Morphological changes in experimental amyotrophic leukospongiosis

A new nosological entity of slow infections provoked by noncanonical viruses was experimentally studied. It was shown that natural human infection and infection induced in guinea pigs had common clinical and morphological parameters and were characterized by severe changes in the central nervous system. Histologically, the death of the motoneurones of the spinal cord, the spongious state of the white matter of the brain and spinal cord, relative preservation of myelin, hypertrophy and proliferation of macroglia were histologically observed.     

Morphological changes in the central nervous system in amyotrophic leukospongiosis

A histological study of a peculiar progressive disease of the central nervous system (CNS) named amyotrophic leukospongiosis was carried out in 5 observations. The regular histological signs included the loss of motor neurons in the spinal cord and encephalon, the status spongiosus of the white matter in the anterior and lateral columns of the spinal cord and different parts of the white matter in the encephalon. Unlike amyotrophic lateral sclerosis, amyotrophic leukospongiosis is characterized by intact myelin fibers of the anterior and lateral columns (including pyramidal tracts). The clinical, epidemiological, and histological data allow the disease to be classified into the group of slow virus infections.     

Reproduction of amyotrophic leukospongiosis in laboratory animals

Amyotrophic leukospongiosis (ALSP) was produced in laboratory animals: hamsters, rabbits, guinea pigs. Guinea pigs were found to be a most suitable laboratory model for the study of ALSP pathogenesis with the longest incubation period. The data are obtained verifying the role of previously isolated unconventional virus in the ALSP etiology.     

Characteristics of the etiological agent of human amyotrophic leukospongiosis

Primary cultures of brain cells from a patient with amyotrophic leukospongiosis (ALSP) and animals with the experimentally reproduced disease yielded an agent which by its physicochemical and molecular biological properties was placed among nonclassical viruses, the agents of spongiform encephalopathies. The agent is small and resistant to a number of detergents, lipid solvents, oxidants, enzymes, UV irradiation, and heating. The role of the isolate in the development of ALSP is verified by experimental reproduction of the disease in guinea pigs inoculated either with a brain suspension from ALSP patient or with the purified and concentrated agent. The true nature of ALSP in experimentally inoculated animals was verified by clinical, morphological, and virological studies.     

Participation of reticuloendothelial system in the pathogenesis of experimental amyotrophic leukospongiosis

Spleen and peripheral blood lymphocytes were found to play an important role in the pathogenesis of amyotrophic leukospongiosis (AL). At early stage of AL they are the sites of reproduction and accumulation of an unconventional virus; they also provide its dissemination in the body of infected animals. In lymph nodes and visceral organs the AL pathogen was detected in much lower quantities and only in the period of clinically manifest disease. The level of the complement was significantly decreased in the serum of animals with experimental AL. This decrease correlated with the development of clinico-morphological lesions and reached its maximum at the terminal stage of disease.     

Viral retrograde-like pattern of neuronal degeneration in experimental amyotrophic leukospongiosis

The pattern of destructive alterations of neurons and their processes at different spinal cord levels in guinea pigs with experimental amyotrophic leukospongiosis (AL) was studied by light and electron microscopy. The destruction of a portion of neurons was found to be of retrograde degeneration type. Electron microscopy of spinal conduction pathways showed that degenerative alterations occurred not only in the neuronal soma or processes but also in synaptic structures. The results indicate primary involvement of nerve cell processes, particularly axons, in experimental AL. It is suggested that AL pathogenesis is pathomorphologically based on the uptake of the agent by axonal terminals.     

Pathogenesis of amyotrophic leukospongiosis reproduced in guinea pigs by retrobulbar infection

Pathogenesis of amyotrophic leukospongiosis (ALSP) with a short incubation period induced in guinea pigs was studied. After retrobulbar inoculation, the unconventional ALSP virus disseminated both neurogenically (along the optic nerve) and hematogenically. At early stages of the disease the spleen appeared to play the leading role in multiplication and/or accumulation of the agent. The earliest morphological sign of the CNS involvement was vacuolation of motoneuron cytoplasm. The ALSP agent first affected the spinal motoneurons, then an ascending pathological process developed. In the terminal stage of the disease, the unconventional ALSP virus was also detected in visceral tissue, besides the CNS, spleen, and peripheral blood lymphocytes.     

