Borna disease virus genome transcribed and expressed in psychiatric patients.

Borna disease virus (BDV) is a neurotropic, negative and single-stranded enveloped RNA virus that persistently infects various domestic animal species. Infection causes disturbances in behaviour and cognitive functions, but can also lead to a fatal neurologic disease. Human infections seemed likely, since serum antibodies were detected in neuropsychiatric patients. Further proof came from our discovery that peripheral blood monocytes carry viral antigens. Here, we present the first data on different viral genomic transcripts in such patients' cells as well as sequence data of transcripts. Both viral markers seem to coincide with acute episodes of mood disorders, thus pointing to a new human virus infection possibly threatening mental health.

Borna disease virus infection and affective disorders in man.

Borna Disease virus (BDV) can persistently infect the central nervous system of a broad spectrum of animal species. The clinical course varies from slight behavioral disturbances to a fatal neurological syndrome. In-vivo diagnosis is based on the strong humoral immune response to BDV antigens. Since also human infections could be confirmed by specific antibodies and increased seroprevalence was found in patients with chronic neurologic or immunologic disorders, the contribution of BDV or a BDV-like human variant to syndromes with yet unknown etiology became of great interest. We presented the first data of a current follow-up study on 70 psychiatric patients who were tested three times each after hospitalization. In contrast to previously found low prevalence of antibody carriers by screening (2-4%), we now found 20% positives by follow-up testing. Furthermore, of the randomly selected patients with different psychiatric diagnosis, the highest proportion of antibody carriers was detected among patients with major depression (more than 30%), compared to only 8% among patients with dysthymia (neurotic depression). This led us to hypothesize that Bornavirus infection might contribute somehow to the syndrome of major depressive illness by altering neuronal cells in the limbic system.

The isolation of cerebral neurons with partial retention of processes.

A novel tissue disaggregation technique has been devised which permits the isolation of neurons with fairly extensive processes attached. Cortex is dissociated by aspiration through nozzles of decreasing size followed by agitation on a vortex mixer, rather than by the usual technique of forcing tissue through sieves. After each aspiration step, dissociated cells are separated from undisrupted tissue by coarse filtration and the latter is subjected to repeated treatment. This prevents unnecessary trauma to the free cells. After disruption is complete, small pieces of undisrupted tissue are removed from the cell suspension by floating on the foam created by degassing the suspension under vacuum. Cells are purified by conventional velocity-gradient centrifugation. This procedure has been applied successfully to fresh rat brain, with or without a preincubation with trypsin, frozen human brain and frozen bovine brain. The cell yields from rat brain were comparable to or better than, those obtained by other procedures (37 X 10(6) cells/g brain) while the purity was comparable. Cell yields from human brain were similar to those from rat brain but the purity was lower. The lowered particle purity of human and bovine cells can probably be attributed to the conditions of storage of the tissue and to trapping of free nuclei in the meshwork of dendritic processes. Values are given for the amount of protein, RNA and DNA per cell.

Neural correlates of recognition memory with and without recollection in patients with Alzheimer's disease and healthy controls.

To dissociate recognition memory with and without recollection, event-related potentials (ERPs) of patients with Alzheimer's disease (AD) and matched controls were recorded in a test of verbal recognition memory accompanied by a source judgement. AD patients who had smaller hippocampi showed a disability to recollect the study context (source). Their ERPs elicited by correctly recognized old words compared to new items were more positive only between 300 and 500 ms with a maximum over the frontal scalp. Controls exhibited a sustained old/new effect over left temporoparietal and frontal sites. The present findings suggest that preserved recognition memory in patients with mild AD is independent of hippocampally mediated processes recollecting episodic memories.

Intracerebral neurinomas in a case of von Recklinghausen's disease (neurofibromatosis).

