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BACKGROUND: Virtually all low-grade gliomas (LGGs) will progress to high-grade gliomas (HGGs), including glioblastoma, the most common malignant primary brain tumor in adults. A key regulator of immunosuppression, fibrinogen-like protein 2 (FGL2), may play an important role in the malignant transformation of LGG to HGG. We sought to determine the mechanism of FGL2 on tumor progression and to show that inhibiting FGL2 expression had a therapeutic effect. METHODS: We analyzed human gliomas that had progressed from low- to high-grade for FGL2 expression. We modeled FGL2 overexpression in an immunocompetent genetically engineered mouse model to determine its effect on tumor progression. Tumors and their associated microenvironments were analyzed for their immune cell infiltration. Mice were treated with an FGL2 antibody to determine a therapeutic effect. Statistical tests were two-sided. RESULTS: We identified increased expression of FGL2 in surgically resected tumors that progressed from low to high grade (n = 10). The Cancer Genome Atlas data showed that LGG cases with overexpression of FGL2 (n = 195) had statistically significantly shorter survival (median = 62.9 months) compared with cases with low expression (n = 325, median = 94.4 months, P < .001). In a murine glioma model, HGGs induced with FGL2 exhibited a mesenchymal phenotype and increased CD4(+) forkhead box P3 (FoxP3)(+) Treg cells, implicating immunosuppression as a mechanism for tumor progression. Macrophages in these tumors were skewed toward the immunosuppressive M2 phenotype. Depletion of Treg cells with anti-FGL2 statistically significantly prolonged survival in mice compared with controls (n = 11 per group, median survival = 90 days vs 62 days, P = .004), shifted the phenotype from mesenchymal HGG to proneural LGG, and decreased M2 macrophage skewing. CONCLUSIONS: FGL2 facilitates glioma progression from low to high grade. Suppressing FGL2 expression holds therapeutic promise for halting malignant transformation in glioma.

Pediatric stroke is a relatively rare occurrence, with an annual incidence of 1.2–13 cases per 100,000. Hemorrhagic strokes account for half of these cases.[28] In adults, hemorrhagic strokes are predominantly hypertensive in etiology. However, in the pediatric population, they are frequently associated with vascular lesions such as AVMs (47%), arteriovenous fistulas, or CMs [Table 1].[21] Other causes of ICH in adults, such as amyloid angiopathy or drug-related vascular damage, are rarely seen in the pediatric population. Workup of pediatric ICH should include vascular imaging consisting of either CTA or DSA. An MRI of the brain should be obtained to detect CMs, which are angiographically occult. MR angiography may lack the sensitivity to allow for visualization of the smaller vessels that may be involved with some of these lesions.[25] In a series of 137 patients with ICH described by Hino et al., 9% were found to have an “occult” vascular lesion that was not visualized on first angiogram. The clinical index of suspicion should guide the workup further if a causative lesion cannot be identified upon initial imaging. This may include repeat DSA, which is considered the gold standard for the assessment of vascular lesions. In the setting of clinically symptomatic hemorrhage, any vascular lesion, including AVM, CM, capillary telangiectasias, or developmental venous anomalies, may present in occult fashion, though AVM is most common.[7] Table 1 Most common etiologies of spontaneous intracerebral hemorrhage in adults and children

// Loyola V. Gressot 1 , Tiffany Doucette 1 , Yuhui Yang 1 , Gregory N. Fuller 2 , Ganiraju Manyam 3 , Arvind Rao 3 , Khatri Latha 1 , Ganesh Rao 1 1 Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA 2 Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA 3 Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA Correspondence to: Khatri Latha, e-mail: klatha@mdanderson.org Ganesh Rao, e-mail: grao@mdanderson.org Keywords: inhibitor of apoptosis, BIRC3, glioma, malignant progression Received: December 23, 2015 Accepted: March 28, 2016 Published: April 8, 2016 ABSTRACT Gliomas, the most common primary brain tumor in humans, include a spectrum of disease. High-grade gliomas (HGG), such as glioblastoma, may arise from low-grade gliomas (LGG) that have a more indolent course. The process of malignant transformation (MT) of LGG to HGG is poorly understood but likely involves the activation of signaling programs that suppress apoptosis. We previously showed that Survivin (BIRC5) plays a role in malignant progression of glioma. Here, we investigated the role of the remaining members of the Inhibitors of Apoptosis (IAP) family on promoting MT in glioma. Utilizing expression data from the cancer genome atlas (TCGA), we identified BIRC3 as a key facilitator of MT from LGG to HGG. TCGA HGGs with high expression of BIRC 3 demonstrated a survival disadvantage and expression levels of BIRC3 were also significantly higher in TCGA HGG compared to TCGA LGG cases. We validated our findings from TCGA by using matched human specimens to show that BIRC expression is increased in HGG compared to their precursor LGG lesions. Using a unique murine model of glioma, we show that overexpression of BIRC3 promotes higher grade glioma and significantly reduces tumor-free survival in mice.

