Transdiscal instrumentation in single-level lumbosacral fusion for high-grade isthmic pediatric spondylolisthesis: Technical note and review of the literature.

Pediatric spondylolisthesis is a common cause of back pain in children, typically managed conservatively with bracing and non-steroidal anti-inflammatory drugs. When posterolateral fusion is performed for refractory pain, pseudarthrosis and implant failure may occur, necessitating reoperation. To improve patient outcomes, there is a need for alternative surgical techniques to effectively manage high-grade isthmic slips. Here, the authors report the case of a child with Meyerding grade III anterolisthesis of L5 on S1 who was treated with a single-level, instrumented fusion using bilateral S1-L5 transdiscal screws, supported with L5-S1 posterolateral instrumentation and arthrodesis. Postoperatively, there was improvement in the patient's symptoms with good clinical and radiographic outcomes. The patient continues to be symptom free with radiographic evidence of hardware stability and bony fusion across the segment. The authors detail a novel surgical technique in children as well as a review of lumbosacral transdiscal screw fixation. Further evidence is required to definitively establish the safety, outcomes, and biomechanical strength of this technique.

Risk of brainstem necrosis in pediatric patients with central nervous system malignancies after pencil beam scanning proton therapy.

Background: Radiation therapy (RT) plays an important role in management of pediatric central nervous system (CNS) malignancies. Centers are increasingly utilizing pencil beam scanning proton therapy (PBS-PT). However, the risk of brainstem necrosis has not yet been reported. In this study, we evaluate the rate of brainstem necrosis in pediatric patients with CNS malignancies treated with PBS-PT.Material and methods: Pediatric patients with non-hematologic CNS malignancies treated with PBS-PT who received dose to the brainstem were included. All procedures were approved by the institutional review board. Brainstem necrosis was defined as symptomatic toxicity. The actuarial rate was analyzed by the Kaplan Meier method.Results: One hundred and sixty-six consecutive patients were reviewed. Median age was 10 years (range 0.5-21 years). Four patients (2.4%) had prior radiation. Median maximum brainstem dose in the treated course was 55.4 Gy[RBE] (range 0.15-61.4 Gy[RBE]). In patients with prior RT, cumulative median maximum brainstem dose was 98.0 Gy [RBE] (range 17.0-111.0 Gy [RBE]). Median follow up was 19.6 months (range, 2.0-63.0). One patient who had previously been treated with twice-daily radiation therapy and intrathecal (IT) methotrexate experienced brainstem necrosis. The actuarial incidence of brainstem necrosis was 0.7% at 24 months (95% CI 0.1-5.1%).Conclusion: The rate of symptomatic brainstem necrosis was extremely low after treatment with PBS-PT in this study. Further work to clarify clinical and dosimetric parameters associated with risk of brainstem necrosis after PBS-PT is needed.

CRAF gene fusions in pediatric low-grade gliomas define a distinct drug response based on dimerization profiles.

Pediatric low-grade gliomas (PLGGs) are commonly associated with BRAF gene fusions that aberrantly activate the mitogen-activated protein kinase (MAPK) signaling pathway. This has led to PLGG clinical trials utilizing RAF- and MAPK pathway-targeted therapeutics. Whole-genome profiling of PLGGs has also identified rare gene fusions involving another RAF isoform, CRAF/RAF1, in PLGGs and cancers occuring in adults. Whereas BRAF fusions primarily dysregulate MAPK signaling, the CRAF fusions QKI-RAF1 and SRGAP3-RAF1 aberrantly activate both the MAPK and phosphoinositide-3 kinase/mammalian target of rapamycin (PI3K/mTOR) signaling pathways. Although ATP-competitive, first-generation RAF inhibitors (vemurafenib/PLX4720, RAFi) cause paradoxical activation of the MAPK pathway in BRAF-fusion tumors, inhibition can be achieved with 'paradox breaker' RAFi, such as PLX8394. Here we report that, unlike BRAF fusions, CRAF fusions are unresponsive to both generations of RAFi, vemurafenib and PLX8394, highlighting a distinct responsiveness of CRAF fusions to clinically relevant RAFi. Whereas PLX8394 decreased BRAF-fusion dimerization, CRAF-fusion dimerization is unaffected primarily because of robust protein-protein interactions mediated by the N-terminal non-kinase fusion partner, such as QKI. The pan-RAF dimer inhibitor, LY3009120, could suppress CRAF-fusion oncogenicity by inhibiting dimer-mediated signaling. In addition, as CRAF fusions activate both the MAPK and PI3K/mTOR signaling pathways, we identify combinatorial inhibition of the MAPK/mTOR pathway as a potential therapeutic strategy for CRAF-fusion-driven tumors. Overall, we define a mechanistic distinction between PLGG-associated BRAF- and CRAF/RAF1 fusions in response to RAFi, highlighting the importance of molecularly classifying PLGG patients for targeted therapy. Furthermore, our study uncovers an important contribution of the non-kinase fusion partner to oncogenesis and potential therapeutic strategies against PLGG-associated CRAF fusions and possibly pan-cancer CRAF fusions.

Reconstructive challenges in the extended endoscopic transclival approach.

