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Trapped or isolated fourth ventricle (TFV) is a rare but critical neurosurgical condition, mostly occurring in pediatric patients, caused by a blockage of the in- and outlets of the fourth ventricle. The purpose of this study is to review all available data on the treatment options of TFV and to compare their safety, efficacy, and durability. MEDLINE, Embase, and Google Scholar were searched from inception to September 13, 2022, for prospective or retrospective cohorts, case-control studies, case series or case reports, reporting detailing outcomes of TFV patients, treated with an endoscopic-, microsurgical-, shunt placement,- or hybrid approaches to TFV. All authors were contacted to provide individual patient data. Eighty-seven articles (314 patients) were included in the individual patient data meta-analysis (IPD) and 9 (151 patients) in the cohort meta-analysis. The IPD revealed that primary endoscopic (aOR 0.21; [95% CI 0.08–0.57]) and microsurgical interventions (aOR 0.21; [95% CI 0.05–0.82]) were associated with a significantly lower revision rate, compared to shunt placement, when adjusted for confounders. Endoscopy was also associated with a significantly higher rate of clinical improvement (aOR 4.56; [95% CI 1.2–18]). The meta-analysis revealed no significant difference in revision rate between the endoscopic (0.33 [95% CI 0.0–0.52]) and shunt group (0.44 [95% CI 0.0–1.0]). Endoscopy should be considered as the first-line treatment of TFV due to its superior efficacy, durability, and similar safety, compared to shunt placement and its minimally invasive nature. Microsurgery should be considered as a second treatment option, due to its similar clinical outcomes and revision rate as endoscopy, but it is more invasive in nature.

OBJECTIVE: To develop a realistic simulation model for laparotomy-assisted fetoscopic spina bifida aperta (SBa) surgery, to be used for training purposes and preoperative planning.METHODS: The predefined general requirement was a realistic model of an exteriorized uterus, allowing all neurosurgical steps of the intervention. The uterus was modelled using ultrasound and MRI images of a 25 weeks' gravid uterus, consisting of flexible polyurethane foam coated with pigmented silicone. The fetal model, contained an opening on the dorsal side for a customizable spinal insert with all the aspects of a SBa, including a cele, placode, and myofascial and skin layer. The model was assessed in a series of validation experiments.RESULTS: Production costs are low, uterus and fetus are reusable. Placental localization and the level and size of the spinal defect are adjustable, enabling case-specific adaptations. All aspects of the simulator were scored close to realistic or higher for both appearance and functional capacities.CONCLUSIONS: This innovative model provides an excellent training opportunity for centers that are starting a fetoscopic SBa repair program. It is the first simulation model with adjustable spinal defect and placental localisation. Further objective validation is required, but the potential for using this model in preoperative planning is promising.

Since the completion of the Management of Myelomeningocoele Study, maternal‐fetal surgery for spina bifida has become a valid option for expecting parents. More recently, multiple groups are exploring a minimally invasive approach and recent outcomes have addressed many of the initial concerns with this approach. Based on a previously published framework, we attempt to delineate the developmental stage of the surgical techniques. Furthermore, we discuss the barriers of performing randomized controlled trials comparing two surgical interventions and suggest that data collection through registries is an alternative method to gather high‐grade evidence., Key Points What's already known about this topic? The use of fetoscopy for spina bifida repair is adopted by an increasing number of centers worldwide. On the other hand, its efficacy has not been established within a randomized controlled trial and thus it is still considered experimental by others. What does this study add? Herein we describe a framework which could be used to determine the developmental stage of novel interventions in the field of maternal‐fetal surgery. Furthermore, we discuss the difficulties of gathering high level evidence for a fetoscopic closure of the spinal defect in fetuses with a spina bifida.

