Incomplete partition type II in its various manifestations: isolated, in association with EVA, syndromic, and beyond; a multicentre international study.

PURPOSE: Incomplete partition type II (IP-II) is characterized by specific histological features and radiological appearance. It may occur in isolation or in association with an enlarged vestibular aqueduct (EVA). Among those with IP-II and EVA, a subset has a diagnosis of Pendred syndrome. This study aimed to explore the prevalence of isolated IP-II, IP-II with EVA, and cases with a genetic or syndromic basis in our cohort. METHODS: From a large, multicentre database of dysplastic cochleae (446 patients, 892 temporal bones), those with imaging features of IP-II were examined in detail, including whether there was a genetic or syndromic association. RESULTS: A total of 78 patients with IP-II were identified. Among these, 55 patients had bilateral IP-II and EVA (only 12 with typical Mondini triad), 8 with bilateral IP-II and normal VA, 2 with bilateral IP-II and unilateral EVA, and 13 with unilateral IP-II (9 with unilateral EVA). Among the group with bilateral IP-II and bilateral EVA in whom genetic analysis was available, 14 out of 29 (48%) had SLC26A4 mutations and a diagnosis of Pendred syndrome, 1 had a FOXI1 mutation, and a few other genetic abnormalities; none had KCNJ10 pathogenic variants. CONCLUSION: Bilateral IP-II-bilateral EVA may be seen in the context of Pendred syndrome (SLC26A4 or FOXI1 mutations) but, in the majority of our cohort, no genetic abnormalities were found, suggesting the possibility of unknown genetic associations. IP-II in isolation (without EVA) is favored to be genetic when bilateral, although the cause is often unknown.

Cannabidiol attenuates seizure susceptibility and behavioural deficits in adult CDKL5R59X knock-in mice.

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is caused by a loss-of-function mutation in CDKL5 gene, encoding a serine-threonine kinase highly expressed in the brain. CDD manifests with early-onset epilepsy, autism, motor impairment and severe intellectual disability. While there are no known treatments for CDD, the use of cannabidiol has recently been introduced into clinical practice for neurodevelopmental disorders. Given the increased clinical utilization of cannabidiol, we examined its efficacy in the CDKL5R59X knock-in (R59X) mice, a CDD model based on a human mutation that exhibits both lifelong seizure susceptibility and behavioural deficits. We found that cannabidiol pre-treatment rescued the increased seizure susceptibility in response to the chemoconvulsant pentylenetetrazol (PTZ), attenuated working memory and long-term memory impairments, and rescued social deficits in adult R59X mice. To elucidate a potential mechanism, we compared the developmental hippocampal and cortical expression of common endocannabinoid (eCB) targets in R59X mice and their wild-type littermates, including cannabinoid type 1 receptor (CB1R), transient receptor potential vanilloid type 1 (TRPV1) and 2 (TRPV2), G-coupled protein receptor 55 (GPR55) and adenosine receptor 1 (A1R). Many of these eCB targets were developmentally regulated in both R59X and wild-type mice. In addition, adult R59X mice demonstrated significantly decreased expression of CB1R and TRPV1 in the hippocampus, and TRPV2 in the cortex, while TRPV1 was increased in the cortex. These findings support the potential for dysregulation of eCB signalling as a plausible mechanism and therapeutic target in CDD, given the efficacy of cannabidiol to attenuate hyperexcitability and behavioural deficits in this disorder.

Utility of Acute and Subacute Blood Biomarkers to Assist Diagnosis in CT-Negative Isolated Mild Traumatic Brain Injury.

