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Objective: Preoperative seizures are a common symptom in meningioma patients. Known risk factors include radiological features, localization but also WHO grading. Recently, brain invasion was added as an independent criterion for WHO II meningioma and its clinical importance was questioned in subsequent[for full text, please go to the a.m. URL], 71. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 9. Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie

Objective: Patients with glioblastoma (GBM) continue to have an unfavorable prognosis. A novel therapeutic approach is pursued with interstitial photodynamic therapy (PDT). After oral administration of a photosensitizing substance, the tumor is irradiated using stereotactically inserted laser probes.[for full text, please go to the a.m. URL], 70. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Skandinavischen Gesellschaft für Neurochirurgie

Very often in vivo diagnosis in patients with dementia lacksprecision. Most diagnostic criteria require a neuropathological examination to establish a definite diagnosis. Hence, except caseswith known mutations in some diseases, to clarify the final diagnosisin vivo, a biopsy is mandatory.We report a case of a 46 year old male patient suffering fromdementia and changed interpersonal behaviour. All clinical andbiochemistry examinations like MRI, FDG-PET, CSF und neu-ropsychology didn’t lead to a satisfying diagnosis. After 3 years oflack of clarity we chose in a multidisciplinary setting brain biopsyfor further investigations. The stereotactic biopsy of the right frontallobe was performed in our department for neurosurgery without anycomplications. The neuropathology showed TDP43-positive depos-its. Post mortem a neuropathology examination and genetic analysishave been conducted. So the diagnosis of frontotemporal dementiawith TDP-43 inclusions was confirmed, but no mutation was found.Brain biopsies are rarely performed in patients with dementia. Inour opinion, stereotactic brain biopsy performed secondary to fulluse of alternative examination techniques in a centre with anappropriate set up may be justified upon individual decision in caseswith unclear dementia a possibility to solve unclear cases.

U. Rub, K. Burk, D. Timmann, W. den Dunnen, K. Seidel, K. Farrag, E. Brunt, H. Heinsen, R. Egensperger, A. Bornemann, S. Schwarzacher, H.-W. Korf, L. Schols, J. Bohl and T. Deller (2012) Neuropathology and Applied Neurobiology 38, 665680 Spinocerebellar ataxia type 1 (SCA1): new pathoanatomical and clinico-pathological insights Aims: Spinocerebellar ataxia type 1 (SCA1) represents the first molecular genetically characterized autosomal dominantly inherited cerebellar ataxia and is assigned to the CAG-repeat or polyglutamine diseases. Owing to limited knowledge about SCA1 neuropathology, appropriate pathoanatomical correlates of a large variety of SCA1 disease symptoms are missing and the neuropathological basis for further morphological and experimental SCA1 studies is still fragmentary. Methods: In the present study, we investigated for the first time serial tissue sections through the complete brains of clinically diagnosed and genetically confirmed SCA1 patients. Results: Brain damage in the three SCA1 patients studied went beyond the well-known brain predilection sites of the underlying pathological process. Along with neuronal loss in the primary motor cortex, it included widespread degeneration of gray components of the basal forebrain, thalamus, brainstem and cerebellum, as well as of white matter components in the cerebellum and brainstem. It involved the motor cerebellothalamocortical and basal ganglia-thalamocortical circuits, the visual, auditory, somatosensory, oculomotor, vestibular, ingestion-related, precerebellar, basal forebrain cholinergic and midbrain dopaminergic systems. Conclusions: These findings show for the first time that the extent and severity of brain damage in SCA1 is very similar to that of clinically closely related spinocerebellar ataxias (that is, SCA2, SCA3 and SCA7). They offer suitable explanations for poorly understood SCA1 disease symptoms and will facilitate the interpretation of further morphological and experimental SCA1 studies.

Background: Spinal glioma are rare and their biological behavior can differ from their cerebral counterparts. Pilomyxoid astrocytoma (PMA, WHO °II) typically occur in the hypothalamic/chiasmatic region of children. The few reported cases of pediatric spinal PMA displayed a particularly aggressive[for full text, please go to the a.m. URL], 57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

Objective: Three different uptake patterns of O-(2-[(18)F]fluoroethyl)-l-tyrosine (18FET) have been shown to occur in patients with suspected WHO II glioma after dynamic PET evaluation: 1) a constantly increasing uptake throughout the entire tumor volume indicative for a grade II glioma. 2)[for full text, please go to the a.m. URL], 63. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie (JNS)

Objective: Metabolic imaging such as O-(2-18F-fluoroethyl)-L thyrosine (FET) positron emission tomography (PET) often revealed heterogeneous findings in suspected WHO grade II glioma showing one or more HOT-SPOT area(s). To which extent these HOT-SPOTS correlate with malignant tumour parts, has never[for full text, please go to the a.m. URL], 60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit den Benelux-Ländern und Bulgarien

Objective: Histological grading of gliomas is mandatory to assess prognosis and determine treatment concepts. Conventional MRI using T1 (± gadolinium) and T2 sequences lacks diagnostic sensitivity and specificity. Significant diagnostic improvement has been shown for metabolic imaging such as [18F]-fluoroethyl-thyrosine[for full text, please go to the a.m. URL], 60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit den Benelux-Ländern und Bulgarien