OBJECTIVE Ten years ago, the authors reported on the outcome of their study investigating the degree of discomfort and pain in newborns with myelomeningocele (MMC), using the parameters of unbearable and hopeless suffering. In the current study, they investigated the quality of life, daily functioning, pain and fatigue, ability to communicate, and number of surgeries in the same cohort of patients. They subdivided their study population into severe (Lorber) and less severe (non-Lorber) cases and compared these cases with a healthy population (non-MMC group) and with each other. METHODS The parents of 22 of 28 patients gave informed consent for this study. The KIDSCREEN-27 and PEDI-CAT (Pediatric Evaluation of Disability Inventory) were used to assess quality of life and daily functioning. Pain and fatigue were self-reported on a 10-point numeric rating scale. Communication and ambulation levels were determined using the Communication Function Classification System (CFCS) and the Hoffer ambulation scale. Using reference data from the KIDSCREEN-27 and PEDI-CAT, the authors created a healthy population comparison group. RESULTS There was no significant difference in health-related quality-of-life (HRQOL) scores between Lorber and non-Lorber patients, except that school environment domain scores were lower in the Lorber group. When comparing the HRQOL of MMC patients with that of the non-MMC group, the physical well-being and parent relations and autonomy domains scored significantly lower. The daily functioning of MMC patients was lower on all domains of the PEDI-CAT compared with the non-MMC group. Lorber MMC patients scored lower on all domains of the PEDI-CAT when compared with non-Lorber patients. All patients were capable of communicating effectively; most patients (n = 18) were considered CFCS level I, and 4 patients were considered CFCS level II. CONCLUSIONS This study shows that MMC is a severe, lifelong condition that affects patients’ lives in many domains. All the patients in this study are capable of effective communication, irrespective of severity of MMC. Overall, the data show that in newborn MMC patients, future unbearable suffering with respect to pain, mobility, cognition, and communication is hard to predict and may not always occur.

OBJECTIVEIntracranial hypertension is a major concern in children with syndromic craniosynostosis (sCS). Cerebral venous hypertension caused by cerebral venous outflow obstruction is believed to contribute to intracranial hypertension. The authors therefore hypothesized that cerebral venous volume would be increased in those children with sCS and intracranial hypertension.METHODSIn a case series of 105 children with sCS, of whom 32 had intracranial hypertension, cerebral MRI techniques were used to quantify the volume of the superior sagittal sinus, straight sinus (StrS), and both transverse sinuses.RESULTSLinear regression showed that total cerebral venous volume increased by 580.8 mm3 per cm increase in occipitofrontal head circumference (p < 0.001). No significant difference was found between the intracranial hypertension group and the nonintracranial hypertension group (p = 0.470). Multivariate ANOVA showed increased StrS volume (as a proportion of total volume) in the intracranial hypertension group (8.5% vs 5.1% in the nonintracranial hypertension group, p < 0.001). Multivariate logistic regression showed that a 100-mm3 increase in StrS volume is associated with increased odds of having intracranial hypertension by 60% (OR 1.60, 95% CI 1.24–2.08).CONCLUSIONSAlthough intracranial hypertension was not associated with total cerebral venous volume increase, it was associated with an isolated increase in StrS volume. Hence, it is unlikely that general cerebral venous outflow obstruction is the mechanism of intracranial hypertension in sCS. Rather, these findings indicate either a central cerebral vulnerability to intracranial hypertension or a mechanism involving venous blood redistribution.

