[Erwin Gustav Niessl von Mayendorf and his impact on the conceptional history of aphasia]. / Der Beitrag von Erwin Gustav Niessl von Mayendorf zur Konzeptgeschichte der Aphasie.

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 antilocationalism. 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.

Laser-induced alteration of collagen substructure allows microsurgical tissue welding.

Tissue welding is a potentially important biomedical application of laser technology. The structural alterations basic to this phenomenon were studied in experimental repair of lesions of the rat carotid artery and sciatic nerve. A modified neodymiumdoped yttrium-aluminum-garnet laser operating at a wavelength of 1.319 micrometers was used in conjunction with conventional suture techniques. Histological and fine-structural analysis revealed a homogenizing change in collagen with interdigitation of altered individual fibrils that appeared to be the structural basis of the welding effect.

Calcium-induced displacement of membrane-associated particles upon aggregation of chromaffin granules.

Isolated chromaffin granules incubated in 10 millimolar calcium chloride aggregated, forming contact sites with a pentalaminar membrane structure. These circular attachment sites were free of membrane-associated particles, which accumulated at the periphery. Incubation in 20 millimolar ethylenediaminetetraacetic acid reversed these changes, which are regarded as initial events in the membrane fusion reaction.

Mild clinical and histopathological features in patients who carry the frequent and causative malignant hyperthermia RyR1 mutation p.Thr2206Met.

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.

Correlation of physical and morphological parameters with release of catecholamines, ATP, and protein from adrenal medulla chromaffin granules.

Exchanging 0.3 M sucrose for 0.3 M glycerol as the bathing medium for isolated bovine adrenal chromaffin granules at 0 degrees C or raising the temperature of granules suspended in 0.3 M sucrose to 37 degrees C causes the release of catecholamines, ATP and soluble protein stored in the granules. These treatments also reduce the turbidity (absorbance at a non-absorbing wavelength) of the same suspensions. The glycerol-induced release is shown by morphology and morphometry to be due to lysis of the granules. Advantage is taken of the difference in density of the intact granules and the granule ghosts to confirm this result by centrifugation of glycerol-incubated samples on continuous gradients of sucrose and metrizamide. Similar centrifugation experiments performed on the granules incubated in sucrose at 37 degrees C show that lysis also accounts for the fast phase of release of granule contents, and not graded selective release of material from otherwise intact granules.

Clinical significance and neuropathology of primary MADD in C34-T and G468-T mutations of the AMPD1 gene.

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.

Progression of neurofibrillary changes and PHF-tau in end-stage Alzheimer's disease is different from plaque and cortical microglial pathology.

In terminal Alzheimer's disease (AD) the frequency of plaques was found to be reduced in single cases. To test this finding in a larger sample, and in order to determine whether the number of plaques labeled with different markers and the distribution of neurofibrillary tangles are correlated positively to each other and to the degree of dementia, a sample of 134 autopsy brains with and 15 without AD-related pathology has been examined. All of the cases were staged according to Braak and Braak. Both the frequency of plaques immunopositive for beta-amyloid, amyloid precursor protein, and apolipoprotein E and that of microglial cells in the cortex and in the white matter were determined semiquantitatively. The content and distribution of PHF-tau was ascertained by ELISA and immunohistochemistry. Both the clinical dementia rating and the global deterioration scale were used as clinical parameters retrospectively. Correlation coefficients were calculated for all parameters and differences were evaluated statistically. With progressive distribution of neurofibrillary tangles and increasing content of PHF-tau the plaque stages and the degree of cortical microglia reaction increased up to the Braak-stages IV and V, thereafter showing a slightly decreasing tendency in the investigated regions. In end-stage AD resorption of beta-amyloid seems to surpass its deposition. The microglial reaction in the white matter correlated neither with the Braak-stage nor with the accumulation of amyloid. With regard to the degree of dementia, both scales correlated well with the pathological changes. Our data show that neuronal cytoskeletal alterations progressively increase with progressive dementia until the end stage of AD in contrast to the frequencies of plaques and cortical microglial cells, and are therefore preferable for staging purposes.

Encephalo-myelo-radiculo-ganglionitis presenting as pandysautonomia.

