GABAB receptor outward currents are transiently disclosed by the convulsant 4-aminopyridine in vitro.

The K+ channel blocker 4-aminopyridine (4AP) has been extensively used to investigate the mechanisms underlying neuronal network synchronization in both in vitro and in vivo animal models of focal epilepsy. 4AP-induced effects are paralleled by an increase in both excitatory and inhibitory neurotransmitter release, but the mechanisms of action of 4AP on neuronal networks remain unclear. By employing simultaneous whole-cell patch clamp and field potential recordings from hippocampal CA3/4 pyramidal layer of acute brain slices obtained from mice (n = 30), we found that the appearance of epileptiform discharges induced by 4AP (100 µM) is consistently preceded by the transient recurrence of presumptive GABAB outward currents, which are not mirrored by any field activity. These GABAB outward currents still occurred during application of ionotropic glutamatergic antagonists (n = 12 cells) but were blocked by the GABAB receptor antagonist CGP55845 (n = 7). Our findings show that the transient occurrence of distinct GABAB outward currents precedes the appearance of 4AP-induced neuronal network synchronization leading to epileptiform activity in the rodent hippocampus in vitro.

mTOR Pathway Somatic Pathogenic Variants in Focal Malformations of Cortical Development: Novel Variants, Topographic Mapping, and Clinical Outcomes.

Background and Objectives: Somatic and germline pathogenic variants in genes of the mammalian target of rapamycin (mTOR) signaling pathway are a common mechanism underlying a subset of focal malformations of cortical development (FMCDs) referred to as mTORopathies, which include focal cortical dysplasia (FCD) type II, subtypes of polymicrogyria, and hemimegalencephaly. Our objective is to screen resected FMCD specimens with mTORopathy features on histology for causal somatic variants in mTOR pathway genes, describe novel pathogenic variants, and examine the variant distribution in relation to neuroimaging, histopathologic classification, and clinical outcomes. Methods: We performed ultra-deep sequencing using a custom HaloPlexHS Target Enrichment kit in DNA from 21 resected fresh-frozen histologically confirmed FCD type II, tuberous sclerosis complex, or hemimegalencephaly specimens. We mapped the variant alternative allele frequency (AAF) across the resected brain using targeted ultra-deep sequencing in multiple formalin-fixed paraffin-embedded tissue blocks. We also functionally validated 2 candidate somatic MTOR variants and performed targeted RNA sequencing to validate a splicing defect associated with a novel DEPDC5 variant. Results: We identified causal mTOR pathway gene variants in 66.7% (14/21) of patients, of which 13 were somatic with AAF ranging between 0.6% and 12.0%. Moreover, the AAF did not predict balloon cell presence. Favorable seizure outcomes were associated with genetically clear resection borders. Individuals in whom a causal somatic variant was undetected had excellent postsurgical outcomes. In addition, we demonstrate pathogenicity of the novel c.4373_4375dupATG and candidate c.7499T>A MTOR variants in vitro. We also identified a novel germline aberrant splice site variant in DEPDC5 (c.2802-1G>C). Discussion: The AAF of somatic pathogenic variants correlated with the topographic distribution, histopathology, and postsurgical outcomes. Moreover, cortical regions with absent histologic FCD features had negligible or undetectable pathogenic variant loads. By contrast, specimens with frank histologic abnormalities had detectable pathogenic variant loads, which raises important questions as to whether there is a tolerable variant threshold and whether surgical margins should be clean, as performed in tumor resections. In addition, we describe 2 novel pathogenic variants, expanding the mTORopathy genetic spectrum. Although most pathogenic somatic variants are located at mutation hotspots, screening the full-coding gene sequence remains necessary in a subset of patients.

Vasospasm following brain tumor resection in children: institutional experience and systematic review.

