Resolving medulloblastoma cellular architecture by single-cell genomics.

Medulloblastoma is a malignant childhood cerebellar tumour type that comprises distinct molecular subgroups. Whereas genomic characteristics of these subgroups are well defined, the extent to which cellular diversity underlies their divergent biology and clinical behaviour remains largely unexplored. Here we used single-cell transcriptomics to investigate intra- and intertumoral heterogeneity in 25 medulloblastomas spanning all molecular subgroups. WNT, SHH and Group 3 tumours comprised subgroup-specific undifferentiated and differentiated neuronal-like malignant populations, whereas Group 4 tumours consisted exclusively of differentiated neuronal-like neoplastic cells. SHH tumours closely resembled granule neurons of varying differentiation states that correlated with patient age. Group 3 and Group 4 tumours exhibited a developmental trajectory from primitive progenitor-like to more mature neuronal-like cells, the relative proportions of which distinguished these subgroups. Cross-species transcriptomics defined distinct glutamatergic populations as putative cells-of-origin for SHH and Group 4 subtypes. Collectively, these data provide insights into the cellular and developmental states underlying subtype-specific medulloblastoma biology.

Development of an online calculator for the prediction of seizure freedom following pediatric hemispherectomy using the Hemispherectomy Outcome Prediction Scale (HOPS).

OBJECTIVES: Although hemispheric surgeries are among the most effective procedures for drug-resistant epilepsy (DRE) in the pediatric population, there is a large variability in seizure outcomes at the group level. A recently developed HOPS score provides individualized estimation of likelihood of seizure freedom to complement clinical judgement. The objective of this study was to develop a freely accessible online calculator that accurately predicts the probability of seizure freedom for any patient at 1-, 2-, and 5-years post-hemispherectomy. METHODS: Retrospective data of all pediatric patients with DRE and seizure outcome data from the original Hemispherectomy Outcome Prediction Scale (HOPS) study were included. The primary outcome of interest was time-to-seizure recurrence. A multivariate Cox proportional-hazards regression model was developed to predict the likelihood of post-hemispheric surgery seizure freedom at three time points (1-, 2- and 5- years) based on a combination of variables identified by clinical judgment and inferential statistics predictive of the primary outcome. The final model from this study was encoded in a publicly accessible online calculator on the International Network for Epilepsy Surgery and Treatment (iNEST) website (https://hops-calculator.com/). RESULTS: The selected variables for inclusion in the final model included the five original HOPS variables (age at seizure onset, etiologic substrate, seizure semiology, prior non-hemispheric resective surgery, and contralateral fluorodeoxyglucose-positron emission tomography [FDG-PET] hypometabolism) and three additional variables (age at surgery, history of infantile spasms, and magnetic resonance imaging [MRI] lesion). Predictors of shorter time-to-seizure recurrence included younger age at seizure onset, prior resective surgery, generalized seizure semiology, FDG-PET hypometabolism contralateral to the side of surgery, contralateral MRI lesion, non-lesional MRI, non-stroke etiologies, and a history of infantile spasms. The area under the curve (AUC) of the final model was 73.0%. SIGNIFICANCE: Online calculators are useful, cost-free tools that can assist physicians in risk estimation and inform joint decision-making processes with patients and families, potentially leading to greater satisfaction. Although the HOPS data was validated in the original analysis, the authors encourage external validation of this new calculator.

Feasibility and antitumour activity of the FGFR inhibitor erdafitnib in three paediatric CNS tumour patients.

Alterations of the fibroblast growth factor (FGF) signalling pathway are increasingly recognized as frequent oncogenic drivers of paediatric brain tumours. We report on three patients treated with the selective FGFR1-4 inhibitor erdafitinib. Two patients were diagnosed with a posterior fossa ependymoma group A (PFA EPN) and one with a low-grade glioma (LGG), harbouring FGFR3/FGFR1 overexpression and an FGFR1 internal tandem duplication (ITD), respectively. While both EPN patients did not respond to erdafitinib treatment, the FGFR1-ITD-harbouring tumour showed a significant decrease in tumour volume and contrast enhancement throughout treatment. The tumour remained stable 6 months after treatment discontinuation.

The Pediatric Epilepsy Surgery Interest Group (PESIG) under the auspice of the ISPN Research Committee: Availability of relevant technology and geographical distribution.

