Determinants of Functional Outcome after Pediatric Hemispherotomy.

OBJECTIVE: We aimed to evaluate determinants of functional outcome after pediatric hemispherotomy in a large and recent multicenter cohort. METHODS: We retrospectively investigated the functional outcomes of 455 children who underwent hemispherotomy at 5 epilepsy centers in 2000-2016. We identified determinants of unaided walking, voluntary grasping with the hemiplegic hand, and speaking through Bayesian multivariable regression modeling using missing data imputation. RESULTS: Seventy-five percent of children were seizure-free, and 44% stopped antiseizure medication at a 5.1-year mean follow-up (range = 1-17.1). Seventy-seven percent of children could walk unaided, 8% could grasp voluntarily, and 68% could speak at the last follow-up. Children were unlikely to walk when they had contralateral magnetic resonance imaging (MRI) abnormalities (40/73, p = 0.04), recurrent seizures following hemispherotomy (62/109, p = 0.04), and moderately (50/61, p = 0.03) or severely impaired (127/199, p = 0.001) postsurgical intellectual functioning, but were likely to walk when they were older at outcome determination (p = 0.01). Children were unlikely to grasp voluntarily with the hand contralateral to surgery when they had Rasmussen encephalitis (0/61, p = 0.001) or Sturge-Weber syndrome (0/32, p = 0.007). Children were unlikely to speak when they had contralateral MRI abnormalities (30/69, p = 0.002) and longer epilepsy duration (p = 0.01), but likely to speak when they had Sturge-Weber syndrome (29/35, p = 0.01), were older at surgery (p = 0.04), and were older at outcome determination (p < 0.001). INTERPRETATION: Etiology and bilaterality of structural brain abnormalities were key determinants of functional outcome after hemispherotomy. Longer epilepsy duration affected language outcomes. Not surprisingly, walking and talking ability increased with older age at outcome evaluation. ANN NEUROL 2024;95:377-387.

Defining benchmark outcomes for mesial temporal lobe epilepsy surgery: A global multicenter analysis of 1119 cases.

OBJECTIVE: Benchmarking has been proposed to reflect surgical quality and represents the highest standard reference values for desirable results. We sought to determine benchmark outcomes in patients after surgery for drug-resistant mesial temporal lobe epilepsy (MTLE). METHODS: This retrospective multicenter study included patients who underwent MTLE surgery at 19 expert centers on five continents. Benchmarks were defined for 15 endpoints covering surgery and epilepsy outcome at discharge, 1 year after surgery, and the last available follow-up. Patients were risk-stratified by applying outcome-relevant comorbidities, and benchmarks were calculated for low-risk ("benchmark") cases. Respective measures were derived from the median value at each center, and the 75th percentile was considered the benchmark cutoff. RESULTS: A total of 1119 patients with a mean age (range) of 36.7 (1-74) years and a male-to-female ratio of 1:1.1 were included. Most patients (59.2%) underwent anterior temporal lobe resection with amygdalohippocampectomy. The overall rate of complications or neurological deficits was 14.4%, with no in-hospital death. After risk stratification, 377 (33.7%) benchmark cases of 1119 patients were identified, representing 13.6%-72.9% of cases per center and leaving 742 patients in the high-risk cohort. Benchmark cutoffs for any complication, clinically apparent stroke, and reoperation rate at discharge were ≤24.6%, ≤.5%, and ≤3.9%, respectively. A favorable seizure outcome (defined as International League Against Epilepsy class I and II) was reached in 83.6% at 1 year and 79.0% at the last follow-up in benchmark cases, leading to benchmark cutoffs of ≥75.2% (1-year follow-up) and ≥69.5% (mean follow-up of 39.0 months). SIGNIFICANCE: This study presents internationally applicable benchmark outcomes for the efficacy and safety of MTLE surgery. It may allow for comparison between centers, patient registries, and novel surgical and interventional techniques.

The anatomy of neuroepithelial tumours.