OBJECTIVE: Delayed cerebral ischemia (DCI) associated with vasospasm is well described in the setting of aneurysmal subarachnoid hemorrhage (SAH). In addition, DCI is very infrequently encountered in patients who have undergone resection of a brain tumor with unclear pathophysiology. The occurrence of DCI in the pediatric population is exceedingly rare, and outcomes in this population have, to the authors' knowledge, never been systematically reviewed. Therefore, the authors present what is to their knowledge the largest series of pediatric patients with this complication and systematically reviewed the literature for individual participant data. METHODS: The authors conducted a retrospective review of 172 sellar and suprasellar tumors in pediatric patients who underwent surgery at the Montreal Children's Hospital between 1999 and 2017 to identify cases of vasospasm occurring after tumor resection. Descriptive statistics, including patient characteristics, intraoperative and postoperative findings, and outcome status, were collected. A systematic review was also conducted using three databases (PubMed, Web of Science, Embase) to identify reported cases available in the literature of vasospasm after tumor resection in children and collect individual participant data on these patients for further analysis. RESULTS: Six patients treated at Montreal Children's Hospital were identified, with an average age of 9.5 years (range 6-15 years). The prevalence of vasospasm after tumor resection was 3.5% (6/172). Vasospasm in all 6 patients occurred after craniotomy was performed to treat a suprasellar tumor. The average interval from surgery to symptoms was 3.25 days (range 12 hours-10 days). The most common tumor etiology was craniopharyngioma, seen in 4 cases. Extensive tumor encasement of blood vessels requiring significant operative manipulation was described in all 6 patients. A rapid decrease in serum sodium (exceeding 12 mEq/L/24 hrs or below 135 mEq/L) was seen in 4 patients. On final follow-up, 3 patients were left with significant disability, and all patients had persistent deficits. A systematic review of the literature revealed a total of 10 other patients whose characteristics and treatment were compared with those of the 6 patients treated at Montreal Children's Hospital. CONCLUSIONS: Vasospasm after tumor resection in children and youth is likely a rare entity, with a prevalence of 3.5% in this case series. Suprasellar tumor location (particularly craniopharyngioma tumor etiology), significant encasement of blood vessels by the tumor, and postoperative hyponatremia may be predictive factors. Outcome is poor, with most patients having significant persistent neurological deficits.

Subtle magnetic resonance imaging differences in tegmental pilocytic astrocytomas as a caution against attempting gross-total resection: illustrative cases.

BACKGROUND: Although surgery within the tegmentum of the midbrain is challenging, resection of tegmental pilocytic astrocytomas (PAs) is a standard treatment because this has been shown to outperform chemotherapy and radiotherapy in terms of long-term tumor control. Gross total resection (GTR) assisted by intraoperative neuroelectrophysiological monitoring can be achieved with a reasonable risk-to-benefit ratio, especially for well-circumscribed tumors, but careful scrutiny of magnetic resonance imaging (MRI) is critical to surgical decision making. The authors present two cases of tegmental PAs, which appeared grossly similar on MRI and were operated on via the same surgical approach using the same intraoperative adjuncts. OBSERVATIONS: The tumors had identical histopathological and molecular diagnoses but drastically different functional outcomes for the patients, with significant long-term complications for one of the children, which the authors believe was due to a slightly more invasive nature of this tumor. The authors demonstrate subtle preoperative MRI findings that might be potential clues to a more infiltrative nature of one PA versus another and present pathological findings supporting this argument. LESSONS: This report serves as a reminder that not all tegmental PAs can be managed by the same surgical approach. Subtle signs of infiltration may indicate that GTR should not be attempted.

K27M in canonical and noncanonical H3 variants occurs in distinct oligodendroglial cell lineages in brain midline gliomas.

