Enhancing educational experience through establishing a VR database in craniosynostosis: report from a single institute and systematic literature review.

Background: Craniosynostosis is a type of skull deformity caused by premature ossification of cranial sutures in children. Given its variability and anatomical complexity, three-dimensional visualization is crucial for effective teaching and understanding. We developed a VR database with 3D models to depict these deformities and evaluated its impact on teaching efficiency, motivation, and memorability. Methods: We included all craniosynostosis cases with preoperative CT imaging treated at our institution from 2012 to 2022. Preoperative CT scans were imported into SpectoVR using a transfer function to visualize bony structures. Measurements, sub-segmentation, and anatomical teaching were performed in a fully immersive 3D VR experience using a headset. Teaching sessions were conducted in group settings where students and medical personnel explored and discussed the 3D models together, guided by a host. Participants' experiences were evaluated with a questionnaire assessing understanding, memorization, and motivation on a scale from 1 (poor) to 5 (outstanding). Results: The questionnaire showed high satisfaction scores (mean 4.49 ± 0.25). Participants (n = 17) found the VR models comprehensible and navigable (mean 4.47 ± 0.62), with intuitive operation (mean 4.35 ± 0.79). Understanding pathology (mean 4.29 ± 0.77) and surgical procedures (mean 4.63 ± 0.5) was very satisfactory. The models improved anatomical visualization (mean 4.71 ± 0.47) and teaching effectiveness (mean 4.76 ± 0.56), with participants reporting enhanced comprehension and memorization, leading to an efficient learning process. Conclusion: Establishing a 3D VR database for teaching craniosynostosis shows advantages in understanding and memorization and increases motivation for the study process, thereby allowing for more efficient learning. Future applications in patient consent and teaching in other medical areas should be explored.

Assessment of transitional care in pediatric neurosurgery: a single-center analysis and survey of patients and parents.

OBJECTIVE: Transitional care in pediatric neurosurgery is challenging for patients and their parents. The specific needs of neurologically affected patients and the unique characteristics of the pathologies affecting pediatric neurosurgical patients compared with adults make a comprehensive, well-organized transition process essential for patient well-being and ensuring continuity of care. Little is known about patients' preferences and opinions on this topic. This study aimed to assess the patients' and parents' expectations and perceptions of the transition process. METHODS: The authors retrospectively identified patients aged 16 to 30 years who underwent surgery in their pediatric neurosurgical department. The patients were divided into two groups: those about to transition and those who had already transitioned. Transition models were identified within the latter group. Parents of eligible patients were contacted for a telephone survey, and the patients themselves were included when possible. A modified version of the established Got Transition questionnaire from the National Alliance to Advance Adolescent Health was used. RESULTS: Thirty-four patients were included, and 44 telephone surveys were conducted with the patients and their parents. Three transition models were applied, with 7 patients (41.2%) transitioned using the continued caregiver model, 9 patients (52.9%) using the shared caregiver model, and 1 patient (5.9%) using the specialized clinic model. Patient and parent satisfaction was highest among the patients transitioned using the continued caregiver and specialized clinic models. CONCLUSIONS: Neurosurgical conditions in children differ significantly from those in adults, creating unique transitional care challenges. The continuing caregiver model has been shown to provide continuity of care and high patient and parent satisfaction. However, there are differences in the perspectives of parents and patients regarding transitional care, with parents typically expressing greater concern and need for detailed information. Implementing a well-structured and individualized transition process is essential to reduce the caregiving burden on families and healthcare institutions.

Management of external ventricular drain: to wean or not to wean?

PURPOSE: External ventricular drain (EVD) is one of the most frequent procedures in neurosurgery and around 15 to 30% of these patients require a permanent cerebrospinal fluid (CSF) diversion. The optimal EVD weaning strategy is still unclear. Whether gradual weaning compared to rapid closure, reduces the rate of permanent CSF diversion remains controversial. The aim of this trial is to compare the rates of permanent CSF diversion between gradual weaning and rapid closure of an EVD. METHODS: This was a single-center, retrospective cohort study including patients between 2010 to 2020. Patients were divided into a weaning (WG) and non-weaning (NWG) group. The primary outcome was permanent CSF diversion rates, secondary outcomes included hospitalization time, EVD-related morbidity, and clinical outcome. RESULTS: Out of 412 patients, 123 (29.9%) patients were excluded due to early death or palliative treatment. We registered 178 (61.6%) patients in the WG and 111 (38.4%) in the NWG. Baseline characteristics were comparable between groups. The VPS rate was comparable in both groups (NWG 37.8%; WG 39.9%, p = 0.728). EVD related infection (13.5% vs 1.8%, p < 0.001), as well as non-EVD related infection rates (2.8% vs 0%, p < 0.001), were significantly higher in the WG. Hospitalization time was significantly shorter in the NWG (WG 24.93 ± 9.50 days; NWG 23.66 ± 14.51 days, p = 0.039). CONCLUSION: Gradual EVD weaning does not seem to reduce the need for permanent CSF diversion, while infection rates and hospitalization time were significantly higher/longer. Therefore, direct closure should be considered in the clinical setting.

