Hypnosis-Assisted Awake Craniotomy for Eloquent Brain Tumors: Advantages and Pitfalls.

BACKGROUND: Awake craniotomy (AC) is recommended for the resection of tumors in eloquent areas. It is traditionally performed under monitored anesthesia care (MAC), which relies on hypnotics and opioids. Hypnosis-assisted AC (HAAC) is an emerging technique that aims to provide psychological support while reducing the need for pharmacological sedation and analgesia. We aimed to compare the characteristics and outcomes of patients who underwent AC under HAAC or MAC. METHODS: We retrospectively analyzed the clinical, anesthetic, surgical, and neuropsychological data of patients who underwent awake surgical resection of eloquent brain tumors under HAAC or MAC. We used Mann-Whitney U tests, Wilcoxon signed-rank tests, and repeated-measures analyses of variance to identify statistically significant differences at the 0.05 level. RESULTS: A total of 22 patients were analyzed, 14 in the HAAC group and 8 in the MAC group. Demographic, radiological, and surgical characteristics as well as postoperative outcomes were similar. Patients in the HAAC group received less remifentanil (p = 0.047) and propofol (p = 0.002), but more dexmedetomidine (p = 0.025). None of them received ketamine as a rescue analgesic. Although patients in the HAAC group experienced higher levels of perioperative pain (p < 0.05), they reported decreasing stress levels (p = 0.04) and greater levels of satisfaction (p = 0.02). CONCLUSION: HAAC is a safe alternative to MAC as it reduces perioperative stress and increases overall satisfaction. Further research is necessary to assess whether hypnosis is clinically beneficial.

Cisternal nicardipine for prevention of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a comparative retrospective cohort study.

PURPOSE: Intrathecal vasoactive drugs have been proposed in patients with aneurysmal subarachnoid hemorrhage (aSAH) to manage cerebral vasospasm (CV). We analyzed the efficacy of intracisternal nicardipine compared to intraventricular administration to a control group (CG) to determine its impact on delayed cerebral ischemia (DCI) and functional outcomes. Secondary outcomes included the need for intra-arterial angioplasties and the safety profile. METHODS: We performed a retrospective analysis of prospectively collected data of all adult patients admitted for a high modified Fisher grade aSAH between January 2015 and April 2022. All patients with significant radiological CV were included. Three groups of patients were defined based on the CV management: cisternal nicardipine (CN), ventricular nicardipine (VN), and no intrathecal nicardipine (control group). RESULTS: Seventy patients met the inclusion criteria. Eleven patients received intracisternal nicardipine, 18 intraventricular nicardipine, and 41 belonged to the control group. No cases of DCI were observed in the CN group (p = 0.02). Patients with intracisternal nicardipine had a reduced number of intra-arterial angioplasties when compared to the control group (p = 0.03). The safety profile analysis showed no difference in complications across the three groups. Intrathecal (ventricular or cisternal) nicardipine therapy improved functional outcomes at 6 months (p = 0.04) when compared to the control group. CONCLUSION: Administration of intrathecal nicardipine for moderate to severe CV reduces the rate of DCI and improved long-term functional outcomes in patients with high modified Fisher grade aSAH. This study also showed a relative benefit of cisternal over intraventricular nicardipine, thereby reducing the number of angioplasties performed in the post-treatment phase. However, these preliminary results should be confirmed with future prospective studies.

Anterior Petrosectomy With Intertentorial Approach.

BACKGROUND AND OBJECTIVES: The extradural anterior petrosal approach (EAPA) can present a challenge because it deals with critical structures in a narrow, confined corridor. It is associated with several potential approach-related risks including temporal lobe and venous injuries. Tentorial peeling has the potential to largely eliminate these risks during the approach and may offer more options for tailoring the dural opening to the anatomic region that one wants to expose. METHODS: Anatomic dissections of five adult injected non-formalin-fixed cadaveric heads were performed. Anterior petrosectomy with intertentorial approach (APIA) through a tentorial peeling was completed. Step-by-step documentation of the cadaveric dissections and diagrammatic representations are presented along with an illustrative case. RESULTS: Tentorial peeling separates the tentorium into a temporal tentorial leaf and posterior fossa tentorial leaf, adding a fourth dural layer to the three classic ones described during a standard EAPA. This opens out the intertentorial space and offers more options for tailoring the dural incisions specific to the pathology being treated. This represents a unique possibility to address brainstem or skull base pathology along the mid- and upper clivus with the ability to keep the entire temporal lobe and basal temporal veins covered by the temporal tentorial leaf. The APIA was successfully used for the resection of a large clival chordoma in the illustrative case. CONCLUSION: APIA is an interesting modification to the classic EAPA to reduce the approach-related morbidity. The risk reduction achieved is by eliminating the exposure of the temporal lobe while maintaining the excellent access to the petroclival region. It also provides several options to tailor the durotomies based on the localization of the lesion.