Many neurological conditions conceal specific anatomical patterns. Their study contributes to the understanding of disease biology and to tailored diagnostics and therapy. Neuroepithelial tumours exhibit distinct anatomical phenotypes and spatiotemporal dynamics that differ from those of other brain tumours. Brain metastases display a preference for the cortico-subcortical boundaries of watershed areas and have a predominantly spherical growth. Primary CNS lymphomas localize to the white matter and generally invade along fibre tracts. In neuroepithelial tumours, topographic probability mapping and unsupervised topological clustering have identified an inherent radial anatomy and adherence to ventriculopial configurations of specific hierarchical orders. Spatiotemporal probability and multivariate survival analyses have identified a temporal and prognostic sequence underlying the anatomical phenotypes of neuroepithelial tumours. Gradual neuroepithelial de-differentiation and declining prognosis follow (i) an expansion into higher order radial units; (ii) a subventricular spread; and (iii) the presence of mesenchymal patterns (expansion along white matter tracts, leptomeningeal or perivascular invasion, CSF spread). While different pathophysiological hypotheses have been proposed, the cellular and molecular mechanisms dictating this anatomical behaviour remain largely unknown. Here we adopt an ontogenetic approach towards the understanding of neuroepithelial tumour anatomy. Contemporary perception of histo- and morphogenetic processes during neurodevelopment permit us to conceptualize the architecture of the brain into hierarchically organized radial units. The anatomical phenotypes in neuroepithelial tumours and their temporal and prognostic sequences share remarkable similarities with the ontogenetic organization of the brain and the anatomical specifications that occur during neurodevelopment. This macroscopic coherence is reinforced by cellular and molecular observations that the initiation of various neuroepithelial tumours, their intratumoural hierarchy and tumour progression are associated with the aberrant reactivation of surprisingly normal ontogenetic programs. Generalizable topological phenotypes could provide the basis for an anatomical refinement of the current classification of neuroepithelial tumours. In addition, we have proposed a staging system for adult-type diffuse gliomas that is based on the prognostically critical steps along the sequence of anatomical tumour progression. Considering the parallels in anatomical behaviour between different neuroepithelial tumours, analogous staging systems may be implemented for other neuroepithelial tumour types and subtypes. Both the anatomical stage of a neuroepithelial tumour and the spatial configuration of its hosting radial unit harbour the potential to stratify treatment decisions at diagnosis and during follow-up. More data on specific neuroepithelial tumour types and subtypes are needed to increase the anatomical granularity in their classification and to determine the clinical impact of stage-adapted and anatomically tailored therapy and surveillance.

Intraoperative ultrasonography in microsurgical resection of vestibular schwannomas via retrosigmoid approach: surgical technique and proof-of-concept illustrative case series.

PURPOSE: Intraoperative ultrasonography (ioUS) is an established tool for the real-time intraoperative orientation and resection control in intra-axial oncological neurosurgery. Conversely, reports about its implementation in the resection of vestibular schwannomas (VS) are scarce. The aim of this study is to describe the role of ioUS in microsurgical resection of VS. METHODS: ioUS (Craniotomy Transducer N13C5, BK5000, B Freq 8 MHz, BK Medical, Burlington, MA, USA) is integrated into the surgical workflow according to a 4-step protocol (transdural preresection, intradural debulking control, intradural resection control, transdural postclosure). Illustrative cases of patients undergoing VS resection through a retrosigmoid approach with the use of ioUS are showed to illustrate advantages and pitfalls of the technique. RESULTS: ioUS allows clear transdural identification of the VS and its relationships with surgically relevant structures of the posterior fossa and of the cerebellopontine cistern prior to dural opening. Intradural ioUS reliably estimates the extent of tumor debulking, thereby helping in the choice of the right moment to start peripheral preparation and in the optimization of the extent of resection in those cases where subtotal resection is the ultimate goal of surgery. Transdural postclosure ioUS accurately depicts surgical situs. CONCLUSION: ioUS is a cost-effective, safe, and easy-to-use intraoperative adjunctive tool that can provide a significant assistance during VS surgery. It can potentially improve patient safety and reduce complication rates. Its efficacy on clinical outcomes, operative time, and complication rate should be validated in further studies.

A T-cell antigen atlas for meningioma: novel options for immunotherapy.

Meningiomas are the most common primary intracranial tumors. Although most symptomatic cases can be managed by surgery and/or radiotherapy, a relevant number of patients experience an unfavorable clinical course and additional treatment options are needed. As meningiomas are often perfused by dural branches of the external carotid artery, which is located outside the blood-brain barrier, they might be an accessible target for immunotherapy. However, the landscape of naturally presented tumor antigens in meningioma is unknown. We here provide a T-cell antigen atlas for meningioma by in-depth profiling of the naturally presented immunopeptidome using LC-MS/MS. Candidate target antigens were selected based on a comparative approach using an extensive immunopeptidome data set of normal tissues. Meningioma-exclusive antigens for HLA class I and II are described here for the first time. Top-ranking targets were further functionally characterized by showing their immunogenicity through in vitro T-cell priming assays. Thus, we provide an atlas of meningioma T-cell antigens which will be publicly available for further research. In addition, we have identified novel actionable targets that warrant further investigation as an immunotherapy option for meningioma.

Safety of microneurosurgical interventions for superficial and deep-seated brain metastases: single-center cohort study of 637 consecutive cases.

