Differentiating radiation necrosis from tumor recurrence: a systematic review and diagnostic meta-analysis comparing imaging modalities.

PURPSOSE: Cerebral radiation necrosis (RN) is often a delayed phenomenon occurring several months to years after the completion of radiation treatment. Differentiating RN from tumor recurrence presents a diagnostic challenge on standard MRI. To date, no evidence-based guidelines exist regarding imaging modalities best suited for this purpose. We aim to review the current literature and perform a diagnostic meta-analysis comparing various imaging modalities that have been studied to differentiate tumor recurrence and RN. METHODS: A systematic search adherent to PRISMA guidelines was performed using Scopus, PubMed/MEDLINE, and Embase. Pooled sensitivities and specificities were determined using a random-effects or fixed-effects proportional meta-analysis based on heterogeneity. Using diagnostic odds ratios, a diagnostic frequentist random-effects network meta-analysis was performed, and studies were ranked using P-score hierarchical ranking. RESULTS: The analysis included 127 studies with a total of 220 imaging datasets, including the following imaging modalities: MRI (n = 10), MR Spectroscopy (MRS) (n = 28), dynamic contrast-enhanced MRI (n = 7), dynamic susceptibility contrast MRI (n = 36), MR arterial spin labeling (n = 5), diffusion-weighted imaging (n = 13), diffusion tensor imaging (DTI) (n = 2), PET (n = 89), and single photon emission computed tomography (SPECT) (n = 30). MRS had the highest pooled sensitivity (90.7%). DTI had the highest pooled specificity (90.5%). Our hierarchical ranking ranked SPECT and MRS as most preferable, and MRI was ranked as least preferable. CONCLUSION: These findings suggest SPECT and MRS carry greater utility than standard MRI in distinguishing RN from tumor recurrence.

A Population-Based Study of Patients with Sleep-Wake Disorders Undergoing Elective Instrumented Spinal Surgery.

BACKGROUND: Sleep-wake disorders (SWDs) are associated with multiple systemic pathologies; however, the clinical risk that such disorders carry for spinal surgery patients is not well understood. In the present population-based study, we comprehensively evaluated the significance of sleep-related risk factors on instrumented spinal surgery outcomes. METHODS: National Inpatient Sample data for the hospitalization of patients who had undergone elective instrumented spine surgery from 2008 to 2014 were analyzed using national estimates. The cohorts were defined as those admissions with or without a coexisting SWD diagnosis identified by International Classification of Diseases, ninth revision, codes. Postoperative complications, mortality rate, length of stay, discharge status, and the total cost of admission were compared between the groups using bivariate and multivariate analyses. RESULTS: A coexisting SWD was present in 234,640 of 2,171,167 instrumented spinal surgery hospitalizations (10.8%). Multivariate binary logistic regression accounting for these variables confirmed that a SWD is a significant risk factor for postoperative complications (odds ratio [OR], 1.160; 95% confidence interval [CI], 1.140-1.179; P < 0.0001), length of stay greater than the 75th percentile (OR, 1.303; 95% CI, 1.288-1.320; P < 0.0001), nonroutine discharge (OR, 1.147; 95% CI, 1.131-1.163; P < 0.0001), and death (OR, 1.533; 95% CI, 1.131-2.078; P < 0.01), but not for total charges greater than the 75th percentile (OR, 0.975; 95% CI, 0.962-0.989; P < 0.001). CONCLUSIONS: SWDs confer an increased risk of morbidity and mortality for elective instrumented spine surgery. Understanding the specific contributions of SWDs to postoperative morbidity and mortality will help physicians implement prophylactic measures to reduce complications and improve postoperative patient recovery.

Magnetic resonance-guided focused ultrasound treatment for essential tremor shows sustained efficacy: a meta-analysis.

Although magnetic resonance-guided focused ultrasound (MRgFUS) is a viable treatment option for essential tremor, some studies note a diminished treatment benefit over time. A PubMed search was performed adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were included if hand tremor scores (HTS), total Clinical Rating Scale for Tremor (CRST) scores, or Quality of Life in Essential Tremor Questionnaire (QUEST) scores at regular intervals following MRgFUS treatment for essential tremor were documented. Data analyses included a random effects model of meta-analysis and mixed-effects model of meta-regression. Twenty-one articles reporting HTS for 395 patients were included. Mean pre-operative HTS was 19.2 ± 5.0. Mean HTS at 3 months post-treatment was 7.4 ± 5.0 (61.5% improvement, p < 0.001). Treatment effect was mildly decreased at 36 months at 9.1 ± 5.4 (8.8% reduction). Meta-regression of time since treatment as a modifier of HTS revealed a downward trend in effect size, though this was not statistically significant (p = 0.208). Only 4 studies included follow-up ≥ 24 months. Thirteen included articles reported total CRST scores with standardized follow-up for 250 patients. Mean pre-operative total CRST score decreased by 46.2% at 3 months post-treatment (p < 0.001). Additionally, mean QUEST scores at 3 months post-treatment significantly improved compared to baseline (p < 0.001). HTS is significantly improved from baseline ≥ 24 months post-treatment and possibly ≥ 48 months post-treatment. There is a current paucity of long-term CRST and QUEST score reporting in the literature.

