Another patient with 12q13 microduplication.

Interstitial duplication of the long arm of chromosome 12 is a rare cytogenetic condition. While several reports describe distal 12q duplication, only one case report of homogeneous, non-mosaic interstitial 12q13 duplication has been documented to date. The authors of that observation proposed that the associated phenotype represented a phenocopy of Wolf-Hirschhorn syndrome [Dallapiccola et al., 2009]. Only a few other recorded patients with deletion 12q13 → 12q21 involved mosaicism. We describe a new patient with homogeneous 12q13 duplication in a 6-year-old girl who, in early infancy, presented with dysmorphic features suggesting Wolf-Hirschhorn syndrome. What is potentially significant about this patient is that her facial phenotype evolved with age, suggesting a different gestalt in older patients.

Morbus Fahr--considerations on a case of sudden death.

Up to now, Fahr's disease has not been established as a cause of sudden death. We present the case of a middle-aged woman with vast bilateral basal ganglia and cerebellar calcifications that led to the diagnosis of Fahr's syndrome and at the same time gave a clue for the fatal outcome.

Ependymoma of the cauda equina.

Myxopapillary ependymomas are benign tumours which occasionally metastasize along cerebrospinal fluid pathways. Extraneural metastases of spinal ependymomas, however, are very rare, even more so when situated in the pleura. We report the case of a 67 year old woman presenting with shortness of breath after recurrent myxopapillary ependymomas of the cauda equina. Chest X-ray showed multiple pleural lesions diagnosed as metastases of a myxopapillary ependymoma. The MIB-1 proliferation index was 3.1% for the initial spinal tumour, 14.2% for the first and 11.2% for the second recurrence while 12.0% for the pleural metastasis.

Melanotic progonoma of the brain: a case report and review.

So far, only 25 melanotic progonomas have been found in the central nervous system (male/female ratio 3.5), mostly located in the cerebellum. The average age is 8 years (range 3.5 months to 69 years) with 85% becoming clinically apparent in the first decade of life; 73.7% of the patients reported succumbed to their disease at a mean age of 2.8 years, with a postoperative survival time of just 9 months. Systemic metastases were reported in 9 cases and had mostly spread via cerebrospinal fluid. In contrast to peripheral melanotic progonomas usually found in the maxilla, cerebral progonomas have a much worse outcome and have to be regarded as malignant. We present the case of a 1-year-old boy suffering from a melanotic progonoma of the pineal gland, who died at the age of 22 months with extensive spinal and abdominal metastases 10 months after partial removal of the tumor.

Cell death mechanisms in multiple system atrophy.

The presence and distribution of apoptotic cell death in multiple system atrophy (MSA) and morphologically related diseases were investigated by means of a modified terminal deoxynucleotidyl transferase-mediated nick end labeling method, comparing their distribution with that of glial cytoplasmic inclusions, immunohistochemically demonstrated bcl-2 protein, bax protein, CD95, TNFalpha, and p53-protein expression, as well as activated microglia. Apoptosis occurred almost exclusively in oligodendrocytes in multiple system atrophy and its general distribution was comparable to the already known oligodendroglial pathology in this disorder. Additionally, in about a quarter of glial cytoplasmic inclusions, there was upregulation of bcl-2-protein and coexpression with ubiquitin, suggesting a final attempt of involved cells to counteract apoptotic cell death. Bax protein was also demonstrated in oligodendroglial cells. A significant neuronal apoptosis was not observed in MSA; these cells might be destroyed secondarily to oligodendroglial apoptosis by necrosis or other forms of programmed cell death. These results emphasize the central role of oligodendroglial pathology in multiple system atrophy, making this disease unique among neurodegenerative diseases.

Coexistence of Alzheimer-type neuropathology in Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD) and Alzheimer's disease (AD) share clinical, neuropathological, and pathogenetic features. To investigate eventual mutual influences, we screened prominently affected neocortex from 110 neuropathologically proven CJD patients for Alzheimer-type pathology with anti-beta/A4, Bielschowsky and anti-tau (immuno)stains. The neuropathological classification of Alzheimer-type pathology was made according to the CERAD criteria. Results were controlled by comparison with Alzheimer-type changes in sections from the same cortical areas in 110 sex- and age-matched non-demented control patients. For comparison, the control patients were also classified according to the CERAD neuropathology criteria as if they had been demented. Alzheimer-type tissue changes as in definite and probable CERAD AD occur in 10.9% of the CJD patients and 19.1% of control patients (P=0.11). The median age of CJD and control patients with CERAD AD is 72 and 68 years, respectively, which differs significantly from the median ages of 64 and 63 years, respectively, in the non-AD/CJD and non-AD control patients. Since CERAD criteria include "presence of other neuropathological lesions likely to cause dementia", an AD diagnosis in CJD patients (all of whom are demented) is solely based on densities of neuritic plaques. Similar Alzheimer-type changes in even higher frequency, however, are also present in elderly non-demented controls. Thus, the coexistence of Alzheimer-type pathology in CJD most likely represents an age-related change. Deposits of prion protein (PrP) frequently accumulate at the periphery of beta/A4 plaques. The presence of beta/A4 amyloid in the brain may influence PrP morphogenesis.

