Abner Wolf

Rapid Production of Acute Disseminated Encephalomyelitis in Rhesus Monkeys by Injection of Brain Tissue With Adjuvants

Rapid production in the monkey of a pathological condition resembling acute disseminated encephalomyelitis, marked by demyelination, can be achieved by the use of adjuvants added to rabbit brain emulsions.

A disease in infants resembling chronic Wernicke's encephalopathy

Summary 1. Three cases are reported of childrensuccumbing to a disease process resembling Wernickes encephalopathy. 2. There is no convincing evidence of a dietary inadequacy of thiamine or other vitamins, nor of a difficulty with intestinal absorption, nor of an abnormally high thiamine requirement in these cases. 3. Two of the patients were siblings of a consanguineous marriage. It is suggested that a congenital metabolic disorder, possibly involving the utilization of thiamine or in the enzymatic processes with which thiamine derivatives are concerned, may be present in these cases.

Autopsy findings in parkinsonism following treatment with levodopa

It is one hundred fifty-three years since James Parkinson wrote his now-famous essay’ on the shaking palsy. This short monograph, only 66 pages, is based on 6 cases, 3 of which he had examined in detail and 3 he knew casually, having observed them on the streets or in public places in London. Despite the paucity of the case material, the clarity and detail of this account and the author’s insight into the nature of the disorder are remarkable-probably unsurpassed in the annals of medicine. Parkinson recognized almost all of the major manifestations and much about the natural history of the disorder, including its onset-over 50 years of age-and its progressive disabling nature. Further, in a day when little was known about central nervous system function, he localized the site of the disease in the central nervous system by indicating that it must be due to an “irregularity in the nervous influence rather than the nerves of the parts.” His reasoned suggestion that the pathological site was in the medulla spinalis and that it progressed by extending into the medulla oblongata was not too far off target, but it has taken more than a century to establish this fact. In writing his monograph, James Parkinson indicated that his purpose was not so much to draw attention to it as a nosological entity but rather to stimulate interest in defining its underlying pathology. It was with this in mind, and hoping to draw the pathological anatomist into investigation of this disorder, that he wrote his essay. A s he states in the concluding para-

Murine Influenza Virus Encephalomyelitis

The development and maturation of neurotropic WS-N strain of influenza virus in encephalitic mice was shown to occur preferentially along the “free” surface of ependymal and choroid plexus cells where it developed from the cell membrane. Virus maturation and “budding” was generally absent along the other surfaces of the same cells where they were apposed to other cells. This may suggest an inhibitory effect of adjacent cell membranes. Electron microscopic observations of ependymal surfaces may be of importance in demonstrating some viruses in human and animal tissues. Most of the virions were rounded in shape with surface spikes but a considerable number of filamentous forms were seen developing at the tips of villi. Filamentous forms had previously been described in tissue culture but not in animal encephalitic tissues. Intracellular virus within vacuoles was seen en masse and a few virus-like structures appeared to form from endoplasmic reticulum. Intracytoplasmic inclusions were demonstrated. The virus appeared ultrastructurally at a time preceding and overlapping the time at which virus replication reaches its maximum. The electron microscopic results were also considered in relation to immunofluorescence evidence in a companion paper, that virus antigen is present in deeper cells even though few mature virions appear in those sites. The combined data suggests that virus initially has a predilection for ependymal cells where mature virions develop at the surface of the cells. Later there is extension of virus antigen to deeper cells with a presumed transfer from cell to cell without the same degree of maturation of virions at cell surfaces.

Murine influenza virus encephalomyelitis. I. Neuropathological and immunofluorescence findings.