A 68-year-old man developed pandysautonomia with severe orthostatic dysfunction, fixed heart rate, low serum levels of norepinephrine and epinephrine, absent sympathetic skin responses, and pupillary abnormalities. CSF protein was 92 mg/dl. In spite of a good recovery following corticosteroid administration, a relapse occurred, with accompanying sensory symptoms confined to both arms. Fatal sudden cardiac arrest occurred after 4 months. Autopsy revealed numerous lymphocytic infiltrates, predominantly in autonomic and sensory ganglia and, to a lesser extent, in the nerve roots, spinal cord, and brainstem without evidence for an underlying tumor. This case provides histopathologic evidence for an inflammatory etiology of panautonomic neuropathy in some patients.

Prolonged extracorporeal CO2-removal in severe adult respiratory distress syndrome. Neuropathological observations in two cases.

Extracorporeal CO2-removal (EC-CO2-R) using a membrane lung system was applied for 12 and 20 days respectively in two young men with adult respiratory distress syndrome (ARDS). Neuropathological examination revealed only moderate hypoxic changes of unusual distribution. In the first case nerve cell loss in Sommer's sector of the hippocampus and focal incomplete necroses in both putamina were interpreted as the result of cardiac arrest at the onset of the disease rather than of chronic hypoxia. Findings in the second case were confined to nerve cell necroses of a minor degree in the cerebral cortex. Remarkably, the cerebellum was spared in both cases. Our observations suggest that EC-CO2-R was not associated with neuropathological findings which could be attributed specifically to this procedure.

The subunits of alpha2-macroglobulin receptor/low density lipoprotein receptor-related protein, native and transformed alpha2-macroglobulin and interleukin 6 in Alzheimer's disease.

To explore the role of alpha2-macroglobulin receptor/low density lipoprotein receptor-related protein (alpha2M-R/LRP) and its ligands in the pathogenesis of Alzheimer's disease (AD), antibodies were raised against its alpha- and beta-subunits and their expression pattern in the CNS in AD and control cases was correlated with that of native and transformed alpha2-macroglobulin (alpha2M) and interleukin 6 (IL-6). The transmembranous beta-subunit of alpha2M-R/LRP and transformed alpha2M were found in plaque cores in AD. Extramembranous alpha-subunit and native alpha2M immunoreactivities were localized in activated plaque-associated astrocytes and extracellularly in plaques. IL-6 immunostaining was associated with neurofibrillary changes, and was also found extracellularly in the center of plaques and in microglial cells. Our finding that plaque cores contain a second transmembranous protein fragment, the beta-subunit of alpha2 M-R/LRP, suggests ongoing membrane-protein degradation. By altering clearance and scavenger-like functions, fragmentation and breakdown of alpha2M-R/LRP may have an important role in extracellular amyloid deposition and the formation of neurofibrillary tangles in AD.

Multiple paraneoplastic syndromes in a patient with antibodies to neuronal nucleoproteins (anti-Hu).

We report the clinical and autopsy studies of a patient with an unusual combination of multiple paraneoplastic neurological syndromes in association with antibodies to a 35-40 kDa neuronal nucleo-protein (anti-Hu). Neurological disease preceded the detection of a small cell carcinoma of the lung. The patient had combined sensory and motor neuronopathy or neuropathy, cerebellar degeneration, brain-stem and limbic encephalitis, and clinical evidence of the Lambert-Eaton myasthenic syndrome and gastrointestinal pseudo-obstruction of paraneoplastic origin.

Gross-total surgery of supratentorial low-grade gliomas under intraoperative MR guidance.

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.

Continuous measurements of cerebral tissue oxygen pressure during hyperbaric oxygenation--HBO effects on brain edema and necrosis after severe brain trauma in rabbits.

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 degrees C) 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 pO2-measurements were performed 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, pO2 measurements showed a significant increase in pO2 between day 1 and day 4, whereas no significant changes were observed in the control group. During the first HBO session, mean pO2 was 169 mm Hg, during the second 305 mm Hg and during the third 420 mm Hg. The mean area of necrosis was 16.2 mm2 in the HBO group, in the control group 19.9 mm2. 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.

Sarcoidosis of the pineal gland. Case report.

The authors report a case of sarcoidosis of the pineal gland with no other organ manifestation of the disease. The tumor was successfully removed by a direct surgical approach.