BACKGROUND AND OBJECTIVES: Blood biomarkers glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) have recently been Food and Drug Administration approved as predictors of intracranial lesions on CT after mild traumatic brain injury (mTBI). However, most cases with mTBI are CT negative, and no biomarkers are approved to assist diagnosis in these individuals. In this study, we aimed to determine the optimal combination of blood biomarkers to assist mTBI diagnosis in otherwise healthy adults younger than 50 years presenting to an emergency department within 6 hours of injury. To further understand the utility of biomarkers, we assessed how biological sex, presence or absence of loss of consciousness and/or post-traumatic amnesia (LOC/PTA), and delayed presentation affected classification performance. METHODS: Blood samples, symptom questionnaires, and cognitive tests were prospectively conducted for participants with mTBI recruited from The Alfred Hospital Level 1 Emergency & Trauma Center and uninjured controls. Follow-up testing was conducted at 7 days. Simoa quantified plasma GFAP, UCH-L1, tau, neurofilament light chain (NfL), interleukin (IL)-6, and IL-1ß. Area under the receiver operating characteristic (AUC) analysis assessed classification accuracy for diagnosed mTBI, and logistic regression models identified optimal biomarker combinations. RESULTS: Plasma IL-6 (AUC 0.91, 95% CI 0.86-0.96), GFAP (AUC 0.85, 95% CI 0.78-0.93), and UCH-L1 (AUC 0.79, 95% CI 0.70-0.88) best differentiated mTBI (n = 74) from controls (n = 44) acutely (<6 hours), with NfL (AUC 0.81, 95% CI 0.72-0.90) the only marker to have such utility subacutely (7 days). Biomarker performance was similar between sexes and for participants with and without LOC/PTA, with the exception at 7 days, where GFAP and IL-6 retained some utility in female participants (GFAP: AUC 0.71, 95% CI 0.55-0.88; IL-6: AUC 0.71, 95% CI 0.55-0.87) and in those with LOC/PTA (GFAP: AUC 0.73, 95% CI 0.59-0.86; IL-6: AUC 0.71, 95% CI 0.57-0.84). Acute IL-6 (R 2 = 0.50, 95% CI 0.34-0.64) outperformed GFAP and UCH-L1 combined (R 2 = 0.35, 95% CI 0.17-0.50), with the best acute model featuring GFAP and IL-6 (R 2 = 0.54, 95% CI 0.34-0.68). DISCUSSION: These findings indicate that adding IL-6 to a panel of brain-specific proteins such as GFAP and UCH-L1 might assist in the acute diagnosis of mTBI in adults younger than 50 years. Multiple markers had high classification accuracy in participants without LOC/PTA. When compared with the best-performing acute markers, subacute measures of plasma NfL resulted in minimal reduction in classification accuracy. Future studies will investigate the optimal time frame over which plasma IL-6 might assist diagnostic decisions and how extracranial trauma affects utility.

Common Neck and Otomastoid Infections in Children.

Neck infections are common in children, though the clinical presentation is often vague and nonspecific. Therefore, imaging plays a key role in identifying the site and extent of infections, evaluating for potentially drainable collections, and assessing for airway and vascular complications. This review focuses on imaging features associated with common and characteristic neck infections in children to include tonsillar, retropharyngeal, and otomastoid infections; suppurative adenopathy; superimposed inflammation or infection of congenital cystic lesions; and Lemierre syndrome.

Within subject rise in serum TNFα to IL-10 ratio is associated with poorer attention, decision-making and working memory in jockeys.

Jockeys work in high-risk environments that rely heavily on attention- and decision-making to perform well and safely. Workplace stress literature has often overlooked the impact of stress on cognition, and designs that include physiological measures are rare. This study assessed the prospective concurrent relationships between workplace stress, depression symptoms and low-grade inflammation with cognitive performance among professional jockeys. Professional jockeys (N = 35, Mage = 32.29) provided information on workplace stress and depression symptoms, with serum levels of inflammatory cytokines (IL-6, IL-10, TNFα) and cytokine balance (IL-6: IL-10, TNFα: IL-10) quantified with SIMOA, and cognitive performance with CogSport computer-based testing battery. These measures were repeated after a twelve-month interval. Increased workplace stress between testing intervals was associated to an increased cytokine imbalance (ß = 0.447, p = .015) after controlling for age and gender. Increases in cytokine imbalance occurred in unison with decreases in attention (ß = 0.516, p = .002), decision-making (ß = 0.452, p = .009) and working memory (ß = 0.492, p = .004). These preliminary findings suggest the underlying mechanisms linking workplace stress and reduced cognitive performance may be influenced by measures of low-grade inflammation and specifically a cytokine imbalance. Our findings suggest a measure of cytokine balance may explain the heterogenous findings in previous studies that have focussed solely on the association of workplace stress with pro-inflammatory cytokines. Future work is needed however, to provide a broader evidence-base for our claims to better inform designs to intervene in the higher workplace stress-poorer cognition relationship.

The effect of resuscitative endovascular balloon occlusion of the aorta, partial aortic occlusion and aggressive blood transfusion on traumatic brain injury in a swine multiple injuries model.