Immunotherapy and potential molecular targets for the treatment of pituitary adenomas resistant to standard therapy: a critical review of potential therapeutic targets and current developments.

INTRODUCTION: Pituitary adenomas (PAs) are primary central nervous system (CNS) tumors, accounting for as much as 25% of intracranial neoplasms. Although existing remedies show success in treating most PAs, treatment of invasive and non-functioning PAs, in addition to functioning PAs unresponsive to standard therapy, remains challenging. With the continually increasing understanding of biochemical pathways involved in tumorigenesis, immunotherapy stands as a promising alternative therapy for pituitary tumors that are resistant to standard therapy. EVIDENCE ACQUISITION: A literature search was conducted of the PubMed database for immunotherapies of PAs. The search yielded a total of 2621 articles, 26 of which were included in our discussion. EVIDENCE SYNTHESIS: Several pathologically expressed molecules could potentially serve as promising targets of current or future immunotherapies for PAs. Programmed death ligand-1, matrix metalloproteinases, EpCAM (Trop1) and Trop2, cancer-testis antigen MAGE-A3, epidermal growth factor receptor (EGFR), folate receptor alpha, vascular endothelial growth factor, and galectin-3 have all been implicated as crucial factors involved with tumor survival and invasion. Inhibition of these pathways may prove efficacious in the management of invasive and treatment-resistant PAs. CONCLUSIONS: Rapid advancements in tumor immunology may increase the probability of successful treatment of PAs by exploitation of the normal immune response or by targeting novel proteins. Current research on many of the targets reviewed in this article are successfully being utilized to manage various neoplastic disease including CNS tumors. These therapies may eventually play a key role in the treatment of PAs that do not respond to standard therapy.

Chiari I malformation with underlying pseudotumor cerebri: Poor symptom relief following posterior decompression surgery.

INTRODUCTION: Pseudotumor cerebri (PTC) patients exhibit clear clinical signs and symptoms of higher intracranial pressure (ICP) without ventricular enlargement or mass lesions. The clinical picture of patients with PTC can sometimes be similar to that of Chiari Malformation type I (CMI). There is some evidence that Chiari I malformation and PTC may coexist, which raises the question of whether PTC is an idiopathic disease or a complication of posterior decompression surgery-treatment of choice for Chiari I malformation. PRESENTATION OF CASES: A retrospective review of electronic medical records of patients diagnosed with PTC at the University of Toledo Medical Center (UTMC) was performed. The objective was to determine whether PTC patients had a concurrent diagnosis of Chiari I malformation and whether the diagnosis of PTC occurred before or after posterior decompression surgery. Out of the 8 eligible patient medical records reviewed, 5 patients diagnosed with PTC had undergone posterior decompression surgery for Chiari I malformation at anywhere from several days to three years prior to being diagnosed with PTC. The diagnosis of PTC was based on temporary symptomatic relief following lumbar puncture which also showed elevated CSF opening pressures. Finally, a VP shunt was placed in each of the 5 patients to relieve the elevated intracranial pressure which resulted in the complete resolution of the patients' symptoms. DISCUSSION: Our study focuses on patients who were diagnosed with and treated for CMI then reported back to the clinic within several days to three years complaining of symptoms of headache. Upon re-presenting to the clinic, a CSF flow study was performed which showed normal flow of CSF. Then, these patients underwent a lumbar puncture which demonstrated an elevated opening pressure (and ICP) and a temporary relief of the headache with lumbar drainage. A VP shunt was placed for each patient to treat for PTC, and the patients' headaches were relieved. CONCLUSION: This study suggests that the presence of Chiari I malformation in a patient conceals the symptoms of PTC which may become apparent following posterior decompression surgery. Other possibilities could be that the patients are misdiagnosed for Chiari I malformation when they are in fact suffering from PTC, or that PTC is a complication of surgery.