Congenital anaplastic astrocytoma with favorable prognosis. Case report.

A large intracranial tumor that caused macrocrania leading to dystocia was demonstrated by prenatal ultrasound examination. After birth, computerized tomography (CT) confirmed the presence of a giant supratentorial tumor with a large cyst. When the infant was 20 days old, the tumor was radically extirpated. Neuropathological examination revealed an astrocytoma with focal signs of anaplasia showing a macrocyst as well as multiple microcysts resulting from hemorrhages into the tumor. Although no adjuvant radio- or chemotherapy was administered, the child had nearly normal psychomotor development without clinical or CT evidence of tumor recurrence, and is now 3 years old.

Findings confirming brainstem generators of auditory evoked potentials by stereotactic lesions in the rabbit.

The origin of brainstem auditory evoked potentials (BAEP) was investigated experimentally with morphologically verified stereotactic lesions in eleven rabbits. Waves were recorded before and after thermocoagulation. The loss of waves III and V following coagulation in the inferior colliculus and the upper pons respectively, supports Jewett's hypothesis.

Optical properties of selected native and coagulated human brain tissues in vitro in the visible and near infrared spectral range.

Medical laser applications require knowledge about the optical properties of target tissue. In this study, the optical properties of selected native and coagulated human brain structures were determined in vitro in the spectral range between 360 and 1100 nm. The tissues investigated included white brain matter, grey brain matter, cerebellum and brainstem tissues (pons, thalamus). In addition, the optical properties of two human tumours (meningioma, astrocytoma WHO grade II) were determined. Diffuse reflectance, total transmittance and collimated transmittance of the samples were measured using an integrating-sphere technique. From these experimental data, the absorption coefficients, the scattering coefficients and the anisotropy factors of the samples were determined employing an inverse Monte Carlo technique. The tissues investigated differed from each other predominantly in their scattering properties. Thermal coagulation reduced the optical penetration depth substantially. The highest penetration depths for all tissues investigated were found in the wavelength range between 1000 and 1100 nm. A comparison with data from the literature revealed the importance of the employed tissue preparation technique and the impact of the theoretical model used to extract the optical coefficients from the measured quantities.

Cystic changes and vascular permeability in meningiomas.

A retrospective study of 397 human meningiomas revealed microcystic and cystic changes in about 10% of tumors, predominantly meningiomas of the meningotheliomatous subtype. The biological behavior of these tumors corresponded to those of meningiomas in general, while one tumor singled out from the microcystic variant and separately described as myxomatous meningioma was characterized by a high recurrency rate. Histochemical and immunohistochemical examination with serum proteins of variable size indicated that the microcystic alterations are associated with local vascular permeability disturbances. Hyaline vascular changes and increased numbers of mast cells were further intriguing observations with respect to the pathogenesis of microcyst formation. Possible clinical implications, in particular in regard to the sometimes severe peritumoral edema, are discussed. Since surgical material is insufficient in this respect due to sampling limitations, an unoperated autopsy case is included in this study.

Carotid artery dissection in a young adult: cystic medial necrosis associated with an increased elastase content.

A dissecting aneurysm of the right internal carotid artery was found in a 22-year-old man, who rapidly became unconscious and hemiparetic after an accident occurring during sport. The dissection was limited to the intima and internal elastic lamina. Patterns of cystic medial necrosis with mucoid degeneration were present in the right internal carotid artery proximal to the site of dissection, in the thoracic aorta, and in several visceral arteries. In the region of the right internal carotid artery affected with cystic medial necrosis, calcification and also splitting of the internal elastic lamina was found. Such calcification was also present at the site of the dissection, at the tip of the ruptured and recoiled elastic lamina. These changes, dissection as well as cystic medial necrosis, were associated with an elevated elastase content, a decrease of desmin and an increase of vimentin expression. Ultrastructurally, in areas affected by cystic medial necrosis a corresponding transformation of medial smooth muscle cell phenotype from the contractile to the metabolic state was found. The topographical relation of dissecting aneurysm, cystic medial necrosis, and an increased elastase content is suggestive of a causal relation, and the possibility of common etiological factors is discussed.

Diffuse plaques in the molecular layer show intracellular A beta(8-17)-immunoreactive deposits in subpial astrocytes.

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.