Search

Background: Primary CNS lymphoma is a highly aggressive and rare type of extranodal non-Hodgkin lymphoma. Although, new therapeutic approaches have led to improved survival, the management of the disease poses a challenge, practice patterns vary across institutions and countries, and remain ill-defined for vulnerable patient subgroups. Material and Methods: Using information from the Austrian Brain Tumor Registry we followed a population-based cohort of 189 patients newly diagnosed from 2005 to 2010 through various lines of treatment until death or last follow-up (12-31-2016). Prognostic factors and treatment-related data were integrated in a comprehensive survival analysis including conditional survival estimates. Results: We find variable patterns of first-line treatment with increasing use of rituximab and high-dose methotrexate (HDMTX)-based poly-chemotherapy after 2007, paralleled by an increase in median overall survival restricted to patients aged below 70 years. In the entire cohort, 5-year overall survival was 24.4% while 5-year conditional survival increased with every year postdiagnosis. Conclusion: In conclusion, we show that the use of poly-chemotherapy and immunotherapy has disseminated to community practice to a fair extent and survival has increased over time at least in younger patients. Annually increasing conditional survival rates provide clinicians with an adequate and encouraging prognostic measure.

Stroke risk is increased in cancer patients and cancer activity has been claimed to play a role in the development of ischaemic stroke (IS). We wanted to further test these assumptions and to explore the impact of such relation on short-term prognosis. We identified all IS patients that were admitted to the neurological department of our primary and tertiary care university hospital between 2008 and 2014 (n = 4918) and reviewed their medical records for an additional diagnosis of cancer. Cancer patients were categorized into those with "active cancer" (AC: recurrent malignant tumour, metastases, ongoing chemo-/radiotherapy) and "non-active cancer" (NAC). We compared demographic, clinical and neuroimaging features of both patient groups and assessed their association with in-hospital mortality. 300 IS patients with known cancer were identified (AC: n = 73; NAC: n = 227). IS patients with AC were significantly younger (70.3 ± 10.6 vs. 74.9 ± 9.9 years), had more severe strokes at admission (NIHSS: median 5 vs. 3), more frequently cryptogenic strokes (50.7 vs. 32.5 %) and more often infarcts in multiple vascular territories of the brain (26 vs. 5.2 %) compared to IS patients with NAC. In-hospital mortality was significantly higher in AC patients (21.9 vs. 6.2 %). Multivariate analysis identified AC (odds ratio [OR] 3.70, 95 % confidence interval [CI] 1.50-9.30), NIHSS at admission (OR 1.10, CI 1.10-1.20) and C-reactive protein level (OR 1.01, CI 1.00-1.02) as factors significantly and independently associated with in-hospital death. Our findings support a direct role of AC in the pathogenesis and prognosis of acute IS. This needs to be considered in the management and counselling of such patients.

BACKGROUND: Tumor Treating Fields (TTFields) are an anti-mitotic, electric-physical treatment modality. An interim analysis of the phase 3 trial comparing TTFields with maintenance temozolomide (TTFields/TMZ) showed superior progression free and overall survival compared to temozolomide alone (TMZ alone) in patients with newly diagnosed GBM. METHODS: After completion of radiotherapy with concomitant temozolomide, patients were randomized (2:1) to TTFields/TMZ or TMZ alone. The main trial endpoints were progression-free survival (PFS) and overall survival (OS). Here we report the quality of life (EORTC QLQ C-30 / BN20), Karnofsky performance scores (KPS) and minimental status exam (MMSE) results in the interim analysis of the first 315 patients randomized, with a median follow-up of 38 months (range 18-60). RESULTS (intent-to-treat): 210 patients were randomized to TTFields/TMZ and 105 patients to TMZ alone. Patient characteristics were balanced. Median PFS was 7.1 and 4.0 months [Hazard ratio (HR) 0.62, p = 0.001], respectively and OS from randomization was 19.6 and 16.6 months (HR 0.74, p = 0.034), respectively, both favoring TTFields/TMZ. Global health status improved in patients treated with TTFields/TMZ (change from baseline to 3 months [CFB3] = +24% and change from baseline to 6 months [CFB6] = +13%), whereas a decrease was seen in patients treated with TMZ alone (CFB3 = -7% and CFB6 = - 17%). A full analysis of all domains of the QLQ C-30/BN-20 will be presented. No differences in KPS or MMSE was seen between treatment groups over time. CONCLUSIONS: Maintenance TTFields/TMZ provides a clinically and statistically significant improvement in progression-free and overall survival in newly diagnosed GBM. Quality of life was not adversely affected by the continuous use of TTFields and may be improved in some domains of the EORTC QLQ C-30 and BN20. Cognitive and functional capabilities were not impeded by the addition of TTFields to TMZ therapy.

