Here, we report on a 28-year old male patient presenting with neck and shoulder pain, dysesthesia of all four limbs and hypesthesia of both hands, without motor deficits. Magnetic resonance imaging showed an intradural, intramedullary mass of the cervical spinal cord of 6.4 cm length and 1.7 cm diameter. The patient underwent surgical resection. Histological and immunohistochemical evaluation showed pleomorphic glial tumor cells, mitoses, calcifications, and atypical ganglioid cells compatible with the morphology of anaplastic ganglioglioma (WHO Grade III). Extensive molecular workup revealed H3F3A K27M, TERT C228T and PDGFRα Y849C mutations indicating poor prognosis. The H3F3A K27M mutation assigned the tumor to the molecular group of diffuse midline glioma (WHO Grade IV). Epigenome-wide methylation profiling confirmed the methylation class of diffuse midline glioma. Thus, this is a very rare case of malignant glioma with H3 K27M genotype phenotypically mimicking anaplastic ganglioglioma. This case emphasizes the importance of comprehensive morphological and molecular workup including methylome profiling for advanced patient care.

BackgroundPenetrating brain injury (PBI) is a heterogeneous condition with many variables. Few data exist on civilian PBI. In some publications, PBI differentiation between low-velocity injury (LVI) and high-velocity injury (HVI) is made, but exact definitions are not given yet. The incidence of PBI depends heavily on the country of origin. Furthermore, captive bolt pistol (CBP) injuries represent a rare type of LVI and almost no reports exist in the human medical literature. Treatment of PBI has been controversially discussed due to high morbidity and mortality with results varying considerably between series. Prognostic factors are of utmost importance to identify patients who presumably benefit from treatment.MethodsA retrospective, single-center analysis of a consecutive patient series was performed from September 2005 to May 2018. We included all patients with PBI who reached our hospital alive and received any neurosurgical operative procedure.ResultsOf 24 patients, 38% died, 17% had an unfavourable outcome, and 46% had a favourable outcome. In total, 58% of patients with PBI were self-inflicted. Leading causes of injury were firearms, while captive bolt pistols were responsible for 21% of injuries. LVI represented 54%, and HVI represented 46%. The outcome in HVI was significantly worse than that in LVI. A favourable outcome was achieved in 69% of LVI and 18% of HVI. Low GCS and pathological pupillary status at admission correlated significantly with an unfavourable outcome and death.ConclusionsPBI is a heterogeneous injury with many variables and major geographical and etiological differences. Differentiation between LVI and HVI is crucial for decision-making and predicting outcomes. In patients presenting with object trajectories crossing the midline, no favourable outcome could be achieved. Nevertheless, in total, a favourable outcome was possible in almost half of the patients who succeeded in surgery.

Here, we report on a patient presenting with two histopathologically distinct gliomas. At the age of 42, the patient underwent initial resection of a right temporal oligodendroglioma IDH mutated 1p/19q co-deleted WHO Grade II followed by adjuvant radiochemotherapy with temozolomide. 15 months after initial diagnosis, the patient showed right hemispheric tumor progression and an additional new left frontal contrast enhancement in the subsequent imaging. A re-resection of the right-sided tumor and resection of the left frontal tumor were conducted. Neuropathological work-up showed recurrence of the right-sided oligodendroglioma with features of an anaplastic oligodendroglioma WHO Grade III, but a glioblastoma WHO grade IV for the left frontal lesion. In depth molecular profiling revealed two independent brain tumors with distinct molecular profiles of anaplastic oligodendroglioma IDH mutated 1p/19q co-deleted WHO Grade III and glioblastoma IDH wildtype WHO grade IV. This unique and rare case of a patient with two independent brain tumors revealed by in-depth molecular work-up and epigenomic profiling emphasizes the importance of integrated work-up of brain tumors including methylome profiling for advanced patient care.

To assess the prognostic profile, clinical outcome, treatment-associated morbidity, and treatment burden of elderly patients with glioblastoma (GBM) undergoing microsurgical tumor resection as part of contemporary treatment algorithms.-METHODS: We retrospectively identified patients with GBM ‡65 years of age who were treated by resection at 2 neuro-oncology centers. Survival was assessed by Kaplan-Meier analyses; log-rank tests identified prognostic factors.-RESULTS: The study population included 160 patients (mean age, 73.1 AE 5.1 years), and the median contrastenhancing tumor volume was 31.0 cm 3 . Biomarker analyses revealed O( 6)-methylguanine-DNA methyltransferasee promoter methylation in 62.7% and wild-type isocitrate dehydrogenase in 97.5% of tumors. The median extent of resection (EOR) was 92.3%, surgical complications were noted in 10.0% of patients, and the median postoperative hospitalization period was 8 days. Most patients (60.0%) received adjuvant radio-/chemotherapy. The overall treatment-associated morbidity was 30.6%. The median progression-free and overall survival were 5.4 months (95% confidence interval [CI], 4.6e6.4 months) and 10.0 months (95% CI, 7.9e11.7 months). The strongest predictors for favorable outcome were patient age £73.0 years (P [ 0.0083), preoperative Karnofsky Performance Status Scale score ‡80% (P [ 0.0179), postoperative modified Rankin Scale score £1 (P < 0.0001), adjuvant treatment (P < 0.0001), and no treatmentassociated morbidity (P [ 0.0478). Increased EOR did not correlate with survival (P [ 0.5046), but correlated significantly with treatment-associated morbidity (P [ 0.0031).-CONCLUSIONS: Clinical outcome for elderly patients with GBM remains limited. Nonetheless, the observed treatment-associated morbidity and treatment burden were moderate in the patients, and patient age and performance status remained the strongest predictors for survival. The risks and benefits of tumor resection in the age of Key words -Adjuvant treatment -Biomarker -Elderly -Glioblastoma multiforme -Outcome -Resection -Treatment-associated morbidity

