Zusammenfassung Erwin Gustav Niessl von Mayendorf (1873 – 1943) beschäftigte sich während der ersten Hälfte des 20. Jhs. mit der Aphasie. Doch blieb er in vorliegenden Konzeptgeschichten der Aphasiologie unberücksichtigt. Die Wiederentdeckung seines Werkes lohnt sich jedoch, da wesentliche seiner Postulate durch den seither erreichten Erkenntnisfortschritt neu bewertet werden können, sie sogar für aktuelle Diskussionen bereichernd erscheinen. Er nahm in der Diskussion der Aphasiologie seiner Zeit eine eigenständige Stellung ein, da er nicht in eine der bekannten ideengeschichtlichen Schubladen passte, sondern eigene Lösungsansätze für Forschungsprobleme anbot. Die Aphasien sah er in Assoziationsstörungen, genauer einer Dysfunktion von funktionellen Assoziationen, begründet. Des Weiteren hob Niessl die Bedeutung der nicht dominanten Hemisphäre für die Sprache und die Entstehung der aphasischen Symptome hervor, was sich heute mithilfe moderner Bildgebung zum Teil bestätigen lassen könnte.

Throughout his life Erwin Gustav Niessl von Mayendorf (1873 - 1943) dealt with aphasia, yet so far his studies have been neglected in the historiography of the illness. Niessl followed a unique approach which stood in contrast to both theories that dominated discussion in the first half of the 20th century - locationalism and anti-locationalism. This may help explain why he fell prey to oblivion. Yet in fact it is worthwhile remembering his studies, in particular since they might enrich present-day discussions. Although supporting the notion that centres where signals and stimuli are perceived could be located in the brain, he strongly rejected the localisation of cognitive processes. For him these were the result of association. Furthermore Niessl stressed the role of the non-dominant and hence untrained right hemisphere for aphasic symptoms standing in to replace the injured or destroyed left one a fact that now may be found from recently published fMRI trials.

OBJECTIVE:Malignant hyperthermia (MH) is a classically unapparent pharmacogenetic disorder of the skeletal muscles triggered by inhalational anesthetics or depolarizing muscle relaxants. The disposition to MH is inherited in an autosomal-dominant manner and is primarily due to mutations in the gene for the ryanodine receptor type 1 (RyR1). The present study intended to analyze whether mild muscular symptoms (elevation of the resting CK, cramps in the calves, slight calf hypertrophy) may be associated with susceptibility to MH and/or with histopathological changes.METHODS:A muscle biopsy was taken from 12 out of 44 blood relatives (three generations) of a large family and was investigated with the halothane/caffeine in vitro contracture test (IVCT). Afterwards a histological, histochemical and immunhistological examination was performed. Altogether in 29 persons the DNA was analyzed for mutations in the RyR1-gene.RESULTS:Eight persons were diagnosed as susceptible to MH (MHS) by the IVCT, 4 were MH negative. All MHS persons carried the MH causative c.6617C > T (Thr2206Met) mutation and showed slight clinical signs of a myopathy as well as mild biopsy changes with isolated hypotrophic fibers and disseminated small areas with reduction of oxidative staining (multi-minicore like lesions). The Thr2206Met mutation was identified in another further 9 relatives who also experienced mild myopathological features. Clinical MH incidents were not reported in this large family.CONCLUSION:The RyR1 Thr2206Met mutation is one of the most frequent mutations in the European MH population but carriers are normally healthy. In this study we could demonstrate that the MH causative Thr2206Met mutation may also be associated both with clinical symptoms of a mild myopathy and histopathological changes in the oxidative inter myofibrillar network.

OBJECTIVE:Primary myoadenylate deaminase deficiency (MADD) is probably the most frequent inborn metabolic myopathy with a prevalence of up to 2%. It is the result of mutations in the AMPDI gene, the most common of which is a C34-T transition in exon 2. The importance of the more rare mutation G468-T in exon 5 is uncertain. Primary objective was to elucidate the clinical significance of the enzyme disorder, which remains unclear since its first description in 1978. We further examined the existence of an association of MADD with other muscle disorders, such as malignant hyperthermia and rhabdomyolysis, as was suspected in earlier studies.MATERIAL AND METHODS:In a large collection of 1673 muscle biopsies that had been stored deep frozen we identified 33 cases of primary MADD, 12 of which without any other coinciding muscle diseases, by histochemical, biochemical and molecular genetic examinations. Clinical and laboratory data was collected. By additional examination of randomly chosen blood samples we identified one person carrying the rare compound heterozygosity C34-T/ G468-T, who was examined in clinical respects and a muscle biopsy was taken.RESULTS:As underlying mutation, the most common transition C34-T/C 143-T was detected in 33 cases. One patient carried the compound heterozygosity C34-T/G468-T. The overall frequency of MADD in the contingent was 1.8%. Only three patients out of 12 with isolated primary MADD suffered from muscle complaints, one of whom did not experience the typical symptoms of exercise related myalgia, muscle cramps and weakness as described by Fishbein. The patient carrying C34-T/G468-T was a fully healthy female. She had never experienced any muscle complaints. Any association with other neuromuscular disorders, if not completely ruled out, was found to be very unlikely.CONCLUSION:The results suggest that MADD itself is unlikely to be solely responsible for the manifestation of muscular symptoms. It is probable that either the loss of a compensation mechanism or coexistent disturbances in muscle metabolism which are unidentified so far are required for the emergence of complaints.