PURPOSE: Microneurosurgical techniques have greatly improved over the past years due to the introduction of new technology and surgical concepts. To reevaluate the role of micro-neurosurgery in brain metastases (BM) resection in the era of new systemic and local treatment options, its safety profile needs to be reassessed. The aim of this study was to analyze the rate of adverse events (AEs) according to a systematic, comprehensive and reliably reproducible grading system after microneurosurgical BM resection in a large and modern microneurosurgical series with special emphasis on anatomical location. METHODS: Prospectively collected cases of BM resection between 2013 and 2022 were retrospectively analyzed. Number of AEs, defined as any deviations from the expected postoperative course according to Clavien-Dindo-Grade (CDG) were evaluated. Patient, surgical, and lesion characteristics, including exact anatomic tumor locations, were analyzed using uni- and multivariate logistic regression and survival analysis to identify predictive factors for AEs. RESULTS: We identified 664 eligible patients with lung cancer being the most common primary tumor (44%), followed by melanoma (25%) and breast cancer (11%). 29 patients (4%) underwent biopsy only whereas BM were resected in 637 (96%) of cases. The overall rate of AEs was 8% at discharge. However, severe AEs (≥ CDG 3a; requiring surgical intervention under local/general anesthesia or ICU treatment) occurred in only 1.9% (n = 12) of cases with a perioperative mortality of 0.6% (n = 4). Infratentorial tumor location (OR 5.46, 95% 2.31-13.8, p = .001), reoperation (OR 2.31, 95% 1.07-4.81, p = .033) and central region tumor location (OR 3.03, 95% 1.03-8.60) showed to be significant predictors in a multivariate analysis for major AEs (CDG ≥ 2 or new neurological deficits). Neither deep supratentorial nor central region tumors were associated with more major AEs compared to convexity lesions. CONCLUSIONS: Modern microneurosurgical resection can be considered an excellent option in the management of BM in terms of safety, as the overall rate of major AEs are very rare even in eloquent and deep-seated lesions.

Impact of Long-Term Antithrombotic and Statin Therapy on the Clinical Outcome in Patients with Cavernous Malformations of the Central Nervous System: A Single-Center Case Series of 428 Patients.

INTRODUCTION: Literature regarding the safety and efficacy of antithrombotic (antiplatelet or anticoagulant) therapy and statins in patients with cavernous malformations (CMs) of the central nervous system is sparse, resulting in uncertainty about its use in clinical practice. The aim of this study was to analyze the impact of antithrombotic therapy and statins on the risk of hemorrhage and focal neurological deficit in patients with CMs. METHODS: The authors' institutional database was screened for all patients with CMs of the central nervous system treated at their institution between 2006 and 2018. Patients with radiological and/or histological diagnosis of CMs, clinical baseline characteristics, available patient's medication history, and follow-up data were included in this study. Time-to-event probability (hemorrhage or focal neurological deficit) as well as the number of events (hemorrhage or focal neurological deficit) during follow-up were assessed in patients who were categorized according to their medical treatment (antithrombotic therapy, statins, combined therapy, or no treatment). RESULTS: Four hundred twenty-eight patients with CMs were eligible and included in the final analysis. Sixty-nine (16.1%) patients were on long-term antithrombotic therapy and 46 (10.6%) on long-term statins, of whom 31 patients were on a combination of both. The probability of experiencing first hemorrhage or focal neurological deficit was less likely in patients on antiplatelet therapy (HR 0.09, 95% CI 0.021-0.39, p = 0.001), anticoagulant therapy (HR 0.12, 95% CI 0.016-0.85, p = 0.034), or the combination thereof (HR 0.12, 95% CI 0.016-0.93, p = 0.043) compared to patients with no antithrombotic treatment. The number of hemorrhages and focal neurological deficits were significantly lower in patients on antithrombotic therapy compared to patients on no treatment during follow-up. In patients on statins alone, the time-to-event probability was comparable to that of patients on no treatment (HR 0.91, 95% CI 0.438-1.91, p = 0.812), and the number of events was similar to patients on no treatment. CONCLUSION: The results of our study provide further evidence that antithrombotic therapy alone or in combination with statins in patients with CMs of the central nervous system does not increase the risk of hemorrhage or focal neurological deficit but, on the contrary, may have some benefit.

Anatomical phenotyping and staging of brain tumours.

