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.

Which parameters influence cognitive, psychiatric and long-term seizure outcome in mesial temporal lobe epilepsy after selective amygdalohippocampectomy?

BACKGROUND: We aimed to analyze potentially prognostic factors which could have influence on postoperative seizure, neuropsychological and psychiatric outcome in a cohort of patients with mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis (HS) after selective amygdalohippocampectomy (SAHE) via transsylvian approach. METHODS: Clinical variables of 171 patients with drug-resistant MTLE with HS (88 females) who underwent SAHE between 1994 and 2019 were evaluated using univariable and multivariable logistic regression models, to investigate which of the explanatory parameters can best predict the outcome. RESULTS: At the last available follow-up visit 12.3 ± 6.3 years after surgery 114 patients (67.9%) were seizure-free. Left hemispheric MTLE was associated with worse postoperative seizure outcome at first year after surgery (OR = 0.54, p = 0.01), female sex-with seizure recurrence at years 2 (OR = 0.52, p = 0.01) and 5 (OR = 0.53, p = 0.025) and higher number of preoperative antiseizure medication trials-with seizure recurrence at year 2 (OR = 0.77, p = 0.0064), whereas patients without history of traumatic brain injury had better postoperative seizure outcome at first year (OR = 2.08, p = 0.0091). All predictors lost their predictive value in long-term course. HS types had no prognostic influence on outcome. Patients operated on right side performed better in verbal memory compared to left (VLMT 1-5 p < 0.001, VLMT 7 p = 0.001). Depression occurred less frequently in seizure-free patients compared to non-seizure-free patients (BDI-II Z = - 2.341, p = 0.019). CONCLUSIONS: SAHE gives an improved chance of achieving good postoperative seizure, psychiatric and neuropsychological outcome in patients with in MTLE due to HS. Predictors of short-term outcome don't predict long-term outcome.

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.

Current Aspects of Intraoperative High-Field (3T) Magnetic Resonance Imaging in Pediatric Neurosurgery: Experiences from a Recently Launched Unit at a Tertiary Referral Center.

OBJECTIVE: To evaluate the neurosurgical and economic effectiveness of a newly launched intraoperative high-field (3T) magnetic resonance imaging (MRI) suite for pediatric tumor and epilepsy neurosurgery. METHODS: Altogether, 148 procedures for 124 pediatric patients (mean age, 8.7 years; range, 0-18 years) within a 2.5-year period were undertaken in a 2-room intraoperative MRI (iopMRI) suite. Surgery was performed mainly for intractable epilepsy (n = 81; 55%) or pediatric brain tumors (n = 65; 44%) in the supine (n = 113; 76%) and prone (n = 35; 24%) positions. The mean time of iopMRI from draping to re-surgery was 50 minutes. RESULTS: IopMRI was applied not in all but in 64 of 148 procedures (43%); in 45 procedures (31%), iopMRI was estimated unnecessary at the end of surgery based on the leading surgeon's decision. In the remaining 39 procedures (26%), ultra-early postoperative MRI was carried out after closure with the patient still sterile in the head coil. Of the 64 procedures with iopMRI, second-look surgery was performed in 26% (in epilepsy surgery in 17%, in tumor surgery in 9%). We did not encounter any infections, wound revisions, or position-related or anesthesiology-related complications. CONCLUSIONS: We used iopMRI in less than half of pediatric tumor and epilepsy surgery for which it was scheduled initially. Therefore, high costs argue against its routine use in pediatric neurosurgery, although it optimized surgical results in one quarter of patients and met high safety standards.

The Site of Origin of Medulloblastoma: Surgical Observations Correlated to Molecular Groups.