The Enhanced Recovery After Surgery protocol for the perioperative management of pituitary neuroendocrine tumors/pituitary adenomas.

OBJECTIVE: Enhanced Recovery After Surgery (ERAS) is a multimodal perioperative care pathway that has radically modified the management of patients in multiple surgical specialties. Until now, no ERAS Society guidelines have been formulated for the management of cranial pathologies. During the process of ERAS certification for their neurosurgical department, the authors formulated an ERAS protocol for the perioperative care of patients with pituitary neuroendocrine tumors (PitNET), along with a compliance checklist to monitor the adherence to it and its feasibility. The authors describe the protocol and checklist and report the results, including a cost-minimization analysis, with the application of the ERAS philosophy. METHODS: The steps that led to the development of this ERAS protocol, including items concerning the preoperative, intraoperative, and postoperative period, are detailed. The authors report their preliminary results through the comparison of the care practice of a historical cohort with a consecutive surgical cohort of patients with PitNET who underwent operation after the implementation of this ERAS protocol. A compliance checklist with key performance indicators was useful to monitor the adherence to the protocol and the changes in the perioperative management. RESULTS: Following the introduction of this ERAS protocol, the authors significantly shortened the duration of the antibiotic therapy (p < 0.00001) and increased the use of mechanical (p < 0.00001) and pharmacological measures to prevent deep venous thrombosis (p = 0.002). The median length of hospital stay was significantly shorter for the ERAS group (p = 0.00014), and there was no increase in readmission rate or postoperative complications. The documentation and data tracking strongly improved in the ERAS cohort and the authors were more attentive in pain evaluation (p = 0.001), postoperative hormonal supplementation (p = 0.001) and early feeding and mobilization (p = 0.0008 and p < 0.00001, respectively). More patients were discharged on day 3 after surgery in the ERAS group (p < 0.00001). The compliance to the whole process increased from 64.2% to 89.5% (p = 0.016), and the compliance per patient was also found to have significantly increased (p < 0.00001). CONCLUSIONS: The introduction of a standardized ERAS protocol for the perioperative management of patients with PitNET allowed the authors to improve the multidisciplinary management of these patients. With the application of simple cost-effective interventions and with the avoidance of unnecessary measures, gains were made in terms of early mobilization and feeding, thereby resulting in a shorter in-hospital stay.

The Enhanced Recovery After Surgery protocol for the surgical management of craniosynostosis: Lausanne experience.

OBJECTIVE: Over the past decade, the Enhanced Recovery After Surgery (ERAS) program has demonstrated its effectiveness and efficiency in improving postoperative care and enhancing recovery across various surgical fields. Preliminary results of ERAS protocol implementation in craniosynostosis surgery are presented. METHODS: An ERAS protocol was developed and implemented for cranial pediatric neurosurgery, focusing on craniosynostosis repair. The study incorporated a pre-ERAS group consisting of a consecutive series of patients who underwent craniosynostosis repair surgery prior to the implementation of the ERAS protocol; the results were compared with a consecutive group of patients who had been prospectively collected since the introduction of the ERAS for craniosynostosis protocol. The safety, feasibility, and efficiency of the ERAS protocol in pediatric neurosurgery was evaluated, through the collection of clinical data from the pre-, intra-, and postoperative phase. Surgery-related complications were evaluated according to the Clavien-Dindo classification. Costs of the stays were obtained using a microcosting approach. RESULTS: A total of 35 pre-ERAS patients and 10 ERAS patients were included. Scaphocephaly was the most common pathology in both groups. The overall compliance with the pre-, intra-, and postoperative criteria significantly increased-from 35.5%, 64.4%, and 54.7%, respectively, in each phase to 94%, 90%, and 84% (p < 0.001). The authors noticed a reduction in the average opioid dose used per patient in the ERAS group (p = 0.004), and they observed a trend toward a decreased mean length of stay from 5.2 days in the pre-ERAS group to 4.6 days in the ERAS group, without an increase of the rate of readmission within 30 days of surgery. The rate of complications decreased but this difference was not statistically significant. The hospital costs lowered significantly: from 21,958 Confederatio Helvetica Francs (CHF) in the pre-ERAS group to 18,936 CHF in the ERAS group (p = 0.02). CONCLUSIONS: The ERAS protocol represents a safe and cost-effective tool for the perioperative management of craniosynostosis. It showed its positive impact on the analgesia provided and on the reduction of in-hospital costs for these patients. ERAS protocols may thus be interesting options in the pediatric neurosurgical field.

