Cognition and health-related quality of life in long-term survivors of high-grade glioma: an interactive perspective from patient and caregiver.

BACKGROUND: The health-related quality of life (HRQoL) and cognition are important indicators for the quality of survival in patients with high-grade glioma (HGG). However, data on long-term survivors and their caregivers are scarce. We aim to investigate the interaction between cognition and HRQoL in long-term survivors, their caregivers' evaluations, and the effect on caregiver strain and burden. METHODS: 21 long-term HGG (8 WHO grade III and 13 WHO grade IV) survivors (survival ≥ 5 years) and 15 caregivers were included. Cognition (verbal memory, attention, executive functioning, and language), HRQoL, anxiety and depression, caregiver strain, and caregiver burden were assessed with standardized measures. Questionnaires were completed by patients and/or their caregivers. RESULTS: Mean survival was 12 years (grade III) and 8 years (grade IV). Cognition was significantly impaired with a large individual variety. Patients' general HRQoL was not impaired but all functioning scales were deviant. Patient-proxy agreement was found in most HRQoL subscales. Three patients (14%) showed indications of anxiety or depression. One-third of the caregivers reported a high caregiver strain or a high burden. Test scores for attention, executive functioning, language, and/or verbal memory were correlated with perceived global health status, cognitive functioning, and/or communication deficits. Caregiver burden was not related to cognitive deficits. CONCLUSIONS: In long-term HGG survivors maintained HRQoL seems possible even when cognition is impaired in a large variety at the individual level. A tailored approach is therefore recommended to investigate the cognitive impairments and HRQoL in patients and the need for patient and caregiver support.

SARS-CoV-2 infection causes dopaminergic neuron senescence.

COVID-19 patients commonly present with signs of central nervous system and/or peripheral nervous system dysfunction. Here, we show that midbrain dopamine (DA) neurons derived from human pluripotent stem cells (hPSCs) are selectively susceptible and permissive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 infection of DA neurons triggers an inflammatory and cellular senescence response. High-throughput screening in hPSC-derived DA neurons identified several FDA-approved drugs that can rescue the cellular senescence phenotype by preventing SARS-CoV-2 infection. We also identified the inflammatory and cellular senescence signature and low levels of SARS-CoV-2 transcripts in human substantia nigra tissue of COVID-19 patients. Furthermore, we observed reduced numbers of neuromelanin+ and tyrosine-hydroxylase (TH)+ DA neurons and fibers in a cohort of severe COVID-19 patients. Our findings demonstrate that hPSC-derived DA neurons are susceptible to SARS-CoV-2, identify candidate neuroprotective drugs for COVID-19 patients, and suggest the need for careful, long-term monitoring of neurological problems in COVID-19 patients.

Incomplete spinal cord injury following minor trauma in two siblings with spondylocostal dysostis type 6.

Biallelic pathogenic variants of the RIPPLY2 gene have been recognized to cause a subtype of autosomal recessive spondylocostal dysostosis (SCDO6), characterized by predominant cervical spine malformation with minor or absent involvement of the ribs. To date, RIPPLY2 associated SCDO6 has been described in ten patients in five studies with accompanying clinical symptoms varying from transient and recurrent torticollis to flaccid quadriplegia. Here, we describe two additional patients in one family in which the c.A238T:p.Arg80* RIPPLY2 mutation in the homozygous state, was associated with severe malformation of the posterior elements of the cervical vertebral column. In both cases neurological symptoms occurred early in life due to spinal cord compromise. These two cases, in keeping with previous reports, highlight the early and progressive natural history of cervical deformity in this rare skeletal dysplasia and the need for close neurological and radiological surveillance. Surgical decision-making needs to carefully balance the need for early intervention to protect spinal cord function on one hand, with the problem of bone malformation and skeletal immaturity on the other.

Sympathetic components in left and right human cervical vagus nerve: implications for vagus nerve stimulation.