Canonical (H3.1/H3.2) and noncanonical (H3.3) histone 3 K27M-mutant gliomas have unique spatiotemporal distributions, partner alterations and molecular profiles. The contribution of the cell of origin to these differences has been challenging to uncouple from the oncogenic reprogramming induced by the mutation. Here, we perform an integrated analysis of 116 tumors, including single-cell transcriptome and chromatin accessibility, 3D chromatin architecture and epigenomic profiles, and show that K27M-mutant gliomas faithfully maintain chromatin configuration at developmental genes consistent with anatomically distinct oligodendrocyte precursor cells (OPCs). H3.3K27M thalamic gliomas map to prosomere 2-derived lineages. In turn, H3.1K27M ACVR1-mutant pontine gliomas uniformly mirror early ventral NKX6-1+/SHH-dependent brainstem OPCs, whereas H3.3K27M gliomas frequently resemble dorsal PAX3+/BMP-dependent progenitors. Our data suggest a context-specific vulnerability in H3.1K27M-mutant SHH-dependent ventral OPCs, which rely on acquisition of ACVR1 mutations to drive aberrant BMP signaling required for oncogenesis. The unifying action of K27M mutations is to restrict H3K27me3 at PRC2 landing sites, whereas other epigenetic changes are mainly contingent on the cell of origin chromatin state and cycling rate.

New interinstitutional, multimodal presurgical evaluation protocol associated with improved seizure freedom for poorly defined cases of focal epilepsy in children.

OBJECTIVE: In an attempt to improve postsurgical seizure outcomes for poorly defined cases (PDCs) of pediatric focal epilepsy (i.e., those that are not visible or well defined on 3T MRI), the authors modified their presurgical evaluation strategy. Instead of relying on concordance between video-electroencephalography and 3T MRI and using functional imaging and intracranial recording in select cases, the authors systematically used a multimodal, 3-tiered investigation protocol that also involved new collaborations between their hospital, the Montreal Children's Hospital, and the Montreal Neurological Institute. In this study, the authors examined how their new strategy has impacted postsurgical outcomes. They hypothesized that it would improve postsurgical seizure outcomes, with the added benefit of identifying a subset of tests contributing the most. METHODS: Chart review was performed for children with PDCs who underwent resection following the new strategy (i.e., new protocol [NP]), and for the same number who underwent treatment previously (i.e., preprotocol [PP]); ≥ 1-year follow-up was required for inclusion. Well-defined, multifocal, and diffuse hemispheric cases were excluded. Preoperative demographics and clinical characteristics, resection volumes, and pathology, as well as seizure outcomes (Engel class Ia vs > Ia) at 1 year postsurgery and last follow-up were reviewed. RESULTS: Twenty-two consecutive NP patients were compared with 22 PP patients. There was no difference between the two groups for resection volumes, pathology, or preoperative characteristics, except that the NP group underwent more presurgical evaluation tests (p < 0.001). At 1 year postsurgery, 20 of 22 NP patients and 10 of 22 PP patients were seizure free (OR 11.81, 95% CI 2.00-69.68; p = 0.006). Magnetoencephalography and PET/MRI were associated with improved postsurgical seizure outcomes, but both were highly correlated with the protocol group (i.e., independent test effects could not be demonstrated). CONCLUSIONS: A new presurgical evaluation strategy for children with PDCs of focal epilepsy led to improved postsurgical seizure freedom. No individual presurgical evaluation test was independently associated with improved outcome, suggesting that it may be the combined systematic protocol and new interinstitutional collaborations that makes the difference rather than any individual test.

The utility of arterial spin labeling in the presurgical evaluation of poorly defined focal epilepsy in children.