Background: Unlike malignant primary central nervous system (CNS) tumours outcome data on non-malignant CNS tumours are scarce. For patients diagnosed from 1996 to 2002 5-year relative survival of only 85.0% has been reported. We investigated this rate in a contemporary patient cohort to update information on survival. Methods: We followed a cohort of 3983 cases within the Austrian Brain Tumour Registry. All patients were newly diagnosed from 2005 to 2010 with a histologically confirmed non-malignant CNS tumour. Vital status, cause of death, and population life tables were obtained by 31 December 2011 to calculate relative survival. Results: Overall 5-year relative survival was 96.1% (95% CI 95.1–97.1%), being significantly lower in tumours of borderline (90.2%, 87.2–92.7%) than benign behaviour (97.4%, 96.3–98.3%). Benign tumour survival ranged from 86.8 for neurofibroma to 99.7% for Schwannoma; for borderline tumours survival rates varied from 83.2 for haemangiopericytoma to 98.4% for myxopapillary ependymoma. Cause of death was directly attributed to the CNS tumour in 39.6%, followed by other cancer (20.4%) and cardiovascular disease (15.8%). Conclusion: The overall excess mortality in patients with non-malignant CNS tumours is 5.5%, indicating a significant improvement in survival over the last decade. Still, the remaining adverse impact on survival underpins the importance of systematic registration of these tumours.

Purpose A randomized, phase III, placebo-controlled, partially blinded clinical trial (REGAL [Recentin in Glioblastoma Alone and With Lomustine]) was conducted to determine the efficacy of cediranib, an oral pan–vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, either as monotherapy or in combination with lomustine versus lomustine in patients with recurrent glioblastoma. Patients and Methods Patients (N = 325) with recurrent glioblastoma who previously received radiation and temozolomide were randomly assigned 2:2:1 to receive (1) cediranib (30 mg) monotherapy; (2) cediranib (20 mg) plus lomustine (110 mg/m2); (3) lomustine (110 mg/m2) plus a placebo. The primary end point was progression-free survival based on blinded, independent radiographic assessment of postcontrast T1-weighted and noncontrast T2-weighted magnetic resonance imaging (MRI) brain scans. Results The primary end point of progression-free survival (PFS) was not significantly different for either cediranib alone (hazard ratio [HR] = 1.05; 95% CI, 0.74 to 1.50; two-sided P = .90) or cediranib in combination with lomustine (HR = 0.76; 95% CI, 0.53 to 1.08; two-sided P = .16) versus lomustine based on independent or local review of postcontrast T1-weighted MRI. Conclusion This study did not meet its primary end point of PFS prolongation with cediranib either as monotherapy or in combination with lomustine versus lomustine in patients with recurrent glioblastoma, although cediranib showed evidence of clinical activity on some secondary end points including time to deterioration in neurologic status and corticosteroid-sparing effects.

Background: Online quizzes are simple, cost-effective methods to provide formative assessment, but their effectiveness in enhancing learning and performance in medical education is unclear. Purpose: The purpose of this article is to determine the extent to which online quiz performance and participation enhances students’ performance on summative examinations. Methods: A retrospective case study investigating relationships between formative and summative assessment in terms of use and outcomes. Results: Online quiz scores and the rates of quiz participation were significantly correlated with corresponding performance on summative examinations. However, correlations were not dependent on the specific quiz content, and changes in patterns of quiz use were not reflected in corresponding changes in summative examination performance. Conclusions: The voluntary use of online quizzes, as well as the score attained, provides a useful general indicator of student performance but is unlikely to be sensitive enough ...

This methodological paper on magnetic resonance tomography imaging recalls the assessment criteria on therapy response of Glioblastoma multiforme as defined by David Macdonald in 1990 that have remained State of the Art since their first publication. It defines the terms "pseudoprogression", "radiation induced necrosis" and "pseudoresponse". These phenomena are seen increasingly since the introduction of radiochemotherapy with Temozolomide as treatment standard in glioblastoma and since the use of antiangiogenetic therapy in malignant gliomas. Therefore, the assessment criteria have been recently updated with the newly proposed "RANO criteria (Response assessment in Neuro-Oncology)". Furthermore, the potential of additional information to conventional MR by MR perfusion, MR diffusion and MR spectroscopy is briefly discussed.