Predictive Value of Sonographic Parameters on the Effects of Cranial Molding Helmet Therapy in Infants with Positional Plagiocephaly.

Positional plagiocephaly is a deformational cranial flattening frequently treated in pediatric neurosurgical practice. Positional maneuvers and orthotic helmet therapy are preferred therapeutic options for moderate-to-severe forms. Treatment response seems to be age-dependent. Nevertheless, predictive data are vague, and cost-efficiency might be a limiting factor for treatment. The purpose of this study was to investigate the early predictive value of sonographic parameters on the efficacy of orthotic helmet therapy through the assessment of changes in skull shape and correlation of the parameters with caliper cephalometry values and with age. A consecutive cohort of 49 patients < 10 months of age, undergoing orthotic helmet therapy for positional plagiocephaly, was recruited prospectively. The authors routinely assessed the patency of the lambdoid sutures by ultrasound and the following additional skull parameters were measured: suture width, adjacent full bone thickness, adjacent cortical bone thickness and occipital angle. Caliper cephalometric values, as well as demographic and clinical data were collected. Retrospective data analysis showed an inverse relation between both cortical and full skull bone thickness and early treatment efficacy, defined by a reduction in the occipital angle. The improvement of sonographic parameters correlated with the development of cranial caliper cephalometry values. In conclusion, the sonographic assessment of skull bone thickness is a safe and cost-effective tool to predict the early efficacy of orthotic helmet therapy in positional plagiocephaly and might, therefore, help the clinician to foresee the potential evolution of the deformity.

Patient-Reported Neurocognitive Outcome After Endoscopic Ventricular Surgery.

BACKGROUND: Endoscopic ventricular surgery (EVS) shows overall reduced morbidity compared to open craniotomy, but carries, however, the risk for neurocognitive impairment caused by fornix-, hypothalamus-, and injuries other structures adjacent to the ventricular system. Objective or subjective neurocognitive impairment after EVS is rarely reported. The aim of this study was to assess the subjective neurocognitive outcome in patients undergoing EVS for various pathologies. METHODS: We conducted a retrospective cohort study in adult patients undergoing EVS at our institution between 2010 and 2021. The primary outcome was subjective neurocognitive outcome after EVS measured by patient-reported outcomes (PROs). Secondary outcomes were objective neurocognitive outcome, return-to-work rate, subjective quality of life and satisfaction with surgery. Descriptive and comparative statistics were conducted for all outcome parameters. RESULTS: Fifty-one patients (median age 48 years, 62.7% female) were included. Patients commonly presented with subjective neurocognitive impairment (54.9%) and hydrocephalus was the most common indication for surgery (54.9%). Worse long-term subjective neurocognitive outcome was observed in 5 (21.7%) patients while 18 (78.3%) patients improved. Worse long-term objective neurocognitive outcome was seen in 2 cases (10.5%), of which 1 patient became worse trough surgery while 15 (78.9%) patients improved. Improved subjective and objective neurocognitive outcome correlated in 73.8% of the cases (r = 0.363, P = 0.018). Return to work was possible for 70% of the patients and subjective quality of life was improved or unchanged in 88.1% of the patients. CONCLUSIONS: Subjective neurocognitive outcome and quality of life improvement are often achieved after EVS and permanent neurocognitive impairment is rare. Further well-designed trials on subjective and objective neurocognitive outcome after EVS are warranted.

Pituitary germinoma after resection of a mature third ventricular teratoma: illustrative case.