Cervical vagus nerve stimulation is in a great variety of clinical situations indicated as a form of treatment. It is textbook knowledge that at the cervical level the vagus nerve contains many different fiber classes. Yet, recently, several reports have shown that this nerve also may contain an additional class of potentially noradrenergic fibers, suggested to denote efferent sympathetic fibers. As such, the nature and presence of these fibers should be considered when choosing a stimulation protocol. We have studied human vagus material extracted from dissection room cadavers in order to further confirm the presence of this class of fibers, to study their origin and direction within the nerve and to determine their distribution and variability between subjects and pairs of left and right nerves of the same individual. Sections were studied with immunohistochemical techniques using antibodies against tyrosine hydroxylase (TH: presumed to indicate noradrenergic fibers), myelin basic protein and neurofilament. Our results show that at least part of the TH-positive fibers derive from the superior cervical ganglion or sympathetic trunk, do not follow a cranial but take a peripheral course through the nerve. The portion of TH-positive fibers is highly variable between individuals but also between the left and right pairs of the same individual. TH-positive fibers can distribute and wander throughout the fascicles but maintain a generally clustered appearance. The fraction of TH-positive fibers generally diminishes in the left cervical vagus nerve when moving in a caudal direction but remains more constant in the right nerve. These results may help to determine optimal stimulation parameters for cervical vagus stimulation in clinical settings.

Does response to vagus nerve stimulation for drug-resistant epilepsy differ in patients with and without Lennox-Gastaut syndrome?

INTRODUCTION: Literature on outcomes of patients with Lennox-Gastaut syndrome (LGS) receiving adjunctive vagus nerve stimulation (VNS) lacks information on seizure types and the time course of therapeutic effects. We have therefore performed what is to our knowledge the largest and most in-depth analysis of the effectiveness of VNS in LGS patients paying special attention to the impact of VNS Therapy on individual seizure types. METHODS: The VNS Therapy Outcomes Registry includes over 7000 patients. A propensity score matching method was employed to match patients with LGS to non-LGS patients with drug-resistant epilepsy (DRE). Overall seizure frequencies were assessed prior to implantation and at 3-, 6-, 12-, 18-, and 24-month follow-ups to derive the main study outcomes: response rates and time to first response. RESULTS: A total of 564 LGS patients with sufficient data were identified in the registry and matched 2:1 to 1128 non-LGS patients. Responder rates at 24 months were 57.5% in the LGS group and 61.5% in the non-LGS group. Median seizure frequency reduction at 24 months was 64.3% versus 66.7% in the LGS versus non-LGS group, respectively. In both groups, VNS was most effective at reducing focal aware seizures, "other" seizures, generalized-onset non-motor seizures, and drop attacks with relative reduction rates for these seizure types at 24 months exceeding 90% in both groups. Time-to-first response did not differ between the groups; however, there was a significantly higher proportion of patients who regressed from bilateral tonic-clonic (BTC) seizure response in the LGS group versus the non-LGS group at 24 months: 22.4% versus 6.7%; p = .015. CONCLUSIONS: Although limited by its retrospective design, the study shows that the effectiveness of VNS is comparable in DRE patients with and without LGS; however, LGS patients may be more prone to fluctuating control of BTCs.

Potential higher risk of tethered spinal cord in children after prenatal surgery for myelomeningocele: A systematic review and meta-analysis.