The pronounced susceptibility effect of macrovessels in MR bolus-tracking studies induces spots of artificially high blood flow and volume in perfusion parameter images. These high-intensity regions impede the detection of perfusion changes and lead to elevated perfusion parameters in adjacent tissues. The purpose of this work was to explore postprocessing methods to reduce the influence of macrovessel signal in dynamic MRI. After data reduction was performed with the use of a principal component analysis (PCA), an independent component analysis (ICA) was applied to separate signal components of different compartments. Based on this decomposition, the dynamic time series were reconstructed with minimized contributions of macrovessel signal and noise. The influence of the temporal resolution and signal-to-noise ratio (SNR) of the source data were investigated by means of a simulation study. A region-of-interest (ROI)-based analysis of corrected and uncorrected in vivo data demonstrated that the influence of arteries and veins was reduced at least by 50%, while gray matter (GM) and white matter (WM) tissues were nearly unaffected by the correction process. Hemodynamic parameter images of the cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) were calculated from corrected and uncorrected scans. The corrected parameter images showed a clearly reduced macrovessel signal and an improved perceptibility of microvascular perfusion changes compared to the uncorrected ones.

BACKGROUND: The use of chemotherapy in patients with malignant gliomas has remained a controversial issue even after the publication of favorable study data and a meta-analysis. The present study was initiated to support the use of chemotherapy in patients with relapsed high-grade gliomas (HGG). PATIENTS AND METHODS: Six Austrian centers recruited 43 patients with histologically confirmed HGG at first recurrence. Twelve chemotherapy-naive patients received oral temozolomide at a dose of 200 mg/m2 once a day for five consecutive days and 26 patients a dose of 150 mg/m2 also for five days after various first-line chemotherapies. TMZ treatment was repeated every four weeks for a total of six cycles. RESULTS: Twenty-one patients (52.5 %) received at least six cycles of therapy. Two patients experienced complete remission and eight patients a partial response. Twenty patients survived at one year after enrolment in the study; eight patients survived beyond three years of follow-up. Hematological toxicities consisted of three thrombocytopenias G4 and 35 lymphocytopenias G3 and G4; these did not cause interstitial pneumonia or require inpatient treatment. Non-hematological toxicities were rare and without clinical relevance. Patients' quality of life was maintained during treatment. CONCLUSION: The study data confirm the feasibility and efficacy of chemotherapy with temozolomide in patients with relapsed/progressive HGG.

Zusammenfassung: Die Positronenemissionstomographie mit F-18-Fluorodeoxy-Glukose (F-18-FDG-PET) stellt eine ideale Moglichkeit dar, den Stoffwechselumsatz des Gehirns in seiner regionalen Verteilung abzubilden, da Glukose der wichtigste Energietrager fur die Nervenzellen ist. In physiologischer Weise wird das Stoffwechselmuster durch den jeweiligen zerebralen Aktivierungszustand beeinflust, welcher durch verschiedenste Stimuli gezielt verandert werden kann um daraus Schlusse auf die Organisationsstruktur des Gehirns zu ziehen. Krankhafte Veranderungen wiederum haben zumeist eine Abnahme des Stoffwechselumsatzes aufgrund von Inaktivitat oder Zugrundegehen von Nervenzellen zur Folge. Sie konnen aber auch von einer Steigerung des Glukoseumsatzes begleitet sein, wie dies zum Beispiel bei aktiven epileptischen Herden oder malignen Tumoren der Fall ist. Die F-18-Fluorodeoxy-Glukose-Positronenemissionstomographie hat sich deshalb als wertvolle funktionelle Untersuchungsmethode etabliert, welche insbesondere zur diagnostischen Klarung bei negativen oder unklaren morphologischen Befunden beitragen kann. Haufige Indikationsbereiche in der Neurologie stellen derzeit die Abklarung dementieller Zustandsbilder, die prachirurgische Epilepsiediagnostik sowie die Neuroonkologie dar. F-18-Fluorodeoxyglucose-Positron Emission Tomography in Neurology Summary: Positron emission tomography using F-18-fluorodeoxyglucose (F-18-FDG-PET) is an ideal tool for imaging regional cerebral metabolism as glucose is the most important source of energy for neurons. Under physiologic conditions the pattern of metabolism reflects the state of cerebral activation which can be modulated by various stimuli to investigate cerebral organization. Pathologic conditions usually cause a drop in metabolism because of neuronal inactivity or loss. They can, however, also be associated with an increased rate of glucose metabolism such as in case of active epileptic foci or malignant tumors. As a consequence F-18-FDG-PET has become a valuable functional imaging modality especially for the diagnostic clarification of non-contributory or negative morphologic imaging results. Dementia, pre-surgical evaluation of epilepsy and neurooncology are currently frequent indications for referral to F-18-FDG-PET in neurology.

