How many people are able to operate an EEG-based brain-computer interface (BCI)?

Ninety-nine healthy people participated in a brain-computer interface (BCI) field study conducted at an exposition held in Graz, Austria. Each subject spent 20-30 min on a two-session BCI investigation. The first session consisted of 40 trials conducted without feedback. Then, a subject-specific classifier was set up to provide the subject with feedback, and the second session--40 trials in which the subject had to control a horizontal bar on a computer screen--was conducted. Subjects were instructed to imagine a right-hand movement or a foot movement after a cue stimulus depending on the direction of an arrow. Bipolar electrodes were mounted over the right-hand representation area and over the foot representation area. Classification results achieved with 1) an adaptive autoregressive model (39 subjects) and 2) band power estimation (60 subjects) are presented. Roughly 93% of the subjects were able to achieve classification accuracy above 60% after two sessions of training.

Predictive value of progression-associated chromosomal aberrations for the prognosis of meningiomas: a retrospective study of 198 cases.

OBJECT: The goal of this study was to determine whether in meningiomas cytogenetic findings are suitable as a predictive parameter relevant to prognosis. METHODS: Between 1992 and 1998 at the Department of Neurosurgery, Saarland University, 198 patients underwent surgery to resect meningiomas. The meningiomas were investigated cytogenetically and the patients were followed up for a mean period of 33 months. On the basis of the cytogenetic findings, the meningiomas were subdivided into four groups: Group 0 meningiomas displayed a normal diploid chromosome set; Group 1 tumors were found to have monosomy 22 as the sole cytogenetic aberration; Group 2 tumors were markedly hypodiploid meningiomas with loss of additional autosomes in addition to monosomy 22; and Group 3 meningiomas had deletions of the short arm of a chromosome 1, as well as additional chromosomal aberrations including loss of one chromosome 22. One hundred ninety-eight patients in whom tumor resections were determined to be Simpson Grade I or II could be followed up after complete tumor extirpation. In 20 patients, one or several recurrences were documented during the period of observation. The tumors were classified according to their different, but mostly uniform chromosomal aberrations. Recurrences were found in six (4.3%) of 139 tumors in Groups 0 and 1 and in two (10.5%) of 19 tumors in Group 2; the highest rate of recurrence was found in 12 (30%) of 40 tumors in Group 3. This supports the notion that the deletion of the short arm of one chromosome 1 is an important prognostic factor in meningiomas. The results of this study document a significant correlation between histological grade (p < 0.0001), location (p < 0.0001), and recurrences of meningiomas (p < 0.0001) (significance determined using chi-square tests). CONCLUSIONS: The cytogenetic classification of meningiomas provides a significant contribution to the predictability of tumor recurrence and is, therefore, a valuable criterion for the neurosurgeon's postoperative management protocol.

Cerebroretinal vasculopathy and leukoencephalopathy mimicking a brain tumor. Report of two early-onset cases with Fanconi's anemia-like phenotypes suggesting an autosomal-recessive inheritance pattern.

We report two sisters affected with a unique disorder characterized by recurrent space-occupying brain lesions and retinal vasculopathy since their early twenties. Affection status was associated with abnormalities characteristic of Fanconi's anemia, i.e. aplastic anemia, microcephaly, short stature, an unusual face and pigmentation abnormalities of skin. In cytogenetic analyses performed in childhood signs of chromosome fragility or any chromosomal aberration were lacking. Histopathological examination of brain biopsy samples in both cases demonstrated identical histomorphological features of an unusual occlusive vasculopathy with multilayered basement membranes and coagulation necroses which were confined to the white matter. A veno-occlusive retinopathy with neovascularization attributed to progressive visual loss. One of the sisters died at an age of just 24 years, the other is now 27 years old. Unlike any other published cases of hereditary cerebroretinal vasculopathy, the sisters' complex early-onset vaso-occlusive CNS-/eye-disease seems to be genetically associated with their Fanconi's anemia-like phenotypes and is suggested to constitute an autosomal-recessive variant. Patchy white matter calcifications, an incidental finding in either of the affected sisters, may represent preclinical manifestation of disease onset in childhood.

[Granulocytic sarcoma (so-called chloroma) as a possible cause of spinal cord compression. Case report and differential diagnosis]. / Granulozytäres Sarkom (sog. Chlorom) als mögliche Ursache einer Rückenmarkskompression. Fallbericht und Differentialdiagnose.

