Several inflammatory cytokines, most notably tumor necrosis factor (TNF) and IL-1, induce anorexia and loss of lean body mass, common manifestations of acute and chronic inflammatory conditions. In C57BL/6 female mice, the administration of TNF, IL-1, and, to a lesser extent, leukemia inhibitory factor (LIF), produced a prompt and dose-dependent increase in serum leptin levels and leptin mRNA expression in fat. IL-10, IL-4, ciliary neurotrophic factor, and IL-2, cytokines not known to induce anorexia or decrease food intake, had no effect on leptin gene expression or serum leptin levels. After administration of Escherichia coli lipopolysaccharide (LPS), leptin gene expression and leptin levels were increased. These findings suggest that leptin levels may be one mechanism by which anorexia is induced during acute inflammatory conditions.

Analysis of results after various treatments indicates that for symptomatic lesions, therapies that reverse intraaneurysmal blood flow and augment distal cerebral perfusion are associated with better outcomes than other strategies, including conservative management. Based on the spectrum of clinical, pathological, neuroimaging, and intraoperative findings, dissection is proposed as the underlying cause of these lesions.

Moyamoya disease is a disorder characterized by bilateral progressive steno-occlusion of the terminal internal carotid arteries with associated development of a fragile network of basal collateral vessels. It most commonly presents in children, but is also frequently seen in adults, especially in the third or fourth decade of life. Adults afflicted with this disease have very different clinical characteristics as compared with children. For example, adults more commonly present with hemorrhage than cerebral ischemia, while children present with cerebral ischemia nearly 75% of the time and very rarely present with hemorrhage. This significantly impacts treatment considerations for the adult-onset moyamoya patient, as cerebral revascularization, though well accepted in the context of cerebral ischemia, is relatively controversial for the prevention of rehemorrhage. The purpose of this article is to review the pertinent general features of moyamoya disease, examine the clinical characteristics associated with the adult-onset form of this disease, and provide a detailed discussion regarding the indications, operative techniques, and outcomes of direct and indirect revascularization surgical procedures.

Care for US military personnel with combat-related concussive traumatic brain injury (TBI) has substantially changed in recent years, yet trends in clinical outcomes remain largely unknown. Our prospective longitudinal studies of US military personnel with concussive TBI from 2008-2013 at Landstuhl Regional Medical Center in Germany and twp sites in Afghanistan provided an opportunity to assess for changes in outcomes over time and analyze correlates of overall disability. We enrolled 321 active-duty US military personnel who sustained concussive TBI in theater and 254 military controls. We prospectively assessed clinical outcomes 6-12 months later in 199 with concussive TBI and 148 controls. Global disability, neurobehavioral impairment, depression severity, and post-traumatic stress disorder (PTSD) severity were worse in concussive TBI groups in comparison with controls in all cohorts. Global disability primarily reflected a combination of work-related and nonwork-related disability. There was a modest but statistically significant trend toward less PTSD in later cohorts. Specifically, there was a decrease of 5.9 points of 136 possible on the Clinician Administered PTSD Scale (-4.3%) per year (95% confidence interval, 2.8-9.0 points, p = 0.0037 linear regression, p = 0.03 including covariates in generalized linear model). No other significant trends in outcomes were found. Global disability was more common in those with TBI, those evacuated from theater, and those with more severe depression and PTSD. Disability was not significantly related to neuropsychological performance, age, education, self-reported sleep deprivation, injury mechanism, or date of enrollment. Thus, across multiple cohorts of US military personnel with combat-related concussion, 6-12 month outcomes have improved only modestly and are often poor. Future focus on early depression and PTSD after concussive TBI appears warranted. Adverse outcomes are incompletely explained, however, and additional studies with prospective collection of data on acute injury severity and polytrauma, as well as reduced attrition before follow-up will be required to fully address the root causes of persistent disability after wartime injury.

A high percentage of LC/A medulloblastomas arise within a background of typical medulloblastomas or medullomyoblastomas. As is the case in conventional medulloblastomas, the presence of 17q is a common early tumorigenic event; however, in a significant percentage of specimens there is also evidence of aneuploidy and/or amplification of c-myc. These findings indicate that LC/A morphological characteristics reflect a more advanced tumor stage than that found in pure medulloblastomas or in typical medullomyoblastomas.