Developmental gene expression data from medulloblastoma (MB) suggest that WNT-MB originates from the region of the embryonic lower rhombic lip (LRL), whereas SHH-MB and non-WNT/non-SHH MB arise from cerebellar precursor matrix regions. This study aimed to analyze detailed intraoperative data with regard to the site of origin (STO) and compare these findings with the hypothesized regions of origin associated with the molecular group. A review of the institutional database identified 58 out of 72 pediatric patients who were operated for an MB at our department between 1996 and 2020 that had a detailed operative report and a surgical video as well as clinical and genetic classification data available for analysis. The STO was assessed based on intraoperative findings. Using the intraoperatively defined STO, "correct" prediction of molecular groups was feasible in 20% of WNT-MB, 60% of SHH-MB and 71% of non-WNT/non-SHH MB. The positive predictive values of the neurosurgical inspection to detect the molecular group were 0.21 (95% CI 0.08-0.48) for WNT-MB, 0.86 (95% CI 0.49-0.97) for SHH-MB and 0.73 (95% CI 0.57-0.85) for non-WNT/non-SHH MB. The present study demonstrated a limited predictive value of the intraoperatively observed STO for the prediction of the molecular group of MB.

Imaging brain tissue architecture across millimeter to nanometer scales.

Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease.

Proof-of-Concept for Liquid Biopsy Disease Monitoring of MYC-Amplified Group 3 Medulloblastoma by Droplet Digital PCR.

BACKGROUND: Liquid biopsy diagnostic methods are an emerging complementary tool to imaging and pathology techniques across various cancer types. However, there is still no established method for the detection of molecular alterations and disease monitoring in MB, the most common malignant CNS tumor in the pediatric population. In the presented study, we investigated droplet digital polymerase chain reaction (ddPCR) as a highly sensitive method for the detection of MYC amplification in bodily fluids of group 3 MB patients. METHODS: We identified a cohort of five MYC-amplified MBs by methylation array and FISH. Predesigned and wet-lab validated probes for ddPCR were used to establish the detection method and were validated in two MYC-amplified MB cell lines as well as tumor tissue of the MYC-amplified cohort. Finally, a total of 49 longitudinal CSF samples were analyzed at multiple timepoints during the course of the disease. RESULTS: Detection of MYC amplification by ddPCR in CSF showed a sensitivity and specificity of 90% and 100%, respectively. We observed a steep increase in amplification rate (AR) at disease progression in 3/5 cases. ddPCR was proven to be more sensitive than cytology for the detection of residual disease. In contrast to CSF, MYC amplification was not detectable by ddPCR in blood samples. CONCLUSIONS: ddPCR proves to be a sensitive and specific method for the detection of MYC amplification in the CSF of MB patients. These results warrant implementation of liquid biopsy in future prospective clinical trials to validate the potential for improved diagnosis, disease staging and monitoring.

Individualized surgical treatment of Chiari 1 malformation: A single-center experience.

OBJECTIVE: To present our experience with an individualized surgical approach to treat Chiari malformation type 1. METHODS: Based on (1) neurological symptoms, (2) the existence and extent of a syrinx and (3) the degree of the tonsillar descent we performed four types of approaches on a case-by-case basis in 81 patients: (1) foramen magnum decompression (FMD) with dura splitting (FMDds); (2) FMD with duraplasty (FMDdp); (3) FMD with duraplasty and tonsillar manipulation (FMDao); and (4) tonsillar resection/reduction (TR). Patient characteristics, Chiari Severity Index (CSI), fourth ventricular roof angle (FVRA) and Chicago Chiari Outcome Scale (CCOS) were analyzed. RESULTS: CCOS was between 13 and 16 points in 8/11 (73 %) patients after FMDds, 38/45 (84 %) patients after FMDdp, and 24/24 (100 %, one patient lost to follow-up) patients after TR. We experienced an overall complication rate of 13.6 % (11/81) in this series, whereas seven of these eleven complications (64 %) occurred in the FMDao group and the complication rate increased with the invasiveness of the approach (0 % FMDds; 4 % FMDdp; 12 % TR). CONCLUSION: Given the clear correlation between the extend of the approach and the complication rate the least invasive approach necessary to achieve clinical improvement should be selected. Due to the high complication rates, FMDao should not be used as a treatment option. The severity of the tonsillar descent, basilar invagination and current CM1 scores could be used to aid in the approach selection.