Granulocytic sarcomas (so-called chloromas) are rare extramedullary tumorlike proliferates of myelogenous precursor cells that may de novo precede acute leukemia or coincide with the first manifestation or relapse of acute myeloid leukemia. Rarely, such tumors represent the initial manifestation of a blast crisis in the course of a chronic myeloproliferative disease, such as chronic myeloid leukemia. If they occur in aleukemic patients incorrect diagnoses may result. Differential diagnostic considerations are being discussed by presenting the case of a 58-year-old man who experienced spinal cord compression by an isolated epidural mass lesion.

[Neuropathological and neuroradiological aspects of acute disseminated encephalomyelitis (ADEM)]. / Neuropathologische und neuroradiologische Aspekte akuter disseminierter Enzephalomyelitiden (ADEM).

Among non-neoplastic lesions of the central nervous system, demyelinating pseudotumors of the group of acute disseminated encephalomyelitis (ADEM) most frequently occasion neurosurgical intervention for purposes of definitive diagnosis and thus enter the domain of the surgical pathologist. Typically, ADEM presents with multifocal, bilateral lesions in an asymmetrical distribution. Especially monolocular manifestations may be diagnostically challenging. Due to the acuteness of clinical symptoms and the expansive, space-occupying character of the lesions a diffuse glioma, a metastatic disease, a primary cerebral Non-Hodgkin's lymphoma, brain abscess, a parasitosis or an ischemic brain tissue necrosis may be suspected. This impression is supported by uptake of contrast-medium most pronounced at the periphery of the lesion and the subcortical location. The histomorphologic feature of relative axonal preservation in areas with acute myelin breakdown and lymphocytic infiltrates make the diagnosis of an acute primary demyelinating disease probable. A diagnosis of glioma may be prompted by the florid, cytologically atypical astrogliosis especially in intraoperative request. Based on a series of 14 cases of radiologically and bioptically documented cases of ADEM typical examples will be demonstrated and discussed.

Deletion of chromosome 1p and loss of expression of alkaline phosphatase indicate progression of meningiomas.

Meningiomas are cytogenetically characterized by loss of one chromosome 22 as a typical primary aberration and progression-associated secondary chromosome changes, of which monosomy 1p is the most common. The aim of this study was to evaluate the significance of monosomy 1p and enzyme activity loss of tissue nonspecific alkaline phosphatase (ALPL), whose gene maps to chromosome 1p36.1-p34, as parameters for the diagnosis of progression-prone meningiomas. We analyzed smear preparations of 56 meningiomas and additional paraffin sections of 17 of the cases by two-color fluorescence in situ hybridization (FISH) using the D1Z1 and D1Z2 probes and by a metaphase cytogenetic analysis of 30 of these tumors. The results were compared to clinical and morphological parameters and the expression of ALPL. Smear preparations showed deletion of 1p36 in 27% of common-type, 70% of atypical (intermediate-type), and 100% of anaplastic meningiomas. Monosomy 1p, as detected by FISH or the karyotype, was strongly associated with complete loss of ALPL activity. Intermediate-type and anaplastic meningiomas of younger patients displayed an increasing rate of cells with trisomy 1q and relative loss of 1p. The highly significant correlation of FISH results and ALPL histochemistry with clinical parameters gives evidence of their strong prognostic relevance. The complete activity loss of ALPL and the immunologically detected loss of ALPL protein in areas of meningiomas with monosomy 1p indicate a cytogenetically undetectable inactivation of the homologous Alpl allele. The apparently homozygous loss of expression of ALPL supports the notion that Alpl is a candidate tumor suppressor gene in meningiomas.

[Spontaneous intracerebral hemorrhages. Neuropathologic aspects]. / Spontane intrazerebrale Blutungen. Neuropathologische Aspekte.

Non-traumatic so-called spontaneous intracerebral hemorrhages can occur in the supra- and infratentorial compartment. Taking into account their different etiologies, hemorrhages within the cerebral hemispheres are commonly divided into two categories, deep and lobar ones, with the first ones being frequently related to hypertensive vasculopathy. Lobar hemorrhages that are usually larger than their counterparts in the basal ganglia or thalamus, may be associated with arterio-venous malformations, leukemia or, especially in the elderly, with cerebral amyloid angiopathy (CAA) that is histopathologically characterized by deposits of betaA4-protein exclusively within the walls of medium-sized and small arteries of the leptomeninges and cerebral cortex.