OBJECTIVE: The authors sought to assess the utility of arterial spin labeling (ASL) perfusion 3T-MRI for the presurgical evaluation of poorly defined focal epilepsy in pediatric patients. METHODS: Pseudocontinuous ASL perfusion 3T-MRI was performed in 25 consecutive children with poorly defined focal epilepsy. ASL perfusion abnormalities were detected qualitatively by visual inspection and quantitatively by calculating asymmetry index (AI) maps and significant z-score cluster maps based on successfully operated cases. ASL results were prospectively compared to scalp EEG, structural 3T-MRI, FDG-PET, ictal/interictal SPECT, magnetoencephalography (MEG), and intracranial recording results, as well as the final surgically proven epileptogenic zone (EZ) in operated patients who had at least 1 year of good (Engel class I/II) seizure outcome and positive histopathology results. RESULTS: Qualitative ASL perfusion abnormalities were found in 17/25 cases (68%), specifically in 17/20 MRI-positive cases (85.0%) and in none of the 5 MRI-negative cases. ASL was concordant with localizing scalp EEG findings in 66.7%, structural 3T-MRI in 90%, FDG-PET in 75%, ictal/interictal SPECT in 62.5%, and MEG in 75% of cases, and with intracranial recording results in 40% of cases. Eleven patients underwent surgery; in all 11 cases the EZ was surgically proven by positive histopathology results and the patient having at least 1 year of good seizure outcome. ASL results were concordant with this final surgically proven EZ in 10/11 cases (sensitivity 91%, specificity 50%). All 10 ASL-positive patients who underwent surgery had positive surgical pathology results and good long-term postsurgical seizure outcome at a mean follow-up of 39 months. Retrospective quantitative analysis based on significant z-score clusters found 1 true-positive result that was missed by qualitative analysis and 3 additional false-positive results (sensitivity 100%, specificity 23%). CONCLUSIONS: ASL supports the hypothesis regarding the EZ in poorly defined focal epilepsy cases in children. Due to its convenience and noninvasive nature, the authors recommend that ASL be added routinely to the presurgical MRI evaluation of epilepsy. Future optimized quantitative methods may improve the diagnostic yield of this technique.

Successful treatment of non-midline primary malignant germ cell tumors with yolk sac components in neonates: report of 2 cases.

Here, the authors present 2 cases of nongerminomatous germ cell tumor (NGGCT): a neonate with a mixed malignant germ cell tumor, 5% yolk sac tumor (YST) and 95% immature teratoma components, originating from the right mesial temporal lobe; and a 2-month-old infant with a pure YST originating from the left middle cranial fossa. These tumors with yolk sac components, which are thought to have a poor prognosis, were successfully treated with complete tumor resection alone and subtotal tumor resection with chemotherapy, respectively. Event-free survival exceeds 5 years for each patient even though neither received radiotherapy. The authors highlight the role of radical surgery and the successful treatment of neonatal YST with aggressive resection (and chemotherapy in 1 case) while avoiding radiation therapy. They also report the very rare non-midline location of these neonatal NGGCTs and emphasize the importance of considering YSTs and mixed NGGCTs with YST components in the differential diagnosis of non-midline hemispheric or skull base tumors in newborns.

Operative Time as the Predominant Risk Factor for Transfusion Requirements in Nonsyndromic Craniosynostosis Repair.

Despite recent advances in surgical, anesthetic, and safety protocols in the management of nonsyndromic craniosynostosis (NSC), significant rates of intraoperative blood loss continue to be reported by multiple centers. The purpose of the current study was to examine our center's experience with the surgical correction of NSC in an effort to determine independent risk factors of transfusion requirements. METHODS: A retrospective cohort study of patients with NSC undergoing surgical correction at the Montreal Children's Hospital was carried out. Baseline characteristics and perioperative complications were compared between patients receiving and not receiving transfusions and between those receiving a transfusion in excess or <25 cc/kg. Logistic regression analysis was carried out to determine independent predictors of transfusion requirements. RESULTS: A total of 100 patients met our inclusion criteria with a mean transfusion requirement of 29.6 cc/kg. Eighty-seven patients (87%) required a transfusion, and 45 patients (45%) required a significant (>25 cc/kg) intraoperative transfusion. Regression analysis revealed that increasing length of surgery was the main determinant for intraoperative (P = 0.008; odds ratio, 18.48; 95% CI, 2.14-159.36) and significant (>25 cc/kg) intraoperative (P = 0.004; odds ratio, 1.95; 95% CI, 1.23-3.07) transfusions. CONCLUSIONS: Our findings suggest increasing operative time as the predominant risk factor for intraoperative transfusion requirements. We encourage craniofacial surgeons to consider techniques to streamline the delivery of their selected procedure, in an effort to reduce operative time while minimizing the need for transfusion.

Selective Dorsal Root Rhizotomy for Spastic Cerebral Palsy: A Longitudinal Case-Control Analysis of Functional Outcome.