High rates of adverse outcomes have been reported following blast-related concussive traumatic brain injury in US military personnel, but the extent to which such adverse outcomes can be predicted acutely after injury is unknown. We performed a prospective, observational study of US military personnel with blast-related concussive traumatic brain injury (n = 38) and controls (n = 34) enrolled between March and September 2012. Importantly all subjects returned to duty and did not require evacuation. Subjects were evaluated acutely 0-7 days after injury at two sites in Afghanistan and again 6-12 months later in the United States. Acute assessments revealed heightened post-concussive, post-traumatic stress, and depressive symptoms along with worse cognitive performance in subjects with traumatic brain injury. At 6-12 months follow-up, 63% of subjects with traumatic brain injury and 20% of controls had moderate overall disability. Subjects with traumatic brain injury showed more severe neurobehavioural, post-traumatic stress and depression symptoms along with more frequent cognitive performance deficits and more substantial headache impairment than control subjects. Logistic regression modelling using only acute measures identified that a diagnosis of traumatic brain injury, older age, and more severe post-traumatic stress symptoms provided a good prediction of later adverse global outcomes (area under the receiver-operating characteristic curve = 0.84). Thus, US military personnel with concussive blast-related traumatic brain injury in Afghanistan who returned to duty still fared quite poorly on many clinical outcome measures 6-12 months after injury. Poor global outcome seems to be largely driven by psychological health measures, age, and traumatic brain injury status. The effects of early interventions and longer term implications of these findings are unknown.

Background and Purpose: Stent-assisted coil embolization using the new generation Neuroform Atlas Stent System has shown promising safety and efficacy. The primary study results of the anterior circulation aneurysm cohort of the treatment of wide-neck, saccular, intracranial, aneurysms with the Neuroform Atlas Stent System (ATLAS trial [Safety and Effectiveness of the Treatment of Wide Neck, Saccular Intracranial Aneurysms With the Neuroform Atlas Stent System]) are presented. Methods: ATLAS IDE trial (Investigational Device Exemption) is a prospective, multicenter, single-arm, open-label study of wide-neck (neck ≥4 mm or dome-to-neck ratio <2) intracranial aneurysms in the anterior circulation treated with the Neuroform Atlas Stent and approved coils. The primary efficacy end point was complete aneurysm occlusion (Raymond-Roy class 1) on 12-month angiography, in the absence of retreatment or parent artery stenosis (>50%) at the target location. The primary safety end point was any major stroke or ipsilateral stroke or neurological death within 12 months. Adjudication of the primary end points was performed by an independent Imaging Core Laboratory and the Clinical Events Committee. Results: A total of 182 patients with wide-neck anterior circulation aneurysms at 25 US centers were enrolled. The mean age was 60.3±11.4 years, 73.1% (133/182) women, and 80.8% (147/182) white. Mean aneurysm size was 6.1±2.2 mm, mean neck width was 4.1±1.2 mm, and mean dome-to-neck ratio was 1.2±0.3. The most frequent aneurysm locations were the anterior communicating artery (64/182, 35.2%), internal carotid artery ophthalmic artery segment (29/182, 15.9%), and middle cerebral artery bifurcation (27/182, 14.8%). Stents were placed in the anticipated anatomic location in all patients. The study met both primary safety and efficacy end points. The composite primary efficacy end point of complete aneurysm occlusion (Raymond-Roy 1) without parent artery stenosis or aneurysm retreatment was achieved in 84.7% (95% CI, 78.6%–90.9%) of patients. Overall, 4.4% (8/182, 95% CI, 1.9%–8.5%) of patients experienced a primary safety end point of major ipsilateral stroke or neurological death. Conclusions: In the ATLAS IDE anterior circulation aneurysm cohort premarket approval study, the Neuroform Atlas stent with adjunctive coiling met the primary end points and demonstrated high rates of long-term complete aneurysm occlusion at 12 months, with 100% technical success and <5% morbidity. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02340585.

Objective: To evaluate whether diffusion tensor imaging (DTI) will noninvasively reveal white matter changes not present on conventional MRI in acute blast-related mild traumatic brain injury (mTBI) and to determine correlations with clinical measures and recovery.Methods: Prospective observational study of 95 US military service members with mTBI enrolled within 7 days from injury in Afghanistan and 101 healthy controls. Assessments included Rivermead Post-Concussion Symptoms Questionnaire (RPCSQ), Post-Traumatic Stress Disorder Checklist Military (PCLM), Beck Depression Inventory (BDI), Balance Error Scoring System (BESS), Automated Neuropsychological Assessment Metrics (ANAM), conventional MRI, and DTI.Results: Significantly greater impairment was observed in participants with mTBI vs controls: RPCSQ (19.7 6 12.9 vs 3.6 6 7.1, p , 0.001), PCLM (32 6 13.2 vs 20.9 6 7.1, p , 0.001), BDI (7.4 6 6.8 vs 2.5 6 4.9, p , 0.001), and BESS ( Conclusions: Somatic, behavioral, and cognitive symptoms and performance deficits are substantially elevated in acute blast-related mTBI. Postconcussive symptoms and performance on measures of posttraumatic stress disorder, depression, and neurocognitive performance at initial presentation correlate with return-to-duty time. Although changes in fractional anisotropy are uncommon and subtle, DTI is more sensitive than conventional MRI in imaging white matter integrity in blast-related mTBI acutely. Blast-related mild traumatic brain injury (mTBI) has emerged as one of the most prevalent war injuries sustained by service members in the conflicts in Afghanistan and Iraq.