[Histopathologic findings in cerebral artery aneurysms after embolization with Guglielmi detachable platinum coils (GDC): report of two cases]. / Histopathologische Befunde in Hirnbasisarterienaneurysmen nach Embolisation mit Guglielmi detachable platinum coils (GDC).Zwei Fallberichte.

UNLABELLED: Following embolization with Guglielmi detachable coils the histomorphological findings and tissue reactions of two cerebral artery aneurysms were examined. METHODS: In order to study GDCs in situ a giant wide-necked aneurysm of the basilar artery (autopsy case; 14 days after embolization) and a resected aneurysm of the middle cerebral artery (resection; 6.5 months after embolization) were embedded in acrylate, cut in thin sections glued on acrylic slides, then grounded to about 10 microm thickness and finally stained with toluidine blue. RESULTS: With the above-described method GDCs became amenable to histopathologic studies. The coils were more densely packed within the dome than the central lumen. In the resected aneurysm this feature was particularly prominent in that the GDCs were embedded in scarred connective tissue. Few giant cells of the foreign body type were found intimately associated with the GDCs.

Unbalanced translocation t(1;3)(p12-13;q11) in meningiomas as the unique feature of chordoid differentiation.

Chordoid meningioma is a rare histological subtype of meningiomas. Cytogenetic analysis of three cases revealed the unique feature of an unbalanced translocation der(1)t(1;3)(p12-13;q11) that was ascertained by chromosome microdissection and reverse fluorescence in situ hybridization. As the t(1;3) has not been observed in other subtypes of meningioma, it may represent a specific cytogenetic marker of chordoid meningiomas. It is not yet clear whether a fusion gene or the combined loss of genes from chromosome arms 1p and 3p is the pathogenetically important outcome of the translocation.

[Classification and grading of gliomas and meningiomas]. / Klassifikation und Grading von Gliomen und Meningeomen.

GLIOMAS: As we demonstrated for supratentorial, diffuse gliomas in adults, a stratification into just two grades of malignancy, 'low' and 'high grade,' proved reliable and prognostically relevant. The discriminating histomorphological criterion for high-grade astrocytoma (WHO glioblastoma) as well as anaplastic oligodendroglioma and anaplastic oligoastrocytoma is endothelial hyperplasia/proliferation, which is usually associated with uptake of contrast medium in computed tomography and magnetic resonance imaging. As neoangiogenesis indicates glioma progression, it is worthwhile considering these radiographic features to judge the representativeness of the tumor samples critically. MENINGIOMAS: The revised edition of the WHO classification of brain tumors now includes the 'atypical' meningioma (WHO 'grade' II): Based on both its histomorphological features and prognosis, it should be placed between the common type and anaplastic meningioma. Nuclear area related Ki-67 proliferation indices, as determined by morphometry, were the prerequisite for outlining its histomorphological spectrum better. Cytogenetically, the most consistent progression-associated feature was loss of the distal part of the short arm of one chromosome 1 (1p-). Thus, a screening method using the tissue non-specific form of alkaline phosphatase (ALPL) as the respective marker enzyme was established. Diagnosing a meningioma of the intermediate type implies careful clinical and radiological patient follow-ups to detect tumor recurrences early.

[Grading of astrocytomas and oligodendrogliomas]. / Grading von Astrozytomen und Oligodendrogliomen.

The histologic determination of the degree of tissue anaplasia and grade of malignancy of gliomas is based upon qualitative histological features (nuclear pleomorphism, mitoses, endothelial proliferation, tumor necrosis). This grading approach is influenced by the subjective interpretation of the pathologist, especially concerning the weighting of criteria (scant, moderate, pronounced). An observer-independent approach seems to be feasible by abandoning the concept of parameter weighting in favor of an binary approach noting only the presence or absence of these structure parameters. This grading procedure is recognized in the revised WHO classification of brain tumors for common type astrocytomas (Ste. Anne-Mayo System, SAMS). Our results indicate that a similar approach is also suitable for grading purposes of oligodendrogliomas and mixed gliomas. Our recent investigations on glioma grading showed, both for astrocytomas and oligodendrogliomas, that a two-tiered grading scheme distinguishing only "low-grade" and "high grade" cases was prognostically relevant. For all glioma entities the onset of tumor angiogenesis with endothelial proliferation and contrast enhancement in CT and MRI seems to be the key criterion indicating irreversible tumor progression to the "high" malignancy grade.