Spondyloptosis refers to complete dislocation of a vertebral body onto another. The L5–S1 level is frequently affected. As this condition is rare, few published reports describing its clinical features and surgical outcomes exist, especially in the pediatric patient population. The authors report the presentation, pathological findings, and radiographic studies of a 2-year-old girl who presented to Texas Children's Hospital with a history since birth of progressive spastic paraparesis. Preoperative CT and MRI showed severe spinal cord compression associated with T11–12 spondyloptosis. The patient underwent a single-stage posterior approach for complete resection of the dysplastic vertebral bodies at the apex of the spinal deformity with reconstruction and stabilization of the vertebral column using a titanium expandable cage and pedicle screws. At the 12-month follow-up, the patient remained neurologically stable without any radiographic evidence of instrumentation failure or loss of alignment. To the best of the authors' knowledge, there have been only 2 other children with congenital thoracolumbar spondyloptosis treated with the above-described strategy. The authors describe their case and review the literature to discuss the aggregate clinical features, surgical strategies, and operative outcomes for congenital thoracolumbar spondyloptosis.

This study aimed to determine if partial removal of the occipital condyle provides a significant increase in visibility and "angle of attack" for treating lesions with extension ventral to the brainstem in children using CT morphometric data. Morphometric analysis was performed in 199 children using CT scans. Angle of attack was measured for both the paracondylar and transcondylar far lateral approach. Statistical analysis was performed using paired or unpaired Student's t-tests (p

Signal transducer and activator of transcription 5b (STAT5b) is likely the relevant STAT5 isoform with respect to the process of malignant progression in gliomas. STAT5b is a latent cytoplasmic protein involved in cell signaling through the modulation of growth factors, apoptosis, and angiogenesis. Previous in vitro studies have shown increased STAT5b expression in glioblastomas relative to low-grade tumors and normal brain. We recently demonstrated that phosphorylated STAT5b associates with delta epidermal growth factor receptor in the nucleus and subsequently binds the promoters of downstream effector molecules, including aurora kinase A. Analysis of TCGA dataset reveals that STAT5b is predominantly expressed in proneural (PN) gliomas relative to mesenchymal and neural gliomas. Here, we modeled ectopic expression of STAT5b in vivo using a platelet-derived growth factor subunit B (PDGFB)-dependent mouse model of PN glioma to determine its effect on tumor formation and progression. We showed that coexpression of STAT5b and PDGFB in mice yielded a significantly higher rate of high-grade gliomas than PDGFB expression alone. We also observed shorter survival in the combined expression set. High-grade tumors from the STAT5b + PDGFB expression set were found to have a lower rate of apoptosis than those from PDGFB alone. Furthermore, we showed that increased expression of STAT5b + PDGFB led to increased expression of downstream STAT5b targets, including Bcl-xL, cyclin D1 and aurora kinase A in high-grade tumors when compared to tumors derived from PDGFB alone. Our findings show that STAT5b promotes the malignant transformation of gliomas, particularly the PN subtype, and is a potential therapeutic target.

Object Prediction of outcome from initial presentation after a gunshot wound to the head (GSWH) is essential to further clinical decision making. The authors' goals are to report the survival and functional outcomes of these patients, to identify prognostic factors, and to propose a scoring system that can predict their outcome. Methods The records of 199 patients admitted with a GSWH with dural penetration between 1990 and 2008 were retrospectively reviewed. The inclusion criterion was a CT scan available for review. Patients declared brain dead on presentation were excluded, which yielded a series of 119 patients. Statistical analysis was performed using a logistic regression model. Results Fifty-eight (49%) of the 119 patients died. Twenty-three patients (19%) had a favorable outcome defined as a 6-month Glasgow Outcome Scale (GOS) score of moderate disability or good recovery, 35 (29%) had a poor outcome (GOS of persistent vegetative state or severe disability), and 3 (3%) were lost to follow-up. Significant prognostic factors for mortality were age older than 35 years, nonreactive pupils, bullet trajectory of bihemispheric (excluding bifrontal), and posterior fossa involvement compared with unihemispheric and bifrontal. Factors that were moderately associated with higher mortality included intracranial pressure (ICP) above 20 mm Hg and Glasgow Coma Scale (GCS) score at presentation of 3 or 4. Upon multivariate analysis, the significant factors for mortality were bullet trajectory and pupillary response. Variables found to be significant for good functional outcome were admission GCS score greater than or equal to 5, pupillary reactivity, and bullet trajectory of unihemispheric or bifrontal. Factors moderately associated with good outcome included age of 35 years or younger, initial ICP 20 mm Hg or lower, and lack of transventricular trajectory. In the multivariate analysis, significant factors for good functional outcome were bullet trajectory and pupillary response, with age moderately associated with improved functional outcomes. The authors also propose a scoring system to estimate survival and functional outcome. Conclusions Age, pupils, GCS score, and bullet trajectory on CT scan can be used to determine likelihood of survival and good functional outcome. The authors advocate assessing patients based on these parameters rather than pronouncing a poor prognosis and withholding aggressive resuscitation based upon low GCS score alone.