The direct inoculation of neurotropic NWS strain of the influenza virus into the brains of Swiss albino white mice results in an acute meningoencephalomyelitis. The myelitis is described for the first time. The cerebral lesions are marked by a severe ventriculitis, characterized by a necrotizing ependymitis and a lesser involvement of the choroid plexus. During the first three to four days of the infection, increasingly frequent and prominent paraventricular inflammatory and degenerative lesions are seen in the brain and paracanalicular ones in the spinal cord. There is a gradual decrease in the number and severity of the lesions from the fifth to the seventh days. Intranuclear inclusions and fewer cytoplasmic ones are described for the first time in this experimental condition and are seen in both cerebral and spinal cord lesions. They are present in nerve cells but not in glial or other cells. Segmental demyelination is encountered sparingly and is most notable in the corpus callosum. Astrocytosis is a prominent and early feature of experimental murine influenzal meningoencephalitis and is probably reactive in character.

Replication of Neurotropic Influenza Virus in Organotypic Cultures of Embryonic Mouse Hypothalamus

Neurotropic influenza virus (WS-N strain) causes cytolytic changes in organotypic neural cultures derived from embryonic mouse hypothalamus. Initially, nerve cells develop enlarged, refractile nucleoli. In later stages, both nerve and glial cells undergo necrotic changes. These alterations are accompanied by synthesis of progeny virus and formation of intracellular viral antigen. Electron microscopic observations of infected cultures reveal virus particles with the morphology and dimensions of influenza virions. Organotypic neural cultures may prove useful in studies of influenza virus neurotropism.

Pathologic changes in the inner ear of audiogenic seizure-susceptible mice treated with 6-aminonicotinamide

Abstract The inner ears were studied histologically to determine a possible morphological basis for our earlier finding of the abolition of sound-induced seizures in inbred audiogenic seizure-susceptible mice treated with 6-aminonicotinamide (6-AN). A single intraperitoneal injection of 20 mg/kg of 6-AN resulted in elimination of sound-induced seizures and produced severe degenerative lesions in the cochlear duct of the seizure-susceptible mice. Similar cochlear lesions were produced in a control mouse strain (CF#1). The earliest lesions, first sought and clearly evident at 24 hours after the injection, were localized in the spiral ligament, the epithelium of the external spiral sulcus, and the lateral portions of the papilla acoustica. The acute degeneration was at its highest 3–5 days after the injection, when the medial portions of the papilla were also involved. The damage to the spiral organ (Corti) seen at that time is incompatible with a normal sensory input. The degree of damage is sufficient to explain the loss of, or marked restriction in, response to auditory stimuli, and the abolition of audiogenic seizures. In all animals treated with 6-AN, the lower basal turn and the upper second turn were more extensively damaged than the rest of the cochlea. However, in the longest surviving 6-AN-treated mice not even a remnant of the spiral organ could be detected. The spiral ganglion nerve cells were not damaged in the acute stage of 6-AN intoxication. The atrophy of the spiral ganglion which appeared in the late stages was, like the degeneration of the spiral organ, most severe in the lower basal and upper second turns. The changes in the spiral ganglion were interpreted as being secondary to the acute destruction of the spiral organ.

Cellular Pathology in Cultures of Embryonic Mouse Hypothalamus Inoculated with Influenza A0 WSN Virus

The pathological changes produced in tissue cultures of explanted embryonic Swiss albino mouse hypothalamus by the inoculation of influenza A0 virus of the WSN strain is described as seen by light and electron microscopy. Nerve cells undergo deterioration and disintegration after a relatively protracted exposure to virus inoculated at a high concentration. Cytoplasmic inclusions appear in nerve cells as early as 24 hours after infection and prior to intranuclear inclusions while neither are seen in uninfected control cultures. Gross foci of degeneration of the tissue leads to a reactive fibrillary astrocytosis. Small intranuclear inclusions are encountered in astrocytes and the question is raised as to whether their reaction is in part due to their infection. With the electron microscope rounded or more elongated virions are seen forming at the plasma membrane or at the luminal membrane of intracytoplasmic vacuoles. Ribosomal clusters and ribosomes clustered around electrondense masses are believed to be an early change in the organization of the cytoplasm in association with the viral infection.