Rasmussen encephalitis: epilepsia partialis continua secondary to chronic encephalitis.

Rasmussen encephalitis is a disease consisting of chronic encephalitis with progressive neurologic deficits and focal intractable seizure activity. The etiology is unknown, but pathologic specimens revealed changes consistent with viral encephalitis. Even though neuro-imaging techniques, such as positron emission tomography and magnetic resonance imaging, offer the prospect of specific, presurgical diagnostic criteria, the initial diagnosis usually is made on a clinical basis. Treatment modalities, including a wide variety of antiepileptic drug therapies and surgical interventions, may result in significant physical and mental impairments. We summarize the clinical presentation, diagnostic considerations, and different treatment protocols in a patient with this rare and debilitating disorder.

Posterior ischemic optic neuropathy due to Aspergillus fumigatus.

A 35-year-old woman with metastatic breast cancer experienced acute monocular visual loss. Her fundus examination was normal. The patient died 48 h later, and autopsy demonstrated hematogenously disseminated aspergillosis. The retrobulbar optic nerve of the affected eye showed infarction due to massive embolization with Aspergillus fumigatus. Although the retrobulbar optic nerve is relatively resistant to ischemia, its meningeal derived blood supply may be occluded by massive showers of emboli.

Familial hemophagocytic lymphohistiocytosis: report of four cases in two families and review of the literature.

Four cases of familial hemophagocytic lymphohistiocytosis (FHL) from two families with first cousins affected in family and siblings in another are presented. The pathological findings, including neuropathology, transmission (TEM), and scanning electron microscopy (SEM), are discussed. This is the first study of this condition to include TEM and SEM. One hundred and fifty-nine cases from the literature, including the author's four cases, are reviewed. The familial occurrence in 116 instances in sibships and consanguinity in 13 of the 73 families support autosomal-recessive inheritance. In five families there were affected first cousins--an observation not readily explained by autosomal-recessive transmission. We suggest that the genetic aspects of FHL be more fully explored and that in future cases parents and other relatives be included in the hematologic, immunologic, and genetic evaluation.

Brain tumors in owl monkeys inoculated with a human polyomavirus (JC virus).

Owl monkeys were inoculated intracerebrally, subcutaneously, and intravenously with JC, BK, or SV40 virus. Two of four adult owl monkeys inoculated with JC virus, a human polyomavirus, developed brain tumors at 16 and 25 months after inoculation, respectively. A grade 3 to grade 4 astrocytoma (resembling a human glioblastoma multiforme) was found in the left cerebral hemisphere and brainstem of one monkey. The second monkey developed a malignant tumor in the left cerebral hemisphere containing both glial and neuronal cell types. Impression smears prepared from unfixed tissue of this tumor showed cells that contained polyomavirus T antigen. Virion antigens were not detected. Tumor cells cultured in vitro also contained T antigen but were negative for virion antigen. Infectious virus was not isolated from extracts of this tumor.

Induction of peripheral neuroblastomas in Syrian hamsters after injection as neonates with JC virus, a human polyoma virus.

Neuroblastomas developed in 10 of 31 Syrian hamsters inoculated intraocularly with JC virus, a human polyoma virus. The latent period was 6 to 11 months. Primary tumors occurred in the abdominal cavity, pelvis, mediastinum, and neck region. The origin of one tumor from the adrenal gland was demonstrated. Metastases were seen in the liver, bone marrow, and lymph nodes. Two neuroblastomas arising in this experiment were transplanted serially in weanling hamsters, and a tissue culture cell line was established from one of the transplanted tumors. T-antigen was detected in three of five primary tumors tested and in the transplanted tumors. Antibody against T-antigen was demonstrated in sera from five of six animals with neuroblastomas. Neuroblastomas also developed after combined s.c. and i.p. injection of JC virus.

Progressive multifocal leukoencephalopathy. A cause of visual loss.

A patient had been treated for chronic lymphocytic leukemia for five years before developing visual blurring as the manifestation of occipital lobe lesions of progressive multifocal leukoencephalopathy (PML). The disease is caused by an infection of the CNS oligodendrocytes by a papovavirus, whose replication is facilitated by an impairment of the host's cell-mediated immunologic system. The multiplying virus destroys the oligodendrocytes and causes extensive demyelination of the white matter of the brain. Antiviral agents, such as cytarabine, may be beneficial in treating patients with PML.

Differential neurooncogenicity of strains of JC virus, a human polyoma virus, in newborn Syrian hamsters.

The neurooncogenicity recently isolated strains of the human polyoma virus, JC virus, was determined by intracerebral inoculation of newborn Syrian golden hamsters. All three strains produced malignant brain tumors in a majority of inoculated animals during a 6.5-month observation period. The results obtained with the MAD-2 strain, 19 of 20 animals with cerebellar medulloblastomas and 0 of 20 animals with pineal gland tumors, were quite similar to those observed previously with the prototypic strain of JC virus, MAD-1. Inoculation of the MAD-4 strain, however, resulted in 10 of 22 animals with pineal gland tumors and only 10 of 22 animals with tumors in the cerebellum. The MAD-3 strain was neurooncogenic, but too few animals lived to be weaned to provide significant additional information. The basis for the apparent predilection of the MAD-4 strain for the pineal gland is unknown. Two hamsters in the experiment developed extracranial neuroblastomas.

Fatal CNS dysgenesis with severe microencephaly, mental retardation, seizures and paucity of myelin, autosomal recessive trait?