Cranial osteosarcoma is very rare in children, rendering the development of optimal treatment algorithms challenging. The authors present 3 cases of pediatric cranial osteosarcoma: a primary calvarial tumor, a cranial metastasis, and a primary osteosarcoma of the cranial base. A review of the literature demonstrates significant variation in the management of cranial osteosarcomas and the outcome for patients with these tumors. This series and literature review is presented to improve the understanding of pediatric cranial osteosarcoma and to reinforce the importance of maximal resection in optimizing outcome.

Nonterminal myelocystocele is a rare type of spinal dysraphism characterized by a closed defect with an underlying CSF-filled cyst, either contiguous with the central spinal canal or attached to the spinal cord by a fibrovascular stalk. The authors report the unusual case of a neonate with a prenatal diagnosis of cervicothoracic nonterminal myelocystocele who underwent postnatal surgical untethering of the lesion. Pathological analysis of the excised lesion revealed neuroglial tissue with an ependymal lining associated with a mature teratoma. Three months after surgery, the patient has normal lower-extremity sensorimotor function and no evidence of bowel or bladder dysfunction. To the best of the authors' knowledge, this is the first report of a patient with a nonterminal myelocystocele found to have an associated mature teratoma.

Anterior encephaloceles are rare congenital abnormalities that ccur most commonly in southeast Asia and are characterized y herniation of intracranial components through the cranial and acial bones due to a defect of closure of the anterior neuropore f the neural tube [1]. Congenital anterior encephaloceles are clasified by their location such as fronto-ethmoidal, trans-ethmoidal asopharyngeal, or orbital [1]. Acquired encephaloceles can also ccur later in life secondary to tumor, hydrocephalus or other cause 2]. Seizures may be the presenting complaint in a wide variety of ntracranial pathology; thus new onset seizures should prompt a horough work up [3]. Seizures present as provoked or unprovoked vents with recurrent unprovoked seizures defining epilepsy. New nset seizures in an adult should prompt neuroimaging to assess or structural anatomic abnormalities [3]. We report the unusual case of a 38 year-old woman who preented to medical attention with new onset seizures, was found o have an opacified right frontal sinus, which was caused by an nterior encephalocele in the right frontal sinus via a defect in the inus’s posterior wall.

Juvenile xanthogranuloma (JXG) is a rare disease that is part of a spectrum of histiocytic dendritic cell disorders. The authors report an unusual case of a 6-week-old male who presented with seizures. Neuroimaging revealed disseminated intracranial disease involving the optic apparatus, basal ganglia, lateral ventricles, and brainstem. The patient did not have any cutaneous lesions or evidence of extracranial disease. The patient underwent open biopsy of a large right midbrain lesion; pathology was consistent with JXG. He underwent postoperative chemotherapy and is doing well 7 months after surgery with regression of the intracranial lesions. To the best of the authors' knowledge, this is the first report of a neonate with disseminated intracranial JXG without cutaneous stigmata.

Object The most common cause of cervical spine arthrodesis in the pediatric population is instability related to congenital or traumatic pathology. Instrumenting the cervical spine can be challenging given smaller anatomical structures, less ossified bone, and future growth potential and development. Studies in adult patients have suggested that using screw constructs results in improved outcomes with lower rates of instrumentation failure. However, the pediatric literature is limited to small retrospective series. Based on a review of the literature and their own patient series, the authors report that instrumenting the pediatric cervical spine with screw constructs may be safer and more effective than using wiring techniques. Methods The authors reviewed the existing pediatric cervical spine arthrodesis literature and contributed 31 of their own cases from September 1, 2007, to January 1, 2011. They reviewed 204 abstracts from January 1, 1966, to December 31, 2010, and 80 manuscripts with 883 total patients were included in the review. They recorded demographic, radiographic, and outcomes data—as well as surgical details—with a focus on fusion rates and complications. Patients were then grouped into categories based upon the procedure performed: 1) patients who underwent fusions bridging the occipitocervical junction and 2) patients who underwent fusion of the cervical spine that did not include the occiput, thus including atlantoaxial and subaxial fusions. Patients were further subdivided according to the type of instrumentation used—some had posterior cervical fusion with wiring (with or without rod implantation); others had posterior cervical fusion with screws. Results The entire series comprised 914 patients with a mean age of 8.30 years. Congenital abnormalities were encountered most often (in 55% of cases), and patients had a mean follow-up of 32.5 months. From the entire cohort, 242 patients (26%) experienced postsurgical complications, and 50 patients (5%) had multiple complications. The overall fusion rate was 94.4%. For occipitocervical fusions (N = 285), both screw and wiring groups had very high fusion rates (99% and 95%, respectively, p = 0.08). However, wiring was associated with a higher complication rate. From a sample of 252 patients, 14% of those treated with screw instrumentation had complications, compared with 50% of patients treated with wiring (p < 0.05). In cervical fusions not involving the occipitocervical junction (N = 181), screw constructs had a 99% fusion rate, whereas wire instrumentation only had an 83% fusion rate (p < 0.05). Similarly, patients who underwent screw fixation had a lower complication profile (15%) when compared with those treated with wiring constructs (54%, p < 0.05). Conclusions The results of this study are limited by variations in construct design, use of orthoses, follow-up duration, and newer adjuvant products promoting fusions. However, a literature review and the authors' own series of pediatric cases suggest that instrumentation of the cervical spine in children may be safer and more efficacious using screw constructs rather than wiring techniques.

