The Prognostic Value of NANO Scale Assessment in IDH-Wild-Type Glioblastoma Patients

Background: IDH-wild-type glioblastoma (GBM) is the most frequent brain-derived malignancy. Despite intense research efforts, it is still associated with a very poor prognosis. Several parameters were identified as prognostic, including general physical performance. In neuro-oncology (NO), special emphasis is put on focal deficits and cognitive (dys-)function. The Neurologic Assessment in Neuro-Oncology (NANO) scale was proposed in order to standardize the assessment of neurological performance in NO. This study evaluated whether NANO scale assessment provides prognostic information in a standardized collective of GBM patients. Methods: The records of all GBM patients treated between 2014 and 2019 at our facility were retrospectively screened. Inclusion criteria were age over 18 years, at least 3 months postoperative follow-up, and preoperative and postoperative cranial magnetic resonance imaging. The NANO scale was assessed pre- and postoperatively as well as at 3 months follow-up. Univariate and multivariate survival analyses were carried to investigate the prognostic value. Results: One hundred and thirty-one patients were included. In univariate analysis, poor postoperative neurological performance (HR 1.13, p = 0.004), poor neurological performance at 3 months postsurgery (HR 1.37, p < 0.001), and neurological deterioration during follow-up (HR 1.38, p < 0.001), all assessed via the NANO scale, were associated with shorter survival. In multivariate analysis including other prognostic factors such as the extent of resection, adjuvant treatment regimen, or age, NANO scale assessment at 3 months postoperative follow-up was independently associated with survival prediction (HR 1.36, p < 0.001). The optimal NANO scale cutoff for patient stratification was 3.5 points. Conclusion: Neurological performance assessment employing the NANO scale might provide prognostic information in patients suffering from GBM

Diffusion-weighted MRI reflects proliferative activity in primary CNS lymphoma

Purpose: To investigate if apparent diffusion coefficient (ADC) values within primary central nervous system lymphoma correlate with cellularity and proliferative activity in corresponding histological samples. Materials and Methods: Echo-planar diffusion-weighted magnetic resonance images obtained from 21 patients with primary central nervous system lymphoma were reviewed retrospectively. Regions of interest were drawn on ADC maps corresponding to the contrast enhancing parts of the tumors. Biopsies from all 21 patients were histologically analyzed. Nuclei count, total nuclei area and average nuclei area were measured. The proliferation index was estimated as Ki-67 positive nuclei divided by total number of nuclei. Correlations of ADC values and histopathologic parameters were determined statistically. Results: Ki-67 staining revealed a statistically significant correlation with ADCmin (r = -0.454, p = 0.038), ADCmean (r = -0.546, p = 0.010) and ADCmax (r = -0.515, p = 0.017). Furthermore, ADCmean correlated in a statistically significant manner with total nucleic area (r = -0.500, p = 0.021). Conclusion: Low ADCmin, ADCmean and ADCmax values reflect a high proliferative activity of primary cental nervous system lymphoma. Low ADCmean values—in concordance with several previously published studies—indicate an increased cellularity within the tumor

Association study of leptin and leptin receptor gene polymorphisms and antipsychotic induced weight gain

