Migraine-Associated Common Genetic Variants Confer Greater Risk of Posterior vs. Anterior Circulation Ischemic Stroke☆.

OBJECTIVE: To examine potential genetic relationships between migraine and the two distinct phenotypes posterior circulation ischemic stroke (PCiS) and anterior circulation ischemic stroke (ACiS), we generated migraine polygenic risk scores (PRSs) and compared these between PCiS and ACiS, and separately vs. non-stroke control subjects. METHODS: Acute ischemic stroke cases were classified as PCiS or ACiS based on lesion location on diffusion-weighted MRI. Exclusion criteria were lesions in both vascular territories or uncertain territory; supratentorial PCiS with ipsilateral fetal posterior cerebral artery; and cases with atrial fibrillation. We generated migraine PRS for three migraine phenotypes (any migraine; migraine without aura; migraine with aura) using publicly available GWAS data and compared mean PRSs separately for PCiS and ACiS vs. non-stroke control subjects, and between each stroke phenotype. RESULTS: Our primary analyses included 464 PCiS and 1079 ACiS patients with genetic European ancestry. Compared to non-stroke control subjects (n=15396), PRSs of any migraine were associated with increased risk of PCiS (p=0.01-0.03) and decreased risk of ACiS (p=0.010-0.039). Migraine without aura PRSs were significantly associated with PCiS (p=0.008-0.028), but not with ACiS. When comparing PCiS vs. ACiS directly, migraine PRSs were higher in PCiS vs. ACiS for any migraine (p=0.001-0.010) and migraine without aura (p=0.032-0.048). Migraine with aura PRS did not show a differential association in our analyses. CONCLUSIONS: Our results suggest a stronger genetic overlap between unspecified migraine and migraine without aura with PCiS compared to ACiS. Possible shared mechanisms include dysregulation of cerebral vessel endothelial function.

Retrospective analysis of the lifetime endocrine response of southern right whale calves to gull wounding and harassment: A baleen hormone approach.

Physiological measurements are informative in assessing the relative importance of stressors that potentially impact the health of wildlife. Kelp Gulls, Larus dominicanus (KG), resident to the region of Península Valdés, Argentina, have developed a unique behavior of landing on the backs of southern right whale adults and calves, Eubalaena australis (SRW), where they feed on their skin and blubber. This parasitic behavior results in large open wounds on the dorsal surface of the whale. Coincidently, the SRW population off the coast of Península Valdés has experienced elevated calf mortality. We quantified levels of glucocorticoids and thyroid hormone extracted from baleen of dead calves to evaluate, retrospectively, the endocrine response of whale calves to gull wounding and harassment. Baleen accumulates hormones as it grows, allowing evaluation of long-term trends in physiological condition. While glucocorticoids (GCs) are known to increase in response to stressors such as disturbance, the metabolic hormone triiodothyronine (T3) has been shown to decrease under sustained food deprivation but is largely unaffected by disturbance stress. We quantified lifetime patterns of GCs and T3 in baleen recovered at necropsy from 36 southern right whale calves with varying severity of wounding from KGs. GC levels in baleen correlated positively with the degree of wounding, while T3 levels remained stable irrespective of the severity of the wounding. Our results suggest no evidence of malnutrition in low vs. severely wounded whales. However, the positive correlation of GCs with wound severity indicates that heavily wounded calves are suffering high levels of physiological stress before they die. This suggests that KG wounding may have contributed to the high southern right whale calf mortality observed in the Península Valdés region of Argentina.

Regional pattern of microgliosis in sporadic Creutzfeldt-Jakob disease in relation to phenotypic variants and disease progression.