INTRODUCTION: We performed a systematic review and meta-analysis on the incidence of secondary tethered spinal cord (TSC) between prenatal and postnatal closure in patients with MMC. The objectives was to understand the incidence of secondary TSC after prenatal surgery for MMC compared to postnatal surgery for MMC. MATERIAL AND METHODS: On May 4, 2023, a systematic search was conducted in Medline, Embase, and the Cochrane Library to gather relevant data. Primary studies focusing on repair type, lesion level, and TSC were included, while non-English or non-Dutch reports, case reports, conference abstracts, editorials, letters, comments, and animal studies were excluded. Two reviewers assessed the included studies for bias risk, following PRISMA guidelines. TSC frequency in MMC closure types was determined, and the relationship between TSC occurrence and closure technique was analyzed using relative risk and Fisher's exact test. Subgroup analysis revealed relative risk differences based on study designs and follow-up periods. A total of ten studies, involving 2,724 patients, were assessed. Among them, 2,293 patients underwent postnatal closure, while 431 received prenatal closure for the MMC defect. In the prenatal closure group, TSC occurred in 21.6% (n = 93), compared to 18.8% (n = 432) in the postnatal closure group. The relative risk (RR) of TSC in patients with prenatal MMC closure versus postnatal MMC closure was 1.145 (95%CI 0.939 to 1.398). Fisher's exact test indicated a statistically non-significant association (p = 0.106) between TSC and closure technique. When considering only RCT and controlled cohort studies, the overall RR for TSC was 1.308 (95%CI 1.007 to 1.698) with a non-significant association (p = .053). For studies focusing on children up until early puberty (maximum 12 years follow-up), the RR for tethering was 1.104 (95%CI 0.876 to 1.391), with a non-significant association (p = 0.409). CONCLUSION AND DISCUSSION: This review found no significant increase in relative risk of TSC between prenatal and postnatal closure in MMC patients, but a trend of increased TSC in the prenatal group. More long-term data on TSC after fetal closure is needed for better counseling and outcomes in MMC.

Development of a simulator for training of fetoscopic myelomeningocele surgery.

OBJECTIVE: To develop a realistic simulation model for laparotomy-assisted fetoscopic spina bifida aperta (SBa) surgery, to be used for training purposes and preoperative planning. METHODS: The predefined general requirement was a realistic model of an exteriorized uterus, allowing all neurosurgical steps of the intervention. The uterus was modelled using ultrasound and MRI images of a 25 weeks' gravid uterus, consisting of flexible polyurethane foam coated with pigmented silicone. The fetal model, contained an opening on the dorsal side for a customizable spinal insert with all the aspects of a SBa, including a cele, placode, and myofascial and skin layer. The model was assessed in a series of validation experiments. RESULTS: Production costs are low, uterus and fetus are reusable. Placental localization and the level and size of the spinal defect are adjustable, enabling case-specific adaptations. All aspects of the simulator were scored close to realistic or higher for both appearance and functional capacities. CONCLUSIONS: This innovative model provides an excellent training opportunity for centers that are starting a fetoscopic SBa repair program. It is the first simulation model with adjustable spinal defect and placental localisation. Further objective validation is required, but the potential for using this model in preoperative planning is promising.

Trapped fourth ventricle: to stent, shunt, or fenestrate-a systematic review and individual patient data meta-analysis.

Trapped or isolated fourth ventricle (TFV) is a rare but critical neurosurgical condition, mostly occurring in pediatric patients, caused by a blockage of the in- and outlets of the fourth ventricle. The purpose of this study is to review all available data on the treatment options of TFV and to compare their safety, efficacy, and durability. MEDLINE, Embase, and Google Scholar were searched from inception to September 13, 2022, for prospective or retrospective cohorts, case-control studies, case series or case reports, reporting detailing outcomes of TFV patients, treated with an endoscopic-, microsurgical-, shunt placement,- or hybrid approaches to TFV. All authors were contacted to provide individual patient data. Eighty-seven articles (314 patients) were included in the individual patient data meta-analysis (IPD) and 9 (151 patients) in the cohort meta-analysis. The IPD revealed that primary endoscopic (aOR 0.21; [95% CI 0.08-0.57]) and microsurgical interventions (aOR 0.21; [95% CI 0.05-0.82]) were associated with a significantly lower revision rate, compared to shunt placement, when adjusted for confounders. Endoscopy was also associated with a significantly higher rate of clinical improvement (aOR 4.56; [95% CI 1.2-18]). The meta-analysis revealed no significant difference in revision rate between the endoscopic (0.33 [95% CI 0.0-0.52]) and shunt group (0.44 [95% CI 0.0-1.0]). Endoscopy should be considered as the first-line treatment of TFV due to its superior efficacy, durability, and similar safety, compared to shunt placement and its minimally invasive nature. Microsurgery should be considered as a second treatment option, due to its similar clinical outcomes and revision rate as endoscopy, but it is more invasive in nature.

Withdrawal of Life-Sustaining Therapies in Children With Severe Traumatic Brain Injury.