BACKGROUND Although prognosis is poor in high-grade glioma (HGG) patients, some become a long-term survivor (LTS). Health-related quality of life (HRQOL) and cognition are seen as indicators for quality of survival in HGG but data in LTS and their caregivers are scarce. We aim to investigate cognition and HRQOL in LTS with evaluation by their proxies. MATERIAL AND METHODS We included LTS with initial HGG-diagnosis between 1999–2014. Cognition was assessed with: Boston Naming Test, shortened Token Test, verbal (Category and Letter) Fluency, Diagnostic Instrument of Mild Aphasia, Hopkins Verbal Learning Test and Trail Making Test (A, B, B/A) and HRQOL with: EORTC Quality of Life Questionnaire (C30) and Brain Cancer Module (BN20). 15 Proxies evaluated patients’ HRQOL with: C30, BN20 and they filled in a burden scale: Caregiver Strain Index (CSI). RESULTS 21 patients with grade III or IV glioma and 7 years (range 5–20 years) median survival after diagnosis participated. Compared to normative data patients deviated significantly on HVLT (direct recall, delayed recall, recognition true positives), TMT (A, B and B/A), BNT and CF (p12 years survival compared to patients with CONCLUSION Most LTS suffer from cognitive impairments. Despite worse prognosis and cognitive impairments, at group level patients report relatively intact QoL, which is supported by their proxies. However, at the individual level severity of impairments is variable and high caregiver strain is reported in one-third of the proxies. Objective cognitive functioning was only modestly associated with subjective experience in patients. A patient-tailored approach is recommended to investigate individual impairments and needs for rehabilitation and support for patients and also for their carers.

COVID-19 patients commonly present with neurological signs of central nervous system (CNS) and/or peripheral nervous system dysfunction. However, which neural cells are permissive to infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been controversial. Here, we show that midbrain dopamine (DA) neurons derived from human pluripotent stem cells (hPSCs) are selectively permissive to SARS-CoV-2 infection both in vitro and upon transplantation in vivo, and that SARS-CoV-2 infection triggers a DA neuron inflammatory and cellular senescence response. A high-throughput screen in hPSC-derived DA neurons identified several FDA approved drugs, including riluzole, metformin, and imatinib, that can rescue the cellular senescence phenotype and prevent SARS-CoV-2 infection. RNA-seq analysis of human ventral midbrain tissue from COVID-19 patients, using formalin-fixed paraffin-embedded autopsy samples, confirmed the induction of an inflammatory and cellular senescence signature and identified low levels of SARS-CoV-2 transcripts. Our findings demonstrate that hPSC-derived DA neurons can serve as a disease model to study neuronal susceptibility to SARS-CoV-2 and to identify candidate neuroprotective drugs for COVID-19 patients. The susceptibility of hPSC-derived DA neurons to SARS-CoV-2 and the observed inflammatory and senescence transcriptional responses suggest the need for careful, long-term monitoring of neurological problems in COVID-19 patients.

Summary Background The aim of this study is to identify if certain types of craniosynostosis and/or surgical procedures are more likely to require a secondary intracranial procedure because of insufficient correction of skull shape or raised ICP after initial surgery. Methods All consecutive cases with craniosynostosis that were operated at our center between January 2010 and January 2019 were included and the number of secondary operations of the vault were determined, as well as diagnosis, the indication and type and timing of initial surgery. Monobloc and facial bipartition procedures were excluded. Results Over a nine year period, 790 vault corrections were performed in 780 patients of which 38 procedures were reoperations in 35 patient because of raised intracranial pressure or an insufficient esthetic result of the skull shape. Particularly patients with a multisutural or syndromic craniosynostosis are represented in this group, as well as three surgical procedures: 1. biparietal outfracturing for sagittal synostosis; 2. endoscopic stripcraniectomy with helmet therapy for unicoronal, multisutural or syndromic craniosynostosis; 3. conventional occipital expansion for syndromic craniosynostosis. Conclusions The risk of a second intracranial correction for insufficient outcome of skull shape or for raised ICP is related to type of synostosis and type of initial surgical technique. Particularly multisutural and syndromic craniosynostosis are more likely to require repeat surgery for these indications. Concerning initial technique, biparietal outfracturing does not correct sagittal synostosis sufficiently, stripcraniectomy with helmet therapy appears to undercorrect unicoronal, multisutural and syndromic synostosis, and conventional occipital expansion for multisutural and syndromic synostosis has poorer outcome than occipital expansion with distraction.

