[Considerations on a room for leave taking]. / Uberlegungen zu einem Verabschiedungsraum.

Many patients die in hospitals and care centers. It is therefore necessary to create an environment for the dying person, as well as for relatives, which allows death to occur with dignity while also permitting a dignified farewell. A special room should be available for taking leave of the loved one and for the mourning of the relatives. This room should, as far as possible, be neutrally decorated while at the same time it should be appropriate for various cultures and religious requirements. In order to be able to take leave symbolically, it is necessary to place the departed in the light, for example from a window.

[Collisiontumour composed of glioblastoma and meningioma-a case report]. / Kollisionstumor des GehirnsTumorkomponenten aus einem Glioblastom und einem Meningeom.

A 51 year old caucasian male presented with headache, facial nerve paresis and continuing contraction of the visual field. CT scan revealed a singular intracerebral contrast enhancing lesion in the left frontal lobe. Intraoperatively the tumour was well demarcated. Frozen sections showed a high grade glioma. Paraffin sections revealed, in addition to the gliomatous component, some sharply demarcated nests of meningothelial cells. Immunohistochemistry with glial fibrillary acidic protein and epithelial membrane antigen confirmed a collision tumour consisting of a glioblastoma WHO-grade IV and a meningothelial meningioma WHO-grade I. The coincidence of these two different tumours at the same time and the same location leads us to the speculation, that the collision tumour might have been caused by malignant transformation of a reactive astrogliosis surrounding the meningioma.

Atypical paraneoplastic syndrome associated with anti-Yo antibodies.

OBJECTIVE: Polyneuropathy, myopathy and spasticity have not been described as a manifestation of a neurologic paraneoplastic syndrome (NPS) associated with anti-Yo antibodies (anti-Yo). CASE HISTORY: The patient is a 60-year-old woman with a history of ovarectomy, salpingectomy, hysterectomy and omentectomy because of ovarian cancer with peritoneal carcinosis. From May to September 1999, she received chemotherapy with carboplatin and docetaxel. In June 1999, weaknesses of the lower limbs began to appear. Neurologic investigation revealed bilateral ptosis with right-sided predominance, exaggerated deep tendon reflexes, discrete distal weakness, wasting of the upper limbs and diffuse weakness of the lower limbs. She had slight CK elevation, elevated lactate dehydrogenase and aldolase levels. Testing for anti-neuronal antibodies revealed high serum titers of antibodies against the cytoplasm of Purkinje cells, confirmed as anti-Yo by immunoblot with recombinant proteins. CSF investigations showed 12/3 cells and positive oligoclonal bands. MRI of the brain showed bilateral, old ischemic basal ganglia lesions exclusively. Visually evoked potentials gave prolonged P100 latencies bilaterally. Nerve conduction studies and electromyography revealed motor polyneuropathy of the lower limbs. Muscle biopsy from the right anterior tibial muscle showed non-specific myopathic features. CONCLUSION: Polyneuropathy, myopathy and tetraspasticity may be the exclusive manifestations of an atypical NPS associated with anti-Yo. Anti-Yo may persist for years without relapse of the primary tumor.

Oligoclonal T-cells in blood and target tissues of patients with anti-Hu syndrome.

T-cell clones of unknown significance (TCUS), assessed by monoclonal or oligoclonal T-cell patterns in PCR-DGGE, were detected in blood of 7/9 patients with anti-Hu syndrome. Clonal patterns were also detected in 2/2 neoplastic lymph nodes, and in 2/2 inflamed dorsal root ganglia from three patients. Only some T-cell clones found in target tissues were also detected in blood or non-target tissues, and likely corresponded to TCUS. In one patient, an identical T-cell clone was found in both neoplastic lymph node tissue and dorsal root ganglia, but not in blood. Dorsal root-infiltrating lymphocytes were cytotoxic CD8(+) TIA-1(+) T-cells. They were often found in close contact to sensory neurons, most of which expressed MHC-1. Taken together, these data support a direct effector role of cytotoxic CD8(+) T-cells, the same clones being likely operative in sensory neuron damage and immune-mediated tumor growth control.

