Antiseizure effect of MEK inhibitor in a child with neurofibromatosis type 1-Developmental and epileptic encephalopathy and optic pathway glioma.

BACKGROUND: Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder due to a mutation in NF1 gene, resulting in phenotypically heterogeneous systemic manifestations. Patients with NF1 are prone to develop neoplasms of the central nervous system (CNS) and are particularly at risk for optic pathway gliomas (OPG). Epilepsy is another recognized neurologic complication in patients with NF1, with a prevalence estimated between 4% and 14%. Several case reports and early phase clinical trials have demonstrated that the mitogen-activated protein kinase inhibitors (MEKi) are effective in NF1-low-grade gliomas (LGGs), but their influence on seizure activity in humans has not been established. CASE STUDY: Here, we report a patient with NF1 and developmental and epileptic encephalopathy (DEE) harboring pharmacoresistant tonic seizures, and progressive optic pathway glioma (OPG). By using a MEKi therapy for her OPG, we observed an end to epileptic seizures as well as a significant improvement of interictal EEG abnormalities, despite a lack of tumor reduction. CONCLUSION: MEK inhibitor therapy should be considered for patients with NF1 and refractory epilepsy.

Repair of Cranial Bone Defects in Children Using Synthetic Hydroxyapatite Cranioplasty (CustomBone).

BACKGROUND: In pediatric cases, the use of autologous bone tissue to repair cranial bone defects is often impossible. The synthetic hydroxyapatite bone substitute (CustomBone) can be a good alternative, especially in case of a large bone defect that has to be repaired. METHODS: This study focuses on a pediatric series of 30 children who underwent cranioplasty with a CustomBone implant. Patient age ranged from 8 months to 16 years, with a mean age of 7 years and 8 months. The most common indication for cranioplasty was posttraumatic decompressive craniectomy. RESULTS: No complications were reported. Cosmetic results were satisfactory in every patient. Only 1 implant had to be changed after severe head trauma because of an epileptic seizure in the early postoperative period. In all patients, cerebral blood flow improved during the postoperative phase. Complete implant osteointegration is a long process because mean time to begin was 13 months (range, 3-22 months). Mean patient follow-up was 6.7 years. Successful prosthesis integration depends on the accuracy of the preoperative model. The minimum thickness of the implant (4 mm) represents a challenge in very young children, but we used it with success in this series. Moreover, high costs represent another limitation for its use. CONCLUSIONS: The CustomBone implant meets all necessary conditions for good clinical outcome: excellent protective properties, restoration of normal intracranial physiology, satisfactory cosmetic results, good integration in the autologous bone, and good resistance in case of trauma.

Postnatal Management of Myelomeningocele: Outcome with a Multidisciplinary Team Experience.

INTRODUCTION: Myelomeningocele (MMC) is a complex neural tube defect. Few studies report the results of modern postnatal management. The goal of this study was to report the long-term outcome of a multidisciplinary approach of patients with MMC. METHODS: Forty-six MMCs were included. Clinical status was evaluated prospectively. RESULTS: Mean follow-up was 8.1 years. The level of the malformation was sacral or lower lumbar (≤L4) in 27 cases, higher lumbar (between L1 and L3) in 5 cases, and thoracic in 14 cases. A Chiari II malformation was present at birth in 78.3% of the cases. Seventy-six percent of the patients were operated on within the first 24 hours of life. Sixty-one percent needed a cerebrospinal fluid diversion procedure. Seven patients underwent a second surgery for a retethering of the spine. Eighty percent presented with orthopedic problems. Sixty-five percent of our patients were able to walk. Only 13% of patients had a normal urinary elimination. Two groups of patients were identified: one group with a malformation at the level of L4 or below (group 1) and another group with a malformation strictly above L4 (group 2). Group 1 had significantly better outcome. CONCLUSIONS: This series proves that modern multidisciplinary postnatal management of MMC is effective. In the light of these results and of the results of prenatal management of MMC, prenatal surgery seems to be a highly valuable tool to improve the outcome of patients with high lesions (level ≥L3).

Complete Reversibility of the Chiari Type II Malformation After Postnatal Repair of Myelomeningocele.

OBJECTIVE: It was believed that Chiari type II malformation (CM-II) was always present in a myelomeningocele (MMC). In fact, it is associated in about 80% of cases. Improvement of the hindbrain herniation after prenatal closure of MMC has challenged the idea that this condition was irreversible. Only 2 studies report ascent of the cerebellar tonsil after postnatal closure. This work aimed to study a large group of patients with MMC who benefited from a postnatal repair to evaluate the rate of long-term total reversibility of CM-II. METHODS: Sixty-one patients were included. Mean time of follow-up was 8.1 years. The presence of CM-II after closure of the MMC was assessed on the most recent brain scan available for each patient. RESULTS: Forty-seven patients (77%) had a CM-II at birth (confirmed before the MMC repair). There was a significant correlation between the level of the malformation and the presence of a CM-II at birth (P = 0.003). After MMC closure, only 28 (45.9%) patients had a remaining CM-II. The reversibility rate was 40.4%. The reversibility was higher in lower level malformations (P = 0.004). The number of patients treated for hydrocephalus was significantly higher in the group of patients with remaining CM-II (P = 0.004). Only 11.5% of the children needed surgery for a symptomatic CM-II. CONCLUSIONS: MMC is not always associated with CM-II. The outcome of CM-II has improved. Postnatal closure can reverse the CM-II. This must be kept in mind when analyzing the result of prenatal series.