Objective The aim of this work is to define competencies and entrustable professional activities (EPAs) to be imparted within the framework of surgical neuro-oncological residency and fellowship training as well as the education of medical students. Improved and specific training in surgical neuro-oncology promotes neuro-oncological expertise, quality of surgical neuro-oncological treatment and may also contribute to further development of neuro-oncological techniques and treatment protocols. Specific curricula for a surgical neuro-oncologic education have not yet been established. Methods We used a consensus-building approach to propose skills, competencies and EPAs to be imparted within the framework of surgical neuro-oncological training. We developed competencies and EPAs suitable for training in surgical neuro-oncology. Result In total, 70 competencies and 8 EPAs for training in surgical neuro-oncology were proposed. EPAs were defined for the management of the deteriorating patient, the management of patients with the diagnosis of a brain tumour, tumour-based resections, function-based surgical resections of brain tumours, the postoperative management of patients, the collaboration as a member of an interdisciplinary and/or -professional team and finally for the care of palliative and dying patients and their families. Conclusions and Relevance The present work should subsequently initiate a discussion about the proposed competencies and EPAs and, together with the following discussion, contribute to the creation of new training concepts in surgical neuro-oncology.

OBJECTIVENeurosurgery is historically seen as a high-risk medical specialty, with a large percentage of neurosurgeons facing complaints during their careers. The Dutch medicolegal system is characterized by a strong emphasis on informal mediation, which can be accompanied or followed by disciplinary actions. To determine if this system is associated with a low overall risk for medical litigation through disciplinary law, the authors conducted a review of disciplinary cases involving neurosurgeons in the Netherlands.METHODSThe authors reviewed legal cases that had been filed against consultant neurosurgeons and neurosurgical residents under the Dutch disciplinary law for medical professions between 2009 and 2019.RESULTSA total of 1322 neurosurgical care–related cases from 2009 to 2019 were reviewed. Fifty-seven (4.3%) cases were filed against neurosurgeons (40 first-instance cases, 17 appeal cases). In total, 123 complaints were filed in the 40 first-instance cases. Most of these cases were related to spine surgery (62.5%), followed by cranial surgery (27.5%), peripheral nerve surgery (7.5%), and pediatric neurosurgery (2.5%). Complaints were filed in all stages of care but were mostly related to preoperative and intraoperative care.CONCLUSIONSThe risk for medically related litigation in neurosurgery in the Netherlands through disciplinary law is low but not negligible. Although the absolute number of cases is low, spinal neurosurgery was found to be a risk factor for complaints. The relatively high number of cases that involved the sharing of information suggests that specific improvements—focusing on communication—can be made in order to lower the risk for future litigation.

Objectives: Lennox-Gastaut syndrome (LGS) is among the most severe epileptic and developmental encephalopathies. A meta-analysis was performed to evaluate the effectiveness of adjunctive vagus nerve stimulation (VNS Therapy) in patients with LGS. Materials & Methods: PubMed database was queried (January 1997 to September 2018) to identify publications reporting on the efficacy of VNS Therapy in patients with LGS, with or without safety findings. Primary endpoint of the meta-analysis was the proportion of responders (≥50% reduction in seizure frequency). Random-effects analysis was used to calculate weighted mean estimates and confidence intervals. Heterogeneity was evaluated by statistical tests including I2. Results: Of 2752 citations reviewed, 17 articles (480 patients) were eligible including 10 retrospective studies and seven prospective studies. A random-effects model produced a pooled proportion of 54% (95% confidence intervals [CI]: 45%, 64%) of patients with LGS who responded to adjunctive VNS Therapy (p for heterogeneity

The authors describe spontaneous externalization of a ventriculo-peritoneal shunt through the navel.

