transitform von schnell verfügbarem Material darstellen, welches entweder in den Perikaryen angehäuft oder in den Fortsätzen zum Ort der Verwendung und/oder Freisetzung transportiert wird.

Fenestrated blood capillaries in rat cranio-spinal sensory ganglia

SummarySeveral fenestrated capillaries were seen in the endoneurium of trigeminal and dorsal root ganglia from two young adult albino rats treated with tetraethylthiuram disulfide. The finding is regarded as normal, although the possibility exists that intoxication with tetraethylthiuram disulfide may have enhanced the intensity and/or rate of this cytologic specialization of some isolated endothelial cells.

Electron microscopic studies of rabbit central and peripheral nervous system in experimental Borna disease.

SummaryThe CNS and posterior root ganglia of rabbits experimentally infected with Borna virus were studied by electron microscopy. Intracytoplasmic crystalline arrays were common in the non-neuronal cell elements of the central and peripheral nervous tissues of all infected animals. Peculiar filamentous collections were seen occasionally in the central and peripheral neurons of one third of the inoculated rabbits. Control animals showed no such changes. In the affected tissues the nuclear density was increased. There were numerous cells grouped around the vessels or scattered singly or in clusters in the parenchyma. Amongst them plasma cells could be recognized as well as mononuclear cells of hematogenous origin, microglia cells in various reactive stages and macrophages derived from either of the latter cell types.The nonspecific character of the crystalline aggregates is emphasized. The questionable viral nature of the filamentous bundles is considered briefly; other explanations as to their nature are also mentioned. Finally, attention is drawn to the heterogeneous composition of the glial nodules and to the ultrastructural variability of the various cell types found in the inflamed tissues.

Intra-astrocytic glycogen granules and corpora amylacea stain positively for polyglucosans: A cytochemical contribution on the fine structural polymorphism of particulate polysaccharides

SummaryA cytochemical procedure for polysaccharides was carried out on a brain biopsy specimen, the thin-section study of which had shown excess glucogen granules and the corpora amylacea variety of polyglucosan bodies. Both granules and amyloid bodies were stained positively in contrast to the remaining structures of the brain tissue which remained unstained. This demonstrates that β-granules as well as filamentous and amorphous components of amyloid bodies are just different aspects of the polysaccharide molecule. Up to now the same kind of cytochemical evidence has been supplied for Lafora bodies of human material and Lafora-like bodies of rat material. The present study on corpora amylacea of human material shows that amyloid. Lafora, and Lafora-like bodies all behave the same way when stained for polysaccharides.

Peripheral nerve changes in porphyric neuropathy: Findings in a sural nerve biopsy

SummaryThe changes in a sural nerve biopsy of a patient with porphyric neuropathy were studied by light and electron microscopy. Linear arrays of myelin ovoids constituted the most common abnormality in whole mounts of teased-fiber preparations. Round or irregular formations of variable osmiophilia were the most frequent finding in thick-section preparations examined by phase contrast microscopy. Lamellar whorls represented the most prevalent lesion in thinsections studied under the electron microscope. In addition, along the teased fibers, segmental demyelination was definitely detected, although rarely; in thick sections, the true extent of the nerve fiber loss was fully appreciated; in thin sections, a variety of axon and myelin changes of a distinct character were discovered. The studies demonstrate that in peripheral nerves of porphyric neuropathy, axonand myelin changes generally run together and proceed pari passu in the same segment of nerve fiber. Furthermore, among the pathogenetic mechanisms invoked to account for the neuropathic changes none are favored to the exclusion of others by these studies. Therefore, a primary axonaland myelinic disorder on the basis of a deranged porphyrin metabolism is as good a possibility as any hitherto advanced explanation of the pathogenesis of the neuropathic changes. The secondary lesions of Wallerian degeneration and segmental demylination may simple be grafted upon the primary lesions evoked by the metabolic abnormality.