Relative survival of patients with non-malignant central nervous system tumours: a descriptive study by the Austrian Brain Tumour Registry.

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.

Interdisciplinary treatment of glioblastoma: analysis of prognostic factors and treatment results in unselected patients.

Aim of the present study was to investigate survival rates of unselected patients with glioblastoma after multimodal treatment and estimation of prognostic factors. Data of 189 patients (118 men; 71 women; median age: 59 years) with histologically confirmed glioblastoma treated from 1999 to 2009 were analyzed retrospectively. Complete tumor resection was performed in 99 patients (52%), subtotal excision in 65 patients (34%), and stereotactic biopsy in 25 patients (13%). In 135 patients (71%), residual tumors were detectable in post-surgical imaging. All patients underwent three-dimensional conformal radiotherapy of the tumor region in shrinking-field technique to a total dose of 60 Gy. Beginning in 2002, 124 patients (66%) received concomitant temozolomide (TMZ) treatment, 76 patients among them were additionally treated with adjuvant TMZ. After disease progression, 74 patients underwent salvage therapy (salvage chemotherapy, n=61; local therapy, n=30). Actuarial 1- and 2- year progression-free survival (PFS) rates were 32% and 7%, overall survival (OS) rates were 54% and 22%, respectively. Without TMZ, 1- and 2- year OS rates were 47% and 11%, with concomitant TMZ 57% and 28%, and with concomitant and adjuvant TMZ 72% and 44%. In multivariate Cox proportional hazards regression models, age (p<0.001), extent of resection (p = 0.001), and TMZ (p < 0.001) were significantly associated with OS. Furthermore, a significant association between salvage therapy and improved survival was observed (p=0.020). RT with concomitant TMZ was well tolerated in the majority of patients and completed as scheduled in 78% of patients. Multimodal treatment including extensive surgical resection, radiotherapy and chemotherapy significantly improves prognosis of patients with glioblastoma and is feasible with acceptable toxicity in routine practice. To achieve optimal results, close coordination among all disciplines is required.

Minimizing macrovessel signal in cerebral perfusion imaging using independent component analysis.

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.

Future aspects of the presurgical evaluation in epilepsy.

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.

[F-18 fluorodeoxyglucose positron emission tomography in neurology]. / F-18-Fluorodeoxy-Glukose-Positronenemissionstomographie in der Neurologie.

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.

Technetium-99m-ECD SPECT fails to show focal hyperemia of acute herpes encephalitis.

This is a case of herpes simplex encephalitis (HSE) examined with 99mTc-ethyl cysteinate dimer (ECD) and 99mTc-hexamethyl propyleneamine oxime (HMPAO) SPECT. Static images obtained with 99mTc-ECD showed a reduced tracer uptake of the temporal lobe but focal hyperactivity using 99mTc-HMPAO. Dynamic images indicated regional increase of cerebral blood perfusion with both tracers. Technetium-99m-ECD had rapid washout from the inflamed tissue, while 99mTc-HMPAO had avid uptake. Hypofixation of 99mTc-ECD leads to failure to detect the characteristic finding of temporal lobe hyperemia in acute HSE.

Language comprehension and regional cerebral defects in frontotemporal degeneration and Alzheimer's disease.

We related profiles of language comprehension difficulty to patterns of reduced cerebral functioning obtained with high-resolution single photon emission computed tomography (SPECT) in patients with neurodegenerative conditions. We found different patterns of reduced relative cerebral perfusion in patients with frontotemporal degeneration (FD) and patients with Alzheimer's disease (AD). Cognitive assessments also showed different patterns of impaired comprehension in patients with FD and patients with AD. Grammatical comprehension difficulty in FD correlated with relative cerebral perfusion in left frontal and anterior temporal brain regions; impaired semantic processing in AD correlated with relative cerebral perfusion in inferior parietal and superior temporal regions of the left hemisphere. These findings are consistent with the hypothesis that a neural network distributed throughout the left hemisphere subserving different aspects of language comprehension, rather than a single brain region, is responsible for understanding language.

Constraints on the cerebral basis for semantic processing from neuroimaging studies of Alzheimer's disease.