BACKGROUND: Metachronous intracranial germ cell tumors (iGCTs)-unrelated, histologically different iGCTs occurring at different time points-occurring within the same patient remain a rarity. Herein, the authors report such a case and discuss the literature and potential pathophysiological mechanisms leading to this phenomenon. OBSERVATIONS: A 9-year-old boy presented with new-onset impaired balance, headaches, nausea, visual disturbances, and left facial paresis. Magnetic resonance imaging (MRI) scans revealed a suspected pineal region teratoma originating from the pineal gland with consecutive obstructive hydrocephalus. A mature teratoma was diagnosed and resected. Postoperative recovery was good, and the patient could return to his normal daily activities. However, a new, slowly progressive lesion in the sellar region with an enlarged infundibular stalk was detected on follow-up MRI 3.5 years after initial pineal region teratoma resection. Biopsy revealed a newly developed pure germinoma. The patient was treated with radiotherapy plus chemotherapy and remained relapse free at the last follow-up. Sixteen other cases have reported a surgically resected primary mature teratoma, wherein patients developed metachronous germinomas during follow-up. Different theories try to elaborate this phenomenon, yet none can completely account for it. LESSONS: Although rare, metachronous iGCT is a phenomenon neurosurgeons should be aware of. In patients treated for iGCT, close long-term clinical, imaging, and laboratory follow-up is recommended. https://thejns.org/doi/10.3171/CASE2443.

Palliative single-level selective dorsal rhizotomy for children with spastic cerebral palsy Gross Motor Function Classification System level IV and V: a case series and systematic review of the literature.

OBJECTIVE: Single-level selective dorsal rhizotomy (SDR), typically indicated for ambulatory patients, is a controversial topic for severe spastic cerebral palsy (CP) with Gross Motor Function Classification System (GMFCS) level IV or V. The objective of this case series and systematic literature review was to outline the indication and outcome of palliative SDR for nonambulatory patients with CP and GMFCS level IV and V, focusing on improvement of spasticity and of patient and caregiver reported quality of life assessment. METHODS: A retrospective case series of patients with CP and GMFCS level IV or V who underwent single-level SDR at the authors' institution is presented. Furthermore, two databases (PubMed and Embase) were searched and a systematic review with a search string based on the terms "selective dorsal rhizotomy," "cerebral palsy," and "outcome" was conducted. The primary outcome was the reduction of spasticity based on the modified Ashworth scale (MAS). Secondary outcomes were change on the Gross Motor Function Measure-66 (GMFM-66), evaluation of patient-reported outcome measures (PROMs), surgical morbidity, and mortality. RESULTS: Eleven consecutive children under the age of 25 years undergoing palliative single-level SDR were included. All patients showed a reduction in MAS score (mean 1.09 ± 0.66 points) and no surgical morbidity and mortality occurred. For the systematic review results from our case series, in addition to 4 reports, 274 total patients were included. Reduction of spasticity based on MAS score was noted in all studies (mean range 1.09-3.2 points). Furthermore, in 2 studies spasticity of the upper extremities showed a MAS score reduction as well (range 1.7-2.8 points). The GMFM-66 score improved in 72% of the patients, while bladder function improved in 78% of the patients. Based on the PROMs, 92% of the patients/caregivers were satisfied with the outcome and their quality of life after the procedure. Two wound infections (2.7%) and one CSF leak (1.3%) occurred, while no surgery-related deaths were described. CONCLUSIONS: This analysis showed an improvement in spasticity, daily care, and comfort for patients with CP and GMFCS levels IV and V. Larger cohorts analyzing the outcome of palliative single-level SDR, based on the MAS, GMFM-66, and PROMs, are still needed and should be the focus of future studies. Systematic review registration no.: CRD42024495762 (https://www.crd.york.ac.uk/prospero/).

EpiDiP/NanoDiP: a versatile unsupervised machine learning edge computing platform for epigenomic tumour diagnostics.