AIMS: The aim of this study was to describe the regional profiles of microglial activation in sporadic Creutzfeldt-Jakob disease (sCJD) subtypes and analyse the influence of prion strain, disease duration and codon 129 genotype. METHODS: We studied the amount/severity and distribution of activated microglia, protease-resistant prion protein (PrPSc ) spongiform change, and astrogliosis in eight regions of 57 brains, representative of the entire spectrum of sCJD subtypes. RESULTS: In each individual subtype, the regional extent and distribution of microgliosis significantly correlated with PrPSc deposition and spongiform change, leading to subtype-specific 'lesion profiles'. However, large differences in the ratio between PrPSc load or the score of spongiform change and microglial activation were seen among disease subtypes. Most significantly, atypical sCJD subtypes such as VV1 and MM2T showed a degree of microglial activation comparable to other disease variants despite the relatively low PrPSc deposition and the less severe spongiform change. Moreover, the mean microglial total load was significantly higher in subtype MM1 than in MM2C, whereas the opposite was true for the PrPSc and spongiform change total loads. Finally, some sCJD subtypes showed distinctive regional cerebellar profiles of microgliosis characterized by a high granular/molecular layer ratio (MV2K) and/or a predominant involvement of white matter (MVK and MM2T). CONCLUSIONS: Microglial activation is an early event in sCJD pathogenesis and is strongly influenced by prion strain, PRNP codon 129 genotype and disease duration. Microglial lesion profiling, by highlighting strain-specific properties of prions, contributes to prion strain characterization and classification of human prion diseases, and represents a valid support to molecular and histopathologic typing.

Correction to: Biological tumour volumes of gliomas in early and standard 20-40 min 18F-FET PET images differ according to IDH mutation status.

The name of M. Unterrainer was inadvertently presented as M. Unterrrainer in the original article.

Biological tumour volumes of gliomas in early and standard 20-40 min 18F-FET PET images differ according to IDH mutation status.

PURPOSE: For the clinical evaluation of O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) PET images, the use of standard summation images obtained 20-40 min after injection is recommended. However, early summation images obtained 5-15 min after injection have been reported to allow better differentiation between low-grade glioma (LGG) and high-grade glioma (HGG) by capturing the early 18F-FET uptake peak specific for HGG. We compared early and standard summation images with regard to delineation of the PET-derived biological tumour volume (BTV) in correlation with the molecular genetic profile according the updated 2016 WHO classification. METHODS: The analysis included 245 patients with newly diagnosed, histologically verified glioma and a positive 18F-FET PET scan prior to any further treatment. BTVs were delineated during the early 5-15 min and standard 20-40 min time frames using a threshold of 1.6 × background activity and were compared intraindividually. Volume differences between early and late summation images of >20% were considered significant and were correlated with WHO grade and the molecular genetic profile (IDH mutation and 1p/19q codeletion status). RESULTS: In 52.2% of the patients (128/245), a significant difference in BTV of >20% between early and standard summation images was found. While 44.3% of WHO grade II gliomas (31 of 70) showed a significantly smaller BTV in the early summation images, 35.0% of WHO grade III gliomas (28/80) and 37.9% of WHO grade IV gliomas (36/95) had a significantly larger BTVs. Among IDH-wildtype gliomas, an even higher portion (44.4%, 67/151) showed significantly larger BTVs in the early summation images, which was observed in 5.3% (5/94) of IDH-mutant gliomas only: most of the latter had significantly smaller BTVs in the early summation images, i.e. 51.2% of IDH-mutant gliomas without 1p/19q codeletion (21/41) and 39.6% with 1p/19q codeletion (21/53). CONCLUSION: BTVs delineated in early and standard summation images differed significantly in more than half of gliomas. While the standard summation images seem appropriate for delineation of LGG as well as IDH-mutant gliomas, a remarkably high percentage of HGG and, particularly, IDH-wildtype gliomas were depicted with significantly larger volumes in early summation images. This finding might be of interest for optimization of treatment planning (e.g. radiotherapy) in accordance with the individual IDH mutation status.

Assessing psychological and supportive care needs in glioma patients - feasibility study on the use of the Supportive Care Needs Survey Short Form (SCNS-SF34-G) and the Supportive Care Needs Survey Screening Tool (SCNS-ST9) in clinical practice.

Neuro-oncological patients experience high symptom and psychosocial burden. The aim was to test feasibility and practicability of the Supportive Care Needs Survey Short Form (SCNS-SF34-G) and the SCNS-Screening Tool (SCNS-ST9) to assess supportive care needs of neuro-oncological patients in clinical routine. A total of 173 patients, most with a primary diagnosis of high-grade glioma (81%), were assessed first using SCNS-SF34-G in comparison to two well-established patient-reported outcome measures, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQC30 + QLQ-BN20) and Distress Thermometer (DT). In a follow-up assessment, SCNS-ST9 was used in a subgroup (n = 90). Questionnaires were completed either with personal guidance offered (group A) or by patients alone (group B). Feasibility was compared between instruments and groups for possible associations with patient and treatment-related factors. Missing values occurred in similar frequencies in all instruments. Errors in completion occurred in SCNS-SF34-G in 20% and in SCNS-ST9 in 16%; difficulties in completion were observed more often in SCNS-SF34-G and SCNS-ST9 (39%) compared to DT and EORTC (13%, p < .001). Distress was found to be associated with difficulties in completion of SCNS (OR 1.4, [95% CI 1.1-1.9], p = .013). SCNS-SF34 and SCNS-ST9 are suitable tools for glioma patients as long as personal guidance is offered.