Cellular transformation in an MDCK culture caused by the agent of amyotrophic leukospongiosis

The possibility of infecting epithelioid MDCK cell culture with the agent of amyotrophic leukospongiosis (AL) was shown. Various morphofunctional changes were observed in the infected cells. In the first subpassage, the saturation density and yields of cells increased, while their mitotic activity decreased and adhesive properties changed. In the second subpassage, the cell morphology and monolayer architectonics changed, the cells losing the ability to form a confluent monolayer. The infected cultures died in further subpassages. Clinical signs of the disease and morphological changes in the CNS typical of AL were observed in the animals infected with a homogenate of cells and culture fluid from the AL-agent-infected cultures.     

Accumulation dynamics of the agent of amyotrophic leukospongiosis and the development of degenerative changes in the central nervous system of guinea pigs

After retrobulbar inoculation into guinea pigs, the agent of amyotrophic leukospongiosis was detected in the central nervous system (CNS) as early as 7 days post-infection (p.i.), whereas specific morphological changes appeared since days 14 to 21 p.i. Virological and morphological findings suggested that motoneurons of the spinal cord were first damaged in the course of the pathologic process which then proceeded upwards.     

Ultrastructural changes of mitochondria in the skeletal muscle of patients with amyotrophic lateral sclerosis

Functional defects and morphological changes of mitochondria have been reported to be in the skeletal muscle of patients with amyotrophic lateral sclerosis (ALS). Recent studies suggested that mitochondrial abnormalities are related to the pathogenesis of ALS. The purpose of this study is to evaluate the ultrastructural changes of muscle mitochondria in ALS patients. The authors examined 49 cases of diagnostic muscle biopsy samples with definite or probable ALS by electron microscopy. Of the 49 cases, 5 (10%) had ultrastructural abnormalities of muscle mitochondria, including giant mitochondria, paracrystalline inclusions, and abnormal cristae. These abnormal mitochondria were mainly observed among subsarcolemmal mitochondrial aggregates.     

Ultrastructural changes in the CNS of monkeys with the chronic form of tick-borne encephalitis

The central nervous system of monkeys with chronic tick-borne encephalitis (TBE) shows the following ultrastructural alterations which differ from those in acute TBE: widespread destructive changes in neurons, astrocytes, oligodendrocytes, processes, myelin, vascular walls, severe edema of brain tissue with the signs of a so-called spongious degeneration and the absence of cell proliferation and perivascular cell infiltrations, glial nodules as well as circulatory disorders (hyperemia, stasis, hemorrhages). Few virions with or without and altered supercapsid membrane are detected in the neuronal cytoplasm or in the intercellular spaces; the signs of active virus reproduction in the cells are lacking. Pathologic process is of a degenerative but not of an inflammatory nature; the latter is typical for acute TBE.     

Infectivity of 18–20 kD proteins isolated from the brain of victims of amyotrophic leukospongiosis

Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 116, N ^o 10, pp. 409–412, October, 1993     

The persistence of the causative agent of amyotrophic leukospongiosis and the astrocyte reaction in monolayer cultures of brain cells

The amyotrophic leukospongiosis (AL) agent which is considered to be an unconventional virus was shown to replicate and amplify in non-neuronal monolayer brain cell cultures. The AL agent persistence was accompanied by complicated morphofunctional changes in astrocytes, some of them developing a specific cytodystrophic process. Phagocytosis in the infected astrocytes came to its end. The dose-dependent effect and selective sensitivity of these cells to the cytodestructive activity of AL was demonstrated. Astrocytes are regarded to be target cells serving as a reservoir for agent amplification.     

The formation of infectious scrapie-like structures in the persistence of the agent of amyotrophic leukospongiosis in a brain cell culture

Electron microscopic analysis of specimens from guinea-pig brain cell cultures infected with amyotrophic leucospongiosis agent (belonging to "unconventional" viruses) revealed accumulation in the culture fluid of abnormal filamentous structures similar to scrapie-associated fibrils (SAF) differing in morphology. Most of these SAF-like structures 10-15 nm in diameter contained helically wound protofilaments with a repeat at certain intervals (50-150 nm). When these structures were inoculated into guinea-pig brain astrocyte cultures they produced dystrophic-destructive changes in some (25%) astrocytes, and their intracerebral inoculation to guinea pigs produced an experimental disease. The abnormal SAF-like structures were reisolated from the brains of the inoculated animals which indicated the relationship between these structures and infectivity.