Introduction Sudden unexpected death in patients with epilepsy (SUDEP) remains a poorly understood entity, and it is unclear whether the same pathomechanisms underlie all sudden deaths occurring in patients with epilepsy. One aspect not included in current models of SUDEP is the role of increased intracranial pressure (ICP) which can be observed immediately upon seizure activity in neurosurgical practice. Methods We conducted a systematic review of the occurrence of edema in patients with epilepsy reported to have died of sudden death who underwent brain autopsy or postmortem brain imaging and discuss how increased ICP may contribute to clinical features of SUDEP. Results 19 eligible studies comprising a total of 623 patients were identified. Edema—mostly mild or moderate—was reported in 17% of cases and 74% of studies. 1% (n = 6) of the overall cases were clearly identified as having Dravet syndrome or an SCN1A mutation. In these patients, edema was found in 4 (67%) of cases. Conclusion Edema is regularly found in patients with epilepsy classified to have died from SUDEP. We argue that seizures preceding SUDEP may in certain cases elicit acute edema which may represent an additional contributing factor in the cascade of events leading to sudden death of patients with epilepsy. Furthermore, we hypothesize that mild edema may especially progress to severe edema in patients with sodium channel mutations which may represent an important mechanism to investigate in the context of understanding the significantly elevated risk of SUDEP in patients with SCN1A mutations., Seizures may in certain cases elicit acute edema which may represent an additional contributing factor in the cascade of events leading to SUDEP. We hypothesize that mild edema may especially progress to severe edema in certain patients e.g. those with sodium channel mutations which may represent an important mechanism to investigate in the context of understanding the significantly elevated risk of SUDEP in patients with SCN1A mutations.

To act or not to act? Developments in prenatal and postnatal care for children with spina bifida aperta Until the middle of the twentieth century, newborns with spina bifida aperta had low chances of survival. Advances in the treatment of hydrocephalus, among other conditions, led to increased chances of survival during the 1960s. This also revealed the downsides of the treatment of spina bifida patients since some considered the quality of life of a number of these patients to be unacceptable. But withholding treatment also had negative consequences, leading to an ethical deadlock. Over the past thirty years - besides postnatal closure of the neural tube defect - more emphasis has been put on selective pregnancy termination and sporadic active termination of life in newborns with very severe forms of spina bifida. At the same time, new treatment strategies, such as foetal surgery, are being developed. With this historical overview, we illustrate the way in which technological developments and ethical dilemmas are constantly affecting each other.

The aim of this study was to report on a single center’s experience with spring-assisted cranial vault expansion (SAE) in patients with Crouzon syndrome and sagittal suture synostosis. Strip craniotomy with SAE has resulted in successful outcomes with low complication and revision rates in patients with isolated scaphocephaly. However, recent experience suggests that outcomes in patients with Crouzon syndrome and sagittal synostosis (SS) who undergo SAE are less favorable compared with the outcomes of those who undergo frontobiparietal (FBP) expansion. The authors reviewed both operations performed at a single center and noticed an upward expansion of the skull, which may be related to ventriculomegaly, with concurrent intracranial hypertension and poor aesthetic outcome. All patients diagnosed with Crouzon syndrome and SS who were treated with SAE required a revision FBP operation. Based on this outcome, the authors consider Crouzon syndrome a contraindication for correcting SS with springs.

Highlights • Analysis of 705 and 1410 DRE patients with and without LGS later treated with VNS. • 40% of LGS-DRE patients had polypharmacy with 3 antiseizure medications. • 42% of e non-LGS-DRE patients had polypharmacy with 2 antiseizure medications. • Monthly seizure counts were similar within the two groups regardless of how many ASMs were being taken. • Median total monthly seizure frequency in the LGS-DRE group was more than double. • Bilateral tonic clonic seizure were the main contributor to the higher seizure frequency., Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy but there is limited literature characterizing the disease burden despite this being crucial for disease management strategies, and for designing and interpreting clinical trials. We searched the Vagus Nerve Stimulation (VNS) Therapy Patient Outcome Registry including over 7000 patients with drug‑resistant epilepsy (DRE). Propensity Score Matching (PSM) matched LGS-DRE patients and non-LGS-DRE patients and frequencies of individual seizure types were assessed. The PSM population included 705 and 1410 DRE patients with and without LGS. 40% of the LGS-DRE group had polypharmacy with 3 antiseizure medications (ASM) while 42% in non-LGS-DRE had polypharmacy with 2 ASMs. Median total monthly seizure frequency was over double in the LGS group: 90 (IQR, 28–312) versus 40 (IQR, 10–150); p

