Gabriele M. ZuRhein

Human papovavirus (JC): induction of brain tumors in hamsters.

Eighty-three percent of hamsters inoculated at birth with JC virus, a human papovavirus isolated from brain tissue of a case of progressive multifocal leukoencephalopathy, developed malignant gliomas within 6 months. Three brain tumors have been serially transplanted as subcutaneous tumors. JC virus was isolated from five of seven tumors tested. Cells from four tumors were cultivated in vitro. These cells contained an intranuclear antigen with the characteristics of a T antigen, and this antigen was antigenically related to SV40 T antigen. Although virus was not recovered from extracts of serially cultured tumor cells, JC virus was rescued when one tumor cell line was fused with permissive cells.

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.

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 authors 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.

Generalized gangliosidosis type II (Juvenile GM1 gangliosidosis)

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 β-galactosidase 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.

A Novel Cerebral Microangiopathy With Endothelial Cell Atypia and Multifocal White Matter Lesions : A Direct Mycoplasmal Infection?

We present 3 sporadic cases of a subacute to chronic, progressive motor (i.e. weakness, ataxia, spasticity, dysarthria, and dysphagia) and cognitive disorder in adults of both sexes, without proven immunocompromise or malignancy. Neuroimaging studies revealed tiny calcifications with atrophy of the cerebrum, pons, and midbrain in 1 patient, cerebral atrophy in another, and cerebral atrophy and periventricular white matter hyperintensities in the third. Clinical diagnoses included cortico-pontine-cerebellar degeneration, mixed neurodegenerative disorder, progressive supranuclear palsy, diffuse Lewy body disease, and Lyme disease. One atrophic brain revealed widely disseminated, millimeter-sized gray lesions in cerebral white matter and obscured anatomic markings of the basis pontis. The most conspicuous microscopic feature in all was capillaries with focally piled up endothelial nuclei, some of which appeared to be multinucleated, or enlarged, hyperchromatic crescentic single nuclei. Although seen mostly without associated damage, they were also noted with white matter lesions displaying vacuolation, demyelination, spheroids, necrosis, vascular fibrosis, and mineralization; these were most severe in the basis pontis. Immunostains and probes to herpes simplex virus-I, -II, and -8; adenovirus, cytomegalovirus, varicella-zoster, Epstein-Barr virus, measles, JC virus, and herpes hominis virus-6 were negative. Electron microscopy revealed no virions in endothelial cells with multilobed or multiple nuclei and duplicated basal laminae. However, mycoplasma-like bodies, mostly 400 to 600 nm in size, were found in endothelial cell cytoplasm and capillary lumina. Platelets adhered to affected endothelial cells. Polymerase chain reaction and immunohistochemistry of fixed samples for Mycoplasma fermentans were negative; other species of Mycoplasma remain viable pathogenic candidates.

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.