Siblings are reported with severe mental retardation, spastic cerebral palsy and seizures; in addition they had progressive or intermittent jaundice and recurrent infections; they died at 3 and 4 years respectively. Neuropathological studies in one showed a small brain with an almost complete lack of myelin in cerebral white matter, brain stem, cerebellum and anterolateral parts of the spinal cord. The condition most likely represents a dysgenesis of myelin (dysmyelination), possibly due to an inability of oligodendrocytes to form myelin and/or metabolic defects in the process of myelination. This mental retardation condition is probably inherited as an autosomal recessive trait and may represent a special type of a primary CNS developmental defect.

Modification of hydroxyindole-O-methyltransferase activity in experimental pineocytomas induced in hamsters by a human papovavirus (JC).

Hydroxyindole-O-methyltransferase (HIOMT) (HIOMT) activity was studied and compared in 7 pineal tumors (pineocytomas) induced in vivo in Syrian hamsters after postnatal inoculation with strains of human papovavirus (JC). Levels of tumor HIOMT activity were correlated with degree of cytologic differentiation of the pineocytes of each neoplasm, as judged from electrom micrographs. The relative capacities of the HIOMT in the tumors to methylate three related substrates gave similar ratios in the individual tumors and were not different from those of HIOMT in normal hamster pineal glands.

JC Papovavirus in progressive multifocal leukoencephalopathy.

Brain tissue from seven patients with progressive multifocal leukoencephalopathy was tested for the presence of papovaviruses. JC virus, ahuman papovavirus, was identified in all seven cases. Virus was isolated in tissue culture from extracts from each of four patients and was detected by immunofluorescence in sections from the other three. The new osolates were indistinguishable from the prototypical JC strain serologically and in all biological characteristics examined. Thus JC virus has, to date, been associated with 20 cases of progressive multifocal leukoencephalopathy.

Experimental pineocytoma of the Syrian hamster induced by a human papovavirus (JC). A light and electron microscopic study.

The gross, light and electron microscopic features of a pineocytoma of the Syrian hamster (mesocricetus auratus) which had been induced by a human oncogenic virus (JC papovavirus) have been defined. For comparison, adult hamster pineal tissue was studied, and the literature was consulted in regard to other pineal parenchymal tumors, and to pineal cell differentiation during ontogeny and phylogeny. Many differentiated tumor cells contained organelles, such as vesicle-crowned lamellae (synaptic ribbons) and microtubular sheaves, as consistent with adult hamster pineocytes. Some cells showed rudimentary photoreceptor-like differentiation as consistent with fetal hamster pineocytes and with cells seen in the pineal systems of some lower vertebrate species. Such tumor cells had lumen-directed specialized cytoplasmic extensions which, by their richness in mitochondria and presence of centrioles and striated rootlets, resembled inner segments. Extending 9+0 cilia were accompanied by occasional lamellar whorls. Oncogenesis seems to have simulated different stages of hamster pineal ontogeny. This observation would support the theory that the secretory mammalian pineocyte derived phylogenetically from the true photoreceptor cell of the pineal system of fishes and amphibians. The possible influences of host and of virus in the accomplishment of tumor morphology were discussed. This tumor differed considerably in pattern and cell detail from the only other pineocytoma studied previously by electron microscopy. It is the first experimentally induced pineocytoma.

Generalized gangliosidosis type II (juvenile GM1 gangliosidosis). A pathological, histochemical and ultrastructural study.

Pathological, histochemical and ultrastructural studies on 3 siblings with GM1 gangliosidosis type II are reported. These studies support a biochemical defect with profound deficiency of beta-galactosidases which results in widespread accumulation of the GM1 ganglioside and its asialo derivative in brain and to a lesser extent in viscera, as well as in storage of a keratan sulphate-like mucopolysaccharide. Striking valvular changes in the heart without myocardial involvement were seen in all cases. The histochemical and ultrastructural changes are similar to those seen in GM1 gangliosidosis type I, though less severe. Autosomal recessive inheritance without apparent ethnic predilection seems likely.

Lateral hypothalamic demyelination and cachexia in a case of "malignant" multiple sclerosis.

A 41-year old woman had profound weight loss and cachexia as a manifestation of rapidly fatal multiple sclerosis. Demyelinating lesions were present in the lateral hypothalamus. Data from animal experiments have indicated that lateral hypothalamic lesions cause a weight loss associated with a lowering of the regulation level or "set-point" for body weight. This case suggests, therefore, that a rapid decline in the level of maintained body weight in a patient without pituitary disease or general organic disorder, or distinct emotional disorder, may represent a clinical manifestation of tissue injury of the lateral hypothalamus.

Comparison of JC and BK human papovaviruses with simian virus 40: restriction endonuclease digestion and gel electrophoresis of resultant fragments.

JC virus was found to have a buoyant density of 1.20 g/cm(3) in linear sucrose-D(2)O and 1.35 g/cm(3) in cesium chloride isopycnic gradients. DNA extracted either from JC-infected cultures or from gradient-purified virions occupied a dense position relative to linear DNA in cesium chloride/ethidium bromide gradients, and the circular configuration of the extracted DNA was confirmed by electron microscopy, with a measured molecular weight of 2.93 x 10(6). DNA from BK virus was similarly prepared and compared to JC and to an SV40 DNA standard by digestion with restriction endonuclease preparations from Haemophilus influenzae, Haemophilus parainfluenzae, and Escherichia coli. Digests were electrophoretically analyzed on gradient polyacrylamide slab gels or agarose gels, and the three viruses were found to have distinctly different cleavage patterns by this form of analysis: JC and BK viruses were almost entirely different from SV40 and significantly different from each other. Thus, JC and BK human papovaviruses appear to be discrete new members of the papovavirus group, rather than SV40 variants.