Cathepsin S increases tau oligomer formation through limited cleavage, but only IL-6, not cathespin S serum levels correlate with disease severity in the neurodegenerative tauopathy progressive supranuclear palsy.

Limited cleavage promotes the aggregation propensity of protein tau in neurodegenerative tauopathies. Cathepsin S (CatS) is overexpressed in brains of patients suffering from tauopathies such as Alzheimer's disease (AD). Furthermore, CatS serum levels correlate with survival in the elderly. The current study investigates whether limited cleavage by CatS promotes tau aggregation, and whether CatS serum levels may correlate with disease severity in tauopathies. Oligomer formation of fluorescently labeled protein tau was monitored by single particle fluorescence spectroscopy after coincubation with CatS. Tau cleavage patterns were investigated by SDS-PAGE. For serum analyses, samples were collected from 42 patients with probable progressive supranuclear palsy (PSP) according to NINDS-PSP criteria. Disease severity was assessed by PSP rating scale (PSP-RS), PSP staging system (PSP-S) and Schwab and England Activities of Daily Living (SEADL). CatS, cystatin C (CysC) and interleukin 6 (IL-6) serum levels were determined by ELISA, ECLIA and turbidimetry, respectively. SDS-PAGE demonstrated a distinct cleavage pattern of protein tau after coincubation with CatS. Furthermore, tau oligomer formation was increased 2.4-fold (p < 0.05) after limited cleavage. Serum CatS and CysC levels did not correlate with disease severity in PSP. Of note, IL-6 correlated with PSP-S (r = 0.41; 95% CI 0.11-0.65; p = 0.008), SEADL (r = -0.37; 95% CI -0.61 to -0.06; p = 0.017) and the history and gait/midline subdomains of the PSP-RS. While CatS facilitates tau aggregation in vitro, serum levels of CatS appear not to correlate with disease severity. The observed correlation of IL-6 with disease severity warrants further investigation of inflammatory markers in PSP.

Frequency and predictors of acute ischaemic lesions on brain magnetic resonance imaging in young patients with a clinical diagnosis of transient ischaemic attack.

BACKGROUND AND PURPOSE: Acute lesions in patients with transient ischaemic attack (TIA) are important as they are associated with increased risk for recurrence. Characteristics associated with acute lesions in young TIA patients were therefore investigated. METHODS: The sifap1 study prospectively recruited a multinational European cohort (n = 5023) of patients aged 18-55 years with acute cerebrovascular event. The detection of acute ischaemic lesions was based on diffusion-weighted imaging (DWI). The frequency of DWI lesions was assessed in 829 TIA patients who met the criteria of symptom duration <24 h and their association with demographic, clinical and imaging variables was analysed. RESULTS: The median age was 46 years (interquartile range 40-51 years); 45% of the patients were female. In 121 patients (15%) ≥1 acute DWI lesion was detected. In 92 patients, DWI lesions were found in the anterior circulation, mostly located in cortical-subcortical areas (n = 63). Factors associated with DWI lesions in multiple regression analysis were left hemispheric presenting symptoms [odds ratio (OR) 1.92, 95% confidence interval (CI) 1.27-2.91], dysarthria (OR 2.17, 95% CI 1.38-3.43) and old brain infarctions on MRI (territories of the middle and posterior cerebral artery: OR 2.43, 95% CI 1.42-4.15; OR 2.41, 95% CI 1.02-5.69, respectively). CONCLUSIONS: In young patients with a clinical TIA 15% demonstrated acute DWI lesions on brain MRI, with an event pattern highly suggestive of an embolic origin. Except for the association with previous infarctions there was no clear clinical predictor for acute ischaemic lesions, which indicates the need to obtain MRI in young individuals with TIA.

Neuroradiological, neurophysiological and molecular findings in infantile Krabbe disease: two case reports.