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.

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.

Sociocultural variables have a major impact on participation in patients treated for paediatric posterior fossa tumours.

BACKGROUND: This study investigates the severeness of participation barriers in patients surviving paediatric posterior fossa tumours (PFT) many years after treatment. In the past, aetiological studies on adverse outcome have primarily focused on pathobiological risk factors. The current analysis aims to investigate the importance of environmental variables. METHODS: On average, 10 years after diagnosis, educational and social difficulties of 42 patients surviving paediatric PFT (mean age 17 years) were inquired using a self-constructed questionnaire following the Psychosocial Resource-Orientated Assessment (PREDI). Educational or social participation barriers were defined by self- and/or proxy-reported difficulties in school or in peer relationships. Accordingly, the children and adolescents were categorized into groups of adequate and limited participation. Subsequently, the study identified potential pathobiological (treatment type, hydrocephalus, tumour relapse, gender, age at diagnosis, seizures and cerebellar mutism) and environmental (parental and maternal education, siblings, main language, discrepancies between personal and environmental values, regular physical activity and private living space) risk factors and investigated whether patients with adequate and limited participation differed in the number of risk factors. RESULTS: Almost one decade after treatment, two thirds of patients experienced educational and/or social difficulties. Patients with limited participation were more frequently associated with environmental factors such as low maternal education degree, siblings, main language other than German, discrepancies between societal and personal values and irregular physical activity, as well as the pathobiological risk factors treatment type, hydrocephalus, tumour relapse, cerebellar mutism and seizures. These variables significantly discriminated between patients with and without limited participation. CONCLUSIONS: Limited participation in patients treated for paediatric PFT is common. Next to pathobiological, also environmental risk factors play a major role in educational and social participation barriers. This highlights the fact that solely considering pathobiology is not sufficient when investigating risk factors for the emergence of late sequelae. Future aetiological studies must adopt a biopsychosocial perspective.

The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location.

Histone 3 lysine27-to-methionine (H3-K27M) mutations most frequently occur in diffuse midline gliomas (DMGs) of the childhood pons but are also increasingly recognized in adults. Their potential heterogeneity at different ages and midline locations is vastly understudied. Here, through dissecting the single-cell transcriptomic, epigenomic and spatial architectures of a comprehensive cohort of patient H3-K27M DMGs, we delineate how age and anatomical location shape glioma cell-intrinsic and -extrinsic features in light of the shared driver mutation. We show that stem-like oligodendroglial precursor-like cells, present across all clinico-anatomical groups, display varying levels of maturation dependent on location. We reveal a previously underappreciated relationship between mesenchymal cancer cell states and age, linked to age-dependent differences in the immune microenvironment. Further, we resolve the spatial organization of H3-K27M DMG cell populations and identify a mitotic oligodendroglial-lineage niche. Collectively, our study provides a powerful framework for rational modeling and therapeutic interventions.

Improved Long-Term Survival of Patients with Recurrent Medulloblastoma Treated with a "MEMMAT-like" Metronomic Antiangiogenic Approach.

