Rare Complications of Cervical Spine Surgery: Horner's Syndrome.

STUDY DESIGN: A multicenter retrospective case series. OBJECTIVE: Horner's syndrome is a known complication of anterior cervical spinal surgery, but it is rarely encountered in clinical practice. To better understand the incidence, risks, and neurologic outcomes associated with Horner's syndrome, a multicenter study was performed to review a large collective experience with this rare complication. METHODS: We conducted a retrospective multicenter case series study involving 21 high-volume surgical centers from the AOSpine North America Clinical Research Network. Medical records for 17 625 patients who received subaxial cervical spine surgery from 2005 to 2011 were reviewed to identify occurrence of 21 predefined treatment complications. Descriptive statistics were provided for baseline patient characteristics. Paired t test was used to analyze changes in clinical outcomes at follow-up compared to preoperative status. RESULTS: In total, 8887 patients who underwent anterior cervical spine surgery at the participating institutions were screened. Postoperative Horner's syndrome was identified in 5 (0.06%) patients. All patients experienced the complication following anterior cervical discectomy and fusion. The sympathetic trunk appeared to be more vulnerable when operating on midcervical levels (C5, C6), and most patients experienced at least a partial recovery without further treatment. CONCLUSIONS: This collective experience suggests that Horner's syndrome is an exceedingly rare complication following anterior cervical spine surgery. Injury to the sympathetic trunk may be limited by maintaining a midline surgical trajectory when possible, and performing careful dissection and retraction of the longus colli muscle when lateral exposure is necessary, especially at caudal cervical levels.

Aggressive resection at the infiltrative margins of glioblastoma facilitated by intraoperative fluorescein guidance.

OBJECTIVE Extent of resection is an important prognostic factor in patients undergoing surgery for glioblastoma (GBM). Recent evidence suggests that intravenously administered fluorescein sodium associates with tumor tissue, facilitating safe maximal resection of GBM. In this study, the authors evaluate the safety and utility of intraoperative fluorescein guidance for the prediction of histopathological alteration both in the contrast-enhancing (CE) regions, where this relationship has been established, and into the non-CE (NCE), diffusely infiltrated margins. METHODS Thirty-two patients received fluorescein sodium (3 mg/kg) intravenously prior to resection. Fluorescence was intraoperatively visualized using a Zeiss Pentero surgical microscope equipped with a YELLOW 560 filter. Stereotactically localized biopsy specimens were acquired from CE and NCE regions based on preoperative MRI in conjunction with neuronavigation. The fluorescence intensity of these specimens was subjectively classified in real time with subsequent quantitative image analysis, histopathological evaluation of localized biopsy specimens, and radiological volumetric assessment of the extent of resection. RESULTS Bright fluorescence was observed in all GBMs and localized to the CE regions and portions of the NCE margins of the tumors, thus serving as a visual guide during resection. Gross-total resection (GTR) was achieved in 84% of the patients with an average resected volume of 95%, and this rate was higher among patients for whom GTR was the surgical goal (GTR achieved in 93.1% of patients, average resected volume of 99.7%). Intraoperative fluorescein staining correlated with histopathological alteration in both CE and NCE regions, with positive predictive values by subjective fluorescence evaluation greater than 96% in NCE regions. CONCLUSIONS Intraoperative administration of fluorescein provides an easily visualized marker for glioma pathology in both CE and NCE regions of GBM. These findings support the use of fluorescein as a microsurgical adjunct for guiding GBM resection to facilitate safe maximal removal.

MRI-localized biopsies reveal subtype-specific differences in molecular and cellular composition at the margins of glioblastoma.