Krabbe disease is an autosomal recessive neurodegenerative disorder due to a defect of the lysosomal enzyme ß-galactocerebrosidase (ß-GALC). Depending on the age of onset, the disease is classified into infantile and later-onset forms. We report neuroradiological, neurophysiological and molecular findings in two Greek patients with the infantile form of Krabbe disease. The index patients presented at the age of 3.5 and 6 months, respectively, due to developmental delay. Magnetic resonance imaging (MRI) of the first patient's brain demonstrated signs of leukodystrophy, while nerve conduction velocities (NCVs) were significantly decreased. The second patient's MRI at the age of 4 months was initially normal, but at 18 months demonstrated leukodystrophic alterations as well, whereas NCVs were also significantly delayed. In both patients, a severe decrease in ß-GALC, activity supported the diagnosis of Krabbe disease, while the final diagnosis was confirmed by molecular genetic testing. Two homozygous mutations of the GALC gene, the c.411_413delTAA [p.K139del] mutation in the first patient, and the c.749T>C [p.I250T] mutation in the second patient, were identified. At their last follow-up visit at the age of 4 and 6 years, respectively, both patients were bedridden and quadri-plegic, suffering from frequent respiratory tract infections and fed through a gastrostomy. Both mutations found in homozygosity in these two unrelated patients of Greek ancestry, could pinpoint a common origin. Genotyping of patients with Krabbe disease is important, in order to contribute to the creation of a European mutation database and to further study possible genotype-phenotype correlations of the disease.

[Recurrent hypoglycemia due to an occult insulinoma]. / Okkultes Insulinom als Ursache rezidivierender Hypoglykämien.

A 64-year-old woman presented with a history of recurrent hypoglycemia. A prolonged fasting test revealed an increased "amended" insulin-glucose ratio. Transabdominal ultrasound (US), computed tomography (CT) scan, and magnetic resonance imaging (MRI) did not show abnormal results. An insulinoma was suspected based on a contrast-enhanced endoscopic US examination as well as a (68)gallium-DOTA-exendin-4 positron-emission tomography (PET)/CT. The diagnosis of an insulinoma was confirmed histologically after surgical removal of the tumor. Hypoglycemia did not occur during the postoperative period. The prolonged fasting test is the gold standard for the diagnosis of an insulinoma. Novel imaging procedures, such as contrast-enhanced endoscopic US or (68)gallium-DOTA-exendin-4 PET/CT are valuable additions to the diagnostic workup.

Heritability of young- and old-onset ischaemic stroke.

BACKGROUND AND PURPOSE: Although the genetic contribution to stroke risk is well known, it remains unclear if young-onset stroke has a stronger genetic contribution than old-onset stroke. This study aims to compare the heritability of ischaemic stroke risk between young and old, using common genetic variants from whole-genome array data in population-based samples. METHODS: This analysis included 4050 ischaemic stroke cases and 5765 controls from six study populations of European ancestry; 47% of cases were young-onset stroke (age < 55 years). To quantify the heritability for stroke risk in these unrelated individuals, the pairwise genetic relatedness was estimated between individuals based on their whole-genome array data using a mixed linear model. Heritability was estimated separately for young-onset stroke and old-onset stroke (age ≥ 55 years). RESULTS: Heritabilities for young-onset stroke and old-onset stroke were estimated at 42% (±8%, P < 0.001) and 34% (±10%, P < 0.001), respectively. CONCLUSIONS: Our data suggest that the genetic contribution to the risk of stroke may be higher in young-onset ischaemic stroke, although the difference was not statistically significant.

[Patient-centered care. Improvement of communication between university medical centers and general practitioners for patients in neuro-oncology]. / Patientenzentrierte Versorgung. Verbesserung der Kommunikation zwischen Universitätsklinik und Hausärzten bei neuroonkologischen Patienten.

INTRODUCTION: Communication between university medical centers and general practitioners (GP) is becoming increasingly more important in supportive patient care. A survey among GPs was performed with the primary objective to assess their opinion on current workflow and communication between GPs and the university medical center. METHODS: The GPs were asked to score (grades 1-6) their opinion on the current interdisciplinary workflow in the care of patients with brain tumors, thereby rating communication between a university medical center in general and the neuro-oncology outpatient center in particular. RESULTS: Questionnaires were sent to1000 GPs and the response rate was 15 %. The mean scored evaluation of the university medical center in general was 2.62 and of the neuro-oncological outpatient clinic 2.28 (range 1-6). The most often mentioned issues to be improved were easier/early telephone information (44 %) and a constantly available contact person (49 %). Interestingly, > 60 % of the GPs indicated they would support web-based tumor boards for interdisciplinary and palliative neuro-oncological care. CONCLUSION: As interdisciplinary care for neuro-oncology patients is an essential part of therapy, improvement of communication between GPs and university medical centers is indispensable. Integrating currently available electronic platforms under data protection aspects into neuro-oncological palliative care could be an interesting tool in order to establish healthcare networks and could find acceptance with GPs.

