The role of inflammation in brain cancer.

Malignant brain tumors are among the most lethal of human tumors, with limited treatment options currently available. A complex array of recurrent genetic and epigenetic changes has been observed in gliomas that collectively result in derangements of common cell signaling pathways controlling cell survival, proliferation, and invasion. One important determinant of gene expression is DNA methylation status, and emerging studies have revealed the importance of a recently identified demethylation pathway involving 5-hydroxymethylcytosine (5hmC). Diminished levels of the modified base 5hmC is a uniform finding in glioma cell lines and patient samples, suggesting a common defect in epigenetic reprogramming. Within the tumor microenvironment, infiltrating immune cells increase oxidative DNA damage, likely promoting both genetic and epigenetic changes that occur during glioma evolution. In this environment, glioma cells are selected that utilize multiple metabolic changes, including changes in the metabolism of the amino acids glutamate, tryptophan, and arginine. Whereas altered metabolism can promote the destruction of normal tissues, glioma cells exploit these changes to promote tumor cell survival and to suppress adaptive immune responses. Further understanding of these metabolic changes could reveal new strategies that would selectively disadvantage tumor cells and redirect host antitumor responses toward eradication of these lethal tumors.

State-of-the-art management and monitoring of brain edema and intracranial hypertension in fulminant hepatic failure. A proposed algorithm.

AIM: Develop an evidence-based clinical algorithm integrating clinical decision making on intracranial pressure (ICP) monitoring and intracranial hypertension (ICH) management in the setting of fulminant hepatic failure (FHF). MATERIAL AND METHODS: An English-language literature review was conducted using the PubMed database in November 2007. In compiling evidence on current management trends of ICP and FHF, the paired keywords: fulminant hepatic failure and either mannitol, hypertonic saline, hyperventilation, bioartificial liver, hypothermia, indomethacin, thiopental, or propofol were used. In compiling evidence on ICP monitoring in FHF, the terms "intracranial pressure monitoring" and "liver failure" were used. Excluded references were either pertinent to animal research or irrelevant to ICP monitoring and ICH management in the setting of FHF. RESULTS: State-of-the-art management of ICH due to brain edema in FHF includes Class I therapies such as mannitol and hypertonic saline. Bioartificial liver, hypothermia and hyperventilation are supported by Class II evidence. Indomethacin and sedation remain Class III. Monitoring ICP is supported by Class II and III evidence. A clinical algorithm was created based on the existing therapeutic armamentarium and corresponding evidence support.

How the elderly fare after brain tumor surgery compared to younger patients within a 30-day follow-up: A National surgical Quality Improvement Program analysis of 30,183 cases.

The growing elderly population in Western societies has led to an increasing number of primary brain tumors occurring in patients beyond the age of 65. The purpose of this study was to assess and compare the safety, efficacy, and outcomes of oncological craniotomy procedures between patients above and below 65 years. We performed a retrospective analysis of the ACS-NSQIP database to identify patients undergoing supratentorial and infratentorial tumor excisions by neurosurgeons between 2008 and 2016. We stratified them based on a cutoff age of 65 years and analyzed for minor and major complications, reoperation, the total length of hospital stay, and mortality within a standardized 30-day follow-up. Among the 30,183 analyzed patients, 9,652 (32%) were elderly (age ≥ 65). The bivariate analysis demonstrated significantly increased risk of complications, including major and minor complications and mortality in patients with metabolic syndrome, preoperative steroid use, and ASA classification ≥3. (p-value ≤ 0.001***). After controlling for confounding variables in our logistic regression models, older age, metabolic syndrome, extended operative time beyond 5 h, dependent functional health status, ASA class ≥3, steroid use pre-operatively, and black/African American race were found to be significant predictors of major and minor complication. Our study provides a comprehensive analysis of perioperative risk factors and predictors of adverse outcomes following craniotomy for supratentorial and infratentorial tumors in elderly patients. We identified increased age as an independent risk factor for minor and major adverse events as well as extended hospitalization.

Metabolic Syndrome Associated with Increased Rates of Medical Complications After Intracranial Tumor Resection.