BACKGROUND: The benefit of selective dorsal rhizotomies (SDR) on motor function relative to the cerebral palsy (CP) natural history remains unknown. OBJECTIVE: To determine the functional benefit of SDR over the longitudinal CP natural history. METHODS: Retrospective, single-center, case-control study of patients post-SDR after 1990. Inclusion criteria were the following: diagnosis of spastic CP, at least 1 preoperative and 1 postoperative Gross Motor Function Measure (GMFM-88), at least 1 yr of postoperative follow-up. GMFM-88 assessments were performed at 1, 2, 3, 5, 10, and 15 yr postoperatively and converted to GMFM-66. Cases were stratified by preoperative Gross Motor Function Classification System (GMFCS) and matched against their expected natural history using published reference centiles. After age 12, our cohort and matched controls were also fitted to published nonlinear mixed models of GMFM-66 evolution over time. RESULTS: Analysis included 190 patients. Median follow-up, 5.3 yr (range: 1-16.9), median age at surgery, 4.6 yr, and 81.6% of patients grouped as GMFCS II or III pre-op. SDR patients performed statistically significantly better than their expected natural history (P < .0005). At 21 yr old, a modeled benefit of 8.435 was observed for GMFCS I (P = .0051), 0.05 for GMFCS II (P = .9647), 6.31 for GMFCS III (P < .0001), and 1.191 for GMFCS IV patients (P = .0207). CONCLUSION: These results support the use of SDR in carefully selected spastic CP children.

Stalled developmental programs at the root of pediatric brain tumors.

Childhood brain tumors have suspected prenatal origins. To identify vulnerable developmental states, we generated a single-cell transcriptome atlas of >65,000 cells from embryonal pons and forebrain, two major tumor locations. We derived signatures for 191 distinct cell populations and defined the regional cellular diversity and differentiation dynamics. Projection of bulk tumor transcriptomes onto this dataset shows that WNT medulloblastomas match the rhombic lip-derived mossy fiber neuronal lineage and embryonal tumors with multilayered rosettes fully recapitulate a neuronal lineage, while group 2a/b atypical teratoid/rhabdoid tumors may originate outside the neuroectoderm. Importantly, single-cell tumor profiles reveal highly defined cell hierarchies that mirror transcriptional programs of the corresponding normal lineages. Our findings identify impaired differentiation of specific neural progenitors as a common mechanism underlying these pediatric cancers and provide a rational framework for future modeling and therapeutic interventions.

Correction to: Efficacy of Dabrafenib for three children with brainstem BRAFV600E positive ganglioglioma.

In the original article, the author names were published incorrectly. The names are correct in this publication.

Hyperacute Infarct on Intraoperative Diffusion Imaging of Pediatric Brain Tumor Surgery.

BACKGROUND: Brain neoplasms are the second-most prevalent cancer of childhood for which surgical resection remains the main treatment. Intraoperative MRI is a useful tool to optimize brain tumor resection. It is, however, not known whether intraoperative MRI can detect complications such as hyperacute ischemic infarcts. METHODS: A retrospective analysis of pre- and intraoperative MRIs including DWI sequence and correlation with early and 3-month postoperative MRIs was conducted to evaluate the incidence of hyperacute arterial infarct during pediatric brain tumor resection. Patient demographics, pathological type, tumor location, resection type as well as preoperative tumoral vessel encasement, evolution of the area of restricted diffusion were collected and analyzed comparatively between the group with acute infarct and the control group. Extent of the hyperacute infarct was compared to both early postsurgical and 3-month follow-up MRIs. RESULTS: Of the 115 cases, 13 (11%) developed a hyperacute arterial ischemic infarct during brain tumor resection. Tumoral encasement of vessels was more frequent in the infarct group (69%) compared to 25.5% in the control group. Four cases showed additional vessel irregularities on intraoperative MRI. On early follow-up, the infarcted brain area had further progressed in six cases and was stable in seven cases. No further progression was noted after the first week post-surgery. CONCLUSIONS: Hyperacute infarcts are not rare events to complicate pediatric brain tumor resection. Tumoral encasement of the circle of Willis vessels appears to be the main risk factor. Intraoperative DWI underestimates the final extent of infarcted tissue compared to early postsurgical MRI.

