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.

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/).

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.

Distal shunt placement in pediatric ventriculoperitoneal shunt surgery: an international survey of practice.

OBJECTIVE: Ventriculoperitoneal shunt (VPS) surgery is a common treatment for hydrocephalus in children and adults, making it one of the most common procedures in neurosurgery. Children being treated with a VPS often require several revisions during their lifetime with a lifetime revision rate of up to 80%. Several different techniques exist for inserting the distal catheter, while mini-laparotomy, trocar, or laparoscopy is traditionally used. As opposed to adults, only few studies exist, comparing the outcome of the different distal catheter placement techniques in children. This international survey aims to investigate the current daily practice concerning distal shunt placement techniques in children. MATERIAL AND METHODS: An online questionnaire investigating the different techniques used to place the distal catheter in pediatric VPS surgery was distributed internationally. All results were analyzed using descriptive and comparative statistics. RESULTS: A total of 139 responses were obtained. Mini-laparotomy was reported to be the most frequently used technique (n = 104, 74.8%) for distal shunt placement in children, while laparoscopic or trocar-assisted placements were only used by 3.6% (n = 5) and 21.6% (n = 30) of all respondents, respectively. Over half (n = 75, 54.0%) of all respondents do not believe that laparoscopic placement improves the outcome. CONCLUSION: This international survey shows that mini-laparotomy is the most frequently used technique for distal VPS placement in children all over the world. Further randomized trials are needed to elucidate this matter.

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.

Early surgical approaches in pediatric epilepsy - a systematic review and meta-analysis.

INTRODUCTION: Drug-resistant epilepsy occurs in up to 30% of children suffering from seizures and about 10% qualify for surgical treatment. The aim of this systematic review and meta-analysis is to analyze the potential benefit of early epilepsy surgery in children concerning primarily seizure and developmental outcome. METHODS: PubMed and Embase databases were searched using a systematic search strategy to identify studies on pediatric epilepsy surgery under 3 years from their inception up to 2022. Outcome measures were seizure outcome, postoperative complications, seizure onset, and reduction rate of antiepileptic drugs. A meta-analysis was thereafter performed for all included cohort studies. A p-value of < 0.05 was considered as statistically significant. RESULTS: A total of 532 patients were analyzed with 401 patients (75%) receiving resective or disconnective surgery under the age of 3 years and 80 patients (15%) receiving surgery older than 3 years. The remaining 51 patients (9%) underwent VNS implantation. Pooled outcome analysis for resective/disconnective surgery showed favorable outcome in 68% (95% CI [0.63; 0.73]), while comparative analysis between the age groups showed no significant difference (77% early group and 75% late group; RR 1.03, 95% CI [0.73; 1.46] p = 0.75). Favorable outcome for the VNS cohort was seen in 52%, 65% in the early and 45.1% in the late group (RR 1.4393, 95% CI [0.87; 2.4] z = 1.42, p = 0.16). Developmental outcome was improved in 26%. Morbidity rate was moderate and showed no significant difference comparing the age groups, and overall surgical mortality rate was very low (0.1%). CONCLUSION: Epilepsy surgery in pediatric age, especially under the age of 3 years, is a feasible and safe way to treat intractable epilepsy. Further comparative studies of prospective nature, analyzing not only seizure but also developmental outcome, should be the focus of future studies.

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.

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.

Minimally invasive image-guided endoscopic evacuation of intracerebral haemorrhage: How I Do it.

BACKGROUND: Minimally invasive endoscopic hematoma evacuation (MEHE) is an emerging surgical technique for treating spontaneous supratentorial intracerebral haemorrhage (SSICH). Multiple studies, analysing whether the outcome after such a procedure is improved, are still ongoing. METHOD: We herein present the indications, advantages, and perioperative considerations for the surgical technique of MEHE applied at our institution. CONCLUSION: MEHE with a view through a transparent brain access device is a valid and safe approach for the surgical evacuation of SSICH.

Risks and benefits of continuation and discontinuation of aspirin in elective craniotomies: a systematic review and pooled-analysis.