PURPOSE: Epilepsy surgery for pediatric drug-resistant epilepsy has been shown to improve seizure control, enhance patient and family QoL, and reduce mortality. However, diagnostic tools and surgical capacity are less accessible worldwide. The International Society Pediatric Neurosurgery (ISPN) has established a Pediatric Epilepsy Surgery Interest Group (PESIG), aiming to enhance global collaboration in research and educational aspects. The goals of this manuscript are to introduce PESIG and analyze geographical differences of epilepsy surgery and technology availability. METHODS: PESIG was established (2022) following an ISPN executive board decision. Using a standardized form, we surveyed the PESIG members, collecting and analyzing data regarding geographical distribution, and availability of various epilepsy treatment-related technologies. RESULTS: Two hundred eighty-two members registered in PESIG from 70 countries, over 6 continents, were included. We categorized the countries by GDP as follows: low, lower-medium, upper-medium, and high income. The most commonly available technology was vagus nerve stimulation 68%. Stereoelectroencephalography was available for 58%. North America had statistically significant greater availability compared to other continents. Europe had greater availability compared to Africa, Asia, and South (Latin) America. Asia had greater availability compared to Africa. High-income countries had statistically significant greater availability compared to other income groups; there was no significant difference between the other income-level subgroups. CONCLUSION: There is a clear discrepancy between countries and continents regarding access to epilepsy surgery technologies. This strengthens the need for collaboration between neurologists and neurosurgeons from around the world, to enhance medical education and training, as well as to increase technological availability.

The telovelar approach for fourth ventricular tumors in children: is removal of the posterior arch of C1 necessary?

PURPOSE: Various surgical nuances of the telovelar approach have been suggested. The necessity of removing the posterior arch of C1 to accomplish optimal tumor exposure is still debated. Therefore, we report on our experience and technical details of the fourth ventricular tumor resection in a modified prone position without systematic removal of the posterior arch of C1. METHODS: A retrospective analysis of all pediatric patients, who underwent a fourth ventricular tumor resection in the modified prone position between 2012 and 2021, was performed. RESULTS: We identified 40 patients with a median age of 6 years and a M:F ratio of 25:15. A telovelar approach was performed in all cases. In 39/40 patients, the posterior arch of C1 was not removed. In the remaining patient, the reason for removing C1 was tumor extension below the level of C2 with ventral extension. Gross or near total resection could be achieved in 34/39 patients, and subtotal resection in 5/39 patients. In none of the patients, a limited exposure, sight of view, or range of motion caused by the posterior arch of C1 was encountered, necessitating an unplanned removal of the posterior arch of C1. Importantly, in none of the cases, the surgeon had the impression of a limited sight of view to the most rostral parts of the fourth ventricle, which necessitated a vermian incision. CONCLUSION: A telovelar approach without the removal of the posterior arch of C1 allows for an optimal exposure of the fourth ventricle provided that critical nuances in patient positioning are considered.

An evaluation of physical and augmented patient-specific intracranial aneurysm simulators on microsurgical clipping performance and skills: a randomized controlled study.

OBJECTIVE: In the era of flow diversion, there is an increasing demand to train neurosurgeons outside the operating room in safely performing clipping of unruptured intracranial aneurysms. This study introduces a clip training simulation platform for residents and aspiring cerebrovascular neurosurgeons, with the aim to visualize peri-aneurysm anatomy and train virtual clipping applications on the matching physical aneurysm cases. METHODS: Novel, cost-efficient techniques allow the fabrication of realistic aneurysm phantom models and the additional integration of holographic augmented reality (AR) simulations. Specialists preselected suitable and unsuitable clips for each of the 5 patient-specific models, which were then used in a standardized protocol involving 9 resident participants. Participants underwent four sessions of clip applications on the models, receiving no interim training (control), a video review session (video), or a video review session and holographic clip simulation training (video + AR) between sessions 2 and 3. The study evaluated objective microsurgical skills, which included clip selection, number of clip applications, active simulation time, wrist tremor analysis during simulations, and occlusion efficacy. Aneurysm occlusions of the reference sessions were assessed by indocyanine green videoangiography, as well as conventional and photon-counting CT scans. RESULTS: A total of 180 clipping procedures were performed without technical complications. The measurements of the active simulation times showed a 39% improvement for all participants. A median of 2 clip application attempts per case was required during the final session, with significant improvement observed in experienced residents (postgraduate year 5 or 6). Wrist tremor improved by 29% overall. The objectively assessed aneurysm occlusion rate (Raymond-Roy class 1) improved from 76% to 80% overall, even reaching 93% in the extensively trained cohort (video + AR) (p = 0.046). CONCLUSIONS: The authors introduce a newly developed simulator training platform combining physical and holographic aneurysm clipping simulators. The development of exchangeable, aneurysm-comprising housings allows objective radio-anatomical evaluation through conventional and photon-counting CT scans. Measurable performance metrics serve to objectively document improvements in microsurgical skills and surgical confidence. Moreover, the different training levels enable a training program tailored to the cerebrovascular trainees' levels of experience and needs.