Medulloblastoma (MB) recurrence is usually incurable despite intensive therapy including high-dose chemotherapy. An evolving alternative approach to conventional chemotherapy aims at interfering with tumor angiogenesis at different levels. We report on a novel combinatorial metronomic antiangiogenic approach. The study is a retrospective observational study of 29 consecutive patients with first or multiple recurrences prospectively treated according to the MEMMAT strategy ("MEMMAT-like") before the formal protocol (MEMMAT; ClinicalTrials.gov Identifier: NCT01356290) started. The study period was 11/2006 to 06/2016. Treatment consisted of daily oral thalidomide, fenofibrate, celecoxib, and alternating 21-day cycles of low-dose oral etoposide and cyclophosphamide supplemented by IV bevacizumab and intraventricular therapy consisting of alternating etoposide and liposomal cytarabine. Median overall survival (OS) after recurrence for the whole group was 29.5 months, OS was 48.3 ± 9.3% at three years and 34.5 ± 8.8% at five years, and progression-free survival was 42.0 ± 9.5% at three years and 29.4 ± 9% at five years. As of 07/2022, 9/29 patients are alive 86 to 164 months after the recurrence that prompted the "MEMMAT-like" therapy. Treatment was primarily out-patient and generally well-tolerated. Toxicities did occur but were manageable. In conclusion, antiangiogenic therapy according to the MEMMAT strategy increased median OS of patients with recurrent MB and may lead to long-term survival. Adherence to the protocol, including intraventricular therapy, appears important.

Evaluation of the Perioperative and Postoperative Course of Surgery for Pineal Germinoma in the SIOP CNS GCT 96 Trial.

Background: CNS germinoma, being marker-negative, are mainly diagnosed by histological examination. These tumors predominantly appear in the suprasellar and/or pineal region. In contrast to the suprasellar region, where biopsy is the standard procedure in case of a suspected germ-cell tumor to avoid mutilation to the endocrine structures, pineal tumors are more accessible to primary resection. We evaluated the perioperative course of patients with pineal germinoma who were diagnosed by primary biopsy or resection in the SIOP CNS GCT 96 trial. Methods: Overall, 235 patients had germinoma, with pineal localization in 113. The relationship between initial symptoms, tumor size, and postoperative complications was analyzed. Results: Of 111 evaluable patients, initial symptoms were headache (n = 98), hydrocephalus (n = 93), double vision (n = 62), Parinaud syndrome (n = 57), and papilledema (n = 44). There was no significant relationship between tumor size and primary symptoms. A total of 57 patients underwent primary resection and 54 underwent biopsy. Postoperative complications were reported in 43.2% of patients after resection and in 11.4% after biopsy (p < 0.008). Biopsy was significantly more commonly performed on larger tumors (p= 0.002). Conclusions: These results support the practice of biopsy over resection for histological confirmation of pineal germinoma.

A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation.

Cerebral organoids differentiated from human-induced pluripotent stem cells (hiPSC) provide a unique opportunity to investigate brain development. However, organoids usually lack microglia, brain-resident immune cells, which are present in the early embryonic brain and participate in neuronal circuit development. Here, we find IBA1+ microglia-like cells alongside retinal cups between week 3 and 4 in 2.5D culture with an unguided retinal organoid differentiation protocol. Microglia do not infiltrate the neuroectoderm and instead enrich within non-pigmented, 3D-cystic compartments that develop in parallel to the 3D-retinal organoids. When we guide the retinal organoid differentiation with low-dosed BMP4, we prevent cup development and enhance microglia and 3D-cysts formation. Mass spectrometry identifies these 3D-cysts to express mesenchymal and epithelial markers. We confirmed this microglia-preferred environment also within the unguided protocol, providing insight into microglial behavior and migration and offer a model to study how they enter and distribute within the human brain.

Evaluating the diagnostic validity of the cerebellar cognitive affective syndrome (CCAS) in pediatric posterior fossa tumor patients.

