Age is Associated with Level of First-Time Anterior Cervical Discectomy and Fusion: An Ordinal Analysis of Factors Influencing Timing of Cervical Degeneration.

BACKGROUND: Symptomatic cervical spondylosis is often treated with anterior cervical discectomy and fusion (ACDF). However, few factors can predict which cervical level will degenerate and require intervention. This analysis evaluates preprocedural factors associated with level of first-time single-level ACDF. METHODS: We performed a retrospective analysis of patients who underwent single-level ACDF without prior history of spine surgery. Mann Whitney U-tests and Spearman rank-order correlation were performed for analyses of associations between variables of interest and ACDF level. Adjusted odds-ratios were calculated by proportional-odds logistic regression, with age, sex, body mass index, current tobacco use, history of neck trauma, preoperative radicular symptoms, and preoperative myelopathic symptoms as covariates. RESULTS: One hundred forty-one patients met inclusion criteria, and age demonstrated a negative correlation with ACDF level, such that younger patients tended to have ACDF performed at inferior subaxial levels (P = 0.0006, rho = -0.31, moderately strong relationship). Patients with preoperative radicular symptoms and myelopathic symptoms were more likely to have ACDF performed at inferior (P = 0.0001) and superior (P < 0.0001) levels, respectively. Patient sex, body mass index, current tobacco use, and history of neck trauma were not predictive of ACDF level. When adjusting for the above variables in a proportional-odds ordinal logistic regression model, a one-year increase in age conferred a 4% increase in the odds of requiring an ACDF at a given superior level compared to the adjacent inferior level. CONCLUSIONS: Age is correlated with level of first-time single level ACDF. Individual subaxial levels may have unique biomechanical properties that influence degeneration.

Immune checkpoint inhibitor-related myositis: from pathophysiology to treatment.

With rapid advances in immuno-oncology, immune checkpoint inhibitors (ICIs) are increasingly used for a broad array of malignancies. This has led to a novel spectrum of adverse effects including ICI-related myositis, a potentially life-threatening neuromuscular complication that must be diagnosed and treated promptly. Significant gaps exist in the current understanding of ICI-related myositis due to the rarity of the condition and the lack of evidence-based guidelines, prompting the need to synthesize the most relevant and recent published works in the field. This review provides a broad overview of ICI-related myositis with an emphasis on pathophysiology, epidemiology, clinical features, workup, management and future directions.

The natural history of non-functioning pituitary adenomas: A meta-analysis of conservatively managed tumors.

BACKGROUND: Non-functioning pituitary adenomas (NFPA) are often discovered incidentally. The natural history of NFPA is not well understood, obfuscating evidence-based management decisions. Meta-data of radiographically followed NFPA may help guide conservative versus operative treatment of these tumors. METHODS: We searched PubMed, Medline, Embase, and Ovid for studies with NFPA managed nonoperatively with radiographic follow-up. Studies on postoperative outcomes after NFPA resection and studies that did not delineate NFPA data from functional pituitary lesions were excluded. NFPA were divided into micro- and macroadenomas based on size at presentation. We performed a meta-analysis of aggregate data for length of follow-up, change in tumor size, rate of apoplexy, and need for resection during follow-up. RESULTS: Our database search yielded 1787 articles, of which 19 were included for final analysis. The studies included 1057 patients with NFPA followed radiographically. Macroadenomas were significantly more likely to undergo growth (34% vs. 12%; p < 0.01) or apoplexy (5% vs. < 1%; p = 0.01) compared to microadenomas. Resection was performed in 11% of all NFPA patients during follow-up regardless of size at presentation. Meta-regression showed that surgery during follow-up was associated with macroadenomas and negatively associated with microadenomas that decreased in size. CONCLUSION: Low-quality evidence suggests that NFPA classified as macroadenomas have an increased rate of growth and apoplexy during follow-up compared to microadenomas. A significant minority of all NFPA patients ultimately underwent surgery. In select patients, nonoperative management may be the appropriate strategy for NFPA. Macroadenomas may require closer follow-up.

Treatment of large infectious extracranial carotid artery pseudoaneurysms in children: a systematic review of the literature.

INTRODUCTION: Extracranial carotid artery pseudoaneurysm is a rare complication of deep neck space infection, and no evidence-based treatment guidelines are available in the literature. METHOD: To clarify the existing experience of the different treatment strategies, the authors performed a systematic literature search using the PubMed, Ovid EMBASE, and Scopus databases in accordance with PRISMA guidelines to review all reported cases of pediatric patients with infectious carotid pseudoaneurysms larger than 1 cm. RESULTS: Twenty-six patients with a median age of 4 years (range 6 months-15 years) were identified. Eighteen patients (69.2%) were treated with endovascular methods, 6 patients (23.1%) with surgical methods, 1 patient (3.8%) with a hybrid endovascular/surgical approach, and 1 patient (3.8%) with conservative management. Recurrence of the pseudoaneurysm occurred in 2 cases (7.7%), both of which were successfully retreated. Of the 6 patients (23.1%) who presented with pre-procedure neurologic deficits, 3 patients had complete or near complete resolution of symptoms after intervention and 3 patients had persistent deficits at last follow-up. Four patients (15.4%) experienced new neurologic deficits post-procedure that resolved at last follow-up. CONCLUSION: The endovascular treatment tends to be the preferred option to treat a large or giant infectious pseudoaneurysm of the carotid artery in the pediatric patient. However, more evidence is necessary to elucidate comparative safety and efficacy profiles of endovascular and surgical management strategies.

Brain metabolism modulates neuronal excitability in a mouse model of pyruvate dehydrogenase deficiency.

Glucose is the ultimate substrate for most brain activities that use carbon, including synthesis of the neurotransmitters glutamate and γ-aminobutyric acid via mitochondrial tricarboxylic acid (TCA) cycle. Brain metabolism and neuronal excitability are thus interdependent. However, the principles that govern their relationship are not always intuitive because heritable defects of brain glucose metabolism are associated with the paradoxical coexistence, in the same individual, of episodic neuronal hyperexcitation (seizures) with reduced basal cerebral electrical activity. One such prototypic disorder is pyruvate dehydrogenase (PDH) deficiency (PDHD). PDH is central to metabolism because it steers most of the glucose-derived flux into the TCA cycle. To better understand the pathophysiology of PDHD, we generated mice with brain-specific reduced PDH activity that paralleled salient human disease features, including cerebral hypotrophy, decreased amplitude electroencephalogram (EEG), and epilepsy. The mice exhibited reductions in cerebral TCA cycle flux, glutamate content, spontaneous, and electrically evoked in vivo cortical field potentials and gamma EEG oscillation amplitude. Episodic decreases in gamma oscillations preceded most epileptiform discharges, facilitating their prediction. Fast-spiking neuron excitability was decreased in brain slices, contributing to in vivo action potential burst prolongation after whisker pad stimulation. These features were partially reversed after systemic administration of acetate, which augmented cerebral TCA cycle flux, glutamate-dependent synaptic transmission, inhibition and gamma oscillations, and reduced epileptiform discharge duration. Thus, our results suggest that dysfunctional excitability in PDHD is consequent to reduced oxidative flux, which leads to decreased neuronal activation and impaired inhibition, and can be mitigated by an alternative metabolic substrate.