Neuroprognostication in severe traumatic brain injury (sTBI) is challenging and occurs in critical care settings to determine withdrawal of life-sustaining therapies (WLST). However, formal pediatric sTBI neuroprognostication guidelines are lacking, brain death criteria vary, and dilemmas regarding WLST persist, which lead to institutional differences. We studied WLST practice and outcome in pediatric sTBI to provide insight into WLST-associated factors and survivor recovery trajectory ≥1 year post-sTBI. This retrospective, single center observational study included patients <18 years admitted to the pediatric intensive care unit (PICU) of Erasmus MC-Sophia (a tertiary university hospital) between 2012 and 2020 with sTBI defined as a Glasgow Coma Scale (GCS) ≤8 and requiring intracranial pressure (ICP) monitoring. Clinical, neuroimaging, and electroencephalogram data were reviewed. Multi-disciplinary follow-up included the Pediatric Cerebral Performance Category (PCPC) score, educational level, and commonly cited complaints. Seventy-eight children with sTBI were included (median age 10.5 years; interquartile range [IQR] 5.0-14.1; 56% male; 67% traffic-related accidents). Median ICP monitoring was 5 days (IQR 3-8), 19 (24%) underwent decompressive craniectomy. PICU mortality was 21% (16/78): clinical brain death (5/16), WLST due to poor neurological prognosis (WLST_neuro, 11/16). Significant differences (p < 0.001) between survivors and non-survivors: first GCS score, first pupillary reaction and first lactate, Injury Severity Score, pre-hospital cardiopulmonary resuscitation, and Rotterdam CT (computed tomography) score. WLST_neuro decision timing ranged from 0 to 31 days (median 2 days, IQR 0-5). WLST_neuro decision (n = 11) was based on neurologic examination (100%), brain imaging (100%) and refractory intracranial hypertension (5/11; 45%). WLST discussions were multi-disciplinary with 100% agreement. Immediate agreement between medical team and caregivers was 81%. The majority (42/62, 68%) of survivors were poor outcome (PCPC score 3 to 5) at PICU discharge, of which 12 (19%) in a vegetative state. One year post-injury, no patients were in a vegetative state and the median PCPC score had improved to 2 (IQR 2-3). No patients died after PICU discharge. Twenty percent of survivors could not attend school 2 years post-injury. Survivors requiring an adjusted educational level increased to 45% within this timeframe. Chronic complaints were headache, behavioral problems, and sleeping problems. In conclusion, two-thirds of sTBI PICU mortality was secondary to WLST_neuro and occurred early post-injury. Median survivor PCPC score improved from 4 to 2 with no vegetative patients 1 year post-sTBI. Our findings show the WLST decision process was multi-disciplinary and guided by specific clinical features at presentation, clinical course, and (serial) neurological diagnostic modalities, of which the testing combination was determined by case-to-case variation. This stresses the need for international guidelines to provide accurate neuroprognostication within an appropriate timeframe whereby overall survivor outcome data provides valuable context and guidance in the acute phase decision process.

Brain stem encephalitis is a rare complication of COVID-19.

Here, we describe the clinical phenotype of SARS-CoV-2-related CNS disease and evaluate the SARS-CoV-2 antibody index as a tool to differentiate between a direct (viral) and indirect etiology. Out of >4000 hospitalized patients with COVID-19, we included 13 patients with neurological symptoms with suspicion of neuroinflammation. On clinical grounds, eight were classified as having a possible/probable relationship between neurological symptoms and COVID-19. A clinically distinctive phenotype of brainstem and cerebellar symptoms was seen in 6/8 patients. As we found a positive SARS-CoV-2 antibody index in 3/5 patients, indicating specific intrathecal SARS-CoV-2 IgG production, a direct link with SARS-CoV-2 is likely.

Newborns with myelomeningocele: their health-related quality of life and daily functioning 10 years later.