In glioma therapy differentiating tumor progression from treatment related changes such as pseudoprogression and radionecrosis is crucial. However, there are no simple reliable tools to distinguish between such modalities. In unclear cases on the conventional MRI-imaging PET with amino acid analogues has been proposed to be a promising adjunctive method. 18F-DOPA PET has the advantage of high tracer uptake in the brain tissue and low in non-neoplastic tissue.

Although glioblastoma multiforme is more common in patients older than 65 years, the elderly population is often excluded from clinical studies. Decision making in this subgroup can be challenging due to the lack of evidence for different neurosurgical and adjuvant treatment strategies.In this retrospective study, we evaluated clinical, treatment and survival data of 124 consecutive patients over 65 years of age with supratentorial glioblastoma multiforme.Median OS was 6.0 months (std. error 0.783, 95% CI 4.456-7.535). Mean OS was 9.7 months (std. error 0.830, 95% CI 8.073-11.327). In univariate regression analysis, low KPS was of negative prognostic value (p0.006 for KPS ≤ 80), while greater advanced age did not have any impact on survival (p = 0.591 for differences between groups). Gross total resection and subtotal resection led to significantly improved overall survival (median 15.0 and 11.0 months; p0.02) compared to partial resection or biopsy (both 4.0 months), but complications were more common in subtotal and partial resections. The last observation did not reach statistical significance (p = 0.06). Combinations of irradiation and Temozolomide chemotherapy proved to be more effective than other adjuvant therapies. Extent of resection (gross total resection vs. all others) and form of adjuvant treatment were the only factors of independent prognostic value in multivariate analysis (p = 0.031 and p0.001, respectively).It appears that more aggressive treatment regimens can lead to longer overall survival in elderly glioblastoma multiforme patients. Gross total resection should be offered whenever safely possible; otherwise, biopsy may be preferred. Non-surgical treatment should consist of postoperative radiotherapy and concomitant and/or adjuvant chemotherapy. Possibly higher rates of hematological side effects in concomitant chemotherapy need to be further investigated.

Development of problem-solving skills is vital to professional education as is factual recall. Student mastery must be measured to document student achievement required for completion of educational requirements and professional certification. These measurements also help determine if the educational process is meeting its goal of helping students develop critical cognitive skills fortherapeutic problem solving. Testing student growth in the ability to solve problems is less understood. Stressing integration of information across disciplines to derive answers is also important. Test items should resemble the real-world task that students are expected to master. That is really the essence of content validity, which means faculty should be biased toward presenting information that way. This article is based on a symposium presented at the annual meeting of the American College of Clinical Pharmacology in September 1996. Symposium goals were to define purposes and uses of student evaluations by type and format, including application of techniques that improve evaluation, precision, and validity. Technical applications of computer-based learningand evaluation of problem-solving skills are described. Actual experience with evaluation of problem solving in the curriculum is discussed. The process by which a medical school developed and implemented an evaluation system for a new problem-based curriculum is presented, followed by a critique of the successes and problems encountered duringthe first year of implementation. Criteria that a well-constructed evaluation program must meet are explored. The approach and philosophy of national standardized testing centers are explained.

Glioblastoma is the most common malignant brain tumor in adults. Since 2005, state-of-the-art treatment consists of maximal safe resection followed by combined radio- and TMZ chemotherapy. A number of population-based outcome and pattern of care studies have documented its successful translation to community practice as well as the associated survival benefit in the general population. However, whether this holds true for Austria has not yet been systematically addressed.Aims:To assess real-world patterns of care for glioblastoma in the Austrian population.Patients & methods:A close cooperation between the Austrian Brain Tumor Registry and the Society of Austrian Neuro-Oncology is the platform for the conduct of this study. Consensus parameters are abstracted from medical records across all Austrian neurooncology units. All data are entered and stored in a dedicated IT database referred to as ABTR-SANOnet.Results:So far, all patients with newly diagnosed glioblastomas from 01-12/2014 have been recorded (n=310, median age=63 ys) with a last follow-up at 12/2015. Median time from onset of symptoms to diagnostic scan was 7 days (range 0–163 days) and another 8 days to surgical intervention. Total or subtotal resections were achieved in 68.7%. The majority of patients (84.5%) started on a combined treatment schedule with a considerable drop-out rate of 23.4% due to treatment toxicity or early tumor progression. Among elderly patients monotherapies stratified by MGMT promoter methylation status were more prevalent.Conclusion:Herein, we report on the first successful real-world pattern of care study on glioblastoma in Austria. Initial data are in line with internationally reported findings and confirm that the current standard of care has been widely adopted across Austrian neurooncology units. Future multivariate survival analyses will provide important insights in prognostic and therapy-associated factors, which act in Austrian patients.