Visual outcomes after anterior temporal lobectomy and transsylvian selective amygdalohippocampectomy: A quantitative comparison of clinical and diffusion data.

OBJECTIVE: Anterior temporal lobectomy (ATL) and transsylvian selective amygdalohippocampectomy (tsSAHE) are effective treatment strategies for intractable temporal lobe epilepsy but may cause visual field deficits (VFDs) by damaging the optic radiation (OpR). Due to the OpR's considerable variability and because it is indistinguishable from surrounding tissue without further technical guidance, it is highly vulnerable to iatrogenic injury. This imaging study uses a multimodal approach to assess visual outcomes after epilepsy surgery. METHODS: We studied 62 patients who underwent ATL (n = 32) or tsSAHE (n = 30). Analysis of visual outcomes was conducted in four steps, including the assessment of (1) perimetry outcome (VFD incidence/extent, n = 44/40), (2) volumetric OpR tractography damage (n = 55), and the (3) relation of volumetric OpR tractography damage and perimetry outcome (n = 35). Furthermore, (4) fixel-based analysis (FBA) was performed to assess micro- and macrostructural changes within the OpR following surgery (n = 36). RESULTS: Altogether, 56% of all patients had postoperative VFDs (78.9% after ATL, 36.36% after tsSAHE, p = .011). VFDs and OpR tractography damage tended to be more severe within the ATL group (ATL vs. tsSAHE, integrity of contralateral upper quadrant: 65% vs. 97%, p = .002; OpR tractography damage: 69.2 mm3 vs. 3.8 mm3 , p = .002). Volumetric OpR tractography damage could reliably predict VFD incidence (86% sensitivity, 78% specificity) and could significantly explain VFD extent (R2  = .47, p = .0001). FBA revealed a more widespread decline of fibre cross-section within the ATL group. SIGNIFICANCE: In the context of controversial visual outcomes following epilepsy surgery, this study provides clinical as well as neuroimaging evidence for a higher risk and greater severity of postoperative VFDs after ATL compared to tsSAHE. Volumetric OpR tractography damage is a feasible parameter to reliably predict this morbidity in both treatment groups and may ultimately support personalized planning of surgical candidates. Advanced diffusion analysis tools such as FBA offer a structural explanation of surgically induced visual pathway damage, allowing noninvasive quantification and visualization of micro- and macrostructural tract affection.

Placement of EVD in pediatric posterior fossa tumors: safe and efficient or old-fashioned? The Vienna experience.

PURPOSE: The perioperative treatment of hydrocephalus in pediatric posterior fossa tumors with an external ventricular drain (EVD) is the treatment of choice in our center. We analyzed our experience in using EVD concerning safety and effectivity. METHODS: This is a single-center retrospective cohort study of 100 consecutive pediatric patients who underwent resection for a newly diagnosed tumor in the posterior fossa between 2011 and 2022. RESULTS: Of the 100 patients with posterior fossa tumors, 80 patients (80%) had radiological signs of hydrocephalus at presentation, 49 patients (49%) of whom underwent placement of an EVD. In 40 patients, the EVD was inserted at a mean of 2.25 days prior to the tumor resection; 9 had the EVD inserted during tumor resection (frontal trajectory in 7 patients, occipital trajectory in 2 patients). Histology revealed pilocytic astrocytoma in 48 patients, medulloblastoma in 32, ependymoma in 11, and other histologic entities in 9 patients. Gross total/near-total resection was achieved in 46 (95.83%) of the 48 pilocytic astrocytomas, 30 (93.75%) of the 32 medulloblastomas, and 11 (100%) of the 11 ependymomas. The mean number of total days with the EVD in place was 8.61 ± 3.82 (range 2-16 days). The mean number of days with an EVD after tumor resection was 6.35 ± 3.8 (range 0-16 days). EVD-associated complications were seen in 6 patients (12.24%) including one infection. None of these resulted in a worse clinical course or any long-term sequelae. Permanent CSF diversion at 6 months after surgery was necessary in 13 patients (13%), including two VP shunt, two SD-shunt, six endoscopic third ventriculostomy (ETV), and three combined VP shunt and ETV procedures. Patients with a medulloblastoma or ependymoma had a higher rate of permanent CSF diversion needed than the group of pilocytic astrocytoma patients (27.9% versus 2.13%, p < 0.001). In patients with metastatic disease, 7 of 17 patients (41.18%) needed a permanent CSF diversion, compared to 6 of 83 patients (7.23%) in the group without metastasis (p = 0.001). CONCLUSION: The treatment of hydrocephalus in pediatric posterior fossa tumors with an EVD as a temporary measure is safe and effective, provided that a multi-professional understanding for its handling is given and there is no need for a long transport of the children.