Glioblastomas (GBMs) diffusely infiltrate the brain, making complete removal by surgical resection impossible. The mixture of neoplastic and nonneoplastic cells that remain after surgery form the biological context for adjuvant therapeutic intervention and recurrence. We performed RNA-sequencing (RNA-seq) and histological analysis on radiographically guided biopsies taken from different regions of GBM and showed that the tissue contained within the contrast-enhancing (CE) core of tumors have different cellular and molecular compositions compared with tissue from the nonenhancing (NE) margins of tumors. Comparisons with the The Cancer Genome Atlas dataset showed that the samples from CE regions resembled the proneural, classical, or mesenchymal subtypes of GBM, whereas the samples from the NE regions predominantly resembled the neural subtype. Computational deconvolution of the RNA-seq data revealed that contributions from nonneoplastic brain cells significantly influence the expression pattern in the NE samples. Gene ontology analysis showed that the cell type-specific expression patterns were functionally distinct and highly enriched in genes associated with the corresponding cell phenotypes. Comparing the RNA-seq data from the GBM samples to that of nonneoplastic brain revealed that the differentially expressed genes are distributed across multiple cell types. Notably, the patterns of cell type-specific alterations varied between the different GBM subtypes: the NE regions of proneural tumors were enriched in oligodendrocyte progenitor genes, whereas the NE regions of mesenchymal GBM were enriched in astrocytic and microglial genes. These subtype-specific patterns provide new insights into molecular and cellular composition of the infiltrative margins of GBM.

Apolipoprotein E-ε4 polymorphism and cognitive dysfunction after carotid endarterectomy.

Approximately 25% of patients undergoing carotid endarterectomy (CEA) exhibit cognitive dysfunction (CD) 1 day and 1 month after CEA. The apolipoprotein E (apoE)-ε4 polymorphism has been previously identified as a robust independent risk factor for CD 1 month after CEA. We aimed to determine whether the apoE-ε4 polymorphism is also an independent risk factor for CD as early as 1 day after CEA and to confirm the previous findings at 1 month. Patients undergoing elective CEA (n=411) were enrolled with written informed consent in this follow-up observational study. CD was evaluated via an extensive neuropsychometric battery. apoE-ε4 carriers exhibited significantly more CD 1 day (30.1% versus 17.9%, p=0.01) and 1 month (25.7% versus 9.8%, p=0.001) after CEA compared to non-carriers. Multivariate regression models were generated to determine independent predictors of CD. At 1 day, apoE-ε4 was significantly associated with higher risk of CD (odds ratio [OR]: 2.24 [95% confidence interval 1.29-3.84], p=0.004), while statin use was significantly associated with lower risk (OR: 0.40 [0.24-0.67], p<0.001). At 1 month, apoE-ε4 was significantly associated with higher risk of CD (OR: 3.14 [1.53-6.38], p=0.002), while symptomatic status was significantly associated with lower risk (OR: 0.45 [0.20-0.94], p=0.03). The apoE-ε4 polymorphism is an independent risk factor for CD as early as 1 day after CEA and is confirmed to be an independent risk factor for CD at 1 month as well.

Phosphodiesterase 4D single-nucleotide polymorphism 83 and cognitive dysfunction in carotid endarterectomy patients.

BACKGROUND: Phosphodiesterase 4D (PDE4D), through the regulation of cyclic AMP, modulates inflammation and other processes that affect atherosclerosis and stroke. A PDE4D polymorphism, single-nucleotide polymorphism (SNP) 83 (rs966221), is associated with ischemic stroke. The association of SNP 83 with postoperative cognitive dysfunction has never been investigated. OBJECTIVE: To determine whether SNP 83 is associated with cognitive dysfunction 1 day and 1 month following carotid endarterectomy (CEA). METHODS: Three hundred fourteen patients with high-grade carotid stenosis scheduled for CEA consented to participate in this single-center cohort study of cognitive dysfunction. RESULTS: Patients with the C/C genotype of SNP 83 exhibited significantly more cognitive dysfunction at 1 day (29.7%) than the C/T (15.8%, P = .008) and T/T (12.7%, P = .01) genotypes. In a multivariate logistic regression model, C/T and T/T genotypes were both associated with significantly decreased odds of cognitive dysfunction compared with the C/C genotype (odds ratio, 0.45 [0.24-0.83], P = .01 and odds ratio, 0.33 [0.12-0.77], P = .02). There were no significant associations at 1 month. CONCLUSION: The C/C genotype of SNP 83 is significantly associated with the highest incidence of cognitive dysfunction 1 day following CEA in comparison with the C/T and T/T genotypes. This PDE4D genotype may lead to accelerated cyclic AMP degradation and subsequently elevated inflammation 1 day after CEA. These observations, in conjunction with previous studies, suggest that elevated inflammatory states may be partially responsible for the development of cognitive dysfunction after CEA, but more investigation is required.