Zusammenfassung Die Schizophrenie ist die schwerwiegendste chronisch psychiatrische Störung multifaktorieller Genese mit einem Lebenszeiterkrankungsrisiko von ca. 1%. Sie ist gekennzeichnet durch starke Minderung des beruflichen und sozialen Leistungsvermögens durch grundlegende und charakteristische Störungen von Denken und Wahrnehmung, sowie inadäquatem oder verflachtem Affekt. Die Schizophrenie ist ein heterogenes Krankheitskonzept, dessen Symptome hinsichtlich des prognostischen Aspekts in Positiv- (u.a. Wahn, Halluzinationen, formale Denkstörungen) und Negativsymptome (u.a. Affektverflachung, Antriebsschwäche, Anhedonie) unterschieden werden. Die medikamentöse Therapie der Schizophrenie erfolgt hauptsächlich mittels atypischer Neuroleptika. Diese zeigen viele klinisch relevante metabolische, endokrinologische, hämatologische und kardiovaskuläre Nebenwirkungen. Der Neuroleptika induzierten Gewichtszunahme kommt besonderer Stellenwert zu, da Übergewicht und Adipositas Risikofaktoren für die Entwicklung eines metabolischen Syndroms und der damit verbundenen deutlich erhöhten kardiovaskulär bedingten Morbidität und Mortalität sind. Darüber hinaus kann eine Gewichtszunahme zu sozialer Stigmatisierung und Reduktion der Lebensqualität beitragen, sowie eine verminderte Bereitschaft zur Therapie verursachen. Vorraussetzung für die angestrebte individualisierte Pharmakotherapie der Schizophreniepatienten sind verlässliche Prädiktoren für die Neuroleptika induzierte Gewichtszunahme. Da jedoch die genauen pathophysiologischen Mechanismen der Neuroleptika induzierten Gewichtszunahme bisher nicht ausreichend geklärt sind, ist bis jetzt keine Prognose hinsichtlich der induzierten Gewichtszunahme möglich. Für den interindividuellen Unterschied der Gewichtszunahme sorgen neben dem Ernährungsverhalten und Bewegung die genetischen Faktoren. Das Leptin- (ob- Gen) bzw. Leptinrezeptorgen sind Kandidatengene auf Chromosom 7, deren genetische Varianten sich in Studien zur Gewichtszunahme als signifikant assoziiert erwiesen. Diese Gene stellen interessante Kandidanten für die Untersuchung der Neuroleptika induzierten Gewichtszunahme dar, da das Leptinsystem eine Schlüsselrolle in der Gewichtsregulation und Energiehomöostase einnimmt. Leptin wird proportional zur Gesamtkörperfettmasse ausgeschüttet und reguliert die Nahrungsaufnahme über hypothalamisch- hypophysäre- und neuroendokrine Strukturen. Hohe Leptinspiegel signalisieren ein Sättigungsgefühl und führen zu einer verminderten Nahrungsaufnahme. In der vorliegenden Arbeit wurde in einer Assoziationsstudie bei 91 schizophrenen Patienten kaukasischer Herkunft eine Beziehung zwischen vier SNPs des Leptingens und vier SNPs der Leptinrezeptorgens mit Neuroleptikainduzierter Gewichtszunahme untersucht. Der Promoterpolymorphismus des Leptingens rs 7799039 und der SNP des Leptinrezeptorgens rs1137101 wurden in Studien von Zhang et al., Mou et al., Templeman et al., Kang et al., Müller et al. und Gregoor et al. als assoziiert mit Neuroleptika induzierter Gewichtszunahme beschrieben. Die Auswahl der übrigen SNPs erfolgte aufgrund ihres Heterozygotenindex und ihrer Validität unter besondere Berücksichtigung der Lokalisation. Die SNPs wurde so gewählt, dass eine möglichst großflächige Abdeckung des zu untersuchenden Genes erlangt wurde. In der vorliegenden Studie konnten übereinstimmende und differente Ergebnisse bezüglich anderer Studien gefunden werden, wie auch neue Ergebnisse zum Leptinsystem hervorgebracht werden. In der dieser Arbeit zeigte sich keine Assoziation des in der Studienliteratur vorbeschriebenen Promoter- Polymorphismus rs7799039, sowie des Markern rs1137101 mit Neuroleptika induzierter Gewichtszunahme und/oder BMI-Zunahme. Es ließ sich jedoch eine Assoziation zwischen den untersuchten Marker rs3828942 (A-Allel), sowie der Marker rs1327120 (A-Allel) und rs1327118 (G-Allel) und Neuroleptikainduzierter Gewichtszunahme bzw. BMI- Zunahme feststellen. Insbesondere erwiesen sich Analysen einer geschlechterspezifischen Untersuchung als interessant. So konnte eine starke Assoziation zwischen dem Marker rs1327120 (A-Allel) des Leptinrezeptorgens bei weiblichen Patientinnen und Neuroleptikainduzierten Gewichtszunahme sowie BMI- Zunahme nach 6 Wochen gefunden werden. Darüber hinaus ließ sich eine Assoziation des Markers rs3828942 (A-Allel) bei Männern und des Markers rs1327120 (A-Allel) bei Frauen mit einer signifikanten Gewichtszunahme zeigen. Diese Arbeit stellt die bisher umfassende Analyse des Leptinsystems (Leptin- und Leptinrezeptorgen) und Neuroleptika induzierter Gewichtszunahme dar. Die vorliegende Arbeit bestätigt eine Assoziation des Leptinsystems mit Neuroleptika induzierter Gewichtszunahme. Um diese Daten zu verifizieren und zu erweitern, sind Genotypisierungen in größeren, unabhängigen Studienpopulation notwendig. Zudem sollte eine längere Erfassung des Verlaufs der Gewichtszunahme über mehrere Monate erfolgen.Schizophrenia is a serious chronic psychiatric disorder of multifactorial genesis with a life time risk of almost 1%. Main symptoms characterize significant loss of social and occupational capabilities due to fundamental disorders of thinking and perception as well as inappropriate and flattened affect. Schizophrenia is a very heterogeneous disease, in terms of their prognostic aspect its symptoms can be split into positive, including auditory hallucinations, paranoid delusions and disorganized speech and thinking and negative symptoms, including anhedonia and lacking in drive. Particularly second and third generation atypical antipsychotic (APs) drugs are used for treatment, that show multiple and severe metabolic, endocrinological, haematological and cardiovascular side effects. The antipsychotic induced weight gain is one of the most serious side effects because overweight and obesity are risk factors for the development of a metabolic syndrome, which has a distinct effect on cardiovascular morbidity and mortality. Furthermore, weight gain can cause social stigmatization and decreased quality of life as well as reduced compliance regarding to continuing antipsychotic long term treatment. The mechanisms of weight gain regulation remains unknown. It is assumed that interactions of different genes cause a dysfunction of the physiological balance neurobiological control circuits, inducing metabolic changes and increasing in appétit and food intake. The leptin gene (ob-gene) and the leptin receptor gene are promising candidate genes on chromosome 7. Genetic variations of these genes have been shown to be significantly associated with antipsychotic induced weight gain in past research studies. The leptin system has major role in weight regulation and energy homeostasis. Circulating leptin correlates with the percent amount of the body adipose tissue signalling the central nerve system the amount of peripheral adipose tissue. An increased level of leptin induces reduction of appetite and ingestion and expansion of energy metabolism through activation of hypothalamical regulatory processes. In this present study, we selected 91 schizophrenic Caucasian patients to investigate weather the chosen four leptin- and four leptin receptor gene polymorphisms are associated with antipsychotic induced weight gain. The chosen promoter polymorphism of the leptin gene rs7799039 and the polymorphism of the leptin receptor gens rs1137101 were significant associated with AP-induced weight gain in studies of Zhang et al., Mou et al., Templeman et al., Kang et al., Müller et al. and Gregoor et al. The selections of the remaining SNPs were chosen according minor allele frequency and validity, potential functional relevance and location on physical and genetic maps. In our study we demonstrate an association of the leptin system and antipsychotic induced weight gain. There was no association between the promoter polymorphism rs7799039 and antipsychotic induced weight gain as in previous studies, as well as there was no association between the marker rs1137101 and antipsychotic induced weight gain. However, we were able to show an association between marker rs3828942 (A-allele), marker rs1327120 (A-allele) and rs1327118 (G-allele) and significant weight gain. Especially our gender specific analyses were very interesting. We were able to show a strong association of weight gain and BMI gain of the leptin receptor gene rs1327120 polymorphism in women after six weeks of treatment. Moreover, we were able to show a significant weight and BMI gain of the marker rs3828942 (A-allele) in men and of the marker rs1327120 (A-allele) in women during antipsychotic treatment. This present study is a comprising analysis of the leptin system (leptin- and leptin receptor gene) and antipsychotic induced weight gain. Our present studies gave evidence that the leptin and the leptin receptor gene could be a factor of individual predisposition for antipsychotic induced weight gain. To verify present data further studies in larger samples are necessary