OBJECTIVE: Ten years ago, the authors reported on the outcome of their study investigating the degree of discomfort and pain in newborns with myelomeningocele (MMC), using the parameters of unbearable and hopeless suffering. In the current study, they investigated the quality of life, daily functioning, pain and fatigue, ability to communicate, and number of surgeries in the same cohort of patients. They subdivided their study population into severe (Lorber) and less severe (non-Lorber) cases and compared these cases with a healthy population (non-MMC group) and with each other. METHODS: The parents of 22 of 28 patients gave informed consent for this study. The KIDSCREEN-27 and PEDI-CAT (Pediatric Evaluation of Disability Inventory) were used to assess quality of life and daily functioning. Pain and fatigue were self-reported on a 10-point numeric rating scale. Communication and ambulation levels were determined using the Communication Function Classification System (CFCS) and the Hoffer ambulation scale. Using reference data from the KIDSCREEN-27 and PEDI-CAT, the authors created a healthy population comparison group. RESULTS: There was no significant difference in health-related quality-of-life (HRQOL) scores between Lorber and non-Lorber patients, except that school environment domain scores were lower in the Lorber group. When comparing the HRQOL of MMC patients with that of the non-MMC group, the physical well-being and parent relations and autonomy domains scored significantly lower. The daily functioning of MMC patients was lower on all domains of the PEDI-CAT compared with the non-MMC group. Lorber MMC patients scored lower on all domains of the PEDI-CAT when compared with non-Lorber patients. All patients were capable of communicating effectively; most patients (n = 18) were considered CFCS level I, and 4 patients were considered CFCS level II. CONCLUSIONS: This study shows that MMC is a severe, lifelong condition that affects patients' lives in many domains. All the patients in this study are capable of effective communication, irrespective of severity of MMC. Overall, the data show that in newborn MMC patients, future unbearable suffering with respect to pain, mobility, cognition, and communication is hard to predict and may not always occur.

Investigating chromosomal instability in long-term survivors with glioblastoma and grade 4 astrocytoma.

Background: Only a small group of patients with glioblastoma multiforme (GBM) survives more than 36 months, so-called long-term survivors. Recent studies have shown that chromosomal instability (CIN) plays a prognostic and predictive role among different cancer types. Here, we compared histological (chromosome missegregation) and bioinformatic metrics (CIN signatures) of CIN in tumors of GBM typical survivors (≤36 months overall survival), GBM long-term survivors and isocitrate dehydrogenase (IDH)-mutant grade 4 astrocytomas. Methods: Tumor sections of all gliomas were examined for anaphases and chromosome missegregation. Further CIN signature activity analysis in the The Cancer Genome Atlas (TCGA)-GBM cohort was performed. Results: Our data show that chromosome missegregation is pervasive in high grade gliomas and is not different between the 3 groups. We find only limited evidence of altered CIN levels in tumors of GBM long-term survivors relative to the other groups, since a significant depletion in CIN signature 11 relative to GBM typical survivors was the only alteration detected. In contrast, within IDH-mutant grade 4 astrocytomas we detected a significant enrichment of CIN signature 5 and 10 activities and a depletion of CIN signature 1 activity relative to tumors of GBM typical survivors. Conclusions: Our data suggest that CIN is pervasive in high grade gliomas, however this is unlikely to be a major contributor to the phenomenon of long-term survivorship in GBM. Nevertheless, further evaluation of specific types of CIN (signatures) could have prognostic value in patients suffering from grade 4 gliomas.

Pragmatism in Pediatric Neurosurgery: More Than a Pipe Dream? A Systematic Literature Review and Analysis.