Object Occipitocervical stabilization in the pediatric age group remains a challenge because of the regional anatomy, poor occipital bone purchase, and, in some instances, significant thinning of the occipital bone. Multiple bicortical fixation points to the occipital bone may be required to increase construct rigidity. The authors evaluated the complications of bicortical occipital screw placement in children with occipital fusion constructs. Methods The records of 20 consecutive pediatric patients who had undergone occipitocervical fusion between September 1, 2007, and November 30, 2010, at Texas Children's Hospital were reviewed. Results The patients consisted of 10 girls and 10 boys, ranging in age from 10 months to 16 years (mean ± SD, 7.7 ± 5.1 years). Two patients were lost to follow-up, 2 died for reasons unrelated to the surgery, and the remaining patients had at least 3 months of follow-up (mean 14 ± 11.8 months) with evaluation via dynamic radiography and CT. Four patients experienced 8 complications: 2 CSF leaks, 2 vigorous venous bleedings, worsening of quadriparesis, wound infection, radiographic pseudarthrosis, and transient dysphagia. Among 114 screws, there were 2 cases of intraoperative dural venous sinus injury and 2 cases of intraoperative CSF leakage, without clinical sequelae from these complications. Only 1 case of radiographic pseudarthrosis was identified in a patient with skeletal dysplasia and a prior failed C1–2 posterior arthrodesis. There were no difficulties with wound healing because of prominent occipital instrumentation, and there was only 1 wound infection. Conclusions Data in this report confirm that including bicortical occipital screw placement in occipitocervical constructs in children may result in a high fusion rate but at the cost of a notable complication rate.

BACKGROUND Melanoma metastases to the spine remain a challenge for neurosurgeons. OBJECTIVE To identify factors associated with survival in a series of patients who underwent spinal surgery for metastatic melanoma. METHODS We retrospectively reviewed all patients (n = 64) who received surgical intervention for melanoma metastases to the spine at the University of Texas MD Anderson Cancer Center between July 1993 and March 2012. RESULTS No patients were excluded from the study, and vital status data were available for all patients. Median overall survival was 5.7 months (95% confidence interval, 2.7-28.7). On univariate survival analysis, diagnosis of spinal metastasis after prior diagnosis of systemic metastasis, higher total spinal disease burden (including but not exclusive to the operative site), presence of progressive systemic disease at the moment of spine surgery, and postoperative complications were associated with poorer overall survival, whereas the presence of only bone metastasis at the moment of surgery was associated with improved overall survival. On multivariate survival analysis, both progressive systemic disease at the moment of spine surgery and total spinal disease burden of ≥3 vertebral levels were significantly associated with worse overall survival (hazard ratio, 6.00; 95% confidence interval, 3.19-11.28; P < .001; and hazard ratio, 2.87; 95% confidence interval, 1.62-5.07; P < .001, respectively). CONCLUSION On multivariate analysis, involvement of ≥3 vertebral bodies and progressive systemic disease were associated with worse overall survival. Consideration of these factors should influence surgical decision making in this patient population.