Présence d'infarctus ischémiques hyper-aigus révélés par des IRM peropératoires de diffusion dans le cas de chirurgies visant à traiter le cancer du cerveau chez l'enfant.Contexte: Chez l'enfant, les néoplasmes du cerveau viennent au second rang des cancers pour lesquels la résection chirurgicale demeure le principal traitement. L'IRM peropératoire est un outil efficace pour maximiser la résection d'une tumeur cérébrale. On ignore toutefois de quelle façon cet outil peut permettre de détecter des complications telles que les infarctus ischémiques hyper-aigus. Méthodes:Nous avons tout d'abord effectué une analyse rétrospective des IRM préopératoires et peropératoires, ce qui inclut des IRM de diffusion. Nous avons aussi cherché à établir des corrélations avec des IRM post-opératoires, certaines effectuées tout juste après une résection et d'autres après 3 mois, afin d'évaluer l'incidence d'infarctus ischémiques hyper-aigus survenant en cours de résection. Des données portant sur les caractéristiques des patients, sur la pathologie tumorale, sur l'emplacement des tumeurs, sur le type de résection ainsi que sur l'envahissement vasculaire tumoral préopératoire et sur l'évolution de la région de diffusion restreinte ont été collectées. Nous avons ensuite effectué une analyse comparative entre notre groupe de patients et un groupe de témoins. L'ampleur des infarctus ischémiques hyper-aigus a été comparée au moyen d'IRM réalisées tout juste après une résection et d'IRM de suivi après trois mois. Résultats:Sur un total de 115 cas, 13 (11 %) ont donné à voir un infarctus ischémique hyper-aigu au cours d'une résection. L'envahissement vasculaire tumoral était plus fréquent dans le groupe de jeunes patients ayant donné à voir un infarctus (69 %) comparativement à 25,5 % dans le groupe des témoins. Quatre cas ont aussi montré, lors d'IRM peropératoires, des irrégularités additionnelles en ce qui a trait aux vaisseaux sanguins. Lors de suivis effectués rapidement après une résection, les régions du cerveau affectées par un infarctus avaient continué à croître davantage chez 6 cas et étaient demeurées stables chez 7 autres cas. Aucune autre progression n'a été notée à la suite d'une IRM menée une semaine plus tard. Conclusions:Les infarctus ischémiques hyper-aigus ne sont pas des événements inhabituels. Comme on le sait, ils peuvent entraîner des complications au moment d'effectuer la résection d'une tumeur cérébrale chez l'enfant. L'envahissement vasculaire tumoral du polygone de Willis semble être ici le principal facteur de risque. Les IRM de diffusion peropératoires ont tendance à sous-estimer l'étendue finale des tissus affectés par un infarctus ischémique comparativement aux IRM effectuées tout juste après une résection.

Routine Postoperative Admission to the Intensive Care Unit Following Repair of Nonsyndromic Craniosynostosis: Is it Necessary?

BACKGROUND: Cranial vault surgery for craniosynostosis is generally managed postoperatively in the intensive care unit (ICU). The purpose of the present study was to examine our center's experience with the postoperative management of otherwise healthy patients with nonsyndromic craniosynostosis (NSC) without routine ICU admission. METHODS: A retrospective cohort study of patients with NSC operated using a variety of vault reshaping techniques in our pediatric center between 2009 and 2017 was carried out. Patients with documented preexisting comorbidities that would have required admission to the ICU regardless of the surgical intervention were excluded. RESULTS: A total of 102 patients were included in the study. Postoperatively, 100 patients (98%) were admitted as planned to a general surgical ward following observation in the recovery room. Two patients (2%) required ICU admission due to adverse intraoperative events. There were no patients who required transfer to the ICU from the recovery area or surgical ward. Within the surgical ward cohort, 6 patients (6%) had minor postoperative complications that were readily managed on the surgical floor. Postoperative anemia requiring transfusion was the most common complication. CONCLUSION: The results from this study suggest that otherwise healthy patients with NSC undergoing cranial vault surgery can potentially be safely managed without routine admission to the ICU postoperatively. Key elements are proper preoperative screening, access to ICU should an adverse intraoperative event occur and necessary postoperative surgical care. The authors hope that this experience will encourage other craniofacial surgeons to reconsider the dogma of routine ICU admission for this patient population.