DNA methylation analysis based on supervised machine learning algorithms with static reference data, allowing diagnostic tumour typing with unprecedented precision, has quickly become a new standard of care. Whereas genome-wide diagnostic methylation profiling is mostly performed on microarrays, an increasing number of institutions additionally employ nanopore sequencing as a faster alternative. In addition, methylation-specific parallel sequencing can generate methylation and genomic copy number data. Given these diverse approaches to methylation profiling, to date, there is no single tool that allows (1) classification and interpretation of microarray, nanopore and parallel sequencing data, (2) direct control of nanopore sequencers, and (3) the integration of microarray-based methylation reference data. Furthermore, no software capable of entirely running in routine diagnostic laboratory environments lacking high-performance computing and network infrastructure exists. To overcome these shortcomings, we present EpiDiP/NanoDiP as an open-source DNA methylation and copy number profiling suite, which has been benchmarked against an established supervised machine learning approach using in-house routine diagnostics data obtained between 2019 and 2021. Running locally on portable, cost- and energy-saving system-on-chip as well as gpGPU-augmented edge computing devices, NanoDiP works in offline mode, ensuring data privacy. It does not require the rigid training data annotation of supervised approaches. Furthermore, NanoDiP is the core of our public, free-of-charge EpiDiP web service which enables comparative methylation data analysis against an extensive reference data collection. We envision this versatile platform as a useful resource not only for neuropathologists and surgical pathologists but also for the tumour epigenetics research community. In daily diagnostic routine, analysis of native, unfixed biopsies by NanoDiP delivers molecular tumour classification in an intraoperative time frame.

Pediatric neurosurgery training during residency in Switzerland and the need for dedicated subspecialization training.

INTRODUCTION: Pediatric Neurosurgery as a subspeciality started to emerge during the late 1950s, with only a few dedicated pediatric neurosurgeons in the Western world. Over the last few decades, the awareness that children require subspecialized care by dedicated pediatric neurosurgeons and an interdisciplinary team has been growing worldwide, leading to an increase in pediatric neurosurgeons. Several studies have shown that subspecialized care for pediatric patients improves outcomes and is cost-effective. This survey aims to assess the current setting of pediatric neurosurgery and training of neurosurgical residents in pediatric neurosurgery in Switzerland. METHODS: We conducted an online survey by sending e-mail invitations in 2021 to all neurosurgical residents in Switzerland. The survey included questions regarding the participants' demographics, current workplace structures, the care of specific pediatric neurosurgical pathologies, and participants' opinions of the Swiss training program for pediatric neurosurgery and possible improvement. We defined at the beginning of the survey that a pediatric neurosurgeon is a board-certified neurosurgeon with at least one year of dedicated pediatric neurosurgical fellowship training abroad. RESULTS: We received a total of 25 responses from residents, of which 20 (80%) were male. Twenty-two participants (88%) worked in one of seven major hospitals in Switzerland at the time of the survey, and four (16%) were interested in pursuing a fellowship in pediatric neurosurgery. Seven (35%) and five residents (25%) feel comfortable taking care on the ward of a craniosynostosis and hydrocephalus patient younger than 6 months, respectively. Twelve residents (60%) feel comfortable taking care of a pediatric brain tumor patient. The majority (n = 22, 88%) of all residents agree that a fellowship-trained pediatric neurosurgeon should treat children, while two (8%) residents state that any neurosurgeon with an interest in pediatric neurosurgery should be able to treat children. All residents (n = 25, 100%) agree that pediatric neurosurgery training and care in Switzerland needs to be improved. CONCLUSION: Pediatric neurosurgery training in Switzerland is rather heterogeneous and not very well structured, with varying frequencies of children-specific neurosurgical pathologies. Most residents agreed that a subspecialized pediatric neurosurgeon should oversee the care of children in neurosurgery, while all agree that pediatric neurosurgical training and care should be improved in Switzerland.

Fulminant hemorrhagic course of a thalamic H3 K27-altered diffuse midline glioma in an adult patient: illustrative case.

BACKGROUND: H3 K27-altered diffuse midline gliomas (DMGs) are rare tumors, which are, regardless of their histological appearance, classified as World Health Organization grade 4 tumors. They are characterized by a diffuse growth pattern, midline anatomical location, and poor prognosis. Although DMGs occur predominantly in childhood, these tumors can also be found in young adults. OBSERVATIONS: The authors present a case of a 29-year-old patient who was found unconscious with a Glasgow Coma Scale score of 4, along with abnormal extensor movements and bilateral middilated nonreactive pupils. Computed tomography revealed obstructive hydrocephalus due to an acute hemorrhage in a right thalamic lesion. To drain the hydrocephalus and relieve the ongoing central herniation, emergent placement of a right-sided, and later a left-sided, extraventricular drain was performed. Despite the postoperative resolution of hydrocephalus, the patient died shortly after because of the central brain herniation that had occurred. Brain autopsy revealed a H3 K27-altered DMG in the right thalamus. LESSONS: Although typically described in the pediatric population and located in the pons, H3 K27-altered DMG should also be considered in young adult patients with midline lesions, particularly if they are located in the thalamus or brainstem. In rare cases, H3 K27-altered DMG may present with an acute tumor-related hemorrhage, leading to a fulminant clinical course.