We report the third case of intracerebral neurinoma in a patient with von Recklinghausen's disease, who died of recurrent subdural hematomas after head injury. A total of ten tumors were found in the brain. Both by histological and ultrastructural standards the multiple tumors resembled neurinomas. The pattern of positivity for S-100 and myelin basic protein indicated the Schwann cell origin of the tumors. The ultrastructural findings indicated Schwann cells and numerous areas showing a well defined basement membrane surrounding spindle-shaped neoplastic cells and other areas lacking basement membrane with Schwann cells embedded in collagen. The present case may be categorized as a mixed form of peripheral and central neurofibromatosis. It seems safe to assume that perivascular nerves are the site of origin of the tumors.

The basal nucleus of Meynert revised: the nerve cell number decreases with age.

There is an age-dependent nerve cell loss in some areas of the brain, while other brain regions are stable with aging. The nucleus basalis of Meynert (NbM) is believed to be the source of cholinergic innervation of the cerebral cortex, and loss of its neurons seems to be followed by cognitive deficits. The normal age kinetics of the NbM are, therefore, of considerable importance. Sixteen autoptic human brains were examined, ages ranging from 35th week of gestation to 90 years of age. Blocks containing the NbM in its entirety were cut into 20-mu thick serial sections; every 25th section was cresyl-violet stained and underwent morphometric analysis. Nerve cell counts were slightly but significantly higher in the right hemisphere. The total number of neurons in the 9th decade was 23% below that in newborns. This decrease was statistically significant. We hypothesize that there is a threshold number of nerve cells below which cognitive failure is highly probable.

Transendothelial vesicular transport of protein in brain edema induced by ultraviolet irradiation.

Focal vasogenic brain edema was induced by ultraviolet irradiation of the exposed cerebral cortex of 16 cats. In 5 animals horseradish peroxidase was intravenously injected at times varying from 30 min to 24 h following irradiation and allowed to circulate for 45 min. Fixation was carried out by perfusion and immersion with glutaraldehyde. The tissue, part of it incubated for peroxidatic activity, was treated for electron microscopy. The UV-irradiation leads to a shallow coagulation of the superficial cortex from which a wide zone of edematous tissue spreads to the deep white matter within 24 h. Arterioles, capillaries and venules of this zone show enhanced pinocytotic activity and a concurrent rise in permeability for horseradish peroxidase which is found in micro- and macropinocytotic vesicles, in tubular vesicle-like structures, in endothelial wall invaginations and apparently not membrane-bound. These changes are most pronounced in venules which after 48 h allow penetration of reaction product though the base membrane into the surrounding neuropil. There is no evidence for the penetration of tight junctions which appear intact.

[Cerebrovascular malformations occult in angiography (author's transl)]. / Angiographisch stumme zerebrovaskuläre Malformationen.

Cerebral angiography still remains the method of choice for the evaluation of cerebral vascular malformations--even in this day and age of CT. In rare cases, however, these conditions can be missed by angiography, whereas CT can provide important though not pathognomonic clues, with a definite diagnosis possible only by surgical exploration.

The ultrastructure of oligodendrogliomas.

Seven Oligodendrogliomas (2 with uniform cell type, 4 with cellular or tissue variability, and 1 with glioblastomatous changes) were examined ultrastructurally. The tumor cells were of two principal types with morphologic transitions between the two main types. The two principal cell types were identified as type 1 (undifferentiated) and type 2 (differentiated) on the basis of the number of anaplastic cells in an individual tumor and on the observations of Mori and Leblond (21) on non-neoplastic oligodendrocytes. Most of the tumor cells in all tumor exhibited similar histologic and ultrastructural characteristics including their arrangement and their tendency to form cytoplasmic processes which sometimes formed short stacks. These features were also recognizable in the glioblastomatous example and confirmed the presence of an oligodendroglial component. In addition to these characteristics, an increase in size and number of mitochondria, abundant intracytoplasmic structures, microtubules were regularly present in virtually all tumor cells. Cells rich in cytoplasmic filaments were present. These were identified as reactive astrocytes or as oligodendroglial tumor cells. Thus neither cytoplasmic filaments nor microtubules appear to be specific morphological markers for oligodendroglia or astrocytes; only the predominance of one of these structures permits cytogenetic identifications. The cytologic characteristics are not specific morphologic markers; however, recognition of their presence provides important diagnostic information.