BACKGROUND: Despite clinical reports of poor outcomes, the degree to which resuscitative endovascular balloon occlusion of the aorta (REBOA) exacerbates traumatic brain injury (TBI) is not known. We hypothesized that combined effects of increased proximal mean arterial pressure (pMAP), carotid blood flow (Qcarotid), and intracranial pressure (ICP) from REBOA would lead to TBI progression compared with partial aortic occlusion (PAO) or no intervention. METHODS: Twenty-one swine underwent a standardized TBI via computer Controlled cortical impact followed by 25% total blood volume rapid hemorrhage. After 30 minutes of hypotension, animals were randomized to 60 minutes of continued hypotension (Control), REBOA, or PAO. REBOA and PAO animals were then weaned from occlusion. All animals were resuscitated with shed blood via a rapid blood infuser. Physiologic parameters were recorded continuously and brain computed tomography obtained at specified intervals. RESULTS: There were no differences in baseline physiology or during the initial 30 minutes of hypotension. During the 60-minute intervention period, REBOA resulted in higher maximal pMAP (REBOA, 105.3 ± 8.8; PAO, 92.7 ± 9.2; Control, 48.9 ± 7.7; p = 0.02) and higher Qcarotid (REBOA, 673.1 ± 57.9; PAO, 464.2 ± 53.0; Control, 170.3 ± 29.4; p < 0.01). Increases in ICP were greatest during blood resuscitation, with Control animals demonstrating the largest peak ICP (Control, 12.8 ± 1.2; REBOA, 5.1 ± 0.6; PAO, 9.4 ± 1.1; p < 0.01). There were no differences in the percentage of animals with hemorrhage progression on CT (Control, 14.3%; 95% confidence interval [CI], 3.6-57.9; REBOA, 28.6%; 95% CI, 3.7-71.0; and PAO, 28.6%; 95% CI, 3.7-71.0). CONCLUSION: In an animal model of TBI and shock, REBOA increased Qcarotid and pMAP, but did not exacerbate TBI progression. PAO resulted in physiology closer to baseline with smaller increases in ICP and pMAP. Rapid blood resuscitation, not REBOA, resulted in the largest increase in ICP after intervention, which occurred in Control animals. Continued studies of the cerebral hemodynamics of aortic occlusion and blood transfusion are required to determine optimal resuscitation strategies for multi-injured patients.

The transclival artery: a variant persistent carotid-basilar arterial anastomosis not previously reported.

During embryological development, primitive anastomoses exist between the carotid and vertebrobasilar arteries. These anastomoses typically regress or are incorporated into the developing vasculature. Persistence beyond fetal development, however, results in vascular anomalies that alter haemodynamic flow with a predisposition for aneurysm formation. The carotid-vertebrobasilar anastomoses mirror the primitive communications and include (from most to least common) the trigeminal, hypoglossal, proatlantal and otic arteries. The hypoglossal and proatlantal variants extend through the hypoglossal canal or foramen magnum, respectively. We present a previously undescribed variant of these persistent fetal anastomoses, the 'transclival artery', which courses through its own transclival skull base canal/foramen.

The Preoperative Sinus CT: Avoiding a "CLOSE" Call with Surgical Complications.

Although functional endoscopic sinus surgery is an effective means of treating patients with recurrent and refractory sinusitis, the procedure is not without risk of serious surgical complications. Preoperative computed tomography (CT) affords radiologists the opportunity to prospectively identify anatomic variants that predispose patients to major surgical complications; however, these critical variants are not consistently evaluated or documented on preoperative imaging reports. The purpose of this review is to illustrate important anatomic variants and landmarks on the preoperative sinus CT with a focus on those that predispose patients to surgical complications. These critical variants and landmarks can be quickly recalled and incorporated into the preoperative imaging report through the use of the mnemonic "CLOSE": Cribriform plate, Lamina papyracea, Onodi cell, Sphenoid sinus pneumatization, and (anterior) Ethmoidal artery. This approach will greatly enhance the value of the preoperative imaging report for referring otolaryngologists and help reduce the risk of surgical complications. (©) RSNA, 2016 Online supplemental material is available for this article.

Clinical indicators of radiographic findings in patients with suspected community-acquired pneumonia: who needs a chest x-ray?

PURPOSE: To develop a prediction rule for the use of chest radiographs in evaluating for community-acquired pneumonia (CAP) based on presenting signs and symptoms. PATIENTS AND METHODS: Adult patients with acute respiratory symptoms and positive chest radiographic results from October 2004 through April 2005 were enrolled as positive cases (n = 350). An equal number of age-matched controls with acute respiratory symptoms but negative radiographic results were included. Data analyses were performed on the 6 most common individual clinical indicators (cough, sputum production, fever, tachycardia, tachypnea, and abnormal physical examination results). Additional analyses were performed for any vital sign abnormality and for the presence of vital sign or physical examination abnormalities. RESULTS: The data show that vital sign and physical examination findings are useful screening parameters for CAP, demonstrating a sensitivity of 95%, a specificity of 56%, and an odds ratio of 24.9 [corrected] in the presence of vital sign or physical examination abnormalities. In light of these results, the authors developed a prediction rule for low-risk patients with reliable follow-up, which states that chest radiographs are unnecessary in the presence of normal vital signs and physical examination findings. CONCLUSION: The data suggest that chest radiographs are unnecessary in patients with acute respiratory symptoms who present with normal vital signs and physical examination findings. Because approximately 5% of cases would be missed, however, these criteria are useful only for patients with reliable follow-up and a low likelihood of morbidity if CAP is not detected initially.