Retrospective comparison of percutaneous balloon compression and radiofrequency-thermocoagulation in the management of trigeminal neuralgia.

PURPOSE: To compare percutaneous balloon compression (PBC) and radiofrequency thermocoagulation (RFTC) for the treatment of trigeminal neuralgia. METHODS: This was a retrospective single-center analysis of data from 230 patients with trigeminal neuralgia who underwent 202 PBC (46%) and 234 RFTC (54%) from 2002 to 2019. Comparison of demographic data and trigeminal neuralgia characteristics between procedures as well as assessment of 1) initial pain relief by an improved Barrow Neurological Institute (BNI) pain intensity scale of I-III; 2) recurrence-free survival of patients with a follow-up of at least 6 months by Kaplan-Meier analysis; 3) risk factors for failed initial pain relief and recurrence-free survival by regression analysis; and 4) complications and adverse events. RESULTS: Initial pain relief was achieved in 353 (84.2%) procedures and showed no significant difference between PBC (83.7%) and RFTC (84.9%). Patients who suffered from multiple sclerosis (odds ratio 5.34) or had a higher preoperative BNI (odds ratio 2.01) showed a higher risk of not becoming pain free. Recurrence-free survival in 283 procedures was longer for PBC (44%) with 481 days compared to RFTC (56%) with 421 days (p=0.036) but without statistical significance. The only factors that showed a significant influence on longer recurrence-free survival rates were a postoperative BNI ≤ II (P=<0.0001) and a BNI facial numbness score ≥ 3 (p = 0.009). The complication rate of 22.2% as well as zero mortality showed no difference between the two procedures (p=0.162). CONCLUSION: Both percutaneous interventions led to a comparable initial pain relief and recurrence-free survival with a low and comparable probability of complications. An individualized approach, considering the advantages and disadvantages of each intervention, should guide the decision-making process. Prospective comparative trials are urgently needed.

Antibody Profiling and In Silico Functional Analysis of Differentially Reactive Antibody Signatures of Glioblastomas and Meningiomas.

Studies on tumor-associated antigens in brain tumors are sparse. There is scope for enhancing our understanding of molecular pathology, in order to improve on existing forms, and discover new forms, of treatment, which could be particularly relevant to immuno-oncological strategies. To elucidate immunological differences, and to provide another level of biological information, we performed antibody profiling, based on a high-density protein array (containing 8173 human transcripts), using IgG isolated from the sera of n = 12 preoperative and n = 16 postoperative glioblastomas, n = 26 preoperative and n = 29 postoperative meningiomas, and n = 27 healthy, cancer-free controls. Differentially reactive antigens were compared to gene expression data from an alternate public GBM data set from OncoDB, and were analyzed using the Reactome pathway browser. Protein array analysis identified approximately 350-800 differentially reactive antigens, and revealed different antigen profiles in the glioblastomas and meningiomas, with approximately 20-30%-similar and 10-15%-similar antigens in preoperative and postoperative sera, respectively. Seroreactivity did not correlate with OncoDB-derived gene expression. Antigens in the preoperative glioblastoma sera were enriched for signaling pathways, such as signaling by Rho-GTPases, COPI-mediated anterograde transport and vesicle-mediated transport, while the infectious disease, SRP-dependent membrane targeting cotranslational proteins were enriched in the meningiomas. The pre-vs. postoperative seroreactivity in the glioblastomas was enriched for antigens, e.g., platelet degranulation and metabolism of lipid pathways; in the meningiomas, the antigens were enriched in infectious diseases, metabolism of amino acids and derivatives, and cell cycle. Antibody profiling in both tumor entities elucidated several hundred antigens and characteristic signaling pathways that may provide new insights into molecular pathology and may be of interest for the development of new treatment strategies.