Acquired neuromyotonia and peripheral neuropathy in a patient with Hodgkin's disease.

Acquired neuromyotonia is characterized by hyperexcitability of motor nerves resulting in continuous muscle fiber activity. It occurs most often as a paraneoplastic syndrome in patients with cancers of the immune system. Antibodies against voltage-gated potassium channels (VGKCs) have been detected in some patients. Peripheral neuropathy is sometimes present. We report on a patient with Hodgkin's lymphoma in complete remission who developed paresthesias followed by neuromyotonia with bulbar involvement. Peripheral sensorimotor neuropathy was diagnosed electrophysiologically and evidence of axonal degeneration and demyelination was detected by sural nerve biopsy. The patient's complaints, including dysarthria, improved after carbamazepine treatment.

Pseudogliomatous growth pattern of anaplastic small cell carcinomas metastatic to the brain.

Carcinomas metastatic to the brain usually grow very well circumscribed, with sharp delineation. Radiosurgery takes advantage of this fact by using the gamma knife for definitive treatment of small metastases. We report a systematic study of the growth pattern of cerebral metastases, focusing on tumor delineation. In 26 cases of 66 metastatic anaplastic small cell carcinomas and in one case of adenocarcinoma, we observed poorly defined borders and a highly diffuse pattern of invasion. Infiltrating carcinoma cells changed to an elongated shape adapting to preexisting tissue structures. This pseudogliomatous growth pattern of some brain metastases--apparently most likely in neuroendocrine carcinomas--is of potential importance for therapeutic strategies in the treatment of brain metastases, especially when considering treatment with radiosurgery and gamma knife.

Neuropathology and general autopsy findings in AIDS during the last 15 years.

A retrospective study of 450 consecutive AIDS autopsy cases (397 males, 53 females; mean age at death 38.4 years) in Vienna, Austria, between 1984 and 1999 compares the central nervous system (CNS) findings in three cohorts: 1984-1992 (190 cases), 1993-1995 (162 cases) and 1996-1999 (98 cases, after introduction of triple antiretroviral therapy) and the relationship of CNS findings to systemic AIDS pathology in the latter two cohorts. In these two groups, following involvement of the lung (85% and 75%, respectively), the brain continued to be the second most frequently involved organ (decrease from 80% to 60%, respectively). Extracerebral protozoal (Pneumocystis carinii, toxoplasmosis), Mycobacterium avium complex, viral [e.g., cytomegalovirus (CMV)], multiple opportunistic organ and CNS infections, and Kaposi sarcoma significantly decreased over time. There was less decrease in fungal infections, while bacterial organ and CNS infections (except for mycobacteriosis), lymphomas, HIV-associated CNS lesions (around 30%), non HIV-associated changes (vascular, metabolic, etc.) and negative CNS findings (10-11%) remained unchanged. Nonspecific CNS changes (e.g., meningeal fibrosis) increased. Extracerebral pathology in subjects with advanced HIV-related CNS lesions showed more frequent but decreasing systemic bacterial and CMV infections than those with negative or nonspecific neuropathology, while other opportunistic and multiple organ infections and lymphomas showed no differences between both groups. In a cohort of drug abusers, HIV encephalitis, progressive multifocal leukoencephalopathy, bacterial infections, hepatic encephalopathy, and negative CNS findings were more frequent than in non-users who showed increased incidence of CMV, toxoplasmosis, or other opportunistic CNS infections, and nonspecific CNS findings; the frequency of lymphomas was similar in both drug abusers and non-users. Similar to a recent autopsy study from San Diego, these data suggest that despite the beneficial effects of modern antiretroviral combination therapy, involvement of the brain in AIDS subjects continues to be a frequent autopsy finding, while the increased incidence of HIV encephalitis in our small cohort of drug users was less than observed in other recent autopsy studies.

T cell-mediated paraneoplastic ganglionitis--an autopsy case.

