Midline pediatric high-grade astrocytomas (pHGAs) are incurable with few treatment targets identified. Most tumors harbor K27M mutations on histone 3 variants. In 40 treatment-naïve midline pHGAs, 39 analyzed by whole-exome sequencing, we find additional somatic mutations specific to tumor location. Gain-of-function mutations in ACVR1 occur in tumors of the pons in conjunction with H3.1 K27M, while FGFR1 mutations/fusions occur in thalamic tumors associated with H3.3 K27M. Hyper-activation of the bone morphogenetic protein (BMP)/ACVR1 developmental pathway in pHGAs harbouring ACVR1 mutations led to increased phospho-SMAD1/5/8 expression and up-regulation of BMP downstream early response genes in tumour cells. Global DNA methylation profiles were significantly associated with the K27M mutation regardless of the mutant H3 variant and irrespective of tumor location, supporting its role in driving the epigenetic phenotype. This significantly expands the potential treatment targets and further justifies pre-treatment biopsy in pHGA as a means to orient therapeutic efforts in this disease.
The extent of treatment for the victims of gunshot wounds to the brain remains quite controversial, particularly when these patients present with extensive neurological dysfunction. We propose guidelines regarding the degree and aggressiveness of therapy. The factors that seem to have a significant impact on the patient's final outcome are the neurological examination at the time of admission, the radiological findings, and the motivation for the shooting. Thus, the authors propose a nonsurgical line of therapy for comatose patients with unilateral or bilateral cerebral gunshot wounds where bone or metal fragments are visualized away from the bullet path on computed tomography scan, particularly when these individuals are suicide victims.
The authors have reviewed available data from 7 pediatric patients with intramedullary spinal cord cavernous angioma (ISCCA) reported in the literature, and added from their own series 2 pediatric patients, for a total of 9 patients. This group of pediatric patients’ clinical presentation, course, management and outcome were compared to their adult counterparts as reported in the literature. In contrast to adults, children with symptomatic ISCCA do not show a gender imbalance and the thoracic spinal cord is not predominantly involved. Pediatric patients commonly present with an acute episode and rapid deterioration. A more favorable outcome has been reported in children as compared to adults in the face of relatively similar presenting deficits. As in adults, magnetic resonance imaging (MRI) remains the diagnostic and postoperative test of choice. Complete resection affords the best chance for cure. Symptomatic children with ISCCA characteristically present with an acute deficit and rapid deterioration. MRI of the entire neuraxis is recommended for lesion multiplicity. An attempt at total resection and long-term MRI follow-up are recommended.
Patients with Klippel-Feil syndrome are often at high risk for neurological injury. The cervicomedullary junction and cervical spinal cord are especially vulnerable. Twenty-one patients examined and treated over a 20-year period are reviewed. The salient features of the syndrome are identified, and an approach to management is proposed.
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