Gliomas are the most common type of brain tumor in both children and adults. Several low-grade gliomas (LGG) have the ability to progress into more aggressive tumors -high-grade gliomas (HGG) including glioblastoma (GB). Although patients harboring a LGG may survive for years, after the tumor transforms to HGG, life expectancy rapidly declines to 12 to 15 months in adults and 40 months in children. Thus, inhibiting this process of malignant transformation (MT) is an attractive therapeutic strategy because of the more indolent course associated with LGGs. Immune response plays a critical role in surveillance against malignant transformation. Our previous study shows that fibrinogen-like protein 2 (FGL2) is a key hub of tumor-mediated immune suppression. Hence, we investigated the role of FGL2 in promoting tumor progression from LGG to HGG in glioma. Analysis of TCGA expression data showed that increased FGL2 expression is associated with poorer survival in LGG and GB patients. And there is a positive correlation of expression level between FGL2 and mesenchymal glioma marker CD44, and a negative correlation between FGL2 and proneural glioma marker OLIG2. Engineered expression of FGL2 in a PDGFB-dependent mouse model of oligodendroglioma, a common glioma subtype, yielded a significantly higher rate of HGGs (72% vs 29%, p=0.034) and poorer-symptom free survival (63 vs 90 days, p=0.003) than PDGFB expression alone. And HGGs from FGL2 + PDGFB expressing mice exhibited a distinct mesenchymal phenotype validating TCGA data. Further, FGL2 induced high numbers of CD4+FoxP3+ cells from an early time point of tumor formation underscoring its role in tumor progression. And FGL2 overexpression educated M2 skew in the tumors characterized by high expression of Iba1 and Arginase1 in macrophages. Finally, treatment with anti-FGL2 antibody significantly improves survival in mice, shifts the phenotype from mesenchymal HGG to proneural LGG, and rescues M2 macrophage skewing. Our results show that FGL2 is critical for malignant progression of glioma by inducing immunosuppression in tumor microenvironment, and raise the potential of FGL2 to be a promising target to suppress/reverse glioma progression and provide survival benefit in clinical. Citation Format: Khatri Latha, Jun Yan, Yuhui Yang, Loyola V. Gressot, Lingyuan Kong, Ganiraju Manyam, Ravesanker Ezhilarasan, Qianghu Wang, Erik P. Sulman, Jingda Xu, Richard E. Davis, Suyun Huang, Gregory N. Fuller, Arvind Rao, Amy B. Heimberger, Shulin Li, Ganesh Rao. Fibrinogen-like protein 2 drives malignant tumor progression in glioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5606. doi:10.1158/1538-7445.AM2017-5606

Signal transducer and activator of transcription 5b (STAT5b) is likely the relevant STAT5 isoform with respect to the process of malignant progression in gliomas. STAT5b is a latent cytoplasmic protein involved in cell signaling through the modulation of growth factors, apoptosis, and angiogenesis. Previous in vitro studies have shown increased STAT5b expression in glioblastomas relative to low-grade tumors and normal brain. We recently demonstrated that phosphorylated STAT5b associates with delta epidermal growth factor receptor in the nucleus and subsequently binds the promoters of downstream effector molecules, including aurora kinase A. Analysis of TCGA dataset reveals that STAT5b is predominantly expressed in proneural (PN) gliomas relative to mesenchymal and neural gliomas. Here, we modeled ectopic expression of STAT5b in vivo using a platelet-derived growth factor subunit B (PDGFB)-dependent mouse model of PN glioma to determine its effect on tumor formation and progression. We showed that coexpression of STAT5b and PDGFB in mice yielded a significantly higher rate of high-grade gliomas than PDGFB expression alone. We also observed shorter survival in the combined expression set. High-grade tumors from the STAT5b + PDGFB expression set were found to have a lower rate of apoptosis than those from PDGFB alone. Furthermore, we showed that increased expression of STAT5b + PDGFB led to increased expression of downstream STAT5b targets, including Bcl-xL, cyclin D1 and aurora kinase A in high-grade tumors when compared to tumors derived from PDGFB alone. Our findings show that STAT5b promotes the malignant transformation of gliomas, particularly the PN subtype, and is a potential therapeutic target.

Cranial osteosarcoma is very rare in children, rendering the development of optimal treatment algorithms challenging. The authors present 3 cases of pediatric cranial osteosarcoma: a primary calvarial tumor, a cranial metastasis, and a primary osteosarcoma of the cranial base. A review of the literature demonstrates significant variation in the management of cranial osteosarcomas and the outcome for patients with these tumors. This series and literature review is presented to improve the understanding of pediatric cranial osteosarcoma and to reinforce the importance of maximal resection in optimizing outcome.

Nonterminal myelocystocele is a rare type of spinal dysraphism characterized by a closed defect with an underlying CSF-filled cyst, either contiguous with the central spinal canal or attached to the spinal cord by a fibrovascular stalk. The authors report the unusual case of a neonate with a prenatal diagnosis of cervicothoracic nonterminal myelocystocele who underwent postnatal surgical untethering of the lesion. Pathological analysis of the excised lesion revealed neuroglial tissue with an ependymal lining associated with a mature teratoma. Three months after surgery, the patient has normal lower-extremity sensorimotor function and no evidence of bowel or bladder dysfunction. To the best of the authors' knowledge, this is the first report of a patient with a nonterminal myelocystocele found to have an associated mature teratoma.