Lesions of high signal intensity at magnetic resonance imaging in vascular dementia.

Twenty-five patients with vascular dementia, 18 patients with senile dementia of Alzheimer type (SDAT) and 17 normal persons were examined by magnetic resonance imaging. Lesions of high signal intensity were always recognizable and were frequently very marked in patients with vascular dementia, while they were absent or mild in patients with pure SDAT and in non-demented patients without vascular disease. The possible nature of this disease as well as the role played in determining the type of dementia are discussed.

Peritumoral edema in meningiomas. A radiological and histological study.

Peritumoral edema associated with 76 supratentorial meningiomas was studied. The results of radiological investigation (CT, NMR, Angiography) and histological studies are described and correlated to each other. Mechanical factors alone are not sufficient to explain edema in the majority of the cases. It may be assumed that a secretory activity of the tumor itself also plays a role. The mechanism of this is described and discussed.

The spreading of focal brain edema induced by ultraviolet irradiation.

Focal brain edema limited to one cerebral hemisphere was produced by ultraviolet irradiation of the exposed cortex. Tissue water content was determined by the gravimetric method which allows microsampling. Therefore, the spread of edema around the small necrotic area could be mapped more precisely than by determination of dry weight which calls for larger samples. As early as 30 min following irradiation, hyperemia and swelling of the brain are observed under the operating microscope. This correlates with venous stasis, hyperemia, and broadened perivascular spaces around venules and large capillaries accompanied by a marked rise in the specific weight of the tissue. After 4 h an edema front can be observed spreading from the perinecrotic zone in which there is a marked rise in endothelial cell vesicular activity. Edema reaches maximum levels in the deep white matter at 48 h post irradiation with normalisation of the tissue water content after 96 h. The velocity at which the edema front spreads from the cortex to the periventricular area lies in the range of 0.25 mm/hr. Edema reabsorption coincides with signs of retrograde micropinocytosis in endothelial cells.

Brain lesions following combined treatment with methotrexate and craniospinal irradiation.

Eight patients with meningeal seeding by carcinoma or lymphomas were treated with intravenous (i.v.) and/or intrathecal (i.th.) Methotrexate (MTX). Seven patients received additional craniospinal irradiation and in all seven a fatal encephalopathy developed. On the bases of clinical and morphological findings we identified an acute and a delayed form of encephalopathy and concluded that the concurrent administration of Methotrexate and of craniospinal irradiation increases considerably the risk of brain damage.

Activated Borna disease virus in affective disorders.

BACKGROUND: Borna disease virus (BDV) is an animal pathogen that causes behavioral changes in animals. Previous studies have found a high prevalence of serum antibodies as well as Borna disease viral antigens (BDVAGs) and RNA in the white blood cells of psychiatric patients, especially those with affective disorders. The present study attempts to offer a better description of the BDVAG cohort using clinical parameters. METHODS: The prevalence of BDVAG was examined in the peripheral mononuclear leukocytes of patients with a major depressive episode. A subgroup of patients underwent further clinical analysis. RESULTS: In this pilot study, at least, there was a significant difference in the prevalence of BDVAG between psychiatric inpatients with a major depressive episode and control individuals. It also appeared that BDVAG is more frequent in patients with recurrent major depression or bipolar disorder than in those with any other psychiatric disorder studied. The number of previous depressive episodes, as well as symptoms involving fatigue and concentration difficulties were positively related to BDVAG. CONCLUSIONS: The high rate of BDVAG, especially in fatigued patients with recurrent major depression or bipolar disorder, may be a nonspecific aspect of immunosuppression. The question remains whether this neurotropic virus may contribute to the pathogenesis of some types of affective disorder.

Intranuclear vacuoles in Creutzfeldt-Jakob disease.

In an electron microscopic study of brain biopsy material from a case with Creutzfeldt-Jakob disease intranuclear vacuoles containing membrano-vesicular structures were found. To our knowledge this finding has not been previously reported in human spongiform encephalopathies. It may represent a specific alteration associated with Creutzfeldt-Jakob disease, and suggests the possibility of nuclear infection.