Unlike other tumours, the anatomical extent of brain tumours is not objectified and quantified through staging. Staging systems are based on understanding the anatomical sequence of tumour progression and its relationship to histopathological dedifferentiation and survival. The aim of this study was to describe the spatiotemporal phenotype of the most frequent brain tumour entities, to assess the association of anatomical tumour features with survival probability and to develop a staging system for WHO grade 2 and 3 gliomas and glioblastoma. Anatomical phenotyping was performed on a consecutive cohort of 1000 patients with first diagnosis of a primary or secondary brain tumour. Tumour probability in different topographic, phylogenetic and ontogenetic parcellation units was assessed on preoperative MRI through normalization of the relative tumour prevalence to the relative volume of the respective structure. We analysed the spatiotemporal tumour dynamics by cross-referencing preoperative against preceding and subsequent MRIs of the respective patient. The association between anatomical phenotype and outcome defined prognostically critical anatomical tumour features at diagnosis. Based on a hypothesized sequence of anatomical tumour progression, we developed a three-level staging system for WHO grade 2 and 3 gliomas and glioblastoma. This staging system was validated internally in the original cohort and externally in an independent cohort of 300 consecutive patients. While primary CNS lymphoma showed highest probability along white matter tracts, metastases enriched along terminal arterial flow areas. Neuroepithelial tumours mapped along all sectors of the ventriculocortical axis, while adjacent units were spared, consistent with a transpallial behaviour within phylo-ontogenetic radial units. Their topographic pattern correlated with morphogenetic processes of convergence and divergence of radial units during phylo- and ontogenesis. While a ventriculofugal growth dominated in neuroepithelial tumours, a gradual deviation from this neuroepithelial spatiotemporal behaviour was found with progressive histopathological dedifferentiation. The proposed three-level staging system for WHO grade 2 and 3 gliomas and glioblastoma correlated with the degree of histological dedifferentiation and proved accurate in terms of survival upon both internal and external validation. In conclusion, this study identified specific spatiotemporal phenotypes in brain tumours through topographic probability and growth pattern assessment. The association of anatomical tumour features with survival defined critical steps in the anatomical sequence of neuroepithelial tumour progression, based on which a staging system for WHO grade 2 and 3 gliomas and glioblastoma was developed and validated.

Cerebrospinal fluid leakage after intradural spinal surgery in children.

PURPOSE: This study aimed to establish the incidence of CSF leakage in children and associated complications after intradural spinal surgery in three tertiary neurosurgical referral centers and to describe the treatment strategies applied. METHODS: Patients of 18 years or younger who underwent intradural spinal surgery between 2015 and 2021 in three tertiary neurosurgical referral centers were included. Patients who died or were lost to follow-up within six weeks after surgery were excluded. The primary outcome measure was CSF leakage within six weeks after surgery, defined as leakage of CSF through the skin. Secondary outcome measures included the presence of pseudomeningocele (PMC), meningitis, and surgical site infection (SSI). RESULTS: We included a total of 75 procedures, representing 66 individual patients. The median age in this cohort was 5 (IQR = 0-13 years. CSF leakage occurred in 2.7% (2/75) of procedures. It occurred on days 3 and 21 after the index procedure, respectively. One patient was treated with a pressure bandage and an external lumbar drain on day 4 after diagnosis of the leak, and the other was treated with wound revision surgery on day 1 after the leak occurred. In total, 1 patient developed a PMC without a CSF leak which was treated with wound revision surgery. SSI occurred in 10.7%, which included both cases of CSF leak. CONCLUSIONS: CSF leakage after intradural spinal surgery in the pediatric population is relatively rare (2.7%). Nevertheless, the clinical consequences with respect to secondary complications such as infection and the necessity for invasive treatment are serious.

Central nervous system tumors in children under 5 years of age: a report on treatment burden, survival and long-term outcomes.

PURPOSE: The challenges of treating central nervous system (CNS) tumors in young children are many. These include age-specific tumor characteristics, limited treatment options, and susceptibility of the developing CNS to cytotoxic therapy. The aim of this study was to analyze the long-term survival, health-related, and educational/occupational outcomes of this vulnerable patient population. METHODS: Retrospective study of 128 children diagnosed with a CNS tumor under 5 years of age at a single center in Switzerland between 1990 and 2019. RESULTS: Median age at diagnosis was 1.81 years [IQR, 0.98-3.17]. Median follow-up time of surviving patients was 8.39 years [range, 0.74-23.65]. The main tumor subtypes were pediatric low-grade glioma (36%), pediatric high-grade glioma (11%), ependymoma (16%), medulloblastoma (11%), other embryonal tumors (7%), germ cell tumors (3%), choroid plexus tumors (6%), and others (9%). The 5-year overall survival (OS) was 78.8% (95% CI, 71.8-86.4%) for the whole cohort. Eighty-seven percent of survivors > 5 years had any tumor- or treatment-related sequelae with 61% neurological complications, 30% endocrine sequelae, 17% hearing impairment, and 56% visual impairment at last follow-up. Most patients (72%) attended regular school or worked in a skilled job at last follow-up. CONCLUSION: Young children diagnosed with a CNS tumor experience a range of complications after treatment, many of which are long-lasting and potentially debilitating. Our findings highlight the vulnerabilities of this population, the need for long-term support and strategies for rehabilitation, specifically tailored for young children.