Complement polymorphisms and cognitive dysfunction after carotid endarterectomy.

OBJECT: The role of genetic polymorphisms in the neurological outcome of patients after carotid endarterectomy (CEA) remains unclear. There are single nucleotide polymorphisms (SNPs) that predispose patients to postoperative cognitive dysfunction (CD). We aim to assess the predictability of three complement cascade-related SNPs for CD in patients having CEAs. METHODS: In 252 patients undergoing CEA, genotyping was performed for the following polymorphisms: complement component 5 (C5) rs17611, mannose-binding lectin 2 (MBL2) rs7096206, and complement factor H (CFH) rs1061170. Differences among genotypes were analyzed via the chi-square test. Patients were evaluated with a neuropsychometric battery for CD 1 day and 1 month after CEA. A multiple logistic regression model was created. All variables with univariate p < 0.20 were included in the final model. RESULTS: The C5 genotypes A/G (OR 0.26, 95% CI 0.11-0.60, p = 0.002) and G/G (OR 0.22, 95% CI 0.09-0.52, p < 0.001) were significantly associated with lower odds of exhibiting CD at 1 day after CEA compared with A/A. The CFH genotypes C/T (OR 3.37, 95% CI 1.69-6.92, p < 0.001) and C/C (OR 3.67, 95% CI 1.30-10.06, p = 0.012) were significantly associated with higher odds of exhibiting CD at 1 day after CEA compared with T/T. Statin use was also significantly associated with lower odds of exhibiting CD at 1 day after CEA (OR 0.43, 95% CI 0.22-0.84, p = 0.01). No SNPs were significantly associated with CD at 1 month after CEA. CONCLUSIONS: The presence of a deleterious allele in the C5 and CFH SNPs may predispose patients to exhibit CD after CEA. This finding supports previous data demonstrating that the complement cascade system may play an important role in the development of CD. These findings warrant further investigation.

Incidence, treatment and survival of patients with craniopharyngioma in the surveillance, epidemiology and end results program.

Craniopharyngioma is a rare primary central nervous system neoplasm. Our objective was to determine factors associated with incidence, treatment, and survival of craniopharyngiomas in the United States. We used the surveillance, epidemiology and end results program (SEER) database to identify patients who received a diagnosis of craniopharyngioma during 2004-2008. We analyzed clinical and demographic information, including age, race, sex, tumor histology, and treatment. Age-adjusted incidence rates and age, sex, and race-adjusted expected survival rates were calculated. We used Cox proportional hazards models to determine the association between covariates and overall survival. We identified 644 patients with a diagnosis of craniopharyngioma. Black race was associated with an age-adjusted relative risk for craniopharyngioma of 1.26 (95% confidence interval [CI], 0.98-1.59), compared with white race. One- and 3-year survival rates of 91.5% (95% CI, 88.9%-93.5%), and 86.2% (95% CI, 82.7%-89.0%) were observed for the cohort; relative survival rates were 92.1% (95% CI, 89.5%-94.0%) and 87.6% (95% CI, 84.1%-90.4%) for 1- and 3-years, respectively. In the multivariable model, factors associated with prolonged survival included younger age, smaller tumor size, subtotal resection, and radiation therapy. Black race, on the other hand, was associated with worse overall survival in the final model. We demonstrated that >85% of patients survived 3 years after diagnosis and that subtotal resection and radiation therapy were associated with prolonged survival. We also noted a higher incidence rate and worse 1- and 3-year survival rates in the black population. Future investigations should examine these racial disparities and focus on evaluating the efficacy of emerging treatment paradigms.

