Loyola V. Gressot

Complications of occipital screw placement for occipitocervical fusion in children

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 Childrens 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.

Osteosarcoma of the cranial vault and skull base in pediatric patients

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.

Iliac screw placement in neuromuscular scoliosis using anatomical landmarks and uniplanar anteroposterior fluoroscopic imaging with postoperative CT confirmation.

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.

Prognostic Factors Influencing the Outcome of 64 Consecutive Patients Undergoing Surgery for Metastatic Melanoma of the Spine

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.

Frontal sinus encephalocele: Case report and review of literature

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.

Disseminated germinoma in the brain and cervical spinal cord 10 years after radiographic resolution of pineal germinoma

Intracranial germinoma, a radiosensitive tumor, is seldom recurrent following initial treatment. When it does recur, it is usually soon after initial treatment and secondary to inadequate radiation field coverage of the tumor. Rarely, there have been case reports of late recurrence many years after initial therapy. Patients with recurrent germinoma in the spine have a less favorable prognosis in terms of treatment response compared to the initial lesion. Thus, careful consideration of the initial lesion, its treatment, and serial imaging of the neural axis with close follow-up is important. We report a patient with a rare delayed recurrence in the brain and cervical spinal cord despite close follow-up with clinical examination and serial imaging.

An Intraoperative Look at Failure of Flow Diversion: When Additional or Alternative Treatments Should Be Considered

BACKGROUND The pipeline embolization device (PED) is a flow-diverting stent that provides an additional treatment modality in the management of intracranial aneurysms. An aneurysm treated with a flow diverter is expected to involute over time, contrary to the immediate obliteration expected by surgical clipping or coiling. Yet, which aneurysms will respond to PED therapy and the time frame to expect full obliteration remain unclear. CASE DESCRIPTION We report the unusual case of a 50-year-old woman with multiple (4 total) intracranial aneurysms who underwent multimodality treatment. Two aneurysms were treated with PEDs. Nine months later, the patient underwent a craniotomy for treatment of an additional aneurysm; at the time of surgery, one of the PED-treated aneurysms was noted to be clearly obliterated, and the other was visualized to be filling. The ophthalmic artery arose from the persistently filling aneurysm. The aneurysm was treated by clip ligation without incident. CONCLUSIONS The rate of PED aneurysm obliteration increases with longer follow-up; however, the time frame for observing a persistently filling aneurysm before additional treatment is considered remains unknown. Some aneurysms may never close even after discontinuation of dual antiplatelet therapy. Ophthalmic artery aneurysms have been noted to fail treatment with PED based on the anatomic relationship of the aneurysm to the ophthalmic artery. This case provokes us to consider factors that may affect the latency to aneurysm obliteration, including aneurysm size, aneurysm morphology, patient gender, failure of previous aneurysm treatment, and duration of time from initial endovascular treatment.

The Role of Fibrinogen-Like Protein 2 on Immunosuppression and Malignant Progression in Glioma

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.

Abstract 5606: Fibrinogen-like protein 2 drives malignant tumor progression in glioma

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

Peripheral nerve tumors

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.