BACKGROUND/AIM: Discontinuation of aspirin (ASA) prior to elective craniotomies is common practice. However, patients treated with ASA for secondary prevention bear a higher risk for thromboembolic complications. Aim of this systematic review is to investigate the risks and benefits of perioperative continuation and discontinuation of ASA in elective craniotomies. METHODS: PubMed and Embase databases were searched. Inclusion criteria were retro- and prospective studies, reporting hemorrhagic and thromboembolic complications in patients in whom ASA was either continued or discontinued perioperatively in elective craniotomies. We excluded shunt operations and emergency cases. The MINORS (Methodological index for non-randomized studies) score was used to quantify the methodological quality of the eligible studies. RESULTS: Out of 523 publications, 7 met the eligibility criteria (cumulative cohort of 646 patients). The mean MINORS score for the comparative studies was 18.7/24 (± SD 2.07, range: 17-22) and 9/16 for the unique non-comparative study, indicating an overall weak methodological quality of the included studies. 57.1% of the patients underwent craniotomy for intra- and extra-axial tumor removal, 39.0% for bypass surgery and 3.9% for neurovascular lesions (other than bypass). In 31.0% of the cases, ASA was prescribed for primary and in 69.0% for secondary prevention. ASA was continued perioperatively in 61.8% and discontinued in 38.2% of the cases. The hemorrhagic complication rate was 3% (95% CI [0.01-0.05]) in the ASA continuation group (Con-Group) and 3% (95% CI [0.01-0.09]) in the discontinuation group (Disc-Group) (p = 0.9). The rate of thromboembolic events in the Con-Group was 3% (95% CI [0.01-0.06]) in comparison to 6% (95% CI [0.02-0.14]) in the Disc-Group (p = 0.1). CONCLUSION: Perioperative continuation of ASA in elective craniotomies does not seem to be associated with an increased hemorrhagic risk. The potential beneficial effect of ASA continuation on thromboembolic events needs to be further investigated in patients under ASA for secondary prevention.

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.

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.

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.

Herniation World Federation of Neurosurgical Societies Scale Improves Prediction of Outcome in Patients With Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Favorable outcomes are seen in up to 50% of patients with World Federation of Neurosurgical Societies (WFNS) grade V aneurysmal subarachnoid hemorrhage. Therefore, the usefulness of the current WFNS grading system for identifying the worst scenarios for clinical studies and for making treatment decisions is limited. We previously modified the WFNS scale by requiring positive signs of brain stem dysfunction to assign grade V. This study aimed to validate the new herniation WFNS grading system in an independent prospective cohort. METHODS: We conducted an international prospective multicentre study in poor-grade aneurysmal subarachnoid hemorrhage patients comparing the WFNS classification with a modified version-the herniation WFNS scale (hWFNS). Here, only patients who showed positive signs of brain stem dysfunction (posturing, anisocoric, or bilateral dilated pupils) were assigned hWFNS grade V. Outcome was assessed by modified Rankin Scale score 6 months after hemorrhage. The primary end point was the difference in specificity of the WFNS and hWFNS grading with respect to poor outcomes (modified Rankin Scale score 4-6). RESULTS: Of the 250 patients included, 237 reached the primary end point. Comparing the WFNS and hWFNS scale after neurological resuscitation, the specificity to predict poor outcome increased from 0.19 (WFNS) to 0.93 (hWFNS) (McNemar, P<0.001) whereas the sensitivity decreased from 0.88 to 0.37 (P<0.001), and the positive predictive value from 61.9 to 88.3 (weighted generalized score statistic, P<0.001). For mortality, the specificity increased from 0.19 to 0.93 (McNemar, P<0.001), and the positive predictive value from 52.5 to 86.7 (weighted generalized score statistic, P<0.001). CONCLUSIONS: The identification of objective positive signs of brain stem dysfunction significantly improves the specificity and positive predictive value with respect to poor outcome in grade V patients. Therefore, a simple modification-presence of brain stem signs is required for grade V-should be added to the WFNS classification. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT02304328.