Development of a 3D printed patient-specific neonatal brain simulation model using multimodality imaging for perioperative management.

BACKGROUND: Medical-imaging-based three-dimensional (3D) printed models enable improvement in skills training, surgical planning, and decision-making. This pilot study aimed to use multimodality imaging and to add and compare 3D ultrasound as a future standard to develop realistic neonatal brain models including the ventricular system. METHODS: Retrospective computed tomography (CT), magnetic resonance imaging (MRI), and 3D ultrasound-based brain imaging protocols of five neonatal patients were analyzed and subsequently segmented with the aim of developing a multimodality imaging-based 3D printed model. The ventricular anatomy was analyzed to compare the MRI and 3D ultrasound modalities. RESULTS: A realistic anatomical model of the neonatal brain, including the ventricular system, was created using MRI and 3D ultrasound data from one patient. T2-weighted isovoxel 3D MRI sequences were found to have better resolution and accuracy than 2D sequences. The surface area, anatomy, and volume of the lateral ventricles derived from both MRI and 3D ultrasound were comparable. CONCLUSIONS: We created an ultrasound- and MRI-based 3D printed patient-specific neonatal brain simulation model that can be used for perioperative management. To introduce 3D ultrasound as a standard for 3D models, additional dimensional correlations between MRI and ultrasound need to be examined. IMPACT: We studied the feasibility of implementing 3D ultrasound as a standard for 3D printed models of the neonatal brain. Different imaging modalities were compared and both 3D isotropic MRI and 3D ultrasound imaging are feasible for printing neonatal brain models with good dimensional accuracy and anatomical replication. Further dimensional correlations need to be defined to implement it as a standard to produce 3D printed models.

How can we optimize the long-term outcome in children with intracranial cavernous malformations? A single-center experience of 61 cases.

The objective is to provide a treatment algorithm for pediatric patients with intracranial cavernous malformations (CMs) based on our experience. Patients < 18 years of age who were treated either surgically or conservatively at the authors' institution between 1982 and 2019 were retrospectively evaluated. A total of 61 pediatric patients were treated at the authors' institution: 39 with lobar CMs; 18 with deep CMs, including 12 in the brainstem and 6 in the basal ganglia; and 4 with CMs in the cerebellar hemispheres. Forty-two patients underwent surgery, and 19 were treated conservatively. The median follow-up time was 65 months (1-356 months). In surgically treated patients, lesions were larger (2.4 cm vs 0.9 cm, p < 0.001). In patients with lobar CMs, seizures were more common (72% vs 21%, p = 0.003) in the surgery group than in conservatively managed patients. In deep CMs, modified Rankin scale (mRS) was higher (4 vs 1, p = 0.003) in the surgery group than in conservatively treated patients. At the time of last follow-up, no differences in Wieser outcome class I were seen (86% vs 67%) in lobar CMs, and mRS scores had aligned between the treatment groups in deep CMs (1 vs 0). We encountered no new permanent neurological deficit at time of last follow-up. We propose a treatment algorithm according to lesion location and size, burden of symptoms, epilepsy workup, and further clinical course during observation. A conservative management is safe in pediatric patients with asymptomatic CMs. Gross total resection should be the aim in patients with symptomatic lobar CMs. A less aggressive approach with subtotal resection, when required to prevent neurological compromise, sustainably improves neurological outcome in patients with deep CMs.

Targeting fibroblast growth factor receptors to combat aggressive ependymoma.

Ependymomas (EPN) are central nervous system tumors comprising both aggressive and more benign molecular subtypes. However, therapy of the high-risk subtypes posterior fossa group A (PF-A) and supratentorial RELA-fusion positive (ST-RELA) is limited to gross total resection and radiotherapy, as effective systemic treatment concepts are still lacking. We have recently described fibroblast growth factor receptors 1 and 3 (FGFR1/FGFR3) as oncogenic drivers of EPN. However, the underlying molecular mechanisms and their potential as therapeutic targets have not yet been investigated in detail. Making use of transcriptomic data across 467 EPN tissues, we found that FGFR1 and FGFR3 were both widely expressed across all molecular groups. FGFR3 mRNA levels were enriched in ST-RELA showing the highest expression among EPN as well as other brain tumors. We further identified high expression levels of fibroblast growth factor 1 and 2 (FGF1, FGF2) across all EPN subtypes while FGF9 was elevated in ST-EPN. Interrogation of our EPN single-cell RNA-sequencing data revealed that FGFR3 was further enriched in cycling and progenitor-like cell populations. Corroboratively, we found FGFR3 to be predominantly expressed in radial glia cells in both mouse embryonal and human brain datasets. Moreover, we detected alternative splicing of the FGFR1/3-IIIc variant, which is known to enhance ligand affinity and FGFR signaling. Dominant-negative interruption of FGFR1/3 activation in PF-A and ST-RELA cell models demonstrated inhibition of key oncogenic pathways leading to reduced cell growth and stem cell characteristics. To explore the feasibility of therapeutically targeting FGFR, we tested a panel of FGFR inhibitors in 12 patient-derived EPN cell models revealing sensitivity in the low-micromolar to nano-molar range. Finally, we gain the first clinical evidence for the activity of the FGFR inhibitor nintedanib in the treatment of a patient with recurrent ST-RELA. Together, these preclinical and clinical data suggest FGFR inhibition as a novel and feasible approach to combat aggressive EPN.