Trametinib for progressive pediatric low-grade gliomas.

INTRODUCTION: Pediatric pilocytic astrocytomas (PAs) are low grade gliomas and the most common brain tumors in children. They often represent a therapeutic challenge when incompletely resected as they can recur and progress despite the use of several lines of chemotherapeutic agents or even radiation therapy. Genetic alterations leading to activation of the mitogen-activated-protein-kinase pathway are a hallmark of this disease and offer an interesting therapeutic alternative through the use of targeted inhibitors. METHODS: Here, we describe six children with sporadic PA who were treated with trametinib, a MEK inhibitor, following progression under conventional therapies. Retrospective chart review was performed. RESULTS: The median age at diagnosis was 2.3 years (y) old [range 11 months (m)-8.5 y old]. KIAA1549-BRAF fusion was identified in five cases, and hotspot FGFR1/NF1/PTPN11 mutations in one. All patients received at least one previous line of chemotherapy (range 1-4). The median time on treatment was 11 m (range 4-20). Overall, we observed two partial responses and three minor responses as best response; three of these patients are still on therapy. Treatment was discontinued in the patient with progressive disease. The most frequent toxicities were minor to moderately severe skin rash and gastro-intestinal symptoms. Two patients had dose reduction due to skin toxicity. Quality of life was excellent with decreased hospital visits and a close to normal life. CONCLUSION: Trametinib appears to be a suitable option for refractory pediatric low-grade glioma and warrants further investigations in case of progression.

Magnetic Resonance Myelography in Congenital Absence of the Cervical Pedicle.

Absence of the cervical pedicle is a very rare congenital anomaly, easily misrecognized as a unilateral facet dislocation in a setting of acute trauma or a neoplastic process like a nerve sheath tumor. Although correct diagnosis can be achieved on the cervical radiograph and confirmed by the CT, MRI Myelography is clearly of additional value because shows the specific relationship and orientation of the nerve roots. To the best to our knowledge, this is the first description of MR Myelography findings.

3-T intraoperative MRI (iMRI) for pediatric epilepsy surgery.

PURPOSE: Three-tesla intraoperative MRI (iMRI) is a promising tool that could help confirm complete resections and disconnections in pediatric epilepsy surgery, leading to improved outcomes. However, a large proportion of epileptogenic pathologies in children are poorly defined on imaging, which brings into question the utility of iMRI for these cases. Our aim was to compare postoperative seizure outcomes between iMRI- and non-iMRI-based epilepsy surgeries. METHODS: We performed a comparative retrospective analysis of non-iMRI- versus iMRI-based epilepsy surgeries with 2-year follow-up. Patients were stratified into well-defined cases (WDCs), poorly defined cases (PDCs), and diffuse hemispheric cases (DHCs). Primary outcomes were rates of complete seizure freedom and surgical complications. Secondary outcomes included good (Engel class I/II) seizure outcome, extent of resection/disconnection, and operative duration. Regression models were used to adjust for confounding. RESULTS: Thirty-nine iMRI-based and 39 non-iMRI-based surgeries were included. The distributions of age, sex, and lesion class in each era were similar, but the distributions of individual pathologies varied. Seizure freedom and complication rates at 2-year follow-up were not different between the groups, but Engel class I/II outcome was more common in the iMRI group. Extent of resection/disconnection and length of surgery were similar in both groups. PDCs had the worst outcomes, which were unchanged by the use of iMRI. CONCLUSION: Three-tesla iMRI-based epilepsy surgery may have the potential to improve patient outcomes. However, we conclude that iMRI, in its current state of use at our institute, does not improve outcomes for children undergoing epilepsy surgery. Given that its use appears safe, further research on this technology is warranted, particularly for the most challenging PDCs.