A 57-year-old woman presented with subacute sensory, ataxic neuronopathy. Clinical investigation revealed a right-sided non-small-cell lung cancer. Serum investigation for specific antineuronal antibodies was negative. Histology showed T lymphocytic infiltrates in dorsal root ganglia. The observed histological pattern is similar to that described in antibody-positive cases. Thus, these findings suggest similar pathways in specific antineuronal antibody-negative and -positive cases of paraneoplastic subacute sensory neuronopathy.

Paraneoplastic neuropathy.

Paraneoplastic neuropathies occur in various settings. This article focuses on recent neuroimmunologic findings regarding paraneoplastic neuropathy. Entities such as sensorimotor and sensory neuropathy, sensory neuronopathy; motor, autonomic, demyelinating and vasculitic mononeuropathies; and cranial nerve lesions and neuropathies in association with leukaemia and paraproteinaemas are discussed. Finally, the article considers the issue of 'overlap' syndromes--the occurrence of several paraneoplastic phenomena in the same patient.

Cortical areas abundant in extracellular matrix chondroitin sulphate proteoglycans are less affected by cytoskeletal changes in Alzheimer's disease.

In the human brain, the distribution of perineuronal nets occurring as lattice-like neuronal coatings of extracellular matrix proteoglycans ensheathing several types of non-pyramidal neurons and subpopulations of pyramidal cells in the cerebral cortex is largely unknown. Since proteoglycans are presumably involved in the pathogenesis of Alzheimer's disease, we analysed the distribution pattern of extracellular chondroitin sulphate proteoglycans in cortical areas, including primary motor, primary auditory and several prefrontal and temporal association areas, in normal human brains and in those showing neuropathological criteria of Alzheimer's disease. In both groups, neurons with perineuronal nets were most numerous in the primary motor cortex (approximately 10% in Brodmann's area 4) and in the primary auditory cortex as a representative of the primary sensory areas. Their number was lower in secondary and higher order association areas. Net-associated pyramidal cells occurred predominantly in layers III and V in motor areas, as well as throughout lower parts of layer III in the primary auditory cortex and neocortical association areas. In the entorhinal cortex, net-associated pyramidal cells were extremely rare. In brains showing hallmarks of Alzheimer's disease, the characteristic patterns of hyperphosphorylated tau protein, stained with the AT8 antibody, largely excluded the zones abundant in perineuronal nets and neuropil-associated chondroitin sulphate proteoglycans. As shown in double-stained sections, pyramidal and non-pyramidal neurons ensheathed by perineuronal nets were virtually unaffected by the formation of neurofibrillary tangles even in severely damaged regions. The distribution patterns of amyloid B deposits overlapped but showed no congruence with that of the extracellular chondroitin sulphate proteoglycans. It can be concluded that low susceptibility of neurons and cortical areas to neurofibrillary changes corresponds with high proportions of aggregating chondroitin sulphate proteoglycans in the neuronal microenvironment.

[Frontal lobe dementia. Clinical-pathologic case reports]. / Frontallappen-Demenzen. Klinisch-pathologische Fallberichte.

Frontal lobe dementia (FLD) is characterised clinically by personality changes and a progressive speech disorder finally leading to mutism. In the course of the disease also other neurological syndromes may occur such as parkinsonism, a partial Klüver-Bucy-syndrome or a degeneration of motoneurons (FLD + MND). The latter leads to death within about three years. The clinical diagnosis of FLD is supported by functional (SPECT) and morphological (CT, MRI) investigations. From 1988 to 1997, 9 cases of FLD (6 female, 3 male) were clinically diagnosed at our department of Gerontology, LNK Linz. In two of these cases the clinical diagnosis was confirmed histopathologically. Characteristically, all except one patients showed a presenile beginning of the disease. The clinical course was slowly progressive with a mean duration of about 10 years. Special attention was given to additional signs and symptoms of motor neuron disease, parkinsonism and hyperorality. Six patients suffered from FLD + MND; parkinsonism (rigid-akinetic type) and a partial Klüver-Bucy-syndrome were diagnosed in 5 cases each. In histopathological investigations the incidence of FLD seems to increase. This type of dementia should be considered as an important diagnosis differential of presenile dementia-syndromes.

