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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Endovascular Treatment and Peri-interventional Management of Ruptured Cerebrovascular Lesions During Pregnancy : Case Series and Case-based Systematic Review.

PURPOSE: Hemorrhagic stroke, particularly occurring from ruptured cerebrovascular malformations, is responsible for 5-12% of all maternal deaths during pregnancy and the puerperium. Whether endovascular treatment is feasible and safe for both the mother and the fetus, is still a matter of debate. The main objective of this case series and systematic review was to share our multi-institutional experience and to assess the feasibility and safety of endovascular treatment during pregnancy, as well as the corresponding maternal and fetal outcomes based on currently available evidence. METHODS: We report a case series of 12 pregnant women presenting with hemorrhagic stroke from ruptured cerebrovascular arteriovenous malformations or aneurysms who underwent endovascular treatment prior to delivery. A systematic literature review of pregnant patients with endovascular treated cerebrovascular malformations, published between 1995 and 2022, was performed. Clinical patient information, detailed treatment strategies, maternal and fetal outcomes as well as information on the delivery were collected and assessed. RESULTS: In most patients the course was uneventful and an excellent outcome without significant neurological deficits (mRS ≤ 1) was achieved. Furthermore, the maternal outcome was not worse compared to the general population who underwent endovascular treatment of ruptured vascular brain lesions. Also, in most cases a healthy fetus was born. CONCLUSION: Endovascular treatment of ruptured cerebrovascular malformations during pregnancy is safe and feasible regarding both aspects, the maternal and fetal outcomes. Still, a stronger knowledge base is needed to correctly approach future cases of intracranial hemorrhage in the pregnant population.

Open versus laparoscopic ventriculoperitoneal shunt placement in children: a systematic review and meta-analysis.

BACKGROUND: Ventriculoperitoneal shunt (VPS) surgery is the traditional method for treating hydrocephalus, remaining one of the most regularly used procedures in pediatric neurosurgery. The reported revision rate of VPS can reach up to 80% and significantly reduces the quality of life in the affected children and has a high socioeconomic burden. Traditionally, distal VPS placement has been achieved open via a small laparotomy. However, in adults several studies have shown a lower rate of distal dysfunction using laparoscopic insertion. As the data in children are scarce, the aim of this systematic review and meta-analysis was to compare open and laparoscopic VPS placement in children regarding complications. METHODS: PubMed and Embase databases were searched using a systematic search strategy to identify studies comparing open and laparoscopic VPS placement up to July 2022. Two independent researchers assessed the studies for inclusion and quality. Primary outcome measure was distal revision rate. A fixed effects model was used if low heterogeneity (I2 < 50%) was present, otherwise a random effects model was applied. RESULTS: Out of 115 screened studies we included 8 studies in our qualitative assessment and three of them in our quantitative meta-analysis. All studies were retrospective cohort studies with 590 analyzed children, of which 231 children (39.2%) received laparoscopic, and 359 children (60.8%) open shunt placement. Similar distal revision rates were observed between the laparoscopic and open group (3.75% vs. 4.3%, RR 1.16, [ 95% CI 0.48 to 2.79], I2 = 50%, z = 0.32, p = 0.74). There was no significant difference in postoperative infection rate between the two groups (laparoscopic 5.6% vs. open 7.5%, RR 0.99, (95% CI [0.53 to 1.85]), I2=0%, z = -0.03, p= 0.97). The meta-analysis showed a significantly shorter surgery time in the laparoscopic group (49.22 (±21.46) vs. 64.13 (±8.99) minutes, SMD-3.6, [95% CI -6.9 to -0.28], I2=99%m z= -2.12, p= 0.03) compared to open distal VPS placement. CONCLUSION: Few studies are available comparing open and laparoscopic shunt placement in children. Our meta-analysis showed no difference in distal revision rate between laparoscopic and open shunt insertion; however, laparoscopic placement was associated with a significantly shorter surgery time. Further prospective trials are needed to assess possible superiority of one of the techniques.

Clinical and patient-reported outcome after patient-specific 3D printer-assisted cranioplasty.