Pediatric sellar teratoma - Case report and review of the literature.

BACKGROUND: Intracranial teratoma represents a rare neoplasm, occurring predominantly during childhood. Characteristic symptoms depend on the location but are mainly hydrocephalus, visual disturbances, hypopituitarism, and diabetes insipidus. Initial diagnosis can be challenging due to similar radiological features in both teratomas and other lesions such as craniopharyngiomas. Gross total resection is recommended if feasible and associated with a good prognosis. CASE DESCRIPTION: A 10-year-old girl presented with newly diagnosed growth retardation, fatigue, cephalgia and bilateral hemianopia. Further laboratory analysis confirmed central hypothyroidism and hypercortisolism. Cranial magnetic resonance imaging showed a cystic space-occupying lesion in the sellar and suprasellar compartment with compression of the optic chiasm without hydrocephalus present, suspicious of craniopharyngioma. Subsequently, an endonasal endoscopic transsphenoidal near-total tumor resection with decompression of the optic chiasm was performed. During postoperative recovery the patient developed transient diabetes insipidus, the bilateral hemianopia remained unchanged. The patient could be discharged in a stable condition, while hormone replacement for multiple pituitary hormone deficiency was required. Surprisingly, histopathology revealed conspicuous areas of skin with formation of hairs and squamous epithelia, compatible with a mature teratoma. CONCLUSIONS: We present an extremely rare case of pediatric sellar teratoma originating from the pituitary gland and a review of literature focusing on the variation in presentation and treatment. Sellar teratomas are often mistaken for craniopharyngioma due to their similar radiographic appearances. However, the primary goal of treatment for both pathologies is to decompress eloquent surrounding structures such as the optic tract, and if applicable, resolution of hydrocephalus while avoiding damage to the pituitary stalk and especially the hypothalamic structures. If feasible, the aim of surgery should be gross total resection.

Management of Patients undergoing Elective Craniotomy under Antiplatelet or Anticoagulation Therapy: An International Survey of Practice.

BACKGROUND: The literature concerning the management of antiplatelet (AP) and anticoagulation (AC) medication in the perioperative phase of craniotomy remains scarce. The aim of this international survey was to investigate the current practice among neurosurgeons regarding their perioperative management of AP and AC medication. METHODS: We distributed an online survey to neurosurgeons worldwide with questions concerning their perioperative practice with AP and AC medication in patients undergoing craniotomy. Descriptive statistics were performed. RESULTS: A total of 130 replies were registered. The majority of responders practice neurosurgery in Europe (79%) or high-income countries (79%). Responders reported in 58.9 and 48.8% to have institutional guidelines for the perioperative management of AP and AC medication. Preoperative interruption time was reported heterogeneously for the different types of AP and AC medication with 40.4% of responders interrupting aspirin (ASA) for 4 to 6 days and 45.7% interrupting clopidogrel for 6 to 8 days. Around half of the responders considered ASA safe to be continued or resumed within 3 days for bypass (55%) or vascular (49%) surgery, but only few for skull base or other tumor craniotomies in general (14 and 26%, respectively). Three quarters of the responders (74%) did not consider AC safe to be continued or resumed early (within 3 days) for any kind of craniotomy. ASA was considered to have the lowest risk of bleeding. Nearly all responders (93%) agreed that more evidence is needed concerning AP and AC management in neurosurgery. CONCLUSION: Worldwide, the perioperative management of AP and AC medication is very heterogeneous among neurosurgeons.

Perioperative continuation or ultra-early resumption of antithrombotics in elective neurosurgical cranial procedures.