Validation of the Clavien-Dindo grading system of complications for microsurgical treatment of unruptured intracranial aneurysms.

OBJECTIVE: Microsurgery plays an essential role in managing unruptured intracranial aneurysms (UIAs). The Clavien-Dindo classification is a therapy-oriented grading system that rates any deviation from the normal postoperative course in five grades. In this study, the authors aimed to test the applicability of the Clavien-Dindo grade (CDG) in patients who underwent microsurgical treatment of UIAs. METHODS: The records of patients who underwent microsurgery for UIAs (January 2013-November 2018) were retrieved from a prospective database. Complications at discharge and at short-term follow-up (3 months) were rated according to the Clavien-Dindo system. Patient outcomes were graded using the modified Rankin Scale (mRS) and the National Institutes of Health Stroke Scale (NIHSS). A descriptive statistic was used for data analysis. RESULTS: Overall, 156 patients underwent 157 surgeries for 201 UIAs (size range 4-42 mm). Thirty-nine patients (25%) had complex UIAs. An adverse event (CDG ≥ I) occurred in 21 patients (13.5%) by the time of discharge. Among these, 10 patients (6.4%) presented with a new neurological deficit. Significant correlations existed between a CDG ≥ I and an increase in mRS and NIHSS scores (p < 0.001). Patients treated for complex aneurysms had a significantly higher risk of developing new neurological deficits (20.5% vs 1.7%, p = 0.007). At the 3-month follow-up, a CDG ≥ I was registered in 16 patients (10.3%); none presented with a new neurological deficit. A CDG ≥ I was associated with a longer hospital length of stay (LOS) (no complication vs CDG ≥ I, 6.2 ± 3.5 days vs 9.3 ± 7.7 days, p = 0.02). CONCLUSIONS: The CDG was applicable to patients who received microsurgery of UIAs. A significant correlation existed between CDG and outcome scales, as well as LOS. The aneurysm complexity was significantly associated with a higher risk for new neurological deficit.

Distinct topographic-anatomical patterns in primary and secondary brain tumors and their therapeutic potential.

PURPOSE: Understanding the topographic-anatomical patterns of brain tumors has the potential to improve our pathophysiological understanding and may allow for anatomical tailoring of surgery and radiotherapy. This study analyzed topographic-anatomical patterns underlying neuroepithelial tumors, primary CNS lymphoma and metastases. METHODS: Any histologically confirmed supra- or infratentorial parenchymal neoplasia of one institution over a 4-year period was included. Using high-resolution magnetic resonance imaging data, a detailed analysis of the topographic-anatomical tumor features was performed. Differences between neuroepithelial tumors, primary central nervous system lymphoma (PCNSL) and metastases were assessed using pairwise comparisons adjusted for multiple testing, upon significance of the omnibus test. RESULTS: Based on image analysis of 648 patients-419 (65%) neuroepithelial tumors, 28 (5%) PCNSL and 201 (31%) metastases-entity-specific topographic-anatomical patterns were identified. Neuroepithelial tumors showed a radial ventriculo-cortical orientation, inconsistent with the current belief of a growth along white matter tracts, whereas the pattern in PCNSL corresponded to a growth along such. Metastases preferentially affected the cortex and subcortical white matter of large arteries' terminal supply areas. This study provides a comprehensive anatomical description of the topography of NT, PCNSL and metastases intended to serve as a topographic reference for clinicians and neuroscientists. CONCLUSIONS: The identified distinct anatomical patterns provide evidence for a specific interaction between tumor and anatomical structures, following a pathoclitic concept. Understanding differences in their anatomical behavior has the potential to improve our pathophysiological understanding and to tailor therapy of brain tumors.

Safety of the paramedian supracerebellar-transtentorial approach for selective amygdalohippocampectomy.