IntroductionLocal treatment concepts are in high demand in the salvage treatment of recurrent brain metastases. Still, their risks and benefits are scarcely characterized. In this study, we analyzed the outcome and risk-/benefit-ratio of salvage CyberKnife (Accuray Incorporated, Sunnyvale, California, US) radiosurgery in the treatment of recurrent brain metastases after whole brain radiotherapy (WBRT).Materials and methodsSeventy-six patients with 166 recurrent brain metastases and a multimodal pretreatment were retrospectively investigated. All patients underwent salvage CyberKnife radiosurgery (single fraction, reference dose: 17-22 Gy). Study endpoints were post-recurrence survival (PRS) after salvage treatment as well as local and distant tumor control rates. Central nervous system (CNS) toxicity was assessed according to the toxicity criteria of the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer (RTOG/EORTC)).ResultsThe population was homogenous regarding its demographic parameters. All patients had a history of WBRT prior to salvage CyberKnife radiosurgery. PRS was 13.3 months (10.4 - 16.2 months), one-year local and distant tumor control rates were 87% (95% CI: 75-99) and 38% (95% CI: 23-52), respectively. Eighteen patients suffered from RTOG/EORTC grade I/II toxicity. No toxicity-related risk factors were identified.DiscussionThis study found indicative survival and tumor control rates as well as a favorable risk/benefit ratio regarding radiotoxicity in salvage CyberKnife radiosurgery. These results point to a proactive therapeutic strategy based on appropriate patient selection instead of therapeutic nihilism.

Background The rate of intracranial aneurysm remnants/recurrences after microsurgical clipping varies widely. The optimal management for these patients remains a matter of debate. Repeat surgery in particular bears a high risk of periprocedural complications due to anatomical distortion from prior procedures. This study aims to evaluate the risk–benefit profile of flow-diverter stents in these patients. Methods The patient database of our neurovascular centre was queried to identify patients with clipped aneurysms who subsequently underwent endovascular treatment with intraluminal flow-diverter stents. The outcome analysis consisted of an assessment of clinical parameters (modified Rankin scale) and the post-interventional angiographic occlusion status (according to the Raymond–Roy occlusion classification). Results Six patients underwent endovascular treatment with flow-diverter stents of recurrent aneurysms after clipping. Treatment was necessary in two patients due to progressive neurological deficits, and due to angiographic proof of an increasing aneurysm size in the other four patients. Median aneurysm size was 0.45 cm. All patients had a prior history of subarachnoid haemorrhage. The time from primary clipping to recurrence was 10.6 years. Complete radiological aneurysm occlusion was feasible in five out of six cases. Two patients who had experienced pre-interventional neurological deficits showed a complete remission of symptoms on last follow-up. No periprocedural morbidity or mortality was recorded and no patient required retreatment within the median follow-up. Conclusion This case series suggests that endovascular treatment with flow-diverter stents of aneurysm remnants after previous microsurgical clipping is a feasible treatment concept with a low-risk profile, which might prevent the treatment burden and risks of repeat surgery.

Background Stereoelectroencephalography (SEEG) allows the identification of deep-seated seizure foci and determination of the epileptogenic zone (EZ) in drug-resistant epilepsy (DRE) patients. We evaluated the accuracy and treatment-associated morbidity of frameless VarioGuide® (VG) neuronavigation-guided depth electrode (DE) implantations. Methods We retrospectively identified all consecutive adult DRE patients, who underwent VG-neuronavigation DE implantations, between March 2013 and April 2019. Clinical data were extracted from the electronic patient charts. An interdisciplinary team agreed upon all treatment decisions. We performed trajectory planning with iPlan® Cranial software and DE implantations with the VG system. Each electrode’s accuracy was assessed at the entry (EP), the centre (CP) and the target point (TP). We conducted correlation analyses to identify factors associated with accuracy. Results The study population comprised 17 patients (10 women) with a median age of 32.0 years (range 21.0–54.0). In total, 220 DEs (median length 49.3 mm, range 25.1–93.8) were implanted in 21 SEEG procedures (range 3–16 DEs/surgery). Adequate signals for postoperative SEEG were detected for all but one implanted DEs (99.5%); in 15/17 (88.2%) patients, the EZ was identified and 8/17 (47.1%) eventually underwent focus resection. The mean deviations were 3.2 ± 2.4 mm for EP, 3.0 ± 2.2 mm for CP and 2.7 ± 2.0 mm for TP. One patient suffered from postoperative SEEG-associated morbidity (i.e. conservatively treated delayed bacterial meningitis). No mortality or new neurological deficits were recorded. Conclusions The accuracy of VG-SEEG proved sufficient to identify EZ in DRE patients and associated with a good risk-profile. It is a viable and safe alternative to frame-based or robotic systems.

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