BACKGROUND: When diagnosed simultaneously, obesity, diabetes, and hypertension form a medical constellation called metabolic syndrome (MetS). The prevalence of MetS in Western cultures has been on a steady increase and MetS has been associated with increased postoperative complications in multiple surgical settings. OBJECTIVE: In this study, we evaluate the relationship between MetS and the outcomes of craniotomy for supratentorial brain tumor. METHODS: Cases of craniotomy for supratentorial brain tumors were extracted from the American College of Surgeons National Surgical Quality Improvement Program for 2012-2016. The 15,136 patients identified were divided into 2 cohorts based on the presence (4.1%) or absence (95.9%) of MetS. We compared the 2 cohorts for preoperative comorbidities, intraoperative details, and postoperative morbidity and mortality. RESULTS: Patients in the MetS+ cohort were significantly older (63.4 vs. 56.1 years) and were more likely to show comorbidities of various organ systems (all P ≤ 0.05). However, operative times were similar (P = 0.573). The number of medical complications was almost double in patients with MetS (15.8% vs. 8.5%; P ≤ 0.001). Unplanned readmissions (14.6% vs. 10.4%; P = 0.004), reoperations (6.9% vs. 4.6%; P = 0.007), and mortality (5.6% vs. 2.9%; P ≤ 0.001) were also more frequent in our MetS+ group. Nevertheless, surgical complications localized to the operative site were not statistically increased (7.4% vs. 5.8%; P = 0.098). CONCLUSIONS: A diagnosis of MetS does not seem to be associated with increased rates of surgical site events. However, neurosurgeons should be aware that these patients have a significantly higher likelihood of general medical complications, readmissions, reoperations, and death.

Computed tomography morphometric analysis of the central clival depression and petroclival angle for application of the presigmoid approach in the pediatric population.

AIMS: Lateral transtemporal approaches are useful for addressing lesions located ventral to the brainstem, especially when the pathologic diagnosis of the tumor dictates that a gross or near total resection improves outcomes. One approach, the presigmoid approach receives little attention in the pediatric population thus far. We sought to characterize morphometric changes, particularly the clival depth and the petroclival Cobb angle, that occur in the temporal bones of children and draw implications about doing a presigmoid approach in children. SETTINGS AND DESIGN: This study was a retrospective study performed at John Sealy Hospital, a level-one trauma center that takes care of pediatric injuries as well. SUBJECTS AND METHODS: We performed a morphometric analysis of noncontrast computed tomography head studies in 96 boys and 67 girls. Central clival depth and petroclival angle were obtained in the axial plane at the level of the internal auditory meatus using the method described by Abdel Aziz et al. STATISTICAL ANALYSIS USED: Descriptive statistics and Student's t-test to compare groups were calculated using Microsoft Excel. RESULTS: We found no gender difference in mean central clival depth or petroclival angle (P = 0.98 and P = 0.61, respectively). However, when we broke our cohort by age into those younger than 9 years of age and those 10 years or older, we found the petroclival angle decreased by 6.2° which was statistically significant (P < 0.000000006). CONCLUSIONS: These findings suggest that a presigmoid retrolabyrinthine approach is useful for children 9 years of age and younger as the petroclival angle appears to decrease resulting in a shallower clival depression in these patients.

Further evidence for the existence of long ascending unmyelinated primary afferent fibers within the dorsal funiculus: effects of capsaicin.

The present study provides further evidence in support of the hypothesis that there is a fine primary afferent system in the dorsal funiculi by determining the effects of capsaicin (8-methyl-N-vanillyl-6-noneamide) on unmyelinated fibers in the cervical fasciculus gracilis of the rat. The neurolytic effect of this procedure was demonstrated by showing an 89% decrease in the number of unmyelinated fibers in the S2 dorsal roots of the experimental animals. Consequently, we feel that unmyelinated primary afferent fibers are largely removed from these animals. Neonatal administration of capsaicin (50 mg/kg) caused a 54% decrease in the number of unmyelinated fibers in the C3 fasciculus gracilis but no significant change in myelinated fiber numbers. The data provide further evidence for the existence of a significant primary afferent unmyelinated fiber system in the dorsal funiculus and suggest a role for the dorsal funiculi in the transmission of noxious information.

Dural arteriovenous fistula presenting with exophthalmos and seizures.

Concomitant seizures and exophthalmos in the context of a temporal dural arteriovenous fistula (dAVF) has not been described before. Here, we report a 55-year-old-male who presented with an 8-month history of progressive painless exophthalmos of his left eye, conjunctival chemosis, reduced vision and new onset complex partial seizures. Cerebral angiography demonstrated Cognard Type IIa left cerebral dAVF fed by branches from the left occipital artery and an accessory meningeal artery, with drainage to the superior ophthalmic vein. Following surgical obliteration of dAVF feeding vessels, our patient had dramatic improvement in visual acuity, proptosis and chemosis along with cessation of clinical seizures.

C4-C5 post-traumatic spondyloptosis with in situ fusion: systematic literature review and case report.

