Arginase overexpression in neurons and its effect on traumatic brain injury.

Arginine is a semi-essential amino acid which serves as a substrate for nitric oxide (NO) production by nitric oxide synthase (NOS) and a precursor for various metabolites including ornithine, creatine, polyamines, and agmatine. Arginase competes with nitric oxide synthase for substrate arginine to produce orthinine and urea. There is contradictory evidence in the literature on the role of nitric oxide in the pathophysiology of traumatic brain injury (TBI). These contradictory perspectives are likely due to different NOS isoforms - endothelial (eNOS), inducible (iNOS) and neuronal (nNOS) which are expressed in the central nervous system. Of these, the role of nNOS in acute injury remains less clear. This study aimed to employ a genetic approach by overexpressing arginase isoforms specifically in neurons using a Thy-1 promoter to manipulate cell autonomous NO production in the context of TBI. The hypothesis was that increased arginase would divert arginine from pathological NO production. We generated 2 mouse lines that overexpress arginase I (a cytoplasmic enzyme) or arginase II (a mitochondrial enzyme) in neurons of FVB mice. We found that two-weeks after induction of controlled cortical injury, overexpressing arginase I but not arginase II in neurons significantly reduced contusion size and contusion index compared to wild-type (WT) mice. This study establishes enhanced neuronal arginase levels as a strategy to affect the course of TBI and provides support for the potential role of neuronal NO production in this condition.

Computed tomography morphometric analysis for lateral mass screw placement in the pediatric subaxial cervical spine.

OBJECT: Lateral mass screws are routinely placed throughout the subaxial cervical spine in adults, but there are few clinical or radiographic studies regarding lateral mass fixation in children. The morphology of pediatric cervical lateral masses may be associated with greater difficulty in obtaining adequate purchase. The authors examined the lateral masses of the subaxial cervical spine in pediatric patients to define morphometric differences compared with adults, establish guidelines for lateral mass instrumentation in children, and define potential limitations of this technique in the pediatric age group. METHODS: Morphometric analysis was performed on CT of the lateral masses of C3-7 in 56 boys and 14 girls. Measurements were obtained in the axial, coronal, and sagittal planes. RESULTS: For most levels and measurements, results in boys and girls did not differ significantly; the few values that were significantly different are not likely to be clinically significant. On the other hand, younger (< 8 years of age) and older children (≥ 8 years of age) differed significantly at every level and measurement except for facet angularity. Sagittal diagonal, a measurement that closely estimates screw length, was found to increase at each successive caudal level from C-3 to C-7, similar to the adult population. A screw acceptance analysis found that all patients ≥ 4 years of age could accept at least a 3.5 × 10 mm lateral mass screw. CONCLUSIONS: Lateral mass screw fixation is feasible in the pediatric cervical spine, particularly in children age 4 years old or older. Lateral mass screw fixation is feasible even at the C-7 level, where pedicle screw placement has been advised in lieu of lateral mass screws because of the small size and steep trajectory of the C-7 lateral mass. Nonetheless, all pediatric patients should undergo high-resolution, thin-slice CT preoperatively to assess suitability for lateral mass screw fixation.

The periinsular functional hemispherotomy.

The surgical treatment of refractory epilepsy has evolved as new innovations have been created. Disconnective procedures such as hemispherectomy have evolved. Presently, hemispherotomy has replaced hemispherectomy to reduce complication rates while maintaining good seizure control. Several disconnective techniques have been described including the Rasmussen, vertical, and lateral approaches. The lateral approach, or periinsular hemispherectomy, was derived from modifications on the functional hemispherectomy and involves removal of the temporal lobe mesial structures, exposure of the atrium via the circular sulcus, internal capsule transection under the central sulcus, intraventricular callosotomy, and frontobasal disconnection. The purpose of this article is to describe and illustrate in detail the anatomy and operative technique for periinsular hemispherotomy, as well as to discuss the nuances and issues involved with this procedure.

Amenorrhea complicating endoscopic third ventriculostomy in the pediatric age group.

Endoscopic third ventriculostomy (ETV) is an accepted option in the treatment of obstructive hydrocephalus in children and is considered by many pediatric neurosurgeons to be the treatment of choice in this population. The procedure involves perforation of the floor of the third ventricle, specifically, the tuber cinereum, which is part of the hypothalamic-pituitary axis of cerebral endocrine regulation. Endocrine dysfunction, such as amenorrhea, weight gain, and precocious puberty, which are recognized only months to years after the procedure, may be underreported because patients and physicians may not relate the endocrine sequelae to the ETV. Few detailed reports of endocrine-related complications following ETV exist to better understand these issues. In this study, the authors add to the literature with case descriptions of and correlative laboratory findings in 2 adolescent girls who underwent ETV for obstructive hydrocephalus and in whom amenorrhea subsequently developed.

Solid variant of aneurysmal bone cyst of the thoracic spine: a case report.