Complementary morphological information is a prerequisite for the detailed analysis of cerebral SPET studies. We therefore developed a technique which allows the alignment of SPET and magnetic resonance scans by imaging identical slices using external landmarks on an individually fitted mask and subsequent two-dimensional image processing for in-plane matching. Regional analysis of tracer activities can be performed directly on the superimposed SPET and MR outline images or by tracing a region of interest on the original MR scan with a parallel display on the matched SPET image, and vice versa. Tests assessing correct in-plane alignment using MRI, inter- and intra-variability of the matching procedure, and its comparability with an objectively determined best-matching position, confirmed the feasibility, accuracy and usefulness of this procedure.

We studied six patients suffering from pure, unilateral brain stem infarction to explore the association of remote cerebral and cerebellar blood flow changes with damage at different sites of this region of the brain. We used single-photon emission computed tomography and [123I]iodoamphetamine to measure regional differences in tracer uptake. Qualitative image analysis and calculated asymmetry indexes were correlated to the location of the infarcted area on magnetic resonance imaging and to the patients' clinical findings. Significant perfusion asymmetries were noted in the two patients with infarction in the upper pons but not in those with lesions below this level. They comprised a contralateral cerebellar and ipsilateral supratentorial hypoactivity that was most marked in the frontoparietal cortex. There was no clear relation between the patterns of cerebral or cerebellar tracer uptake and specific neurological findings. Remote perfusion changes after pure brain stem infarction may be seen both infratentorially and supratentorially and depend on the lesion site rather than on the neurological deficit. In this context, our study confirmed damage to the corticopontocerebellar pathways as the key event in the genesis of a crossed cerebellar diaschisis. The exact mechanisms causing ipsilateral cerebral hemispheric diaschisis await further clarification.

SYNOPSIS Studies on the prevalence of MRI signal abnormalities in the brains of migraineurs have yielded controversial results. In order to provide further data on this issue we reviewed the MRI scans of 38 migraine patients without current neurologic symptoms (mean age 35.8 ± 11.9 years). In addition, we compared the findings in those 24 migraineurs under 50 years without major cerebrovascular risk factors (mean age 30.1 ± 9.0 years) to that in 14 headache and risk factor free volunteers (mean age 37.8 ± 5.3 years). Overall, focal areas of hyperintense signal were seen in 15 (39%) patients. They were present on both proton density and T2-weighted spin-echo sequences. Lesion prevalence varied according to the type of headache (18% in migraine without aura, 53% in migraine with typical aura, 38% in basilar migraine). The subset of migraine patients under 50 years exhibited MRI signal abnormalities more than twice as often as controls (33% vs. 14%). Punctate white matter hyperintensities were the predominant finding and were seen in 10 of 15 individuals with MRI lesions. More striking signal abnormalities consisted of symmetrical areas of hyperintensity lateral to the posterior horns in two 24 year old patients and of extensive white matter damage with lacunar infarcts in a 59 year old woman. Our findings confirm a higher prevalence of MRI lesions in a mixed group of migraineurs than in headache free individuals. Signal abnormalities are most often non-specific, however their occurrence relates to the type of migraine.

The contribution of MRI is reported in four adult patients with tuberculous meningoencephalitis (TbM) and with autopsy correlation in one. Contrast-enhanced T1-weighted MRI revealed the characteristic basal meningeal inflammation of TbM and its focal spreading into adjacent brain. Mixed and T2-weighted pulse sequences delineated a plethora of parenchymal abnormalities. Their relation to TbM was established by a close matching of the patient's neurological findings, contrast enhancement or a change in lesion size. The latter accurately reflected the clinical course in all patients. It remained difficult, however, to distinguish between ischaemic and inflammatory changes, which in some locations were intermixed even histologically. From our experience and that of other groups, MRI provides more diagnostic information in TbM than CT. Moreover, MRI promises to be a useful tool for monitoring treatment response.