Multivariate logistic analysis of dose-effect relationship and latency of radiomyelopathy after hyperfractionated and conventionally fractionated radiotherapy in animal experiments.

PURPOSE: We examined in rats whether the radiation tolerance of spinal cord is enhanced by using hyperfractionated radiotherapy compared to a conventional schedule. Higher tolerable doses to the spinal cord would allow dose escalation to the tumor and thus possibly lead to higher cure rates, especially in tumors with high cell proliferation. METHODS AND MATERIALS: Cervical spinal cord of 276 healthy rats was irradiated over 6 weeks hyperfractionally with single doses ranging from 0.75-2.5 Gy up to total doses ranging from 45-150 Gy (60 fractions) and conventionally with single doses of 1.5-4.0 Gy up to total doses of 45-120 Gy (30 fractions). The rats were examined neurologically and sacrificed when paralysis of the hind legs occurred. After fixation, spinal cord was removed and examined histologically. Dose-effect relationship and latency from the beginning of radiotherapy to the onset of paralysis were computed and analyzed using a multivariate logistic regression model. RESULTS: The model fitted the observed data excellently. There were highly significant effects both for the dose level and for the treatment regimen. Latency analysis showed earlier and more intense acute side effects after hyperfractionation but radiomyelopathy occurred markedly later. CONCLUSIONS: The sparing effect of hyperfractionation on spinal cord as predicted by radiobiologists could be confirmed in our experiments. Thus, it seems possible to escalate tumor doses using hyperfractionation without enhanced risk to spinal cord but with higher probability of tumor cure.

Histologic and morphometric grading of gliomas. A comparative survival analysis.

OBJECTIVE: A grading system based upon morphometrically assessed quantitative parameters (HOM system) was correlated with the results of classical histologic grading (St. Anne/Mayo system [SAMS], 1988, and World Health Organization classification, 1993). Validation was done by comparison with survival data. STUDY DESIGN: This retrospective study consisted of representative paraffin-embedded tissue sections of 139 adults who had been surgically treated for supratentorial common gliomas between 1988 and 1994. Histologic grading diagnoses were adapted to the latest standard. Computer-assisted image analysis of Ki-67 (MIB1)/ Feulgen-stained sections provided nuclear parameters appropriate to define homogeneous grades of malignancy by multivariate statistical analyses: average segment length of the minimum spanning trees (ASLMST) for the quantitation of tumor growth pattern; nuclear area percentage (NAP), reflecting cellularity; and volume-weighted mean nuclear volumes (vV) for estimating nuclear size and pleomorphism. RESULTS: Analysis of survival data yielded no statistically significant differences between astrocytomas and oligoastroacytomas (Lee-Desu test, alpha = 5%). Furthermore, only two prognostically different grades could be established, "low grade" and "high grade" gliomas, with the first representing SAMS grades 2 and 3 and the latter SAMS grade 4 (alpha = .1%). The same applied to HOM grades (alpha = .1%). Cox regression analysis of survival data demonstrated that histologic grading diagnoses and NAP tallied best with patients' outcome.

Loss of alkaline phosphatase activity in meningiomas: a rapid histochemical technique indicating progression-associated deletion of a putative tumor suppressor gene on the distal part of the short arm of chromosome 1.

Apart from defined histomorphologic features, increased Ki-67 indices and various numeric and structural chromosome aberrations, meningiomas of the intermediate (WHO grade II, atypical meningioma) and anaplastic type (WHO grade III) are cytogenetically distinguished from common-type meningiomas (WHO grade I) by frequent loss of the distal part of the short arm of one chromosome 1 (1p-), which formerly proved to be an independent predictor of shorter recurrence-free intervals. Histochemically, loss of alkaline phosphatase activity (ALPL, liver/bone/kidney type, EC 3.1.3.1) was another frequent, specific finding in meningiomas with signs of dedifferentiation. In a prospective study including 66 meningiomas, all common-type meningiomas except one case (18/19) were reactive for ALPL, whereas 75% (30/39) of intermediate type and all anaplastic meningiomas (8/8) showed loss of enzyme activity in large areas of the tumor. Exclusively, the ALPL negative phenotype was associated with 1p loss (15/19). Our data suggest that ALPL, which is coded as a single copy gene on chromosome 1p36.1-p34, is a useful marker enzyme for the loss of a putative regulatory (tumor suppressor) gene on chromosome 1p, or that ALPL itself represents a new tumor suppressor gene homozygously inactivated in meningiomas.