Background: The aim of this case-control study was to investigate the severity of the cerebellar cognitive affective syndrome (CCAS) in patients treated for pediatric posterior fossa tumors (PFT) and evaluate its diagnostic validity and predictive value for long-term effects. Methods: Using neuropsychological test data from 56 patients with PFT (average age: 14 years), the severity of deficits in the CCAS core areas (executive functions, verbal functions, visuospatial abilities and emotions/behaviour) was examined. Neuropsychological and academic long-term outcomes of patients with CCAS were compared to two control groups of PFT patients (treated with either surgery or surgery followed by radio-/chemotherapy) without the syndrome. Risk factors associated with various deficits were considered. Results: All but one PFT patient suffered from slight to severe impairments in at least one CCAS domain, while complete CCAS occurred in 35.7%. Seven years after tumor diagnosis CCAS patients performed worse in information processing, logical reasoning, verbal functions, visuospatial skills, and executive functioning and required more special educational support compared to the control groups. CCAS patients performed equally poor as patients treated with chemo-/radiotherapy in tasks measuring information processing speed. Risk factors were significantly associated with deficits in information processing speed but not CCAS emergence. Conclusions: Deficits in the core CCAS domains are commonly found in PFT patients, but varying in severity, which suggests the syndrome to be continuous rather than dichotomous. However, the validity of CCAS diagnosis was low and unspecific. The exclusion of relevant functions typically impaired in PFT patients (eg, information processing) resulted in difficulties being overlooked.

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.

Impact of childhood cerebellar tumor surgery on cognition revealed by precuneus hyperconnectivity.

Background: Childhood cerebellar pilocytic astrocytomas harbor excellent overall survival rates after surgical resection, but the patients may exhibit specific cognitive and behavioral problems. Functional MRI has catalyzed insights into brain functional systems and has already been linked with the neuropsychological performance. We aimed to exploit the question of whether resting-state functional MRI can be used as a biomarker for the cognitive outcome assessment of these patients. Methods: We investigated 13 patients (median age 22.0 years; range 14.9-31.3) after a median interval between surgery and examination of 15.0 years (range 4.2-20.5) and 16 matched controls. All subjects underwent functional 3-Tesla MRI scans in a resting-state condition and battery neuropsychological tests. Results: Patients showed a significantly increased functional connectivity in the precuneus compared with controls (P < .05) and at the same time impairments in various domains of neuropsychological functioning such as a lower mean Wechsler Intelligenztest für Erwachsene (WIE) IQ percentile (mean [M] = 48.62, SD = 29.14), lower scores in the Trail Making Test (TMT) letter sequencing (M = 49.54, SD = 30.66), worse performance on the WIE subtest Digit Symbol Coding (M = 38.92, SD = 35.29), subtest Symbol Search (M = 40.75, SD = 35.28), and test battery for attentional performance (TAP) divided attention task (M = 783.92, SD = 73.20). Conclusion: Childhood cerebellar tumor treated by resection only strongly impacts the development of precuneus/posterior cingulate cortex functional connectivity. Functional MRI has the potential to help deciphering the pathophysiology of cerebellar-related cognitive impairments in these patients and could be an additional tool in their individual assessment and follow-up.

Unique Finding of a Primary Central Nervous System Neuroendocrine Carcinoma in a 5-Year-Old Child: A Case Report.

Neuroendocrine tumors (NETs) are rare neoplasms predominantly arising in the gastrointestinal-tract or the lungs of adults. To date, only ten cases of primary central nervous system (CNS) NETs have been reported, with just three of them describing a neuroendocrine carcinoma (NECA) and none occurring in a child. We report on a previously healthy 5-year-old boy, who presented with headaches, nausea and vomiting, and was diagnosed with a left cerebellar solid mass with a cystic component. After gross-total resection, histology revealed a neuroendocrine carcinoma. Molecular analysis of the tumor tissue showed a KRAS-splice-site mutation (c451-3C > T). The KRAS-mutation was discovered to be a maternal germline mutation, previously described as likely benign. After extensive search for an extracranial primary tumor, including Ga-68 DOTANOC-PET-CT, the diagnosis of a primary CNS NECA was established, and proton irradiation was performed. Unfortunately, the patient developed an in-field recurrence just 5 weeks after the end of radiotherapy. The tumor was re-resected with vital tumor tissue. Six cycles of chemotherapy were initiated, consisting of cisplatin, carboplatin, etoposide and ifosfamide. The patient remains disease free 22 months after the end of treatment, supporting the beneficial effect of platinum- and etoposide-based chemotherapy for this tumor entity.