Adverse hemorheologic effects induced by erythropoietin (EPO) treatment of renal anemia may pose a cerebrovascular risk. We therefore investigated the changes in cerebral perfusion, cerebral blood flow velocity (BFV) and neuropsychologic performance in 11 patients (mean age 37 years) receiving EPO. In response to EPO there was a significant (p less than 0.01) increase in hematocrit (35%), hemoglobin (43%) and whole-blood viscosity (50% at high and 90% at low shear rate). The initially increased blood flow velocity dropped significantly (p less than 0.05) and returned toward normal values in the middle cerebral arteries and the basilar artery (22 and 19% decrease, respectively). Global cerebral blood flow (CBF) decreased by 10% (not significant). The score of the Wechsler Adult Intelligence Scale digit symbol test improved significantly (p less than 0.01) after EPO treatment. None of the patients developed cerebrovascular symptoms or side effects. We conclude that the hematologic and rheologic changes following EPO treatment cause CBF and BFV to return toward normal and improve neuropsychologic performance in patients with end-stage renal disease.

With the increasing use of computers in the classroom and the advancement of information technology, a requirement to investigate and evaluate different strategies for the presentation of verbal information in interactive and dynamic visualizations has risen to a high level of importance. There is a need for research efforts that apply cognitive load theory (CLT), cognitive learning strategies, and established principles of multimedia design to conduct empirical research that will add to our knowledge of designing and developing dynamic visualizations for teaching and learning anatomy. The impact of improved teaching and learning of anatomical sciences and the development of a set of guiding principles to facilitate the design and development of effective dynamic visualizations represent a significant achievement for medical education with wide application. This theoretical paper presents the foundations of CLT, cognitive learning strategies, and principles of multimedia design to guide the needed research on dynamic visualizations.

Epilepsy surgery is a successful therapeutic approach in patients with medically intractable epilepsy. The presurgical evaluation aims to detect the epileptogenic brain area by use of different diagnostic techniques. In this review article the current diagnostic procedures applied for this purpose are described. The diagnostic armamentarium can be divided conceptually into three different groups: assessment of function/dysfunction, structural/morphologic imaging methods and functional neuroimaging techniques. Properties, diagnostic power and limits of all diagnostic tools used in the diagnostic evaluation are discussed. In addition, future perspectives and the diagnostic value of new technologies are mentioned. Some are increasingly gaining acceptance in the routine preoperative diagnostic procedure like MR volumetry or MR spectroscopy of the hippocampus in patients with temporal lobe epilepsy. Some, on the other hand, like MEG and 11C-flumazenil PET, still remain experimental diagnostic tools as they are technically demanding and cost intensive. Besides the refinement of established techniques, co-registration of different modalities like spike-triggered functional MRI will play an important role in the non-invasive detection of the epileptic seizure focus and may change the regimen of the preoperative diagnostic work up of epilepsy patients in the future.

1. The authors examined the regional cerebral distribution of [Tc-99m] HMPAO using single photon emission computed tomography (SPECT) in patients with major depression and in healthy controls. 2. 19 patients and 16 healthy controls had SPECT images of the brain acquired with 740 MBq (20 mCl) of [Tc-99m] HMPAO on a triple-headed camera equipped with fan beam collimators. 3. Mean counts per pixel were measured in 13 regions of each hemisphere and compared to the mean activity in the whole brain, the ipsilateral hemisphere, and cerebellum. A "laterality score" was calculated for each structure by subtracting the mean counts per pixel in a region of the right hemisphere from the mean counts in the homotopic region of the left hemisphere and normalizing the difference by the average in both regions. The degree of hemispheric asymmetry was calculated from the absolute values of the laterality scores. 4. The distribution of HMPAO was more variable in patients than in controls; while the mean activity ratios were not significantly different in any region. Asymmetries between homotopic regions of the limbic system were more pronounced in patients than in controls. However, there were no consistent left-to-right asymmetries in either group. 5. The present data indicate that regional cerebral distribution of HMPAO may not be discretely abnormal in depression, but demonstrates heightened variability in depressives (vs. control subjects).