OBJECTIVE: We wanted to present our experience with the extended endoscopic approach to clival pathology, focusing on cerebrospinal fluid leak and reconstruction challenges. METHODS: We examined a consecutive series of 37 patients undergoing the extended endoscopic approach for skull base tumours, 9 patients with clival pathology. Patients were examined for the incidence of post-operative cerebrospinal fluid leak in relation to tumour pathology, location, size, reconstruction and lumbar drain. RESULTS: The overall incidence of post-operative cerebrospinal fluid leak was 10.8 per cent. Seventy-five per cent of patients who had a post-operative cerebrospinal fluid leak underwent a transclival approach (p < 0.05). All patients with clival pathology who underwent an intradural dissection had a post-operative cerebrospinal fluid leak (p < 0.05). CONCLUSION: Post-operative cerebrospinal fluid leak rates after the extended endoscopic approach have improved significantly after advancements including the vascularised nasoseptal flap. Despite this, transclival approaches continue to pose much difficulty. Further investigation is necessary to develop technical improvements that can meet the unique challenges associated with this region.

Magnetoencephalography for pediatric epilepsy: how we do it.

Magnetoencephalography (MEG) is increasingly being used in the preoperative evaluation of pediatric patients with epilepsy. The ability to noninvasively localize ictal onset zones (IOZ) and their relationships to eloquent functional cortex allows the pediatric epilepsy team to more accurately assess the likelihood of postoperative seizure freedom, while more precisely prognosticating the potential functional deficits that may be expected from resective surgery. Confirmation of clinically suggested multifocality may result in a recommendation against resective surgery because the probability of seizure freedom will be low. Current paradigms for motor and somatosensory testing are robust. Paradigms allowing localization of those regions necessary for competent language function, though promising, are under continuous optimization. MR imaging white matter trajectory data, created from diffusion tensor imaging obtained in the same setting as the localization brain MR imaging, provide ancillary information regarding connectivity of the IOZ to sites of rapid secondary spread and the spatial relationship of the IOZ to functionally important white matter bundles, such as the corticospinal tracts. A collaborative effort between neuroradiology, neurology, neurosurgery, neuropsychology, technology, and physics ensures successful implementation of MEG within a pediatric epilepsy program.

Human "memories" can be evoked by stimulation of the lateral temporal cortex after ipsilateral medial temporal lobe resection.

A patient with medically intractable seizures and mesial temporal sclerosis underwent a left anterior temporal lobectomy and amygdalohippocampectomy. After 4 months, his seizures recurred and a left temporal, subdural grid of electrodes was placed to localise his seizure focus. Stimulation through the grid evoked four distinct "memories", or experiential phenomena, despite absence of the ipsilateral medial temporal lobe. To our knowledge, this is the first documented case of experiential phenomena evoked by cortical stimulation in the absence of the ipsilateral medial temporal lobe.

Reversible posterior leukoencephalopathy occurring during resection of a posterior fossa tumor: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: Our goal was to present a clinically and radiographically documented case of reversible posterior leukoencephalopathy (RPL) that occurred during resection of a posterior fossa tumor. Although RPL has been previously described in multiple nonsurgical settings, we hope that this case description makes RPL more clinically and radiographically recognizable to neurosurgeons. CLINICAL PRESENTATION: RPL is the clinical syndrome of headaches, altered mental status, seizures, and visual loss, with radiographic findings of reversible parieto-occipital changes on cerebral computed tomographic and magnetic resonance imaging scans. It has been previously reported in the settings of malignant hypertension, renal disease, eclampsia, and immunosuppression. To our knowledge, the patient presented represents the first clinically and radiographically documented case of RPL occurring during resection of a posterior fossa tumor. The patient intraoperatively exhibited wide fluctuations in blood pressure and awoke with clinical and radiographic findings consistent with RPL. INTERVENTION: Aggressive intraoperative and postoperative management of the patient's blood pressure, supportive intensive care, rehabilitation, and close radiographic follow-up were performed. CONCLUSION: RPL can occur as a result of intraoperative variations in blood pressure, even among young, previously healthy individuals. With the aforementioned interventions, the patient experienced significant clinical and radiographic recovery.

Gravity detection through bifurcation.

Bifurcation is a phenomenon in which a physical system is forced to make a choice between one of the several possible states to which it can evolve. In this process the system can become extremely sensitive to very small influences--smaller than the size of the fluctuations--that favor one of the states. A general theory of this sensitivity and a simple model for gravity detection is presented. The difference between systems in thermodynamic equilibrium and those that are far from equilibrium is also discussed.

Evaluation of pedal lymphangiography in staging non-seminomatous testicular carcinoma.

An analysis is presented on 45 patients undergoing pedal lymphangiography followed by retroperitoneal lymphadenectomy for non-seminomatous testicular carcinoma. Retroperitoneal node metastases were predicted correctly with the lymphangiogram in 10 of 20 patients (50 per cent). The over-all predictive accuracy was 62 per cent.

Mediastinal choriocarcinoma in a chromatin-positive boy.

A case of primary mediastinal choriocarcinoma in a chromatin-positive boy is reported. The incidence of neoplasms in patients with so-called Klinefelter's syndrome is discussed as well as embryogenesis and diagnostic evaluation in patients presenting with this tumor.