Signal Intensities in Preoperative MRI Do Not Reflect Proliferative Activity in Meningioma

BACKGROUND: Identification of high-grade meningiomas in preoperative magnetic resonance imaging (MRI) is important for optimized surgical strategy and best possible resection. Numerous studies investigated subjectively determined morphological features as predictors of tumor biology in meningiomas. The aim of this study was to identify the predictive value of more reliable, quantitatively measured signal intensities in MRI for differentiation of high- and low-grade meningiomas and identification of meningiomas with high proliferation rates, respectively. PATIENTS AND METHODS: Sixty-six patients (56 World Health Organization [WHO] grade I, 9 WHO grade II, and 1 WHO grade I) were included in the study. Preoperative MRI signal intensities (fluid-attenuated inversion recovery [FLAIR], T1 precontrast, and T1 postcontrast as genuine and normalized values) were correlated with Ki-67 expression in tissue sections of resected meningiomas. Differences between the groups (analysis of variance) and Spearman rho correlation were computed using SPSS 22. RESULTS: Mean values of genuine signal intensities of meningiomas in FLAIR, T1 native, and T1 postcontrast were 323.9 ± 59, 332.8 ± 67.9, and 768.5 ± 165.3. Mean values of normalized (to the contralateral white matter) signal intensities of meningiomas in FLAIR, T1 native, and T1 postcontrast were 1.5 ± 0.3, 0.8 ± 0.1, and 1.9 ± 0.4. There was no significant correlation between MRI signal intensities and WHO grade or Ki-67 expression. Signal intensities did not differ significantly between WHO grade I and II/III meningiomas. Ki-67 expression was significantly increased in high-grade meningiomas compared with low-grade meningiomas (P < 0.01). Objectively measured values of MRI signal intensities (FLAIR, T1 precontrast, and T1 postcontrast enhancement) did not distinguish between high-grade and low-grade meningiomas. Furthermore, there was no association between MRI signal intensities and Ki-67 expression representing proliferative activity