// Subramanian Venkatesan 1 , Marlous Hoogstraat 2, 3 , Ester Caljouw 4 , Tessa Pierson 1 , Jochem K.H. Spoor 1 , Lona Zeneyedpour 5 , Hendrikus J. Dubbink 6 , Lennard J. Dekker 5 , Marielle van der Kaaij 1 , Jenneke Kloezeman 1 , Lotte M.E. Berghauser Pont 1 , Nicolle J.M. Besselink 2, 3, 7 , Theo M. Luider 5 , Jos Joore 4 , John W. Martens 8, 9 , Martine L.M. Lamfers 1 , Stefan Sleijfer 3, 8, 9 , Sieger Leenstra 1, 10 1 Department of Neurosurgery, Brain Tumor Center Erasmus MC, Rotterdam, The Netherlands 2 Department of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands 3 Center for Personalized Cancer Treatment (CPCT), University Medical Center Utrecht, Utrecht, The Netherlands 4 Pepscope BV, Utrecht, The Netherlands 5 Department of Neurology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands 6 Department of Pathology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands 7 Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands 8 Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands 9 Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Rotterdam, The Netherlands 10 Department of Neurosurgery, St. Elisabeth Hospital Tilburg, Tilburg, The Netherlands Correspondence to: Sieger Leenstra, email: s.leenstra@erasmusmc.nl Keywords: brain tumor, personalized medicine, genetic biomarkers, small molecule kinase inhibitors, resistance Received: January 11, 2016 Accepted: July 26, 2016 Published: August 11, 2016 ABSTRACT Background: Glioblastoma is the most malignant tumor of the central nervous system and still lacks effective treatment. This study explores mutational biomarkers of 11 drugs targeting either the RTK/Ras/PI3K, the p53 or the Rb pathway using 25 patient-derived glioblastoma stem-like cell cultures (GSCs). Results: We found that TP53 mutated GSCs were approximately 3.5 fold more sensitive to dual inhibition of mammalian target of rapamycin complex 1 and 2 (mTORC1/2) compared to wild type GSCs. We identified that Bcl-2(Thr56/Ser70) phosphorylation contributed to the resistance of TP53 wild type GSCs against dual mTORC1/2 inhibition. The Bcl-2 inhibitor ABT-263 (navitoclax) increased sensitivity to the mTORC1/2 inhibitor AZD8055 in TP53 wild type GSCs, while sensitivity to AZD8055 in TP53 mutated GSCs remained unchanged. Conclusion: Our data suggest that Bcl-2 confers resistance to mTORC1/2 inhibitors in TP53 wild type GSCs and that combined inhibition of both mTORC1/2 and Bcl-2 is worthwhile to explore further in TP53 wild type glioblastomas, whereas in TP53 mutated glioblastomas dual mTORC1/2 inhibitors should be explored.