Ziele: Untersuchungen zur Genauigkeit des intraoperativen Ultraschalls (ioUS) im Vergleich zur prä- bzw. früh postoperativen MRT in der Bestimmung von initialem Tumorvolumen und Größe des verbliebenen Resttumors. Methode: Bei 17 Patienten wurde an Hand präoperativer T1w 3D-Messungen (nach Gd-DTPA) das initiale Tumorvolumen bestimmt. Die US-Vergleichsmessung dazu wurde intraoperativ in 2 Ebenen vor Duraeröffnung durchgeführt. Die Tumoresektion erfolgte mit dem Ziel der vollständigen Entfernung der Läsion, basierend auf der mikroskopischen Sicht und in Kenntnis von Neuronavigationsdaten, ergänzt durch den ioUS. Dennoch verbliebene Resttumorareale wurden vor Duraverschluss mittels US vermessen. Zum Vergleich erfolgte eine frühe postoperative MRT (<72h nach OP, T1w SE vor/nach Gd-DTPA) zur Bestimmung des MR-tomografisch nachweisbaren Resttumorvolumens. Ergebnis: Präoperativ fand sich eine gute Übereinstimmung der Tumorvolumina bei drittgradigen glialen Tumoren (n=2), bei primären GBM (n=7) und bei Metastasen (n=3). Dagegen ergaben sich teilweise erhebliche Diskrepanzen bei Rezidiv-GBM (n=3). Bei den miterfassten Lymphomen (n=2) ließ sich eine Läsion primär im ioUS fast gar nicht abgrenzen, bei dem anderen Patienten ergab sich eine massive Unterschätzung des Tumorvolumens im US. Im Vergleich der verbliebenen Resttumorareale zeigte der ioUS bis auf drei Patienten eine vollständige Resektion an. Demgegenüber stellte die MRT nur in 4/15 Patienten eine vollständige Resektion dar. Die verbliebenen Resttumorvolumina schwankten zwischen 1,1 und 33,9cm3. Schlussfolgerung: Trotz des kleinen, inhomogenen Kollektivs zeichnen sich zwei Aussagen ab: Bei der präoperativen Volumenbestimmung intrakranieller Tumore kann der ioUS in Abhängigkeit von der Tumorentität partiell zuverlässige Werte liefern. Insbesondere aber bei Lymphomen und Rezidiv-GBM erscheint die Tumorabgrenzbarkeit mittels US fraglich. Bei der Resttumorbestimmung mittels ioUS ergibt sich in der Regel eine Unterschätzung des verbliebenen Tumorrestes.

Diffuse astrocytomas are highly variable tumors and show complex biologic behavior that is based on multi-step oncogenesis. We report cytogenetic and molecular cytogenetic investigations in 23 cases of diffuse astrocytomas. The results of conventional karyotyping, interphase fluorescence in situ hybridization (FISH), comparative genomic hybridization, multicolor FISH, and spectral karyotyping are reported. Various numerical and structural chromosomal aberrations were identified. Clustering of structural alterations in the short arm of chromosome 2 (2p) and the long arm of chromosome 7 (7q) were detected. Using spectral karyotyping, additional chromosome rearrangements not detectable by conventional methods were found. Some of these anomalies have not been previously described in diffuse astrocytomas. An independent validation of these discrepant findings is required.

A case of symmetrical neurofibroma with onion bulbs in various stages of development and progression to microneurinomas is presented. Immunohistochemistry with differentiation and growth factor markers as well as electron microscopy showed a Schwann cell origin of the concentrically arranged cells. The onion bulbs differed from those of hypertrophic neuropathy by their more compact structure. A partial expression of cellular proliferation markers in the onion bulbs was consistent with a multifocal proliferative activity, confirming the neoplastic nature of the lesion.