Endoscopic endonasal pituitary surgery: How we do it. Consensus statement on behalf of the EANS skull base section.

Introduction and research question: The use of an endoscope in skull base surgery provides a panoramic close-up view over the intracranial structures from multiple angles with excellent illumination, thus permitting greater extent of resection of tumors arising at sellar area, mostly represented by PitNet - Pituitary neuroendocrine tumors, with higher likelihood of preserving vital/intact gland tissue. For this refined specialty of neurosurgery, unique skills need to be acquired along a steep learning curve. Material and methods: EANS (European Association of Neurosurgical Societies) skull base section panelists were enrolled and 11 completed the survey: the goal was to provide a consensus statement of the endoscopic endonasal approach for pituitary adenoma surgery. Results: The survey consisted of 44 questions covering demographics data (i.e., academic/non-academic center, case load, years of experience), surgical techniques (i.e., use of neuronavigation, preoperative imaging), and follow-up management. Discussion and conclusions: In this paper we identified a series of tips and tricks at different phases of an endoscopic endonasal pituitary surgery procedure to underline the crucial steps to perform successful surgery and reduce complications: we took in consideration the principles of the surgical technique, the knowledge of the anatomy and its variations, and finally the importance of adjoining specialties experts.

The Role of Cisternostomy and Cisternal Drainage in the Treatment of Aneurysmal Subarachnoid Hemorrhage: A Comprehensive Review.

Aneurysmal subarachnoid hemorrhage (aSAH) provokes a cascade reaction that is responsible for early and delayed brain injuries mediated by intracranial hypertension, hydrocephalus, cerebral vasospasm (CV), and delayed cerebral ischemia (DCI), which result in increased morbidity and mortality. During open microsurgical repair, cisternal access is achieved essentially to gain proximal vascular control and aneurysm exposition. Cisternostomy also allows brain relaxation, removal of cisternal clots, and restoration of the CSF dynamics through the communication between the anterior and posterior circulation cisterns and the ventricular system, with the opening of the Membrane of Liliequist and lamina terminalis, respectively. Continuous postoperative CSF drainage through a cisternal drain (CD) is a valuable option for treating acute hydrocephalus and intracranial hypertension. Moreover, it efficiently removes the blood and toxic degradation products, with a potential benefit on CV, DCI, and shunt-dependent hydrocephalus. Finally, the CD is an effective pathway to administer vasoactive, fibrinolytic, and anti-oxidant agents and shows promising results in decreasing CV and DCI rates while minimizing systemic effects. We performed a comprehensive review to establish the adjuvant role of cisternostomy and CD performed in cases of direct surgical repair for ruptured intracranial aneurysms and their role in the prevention and treatment of aSAH complications.

PD-L1 Expression in Pituitary Neuroendocrine Tumors/Pituitary Adenomas.

