Responsive neurostimulation for refractory epilepsy in the pediatric population: A single-center experience.

Drug-resistant focal epilepsy (DRFE) in children can impair cognition and behavior, and lead to premature death. Increased pediatric epilepsy surgery numbers reflect the improvements in seizure control and long-term developmental outcomes. Yet, many children with DRFE are not candidates for surgical resection due to overlap of the seizure network with eloquent cortex or multiple seizure-onset zones, making surgery dangerous or ineffective. In adults, responsive neurostimulation (RNS System) therapy is safe and effective treatment for DRFE with one or two seizure foci, especially when the seizure focus is in eloquent cortex. We present six pediatric patients with DRFE who underwent RNS implantation. Our outcomes demonstrate safety, decreased clinical seizure frequency, as well as improved functional status and quality of life. Changes in the clinical seizure semiology and frequency occurred in conjunction with adjustments to the stimulation parameters, supporting the efficacy of responsive neuromodulation in children.

5-Aminolevulinic acid-assisted resection of pediatric dysembryoplastic neuroepithelial tumor: illustrative case.

BACKGROUND: 5-Aminolevulinic acid (5-ALA) is approved as an adjunct for the resection of high-grade gliomas and is associated with improved outcomes. Dysembryoplastic neuroepithelial tumors (DNETs) are benign glioneural tumors occurring primarily in pediatric patients and often manifesting with seizure disorder. The goal of the surgical intervention is to obtain gross-total resection, which is associated, in the majority of cases, with seizure freedom. OBSERVATIONS: The authors present the first case report of a pediatric patient who underwent gross-total resection of a 5-ALA-positive DNET with no evidence of recurrent seizures (Engel class I). LESSONS: Fluorescence-guided surgery using 5-ALA facilitated gross-total resection of the mass.

Minimally Invasive Parafascicular Surgical Approach for the Management of a Pediatric Third Ventricular Ependymoma: Case Report and Review of Literature.

BACKGROUND: Minimally invasive parafascicular surgery (MIPS) has evolved into a safe alternative to access deep-seated subcortical and intraventricular pathologies. We present a case of a port-mediated resection of a pediatric third ventricular tumor. CASE DESCRIPTION: The patient is a 7-year-old boy who presented with worsening headache, nausea, vomiting, dizziness, unsteady gait, photophobia, and blind spots with positional changes. Magnetic resonance imaging (MRI) scan revealed a large isointense mass, with areas of hyperintensities suggestive of intratumoral hemorrhage, centered in the posterior segment of the third ventricle with extension into the aqueduct of Sylvius. The superior frontal sulcus was used as an access corridor for the port to the frontal horn of the lateral ventricle en route to the third ventricle. Intraoperative visualization was aided with a 3-dimensional exoscopic system. After cannulation, the tumor was seen within the foramen of Monro and tethered to the thalamostriate vein. The tumor was removed completely, with the exception of small residual attached to the thalamostriate vein, which was left intentionally. A flexible endoscope was placed through the port to verify the absence of residual along the superior wall of the third ventricle. Intraoperative MRI scan confirmed presence of residual, along with normal postoperative changes, including pneumocephalus. Postoperative MRI scan revealed cortical recovery along the sulcal path and resolution of ventriculomegaly. CONCLUSIONS: The patient improved from baseline, with no remaining visual deficits, headaches, or balance issues. Pathology reported a World Health Organization grade II tanycytic ependymoma. To our knowledge, few cases have reported the utilization of port-based MIPS in pediatric patients.

Combined open microsurgical and endoscopic resection of hypothalamic hamartomas.

Hypothalamic hamartomas (HHs) are typically located within the vicinity of the third ventricle. They can be attached to the walls of the third ventricle, within the interpeduncular cistern (third ventricle floor), and/or attached to the mammillary bodies and hypothalamus. Depending on their location, resection is performed either through the third ventricle, approaching from above, or via a frontotemporal craniotomy (pterional or frontoorbital), approaching from below. "Above" approaches typically include the transcallosal-anterior interforniceal approach, and recently, purely endoscopic approaches performed transforaminally. The authors present a combined open and endoscopic approach for resection of HHs located within the third ventricle. They used this approach in 2 young girls with relatively small lateral and third ventricles. Following an interhemispheric, transcallosal approach and exposure of the right foramen of Monro, an endoscope was inserted through the foramen, which enabled safe resection of the HH. The main advantage of the combined approach is when the lateral and third ventricles are relatively small, making a purely endoscopic approach more challenging and possibly riskier.

Enhanced survival and neurite network formation of human umbilical cord blood neuronal progenitors in three-dimensional collagen constructs.

Umbilical cord blood (CB) stem cells have been proposed for cell-based therapeutic applications for diverse diseases of the CNS. We hypothesized that tissue-engineering strategies may extend the efficacy of these approaches by improving the long-term viability and function of stem cell-derived neuronal progenitors. To test our hypothesis, we explored the survival and differentiation of human CB-derived neuronal progenitors (HUCBNP) in a three-dimensional (3D) collagen construct. In contrast to two-dimensional culture conditions, the cells survived in 3D for an extended period of time of more than 2 months. Under 3D conditions, HUCBNP underwent spontaneous neuronal differentiation, which was further enhanced by treatment with neuronal conditioned medium (CM) and nerve growth factor (NGF). Neurite outgrowth, quantified by assessing the fractal dimension (D f) of the complex neuronal networks, was significantly enhanced under 3D conditions in the presence of CM/NGF, concomitant with a reduced expression of the early neuronal marker nestin (1.9-fold), and increased levels of mature neuronal markers such as MAP-2 (3.6-fold), ß-tubulin (1.5-fold), and neuronal specific enolase (6.6-fold) and the appearance of the synaptic marker synaptophysin. To assess the feasibility for clinical usage, HUCBNP were also isolated from frozen CB samples and cultured under 3D conditions. The data indicate the essential complete preservation of neurotrophic (survival) and neurotropic (neurite outgrowth) properties. In conclusion, 3D culture conditions are proposed as an essential step for both maintenance of CB neuronal progenitors in vitro and for investigating specific features of neuronal differentiation towards future use in regenerative therapy.

Neuroprotection by cord blood neural progenitors involves antioxidants, neurotrophic and angiogenic factors.

Human umbilical cord blood (HUCB) is a valuable source for cell therapy since it confers neuroprotection in stroke animal models. However, the responsible sub-populations remain to be established and the mechanisms involved are unknown. To explore HUCB neuroprotective properties in a PC12 cell-based ischemic neuronal model, we used an HUCB mononuclear-enriched population of collagen-adherent cells, which can be differentiated in vitro into a neuronal phenotype (HUCBNP). Upon co-culture with insulted-PC12 cells, HUCBNP conferred approximately 30% neuroprotection, as evaluated by decreased lactate dehydrogenase and caspase-3 activities. HUCBNP decreased by 95% the level of free radicals in the insulted-PC12 cells, in correlation with the appearance of antioxidants, as measured by changes in the oxidation-reduction potential of the medium using cyclic-voltammetry. An increased level of nerve growth factor (NGF), vascular endothelial growth factor and basic fibroblast growth factor in the co-culture medium was temporally correlated with a -medium neuroprotection effect, which was partially abolished by heat denaturation. HUCBNP-induced neuroprotection was correlated with changes in gene expression of these neurotrophic factors, while blocked by K252a, an antagonist of the TrkA/NGF receptor. These findings indicate that HUCBNP-induced neuroprotection involves antioxidant(s) and neurotrophic factors, which, by paracrine and/or autocrine interactions between the insulted-PC12 and the HUCBNP cells, conferred neuroprotection.