Ganglionitis in paraneoplastic subacute sensory neuronopathy: a morphologic study.

A 69-year-old woman presented with subacute sensory neuropathy and autonomic dysfunction of 9 months' duration, associated with high serum titers of anti-Hu antibodies. A small cell carcinoma of the lung was diagnosed by biopsy. She died after cardiorespiratory arrest. At autopsy, spinal and autonomic ganglia showed subacute inflammation with diffuse endoneurial T-cell, B-cell, and plasma cell infiltration. The cytoplasm and nuclei of some ganglion neurons displayed IgG immunocytochemical positivity. CD8+ T cells were tightly attached to, and indented the cell surface of, IgG-positive and IgG-negative neurons. This observation suggests that both cytotoxic T-cell-mediated attack against neurons and humoral mechanisms play a role in paraneoplastic subacute sensory neuronopathy.

[Hyperthyroidism caused by TSH producing hypophyseal adenoma]. / Hyperthyreose durch ein TSH-produzierendes Hypophysenadenom.

Thyrotropin (TSH-)producing adenomas of the anterior pituitary gland are the least frequently encountered ones and constitute a very rare cause of hyperthyroidism. The case is presented of a 58 year old male patient with a well-known history of hyperthyroidism over a period of at least 9 years growing goiter. Despite different forms of medical treatment he presented a constant clinical pattern consisting of restlessness and paroxysmal tachycardial atrial fibrillation. Laboratory findings revealed elevated levels of circulating thyroid hormones despite inadequately high levels of TSH. MRI scan revealed an adenoma of the pituitary measuring 9 mm in diameter. After microsurgery, consisting of transphenoidal resection of the tumor, the patient recorded no clinical symptoms. Histological examination revealed positive immunohistochemical staining, with antibodies to TSH, but a negative reaction against the GH, PRL, FSH, LH and ACTH hormone antibodies. Moreover, the levels of circulating hormones (GH, PRL, FSH, LH and ACTH) were normal. TSH-alpha subunits were not elevated. Before the correct diagnosis was reached, this patient was treated for nine years with antithyroid drugs. Five months after the operation the patient showed normal values of circulating thyroid hormones and TSH and thus no thyroid-specific medication was necessary.

Antibodies of the anti-Yo and anti-Ri type in the absence of paraneoplastic neurological syndromes: a long-term survey of ovarian cancer patients.

In recent years several authors have described a close correlation between circulating antineuronal antibodies of different types and the occurrence of paraneoplastic neurological syndromes. Because this has not been widely accepted, we screened 300 serum samples from 181 ovarian cancer patients for the presence of circulating antineuronal antibodies by immunofluorescence. The findings were confirmed by immunoblotting. In 11 patients circulating antineuronal antibodies were detected. In 4 patients they were classified as anti-Yo and in 7 as anti-Ri, titres ranging from 1:400 to 1: 204,800. All the patients underwent thorough neurological and neurophysiological investigations, with special regard to paraneoplastic syndrome. None of them had symptoms pointing to a paraneoplastic neurological syndrome, although patients were followed up to 2 years after the first examination. Thus the frequency of circulating antineuronal antibodies in ovarian cancer patients is higher than the frequency of paraneoplastic syndromes, and antibody positivity does not necessarily lead to the appearance of a neurological paraneoplastic syndrome.

[Histopathologic studies in dementia--comparison with clinical findings]. / Histopathologische Untersuchungen bei Demenz--Vergleich zum klinischen Befund.

This paper compares the clinical diagnosis of dementia with the result of the neuropathological brain examination in 23 patients. Aim of this investigation was a verification of the clinical diagnosis. The diagnosis was based on the clinical findings, the Mini Mental State Examination, DSM-III-R classification of dementia, the NINCDS-ADRDA-criteria, results of laboratory tests, EEG, CCT and sonography. A total of 70% of the clinical diagnosis corresponded to the neuropathological results. In 25% of these cases which clinically showed the characteristics of Alzheimer's disease histopathological findings delineated dementia of non-Alzheimer-type. These results underline the importance of additional histopathological investigations in the diagnosis of dementia.