OBJECTIVE: The goal of this study was to assess the reproducibility and safety of the recently introduced paramedian supracerebellar-transtentorial (PST) approach for selective amygdalohippocampectomy (SA). METHODS: The authors performed a retrospective analysis of prospectively collected data originating from their surgical register of patients undergoing SA via a PST approach for lesional medial temporal lobe epilepsy. All patients received thorough pre- and postoperative clinical (neurological, neuropsychological, psychiatric) and instrumental (ictal and long-term EEG, invasive EEG if needed, MRI) workup. Surgery-induced complications were assessed at discharge and at every follow-up thereafter and were classified according to Clavien-Dindo grade (CDG). Epilepsy outcome was defined according to Engel classification. Data were reported according to common descriptive statistical methods. RESULTS: Between May 2015 and May 2018, 17 patients underwent SA via a PST approach at the authors' institution (hippocampal sclerosis in 13 cases, WHO grade II glioma in 2 cases, and reactive gliosis in 2 cases). The median postoperative follow-up was 7 months (mean 9 months, range 3-19 months). There was no surgery-related mortality and no complication (CDG ≥ 2) in the whole series. Transitory CDG 1 surgical complications occurred in 4 patients and had resolved in all of them by the first postoperative follow-up. One patient showed a deterioration of neuropsychological performance with new slight mnestic deficits. No patient experienced a clinically relevant postoperative visual field defect. No morbidity due to semisitting position was recorded. At last follow-up 13/17 (76.4%) patients were in Engel class I (9/17 [52.9%] were in class IA). CONCLUSIONS: The PST approach is a reproducible and safe surgical route for SA. The achievable complication rate is in line with the best results in the literature. Visual function outcome particularly benefits from this highly selective, neocortex-sparing approach. A larger patient sample and longer follow-up will show in the future if the seizure control rate and neuropsychological outcome also compare better than those achieved with current common surgical techniques.

Development of machine learning-based preoperative predictive analytics for unruptured intracranial aneurysm surgery: a pilot study.

BACKGROUND: The decision to treat unruptured intracranial aneurysms (UIAs) or not is complex and requires balancing of risk factors and scores. Machine learning (ML) algorithms have previously been effective at generating highly accurate and comprehensive individualized preoperative predictive analytics in transsphenoidal pituitary and open tumor surgery. In this pilot study, we evaluate whether ML-based prediction of clinical endpoints is feasible for microsurgical management of UIAs. METHODS: Based on data from a prospective registry, we developed and internally validated ML models to predict neurological outcome at discharge, as well as presence of new neurological deficits and any complication at discharge. Favorable neurological outcome was defined as modified Rankin scale (mRS) 0 to 2. According to the Clavien-Dindo grading (CDG), every adverse event during the post-operative course (surgery and not surgery related) is recorded as a complication. Input variables included age; gender; aneurysm complexity, diameter, location, number, and prior treatment; prior subarachnoid hemorrhage (SAH); presence of anticoagulation, antiplatelet therapy, and hypertension; microsurgical technique and approach; and various unruptured aneurysm scoring systems (PHASES, ELAPSS, UIATS). RESULTS: We included 156 patients (26.3% male; mean [SD] age, 51.7 [11.0] years) with UIAs: 37 (24%) of them were treated for multiple aneurysm and 39 (25%) were treated for a complex aneurysm. Poor neurological outcome (mRS ≥ 3) was seen in 12 patients (7.7%) at discharge. New neurological deficits were seen in 10 (6.4%), and any kind of complication occurred in 20 (12.8%) patients. In the internal validation cohort, area under the curve (AUC) and accuracy values of 0.63-0.77 and 0.78-0.91 were observed, respectively. CONCLUSIONS: Application of ML enables prediction of early clinical endpoints after microsurgery for UIAs. Our pilot study lays the groundwork for development of an externally validated multicenter clinical prediction model.

Smoking status and perioperative adverse events in patients undergoing cranial tumor surgery.

INTRODUCTION: Smoking is agreed to be a major health risk factor, but it is debated whether it has an influence on perioperative adverse events (AEs) in elective cranial tumor surgery. METHODS: We analyzed the 2013-2016 data from our prospective institutional patient registry. Consecutive patients undergoing elective microsurgical tumor surgery of a glioma or a meningioma were included. Patients were categorized as active smokers, former smokers, and non-smokers. AE were graded by the therapy-oriented Clavien-Dindo scale. Possible predictors of postoperative AE were identified with the help of a binomial logistic regression model. RESULTS: We identified 798 patients, out of which 480 were non-smokers, 193 active smokers, and 125 former smokers. The rate of AEs for active smokers (30%, 95% CI [23-37%]) was indistinguishable from the AE rate of non-smokers (32%, 95% CI [28-37%]). No difference between smoking status was found looking at all AE individually, the odds ratio of suffering from local AE and systemic AE respectively were the same between all smoking groups. The modified Rankin scale at hospital admission was a strong and significant predictor of postoperative AE (P = 0.013). CONCLUSIONS: Active smoking was not associated with an increased risk for postoperative AE, neither looking at the total number of AE nor looking at individual AE. Smoking status should therefore not be a major factor in preoperative decision making. Although not based on data of this study, doctors should always encourage patients to stop smoking due to its well-known detrimental health effect.

