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Patients requiring re-irradiation for recurrent glioblastoma multiforme (GBM) may benefit from individualized therapy. This study aimed to identify predictors of survival and contribute to treatment personalization. In 28 patients with recurrent GBM, nine factors were analyzed for associations with survival: Main location and type of recurrence, Karnofsky performance score (KPS), age, gender, interval between primary radiotherapy and recurrence, gross total resection (GTR), equivalent dose in 2-Gy fractions (EQD2) of re-irradiation and cumulative EQD2 of primary and re-irradiation. On univariate analyses, GTR (p=0.047), EQD2 ≥30 Gy (p=0.029) and cumulative EQD2 ≥90 Gy (p=0.023) were significantly associated with better survival; frontal location (p=0.119) and KPS 80-100% (p=0.067) showed trends. In multivariate analyses, frontal location (p=0.032) and cumulative EQD2 ≥90 Gy (p=0.038) were significant; KPS 80-100% (p=0.110) and EQD2 ≥30 Gy (p=0.083) showed trends. Predictors of survival after re-irradiation for recurrent GBM were identified that can help when designing personalized treatments. Use of irradiation with EQD2 ≥30 Gy appeared superior to lower doses.

Glioblastoma multiforme (GBM) and the GBM variant gliosarcoma (GS) are among the tumors with the highest morbidity and mortality, providing only palliation. Stem-like glioma cells (SLGCs) are involved in tumor initiation, progression, therapy resistance, and relapse. The identification of general features of SLGCs could contribute to the development of more efficient therapies. Commercially available protein arrays were used to determine the cell surface signature of eight SLGC lines from GBMs, one SLGC line obtained from a xenotransplanted GBM-derived SLGC line, and three SLGC lines from GSs. By means of non-negative matrix factorization expression metaprofiles were calculated. Using the cophenetic correlation coefficient (CCC) five metaprofiles (MPs) were identified, which are characterized by specific combinations of 7–12 factors. Furthermore, the expression of several factors, that are associated with GBM prognosis, GBM subtypes, SLGC differentiation stages, or neural identity was evaluated. The investigation encompassed 24 distinct SLGC lines, four of which were derived from xenotransplanted SLGCs, and included the SLGC lines characterized by the metaprofiles. It turned out that all SLGC lines expressed the epidermal growth factor EGFR and EGFR ligands, often in the presence of additional receptor tyrosine kinases. Moreover, all SLGC lines displayed a neural signature and the IDH1 wildtype, but differed in their p53 and PTEN status. Pearson Correlation analysis identified a positive association between the pluripotency factor Sox2 and the expression of FABP7, Musashi, CD133, GFAP, but not with MGMT or Hif1α. Spherical growth, however, was positively correlated with high levels of Hif1α, CDK4, PTEN, and PDGFRβ, whereas correlations with stemness factors or MGMT (MGMT expression and promoter methylation) were low or missing. Factors highly expressed by all SLGC lines, irrespective of their degree of stemness and growth behavior, are Cathepsin-D, CD99, EMMPRIN/CD147, Intβ1, the Galectins 3 and 3b, and N-Cadherin.

BackgroundFor endovascular rescue therapy (ERT) of cerebral vasospasm (CVS) due to spontaneous subarachnoid haemorrhage (sSAH), non-compliant (NCB) and compliant (CB) balloons are used with both balloon types bearing the risk of vessel injury due to specific mechanical properties. Although severe delayed arterial narrowing after transluminal balloon angioplasty (TBA) for CVS has sporadically been described, valid data concerning incidence and relevance are missing. Our aim was to analyse the radiological follow-up (RFU) of differently TBA-treated arteries (CB or NCB).MethodsTwelve patients with utilisation of either NCB or CB for CVS were retrospectively analysed for clinical characteristics, ERT, functional outcome after 3 months and RFU. Compared with the initial angiogram, we classified delayed arterial narrowing as mild, moderate and severe (<30%, 30%–60%, respectively >60% calibre reduction).ResultsTwenty-three arteries were treated with CB, seven with NCB. The median first RFU was 11 months after TBA with CB and 10 after NCB. RFU was performed with catheter angiography in 18 arteries (78%) treated with CB and in five (71%) after NCB; magnetic resonance angiography was acquired in five vessels (22%) treated with CB and in two (29%) after NCB. Mild arterial narrowing was detected in three arteries (13%) after CB and in one (14%) after NCB. Moderate or severe findings were neither detected after use of CB nor NCB.ConclusionWe found no relevant delayed arterial narrowing after TBA for CVS after sSAH. Despite previous assumptions that CB provides for more dilatation in segments adjacent to CVS, we observed no disadvantages concerning long-term adverse effects. Our data support TBA as a low-risk treatment option.