Comparison of the real-world effectiveness of vertical versus lateral functional hemispherotomy techniques for pediatric drug-resistant epilepsy: A post hoc analysis of the HOPS study.

OBJECTIVE: This study was undertaken to determine whether the vertical parasagittal approach or the lateral peri-insular/peri-Sylvian approach to hemispheric surgery is the superior technique in achieving long-term seizure freedom. METHODS: We conducted a post hoc subgroup analysis of the HOPS (Hemispheric Surgery Outcome Prediction Scale) study, an international, multicenter, retrospective cohort study that identified predictors of seizure freedom through logistic regression modeling. Only patients undergoing vertical parasagittal, lateral peri-insular/peri-Sylvian, or lateral trans-Sylvian hemispherotomy were included in this post hoc analysis. Differences in seizure freedom rates were assessed using a time-to-event method and calculated using the Kaplan-Meier survival method. RESULTS: Data for 672 participants across 23 centers were collected on the specific hemispherotomy approach. Of these, 72 (10.7%) underwent vertical parasagittal hemispherotomy and 600 (89.3%) underwent lateral peri-insular/peri-Sylvian or trans-Sylvian hemispherotomy. Seizure freedom was obtained in 62.4% (95% confidence interval [CI] = 53.5%-70.2%) of the entire cohort at 10-year follow-up. Seizure freedom was 88.8% (95% CI = 78.9%-94.3%) at 1-year follow-up and persisted at 85.5% (95% CI = 74.7%-92.0%) across 5- and 10-year follow-up in the vertical subgroup. In contrast, seizure freedom decreased from 89.2% (95% CI = 86.3%-91.5%) at 1-year to 72.1% (95% CI = 66.9%-76.7%) at 5-year to 57.2% (95% CI = 46.6%-66.4%) at 10-year follow-up for the lateral subgroup. Log-rank test found that vertical hemispherotomy was associated with durable seizure-free progression compared to the lateral approach (p = .01). Patients undergoing the lateral hemispherotomy technique had a shorter time-to-seizure recurrence (hazard ratio = 2.56, 95% CI = 1.08-6.04, p = .03) and increased seizure recurrence odds (odds ratio = 3.67, 95% CI = 1.05-12.86, p = .04) compared to those undergoing the vertical hemispherotomy technique. SIGNIFICANCE: This pilot study demonstrated more durable seizure freedom of the vertical technique compared to lateral hemispherotomy techniques. Further studies, such as prospective expertise-based observational studies or a randomized clinical trial, are required to determine whether a vertical approach to hemispheric surgery provides superior long-term seizure outcomes.

Hemispherectomy Outcome Prediction Scale: Development and validation of a seizure freedom prediction tool.

OBJECTIVE: To develop and validate a model to predict seizure freedom in children undergoing cerebral hemispheric surgery for the treatment of drug-resistant epilepsy. METHODS: We analyzed 1267 hemispheric surgeries performed in pediatric participants across 32 centers and 12 countries to identify predictors of seizure freedom at 3 months after surgery. A multivariate logistic regression model was developed based on 70% of the dataset (training set) and validated on 30% of the dataset (validation set). Missing data were handled using multiple imputation techniques. RESULTS: Overall, 817 of 1237 (66%) hemispheric surgeries led to seizure freedom (median follow-up = 24 months), and 1050 of 1237 (85%) were seizure-free at 12 months after surgery. A simple regression model containing age at seizure onset, presence of generalized seizure semiology, presence of contralateral 18-fluoro-2-deoxyglucose-positron emission tomography hypometabolism, etiologic substrate, and previous nonhemispheric resective surgery is predictive of seizure freedom (area under the curve = .72). A Hemispheric Surgery Outcome Prediction Scale (HOPS) score was devised that can be used to predict seizure freedom. SIGNIFICANCE: Children most likely to benefit from hemispheric surgery can be selected and counseled through the implementation of a scale derived from a multiple regression model. Importantly, children who are unlikely to experience seizure control can be spared from the complications and deficits associated with this surgery. The HOPS score is likely to help physicians in clinical decision-making.