Objective: Epigenetic silencing of the MGMT gene has been linked to favorable prognosis in glioblastomas (GBM) after treatment according to the EORTC protocol even when stratified for the extent of surgery except for patients who undergo biopsy only. Aim of this study was to evaluate the prognostic [for full text, please go to the a.m. URL], 60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit den Benelux-Ländern und Bulgarien

A number of susceptibility loci for Alzheimer's disease (AD) have been identified including a region on Chromosome 10q21-q22. Within this region the plasminogen activator urokinase gene (PLAU) was considered as a reasonable candidate from its functional implication in plasmin generation, a serine protease capable of degrading beta-Amyloid (A beta) protein. We screened 56 single nucleotide polymorphisms (SNPs) around PLAU using 1751 individuals from four independent case-control samples (Munich, N=679; Bonn N=282; Brescia (Italy) N=219; Perth (Australia) N=557 and one discordant sib-pair sample (Munich N=622). In brain tissue samples of neuropathologically confirmed cases with AD (N=33) we analyzed plaque counts according to the risk allele. We identified that one functional exonic SNP (rs2227564) is associated with development of AD using the four independent case-control samples (Munich, P=0.02; Bonn, P=0.005; Brescia (Italy), P=0.001; Perth (Australia), P=0.03) and the discordant sib-pair sample (P=0.001). In brain tissue, from neuropathologically confirmed cases with AD, we identified significantly higher plaque counts in carriers of the risk allele (N=6; 60.3 +/- 16.9) compared with non-carriers (N=9; 26.3 +/- 8.8; P=0.007). This study provides compelling evidence of a genetic and functional involvement of a common PLAU variant into the pathogenesis of AD. Further functional investigations are warranted to elucidate the specific role of PLAU, respectively, PLAU variants in the metabolism of A beta proteins.

Hel-N1 and HuD belong to the elav gene family and have a considerable role in neuronal development. However, there is only limited information available on the expression profile in human brain and neural tumor cell lines.Therefore, RT-PCR analysis has been performed on human fetal, normal adult, and psychiatric brains (from patients with schizophrenia, Alzheimer's disease, and alcoholism) as well as 20 glioblastoma and 9 medulloblastoma cell lines.Both, Hel-N1 and HuD were abundantly expressed in all brain samples with no obvious difference. However, the neural tumor cell lines showed a differential expression pattern. The medulloblastoma cell lines expressed at least one of the genes in a frequency of 67% for HuD and 78% for Hel-N1 transcripts, respectively. In contrast to the glioblastoma cell lines, which revealed no evidence for HuD RT-PCR products. Surprisingly, 55% of the glioblastoma cell lines showed Hel-N1 expression.These observations indicate that Hel-N1 and HuD participate in molecular processes in human brain, both during development and in the mature adult brain. Hel-N1 and HuD transcriptional activity are stable markers for medulloblastoma cell lines, a tumor, which is thought to be derived from a neuronal precursor cell. The role of Hel-N1 in glioblastomas, the most prominent representative of the glial tumors is presently unclear. This finding is the first indication for a possible involvement of an Elav-like gene product in the glial cell lineage.

To study the death of photoreceptors in normally developing and dystrophic retina and to test the role of hypoxia in causing that death.Death of photoreceptors was detected in the albino, hooded, and Royal College of Surgeons (RCS) strains of rat, and in the rabbit and cat, using the TUNEL technique. Retinas of selected ages from animals raised normally and those from rat pups raised for periods in hyperoxia (75% oxygen) or hypoxia (10% oxygen) were studied.In all species and strains examined, a naturally occurring wave of photoreceptor death was detected during the last stages of retinal development. In the albino rat, this wave, which began approximately at postnatal day 15 (P15) and peaked at P22, was reduced by hyperoxia and was intensified by hypoxia, producing a "hypoxic dystrophy" of photoreceptors. In the RCS rat, photoreceptor death also commenced at approximately P15 and then proceeded to exhaustion. This degeneration was greatly reduced by hyperoxia. In the RCS rat, hyperoxia was effective in photoreceptor rescue only during a discrete period, from P16 to P22. In the albino rat, the effectiveness of hypoxia in inducing photoreceptor death was much greater between P15 and P21 than at earlier ages, or in the adult.During a critical period extending approximately from P15 to P22, tissue oxygen levels strongly influence photoreceptor death and survival in dystrophic and normally developing strains of rat. This period is evident in normal development as a period of naturally occurring photoreceptor death and is evident experimentally as a period during which hyperoxia is effective in rescuing dying photoreceptors and during which hypoxia is effective in inducing death of otherwise viable photoreceptors.

Protective proteases are key elements of protein quality control pathways that are up-regulated, for example, under various protein folding stresses. These proteases are employed to prevent the accumulation and aggregation of misfolded proteins that can impose severe damage to cells. The high temperature requirement A (HtrA) family of serine proteases has evolved to perform important aspects of ATP-independent protein quality control. So far, however, no HtrA protease is known that degrades protein aggregates. We show here that human HTRA1 degrades aggregated and fibrillar tau, a protein that is critically involved in various neurological disorders. Neuronal cells and patient brains accumulate less tau, neurofibrillary tangles, and neuritic plaques, respectively, when HTRA1 is expressed at elevated levels. Furthermore, HTRA1 mRNA and HTRA1 activity are up-regulated in response to elevated tau concentrations. These data suggest that HTRA1 is performing regulated proteolysis during protein quality control, the implications of which are discussed. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.