Various cranioplasty techniques exist for the reconstruction of cranial bone defects. Patient-specific implants can be produced in-house using a recently developed 3D printer-assisted cranioplasty technique. However, the resulting cosmetic outcomes from the patient's perspective are underreported. With our case series, we aim to present the clinical outcome, morbidity rate, patient-reported cosmetic results, and cost-effectiveness of patient-specific3D printer-assisted cranioplasty technique. This is a consecutive retrospective case series of adult patients undergoing cranioplasty using the patient-specific 3D printer-assisted technique. As primary endpoint, the functional outcome based on modified Rankin scale (mRS) at discharge and follow-up was assessed. A prospective telephone survey was conducted to collect and provide patient-reported outcomes. Thirty-one patients underwent patient-specific 3D printer-assisted cranioplasty, mostly to reconstruct frontotemporoparietal (61.3%) and frontotemporal defects with orbital involvement (19.4%). Good functional outcome (mRS ≤ 2) at discharge and during the last follow-up was achieved in 54.8% (n = 17) and 58.1% (n = 18) patients. Overall, the rate of clinically relevant surgery-related complications was 35.5% (n = 11). Postoperative epidural hematoma/collection (16.1%) and infections (12.9%) were the most frequent complications. Permanent morbidity occurred in one patient (3.2%) with postoperative acute ipsilateral vision loss after frontotemporal cranioplasty with orbital involvement. No surgery-related mortality occurred. The mean patient-reported cosmetic satisfaction score was 7.8 ± 1.5, with 80% of patients reporting satisfying or very satisfying cosmetic results. No significant differences were seen between the different defect localization regarding the cosmetic outcome. The mean manufacturing costs of a patient-specific 3D printer-assisted implant ranged from 748 to 1129 USD. Based on our case series, patient-specific 3D printer-assisted cranioplasty is cost-effective and leads to satisfying cosmetic results, especially in large defects and/or defects with complex geometry.

Patient- and Caregiver-Reported Outcome Measures after Single-Level Selective Dorsal Rhizotomy in Pediatric and Young Adult Patients with Spastic Cerebral Palsy.

INTRODUCTION: The aim of this cohort study was to assess the outcome of single-level selective dorsal rhizotomy (SDR) in children and young adults with spastic cerebral palsy (CP) treated at our institution, focusing on patient-reported outcome measures (PROMs) and quality of life (QoL) of patients and their caregivers. METHODS: We included consecutive patients undergoing SDR from 2018 to 2020 at our institution. Subjective outcome was measured through PROMs, while functional outcome was measured through baseline characteristics, operative outcome, as well as short- and long-term follow-up. Furthermore, the effect of age at the time of surgery on patient/caregiver satisfaction was analyzed. RESULTS: Seven patients (3 female, 43%) with a median age at surgery of 11.9 years (IQR 8.7-15.5) were included. All patients had a Gross Motor Function Classification (GMFCS) score of at least IV before surgery. Five surgeries were palliative and two non-palliative. Based on PROMs, SDR showed very good QoL and health-related outcome measures for both palliative and non-palliative patients. Patient/caregiver satisfaction was higher for the early subgroup (age ≤11) than the late subgroup (age >11). Functional outcome showed reduced spasticity in both groups. Blood transfusions were never needed, while no cerebrospinal fluid leak, infection, or permanent morbidity was seen. CONCLUSION: Based on PROMs, SDR leads to high satisfaction and improved QoL, especially if done at an early age. Further studies with larger cohorts are necessary to underline and confirm our observations.

Machine Learning for Onset Prediction of Patients with Intracerebral Hemorrhage.

OBJECTIVE: Intracerebral hemorrhage (ICH) has a high mortality and long-term morbidity and thus has a significant overall health-economic impact. Outcomes are especially poor if the exact onset is unknown, but reliable imaging-based methods for onset estimation have not been established. We hypothesized that onset prediction of patients with ICH using artificial intelligence (AI) may be more accurate than human readers. MATERIAL AND METHODS: A total of 7421 computed tomography (CT) datasets between January 2007-July 2021 from the University Hospital Basel with confirmed ICH were extracted and an ICH-segmentation algorithm as well as two classifiers (one with radiomics, one with convolutional neural networks) for onset estimation were trained. The classifiers were trained based on the gold standard of 644 datasets with a known onset of >1 and <48 h. The results of the classifiers were compared to the ratings of two radiologists. RESULTS: Both the AI-based classifiers and the radiologists had poor discrimination of the known onsets, with a mean absolute error (MAE) of 9.77 h (95% CI (confidence interval) = 8.52-11.03) for the convolutional neural network (CNN), 9.96 h (8.68-11.32) for the radiomics model, 13.38 h (11.21-15.74) for rater 1 and 11.21 h (9.61-12.90) for rater 2, respectively. The results of the CNN and radiomics model were both not significantly different to the mean of the known onsets (p = 0.705 and p = 0.423). CONCLUSIONS: In our study, the discriminatory power of AI-based classifiers and human readers for onset estimation of patients with ICH was poor. This indicates that accurate AI-based onset estimation of patients with ICH based only on CT-data may be unlikely to change clinical decision making in the near future. Perhaps multimodal AI-based approaches could improve ICH onset prediction and should be considered in future studies.