INTRODUCTION: The solid variant of aneurysmal bone cyst is rare, and only 13 cases involving the spine have been reported to date, including seven in the thoracic vertebrae. The diagnosis is difficult to secure radiographically before biopsy or surgery. CASE REPORT: An 18-year-old Hispanic man presented to our facility with a one-year history of left chest pain without any significant neurological deficits. An MRI scan demonstrated a 6 cm diameter enhancing multi-cystic mass centered at the T6 vertebral body with involvement of the left proximal sixth rib and extension into the pleural cavity; the spinal cord was severely compressed with evidence of abnormal T2 signal changes. Our patient was taken to the operating room for a total spondylectomy of T6 with resection of the left sixth rib from a single-stage posterior-only approach. The vertebral column was reconstructed in a 360° manner with an expandable titanium cage and pedicle screw fixation. Histologically, the resected specimen showed predominant solid fibroblastic proliferation, with minor foci of reactive osteoid formation, an area of osteoclastic-like giant cells, and cyst-like areas filled with erythrocytes and focal hemorrhage, consistent with a predominantly solid variant of aneurysmal bone cyst. At 16 months after surgery, our patient remains neurologically intact with resolution of his chest and back pain. CONCLUSIONS: Because of its rarity, location, and radical treatment approach, we considered this case worthy of reporting. The solid variant of aneurysmal bone cyst is difficult to diagnose radiologically before biopsy or surgery, and we hope to remind other physicians that it should be included in the differential diagnosis of any lytic expansile destructive lesion of the spine.

Emergent medical and surgical management of mediastinal infantile hemangioma with symptomatic spinal cord compression: case report and literature review.

PURPOSE: We report an extremely rare case of a patient with a large, cervical, and upper thoracic cutaneous hemangioma associated with a separate, underlying mediastinal hemangioma extending to the epidural space causing significant spinal cord compression. CASE REPORT: A 6-week-old female presented with decreased movement of her right arm and bilateral lower extremity hyperreflexia. Her arm weakness progressed to paralysis over the course of 24 h. She underwent emergent surgical decompression and medical therapy with propranolol and systemic corticosteroids. CONCLUSION: While several recent reports have described dramatic responses of hemangiomas to propranolol, this is the first case in which it was used as part of a multimodal approach to symptomatic spinal cord compression. The infant improved immediately after surgery. She is neurologically intact and has radiographic regression of the hemangiomas on follow-up examination 6 months later.

Management of brain metastases: the indispensable role of surgery.

Brain metastases are the most common neurological complication of systemic cancer and carry a very poor prognosis. The management of patients with brain metastases has become more important recently because of the increased incidence of these tumors and the prolonged patient survival times that have accompanied increased control of systemic cancer. In this article, we review the current perspectives on surgical treatment of brain metastases in terms of patient selection criteria, intraoperative adjuncts, whole-brain radiation therapy (WBRT) as a postoperative adjuvant, reoperation for tumor recurrence, and resection of multiple and single metastases. Achieving the best outcome in treatment of brain metastasis requires the judicious and complementary use of surgical resection along with modalities such as whole-brain radiation therapy and stereotactic radiosurgery.

Therapeutic cloning in individual parkinsonian mice.

Cell transplantation with embryonic stem (ES) cell progeny requires immunological compatibility with host tissue. 'Therapeutic cloning' is a strategy to overcome this limitation by generating nuclear transfer (nt)ES cells that are genetically matched to an individual. Here we establish the feasibility of treating individual mice via therapeutic cloning. Derivation of 187 ntES cell lines from 24 parkinsonian mice, dopaminergic differentiation, and transplantation into individually matched host mice showed therapeutic efficacy and lack of immunological response.

Human ES cell-derived neural rosettes reveal a functionally distinct early neural stem cell stage.

Neural stem cells (NSCs) yield both neuronal and glial progeny, but their differentiation potential toward multiple region-specific neuron types remains remarkably poor. In contrast, embryonic stem cell (ESC) progeny readily yield region-specific neuronal fates in response to appropriate developmental signals. Here we demonstrate prospective and clonal isolation of neural rosette cells (termed R-NSCs), a novel NSC type with broad differentiation potential toward CNS and PNS fates and capable of in vivo engraftment. R-NSCs can be derived from human and mouse ESCs or from neural plate stage embryos. While R-NSCs express markers classically associated with NSC fate, we identified a set of genes that specifically mark the R-NSC state. Maintenance of R-NSCs is promoted by activation of SHH and Notch pathways. In the absence of these signals, R-NSCs rapidly lose rosette organization and progress to a more restricted NSC stage. We propose that R-NSCs represent the first characterized NSC stage capable of responding to patterning cues that direct differentiation toward region-specific neuronal fates. In addition, the R-NSC-specific genetic markers presented here offer new tools for harnessing the differentiation potential of human ESCs.

Isolation and directed differentiation of neural crest stem cells derived from human embryonic stem cells.

Vertebrate neural crest development depends on pluripotent, migratory precursor cells. Although avian and murine neural crest stem (NCS) cells have been identified, the isolation of human NCS cells has remained elusive. Here we report the derivation of NCS cells from human embryonic stem cells at the neural rosette stage. We show that NCS cells plated at clonal density give rise to multiple neural crest lineages. The human NCS cells can be propagated in vitro and directed toward peripheral nervous system lineages (peripheral neurons, Schwann cells) and mesenchymal lineages (smooth muscle, adipogenic, osteogenic and chondrogenic cells). Transplantation of human NCS cells into the developing chick embryo and adult mouse hosts demonstrates survival, migration and differentiation compatible with neural crest identity. The availability of unlimited numbers of human NCS cells offers new opportunities for studies of neural crest development and for efforts to model and treat neural crest-related disorders.