Use of the Complete Rockall Score and the Forrest Classification to Assess Outcome in Patients with Non-variceal Upper Gastrointestinal Bleeding Subject to After-hours Endoscopy: A Retrospective Cohort Study.

OBJECTIVES: To evaluate the usefulness of the Forrest classification and the complete Rockall score with customary cut-off values for assessing the risk of adverse events in patients with upper gastrointestinal bleeding (UGI-B) subject to after-hours emergency oesophago-gastro-duodenoscopy (E-EGD) within six hours after admission. METHODS: The medical records of patients with non-variceal UGI-B proven by after-hours endoscopy were analysed. For 'high risk' situations (Forrest stage Ia-IIb/complete Rockall score > 2), univariate analysis was conducted to evaluate odds ratio for reaching the study endpoints (30-day and one-year mortality, re-bleeding, hospital stay ≥ 3 days). RESULTS: During the study period (75 months), 86 cases (85 patients) met the inclusion criteria. Patients' age was 66.36 ± 14.38 years; 60.5% were male. Mean duration of hospital stay was 15.21 ± 19.24 days. Mortality rate was 16.7% (30 days) and 32.9% (one year); 14% of patients re-bled. Univariate analysis of post-endoscopic Rockall score ≥ 2 showed an odds ratio of 6.09 for death within 30 days (p = 0.04). No other significant correlations were found. CONCLUSION: In patients with UGI-B subject to after-hours endoscopy, a 'high-risk' Rockall score permits an estimation of the risk of death within 30 days but not of re-bleeding. A 'high-risk' Forrest score is not significantly associated with the study endpoints.

The combination of carmustine wafers and temozolomide for the treatment of malignant gliomas. A comprehensive review of the rationale and clinical experience.

Current treatment strategies in patients with newly-diagnosed glioblastoma include surgical resection with post-operative radiotherapy and concomitant/adjuvant temozolomide (the "Stupp protocol") or resection with implantation of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) wafers in the surgical cavity followed by radiotherapy. In clinical practice, patients with malignant glioma treated with BCNU wafer often also receive adjuvant temozolomide. However, current treatment guidelines are unclear on whether and how these treatment practices can be combined, and no prospective phase 3 study has assessed the safety and efficacy of combining BCNU wafers with temozolomide and radiation in high-grade malignant glioma. The rationale for multimodal therapy comprising surgical resection with adjunct local BCNU wafers followed by radiotherapy and temozolomide is based on complementary and synergistic mechanisms of action between BCNU and temozolomide in preclinical studies; a shared primary resistance pathway, methylguanine-DNA methyltransferase (MGMT); and the opportunity to overcome resistance through MGMT depletion to boost cytotoxic activity. A comprehensive review of the literature identified 19 retrospective and prospective studies investigating the use of this multimodal strategy. Median overall survival in 14 studies of newly-diagnosed patients suggested a modest improvement versus resection followed by Stupp protocol or resection with BCNU wafers, with an acceptable and manageable safety profile.

Detection of intracranial circulatory arrest in brain death using cranial CT-angiography.

BACKGROUND AND PURPOSE: Computed tomographic-angiography (CT-A) is becoming more accepted in detecting intracranial circulatory arrest in brain death (BD). An international consensus about the use and the parameters of this technique is currently not established. We examined intracranial contrast enhancement in CT-A after clinically confirmed BD, compared the results with electroencephalography (EEG) and Transcranial Doppler Ultrasonography (TCD) findings and developed a commonly applicable CT-A protocol. METHODS: Prospective, monocentric study between April 2008 and October 2011. EEG, TCD and CT-A were performed in 63 patients aged between 18 and 88 years (mean, 55 years) who fulfilled clinical criteria of BD. Evaluation of opacification of cerebral vascular territories in CT-A was performed in arterial as well as in venous scanning series by a neuroradiologist and a neurointensivist/neurosurgeon together. RESULTS: CT-A demonstrated a 95% sensitivity in detecting intracranial circulatory arrest when analysing arterial scanning series. We never observed venous blood return in internal cerebral veins. In three cases, BD confirmation by EEG failed because of artefacts. Confirmation of BD by TCD failed in two cases because of absent temporal window. In three cases, TCD demonstrated residual blood flow. CONCLUSION: CT-A is easily accessible in almost every hospital, offers a high spatio-temporal resolution, is operator independent and inexpensive. The results of CT-A are comparable to other established brain perfusion techniques in BD. An international consensus should be established to ascertain consistent parameters similar to fixed guidelines for other ancillary procedures to determine BD in order to prevent different scanning and evaluation protocols for detecting intracranial circulatory arrest.