BACKGROUND: Classic randomized controlled trials (RCTs) form the cornerstone for medical guidelines and protocols. However, in neurosurgery, RCTs are not always applicable to everyday clinical practice. Pragmatic controlled trials aim to incorporate real-life data with the preservation of the methodologic quality. This study is a systematic literature review of all pediatric neurosurgical RCTs published between 2000 and 2020 and an analysis of their pragmatism. METHODS: An electronic database search was performed in PubMed, EMBASE, and the Cochrane Library to identify all relevant trials. Pragmatism was evaluated retrospectively on 9 domains: eligibility, recruitment, setting, organization, flexibility (delivery and adherence), follow-up, primary outcome, and primary analysis. RESULTS: Of the 1862 studies included, 15 met the inclusion criteria. On average, studies scored between equally pragmatic/explanatory and rather pragmatic (M = 3.59, standard deviation [SD] = 0.56). Lowest ratings were seen for setting (M = 2.80, SD = 1.66) and eligibility (M = 3.20, SD = 1.66). Highest scores of pragmatism were given to analysis (M = 4.67, SD = 0.82) and intervention organization (M = 4.60, SD = 1.06). There was no significant difference between studies based on number of patients included, main subject, or publication year. CONCLUSIONS: Pediatric neurosurgical RCTs scored reasonably well on overall pragmatism. In the future, there will be a greater need for pragmatic controlled trials in pediatric neurosurgery to bridge the divide between real-life data and reliable methodological quality. There is an opportunity to develop further applications of pragmatism tailored to surgical interventions.

Quantifying the burden of disease in patients with Lennox Gastaut syndrome.

Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy but there is limited literature characterizing the disease burden despite this being crucial for disease management strategies, and for designing and interpreting clinical trials. We searched the Vagus Nerve Stimulation (VNS) Therapy Patient Outcome Registry including over 7000 patients with drug­resistant epilepsy (DRE). Propensity Score Matching (PSM) matched LGS-DRE patients and non-LGS-DRE patients and frequencies of individual seizure types were assessed. The PSM population included 705 and 1410 DRE patients with and without LGS. 40% of the LGS-DRE group had polypharmacy with 3 antiseizure medications (ASM) while 42% in non-LGS-DRE had polypharmacy with 2 ASMs. Median total monthly seizure frequency was over double in the LGS group: 90 (IQR, 28-312) versus 40 (IQR, 10-150); p < 0.001. This analysis suggests that seizure frequency in LGS patients who later receive VNS is more than double than in non-LGS DRE patients with mostly bilateral tonic-clonic seizures contributing to this difference. Furthermore, ASM burden with poorer seizure control may be greater in LGS patients, however data collection ceased in 2003 and therefore does not take recent ASMs approved for LGS into account. This analysis offers quantitative insight into the burden of disease in patients with LGS.

SARS-CoV-2 Infection Causes Dopaminergic Neuron Senescence.

COVID-19 patients commonly present with neurological signs of central nervous system (CNS)1-3 and/or peripheral nervous system dysfunction4. However, which neural cells are permissive to infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been controversial. Here, we show that midbrain dopamine (DA) neurons derived from human pluripotent stem cells (hPSCs) are selectively permissive to SARS-CoV-2 infection both in vitro and upon transplantation in vivo, and that SARS-CoV-2 infection triggers a DA neuron inflammatory and cellular senescence response. A high-throughput screen in hPSC-derived DA neurons identified several FDA approved drugs, including riluzole, metformin, and imatinib, that can rescue the cellular senescence phenotype and prevent SARS-CoV-2 infection. RNA-seq analysis of human ventral midbrain tissue from COVID-19 patients, using formalin-fixed paraffin-embedded autopsy samples, confirmed the induction of an inflammatory and cellular senescence signature and identified low levels of SARS-CoV-2 transcripts. Our findings demonstrate that hPSC-derived DA neurons can serve as a disease model to study neuronal susceptibility to SARS-CoV-2 and to identify candidate neuroprotective drugs for COVID-19 patients. The susceptibility of hPSC-derived DA neurons to SARS-CoV-2 and the observed inflammatory and senescence transcriptional responses suggest the need for careful, long-term monitoring of neurological problems in COVID-19 patients.

Proposed definition of competencies for surgical neuro-oncology training.