STUDY DESIGN: A case report with systematic review of the literature. OBJECTIVE: To report a case of post-traumatic C4-C5 spondyloptosis without neurological deficit not associated with posterior element fractures and presenting in a delayed fashion with fusion in situ of C4 and C5 vertebral bodies influencing the management strategy. SUMMARY OF BACKGROUND DATA: Traumatic spondyloptosis of the subaxial cervical spine is typically associated with neurological injury. To the best of the author's knowledge, this is the first case of spondyloptosis not associated with fractures of the posterior elements but with locked facets at C4-C5 and fusion in situ, presenting in a delayed fashion with remarkable paucity of symptoms that was managed surgically. METHODS: A 45-year-old male presented 8 months after a motor vehicle collision with radicular arm pain and mild spasticity involving the legs. Cervical radiograph, computed tomographic scan, and magnetic resonance image revealed bilateral locked facets at C4-C5 with spondyloptosis. Fusion had occurred in situ. RESULTS: Traction did not correct alignment and the patient underwent circumferential reduction and fusion and postoperative halo-vest placement. At 6-month follow-up, the patient remained neurologically intact with regression of preoperative symptoms. CONCLUSION: Longstanding post-traumatic spondyloptosis may lead to fusion in situ complicating the surgical management. Insufficient suspicion during workup can lead to the omission of this important diagnosis, further complicating operative intervention. Traction is not useful when in situ fusion has occurred in delayed presentation cases. LEVEL OF EVIDENCE: N/A.

Neurosurgery simulation in residency training: feasibility, cost, and educational benefit.

BACKGROUND: The effort required to introduce simulation in neurosurgery academic programs and the benefits perceived by residents have not been systematically assessed. OBJECTIVE: To create a neurosurgery simulation curriculum encompassing basic and advanced skills, cadaveric dissection, cranial and spine surgery simulation, and endovascular and computerized haptic training. METHODS: A curriculum with 68 core exercises per academic year was distributed in individualized sets of 30 simulations to 6 neurosurgery residents. The total number of procedures completed during the academic year was set to 180. The curriculum includes 79 simulations with physical models, 57 cadaver dissections, and 44 haptic/computerized sessions. Likert-type evaluations regarding self-perceived performance were completed after each exercise. Subject identification was blinded to junior (postgraduate years 1-3) or senior resident (postgraduate years 4-6). Wilcoxon rank testing was used to detect differences within and between groups. RESULTS: One hundred eighty procedures and surveys were analyzed. Junior residents reported proficiency improvements in 82% of simulations performed (P < .001). Senior residents reported improvement in 42.5% of simulations (P < .001). Cadaver simulations accrued the highest reported benefit (71.5%; P < .001), followed by physical simulators (63.8%; P < .001) and haptic/computerized (59.1; P < .001). Initial cost is $341,978.00, with $27,876.36 for annual operational expenses. CONCLUSION: The systematic implementation of a simulation curriculum in a neurosurgery training program is feasible, is favorably regarded, and has a positive impact on trainees of all levels, particularly in junior years. All simulation forms, cadaver, physical, and haptic/computerized, have a role in different stages of learning and should be considered in the development of an educational simulation program.

A large animal neuropathic pain model in sheep: a strategy for improving the predictability of preclinical models for therapeutic development.

BACKGROUND: Evaluation of analgesics in large animals is a necessary step in the development of better pain medications or gene therapy prior to clinical trials. However, chronic neuropathic pain models in large animals are limited. To address this deficiency, we developed a neuropathic pain model in sheep, which shares many anatomical similarities in spine dimensions and cerebrospinal fluid volume as humans. METHODS: A neuropathic pain state was induced in sheep by tight ligation and axotomy of the common peroneal nerve. The analgesic effect of intrathecal (IT) morphine was investigated. Interspecies comparison was conducted by analyzing the ceiling doses of IT morphine for humans, sheep, and rats. RESULTS: Peroneal nerve injury (PNI) produced an 86% decrease in von-Frey filament-evoked withdrawal threshold on postsurgery day 3 and the decrease lasted for the 8-week test period. Compared to the pre-injury, sham, and contralateral hindlimb, the IT morphine dose that produces 50% of maximum analgesia (ED(50)) for injured PNI hindlimb was 1.8-fold larger and E(max), the dose that produces maximal analgesia, was 6.1-fold lower. The sheep model closely predicts human IT morphine ceiling dose by allometric scaling. This is in contrast to the approximately 10-fold lower morphine ceiling dose predicted by the rat spinal nerve ligated or spared nerve injury models. CONCLUSION: PNI sheep model has a fast onset and shows stable and long-lasting pain behavioral characteristics. Since the antinociceptive properties of IT morphine are similar to those observed in humans, the PNI sheep model will be a useful tool for the development of analgesics. Its large size and consistent chronic pain behavior will facilitate the development and evaluation of surgical intervention and gene therapy. The PNI sheep pain model provides us with the opportunity for multi-species testing, which will improve the success of clinical trials.