We related the histopathologic changes associated with incidental white matter signal hyperintensities on MRIs from 11 elderly patients (age range, 52 to 82 years) to a descriptive classification for such abnormalities. Punctate, early confluent, and confluent white matter hyperintensities corresponded to increasing severity of ischemic tissue damage, ranging from mild perivascular alterations to large areas with variable loss of fibers, multiple small cavitations, and marked arteriolosclerosis. Microcystic infarcts and patchy rarefaction of myelin were also characteristic for irregular periventricular high signal intensity. Hyperintense periventricular caps and a smooth halo, however, were of nonischemic origin and constituted areas of demyelination associated with subependymal gliosis and discontinuity of the ependymal lining. Based on these findings, our classification appears to reflect both the different etiologies and severities of incidental MRI signal abnormalities, if it is modified to treat irregular periventricular and confluent deep white matter hyperintensities together.

Numerous study commissions have contended that departmental territoriality and lack of coordinated planning are stagnating contemporary medical education. As a cure, these commissions have recommended the creation of centralized academic management units empowered to oversee revitalization of the curriculum through a series of reforms, including better definition of graduation competencies, community-based training, interdisciplinary courses, problem-based learning, and modernization of evaluation strategies. To determine the extent to which these recommendations were being adopted, in 1990 the authors sent a questionnaire on curriculum committee functions, current innovation efforts, and future priorities to academic administrators and members of medical school curriculum committees at 143 North American medical schools. Responses were received from administrators (primarily associate deans for academic affairs) at 118 schools and committee members (primarily faculty) at 111 schools. Recommendations for enhancing curriculum committee effectiveness were also elicited. The authors conclude that centralization of curricular management has occurred at very few institutions, and that the commonly mentioned reforms are being adopted at a modest pace. The results are analyzed in light of theories of the institutional change process and strategies for introducing educational innovations into established institutions.

Repeated bleeding into CSF spaces may cause superficial siderosis with progressive neurologic impairment. The unique physical properties of MRI provide a basis for the in vivo diagnosis of this entity.

To test the reliability of four previously proposed MRI criteria for the diagnosis of MS, we reviewed 1,500 consecutive brain scans for the presence, number, size, and location of areas of increased signal (AIS) on proton-density and T2-weighted images, unaware of the patients' clinical presentations and ages. This series included 134 subjects with a clinical diagnosis of MS. Relying exclusively on the presence of at least three or four AIS for a positive diagnosis of MS resulted in high sensitivity (90% for three AIS and 87% for four) but inadequate specificity (71% for three AIS and 74% for four) and positive predictive value (23% for three AIS and 25% for four). If one of these lesions was required to border the lateral ventricles, specificity was 92% and positive predictive value was 50% at a sensitivity of 87%. Using the Fazekas criteria (at least three AIS and two of the following features: abutting body of lateral ventricles, infratentorial lesion location, and size > 5 mm) led to a further highly significant improvement of specificity (96%; p = 0.0000) and increase of the positive predictive value (65%) at the expense of a less significant decrease in sensitivity (81%; p < 0.01).

We undertook a study to determine (1) the frequency and prognostic significance of preexisting MRI brain abnormalities in patients undergoing coronary artery bypass grafts (CABG) and (2) whether MRI can detect surgery-related brain damage in 31 neurologically asymptomatic CABG patients (mean age, 61.0 +/- 6.6 years). MRIs were performed within 7 days before and 8 to 17 days after surgery. When we compared the preoperative images with those of 31 age- and risk factor-matched neurologically asymptomatic controls free of cardiac disease (mean age, 60.3 +/- 6.1 years), higher rates of thromboembolic infarcts (16% versus 0%), lacunes (58.1% versus 32.3%), and brainstem lesions (22.6% versus 3.8%) were noted. Subjective rating demonstrated significantly larger ventricles in patients than in controls (p = 0.002). CABG candidates also had significantly increased ventricular-to-intracranial cavity ratios (VICR) as determined by semiquantitative volumetric measurements (6.9 +/- 2.5% versus 4.9 +/- 1.6%; p = 0.0004). Eleven patients had postsurgical complications, with eight having symptoms consistent with diffuse encephalopathy. The only MRI finding that separated encephalopathic from complication-free patients was ventricular size (VICR 9.0 +/- 2.5% versus 4.9 +/- 1.6%; p = 0.006). This difference remained statistically significant after adjustment for the effects of age (p = 0.04). Postoperative MRI consistently failed to demonstrate surgery-related brain damage responsible for the encephalopathy.