Mortality of Surgically Treated Neurotrauma in Elderly Patients and the Development of a Prediction Score: Geriatric Neurotrauma Mortality Score.

BACKGROUND: As the population worldwide is aging, the need for surgery in elderly patients with neurotrauma is increasing. The aim of this study was to compare the outcome of elderly patients undergoing surgery for neurotrauma with younger patients and to identify the risk factors for mortality. METHODS: We retrospectively analyzed consecutive patients undergoing craniotomy or craniectomy for neurotrauma at our institution from 2012 to 2019. Patients were divided into two groups (≥70 years or <70 years) and compared. The primary outcome was the 30-day mortality rate. Potential risk factors for 30-day mortality were assessed in a uni- and multivariate regression model for both age groups, forming the basis of a 30-day mortality prediction score. RESULTS: We included 163 consecutive patients (average age 57.98 ± 19.87 years); 54 patients were ≥70 years. Patients ≥70 years showed a significantly better median preoperative Glasgow Coma Scale (GCS) score compared with young patients (P < 0.001), and fewer pupil asymmetry (P = 0.001), despite having a higher Marshall score (P = 0.07) at admission. Multivariate regression analysis identified low pre- and postoperative GCS scores and the lack of prompt postoperative prophylactic low-molecular-weight heparin treatment as risk factors for 30-day mortality. Our score showed moderate accuracy in predicting 30-day mortality with an area under the curve of 0.76. CONCLUSIONS: Elderly patients after neurotrauma present with a better GCS at admission despite having more severe radiographic injuries. Mortality and favorable outcome rates are comparable between the age groups.

Doublecortin and Glypican-2 concentrations in the cerebrospinal fluid from infants are developmentally downregulated.

OBJECTIVE: Doublecortin (DCX) and glypican-2 (GPC2) are neurodevelopmental proteins involved in the differentiation of neural stem/progenitor cells (NSPCs) to neurons, and are developmentally downregulated in neurons after birth. In this study, we investigated whether the concentrations of DCX and GPC2 in the cerebrospinal fluid (CSF) from human pediatric patients reflect this developmental process or are associated with cerebral damage or inflammatory markers. METHODS: CSF was collected from pediatric patients requiring neurosurgical treatment. The concentrations of DCX, GPC2, neuron-specific enolase (NSE), S100 calcium-binding protein B (S100B), and cytokines (IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, IFN-γ, and TNF-⍺) were measured using immunoassays. RESULTS: From March 2013 until October 2018, 63 CSF samples were collected from 38 pediatric patients (20 females; 17 patients with repeated measurements); the median term born-adjusted age was 3.27 years [Q1: 0.31, Q3: 7.72]. The median concentration of DCX was 329 pg/ml [Q1: 192.5, Q3: 1179.6] and that of GPC2 was 26 pg/ml [Q1: 13.25, Q3: 149.25]. DCX and GPC2 concentrations independently significantly associated with age, and their concentration declined with advancing age, reaching undetectable levels at 0.3 years for DCX, and plateauing at 1.5 years for GPC2. Both DCX and GPC2 associated with hydrocephalus, NSE, IL-1ß, IL-2, IL-8, IL-13. No relationship was found between sex, acute infection, S100B, IL-4, IL-6, IL-10, IFN-γ, TNF-α and DCX or GPC2, respectively. CONCLUSIONS: Concentrations of DCX and GPC2 in the CSF from pediatric patients are developmentally downregulated, with the highest concentrations measured at the earliest adjusted age, and reflect a neurodevelopmental stage rather than a particular disease state.