Object Cervical spondylolysis is a rare condition that results from a pars interarticularis defect. The C-6 level is the most frequently involved site in the cervical spine. Its clinical presentations range from incidental radiographic findings to neck pain and, rarely, neurological deficits. Although 150 patients with subaxial cervical spondylolysis have been reported, a mere 24 adult and pediatric patients with C-2 spondylolysis have been described. The long-term outcomes of very young children with bilateral C-2 spondylolysis are of great interest, yet only a few longitudinal studies exist. Methods The authors retrospectively reviewed 5 cases of bilateral C-2 spondylolysis at Texas Children's Hospital and Riley Children's Hospital; these were combined with 5 other cases in the literature, yielding a total of 10 patients. Data regarding the patients' age, sex, C2–3 angulation and displacement, associated spine anomalies, neurological deficits, treatment, and most recent follow-up were recorded. Results The patients' ages ranged from 3 to 36 months (mean 12.9 months). There were 6 boys and 4 girls. The C2–3 angulation, displacement, and width of pars defect were measured when available. The mean C2–3 angulation was 9.5° (range 1–34°), the mean C2–3 displacement was 4.78 mm (range 1.1–10.8 mm), and the mean width of the pars defect was 4.16 mm (range 0.9–7 mm). One patient developed myelopathy and spinal cord injury. All 10 of the patients were treated initially with conservative therapy: 3 with close observation alone, 1 with a rigid cervical collar, 4 with a Minerva jacket, 1 with a sternal-occipital-mandibular immobilizer, and 1 with a halo vest. Three patients ultimately underwent surgery for internal fixation due to progressive instability or development of neurological symptoms. All patients were neurologically intact at the last follow-up (mean 44.3 months, range 14–120 months). Conclusions Based on the literature and the authors' own experience, they conclude that most very young children with C-2 spondylolysis remain neurologically intact and maintain stability in long-term follow-up despite the bony defect. This defect is often an asymptomatic incidental finding and may be managed conservatively. More aggressive therapy including surgery is indicated for those patients with a neurological deficit from spinal cord compromise secondary to stenosis and local C-2 kyphosis, progressive deformity, or worsening C2–3 instability.

Object Neuromuscular scoliosis is a challenging pathology to treat. Surgical correction can involve long fusion constructs extending to the pelvis. The deformity inherent in these patients makes it difficult to obtain adequate lateral intraoperative radiographs for traditional image-guided placement of iliac screws. Methods A clinical and radiographic assessment of 14 patients with neuromuscular spinal deformity was conducted. From 2007 to 2013, 12 of these patients (mean age 14.25 years, range 10–20 years) underwent long spinal instrumentation (mean 15 levels, range 10–18 levels) and fusion to the pelvis, and 2 underwent placement of a growing rod construct with iliac screw placement at a single institution. The average length of follow-up was 33.7 months (range 6–64 months). Iliac screws were placed after identifying the posterior superior iliac spine and using only anteroposterior fluoroscopy (view of the inlet of the pelvis), rather than the technique of direct palpation of the sciatic notch. The accuracy of iliac screw placement was assessed with routine postoperative CT. Results A total of 12 patients had 24 screws placed as part of a long-segment fusion to the pelvis, and 2 patients had two iliac screws placed as part of a growing rod construct for neuromuscular scoliosis. There were no iliac screw misplacements, and no complications directly related to the technique of iliac screw placement. For cases of definitive fusion (n = 12), the average coronal Cobb angle of patients with neuromuscular spinal deformity measured 62° before surgery and 44.3° immediately after surgery. The average preoperative thoracic kyphosis and lumbar sagittal lordosis measured 37.3° and 60.7°, respectively. Immediately after surgery, the thoracic and lumbar angles measured 30° and 41.1°, respectively. At last follow-up, the average coronal Cobb angle was maintained at 45.1°, and the thoracic and lumbar sagittal angles were maintained at 32.8° and 45.3°, respectively. Conclusions A less invasive technique for iliac screw placement can be performed safely with a low likelihood of screw misplacement. This technique offers the biomechanical advantages of iliac fixation without the soft tissue exposure typically needed for safe screw insertion. The technique relies on identification of the posterior superior iliac spine and high quality anteroposterior fluoroscopic imaging for a view of the pelvic inlet.

Juvenile xanthogranuloma (JXG) is a rare disease that is part of a spectrum of histiocytic dendritic cell disorders. The authors report an unusual case of a 6-week-old male who presented with seizures. Neuroimaging revealed disseminated intracranial disease involving the optic apparatus, basal ganglia, lateral ventricles, and brainstem. The patient did not have any cutaneous lesions or evidence of extracranial disease. The patient underwent open biopsy of a large right midbrain lesion; pathology was consistent with JXG. He underwent postoperative chemotherapy and is doing well 7 months after surgery with regression of the intracranial lesions. To the best of the authors' knowledge, this is the first report of a neonate with disseminated intracranial JXG without cutaneous stigmata.