The clinical relevance of laboratory prognostic scores for patients with radiosurgically treated brain metastases of non-pulmonary primary tumor.

PURPOSE: To investigate the clinical value of the inflammation based prognostic scores for patients with radiosurgically treated brain metastases (BM) originating from non-pulmonary primary tumor (PT). METHODS: A retrospective analysis of 340 BM patients of different PT origin (melanoma, breast, gastrointestinal, or genitourinary cancer) was performed. Pre-radiosurgical laboratory prognostic scores, such as the Neutrophil-to-Lymphocyte Ratio (NLR), the Platelet-to-Lymphocyte Ratio (PLR), Lymphocyte-to-Monocyte Ratio (LMR), and the modified Glasgow Prognostic Score (mGPS), were investigated within 14 days before the first Gamma Knife radiosurgical treatment (GKRS1). RESULTS: In our study cohort, the estimated survival was significantly longer in patients with NLR < 5 (p < 0.001), LMR > 4 (p = 0.001) and in patients with a mGPS score of 0 (p < 0.001). Furthermore, univariate and multivariate Cox regression models revealed NLR ≥ 5, LMR < 4 and mGPS score ≥ 1 as independent prognostic factors for an increased risk of death even after adjusting for age, sex, KPS, extracranial metastases status, presence of neurological symptoms and treatment with immunotherapy (IT) or targeted therapy (TT). CONCLUSIONS: Summarizing previously published and present data, pre-radiosurgical mGPS and NLR groups seem to be the most effective and simple independent prognostic factors to predict clinical outcome in radiosurgically treated BM patients.

Pre-radiosurgery leucocyte ratios and modified glasgow prognostic score predict survival in non-small cell lung cancer brain metastases patients.

INTRODUCTION: The predictive value of the pre-radiosurgery Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Lymphocyte-to-Monocyte Ratio (LMR) and the modified Glasgow Prognostic Score (mGPS) was assessed for the first time in a homogenous group of NSCLC brain metastaes (BM) patients. METHODS: We retrospectively evaluated 185 NSCLC-BM patients, who were treated with Gamma Knife Radiosurgery (GKRS). Patients with immunotherapy or targeted therapy were excluded. Routine laboratory parameters were reviewed within 14 days before GKRS1. RESULTS: Median survival after GKRS1 was significantly longer in patients with NLR < 5 (p < 0.001), PLR < 180 (p = 0.003) and LMR ≥ 4 (p = 0.023). The Cox regression model for the continuous metric values revealed that each increase in the NLR of 1 equaled an increase of 4.3% in risk of death (HR: 1.043; 95%CI = 1.020-1.067, p < 0.001); each increase in the PLR of 10 caused an increase of 1.3% in risk of death (HR: 1.013; 95%CI = 1.004-1.021; p = 0.003) and each increase in the LMR of 1 equaled a decrease of 20.5% in risk of death (HR: 0.795; 95%CI = 0.697-0.907; p = 0.001). Moreover, the mGPS group was a highly significant predictor for survival after GKRS1 (p < 0.001) with a HR of 2.501 (95%CI = 1.582-3.954; p < 0.001). NLR, PLR, LMR values and mGPS groups were validated as independent prognostic factors for risk of death after adjusting for sex, KPS, age and presence of extracranial metastases. CONCLUSION: NLR, PLR, LMR and mGPS represent effective and simple tools to predict survival in NSCLC patients prior to radiosurgery for brain metastases.

New-onset seizures after cranioplasty-a different view on a putatively frequently observed phenomenon.