BACKGROUND AND AIM: About a third of Pituitary Neuroendocrine Tumors (PitNETs) may show aggressive behavior. Many efforts have been performed for identifying possible predictive factors to early determine the future behavior of PitNETs. Programmed cell death ligand 1 (PD-L1) expression was associated with a more aggressive biology in different solid tumors, but its role in PitNET is not well-established yet. Our study aims to analyze PD-L1 expression in a surgical cohort of PitNETs to determine its association with radiological invasion and pathology findings, as well as with long-term recurrence rates. METHODS: We performed a retrospective analysis in a series of 86 PitNETs. Clinical presentation and radiological features of the preoperative period were collected, as well as pathological data and follow-up data. The rate of PD-L1 expression was immunohistochemically evaluated and expressed as a tumor proportion score (TPS). We assessed its relationship with cavernous sinus invasion and Trouillas' classification as primary outcomes. Secondary outcomes included the TPS' relationship with histopathological markers of proliferation, hormonal expression, tumor size and long-term recurrence rates. We calculated the optimal cut-point for the primary outcomes while maximizing the product of the sensitivity and specificity and then we evaluated the significance of secondary outcomes with logistic regression analysis. RESULTS: Eighty-six patients were included in the analysis; 50 cases were non-functional PitNETs. The TPS for PD-L1 showed a highly right-skewed distribution in our sample, as 30.2% of patients scored 0. Using Trouillas' classification, we found that "proliferative" cases have a significantly higher probability to express PD-L1 in more than 30% of tumor cells (OR: 5.78; CI 95%: 1.80-18.4). This same cut-point was also associated with p53 expression. A positive association was found between PD-L1 expression and GH expression (p = 0.001; OR: 5.44; CI 95%: 1.98-14.98), while an inverse relationship was found with FSH/LH expression (p = 0.014; OR = 0.27, CI 95%: 0.10-0.76). No association was found with CS invasion, tumor size, bone erosion or dura invasion. We could not find any association between PD-L1 expression and recurrence. CONCLUSIONS: PD-L1 expression was associated with proliferative grades of Trouillas' classification and p53 expression. We also confirmed a higher expression of PD-L1 in somatotroph tumors. Larger studies are necessary to investigate the relationship between PD-L1 expression and aggressive behaviors.

Pituitary surgery outcome in patients 75 years and older: a retrospective study.

BACKGROUND: As the population ages, the number of elderly patients with an indication for pituitary surgery is rising. Information on the outcome of patients aged over 75 is limited. This study reports a large series assessing the feasibility of surgical resection in this specific age range, focusing on surgical complications and postoperative results. METHODS: A retrospective cohort study of patients with pituitary adenomas and Rathke's cleft cysts was conducted. All patients were aged 75 years or over and treated by a single expert neurosurgical team. A control population included 2379 younger adult patients operated by the same surgeons during the same period. RESULTS: Between 2008 and 2022, 155 patients underwent surgery. Indication was based on vision impairment in most patients (79%). Median follow-up was 13 months (range: 3-96). The first surgery was performed with an endoscopic transsellar approach, an extended endonasal transtuberculum approach and a microscopic transcranial approach in 96%, 3%, and 1% of patients, respectively. Single surgery was sufficient to obtain volume control in 97% of patients. From Kaplan-Meier estimates, 2-year and 5-year disease control with a single surgery were 97.3% and 86.2%, respectively. Resection higher than 80% was achieved in 77% of patients. No vision worsening occurred. In acromegaly and Cushing's disease, endocrine remission was obtained in 90% of non-invasive adenomas. Surgical complications were noted in 5% of patients, with 30-day mortality, hematoma, cerebrospinal fluid leak, meningitis, and epistaxis occurring in 0.6%, 0.6%, 1.9%, 0.6%, and 1.3% respectively. New endocrine anterior deficits occurred in only 5%, while no persistent diabetes insipidus was noted. Compared with younger patients, the complication rate was not statistically different. CONCLUSIONS: Surgery beyond the age of 75, mainly relying on an endoscopic endonasal transsellar approach, is effective and safe, provided that patients are managed in tertiary centers.

Implementation of the Enhanced Recovery After Surgery (ERAS®) program in neurosurgery.

BACKGROUND: Over the past decade, Enhanced Recovery After Surgery (ERAS®) guidelines have been proven to simplify postoperative care and improve recovery in several surgical disciplines. The authors set out to create and launch an ERAS® program for cranial neurosurgery that meets official ERAS® Society standards. The authors summarize the successive steps taken to achieve this goal in two specific neurosurgical conditions and describe the challenges they faced. METHODS: Pituitary neuroendocrine tumors (Pit-NET) resected by a transsphenoidal approach and craniosynostosis (Cs) repair were selected as appropriate targets for the implementation of ERAS® program in the Department of Neurosurgery. A multidisciplinary team with experience in managing these pathologies was created. A specialized ERAS® nurse coordinator was hired. An ERAS® certification process was performed involving 4 seminars separated by 3 active phases under the supervision of an ERAS® coach. RESULTS: The ERAS® Pit-NET team included 8 active members. The ERAS® Cs team included 12 active members. Through the ERAS® certification process, areas for improvement were identified, local protocols were written, and the ERAS® program was implemented. Patient-centered strategies were developed to increase compliance with the ERAS® protocols. A prospective database was designed for ongoing program evaluation. Certification was achieved in 18 months. Direct costs and time requirements are reported. CONCLUSION: Successful ERAS® certification requires a committed multidisciplinary team, an ERAS® coach, and a dedicated nurse coordinator.