A unique case of cerebral spleen.

We present the first case of cerebral splenosis, occurring in a 20-year-old man 15 years after posttraumatic splenectomy. He became symptomatic through seizures and was operated on for suspected meningioma of the right occipital pole. Histologic evaluation of the lesion revealed splenic tissue with matching immunohistochemical results. Because no penetrating head injuries were reported at the time of trauma, a hematogenous spread of splenic tissue has to be assumed.

High amino acid uptake in a low-grade desmoplastic infantile ganglioglioma in a 14-year-old patient.

Amino acid uptake is higher in high-grade than in low-grade gliomas; this is the rationale for using radioactively labelled amino acids for the non-invasive grading of brain neoplasms. We present a 14-year-old boy with a low-grade desmoplastic infantile ganglioglioma (DIG) that exhibited marked contrast enhancement on magnetic resonance imaging (MRI), but no signs of infiltration and only minimal surrounding edema. In this benign neoplasm the relative uptake of the radioactively labelled amino acid I-123-alpha-methyl tyrosine (IMT), determined using single-photon emission computed tomography (SPECT), was 3.24; it was considerably higher than that of eleven other pretherapeutic low-grade gliomas where it ranged from 1.06 to 1.94 and also markedly above that average value of 2.37 found in 20 high-grade gliomas. This case report illustrates that results from emission tomography with radioactively labelled amino acids must be interpreted with caution, particularly when rare tumor entities are considered in view of uncommon clinical or radiological findings.

Oligodendrocyte and axon pathology in clinically silent multiple sclerosis lesions.

Oligodendrocyte and axon pathology was studied in 11 autopsy cases of clinically silent multiple sclerosis. A total of 54 lesions, either demyelinated or late remyelinated, were distributed through the whole brain and spinal cord with 39% of the lesions located in periventricular areas. Determination of axon density revealed an average reduction of 64% and 59% in demyelinated and remyelinated lesions with an extreme variation between different plaques and cases. Oligodendrocytes were identified by immunocytochemistry for myelin oligodendrocyte glycoprotein (MOG) and in situ hybridization for proteolipid protein (PLP) mRNA. Oligodendrocytes were almost completely lost in demyelinated lesions; remyelinated lesions revealed preservation of a considerable number of oligodendrocytes within the lesions. At the border between plaques and the periplaque white matter, similar oligodendrocyte numbers as in remyelinated lesions were found. Different factors including lesion site, axonal preservation and remyelination may thus contribute to the clinical nonappearance of multiple sclerosis lesions.

Hyposexuality produced by temporal lobe epilepsy in the cat.

PURPOSE: The hypothesis tested in this study was that a unilateral irritative focal epileptic lesion in the temporal lobe results in hyposexuality. METHODS: Focal epilepsy was produced in male cats by unilateral injection of aluminum hydroxide into either the basolateral amygdala (temporal lobe group) or anterior sigmoid gyrus (motor cortex group). Weekly sex testing trials with estrous females were conducted prior to and after aluminum hydroxide injection, and mating performance scores were compared with those of normal, unoperated cats (normal control group). RESULTS: All animals receiving aluminum hydroxide developed electroencephalographic and behavioral manifestations of epilepsy; i.e., interictal EEG spiking and partial or generalized seizures. Cats in the temporal lobe group exhibited a dramatic and complete suppression of sexual behavior at periods from 6 to 26 weeks after aluminum hydroxide injection. The duration of the hyposexuality varied between individual animals and returned to normal as suddenly as the onset occurred, despite the use of AEDs to prevent or control generalized seizure activity. Interictal EEG epileptiform spiking in the amygdala preceded the onset of hyposexuality by 1-12 weeks. By contrast, cats in the motor cortex and normal control groups showed no sign of sexual dysfunction throughout the experimental period, independent of seizure activity and/or antiepileptic drug (AED) treatment. CONCLUSIONS: These data support the hypothesis that hyposexuality occurs as a result of epileptiform activity in the temporal lobe, but not in the motor cortex. The precise mechanisms by which this occurs are unknown, but are likely to involve abnormally high-frequency neuronal activity in temporal lobe structures known to connect with and/or to regulate hypothalamic nuclei that organize male sexual behavior toward receptive females.