OBJECTIVE: Functional activation studies of semantic processing in healthy adults have yielded conflicting results. The purpose was to evaluate the relative role of the brain regions implicated in semantic processing with converging evidence from imaging studies of patients with impaired semantic processing. METHODS: Semantic memory was assessed in patients with Alzheimer's disease using two measures, and these performance patterns were related to profiles of reduced cerebral functioning obtained with high resolution single photon emission computed tomography (SPECT). Patients with frontotemporal degeneration were similarly evaluated as a control group. RESULTS: Reduced relative cerebral perfusion was seen in parietal and posterior temporal brain regions of patients with Alzheimer's disease but not patients with frontotemporal degeneration. Impairments on semantically guided category membership decision tasks were also seen in patients with Alzheimer's disease but not those with frontotemporal degeneration. Performance on the semantic measures correlated with relative cerebral perfusion in inferior parietal and superior temporal regions of the left hemisphere only in Alzheimer's disease. Relative perfusion was significantly lower in these regions in patients with Alzheimer's disease with semantic difficulty compared with patients with Alzheimer's disease with relatively preserved semantic processing. CONCLUSION: These findings provide converging evidence to support the contribution of superior temporal and inferior parietal regions of the left hemisphere to semantic processing.

The relation of cerebral magnetic resonance signal hyperintensities to Alzheimer's disease.

To further elucidate the relation of cerebral magnetic resonance signal hyperintensities to Alzheimer's disease (AD) we performed a case-control comparison between 30 consecutive patients with probable AD (age range 49-76, mean 65 years) and 60 asymptomatic volunteers matched for age, sex, and major cerebrovascular risk factors. We used a 1.5T magnet and determined the extent of morphologic abnormalities both by visual grading and measurement. AD patients showed comparable grades of deep/subcortical white matter hyperintensities (WMH) and a similar extent of the total WMH area as controls (3.3 cm2 +/- 8.8 vs. 2.0 cm2 +/- 4.6). They had significantly more often a "halo' of periventricular hyperintensity (PVH) (p < 0.0005) and an increased mean PVH thickness (3.0 mm +/- 1.9 vs. 1.3 mm +/- 1.2; p < 0.001). This PVH thickness correlated significantly with measures of ventricular enlargement. While univariate logistic regression also suggested a significant association of PVH thickness with a diagnosis of AD this association was lost against atrophy measures in a multivariate analysis. Our results confirm a significantly greater extent of PVH in AD patients than controls even when matched for cerebrovascular risk factors. However, this abnormality was not independently related to the disease but rather appears to be an epiphenomenon of brain atrophy.

Cerebral HMPAO SPECT in patients with major depression and healthy volunteers.

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).

Morphology-oriented analysis of cerebral SPET using matched magnetic resonance images.

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.

Single photon emission computed tomography in Alzheimer's disease and related disorders.

Alzheimer's disease and other dementia syndromes can be characterized by single photon emission computed tomography (SPECT). SPECT can be used to measure cerebral blood flow or neurotransmitter activity in these disorders. SPECT can help distinguish various neurologic disorders and also help elucidate their pathophysiologic processes. This article focuses on the use of SPECT in the study of Alzheimer's disease and related neurologic disorders.

Pathologic correlates of incidental MRI white matter signal hyperintensities.

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.

Brain stem infarction and diaschisis. A SPECT cerebral perfusion study.

BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Assessment of MRI criteria for a diagnosis of MS.

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).

Brain magnetic resonance imaging in coronary artery bypass grafts: a pre- and postoperative assessment.

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.

Bilateral medial medullary infarction: magnetic resonance imaging and correlative histopathologic findings.

Bilateral medial medullary infarction is a rare event which clinically presents with flaccid tetraplegia sparing the face, bilateral disturbance of deep sensation, hypoglossal nerve palsy and respiratory failure. We here report a patient with such symptoms in whom magnetic resonance imaging enabled the detection of signal abnormalities in the lower brainstem as soon as 9 h after onset. Results of a control study 3 weeks later correlated well with the extent of infarction that was seen at autopsy. Early lesion detection in the lower medulla by magnetic resonance imaging and the unfavorable prognosis of patients with ischemic damage at that location may provide the rationale for aggressive therapeutic strategies in such a condition.

Magnetic resonance imaging signal hyperintensities in the deep and subcortical white matter. A comparative study between stroke patients and normal volunteers.

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.

The prevalence of cerebral damage varies with migraine type: a MRI study.

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.