Repeated craniotomies for intracranial tumors: is the risk increased? Pooled analysis of two prospective, institutional registries of complications and outcomes.

PURPOSE: Deciding whether to re-operate patients with intracranial tumor recurrence or remnant is challenging, as the data on safety of repeated procedures is limited. This study set out to evaluate the risks for morbidity, mortality, and complications after repeated operations, and to compare those to primary operations. METHODS: Retrospective observational two-center study on consecutive patients undergoing microsurgical tumor resection. The data derived from independent, prospective institutional registries. The primary endpoint was morbidity at 3 months (M3), defined as significant decrease on the Karnofsky Performance Scale (KPS). Secondary endpoints were mortality, rate and severity of complications according to the Clavien-Dindo Grade (CDG). RESULTS: 463/2403 (19.3%) were repeated procedures. Morbidity at M3 occurred in n = 290 patients (12.1%). In univariable analysis, patients undergoing repeated surgery were 98% as likely as patients undergoing primary surgery to experience morbidity (OR 0.98, 95% CI 0.72-1.34, p = 0.889). In multivariable analysis adjusted for age, sex, tumor size, histology and posterior fossa location, the relationship remained stable (aOR 1.25, 95% CI 0.90-1.73, p = 0.186). Mortality was n = 10 (0.4%) at discharge and n = 95 (4.0%) at M3, without group differences. At least one complication occurred in n = 855, and the rate (35.5% vs. 35.9%, p = 0.892) and severity (CDG; p = 0.520) was similar after primary and repeated procedures. Results were reproduced in subgroup analyses for meningiomas, gliomas and cerebral metastases. CONCLUSIONS: Repeated surgery for intracranial tumors does not increase the risk of morbidity. Mortality, and both the rate and severity of complications are comparable to primary operations. This information is of value for patient counseling and the informed consent process.

Historical controversies about the thalamus: from etymology to function.

The authors report on and discuss the historical evolution of the 3 intellectual and scientific domains essential for the current understanding of the function of the human thalamus: 1) the identification of the thalamus as a distinct anatomical and functional entity, 2) the subdivision of thalamic gray matter into functionally homogeneous units (the thalamic nuclei) and relative disputes about nuclei nomenclature, and 3) experimental physiology and its limitations.Galen was allegedly the first to identify the thalamus. The etymology of the term remains unknown although it is hypothesized that Galen may have wanted to recall the thalamus of Odysseus. Burdach was the first to clearly and systematically define the thalamus and its macroscopic anatomy, which paved the way to understanding its internal microarchitecture. This structure in turn was studied in both nonhuman primates (Friedemann) and humans (Vogt and Vogt), leading to several discrepancies in the findings because of interspecies differences. As a consequence, two main nomenclatures developed, generating sometimes inconsistent (or nonreproducible) anatomo-functional correlations. Recently, considerable effort has been aimed at producing a unified nomenclature, based mainly on functional data, which is indispensable for future developments. The development of knowledge about macro- and microscopic anatomy has allowed a shift from the first galenic speculations about thalamic function (the "thalamus opticorum nervorum") to more detailed insights into the sensory and motor function of the thalamus in the 19th and 20th centuries. This progress is mostly the result of lesion and tracing studies. Direct evidence of the in vivo function of the human thalamus, however, originates from awake stereotactic procedures only.Our current knowledge about the function of the human thalamus is the result of a long process that occurred over several centuries and has been inextricably intermingled with the increasing accumulation of data about thalamic macro- and microscopic anatomy. Although the thalamic anatomy can currently be considered well understood, further studies are still needed to gain a deeper insight into the function of the human thalamus in vivo.

Ultrasonic aspiration in neurosurgery: comparative analysis of complications and outcome for three commonly used models.

INTRODUCTION: Ultrasonic aspiration (UA) devices are commonly used for resecting intracranial tumors, as they allow for internal debulking of large tumors, hereby avoiding damage to adjacent brain tissue during the dissection. Little is known about their comparative safety profiles. METHODS AND MATERIALS: We analyzed data from a prospective patient registry. Procedures using one of the following UA models were included: Integra® CUSA, Söring®, and Stryker® Sonopet. The primary endpoint was morbidity at discharge, defined as significant worsening on the Karnofsky Performance Scale. Secondary endpoints included morbidity and mortality until 3 months postoperative (M3), occurrence, type, and etiology of complications. RESULTS: Of n = 1028 procedures, the CUSA was used in n = 354 (34.4 %), the Söring in n = 461 (44.8 %), and the Sonopet in n = 213 (20.7 %). There was some heterogeneity of study groups. In multivariable analysis, patients in the Söring (adjusted odds ratio (aOR) 1.29; 95 % confidence interval (CI), 0.80-2.08; p = 0.299), and Sonopet group (aOR, 0.86; 95 % CI, 0.46-1.61; p = 0.645) were as likely as patients in the CUSA group to experience discharge morbidity. At M3, patients in the Söring (aOR, 1.20; 95 % CI, 0.78-1.86; p = 0.415) and Sonopet group (aOR, 0.53; 95 % CI, 0.26-1.08; p = 0.080) were as likely as patients in the CUSA group to experience morbidity. There were also no differences for M3 morbidity in subgroup analyses for gliomas, meningiomas, and metastases. The grade (p = 0.608) and etiology (p = 0.849) of postoperative complications were similar. CONCLUSIONS: Neurosurgeons select UA types with regard to certain case-specific characteristics. The safety profiles of three commonly used UA types appear mostly similar.