Laser-induced thermotherapy (LITT) is a minimally invasive neurosurgical approach to the stereotactic treatment of brain tumors in poorly accessible regions. Its clinical applicability has been shown in several experimental and clinical studies under on-line monitoring by magnetic resonance imaging (MRI). This review characterizes LITT as an alternative neurosurgical approach with specific focus on the typical histological alterations and ultrastructural cellular changes following laser irradiation in the central nervous system. The spatial and temporal pattern of these changes is discussed in their relevance to the neurosurgical treatment of neoplastic lesions using LITT.

Introduction: Severe brain injury is one of the most frequent causes of severe disability in the young. In acute management of brain trauma, new approaches based on experimental animal investigations should be sought. Methods: Twenty male, juvenile Chinchilla-Bastard rabbits received standardized cold-injury-induced-brain-trauma (CIBT). A metal probe (temperature -196 degreesC) was applied epidurally over 10 s. The hyperbaric oxygenation (HBO) group (n = 10) underwent 90-min HBO sessions with 100% oxygen at 2.5 atmospheres absolute (1 h, 24 +/- 2 h, 48 +/- 2 h after CIBT). Cerebral tissue pO(2)-measurements were pet-formed 60 min after CIBT, during the three HBO sessions and on day 4. The control group (n = 10) underwent no treatment. Animals were sacrificed on day 4, and brains were analyzed histologically. Results: In the HBO group, pO(2) measurements showed a significant increase in pO(2) between day 1 and day 4, whereas no significant changes were observed in the control group. During the first HBO session, mean pO(2) was 169 min Hg, during the second 305 mm Hg and during the third 420 mm Hg. The mean area of necrosis was 16.2 mm(2) in the HBO group, in the control group 19.9 mm(2). The areas of brain edema were significantly smaller in the HBO group. Mortality in the HBO group was 0%, in the control group 20%. Conclusion: HBO appears to be beneficial as an adjunct treatment of severe head trauma. To find optimal treatment protocols, further clinical studies must be developed. (C) 2004 Elsevier B.V. All rights reserved.

Background and Objectives: Laser-induced thermotherapy (LITT) is an approach to the treatment of brain tumors especially in poorly accessible regions. Its clinical applicability with tumor cell destruction has been shown in several studies. However, no data are known about specific effects on tumors cells due to LITT in the time course of the lesion.Study Design/Materials and Methods: LITT was performed in adult Lewis rats with implanted glioma cells in the brain using a standard exposure of 3 W for 30 seconds. Before and following LITT, neoplastic lesions were monitored by MRI. Proliferation of implanted cells and gliosis were assessed by several histological techniques and immunohistochemistry. Apoptosis was detected by TUNEL staining.Results: Our experiments show a destruction of neoplastic cells by LITT but surviving tumor cells at the margin of the lesion. Apoptosis was detected following LITT restricted to residual neoplastic cells. Marginal survival of tumor cells lead to a secondary outgrowth into the necrotic lesion adjacent to sprouting capillaries.Conclusions: LITT is a suitable technique for the treatment of brain neoplasms. However, further investigations are necessary to prevent tumor recurrences after LITT. Lasers Surg. Med. 30:227-232, 2002. (C) 2002 Wiley-Liss, Inc.

BACKGROUND AND PURPOSE:Length of survival of patients with low-grade glioma correlates with the extent of tumor resection. These tumors, however, are difficult to distinguish intraoperatively from normal brain tissue, often leading to incomplete resection. Our goal was to evaluate the effectiveness of intraoperative MR guidance in achieving gross-total resection.METHODS:We studied 12 patients with low-grade glioma who underwent surgery within a vertically open 0.5-T MR system. During surgery, localization of residual tumor tissue was guided by interactive, near real-time imaging. The amount of residual tumor tissue on MR images was evaluated at the point of the operation at which the neurosurgeon would have terminated the procedure under conventional conditions (first control) and again before closing the craniotomy.RESULTS:Significant residual tumor (more than 10% of original tumor volume) was shown in eight patients at the first control condition. The percentage of resection varied from 26% to 100% (mean, 68%) at this time. Twelve tissue samples from seven patients were obtained in areas identified as residual tumor on MR images. In 10 cases, the neuropathologic investigation confirmed the presence of residual low-grade glioma; in two cases, the borderzone of tumor was identified. In evaluating the final sets of images, we found total resection in six cases, over 90% resection in five cases, and 85% resection in one case (mean, 96%).CONCLUSION:Surgical treatment of low-grade gliomas under intraoperative MR guidance provides improved resection results with maximal patient safety.