Comparison of 4D Flow MRI to 2D Flow MRI in the pulmonary arteries in healthy volunteers and patients with pulmonary hypertension.

PURPOSE:4D and 2D phase-contrast MRI (2D Flow MRI, 4D Flow MRI, respectively) are increasingly being used to noninvasively assess pulmonary hypertension (PH). The goals of this study were i) to evaluate whether established quantitative parameters in 2D Flow MRI associated with pulmonary hypertension can be assessed using 4D Flow MRI; ii) to compare results from 4D Flow MRI on a digital broadband 3T MR system with data from clinically established MRI-techniques as well as conservation of mass analysis and phantom correction and iii) to elaborate on the added value of secondary flow patterns in detecting PH. METHODS:11 patients with PH (4f, 63 ± 16y), 15 age-matched healthy volunteers (9f, 56 ± 11y), and 20 young healthy volunteers (13f, 23 ± 2y) were scanned on a 3T MR scanner (Philips Ingenia). Subjects were examined with a 4D Flow, a 2D Flow and a bSSFP sequence. For extrinsic comparison, quantitative parameters measured with 4D Flow MRI were compared to i) a static phantom, ii) 2D Flow acquisitions and iii) stroke volume derived from a bSSFP sequence. For intrinsic comparison conservation of mass-analysis was employed. Dedicated software was used to extract various flow, velocity, and anatomical parameters. Visualization of blood flow was performed to detect secondary flow patterns. RESULTS:Overall, there was good agreement between all techniques, 4D Flow results revealed a considerable spread. Data improved after phantom correction. Both 4D and 2D Flow MRI revealed concordant results to differentiate patients from healthy individuals, especially based on values derived from anatomical parameters. The visualization of a vortex, indicating the presence of PH was achieved in 9 /11 patients and 2/35 volunteers. DISCUSSION:This study confirms that quantitative parameters used for characterizing pulmonary hypertension can be gathered using 4D Flow MRI within clinically reasonable limits of agreement. Despite its unfavorable spatial and lesser temporal resolution and a non-neglible spread of results, the identification of diseased study participants was possible

Usefulness and Limits of Tractography for Surgery in the Precentral Gyrus—A Case Report

The resection of tumors within the primary motor cortex is a constant challenge. Although tractography may help in preoperative planning, it has limited application. While it can give valuable information on subcortical fibers, it is less accurate in the cortical layer of the brain. A 38-year-old patient presented with paresis of the right hand and focal epileptic seizures due to a tumor in the left precentral gyrus. Transcranial magnetic stimulation was not applicable due to seizures, so microsurgical resection was performed with preoperative tractography and intraoperative direct electrical stimulation. A histopathological assessment revealed a diagnosis of glioblastoma. Postoperative magnetic resonance imaging (MRI) showed complete resection. The paresis dissolved completely during follow-up. Surgery within the precentral gyrus is of high risk and requires multimodal functional planning. If interpreted with vigilance and consciousness of the underlying physical premises, tractography can provide helpful information within its limitations, which is especially subcortically. However, it may also help in the identification of functional cortex columns of the brain in the presence of a tumor

Usefulness and Limits of Tractography for Surgery in the Precentral Gyrus: A Case Report