The influence of preoperative dependency on mortality, functional recovery and complications after microsurgical resection of intracranial tumors.

INTRODUCTION: The decision whether to operate on patients with intracranial tumors is complex and influenced by patient-specific factors, including the preoperative functional status. This work assesses the risks for mortality and complications, and post-operative recovery in functionally dependent patients undergoing microsurgical resection of intracranial tumors. METHODS: Observational two-center study, analyzing institutional registry data. Dependency was defined as admission Karnofsky Performance Scale (KPS) of ≤ 50. The primary endpoint was in-hospital mortality. Secondary endpoints were rate and type [Clavien-Dindo grade (CDG)] of complications, as well as postoperative change in KPS until the 3-month follow-up (M3). RESULTS: Of n = 1951 patients, n = 98 (5.0%) were dependent. Mortality rates were 2.0% for dependent and 0.4% for independent patients (p = 0.018). In univariable analysis, dependent patients were more likely than independent patients to die in hospital (OR 5.49, 95% CI 1.12-26.8, p = 0.035). In a multivariable model, the effect was slightly attenuated (OR 4.75, 95% CI 0.91-24.7, p = 0.064). Dependent patients tended to experience more postoperative complications. They were more likely to suffer from a severe complication (CDG 4 and 5; OR 3.55, 95% CI 1.49-8.46, p = 0.004). In 40.8 and 52.4% of cases, dependent patients regained functional independence at discharge and M3, respectively. CONCLUSIONS: In operated patients with intracranial tumors presenting functionally dependent at admission, the risk for in-hospital mortality and complications is elevated. However, if conducted successfully, surgery may lead to regain of independence in every second patient within 3 months.

Ultrasonographic features of focal cortical dysplasia and their relevance for epilepsy surgery.

OBJECTIVE Surgery has proven to be the best therapeutic option for drug-refractory cases of focal cortical dysplasia (FCD)-associated epilepsy. Seizure outcome primarily depends on the completeness of resection, rendering the intraoperative FCD identification and delineation particularly important. This study aims to assess the diagnostic yield of intraoperative ultrasound (IOUS) in surgery for FCD-associated drug-refractory epilepsy. METHODS The authors prospectively enrolled 15 consecutive patients with drug-refractory epilepsy who underwent an IOUS-assisted microsurgical resection of a radiologically suspected FCD between January 2013 and July 2016. The findings of IOUS were compared with those of presurgical MRI postprocessing and the sonographic characteristics were analyzed in relation to the histopathological findings. The authors investigated the added value of IOUS in achieving completeness of resection and improving postsurgical seizure outcome. RESULTS The neurosurgeon was able to identify the dysplastic tissue by IOUS in all cases. The visualization of FCD type I was more challenging compared to FCD II and the demarcation of its borders was less clear. Postsurgical MRI showed residual dysplasia in 2 of the 3 patients with FCD type I. In all FCD type II cases, IOUS allowed for a clear intraoperative visualization and demarcation, strongly correlating with presurgical MRI postprocessing. Postsurgical MRI confirmed complete resection in all FCD type II cases. Sonographic features correlated with the histopathological classification of dysplasia (sonographic abnormalities increase continuously in the following order: FCD IA/IB, FCD IC, FCD IIA, FCD IIB). In 1 patient with IOUS features atypical for FCD, histopathological investigation showed nonspecific gliosis. CONCLUSIONS Morphological features of FCD, as identified by IOUS, correlate well with advanced presurgical imaging. The resolution of IOUS was superior to MRI in all FCD types. The appreciation of distinct sonographic features on IOUS allows the intraoperative differentiation between FCD and non-FCD lesions as well as the discrimination of different histological subtypes of FCD. Sonographic demarcation depends on the underlying degree of dysplasia. IOUS allows for more tailored resections by facilitating the delineation of the dysplastic tissue.