BACKGROUND: New-onset seizures after cranioplasty (NOSAC) are reported to be a frequent complication of cranioplasty (CP) after decompressive hemicraniectomy (DHC). There are considerable differences in the incidence of NOSAC and contradictory data about presumed risk factors in the literature. We suggest NOSAC to be a consequence of patients' initial condition which led to DHC, rather than a complication of subsequent CP. We conducted a retrospective analysis to verify our hypothesis. METHODS: The medical records of all patients ≥ 18 years who underwent CP between 2002 and 2017 at our institution were evaluated including incidence of seizures, time of seizure onset, and presumed risk factors. Indication for DHC, type of implant used, timing of CP, patient age, presence of a ventriculoperitoneal shunt (VP shunt), and postoperative complications were compared between patients with and without NOSAC. RESULTS: A total of 302 patients underwent CP between 2002 and 2017, 276 of whom were included in the outcome analysis and the incidence of NOSAC was 23.2%. Although time between DHC and CP differed significantly between DHC indication groups, time between DHC and seizure onset did not differ, suggesting the occurrence of seizures to be independent of the procedure of CP. Time of follow-up was the only factor associated with the occurrence of NOSAC. CONCLUSION: New-onset seizures may be a consequence of the initial condition leading to DHC rather than of CP itself. Time of follow-up seems to play a major role in detection of new-onset seizures.

Cranioplasty following ventriculoperitoneal shunting: lessons learned.

OBJECTIVE: Cranioplasty (CP) is considered as a straightforward and technically unchallenging operation; however, complication rates are high reaching up to 56%. Presence of a ventriculoperitoneal shunt (VPS) and timing of CP are reported risk factors for complications. Pressure gradients and scarring at the site of the cranial defect seem to be critical in this context. The authors present their experiences and lessons learned. METHODS: A consecutive series of all patients who underwent CP at the authors' institution between 2002 and 2017 were included in this retrospective analysis. Complications were defined as all events that required reoperation. Logistic regression analysis and chi-squared test were conducted to evaluate the complication rates according to suspected risk factors. RESULTS: A total of 302 patients underwent cranioplasty between 2002 and 2017. The overall complication rate was 17.5%. Complications included epi-/subdural fluid collection (7.3%) including hemorrhage (4.6%) and hygroma (2.6%), bone graft resorption (5.3%), bone graft infection (2.0%), and hydrocephalus (5.7%). Overall, 57 patients (18.9%) had undergone shunt implantation prior to CP. The incidence of epi-/subdural fluid collection was 19.3% in patients with VPS and 4.5% in patients without VPS, OR 5.1 (95% CI 2.1-12.4). Incidence of hygroma was higher in patients who underwent early CP. Patients with temporary shunt ligation for CP did not suffer from complications. CONCLUSION: CP in patients with a VPS remains a high-risk procedure. Any effort to understand the pressure dynamics and to reduce factors that may trigger the formation of a large epidural space must be undertaken.

Microvascular decompression in trigeminal neuralgia: predictors of pain relief, complication avoidance, and lessons learned.

OBJECTIVE: To analyze characteristics associated with long-term pain relief after microvascular decompression (MVD) for trigeminal neuralgia (TGN). Description of associated morbidity and complication avoidance. METHODS: One hundred sixty-five patients with TGN underwent 171 MVD surgeries at the authors' institution. Patient characteristics and magnetic resonance imaging (MRI) datasets were obtained through the hospital's archiving system. Patients provided information about pre- and post-operative pain characteristics and neurologic outcome. Favorable outcome was defined as a Barrow Neurological Institute (BNI) pain intensity score of I to III with post-operative improvement of I grade. RESULTS: Type of TGN pain with purely paroxysmal pain (p = 0.0202*) and TGN classification with classical TGN (p = 0.0372*) were the only significant predictors for long-term pain relief. Immediate pain relief occurred in 90.6% of patients with a recurrence rate of 39.4% after 3.5 ± 4.6 years. MRI reporting of a neurovascular conflict had a low negative predictive value of 39.6%. Mortality was 0% with major complications observed in 8.2% of patients. Older age was associated with lower complication rates (p = 0.0009***). Re-MVD surgeries showed improved long-term pain relief in four out of five cases. CONCLUSIONS: MVD is a safe and effective procedure even in the elderly. It has the unique potential to cure TGN if performed on a regular basis, and if key surgical steps are respected. Early MVD should be offered in case of medical treatment failure and paroxysmal pain symptoms. The presence of a neurovascular conflict on MRI is not mandatory. In case of recurrence, re-MVD is a good treatment option that should be discussed with patients. HIGHLIGHTS: • Long-term analysis of pain relief after MVD. • Positive predictors for outcome: classical TGN and purely paroxysmal pain. • Presence of neurovascular conflict in MRI is not mandatory for MVD surgery. • Analysis of complications and surgical nuances for avoidance. • MVD is a safe procedure also in the elderly.