OBJECTIVE: Discontinuation of antithrombotics (AT) prior to elective cranial procedures is common practice, despite the higher risk of thromboembolic complications in these patients. The aim of this study was to investigate the risks and benefits of a new perioperative management protocol of continuation or ultra-early AT resumption in elective cranial procedures. METHODS: This study was an analysis of a prospectively collected cohort of patients undergoing elective cranial surgery with (AT group) and without (control group) AT. For extraaxial or shunt surgeries, acetylsalicylic acid (ASA) was continued perioperatively. For intraaxial pathologies, ASA was discontinued 2 days before surgery and resumed on postoperative day 3. All other AT were discontinued according to their pharmacokinetics, and resumed on postoperative day 3 after unremarkable postoperative imaging. Additionally, the authors performed a retrospective analysis of patients with AT who underwent surgery before implementation of this new AT management protocol (historical AT group). Primary and secondary outcomes were the incidence of hemorrhagic and thromboembolic complications within 3 months after surgery. RESULTS: Outcomes of 312 patients were analyzed (83 [27%] in the AT group, 106 [34%] in the control group, and 123 [39%] in the historical AT group). For all 3 patient groups, the most common type of surgery was craniotomy for intraaxial tumors (14 [17%] in the AT group, 28 [26%] in the control group, and 60 [49%] in the historical AT group). The most commonly used AT were ASA (38 [46%] in the AT group and 78 [63%] in the historical AT group), followed by non-vitamin K oral anticoagulants (32 [39%] in the AT group and 18 [15%] in the historical AT group). The total perioperative discontinuation time in the AT group was significantly shorter than in the historical AT group (median of 4 vs 16 days; p < 0.001). The rate of hemorrhagic complications was 4% (95% CI 1-10) (n = 3/83) in the AT group, 6% (95% CI 2-12) (n = 6/106) in the control group, and 7% (95% CI 3-13) (n = 9/123) in the historical AT group (p = 0.5). The rate of thromboembolic complications was 5% (95% CI 1-12) (n = 4/82) in the AT group, 8% (95% CI 3-15) (n = 8/104) in the control group, and 7% (95% CI 3-13) (n = 8/120) in the historical AT group (p = 0.7). CONCLUSIONS: The presented perioperative management protocol of continuation or ultra-early resumption of AT in elective cranial procedures does not seem to increase the hemorrhagic risk. Moreover, it appears to potentially protect patients from thromboembolic complications.

Delayed headache 11 years after a pub fight: an unusual spontaneous intracerebral hemorrhage succeeding a temporal glass shard injury. Illustrative case.

BACKGROUND: Intracerebral hemorrhage (ICH) in young patients is rare and often associated with vascular malformations, drug abuse, or genetic conditions. Early diagnosis and treatment are critical because of the potential risk of rebleeding and long-term consequences. This case report presents an unusual correlation between a prior traumatic incident and the manifestation of an atypical ICH 11 years later. OBSERVATIONS: A 37-year-old male presented with retroorbital headaches, confusion, and seizures. Imaging revealed an atypical ICH in the left middle temporal gyrus, accompanied by retained glass shards in the adjacent temporal muscle and bone. Angiography ruled out vascular malformations but suggested an eroded middle cerebral artery branch underneath an osseous defect potentially caused by a bone-transgressing glass shard. Surgical exploration confirmed the vessel as the source of the ICH and was followed by an uneventful hematoma removal and postoperative course. LESSONS: This case underscores the significance of recognizing delayed complications resulting from retained foreign bodies (FBs). Complete removal of extracranial FBs is imperative to prevent further harm. Clinicians should maintain an awareness of the potential long-term consequences and complications associated with FBs, utilizing comprehensive diagnostics to detect and localize FBs. Timely intervention such as resection or planned follow-up is essential for effective management and mitigation of adverse outcomes.

Sex-specific differences in metabolic hormone and adipose tissue dynamics induced by moderate low-carbohydrate and ketogenic diet.

Low-carbohydrates diets are increasingly used to treat obesity and metabolic disorders. A very low-carbohydrate, ketogenic diet is hard to follow and, due to the very high fat content, linked to severe side effects, like hyperlipidemia and atherogenesis. Therefore, a less restrictive, unsaturated fat-based low-carbohydrate diet appears as a promising alternative. Since neither sex differences, nor their effect on specific metabolic hormones and adipose tissue compartments have been investigated thoroughly in these diets, we aimed to analyze their dynamics and metabolic factors in mice. We found a significant sexual dimorphism with decreased body weight and subcutaneous fat only in males on ketogenic diet, while diminished insulin, elevated ghrelin and FGF-21 were present with a differential time course in both sexes. The non-ketogenic moderate low-carbohydrate diet increased body weight and perigonadal fat in females, but induced leptin elevation in males. Both diets enhanced transiently TNFɑ only in males and had no impact on behavior. Altogether, these results reveal complex sex-dependent effect of dietary interventions, indicating unexpectedly females as more prone to unfavorable metabolic effects of low-carbohydrate diets.