Convection enhanced drug delivery of BDNF through a microcannula in a rodent model to strengthen connectivity of a peripheral motor nerve bridge model to bypass spinal cord injury.

Models employing peripheral nerve to bypass spinal cord injury (SCI), although highly promising, may benefit from improved nerve regeneration and motor bridge connectivity. Recent studies have demonstrated that neuronal growth factor-induced enhancement of endogenous neurorestoration may improve neuronal connectivity after severe neurologic injury, particularly if delivered intraparenchymally with zero-order kinetics. We sought to investigate the effect of convection-enhanced delivery of brain-derived neurotrophic factor (BDNF), a neuronal growth factor, on the connectivity of a peripheral motor-nerve bridge in a rodent model using electrophysiology and immunohistochemistry (IHC). Spinal cords of 29 female rats were hemisected at the L1 level. Ipsilateral T13 peripheral nerves were dissected from their muscular targets distally, while maintaining their connections with the spinal cord, and inserted caudal to the injury site to establish the nerve bridge. A microcannula attached to a six-week mini-osmotic pump was used to deliver either BDNF (n=12), saline (n=14), or fluorescein dye (n=3) directly into the spinal cord parenchyma between the site of nerve insertion and hemisection to a depth of 2mm into the area of the lateral motor pool. After four weeks, gastrocnemius muscle activation was assessed electromyographically in five animals from each group. Spinal cords were harvested and analyzed with IHC for cannula-associated injury, and nerve regeneration. Strength of motor bridge connection was illustrated by electrophysiology data. Intraspinal BDNF levels were measured using enzyme-linked immunosorbent assay. IHC revealed increased intraparenchymal BDNF concentration at the nerve bridge insertion site with evidence of minimal trauma from cannulation. BDNF infusion resulted in stronger connections between bridge nerves and spinal motor axons. Bridge nerve electrical stimulation in BDNF-treated rats evoked hind leg electromyogram responses of shorter latency and larger amplitudes than saline-infused controls. Thus, direct convection-assisted delivery provides reliable administration of potent growth factors directly into the spinal cord parenchyma. Delivery of BDNF at the peripheral nerve bridge site results in enhanced connectivity of the peripheral motor bridge in a rodent model of SCI.

Spinal cord bypass surgery with intercostal and spinal accessory nerves: an anatomical feasibility study in human cadavers.

OBJECT: Despite extensive study, no meaningful progress has been made in encouraging healing and recovery across the site of spinal cord injury (SCI) in humans. Spinal cord bypass surgery is an unconventional strategy in which intact peripheral nerves rostral to the level of injury are transferred into the spinal cord below the injury. This report details the feasibility of using spinal accessory nerves to bypass cervical SCI and intercostal nerves to bypass thoracolumbar SCI in human cadavers. METHODS: Twenty-three human cadavers underwent cervical and/or lumbar laminectomy and dural opening to expose the cervical cord and/or conus medullaris. Spinal accessory nerves were harvested from the Erb point to the origin of the nerve's first major branch into the trapezius. Intercostal nerves from the T6-12 levels were dissected from the lateral border of paraspinal muscles to the posterior axillary line. The distal ends of dissected nerves were then transferred medially and sequentially inserted 4 mm deep into the ipsilateral cervical cord (spinal accessory nerve) or conus medullaris (intercostals). The length of each transferred nerve was measured, and representative distal and proximal cross-sections were preserved for axonal counting. RESULTS: Spinal accessory nerves were consistently of sufficient length to be transferred to caudal cervical spinal cord levels (C4-8). Similarly, intercostal nerves (from T-7 to T-12) were of sufficient length to be transferred in a tension-free manner to the conus medullaris. Spinal accessory data revealed an average harvested nerve length of 15.85 cm with the average length needed to reach C4-8 of 4.7, 5.9, 6.5, 7.1, and 7.8 cm. The average length of available intercostal nerve from each thoracic level compared with the average length required to reach the conus medullaris in a tension-free manner was determined to be as follows (available, required in cm): T-7 (18.0, 14.5), T-8 (18.7, 11.7), T-9 (18.8, 9.0), T-10 (19.6, 7.0), T-11 (18.8, 4.6), and T-12 (15.8, 1.5). The number of myelinated axons present on cross-sectional analysis predictably decreased along both spinal accessory and intercostal nerves as they coursed distally. CONCLUSIONS: Both spinal accessory and intercostal nerves, accessible from a posterior approach in the prone position, can be successfully harvested and transferred to their respective targets in the cervical spinal cord and conus medullaris. As expected, the number of axons available to grow into the spinal cord diminishes distally along each nerve. To maximize axon "bandwidth" in nerve bypass procedures, the most proximal section of the nerve that can be transferred in a tension-free manner to a spinal level caudal to the level of injury should be implanted. This study supports the feasibility of SAN and intercostal nerve transfer as a means of treating SCI and may assist in the preoperative selection of candidates for future human clinical trials of cervical and thoracolumbar SCI bypass surgery.