BackgroundRecently, antibodies against the alpha isoform of the glial-fibrillary-acidic-protein (GFAPα) were identified in a small series of patients with encephalomyelitis. Coexisting autoantibodies (NMDA receptor, GAD65 antibodies) have been described in a few of these patients. We describe a patient with rapidly progressive encephalomyeloradiculitis and a combination of anti-ITPR1, anti-GFAP and anti-MOG antibodies.Case presentation and literature reviewA 44-year old caucasian woman with a flu-like prodrome presented with meningism, progressive cerebellar signs and autonomic symptoms, areflexia, quadriplegia and respiratory insufficiency. MRI showed diffuse bilateral T2w-hyperintense brain lesions in the cortex, white matter, the corpus callosum as well as a longitudinal lesion of the medulla oblongata and the entire spinal cord. Anti-ITPR1, anti-GFAP and anti-MOG antibodies were detected in cerebrospinal fluid along with lymphocytic pleocytosis. Borderline tumor of the ovary was diagnosed. Thus, the disease of the patient was deemed to be paraneoplastic. The patient was treated by surgical removal of tumor, steroids, immunoglobulins, plasma exchange and rituximab. Four months after presentation, the patient was still tetraplegic, reacted with mimic expressions to pain or touch and could phonate solitary vowels. An extensive literature research was performed.ConclusionOur case and the literature review illustrate that multiple glial and neuronal autoantibodies can co-occur, that points to a paraneoplastic etiology, above all ovarian teratoma or thymoma. Clinical manifestation can be a mixture of typically associated syndromes, e.g. ataxia associated with anti-ITPR1 antibodies, encephalomyelitis with anti-GFAPα antibodies and longitudinal extensive myelitis with anti-MOG antibodies.

Background Volatile sedation is still used with caution in patients with acute brain injury because of safety concerns. We analyzed the effects of sevoflurane sedation on systemic and cerebral parameters measured by multimodal neuromonitoring in patients after aneurysmal subarachnoid hemorrhage (aSAH) with normal baseline intracranial pressure (ICP). Methods In this prospective observational study, we analyzed a 12-h period before and after the switch from intravenous to volatile sedation with sevoflurane using the Sedaconda Anesthetic Conserving Device with a target Richmond Agitation Sedation Scale score of − 5 to − 4. ICP, cerebral perfusion pressure (CPP), brain tissue oxygenation (PBrO 2 ), metabolic values of cerebral microdialysis, systemic cardiopulmonary parameters, and the administered drugs before and after the sedation switch were analyzed. Results We included 19 patients with a median age of 61 years (range 46–78 years), 74% of whom presented with World Federation of Neurosurgical Societies grade 4 or 5 aSAH. We observed no significant changes in the mean ICP (9.3 ± 4.2 vs. 9.7 ± 4.2 mm Hg), PBrO 2 (31.0 ± 13.2 vs. 32.2 ± 12.4 mm Hg), cerebral lactate (5.0 ± 2.2 vs. 5.0 ± 1.9 mmol/L), pyruvate (136.6 ± 55.9 vs. 134.1 ± 53.6 µmol/L), and lactate/pyruvate ratio (37.4 ± 8.7 vs. 39.8 ± 9.2) after the sedation switch to sevoflurane. We found a significant decrease in mean arterial pressure (MAP) (88.6 ± 7.6 vs. 86.3 ± 5.8 mm Hg) and CPP (78.8 ± 8.5 vs. 76.6 ± 6.6 mm Hg) after the initiation of sevoflurane, but the decrease was still within the physiological range requiring no additional hemodynamic support. Conclusions Sevoflurane appears to be a feasible alternative to intravenous sedation in patients with aSAH without intracranial hypertension, as our study did not show negative effects on ICP, cerebral oxygenation, or brain metabolism. Nevertheless, the risk of a decrease of MAP leading to a consecutive CPP decrease should be considered.

Standard radiotherapy (RT) for glioblastoma lasts 6 weeks. We aimed to identify patients who would benefit from a hypofractionated approach. In 167 patients receiving standard fractionation, 10 factors were analyzed for local control (LC) and overall survival (OS). A survival score was developed and compared to a previous instrument. On multivariate analysis, better LC was significantly associated with the presence of only one lesion and O -methylguanine-DNA methyltransferase (MGMT) promoter methylation. Better OS was associated with one lesion, better performance status, MGMT promoter methylation, and receipt of chemotherapy. Lesion diameter ≤40 mm and upfront resection were associated with improved OS on univariate analyses. Based on assigning scores to these six factors, three groups, with 32-35, 36-44 and 45-48 points, were designed with 12-month OS-rates of 0%, 56%, and 92%, respectively. Accuracy in predicting death within 12 months and survival ≥12 months was 100% and 92%, respectively, versus 67% and 83% with the previous scoring system. A new survival score with higher accuracy was developed for patients with glioblastoma. Our model can be utilized to individualize RT dose-fractionation recommendations for glioblastoma.