Genotype-phenotype and genotype-origin correlations in children with mediterranean fever in Germany - an AID-net study.

Familial Mediterranean fever (FMF) is the most inherited common autoinflammatory disease (AID) with mutations in the MEFV (MEditerraneanFeVer) gene.The Mor- and Pras-Score modified for children and C-reactive protein (CRP) were used to assess FMF disease severity in Germany. We evaluate the applicability of the 2 severity scores and the correlations between ethnic origin, phenotype, and genotype.Among 242 children (median 5 age at diagnosis), we detected 431 pyrin mutations and 22 different sequence variants, including one new mutation (p.Gly488Asp). The 5 most -frequent alterations were p.Met694Val (55.2%), p.Met680lle (11.8%), p.Val726Ala (10%), p.Glu148Gln (7.9%) and p.Met694IIe (2.3%). The prevailing ancestries of 223 cases were Turkish (82.5%) and Lebanese (8.1%). Homozygous p.Met694Val substitution (30.2%) was associated with a more severe disease activity by Mor-Score, as well as with a higher mean CRP (74 mg/l) compared to patients with other mutations. Indeed, Mor- and Pras-Score were inconsistent with each other. A typical distribution of mutations in different ethnic populations was obvious, but not statistically verifiable due to the low number of cases.The homozygous p.Met694Val substitution was associated with a more severe disease activity in our German cohort. The common severity scores were inconsistent in -children.

Toxicity and survival in primary glioblastoma patients treated with concomitant plus adjuvant temozolomide versus adjuvant temozolomide: results of a single-institution, retrospective, matched-pair analysis.

BACKGROUND: To compare survival and hematological toxicity rates between two postoperative therapy regimens in patients with primary glioblastoma (GBM), namely temozolomide (TMZ) concomitant to radiation, followed by adjuvant TMZ, versus adjuvant TMZ after radiation only. PATIENTS AND METHODS: A total of 191 patients with primary GBM were postoperatively treated with either radiation and concomitant TMZ, followed by adjuvant TMZ (Stupp protocol) (n = 154), or radiation followed by adjuvant TMZ (n = 37). The incidence of hematological adverse effects (AE) was recorded for all patients. From both treatment groups, 26 patients were matched according to age, Karnofsky performance scale (KPS) score, and O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation. RESULTS: Hematological AEs were mild in both unmatched groups, but were significantly more frequent in the concomitant plus adjuvant TMZ group (p < 0.001). Matched-pair analysis confirmed significantly more frequent hematological AEs in the concomitant and adjuvant group compared to the sequential (adjuvant) TMZ group (p = 0,012). Patients treated with concomitant plus adjuvant TMZ showed significantly longer progression-free survival (PFS) (10.6 versus 6.6 months; p = 0.014), but no prolonged overall survival (OS) (16.9 vs. 15.6 months; p = 0.717) compared to patients who received the sequential treatment regimen. CONCLUSION: In this retrospective study, the OS in patients with primary GBM treated with sequential TMZ following radiation appeared to be similar to that in patients treated with concomitant plus adjuvant TMZ. Given the significantly higher risk of hematological AE for concomitant treatment, the role of concomitant plus adjuvant TMZ use compared to sequential administration of TMZ, especially for patients with MGMT-unmethylated tumors, should be further evaluated.

Postsurgical screening for psychosocial disorders in neurooncological patients.