Feasibility and value of preoperative embolization of a congenital choroid plexus tumour in the premature infant: An illustrative case report with technical details.

We present a case of a preterm boy (born at 35 weeks of pregnancy) who was delivered urgently by a caesarean section due to placental abruption. The baby was found to have a tense fontanelle leading to imaging that showed a 5.5 cm right intraventricular mass centred in the atrium, hydrocephalus and extensive surrounding vasogenic oedema. The mass was avidly enhancing with a few large associated vessels suggesting high vascularity. The condition of the baby was acutely deteriorating. He had multiple seizures followed by persistent low level of consciousness in the third day of life. His clinical decline prompted decision to proceed with surgical resection and preoperative embolization. A large single feeder (the right posterolateral choroidal artery) was embolized leading to near complete obliteration of the tumour blush. Embolization likely facilitated subsequent surgery the next day. This is based on an estimated blood loss of 250 ml in this 3 kg baby without haemodynamic instability. Gross total resection was achieved with a single surgery and the diagnosis was choroid plexus papilloma. Utilization of this combined approach in this preterm baby had led to survival in this potentially curable disease.

Comprehensive analysis of the clinical and urodynamic outcomes of secondary tethered spinal cord before and after spinal cord untethering.

OBJECTIVE: Secondary tethering of the spinal cord (TSC) occurs in 3-30% of patients with history of spinal cord dysraphism repair. As many patients with spinal cord dysraphism already have symptoms, it might be difficult to diagnose secondary TSC. Regular clinical/urodynamic (UDS) evaluation is therefore advised to pick-up changes early before they progress. This study aimed at presenting clinical/UDS outcomes for patients with secondary TSC who underwent spinal cord untethering (SCU). STUDY DESIGN: Charts of patients with secondary TSC between 1998 and 2010 were reviewed retrospectively. Patients who underwent pre/post SCU clinical/UDS evaluation were included. All patients were followed-up for a minimum of 5 years for proper clinical outcomes assessment. Urologic, neuro-orthopedic, and UDS outcomes were collected and studied. Continence status was assessed in children aged ≥5 years. Patients were considered continent if they were dry for ≥4 h or socially continent if they stayed dry most of the day using maximum 1-2 pads/day. Categorical data were compared using the Fisher-Exact test and continuous variables were compared using the Wilcoxon Signed Rank test. A p-value < 0.05 was considered significant. RESULTS: Twenty-three patients met our inclusion criteria. The median age at time of SCU was 8.8 (range 2.3-16.2) years. The median age at time of UDS follow-up after SCU was 8.8 (range 2.9-17) years. The median follow-up time was 5 (range 5-13.4) years. Urological symptoms were reported in 56.5% of patients before SCU and improved in 61.5% post SCU. Neuro-orthopedic symptoms were reported in 87% of patients before SCU and improved in 65% post SCU. Continence was achieved in 73.9% of the entire cohort on long-term follow-up, while 26.1% had socially acceptable continence. UDS outcomes are summarized in the Table. CONCLUSIONS: Patients with secondary TSC are expected to have progression of their symptoms over time if not untethered. From here comes the importance of closely performing clinical/UDS evaluation to pick-up changes early before they progress. Surprisingly, clinical outcomes after SCU with detailed description of the auxiliary management are sparse in the literature. Most studies focus on UDS outcomes. We provided in the current study a detailed discussion of the clinical outcomes, auxiliary-managements used to achieve continence, and the UDS outcomes. Careful periodic clinical/UDS evaluation is recommended for early pick-up of changes suggestive of TSC. SCU could improve existing symptoms, and prevent worsening or development of new symptoms. UDS parameters that showed most improvement were intravesical pressure at TCBC and bladder compliance.