Tranexamic Acid for Intracerebral Hemorrhage in Patients on Non-Vitamin K Antagonist Oral Anticoagulants (TICH-NOAC): A Multicenter, Randomized, Placebo-Controlled, Phase 2 Trial.

BACKGROUND: Evidence-based hemostatic treatment for intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOACs) is lacking. Tranexamic acid (TXA) is an antifibrinolytic drug potentially limiting hematoma expansion. We aimed to assess the efficacy and safety of TXA in NOAC-ICH. METHODS: We performed a double-blind, randomized, placebo-controlled trial at 6 Swiss stroke centers. Patients with NOAC-ICH within 12 hours of symptom onset and 48 hours of last NOAC intake were randomized (1:1) to receive either intravenous TXA (1 g over 10 minutes followed by 1 g over 8 hours) or matching placebo in addition to standard medical care via a centralized Web-based procedure with minimization on key prognostic factors. All participants and investigators were masked to treatment allocation. Primary outcome was hematoma expansion, defined as ≥33% relative or ≥6 mL absolute volume increase at 24 hours and analyzed using logistic regression adjusted for baseline hematoma volume on an intention-to-treat basis. RESULTS: Between December 12, 2016, and September 30, 2021, we randomized 63 patients (median age, 82 years [interquartile range, 76-86]; 40% women; median hematoma volume, 11.5 [4.8-27.4] mL) of the 109 intended sample size before premature trial discontinuation due to exhausted funding. The primary outcome did not differ between TXA (n=32) and placebo (n=31) arms (12 [38%] versus 14 [45%]; adjusted odds ratio, 0.63 [95% CI, 0.22-1.82]; P=0.40). There was a signal for interaction with onset-to-treatment time (Pinteraction=0.024), favoring TXA when administered within 6 hours of symptom onset. Between the TXA and placebo arms, the proportion of participants who died (15 [47%] versus 13 [42%]; adjusted odds ratio, 1.07 [0.37-3.04]; P=0.91) or had major thromboembolic complications within 90 days (4 [13%] versus 2 [6%]; odds ratio, 1.86 [0.37-9.50]; P=0.45) did not differ. All thromboembolic events occurred at least 2 weeks after study treatment, exclusively in participants not restarted on oral anticoagulation. CONCLUSIONS: In a smaller-than-intended NOAC-ICH patient sample, we found no evidence that TXA prevents hematoma expansion, but there were no major safety concerns. Larger trials on hemostatic treatments targeting an early treatment window are needed for NOAC-ICH. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT02866838.

Rapid Versus Gradual Weaning of External Ventricular Drain: A Systematic Literature Review and Meta-analysis.

The insertion of an external ventricular drain (EVD) is one of the most common neurosurgical procedures. Whether the weaning method (gradual or rapid) influences the ventriculoperitoneal shunt (VPS) insertion rate has not been conclusively established. The aim of this study is to provide a systematic literature review and conduct a meta-analysis of studies comparing gradual with rapid EVD weaning regarding VPS insertion rate. Articles were identified by searching the Pubmed/Medline, Embase, and Web of Science databases throughout October 2022. Two independent researchers assessed the studies for inclusion and quality. We included randomized trials, prospective cohort studies, and retrospective cohort studies, which compared gradual and rapid EVD weaning. The primary outcome was VPS insertion rate, whereas secondary outcomes were EVD-associated infection (EVDAI) rate and length of stay in the hospital and intensive care unit (ICU). Four studies directly comparing rapid versus gradual EVD weaning, with 1337 patients suffering from subarachnoid hemorrhage, were identified and included in the meta-analysis. VPS insertion rate was 28.1% and 32.1% in patients with gradual and rapid EVD weaning, respectively (relative risk 0.85, 95% confidence interval 0.49-1.46, p = 0.56). Further, the EVDAI rate was comparable between the groups (gradual group 11.2%, rapid group 11.5%, relative risk 0.67, 95% confidence interval 0.24-1.89, p = 0.45), whereas length of stay in the ICU and hospital were significantly shorter in the rapid weaning group (2.7 and 3.6 days, respectively; p < 0.01). Rapid EVD weaning seems comparable to gradual EVD weaning concerning VPS insertion rates and EVDAI, whereas hospital and ICU length of stay is significantly reduced.

Selective Inhibition of Soluble Tumor Necrosis Factor Alters the Neuroinflammatory Response following Moderate Spinal Cord Injury in Mice.