Differences in intraoperative sampling during meningioma surgery regarding CNS invasion - Results of a survey on behalf of the EANS skull base section.

Introduction: and Research Question: Invasive growth of meningiomas into CNS tissue is rare but of prognostic significance. While it has entered the WHO classification as a stand-alone criterion for atypia, its true prognostic impact remains controversial. Retrospective analyses, on which the current evidence is based, show conflicting results. Discordant findings might be explained by different intraoperative sampling methodologies. Material and methods: To assess the applied sampling methods in the light of the novel prognostic impact of CNS invasion, an anonymous survey was designed and distributed via the EANS website and newsletter. The survey was open from June 5th until July 15th, 2022. Results: After exclusion of 13 incomplete responses, 142 (91.6%) datasets were used for statistical analysis. Only 47.2% of participants' institutions utilize a standardized sampling method, and 54.9% pursue a complete sampling of the area of contact between the meningioma surface and CNS tissue. Most respondents (77.5%) did not change their sampling practice after introduction of the new grading criteria to the WHO classification of 2016. Intraoperative suspicion of CNS invasion changes the sampling for half of the participants (49.3%). Additional sampling of suspicious areas of interest is reported in 53.5%. Dural attachment and adjacent bone are more readily sampled separately if tumor invasion is suspected (72.5% and 74.6%, respectively), compared to meningioma tissue with signs of CNS invasion (59.9%). Discussion and conclusions: Intraoperative sampling methods during meningioma resection vary among neurosurgical departments. There is need for a structured sampling to optimize the diagnostic yield of CNS invasion.

Central quadrantotomy for intractable childhood epilepsy: operative technique and functional neuroanatomy.

Refractory subhemispheric epilepsy has been traditionally treated by resection. The last few decades have seen the emergence of disconnective techniques, for both hemispheric and subhemispheric disease. The aim of this study was to describe the technique for a disconnective surgery for large epileptogenic lesions involving the central (perirolandic cortices), parietal, and occipital lobes. This junctional cortex within the hemisphere (in contrast to anterior and posterior quadrantotomies) presents unique challenges when contemplating a complete disconnection of the region. The surgical technique is achieved through six distinct steps: fronto-central, inferior frontoparietal, lateral temporo-occipital, medial frontal, basal temporo-occipital, and posterior parasagittal callosal disconnections. The functional neuroanatomy of each step is described, along with cadaveric dissections. The authors describe this technique and include a case description of a young girl who presented with childhood-onset intractable epilepsy associated with cognitive stagnation. The postoperative seizure outcome in this patient remains excellent at 2 years' follow-up, with gains in cognition and behavior. Excellent seizure outcomes can be achieved if the network encompassing the entire epileptogenic cortex is disconnected while ensuring preservation of fiber systems that link functionally eloquent uninvolved cortices adjacent to the central quadrant.

Radiological Evolution of Fat Graft Used for Optic Neuropexy During Surgery for Parasellar Meningiomas.

BACKGROUND: Stereotactic radiosurgery (SRS) is an effective adjuvant therapy for residual tumor after subtotal resection of parasellar meningiomas. Fat graft placement between the optic nerve/chiasm and residual tumor (optic neuropexy [OPN]) allows for safe SRS therapy. OBJECTIVE: To evaluate the radiological temporal profile of the fat graft after OPN, immediately after surgery and at 3, 6, and 12 months intervals, to elucidate the optimal time point of adjuvant SRS. METHODS: A single-center, retrospective, cohort study of 23 patients after surgery for parasellar meningioma was conducted. Fat graft volume and MRI signal ratios were calculated. SRS dosimetric parameters (tumor/optic nerve) were measured at the time of SRS and compared with a hypothetical dosimetric plan based on an early postoperative MRI. RESULTS: Of 23 patients, 6 (26%) had gross total resection and 17 (74%) had subtotal resection. Fat grafts showed a progressive loss of volume and signal ratio over time. Radiosurgery was performed in 14 (82.3%; 8 hypofractionated radiosurgery and 6 single fraction). At 3 months, there is a loss of 46% of the fat volume and degradation of its tissue intensity, decreasing differentiation from tumor and nerve. The hypothetical treatment plan (performed on an early postoperative MRI) showed that single-fraction SRS would have been possible in 6 of the 8 hypofractionated cases. CONCLUSION: OPN is a technique that can be safely performed after resection of parasellar meningiomas. Because of the reduction of the fat volume and tissue differentiation between fat and tumor/nerves, adjuvant radiosurgery is better performed within the first 3 months after surgery.