Prone positioning (PP) is an established treatment modality for respiratory failure. After aneurysmal subarachnoid hemorrhage (aSAH), PP is rarely performed considering the risk of intracranial hypertension. The aim of this study was to analyze the effects of PP on intracranial pressure (ICP), cerebral perfusion pressure (CPP) and cerebral oxygenation following aSAH. Patients and methods: Demographic and clinical data of aSAH patients admitted over a 6-year period and treated with PP due to respiratory insufficiency were retrospectively analyzed. ICP, CPP, brain tissue oxygenation (pBrO2), respiratory parameters and ventilator settings were analyzed before and during PP. Thirty patients receiving invasive multimodal neuromonitoring were included. Overall, 97 PP sessions were performed. Mean arterial oxygenation and pBrO2 increased significantly during PP. We found a significant increase in median ICP compared to the baseline level in supine position. No significant changes in CPP were observed. Five PP sessions had to be terminated early due to medically refractory ICP-crisis. The affected patients were younger (p = 0.02) with significantly higher baseline ICP values (p = 0.009). Baseline ICP correlates significantly (p < 0.001) with ICP 1 h (R: 0.57) and 4 h (R: 0.55) after onset of PP. PP in aSAH patients with respiratory insufficiency is an effective therapeutic option improving arterial and global cerebral oxygenation without compromising CPP. The significant increase in ICP was moderate in most sessions. However, as some patients experience intolerable ICP crises during PP, continuous ICP-Monitoring is considered mandatory. Patients with elevated baseline ICP and reduced intracranial compliance should not be considered for PP. •Prone positioning improves cerebral oxygenation in SAH patients.•Prone positioning significantly increases ICP in SAH patients.•Medically refractory ICP crisis occur in about 5% of proning sessions.•‘Younger age’ might pose a risk factors for medically refractory ICP crisis.

After spontaneous subarachnoid hemorrhage (sSAH), cerebral vasospasm (CVS) is a common complication, potentially resulting in infarction mainly responsible for a poor outcome. Intra-arterial vasodilators lead to transient increase of brain perfusion, but only transluminal balloon angioplasty (TBA) promises longer-lasting effects, though it poses the risk of severe complications. Until now, the precise impact of TBA on the course of CVS is not yet finally clarified. Thus we aimed to identify risk factors of recurrent CVS and vasospasm-related infarction following TBA. We analyzed 35 patients with CVS after sSAH who received TBA (41 procedures, 99 vessel segments). Gender, age, WFNS grade and Fisher scale, occurrence of intraventricular and intracerebral hemorrhage, localization of the aneurysm and the initial treatment modality were obtained. We assessed functional outcome after 3 months and in-hospital mortality. TBA was analyzed concerning time point, localization, technique, complications and angiographic response. Furthermore, recurrence of CVS and vasospasm-related infarction after TBA were described and risk factors were identified with logistic regression analyses. In 7 of 35 patients (20%) and in 16 of 99 vessel segments (16%) previously treated with TBA, we found recurrent CVS. Vasospasm-related infarction occurred in 18 cases (18%) in the arterial territories of the TBA-treated vessel segments. The angiographic effect after TBA was mostly classified as good (87%), good response was negatively associated with recurrent CVS (p = 0.004) and vasospasm-related infarction (p = 0.001). We identified only the male gender as a risk factor for vasospasm-related infarction after TBA (p = 0.040). In connection with TBA, only one complication occurred (intracranial dissection). Our data support TBA as a safe and effective therapy for CVS. Nevertheless, recurrent CVS and vasospasm-related infarction were common after TBA and not predictable by clinical conditions on admission or the localization of CVS. A moderate or poor angiographic response after TBA was identified as a risk factor for both, recurrent CVS and vasospasm-related infarction, while male gender was associated with a higher risk of vasospasm-related infarction. Our results augment the still sparse evidence concerning optimal patient selection for this method and provide new aspects for individual therapy decisions.

In patients with recurrent glioblastoma, very little data are available regarding the prognostic value of platelet-to-lymphocyte (PLR) and neutrophil-to-lymphocyte (NLR) ratios. This study investigated potential associations between PLR or NLR and treatment outcomes. PLR and NLR at diagnosis of recurrence plus 10 additional characteristics were retrospectively analyzed for associations with progression-free survival (PFS) and overall survival (OS) in 75 patients with recurrent glioblastoma. On multivariate analyses, maximal cumulative diameter of recurrent lesion(s) <40 mm (p=0.015) and systemic therapy (p<0.001) were associated with improved PFS. On multivariate analysis of OS, improved outcomes were significantly associated with PLR ≤150 (p=0.029), maximal cumulative diameter <40 mm (p=0.030), and systemic therapy (p=0.010). In addition to other characteristics, PLR at the time of recurrence was identified as an independent predictor of OS in patients with recurrent glioblastoma. PLR may be useful when designing personalized treatment approaches or clinical trials.