OBJECTIVE: The aim of this work is to define competencies and entrustable professional activities (EPAs) to be imparted within the framework of surgical neuro-oncological residency and fellowship training as well as the education of medical students. Improved and specific training in surgical neuro-oncology promotes neuro-oncological expertise, quality of surgical neuro-oncological treatment and may also contribute to further development of neuro-oncological techniques and treatment protocols. Specific curricula for a surgical neuro-oncologic education have not yet been established. METHODS: We used a consensus-building approach to propose skills, competencies and EPAs to be imparted within the framework of surgical neuro-oncological training. We developed competencies and EPAs suitable for training in surgical neuro-oncology. RESULT: In total, 70 competencies and 8 EPAs for training in surgical neuro-oncology were proposed. EPAs were defined for the management of the deteriorating patient, the management of patients with the diagnosis of a brain tumour, tumour-based resections, function-based surgical resections of brain tumours, the postoperative management of patients, the collaboration as a member of an interdisciplinary and/or -professional team and finally for the care of palliative and dying patients and their families. CONCLUSIONS AND RELEVANCE: The present work should subsequently initiate a discussion about the proposed competencies and EPAs and, together with the following discussion, contribute to the creation of new training concepts in surgical neuro-oncology.

Disappointing results of spring-assisted cranial vault expansion in patients with Crouzon syndrome presenting with sagittal synostosis.

The aim of this study was to report on a single center's experience with spring-assisted cranial vault expansion (SAE) in patients with Crouzon syndrome and sagittal suture synostosis. Strip craniotomy with SAE has resulted in successful outcomes with low complication and revision rates in patients with isolated scaphocephaly. However, recent experience suggests that outcomes in patients with Crouzon syndrome and sagittal synostosis (SS) who undergo SAE are less favorable compared with the outcomes of those who undergo frontobiparietal (FBP) expansion. The authors reviewed both operations performed at a single center and noticed an upward expansion of the skull, which may be related to ventriculomegaly, with concurrent intracranial hypertension and poor aesthetic outcome. All patients diagnosed with Crouzon syndrome and SS who were treated with SAE required a revision FBP operation. Based on this outcome, the authors consider Crouzon syndrome a contraindication for correcting SS with springs.

Fetoscopic myelomeningocoele closure: Is the scientific evidence enough to challenge the gold standard for prenatal surgery?

Since the completion of the Management of Myelomeningocoele Study, maternal-fetal surgery for spina bifida has become a valid option for expecting parents. More recently, multiple groups are exploring a minimally invasive approach and recent outcomes have addressed many of the initial concerns with this approach. Based on a previously published framework, we attempt to delineate the developmental stage of the surgical techniques. Furthermore, we discuss the barriers of performing randomized controlled trials comparing two surgical interventions and suggest that data collection through registries is an alternative method to gather high-grade evidence.

Vagus nerve stimulation in patients with Lennox-Gastaut syndrome: A meta-analysis.

OBJECTIVES: Lennox-Gastaut syndrome (LGS) is among the most severe epileptic and developmental encephalopathies. A meta-analysis was performed to evaluate the effectiveness of adjunctive vagus nerve stimulation (VNS Therapy) in patients with LGS. MATERIALS & METHODS: PubMed database was queried (January 1997 to September 2018) to identify publications reporting on the efficacy of VNS Therapy in patients with LGS, with or without safety findings. Primary endpoint of the meta-analysis was the proportion of responders (≥50% reduction in seizure frequency). Random-effects analysis was used to calculate weighted mean estimates and confidence intervals. Heterogeneity was evaluated by statistical tests including I2 . RESULTS: Of 2752 citations reviewed, 17 articles (480 patients) were eligible including 10 retrospective studies and seven prospective studies. A random-effects model produced a pooled proportion of 54% (95% confidence intervals [CI]: 45%, 64%) of patients with LGS who responded to adjunctive VNS Therapy (p for heterogeneity <0.001, I2 =72.9%). Per an exploratory analysis, the calculated incidence of serious adverse events associated with VNS Therapy was 9% (95% CI: 5%, 14%); the rate was higher than in long-term efficacy studies of heterogeneous cohorts with drug-resistant epilepsy and likely attributed to variable definitions of serious adverse events across studies. CONCLUSIONS: The meta-analysis of 480 patients with LGS suggests that 54% of patients responded to adjunctive VNS Therapy and that the treatment option was safe and well-tolerated. The response in patients with LGS was comparable to heterogeneous drug-resistant epilepsy populations. A clinical and surgical overview has been included to facilitate the use of VNS in LGS.