The resection of tumors within the primary motor cortex is a constant challenge. Although tractography may help in preoperative planning, it has limited application. While it can give valuable information on subcortical fibers, it is less accurate in the cortical layer of the brain. A 38-year-old patient presented with paresis of the right hand and focal epileptic seizures due to a tumor in the left precentral gyrus. Transcranial magnetic stimulation was not applicable due to seizures, so microsurgical resection was performed with preoperative tractography and intraoperative direct electrical stimulation. A histopathological assessment revealed a diagnosis of glioblastoma. Postoperative magnetic resonance imaging (MRI) showed complete resection. The paresis dissolved completely during follow-up. Surgery within the precentral gyrus is of high risk and requires multimodal functional planning. If interpreted with vigilance and consciousness of the underlying physical premises, tractography can provide helpful information within its limitations, which is especially subcortically. However, it may also help in the identification of functional cortex columns of the brain in the presence of a tumor

Usefulness and Limits of Tractography for Surgery in the Precentral Gyrus&mdash;A Case Report

The resection of tumors within the primary motor cortex is a constant challenge. Although tractography may help in preoperative planning, it has limited application. While it can give valuable information on subcortical fibers, it is less accurate in the cortical layer of the brain. A 38-year-old patient presented with paresis of the right hand and focal epileptic seizures due to a tumor in the left precentral gyrus. Transcranial magnetic stimulation was not applicable due to seizures, so microsurgical resection was performed with preoperative tractography and intraoperative direct electrical stimulation. A histopathological assessment revealed a diagnosis of glioblastoma. Postoperative magnetic resonance imaging (MRI) showed complete resection. The paresis dissolved completely during follow-up. Surgery within the precentral gyrus is of high risk and requires multimodal functional planning. If interpreted with vigilance and consciousness of the underlying physical premises, tractography can provide helpful information within its limitations, which is especially subcortically. However, it may also help in the identification of functional cortex columns of the brain in the presence of a tumor

Perioperative anticoagulation in patients with intracranial meningioma: No increased risk of intracranial hemorrhage?

ObjectiveAnticoagulation (AC) is a critical topic in perioperative and post-bleeding management. Nevertheless, there is a lack of data about the safe, judicious use of prophylactic and therapeutic anticoagulation with regard to risk factors and the cause and modality of brain tissue damage as well as unfavorable outcomes such as postoperative hemorrhage (PH) and thromboembolic events (TE) in neurosurgical patients. We therefore present retrospective data on perioperative anticoagulation in meningioma surgery.MethodsData of 286 patients undergoing meningioma surgery between 2006 and 2018 were analyzed. We followed up on anticoagulation management, doses and time points of first application, laboratory values, and adverse events such as PH and TE. Pre-existing medication and hemostatic conditions were evaluated. The time course of patients was measured as overall survival, readmission within 30 days after surgery, as well as Glasgow Outcome Scale (GOS) and modified Rankin Scale (mRS). Statistical analysis was performed using multivariate regression.ResultsWe carried out AC with Fraxiparin and, starting in 2015, Tinzaparin in weight-adapted recommended prophylactic doses. Delayed (216 ± 228h) AC was associated with a significantly increased rate of TE (p = 0.026). Early (29 ± 21.9h) prophylactic AC, on the other hand, did not increase the risk of PH. We identified additional risk factors for PH, such as blood pressure maxima, steroid treatment, and increased white blood cell count. Patients' outcome was affected more adversely by TE than PH (+3 points in modified Rankin Scale in TE vs. +1 point in PH, p = 0.001).ConclusionEarly prophylactic AC is not associated with an increased rate of PH. The risks of TE seem to outweigh those of PH. Early postoperative prophylactic AC in patients undergoing intracranial meningioma resection should be considered

Usefulness and Limits of Tractography for Surgery in the Precentral Gyrus: A Case Report

The resection of tumors within the primary motor cortex is a constant challenge. Although tractography may help in preoperative planning, it has limited application. While it can give valuable information on subcortical fibers, it is less accurate in the cortical layer of the brain. A 38-year-old patient presented with paresis of the right hand and focal epileptic seizures due to a tumor in the left precentral gyrus. Transcranial magnetic stimulation was not applicable due to seizures, so microsurgical resection was performed with preoperative tractography and intraoperative direct electrical stimulation. A histopathological assessment revealed a diagnosis of glioblastoma. Postoperative magnetic resonance imaging (MRI) showed complete resection. The paresis dissolved completely during follow-up. Surgery within the precentral gyrus is of high risk and requires multimodal functional planning. If interpreted with vigilance and consciousness of the underlying physical premises, tractography can provide helpful information within its limitations, which is especially subcortically. However, it may also help in the identification of functional cortex columns of the brain in the presence of a tumor