Mesenchymal stem cell therapy in perinatal arterial ischemic stroke: systematic review of preclinical studies.

BACKGROUND: Perinatal arterial ischemic stroke (PAIS) is a neurologic disorder leading to long-term complications. Mesenchymal stem cells (MSCs) have emerged as a novel therapeutic agent. This systematic review aims to determine the effects of stem cell-based interventions for the treatment of PAIS in preclinical studies. METHODS: We included all controlled studies on MSCs in neonatal animals with PAIS. Functional outcome was the primary outcome. The literature search was performed in February 2021. RESULTS: In the 20 included studies, MSCs were most frequently delivered via intracerebral injection (n = 9), 3 days after the induction of PAIS (n = 8), at a dose ranging from 5 × 104 to 5 × 106 cells. The meta-analysis showed an improvement on the cylinder rearing test (MD: -10.62; 95% CI: -14.38 to -6.86) and on the water maze test (MD: 1.31 MD; 95% CI: 0.80 to 1.81) in animals treated with MSCs compared to the control group animals. CONCLUSION: MSCs appear to improve sensorimotor and cognitive performance in PAIS-injured animals; however, the certainty of the evidence is low. Registration of the protocol of preclinical studies, appropriate sample size calculation, rigorous randomization, and reporting of the data on animal sex and survival are warranted. PROSPERO registration number: CRD42021239642. IMPACT: This is the first systematic review and meta-analysis of preclinical studies investigating the effects of MSCs in an experimental model of PAIS. MSCs appear to improve sensorimotor and cognitive performance in PAIS-injured neonatal animals. The certainty of the evidence is low due to high or unclear risk of bias in most domains.

Toward optoacoustic sciatic nerve detection using an all-fiber interferometric-based sensor for endoscopic smart laser surgery.

OBJECTIVES: Laser surgery requires efficient tissue classification to reduce the probability of undesirable or unwanted tissue damage. This study aimed to investigate acoustic shock waves (ASWs) as a means of classifying sciatic nerve tissue. MATERIALS AND METHODS: In this study, we classified sciatic nerve tissue against other tissue types-hard bone, soft bone, fat, muscle, and skin extracted from two proximal and distal fresh porcine femurs-using the ASWs generated by a laser during ablation. A nanosecond frequency-doubled Nd:YAG laser at 532 nm was used to create 10 craters on each tissue type's surface. We used a fiber-coupled Fabry-Pérot sensor to measure the ASWs. The spectrum's amplitude from each ASW frequency band measured was used as input for principal component analysis (PCA). PCA was combined with an artificial neural network to classify the tissue types. A confusion matrix and receiver operating characteristic (ROC) analysis was used to calculate the accuracy of the testing-data-based scores from the sciatic nerve and the area under the ROC curve (AUC) with a 95% confidence-level interval. RESULTS: Based on the confusion matrix and ROC analysis of the model's tissue classification results (leave-one-out cross-validation), nerve tissue could be classified with an average accuracy rate and AUC result of 95.78  ± 1.3% and 99.58  ± 0.6%, respectively. CONCLUSION: This study demonstrates the potential of using ASWs for remote classification of nerve and other tissue types. The technique can serve as the basis of a feedback control system to detect and preserve sciatic nerves in endoscopic laser surgery.

Resection of brain lesions with a neuroendoscopic ultrasonic aspirator - a systematic literature review.