[Meningioma. Classification and grading]. / Meningeome. Klassifikation und Grading.

Meningiomas account for the most frequent primary intracranial neoplasms in adults. In 1993, the so-called atypical meningioma has additionally been introduced in the revised edition of the WHO Classification of Tumors of the Central Nervous System and should characterize meningiomas with an increased propensity to recur. Since the given qualitative histological criteria apply both to the "atypical" and anaplastic meningioma, mere histological grading appears somewhat critical. Therefore, additional parameters were tested for their contribution to meningioma grading: First of all, we succeeded in defining 3 meningioma "grades" by calculating corresponding 95% confidence intervals for the morphometrically assessed Ki-67 indices of 160 meningiomas in total, the validity of which was proved by comparison with the "recurrence"-free intervals. Histologically, atypical meningiomas were distinguished by a "syncytial", poorly structured growth pattern and macronucleoli. Only occasionally, nuclear pleomorphism, necroses and mitotic figures were found. Cytogenetics revealed, in 50% of the "atypical" and anaplastic meningiomas, partial loss of the short arm of one chromosome 1 (1p-). Histochemically, we could demonstrate, that the tissue non-specific type of alkaline phosphatase (ALPL), which is coded on chromosome 1p, is a convenient recurrence- and progression-associated marker enzyme for meningiomas with 1p-loss (loss of enzyme activity in 30/39 of intermediate and 8/8 anaplastic meningiomas). We favor to address the WHO "atypical" meningioma as meningioma of the intermediate type, since the attribute "atypical" in the context of histological diagnoses is highly susceptible to misinterpretations.

Characterization of intermediate type (WHO "atypical") meningiomas.

The intermediate type meningioma (formerly "meningioma variant with signs of increased proliferation activity"; WHO "atypical" meningioma) represents a meningioma group the mean Ki-67 index and the recurrence rate of which lie between those of the ordinary and the anaplastic type [Kolles et al. 1995]. In the study cited (n = 160) the percentage of recurrences was 9% in the common, 29% in the intermediate, and 50% in the anaplastic type. The present study focuses on 49 subsequently diagnosed meningiomas of the intermediate type. Apart from certain histopathological features, the most important independent factors associated with recurrence were Ki-67 indices covering the 95% confidence interval between 3.7% and 4.9%. At the light-microscopic level, however, meningiomas in general, and especially those supposed to belong to the intermediate type, are highly variable in tissue architecture and do, in contrast to the anaplastic type, not display frank histological features of anaplasia. Morphologically, the growth pattern of solid ("syncytial") sheets, micronecroses, and large distinct nucleoli are suspicious. Cytogenetically, independent of the loss of one chromosome 22, it has been shown that terminal loss of the short arm of one chromosome 1 (1p-) or complete loss of this chromosome were useful additional indicators of meningioma progression.

Data-driven approaches to decision making in automated tumor grading. An example of astrocytoma grading.

OBJECTIVE: To compare four data-driven approaches to automated tumor grading based on morphometric data. Apart from the statistical procedure of linear discriminant analysis, three other approaches from the field of neural computing were evaluated. STUDY DESIGN: The numerical basis of this study was computed tomography-guided, stereotactically obtained astrocytoma biopsies from 86 patients colored with a combination of Feulgen and immunhistochemical Ki-67 (MIB1) staining. In these biopsies the cell nuclei in four consecutive fields of vision were evaluated morphometrically and the following parameters determined: relative nuclei area, secant lengths of the minimal spanning trees and relative volume-weighted mean nuclear volumes of the proliferating nuclei. RESULTS: Based on the analysis of these morphometric features, the multivariate-generated HOM grading system provides the highest correct grading rates (> 90%), whereas the two widely employed qualitative histologic grading systems for astrocytomas yield correct grading rates of about 60%. For automated tumor grading all approaches yield similar grading results; however, back-propagation networks provide reliable results only following an extensive training phase, which requires the use of a supercomputer. All other neurocomputing models can be run on simple UNIX workstations (AT&T, U.S.A). CONCLUSION: In contrast to discriminant analysis, backpropagation and Kohonen networks, the newly developed neural network architecture model of self-editing nearest neighbor nets (SEN3) provides incremental learning; i.e., the training phase does not need to be restarted each time when there is further information to learn. Trained SEN3 networks can be considered ready-to-use knowledge bases and are appropriate to integrating further morphometric data in a dynamic process that enhances the diagnostic power of such a network.