OBJECTIVEThe health care costs for instrumented spine surgery have increased dramatically in the last few decades. The authors present a novel noninstrumented surgical approach for patients with isthmic spondylolisthesis, with clinical and radiographic results.METHODSCharts of patients who underwent this technique were reviewed. The procedure consisted of nerve root decompression by reconstruction of the intervertebral foramen. This was achieved by removal of the pedicle followed by noninstrumented posterolateral fusion in which autologous bone graft from the right iliac crest was used. Outcomes regarding radicular complaints, bony fusion, progression of the slip, and complications were evaluated using patient history and radiographs obtained at follow-up intervals of 3–18 months after surgery.RESULTSA total of 58 patients with a mean age of 47 years were treated with this method. Partial removal of the pedicle was performed in 93.1% of the cases, whereas in 6.9% of the cases the entire pedicle was removed. The mean duration of surgery was 216.5 ± 54.5 minutes (range 91–340 minutes). The mean (± SD) duration of hospitalization was 10.1 ± 2.9 days (range 5–18 days).After 3 months of follow-up, 86% of the patients reported no leg pain, and this dropped to 81% at last follow-up. Radiographic follow-up showed bony fusion in 87.7% of the patients. At 1 year, 5 patients showed progression of the slip, which in 1 patient prompted a second operation within 1 year. No major complications occurred.CONCLUSIONSTreatment of isthmic spondylolisthesis by reconstruction of the intervertebral neuroforamen and posterolateral fusion in situ is a safe procedure and has comparable results with the existing techniques. Cost-effectiveness research comparing this technique to conventional instrumented fusion techniques is necessary to evaluate the merits for both patients and society.

Glioblastoma has shown resistance to histone deacetylase inhibitors (HDACi) as radiosensitizers in cultures with Bcl-XL over-expression. We study the efficacy of SAHA/RTx and LBH589/RTx when manipulating Bcl-2 family proteins using the Bcl- 2 inhibitor Obatoclax in patient-derived glioblastoma stem-like cell (GSC) cultures. GSC cultures in general have a deletion in phosphatase and tensin homolog (PTEN). Synergy was determined by the Chou Talalay method. The effects on apoptosis and autophagy were studied by measuring caspase-3/7, Bcl-XL, Mcl-1 and LC3BI/ II proteins. The relation between treatment response and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, recurrence and gene expression levels of the tumors were studied. Obatoclax synergized with SAHA and LBH589 and sensitized cells to HDACi/RTx. Over 50% of GSC cultures were responsive to Obatoclax with either single agent. Combined with HDACi/RTx treatment, Obatoclax increased caspase-3/7 and inhibited Bcl-2 family proteins Bcl-XL and Mcl-1 more effectively than other treatments. Genes predictive for treatment response were identified, including the F-box/WD repeat-containing protein-7, which was previously related to Bcl-2 inhibition and HDACi sensitivity. We emphasize the functional relation between Bcl-2 proteins and radiosensitization by HDACi and provide a target for increasing responsiveness in glioblastoma by using the Bcl-2 inhibitor Obatoclax.

Calcification of the ligamentum flavum (CLF) can cause myelopathy due to spinal cord compression. Only several cases in Caucasian patients have been described. Neurological deterioration can only be stopped by surgical decompression. We report a 63-year-old Caucasian woman presenting with progressive pins-and-needles sensations in both hands, worsened by painful paresthesia in both lower extremities. MRI showed a dorsal compressive mass extending from C2 to Th3 vertebrae with myelopathy at the level of C6. A laminectomy was performed, which improved clinical symptoms. Histological examination showed CLF. Early recognition of CLF and early spinal cord decompression are needed to improve neurological outcome.

Background The out-of-body experience (OBE), during which a person feels as if he or she is spatially removed from the physical body, is a mystical phenomenon because of its association with near-death experiences. Literature implicates the cortex at the temporoparietal junction (TPJ) as the possible anatomic substrate for OBE. Case Description We present a patient who had an out-of-body experience during an awake craniotomy for resection of low-grade glioma. During surgery, stimulation of subcortical white matter in the left TPJ repetitively induced OBEs, in which the patient felt as if she was floating above the operating table looking down on herself. Conclusions We repetitively induced OBE by subcortical stimulation near the left TPJ during awake craniotomy. Diffusion tensor imaging tractography implicated the posterior thalamic radiation as a possible substrate for autoscopic phenomena.