Predictive Factors for the Occurrence of Perioperative Complications in Pediatric Posterior Fossa Tumors.

OBJECTIVE: Central nervous system tumors are the most common solid neoplasm in children, 60%-70% occurring in the posterior fossa. Surgery is the mainstay of treatment but surgery in the pediatric population is associated with a high risk of perioperative complications. We aimed at analyzing the perioperative complications after posterior fossa surgery in a pediatric population and identifying the associated risk factors. METHODS: Retrospective study of all pediatric patients undergoing surgery for resection of a posterior fossa tumor between 1999 and 2019, at the University Hospital of Lausanne. Data were collected including age, clinical presentation, tumor localization, presence of preoperative hydrocephalus, timing of surgery, surgical approach, surgical team, extent of surgical resection, perisurgical complications, and histopathological diagnosis. Statistical analysis was performed to correlate the data with the risk of complications. RESULTS: Sixty-seven patients were included. Perisurgical complications were identified in 39 patients (58.2%), of which 14 (35.9%) required corrective interventions. The perioperative mortality rate was zero. In the univariate analysis, surgery performed under emergency conditions, transvermian and telovelar approaches were statistically correlated with an increased rate of complications. Extent of resection, hydrocephalus, and Lansky index at presentation were not predictive of perioperative complications. Midline tumor, tumor volume >25 cm3, and surgery performed by a nonspecialized pediatric onconeurosurgeon were found to be independent risk factors in the multivariate analysis. CONCLUSIONS: Surgery in the posterior fossa in the pediatric population harbors a high risk of complications. Identifying the variables contributing to these complications is important in order to improve surgical management of these patients.

The positive impact of cisternostomy with cisternal drainage on delayed hydrocephalus after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Hydrocephalus is one of the major complications of aneurysmal subarachnoid haemorrhage (aSAH). In the acute setting, an external ventricular drain (EVD) is used for early management. A cisternal drain (CD) coupled with the micro-surgical opening of basal cisterns can be an alternative when the aneurysm is clipped. Chronic hydrocephalus after aSAH is managed with ventriculo-peritoneal (VP) shunt, a procedure associated with a wide range of complications. The aim of this study is to analyse the impact of micro-surgical opening of basal cisterns coupled with CD on the incidence of VP shunt, compared to patients treated with EVD. METHODS: The authors conducted a retrospective review of 89 consecutive cases of patients with aSAH treated surgically and endovascularly with either EVD or CD between January 2009 and September 2021. Patients were stratified into two groups: Group 1 included patients with EVD, Group 2 included patients with CD. Subgroup analysis with only patients treated surgically was also performed. We compared their baseline characteristics, clinical outcomes and shunting rates. RESULTS: There were no statistically significant differences between the two groups in terms of epidemiological characteristics, WFNS score, Fisher scale, presence of intraventricular hemorrhage (IVH), acute hydrocephalus, postoperative meningitis or of clinical outcomes at last follow-up. Cisternostomy with CD (Group 2) was associated with a statistically significant reduction in VP-shunt compared with the use of an EVD (Group 1) (9.09% vs 53.78%; p < 0.001). This finding was confirmed in our subgroup analysis, as among patients with a surgical clipping, the rate of VP shunt was 43.7% for the EVD group and 9.5% for the CD group (p = 0.02). CONCLUSIONS: Cisternostomy with CD may reduce the rate of shunt-dependent hydrocephalus. Cisternostomy allows the removal of subarachnoid blood, thereby reducing arachnoid inflammation and fibrosis. CD may enhance this effect, thus resulting in lower rates of chronic hydrocephalus.

Direct cochlear nerve stimulation monitoring through evoked muscle responses during retrosigmoid vestibular schwannoma resection surgery: technical note.