Beneficial use of a new hand-held CO2 laser fiber in resection of a calcified and vascular intraventricular tumor.

BACKGROUND: The progression of laser technology in neurosurgery has been limited by the poor maneuverability of traditional line-of-sight carbon dioxide (CO2) lasers and the propensity of other laser energies to cause collateral thermal injury to adjacent neural structures. The advent of a dielectric omnidirectional reflector and the subsequent development of phototonic bandgap fibers (PBF) have transformed the CO2 laser into a low-profile instrument with considerable dexterity and many potential new neurosurgical applications. CASE DESCRIPTION: A 48-year-old woman presented with a large mass in the left lateral ventricle that was first diagnosed>20 years ago. The patient was asymptomatic until 1 month before presentation, when she began to experience progressive memory loss and neurocognitive decline. RESULTS: The hand-held CO2 laser was used to debulk the tumor. The CO2 laser vaporized neoplastic cellular material and simultaneously cauterized microvascular structures. CONCLUSIONS: The CO2 laser was exceptionally useful in the resection of this long-standing and extremely calcified, yet vascular mass. A review of the evolution of laser technology applications in neurosurgery is presented, with a specific focus on the innovations that led to the development of the new PBF CO2 laser. This new technology may be advantageous in tumor surgery, particularly in the resection of long-standing calcified and vascular tumors that are not amendable to traditional surgical techniques.

Simulation in neurosurgery: a review of computer-based simulation environments and their surgical applications.

BACKGROUND: Computer-based surgical simulators create a no-risk virtual environment where surgeons can develop and refine skills through harmless repetition. These applications may be of particular benefit to neurosurgeons, as the vulnerability of nervous tissue limits the margin for error. The rapid progression of computer-processing capabilities in recent years has led to the development of more sophisticated and realistic neurosurgery simulators. OBJECTIVE: To catalogue the most salient of these advances and characterize our current effort to create a spine surgery simulator. METHODS: An extensive search of the databases Ovid-MEDLINE, PubMed, and Google Scholar was conducted. Search terms included, but were not limited to: neurosurgery combined with simulation, virtual reality, haptics, and 3-dimensional imaging. RESULTS: A survey of the literature reveals that surgical simulators are evolving from platforms used for preoperative planning and anatomic education into programs that aim to simulate essential components of key neurosurgical procedures. This evolution is predicated upon the advancement of 3 main components of simulation: graphics/volume rendering, model behavior/tissue deformation, and haptic feedback. CONCLUSION: The computational burden created by the integration of these complex components often limits the fluidity of real-time interactive simulators. Although haptic interfaces have become increasingly sophisticated, the production of realistic tactile sensory feedback remains a formidable and costly challenge. The rate of future progress may be contingent upon international collaboration between research groups and the establishment of common simulation platforms. Given current limitations, the most potential for growth lies in the innovative design of models that expand the procedural applications of neurosurgery simulation environments.