The development of minimally invasive neuroendoscopy has advanced in recent years. The introduction of the neuroendoscopic ultrasonic aspirator (NUA) increased the treatment spectrum of neuroendoscopy. This review aimed to present a systematic overview of the extent of resection, lesion characteristics, technical aspects, complications, and clinical outcomes related to using the NUA. Articles were identified by searching the PubMed/Medline, Embase, and Web of Science database through June 2022 with restriction to the last 20 years. We included case series, case reports, clinical trials, controlled clinical trials, meta-analyses, randomized controlled trials, reviews, and systematic reviews written in English. Studies reporting on endonasal approach or hematoma evacuation using the NUA were excluded. The references of the identified studies were reviewed as well. Nine full-text articles were included in the analysis, with a total of 40 patients who underwent surgery for a brain tumor using NUA. The most common underlying pathology treated by NUA was colloid cyst (17.5%), pilocytic astrocytoma (12.5%), subependymal giant cell astrocytoma (7.5%), subependymoma (7.5%), and craniopharyngioma (7.5%). Complete or near-total resection was achieved in 62.5%. The most frequently reported postoperative complication was secondary hydrocephalus (10%), meningitis/-encephalitis (7.5%), cognitive impairment (7.5%), and subdural hygroma (7.5%). In one case (2.5%), surgery-related death occurred due to a severe course of meningoencephalitis. According to the preliminary data, NUA seems to be a safe and efficient minimally invasive alternative to conventional microscopic resection of brain tumors. Further studies to investigate advantages and disadvantages of using the NUA are needed.

Focal lesionectomy as surgical treatment of epilepsy in patients with Sturge-Weber syndrome: a case-based systematic review and meta-analysis.

OBJECTIVE: Sturge-Weber syndrome (SWS) is a rare neurocutaneous disorder presenting mostly with a facial port-wine stain and leptomeningeal angiomatosis. More than 85% of the patients are affected by epilepsy by the age of 2 years. Seizure and symptom control is the focus of SWS treatment, since no causal therapy exists yet. For pharmacologically intractable epilepsy, surgery is a treatment option. The aim of this systematic review and meta-analysis was to provide an overview of the literature regarding lesionectomy in SWS with a focus on seizure outcome, complications, and motor and cognitive development. METHODS: The PubMed and Embase databases were searched using a systematic search strategy to identify studies on SWS from their inception until 2021. Two independent researchers assessed the studies for inclusion and quality. Outcome measures were seizure outcome, postoperative complications, and motor and cognitive development. Thereafter, a systematic review was conducted, and a meta-analysis was performed for all included cohort studies. Risk of bias was assessed using the Newcastle-Ottawa Scale. Forest plots have been generated for all outcomes; risk ratio was used for pooled outcomes. A p value < 0.05 was considered as statistically significant. RESULTS: After removal of duplicates, the authors screened 439 articles, of which 9 articles with 150 patients were included. Our case and 5 case reports and 4 retrospective cohort studies were included for systematic review. The latter 4 studies qualified for the meta-analysis. In these 4 articles, 144 patients received surgical treatment: 81 (56%) underwent focal lesionectomy and 63 (44%) hemispherectomy. Pooled outcome analysis for postoperative favorable seizure outcome showed a nonsignificant difference between lesionectomy and hemispherectomy (69.2% vs 87.3%; RR 0.73, 95% CI 0.50-1.08; t = -2.56, p = 0.08). Lesionectomy showed a significantly lower rate for developmental delay and postoperative hemiparesis in comparison with hemispherectomy (29.8% vs 76.3%; RR 0.41, 95% CI 0.28-0.59; z = -4.77, p < 0.0001 and 18.1% vs 100%; RR 0.11, 95% CI 0.06-0.21; z = -6.58, p < 0.0001, respectively). CONCLUSIONS: Based on the limited literature available, lesionectomy leads to a nonsignificant lower seizure control rate, while postoperative developmental or motor deficits are significantly lower compared with hemispherectomy. Therefore, focal lesionectomy remains a valid alternative to hemispherectomy in SWS with a clearly localized epileptogenic area; however, individual case-based decisions in a specialized multidisciplinary team are of paramount importance.

Minimal invasive interlaminar approach for untethering of fatty filum terminale in pediatric patients - how I do it.

BACKGROUND: Fatty filum terminale is a form of spinal dysraphism and a third of all patients develop symptoms such as sensory, motor, and urinary impairment. Early surgery at 6 months has the advantage that the bone density is still soft, and the patients are not ambulatory yet, promoting faster healing. METHOD: We present our minimal invasive surgical technique for FFT untethering. CONCLUSION: Due to the low complication rate and the potentially high benefit of surgery, prophylactic untethering is recommended.