Mixed population studies suggest a relationship between deep and subcortical white matter hyperintensities on magnetic resonance imaging and cerebrovascular disease. To further clarify this issue we compared the prevalence and extent of such signal abnormalities between a group of 133 consecutive stroke patients (mean age, 54.7 +/- 16.7 years) and 101 normal volunteers (mean age, 54.7 +/- 13.1 years). Diabetes and cardiac disease were significantly more common in patients than in normal subjects. Prevalence rates of clinically silent lesions were 44% and 47.5%, respectively. Beginning confluent and confluent foci were seen in 19.5% of patients, but in only 7.5% of normal subjects. Significant univariate correlations were found for the presence and extent of lesions with age, diabetes, cardiac disease, severity of extracranial carotid arteriosclerosis, and arterial hypertension, but not with the diagnosis of stroke or the type of brain infarction. Multivariate regression analysis established age and diabetes mellitus as the only independent predictors of white matter damage. We conclude that more extensive white matter abnormalities in stroke patients stem from their higher rate of cerebrovascular risk factors but are unrelated to the occurrence of ischemic attacks per se.

PurposeNovoTTF-100A is a portable device delivering low-intensity, intermediate frequency electric fields via non-invasive, transducer arrays. Tumour Treatment Fields (TTF), a completely new therapeutic modality in cancer treatment, physically interfere with cell division.MethodsPhase III trial of chemotherapy-free treatment of NovoTTF (20–24h/day) versus active chemotherapy in the treatment of patients with recurrent glioblastoma. Primary end-point was improvement of overall survival.ResultsPatients (median age 54years (range 23–80), Karnofsky performance status 80% (range 50–100) were randomised to TTF alone (n=120) or active chemotherapy control (n=117). Number of prior treatments was two (range 1–6). Median survival was 6.6 versus 6.0months (hazard ratio 0.86 [95% CI 0.66–1.12]; p=0.27), 1-year survival rate was 20% and 20%, progression-free survival rate at 6months was 21.4% and 15.1% (p=0.13), respectively in TTF and active control patients. Responses were more common in the TTF arm (14% versus 9.6%, p=0.19). The TTF-related adverse events were mild (14%) to moderate (2%) skin rash beneath the transducer arrays. Severe adverse events occurred in 6% and 16% (p=0.022) of patients treated with TTF and chemotherapy, respectively. Quality of life analyses favoured TTF therapy in most domains.ConclusionsThis is the first controlled trial evaluating an entirely novel cancer treatment modality delivering electric fields rather than chemotherapy. No improvement in overall survival was demonstrated, however efficacy and activity with this chemotherapy-free treatment device appears comparable to chemotherapy regimens that are commonly used for recurrent glioblastoma. Toxicity and quality of life clearly favoured TTF.

Two 46,XY phenotypic female siblings, aged 1 1/2 and 8 1/2 years, have peculiar facies, cardiac, renal, musculoskeletal, and ectodermal anomalies, short stature, streak gonads, and mild developmental delay. Previous reported cases of 46,XY gonadal dysgenesis have not had major associated malformations. These children present a new constellation of anomalies unlike those seen in other types of gonadal dysgenesis and represent a new familial syndrome of 46,XY gonadal dysgenesis.

Recent studies of experimental testicular torsion in rats, rabbits, and guinea pigs have demonstrated conflicting evidence regarding contralateral testicular damage. Those studies in which cellular damage has been found are postulated to result from an immunological mechanism whereby the blood-testis barrier is disrupted with subsequent autoantibody formation. In this study, the histologic and immunologic effects of testicular torsion on the contralateral testicle were investigated in prepubertal Chinese hamsters. Four study groups were established; (1) Left orchiectomy only, (2) sham surgery (scrotal incision), (3) 720 degrees left testicular torsion with left orchiectomy 24 hours later, (4) 720 degrees torsion of left testicle with detorsion after 24 hours. The initial procedure was performed at 1 month of age with subsequent biopsies of the contralateral testicle at 1 week, 1 month, and 6 months after the initial procedure. Testicular tissue was examined for immunofluorescent activity using fluorescent labeled goat anti-hamster IgG. Positive controls were established by rabbit immunization (rabbit anti-hamster immunoglobulin) which was subsequently combined with fluorescent labeled goat antirabbit IgG. There was no appreciable difference in immunologic activity between control and experimental animals. Representative sections were examined histologically and no tubular damage was demonstrated and active spermatogenesis was noted at 6 months in all groups. We believe that our results support the premise that testicular torsion in the prepubertal period has no effect on the contralateral testicle.

981 THE EFFECT OF UNILATERAL TESTICULAR TORSION ON THE CONTRALATERAL TESTICLE IN PREPUBERTAL CHINESE HAMSTERS