BACKGROUND: The diagnosis of a brain tumor can cause severe psychosocial distress, which can have a variety of negative consequences on patients' physical and mental well-being. The detection of psychosocial distress in daily clinical routine is difficult and subsequent referral to mental health professionals is rare. The aim of this study was to determine the incidence of psychological disorders of patients early postoperatively and to investigate both the Hornheide Screening Instrument (HSI) and Distress Thermometer (DT) as screening tools in neurooncological practice. METHODS: One hundred and thirty-four patients with brain tumors of different histology were postoperatively evaluated by the Distress Thermometer and Hornheide Screening Instrument. Additionally, correlation to gender, age, localization of the tumor, Karnofsky performance score and tumor entity were analyzed. RESULTS: After initial surgery 36 patients (26.9 %) showed pathologic results in the HSI and 50 patients (36.7 %) were severely distressed (DT Score≥6). Women had the highest rate of psychological disorders, followed by patients suffering from gliomas and meningiomas. Further highlighting the results of both tests, over 80 % of those patients who scored pathologically in both tests were in need of professional psychiatric help due to depression. CONCLUSION: Both the DT and HSI are suitable instruments for identifying patients in psychological distress after brain tumor surgery in neurooncological routine. Our results confirm that nearly one third of patients are unable to overcome the difficulties facing the diagnosis of a brain tumor in this early situation and should be supported by mental health professionals.

MGMT promoter methylation status and prognosis of patients with primary or recurrent glioblastoma treated with carmustine wafers.

The prognostic role of O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastoma patients treated with carmustine (BCNU) wafer implantation is unclear. Here, we report on a retrospective study of 47 patients with either newly diagnosed (30 patients) or recurrent (17 patients) glioblastoma (WHO grade IV) treated with BCNU (bis-chloroethylnitrosourea) wafers. Thirteen of the newly diagnosed patients received local BCNU and irradiation only (first-line BCNU), while 17 patients additionally received concomitant and adjuvant temozolomide (TMZ) radiochemotherapy (first-line BCNU + TMZ). Of the 17 patients treated for recurrent glioblastoma (second-line BCNU), 16 had received radiotherapy with concomitant and adjuvant TMZ as an initial treatment. Median overall survival (OS) did not significantly differ between 19 patients with MGMT promoter methylated tumors when compared to 28 patients with unmethylated tumors (18.9 vs 15.0 months; p = 0.1054). In the first-line BCNU + TMZ group, MGMT promoter methylation was associated with longer OS (21.0 vs 11.1 months, p = 0.0127), while no significant survival differences were detected in the other two subgroups. Progression-free survival did not significantly differ between patients with and without MGMT promoter methylated tumors in the entire patient cohort or any of the three subgroups. The first-line BCNU + TMZ group showed no significant difference in OS when compared to the first-line BCNU group (18.9 vs 14.7 months), but tended to have more therapy-related adverse effects (53% vs 24%, p = 0.105). In summary, MGMT promoter methylation showed a non-significant trend toward longer survival in our patient cohort. The combination of TMZ radiochemotherapy with local delivery of BCNU did not provide a significant survival benefit compared to local BCNU alone, but was associated with a higher rate of adverse effects. Owing to the small number of patients investigated, however, these findings would need to be corroborated in larger patient cohorts.

[Self-medication to treat pain in attacks of familial Mediterranean fever: aiming to find a new approach to pain management]. / Schmerztherapeutische Bedarfsmedikation bei Attacken von familiärem Mittelmeerfieber : Auf der Suche nach einem schmerztherapeutischen Ansatz.

BACKGROUND: Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by bouts of fever and serositis. Morbidity caused by bouts as well as self-medication were assessed among patients of Turkish ancestry living in Germany (D) or Turkey (T) in order to evaluate current analgetic concepts from a patient's perspective. MATERIAL AND METHODS: D and T were asked about the 3 months preceding the interview. RESULTS: A total of 40 D and 40 T were included; 35/40 D and 40/40 T were on colchicine. In the last 3 months, 61.3 % had ≥ 1 bout and suffered from peritonitis (87.8 %), fever (61.2 %), myalgia (45 %), pleuritis (42.8 %), arthralgia (36.7 %), and cephalgia (32.6 %). Of the patients, 65.3 % were bedridden during bouts, 61.2 % sought the attention of a physician, 53.1 % were unable to work or attend school, and 38.8 % were hospitalized. The following drugs were taken: NSAIDs (45.6 %), NSAIDs and paracetamol (42.6 %), and combinations of NSAIDs with other analgesics. NSAIDs (58.6 %) and paracetamol (20.7 %) were considered the most potent substances. CONCLUSION: FMF inflicts substantial morbidity. Patients most commonly rely on NSAIDs and paracetamol to relieve symptoms of FMF bouts.