Factor XIIIa-immunoreactivity in tumors of the central nervous system.

The clotting factor XIIIa (FXIIIa) has been shown to be present both in tumor cells and in tumor-associated macrophages of different neoplasms such as Hodgkin's disease, giant cell tumor of bone, malignant fibrous histiocytoma, meningeal tumors, and hemangiopericytoma. The biological significance of these findings, however, are still unclear. This study investigates the immunohistochemical distribution of FXIIIa in 186 tumors of the central nervous system (CNS) in order to evaluate its possible diagnostic or prognostic significance in neuro-oncology. High-grade gliomas such as glioblastoma, gliosarcoma, astrocytoma (grade III WHO), and ependymoma (III) as well as meningiomas and meningeal hemangiopericytomas consistently contained factor XIIIa-positive cells, whereas low-grade glial tumors did not do so. One desmoplastic medulloblastoma and one anaplastic schwannoma also showed FXIIIa-positive cells. With the exception of hemangiopericytomas, however, the major source of FXIIIa expression in all these tumors consisted of a subpopulation of tumor-associated macrophages, the exact role of which still remains unclear. Because of its non-discriminatory staining in a wide variety of CNS tumors, the differential diagnostic contribution of FXIIIa in neuro-oncology seems to be limited.

Detection of JC virus in two African cases of progressive multifocal leukoencephalopathy including identification of JCV type 3 in a Gambian AIDS patient.

Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating central nervous system (CNS) infection, affecting mainly oligodendrocytes, but also occasional astrocytes. In the USA, Europe and Asia, PML is caused by the human polyomavirus JC virus (JCV) and in autopsy series occurs in about 4-7% of AIDS patients. In Africa, the prevalence of PML in AIDS patients is uncertain and the causative agent is unknown. This study reports immunocytochemical and PCR confirmation of PML in the CNS of an AIDS patient dying in Uganda, East Africa (case 1). In a Gambian patient infected with HIV-2 who died 3 months after onset of AIDS/PML in Germany (case 2), it was possible to confirm the identity of the virus by DNA sequencing of the PCR amplified JCV product. This African genotype of the virus (type 3) showed an unusual re-arrangement of the regulatory region, and could be distinguished at several sites from East African and African-American JCV strains described previously. This study has confirmed that PML is a complication of African AIDS as it is in Europe and the USA, and that JCV type 3 is pathogenic in African AIDS patients. Furthermore, the finding of an African genotype of JCV in a patient dying in Germany suggests that in this individual JCV represented a latent infection acquired in Africa.

Primary intracranial neoplasms of infancy and early childhood.

We investigated the age-related location, gender distribution, and histology of 107 brain tumors in children under 4 years of age seen in our department between 1984 and 1997. The male-to-female ratio was 1.4 (62/45 cases) with a prevalence of supratentorial tumors (60/47 = 1.3); the main histological entity was astrocytoma (33.6%), followed by ependymoma (14.0%). In the 1st year of life 22 cerebral neoplasms became clinically apparent. A higher ratio for supratentorial tumors was revealed (17/5 = 3.4), but without gender preference, and primitive neuroectodermal tumors (PNET) were the most frequent (5/22). In the 2nd year 25 tumors were found. The male-to-female ratio was 1.5 (15/10) and the supratentorial-to-infratentorial ratio, 1.1 (13/12). The two most common entities were astrocytoma and ependymoma (6 cases each). In addition, a survey of previously published investigations into this subject was performed and a compilation of data on 1960, 545 and 1084 tumors in children below the age of 1, 2 and 4 years, respectively, was prepared, which makes it the most extensive review of brain tumors of infancy and early childhood yet undertaken.

Congenital immature teratoma of the fetal brain.

Congenital intracranial tumors are very rare and only account for 0.5-1.5% of all childhood brain tumors. Even rarer are those with prenatal manifestation. The most common of these present at birth are teratomas, which show divergent differentiation with 90% of them containing tissues from all three germ layers. We report a rare case of an intrauterine congenital immature teratoma in a female fetus at 23 weeks of gestation, which was sonographically diagnosed in vivo by detection of the tumor and associated craniomegaly. Because of the poor prognosis, termination of the pregnancy was induced by Rivanol instillation. The cerebral tumor was confirmed at autopsy and was not associated with any other malformations. Histological and immunohistochemical features of this tumor are presented.