OBJECTIVE: Cochlear nerve preservation during surgery for vestibular schwannoma (VS) may be challenging. Brainstem auditory evoked potentials and cochlear compound nerve action potentials have clearly shown their limitations in surgeries for large VSs. In this paper, the authors report their preliminary results after direct electrical intraoperative cochlear nerve stimulation and recording of the postauricular muscle response (PAMR) during resection of large VSs. METHODS: The details for the electrode setup, stimulation, and recording parameters are provided. Data of patients for whom PAMR was recorded during surgery were prospectively collected and analyzed. RESULTS: PAMRs were recorded in all patients at the ipsilateral vertex-earlobe scalp electrode, and in 90% of the patients they were also observed in the contralateral electrode. The optimal stimulation intensity was found to be 1 mA at 1 Hz, with a good cochlear response and an absent response from other nerves. At that intensity, the ipsilateral cochlear response had an initial peak at a mean (± SEM) latency of 11.6 ± 1.5 msec with an average amplitude of 14.4 ± 5.4 µV. One patient experienced a significant improvement in his audition, while that of the other patients remained stable. CONCLUSIONS: PAMR monitoring may be useful in mapping the position and trajectory of the cochlear nerve to enable hearing preservation during surgery.

Aesthetic results in children with single suture craniosynostosis: proposal for a modified Whitaker classification.

OBJECTIVE: Aesthetic assessment after surgery for non-syndromic single suture craniosynostosis (SSC) is crucial. Surgeons' evaluation is generally based on Whitaker classification, while parental impression is generally neglected. The aim of this paper is to compare aesthetic perceptions of parents and surgeons after surgery for SSC, expressed by a 10-item questionnaire that complement Whitaker's classification. METHODS: The authors submitted a 10-item questionnaire integrating Whitaker's classification in order to evaluate the degree of satisfaction, the detailed aesthetics results and the need for surgical revision, to surgeons and parents of a consecutive series of patients operated for SSC between January 2007 and December 2018. The results were collected blindly. RESULTS: A total of 70 patients were included in the study. Scaphocephaly and trigonocephaly were the two most frequent craniosynostosis. Parents and surgeons general aesthetics evaluation and average rating for Whitaker's classification were 1.86 vs 1.67 (p = 0.69) and 1.19 vs 1.1 (p = 0.45) respectively. Parents' evaluation for scar perception and alopecia (p < 0.00001), the presence of bony crest (0.002), bony bump (p < 0.00001), or other bone irregularities (p = 0.02) are significantly worse when compared to surgeons' perception. CONCLUSIONS: Parents seem to be more sensitive to the detection of some aesthetic anomalies and their opinion should not be neglected. The authors propose a modified Whitaker classification based on their results to better stratify the aesthetic outcome after surgery for SSC.

BET protein inhibition sensitizes glioblastoma cells to temozolomide treatment by attenuating MGMT expression.

Bromodomain and extra-terminal tail (BET) proteins have been identified as potential epigenetic targets in cancer, including glioblastoma. These epigenetic modifiers link the histone code to gene transcription that can be disrupted with small molecule BET inhibitors (BETi). With the aim of developing rational combination treatments for glioblastoma, we analyzed BETi-induced differential gene expression in glioblastoma derived-spheres, and identified 6 distinct response patterns. To uncover emerging actionable vulnerabilities that can be targeted with a second drug, we extracted the 169 significantly disturbed DNA Damage Response genes and inspected their response pattern. The most prominent candidate with consistent downregulation, was the O-6-methylguanine-DNA methyltransferase (MGMT) gene, a known resistance factor for alkylating agent therapy in glioblastoma. BETi not only reduced MGMT expression in GBM cells, but also inhibited its induction, typically observed upon temozolomide treatment. To determine the potential clinical relevance, we evaluated the specificity of the effect on MGMT expression and MGMT mediated treatment resistance to temozolomide. BETi-mediated attenuation of MGMT expression was associated with reduction of BRD4- and Pol II-binding at the MGMT promoter. On the functional level, we demonstrated that ectopic expression of MGMT under an unrelated promoter was not affected by BETi, while under the same conditions, pharmacologic inhibition of MGMT restored the sensitivity to temozolomide, reflected in an increased level of γ-H2AX, a proxy for DNA double-strand breaks. Importantly, expression of MSH6 and MSH2, which are required for sensitivity to unrepaired O6-methylguanine-lesions, was only briefly affected by BETi. Taken together, the addition of BET-inhibitors to the current standard of care, comprising temozolomide treatment, may sensitize the 50% of patients whose glioblastoma exert an unmethylated MGMT promoter.