Neuromuscular scoliosis is a challenging pathology to treat with high incidence of complications and failure of surgical fusion. Surgical correction can entail long fusion constructs extending to the pelvis. We report our experience in the use of bone morphogenetic protein (BMP) to augment L5–S1 arthrodesis in long segment fusions in pediatric patients with neuromuscular scoliosis. Retrospective review of 11 pediatric patients with neuromuscular spinal deformity (mean, age 13.7 years; range, 10–20 years) who underwent long (mean, 15 levels; range, 10–18 levels) spinal instrumentation and fusion to the pelvis at a single institution from 2007 to 2012 with an average follow-up of 34 months (range, 11–62 months). Of the 11 patients, one had pseudoarthrosis at L5–S1. The average coronal Cobb angle measured 59° before surgery and 42° immediately after surgery. The average preoperative thoracic kyphosis and lumbar sagittal lordosis measured 34 and 59°, respectively. Immediately after surgery, the thoracic and lumbar angles measured 28 and 39°, respectively. At last follow-up, the average coronal Cobb angle was maintained at 43° and the thoracic and lumbar sagittal angles were 28 and 44°, respectively. An average of 14.2 mg of recombinant human bone morphogenetic protein-2 (rh-BMP-2) was used for each case. L5–S1 arthrodesis may be effectively achieved in long fusions for pediatric neuromuscular spinal deformity with posterolateral fusion supplemented with rh-BMP-2. This surgical strategy may be associated with lower complication rates, decreased blood loss, and shorter operative times than circumferential fusion, which is particularly important in this complex fragile patient population.

Peripheral nerve tumors include the benign neural sheath origin and other benign tumors that are not of neural sheath origin but involve the peripheral nerves. Malignant nerve tumors are divided into those of neural sheath origin and those of non-neural origin compressing or directly involving nerve by either direct extension or metastasis. Each of these categories of nerve tumors is discussed in this chapter.

The most common cause of cervical spine arthrodesis in the pediatric population is instability related to congenital or traumatic pathology. Instrumenting the cervical spine can be challenging given smaller anatomical structures, less ossified bone, and future growth potential and development. Studies in adult patients have suggested that using screw constructs results in improved outcomes with lower rates of instrumentation failure. However, the pediatric literature is limited to small retrospective series. Based on a review of the literature and their own patient series, the authors report that instrumenting the pediatric cervical spine with screw constructs may be safer and more effective than using wiring techniques.The authors reviewed the existing pediatric cervical spine arthrodesis literature and contributed 31 of their own cases from September 1, 2007, to January 1, 2011. They reviewed 204 abstracts from January 1, 1966, to December 31, 2010, and 80 manuscripts with 883 total patients were included in the review. They recorded demographic, radiographic, and outcomes data-as well as surgical details-with a focus on fusion rates and complications. Patients were then grouped into categories based upon the procedure performed: 1) patients who underwent fusions bridging the occipitocervical junction and 2) patients who underwent fusion of the cervical spine that did not include the occiput, thus including atlantoaxial and subaxial fusions. Patients were further subdivided according to the type of instrumentation used-some had posterior cervical fusion with wiring (with or without rod implantation); others had posterior cervical fusion with screws.The entire series comprised 914 patients with a mean age of 8.30 years. Congenital abnormalities were encountered most often (in 55% of cases), and patients had a mean follow-up of 32.5 months. From the entire cohort, 242 patients (26%) experienced postsurgical complications, and 50 patients (5%) had multiple complications. The overall fusion rate was 94.4%. For occipitocervical fusions (N = 285), both screw and wiring groups had very high fusion rates (99% and 95%, respectively, p = 0.08). However, wiring was associated with a higher complication rate. From a sample of 252 patients, 14% of those treated with screw instrumentation had complications, compared with 50% of patients treated with wiring (p0.05). In cervical fusions not involving the occipitocervical junction (N = 181), screw constructs had a 99% fusion rate, whereas wire instrumentation only had an 83% fusion rate (p0.05). Similarly, patients who underwent screw fixation had a lower complication profile (15%) when compared with those treated with wiring constructs (54%, p0.05).The results of this study are limited by variations in construct design, use of orthoses, follow-up duration, and newer adjuvant products promoting fusions. However, a literature review and the authors' own series of pediatric cases suggest that instrumentation of the cervical spine in children may be safer and more efficacious using screw constructs rather than wiring techniques.