Prenatal diagnosis of a highly undifferentiated brain tumour--a case report and review of the literature.

Intracranial tumours, often presenting with progressive hydrocephalus, are rare congenital diseases accounting for 0.5-1.5 per cent of all cases of brain tumours diagnosed during childhood. The differential diagnosis includes vascular malformations, infarctions, and haemorrhages. Sonographic signs suggestive of glioblastoma, teratoma, and astrocytoma do not establish the histological diagnosis, however. We report a case of an undifferentiated fetal glioma detected at 29 weeks' gestation. The diagnosis of an undifferentiated brain tumour was suspected by sonography because of the lack of normal brain structures in conjunction with a diffuse echogenic central lesion and an external hydrocephalus. Because of the very poor prognosis, we induced labour by intravaginal and intravenous administration of prostaglandin E2 and achieved the vaginal delivery of a stillborn child whose head circumference corresponded to 38 weeks of pregnancy. Histological and immunochemical features of this undifferentiated congenital glioma (glioblastoma) are presented.

Iodine-123-alpha-methyl tyrosine in gliomas: correlation with cellular density and proliferative activity.

UNLABELLED: Amino acid transport rate in gliomas can be assessed using SPECT and the amino acid L-123I-alpha-methyl tyrosine (IMT). This study attempted to correlate the uptake of IMT by gliomas with the proliferative activity and cellular density of these neoplasms. METHODS: The study used 27 patients with gliomas, including 18 patients with high-grade tumors and nine patients with low-grade neoplasms. Amino acid transport rate was determined using IMT and the triple-headed SPECT camera. Proliferative activity was immunohistochemically assessed as the relative number of cells expressing the Ki-67 nuclear antigen; cellular density was evaluated using light microscopy. RESULTS: Relative IMT uptake correlated significantly with the proliferative fraction of tumor cells (r = 0.6, p < 0.001). There was no significant correlation between IMT uptake and cellular density (r = 0.25, p > 0.05). CONCLUSION: The uptake of the SPECT radiopharmaceutical IMT is related to proliferative activity rather than to the cellular density of gliomas.

Cytomegalovirus encephalomyelomeningoradiculitis in acquired immunodeficiency syndrome (AIDS).

Acute inflammatory polyradiculitis represents an uncommon peripheral nerve complication during HIV infection. The case of an HIV-seropositive patient who was admitted to hospital for a cauda equina syndrome is reported. Despite early application of anticytomegalic medication, a cytomegalovrirus (CMV) infection spread out to the central nervous system (CNS), causing the patient's death. A post-mortem examination confirmed the diagnosis of CMV-encephalomyelomeningoradiculitis. To the authors' knowledge, such a progress of a CMV-related polyradiculitis to an encephalomyelomeningoradiculitis has not yet been described. The clinical features of this case will aid in the recognition of CMV-related neurological complications, and may permit earlier and perhaps more successful treatment.

Three-dimensional reconstruction of senile plaques in Alzheimer's disease.

So far, the three-dimensional approach to senile plaques, one of the principal histopathological hallmarks in Alzheimer's disease besides neurofibrillary tangles, has been scarce. Two main problems in three-dimensional reconstruction of histological specimens are the horizontal distortion during the preparation of serial thin tissue-slides and the need for consecutive vertical readjustment. This is greatly facilitated by the reflection contrast microscope (Leica, Germany) which is a light microscopical instrument causing interference patterns and reflections along interfaces by means of circularly polarized epi-illumination. Using this technique, one can obtain distinct optical sections of a depth of 1.5 microns within specimens up to 30 microns in thickness, thus preserving the integrity of the observed object and rendering a manual alignment superfluous. We applied the reflection contrast microscope (RCM) on thick tissue-slides of the cerebral cortex of a patient suffering from Alzheimer's disease which had been dyed according to Campbell. This is a silver-based staining method detecting beta A4-amyloid, the main component of senile plaques. Under the RCM, these silver-stained extracellular amyloid deposits cause reflections which allow the assessment of their three-dimensional distribution by focusing through the specimen. The optical sections obtained in this way were digitized, and the identified senile plaques reconstructed by the grey-scale image analysis system VIDAS 2.5 (Zeiss/Kontron, Germany).