Clinical and animal model studies have implicated inflammation and glial and peripheral immune cell responses in the pathophysiology of spinal cord injury (SCI). A key player in the inflammatory response after SCI is the pleiotropic cytokine tumor necrosis factor (TNF), which exists both in both a transmembrane (tmTNF) and a soluble (solTNF) form. In the present study, we extend our previous findings of a therapeutic effect of topically blocking solTNF signaling after SCI for three consecutive days on lesion size and functional outcome to study the effect on spatio-temporal changes in the inflammatory response after SCI in mice treated with the selective solTNF inhibitor XPro1595 and compared to saline-treated mice. We found that despite comparable TNF and TNF receptor levels between XPro1595- and saline-treated mice, XPro1595 transiently decreased pro-inflammatory interleukin (IL)-1ß and IL-6 levels and increased pro-regenerative IL-10 levels in the acute phase after SCI. This was complemented by a decrease in the number of infiltrated leukocytes (macrophages and neutrophils) in the lesioned area of the spinal cord and an increase in the number of microglia in the peri-lesion area 14 days after SCI, followed by a decrease in microglial activation in the peri-lesion area 21 days after SCI. This translated into increased myelin preservation and improved functional outcomes in XPro1595-treated mice 35 days after SCI. Collectively, our data suggest that selective targeting of solTNF time-dependently modulates the neuroinflammatory response by favoring a pro-regenerative environment in the lesioned spinal cord, leading to improved functional outcomes.

Intracranial Neuroendoscopy in Children and Adults: Where Do the Differences Lie?

BACKGROUND: Intraventricular neuroendoscopy has evolved into an essential adjunct in neurosurgery and is used across all age groups for various indications. However, studies comparing neuroendoscopic procedures between children and adults are scarce. The aim of this study is to compare various aspects between adults and children undergoing neuroendoscopy. METHODS: We retrospectively analyzed the data from consecutive patients dichotomized into 2 cohorts, pediatric (age <18 years) and adult (age ≥18 years) groups, in whom intracranial neuroendoscopy was performed between 2013 and 2020 (pediatric group) and 2010 and 2020 (adult group). RESULTS: Of 132 patients who underwent intracranial neuroendoscopic surgery, 47 (35.6%) were children and 85 (64.4%) were adults. The most common indications for the children and adults were intraventricular or paraventricular tumors (23.4%) and aqueduct stenosis (40%), respectively. Their clinical condition at the last follow-up was unchanged or improved for 90.5% of the children and 92.1% of the adults. An increased endoscopic third ventriculostomy success score was predictive of endoscopic third ventriculostomy success in the pediatric cohort (odds ratio, 1.073; P = 0.043). The postoperative rates of transient (pediatric, 23.4%; adult, 18.8%) and permanent (pediatric, 0%; adult, 1.2%) complications were comparable. The rate of secondary surgery was higher for the pediatric cohort (38.3%) than for the adult cohort (17.6%). CONCLUSIONS: The indications for neuroendoscopy vary between adults and children, although the long-term clinical outcome is comparable. The rate of secondary surgery is significantly higher for pediatric patients, especially for those aged <1 year. Because neuroendoscopy is considerably more frequent in pediatric patients, including pediatric neurosurgeons in adult neuroendoscopic cases could potentially help lower the complication rates and increase the success rates.

Mesenchymal Stem Cells in Nerve Tissue Engineering: Bridging Nerve Gap Injuries in Large Animals.

Cell-therapy-based nerve repair strategies hold great promise. In the field, there is an extensive amount of evidence for better regenerative outcomes when using tissue-engineered nerve grafts for bridging severe gap injuries. Although a massive number of studies have been performed using rodents, only a limited number involving nerve injury models of large animals were reported. Nerve injury models mirroring the human nerve size and injury complexity are crucial to direct the further clinical development of advanced therapeutic interventions. Thus, there is a great need for the advancement of research using large animals, which will closely reflect human nerve repair outcomes. Within this context, this review highlights various stem cell-based nerve repair strategies involving large animal models such as pigs, rabbits, dogs, and monkeys, with an emphasis on the limitations and strengths of therapeutic strategy and outcome measurements. Finally, future directions in the field of nerve repair are discussed. Thus, the present review provides valuable knowledge, as well as the current state of information and insights into nerve repair strategies using cell therapies in large animals.