Occipitocervical stabilization in the pediatric age group remains a challenge because of the regional anatomy, poor occipital bone purchase, and, in some instances, significant thinning of the occipital bone. Multiple bicortical fixation points to the occipital bone may be required to increase construct rigidity. The authors evaluated the complications of bicortical occipital screw placement in children with occipital fusion constructs.The records of 20 consecutive pediatric patients who had undergone occipitocervical fusion between September 1, 2007, and November 30, 2010, at Texas Children's Hospital were reviewed.The patients consisted of 10 girls and 10 boys, ranging in age from 10 months to 16 years (mean ± SD, 7.7 ± 5.1 years). Two patients were lost to follow-up, 2 died for reasons unrelated to the surgery, and the remaining patients had at least 3 months of follow-up (mean 14 ± 11.8 months) with evaluation via dynamic radiography and CT. Four patients experienced 8 complications: 2 CSF leaks, 2 vigorous venous bleedings, worsening of quadriparesis, wound infection, radiographic pseudarthrosis, and transient dysphagia. Among 114 screws, there were 2 cases of intraoperative dural venous sinus injury and 2 cases of intraoperative CSF leakage, without clinical sequelae from these complications. Only 1 case of radiographic pseudarthrosis was identified in a patient with skeletal dysplasia and a prior failed C1-2 posterior arthrodesis. There were no difficulties with wound healing because of prominent occipital instrumentation, and there was only 1 wound infection.Data in this report confirm that including bicortical occipital screw placement in occipitocervical constructs in children may result in a high fusion rate but at the cost of a notable complication rate.

Adult studies have shown that sectioning the C2 nerve root and ganglion may facilitate placement of C1 lateral mass screws and lead to decreased operative time and blood loss. We report the functional outcomes and complications following routine sectioning of the C2 nerve root and ganglion, which have not been reported in pediatric patients.Fifteen consecutive pediatric patients underwent C1 lateral mass screw insertion and bilateral C2 nerve root and ganglion sectioning. Clinical and radiographic assessments were performed at follow-up. Numbness in the C2 distribution and/or occipital neuralgia, operative times, estimated blood loss (EBL), length of stay (LOS), and complications were recorded.Average follow-up time was 35.7 months. Overall mean operative time was 250.5 min, LOS was 8.46 days, and EBL was 337 cc. When considering only atlantoaxial fusions, mean operative time was 180.7 min and EBL was 97.1 cc. There were no intraoperative complications, and no patient reported new onset occipital neuralgia or numbness in the C2 distribution that would interfere with daily living. Of the patients, 93 % achieved Lenke fusion grade A; one achieved Lenke fusion grade B.Routine C2 nerve root sectioning and ganglionectomy enhanced surgical exposure of the C1 lateral mass and C1-2 facet joint, potentially maximizing fusion rate and minimizing intraoperative complications. This technique may yield favorable operative times, EBL, and LOS in children undergoing C1 lateral mass screw insertion without negatively affecting functional outcome.

Technology that assists in obtaining a safe, complete resection of central nervous system (CNS) tumors can have a tremendous impact on patient outcomes. Indocyanine green (ICG) is a fluorescent dye that has established utility in the intraoperative visualization of intracranial vasculature during aneurysm surgery. Recently, the use of ICG as an adjunct in tumor resection has been described. Intraoperative ICG use may help visualize vascular tumors, such as hemangioblastomas, to ascertain the tumor margins and to assure that no residual tumor remains. ICG can also assist in intraoperative localization of tumors and operative planning by visualizing the tumor in real time. Intraoperative ICG videography has the potential to become a powerful adjunct in the resection of specific CNS neoplasms.

We sought to clarify the effect of applying derotation maneuvers in the correction of adolescent idiopathic scoliosis (AIS) on the sagittal plane.We retrospectively queried a large, multicenter, prospectively collected database for patients who underwent surgical correction of AIS. All patients had at least 2 years of follow-up and documentation as to whether or not a derotation maneuver was performed during surgery. All patients underwent posterior spinal fusion with pedicle screw constructs. Patients who underwent concurrent anterior procedures were excluded.A total of 323 patients were identified, of whom 66 did not have direct vertebral body derotation (DVBD) maneuvers applied during the deformity correction. The remaining 257 had a vertebral body derotation maneuver performed during their surgical correction. Although no significant differences were identified between the two groups when comparing pre-op and post-op thoracic kyphosis using T2-12 and T5-12 endplates, the absolute change in angulation measured from T2-12 was significantly different between the two groups. Postoperatively, the derotation group had a mean decrease in thoracic kyphosis of 5.1±15.3° as compared to 10.8±18.9° in the control group, P = 0.03.Although patients in both groups had decreased mean thoracic kyphosis postoperatively, application of DVBD in the correction of scoliosis did not additionally worsen the sagittal profile.