Abnormal phosphorylation of the τ-protein is regarded as a crucial step in the formation of neurofibrillary tangles in the neuronal cell body and neuropil threads in dendrites. We studied the effects of τ-pathology on the clinical expression of dementia in 106 autopsy cases in the entorhinal region, the hippocampal stratum oriens, the stratum radiatum, and the perforant path target zone. The first cytoskeletal lesions were located in the perikarya and dendrites of the pre-α cells of the transentorhinal and entorhinal region. Next, abnormally phosphorylated τ-protein (PHF-τ) was found in the neuropil of the CA1-subiculum region. Thereafter, the stratum radiatum and stratum oriens began to be involved in PHF-τ pathology in Braak stage II. In the Braak stages IV and V, the stratum radiatum was completely involved, the stratum oriens increasingly so. Beginning in Braak stage III, we noted cases having PHF-τ pathology in the perforant path target zone of the outer molecular layer of the dentate gyrus. The increase of this pathology with ever greater involvement on the part of the entorhinohippocampal circuit correlated significantly not only with the Braak stages and with the neurochemically determined hippocampal content of PHF-τ but also with the degree of dementia as defined by the clinical dementia rating (CDR) scale. The affection of the stratum oriens in combination with PHF-τ pathology in the stratum radiatum and in the outer molecular layer of the dentate gyrus was encountered almost exclusively in demented individuals (CDR 1–3). These results indicate that axonal PHF-τ pathology in hippocampal pathways presumably is critical for the clinical expression of dementia and may constitute an anatomical substrate of clinically verifiable memory dysfunction in Alzheimer's disease.

DNA-cytophotometry is one of the methods that may contribute to a more precise evaluation of the biological behaviour of tumours in addition to the WHO-classification. In this study 121 tumour specimens of 50 patients suffering from gliomas with one or up to three recurrencies were investigated. In all cases the histological type and WHO-grade and the Ki-67/MIB1 labeling index were determined. DNA cytophotometry was performed after single cell preparation on Feulgen-stained preparations, and the following parameters were calculated: stemline ploidy, 5c-exceeding rate, and 2c-deviation index. Statistical evaluation revealed a highly significant correlation between recurrence-free interval and WHO-grade only. The DNA parameters, however, furnished additional information about increasing genetic instability in the majority of the recurrencies independently of changes in the WHO-grade. They thus seem to be useful as additional parameters for the determination of glioma progression.

The presence of A beta protein- (A beta) containing astrocytes in diffuse plaques of the cortical layers II-VI has recently been demonstrated with antibodies directed against A beta(17-23) and C-terminal epitopes, of A beta. We here confirm and extend this finding by use of immunocytochemical double-labeling and preembedding immune-electron microscopy. Diffuse subpial plaques are associated with both anti-A beta(8-17) and anti-A beta(17-23)-positive granules in astrocytes. The ultrastructural nature of these intracellular deposits has been demonstrated to be lysosomal and the deposits have a lipofuscin-like appearance. These data point to a role of subpial astrocytes in the degradation of A beta by lysosomal processing.

Zusammenfassung Eine genaue Bestimmung der biologischen Wertigkeit glialer Tumoren erfordert über die WHO-Klassifikation hinaus die Entwicklung und den Einsatz von Spezialmethoden, wozu auch die DNA-Zytophotometrie gehört. In der vorliegenden Studie wurden an insgesamt 121 histopathologisch klassifizierten Proben von Gliomen bei 50 Patienten mit mindestens 1 und bis zu 3 Rezidiven eine Reihe von DNA-Parametern (Stammlinienploidie, 5c-exceeding rate, 2c-deviation index) nach Zellvereinzelung und Feulgen-Reaktion mittels statischer Feulgen-DNA-Zytometrie bestimmt. Daneben wurde die Proliferationsaktivität (immunhistochemischer Ki-67/MIB-1-labeling index) morphometrisch ermittelt. Diese Parameter wurden mit den WHO-Graden und der Länge der rezidivfreien Intervalle statistisch verglichen. In den Rezidiven sowohl mit ansteigendem als auch mit gleichbleibendem WHO-Grad fand sich eine statistisch signifikante Zunahme des 2c DI, der 5c ER und des Ki-67/MIB-1 LI. Dabei ergab sich eine hochsignifikante Korrelation zwischen den WHO-Graden und der Länge der rezidivfreien Intervalle p <0,00001). Eine statistisch signifikante Korrelation zwischen den DNA- bzw. Proliferationsparametern ließ sich zur Länge des rezidivfreien Intervalls nicht, zum WHO-Grad nur im Falle der ersten Rezidive für die DNA-Parameter herstellen. Die Ergebnisse bestätigen die hohe prognostische Relevanz des WHO-Grades. Die Bestimmung der DNA-Parameter liefert insbesondere bei gleichbleibendem WHO-Grad zusätzliche Informationen über die zunehmende genetische Instabilität des Tumors, welche wie die zunehmende Proliferationsaktivität für die weitere Tumorprogression von Bedeutung ist.