Sleep Disorders and Circadian Disruption in Huntington's Disease.

Sleep and circadian alterations are common in patients with Huntington's disease (HD). Understanding the pathophysiology of these alterations and their association with disease progression and morbidity can guide HD management. We provide a narrative review of the clinical and basic-science studies centered on sleep and circadian function on HD. Sleep/wake disturbances among HD patients share many similarities with other neurodegenerative diseases. Overall, HD patients and animal models of the disease present with sleep changes early in the clinical course of the disease, including difficulties with sleep initiation and maintenance leading to decreased sleep efficiency, and progressive deterioration of normal sleep architecture. Despite this, sleep alterations remain frequently under-reported by patients and under-recognized by health professionals. The degree of sleep and circadian alterations has not consistently shown to be CAG dose-dependent. Evidence based treatment recommendations are insufficient due to lack of well-designed intervention trials. Approaches aimed at improving circadian entrainment, such as including light therapy, and time-restricted feeding have demonstrated a potential to delay symptom progression in some basic HD investigations. Larger study cohorts, comprehensive assessment of sleep and circadian function, and reproducibility of findings are needed in future in order to better understand sleep and circadian function in HD and to develop effective treatments.

Cerebral Blood Flow of the Neonatal Brain after Hypoxic-Ischemic Injury.

OBJECTIVE: Hypoxic-ischemic encephalopathy (HIE) in infants can have long-term adverse neurodevelopmental effects and markedly reduce quality of life. Both the initial hypoperfusion and the subsequent rapid reperfusion can cause deleterious effects in brain tissue. Cerebral blood flow (CBF) assessment in newborns with HIE can help detect abnormalities in brain perfusion to guide therapy and prognosticate patient outcomes. STUDY DESIGN: The review will provide an overview of the pathophysiological implications of CBF derangements in neonatal HIE, current and emerging techniques for CBF quantification, and the potential to utilize CBF as a physiologic target in managing neonates with acute HIE. CONCLUSION: The alterations of CBF in infants during hypoxia-ischemia have been studied by using different neuroimaging techniques, including nitrous oxide and xenon clearance, transcranial Doppler ultrasonography, contrast-enhanced ultrasound, arterial spin labeling MRI, 18F-FDG positron emission tomography, near-infrared spectroscopy (NIRS), functional NIRS, and diffuse correlation spectroscopy. Consensus is lacking regarding the clinical significance of CBF estimations detected by these different modalities. Heterogeneity in the imaging modality used, regional versus global estimations of CBF, time for the scan, and variables impacting brain perfusion and cohort clinical characteristics should be considered when translating the findings described in the literature to routine practice and implementation of therapeutic interventions. KEY POINTS: · Hypoxic-ischemic injury in infants can result in adverse long-term neurologic sequelae.. · Cerebral blood flow is a useful biomarker in neonatal hypoxic-ischemic injury.. · Imaging modality, variables affecting cerebral blood flow, and patient characteristics affect cerebral blood flow assessment..

Validation of Sonographic Fronto-Occipital Ratio Based on Anatomical Landmarks Compared to MR/CT-Derived Indexes in Children with Chiari II and Ventriculomegaly.

INTRODUCTION: Ultrasound (US)-based indexes such as fronto-occipital ratio (FOR) can be used to obtain an acceptable estimation of ventricular volume. Patients with colpocephaly present a unique challenge due to the shape of their ventricles. In the present study, we aimed to evaluate the validity and reproducibility of the modified US-FOR index in children with Chiari II-related ventriculomegaly. METHODS: In this retrospective study, we evaluated Chiari II patients younger than 1 year who underwent head US and MR or CT scans for ventriculomegaly evaluation. MR/CT-based FOR was measured in the axial plane by identifying the widest diameter of frontal horns, occipital horns, and the interparietal diameter (IPD). US-based FOR (US-FOR) was measured using the largest diameter based on the following landmarks: frontal horn and IPD in the coronal plane at the level of the foramen of Monro, IPD just superior to the Sylvian fissures, and occipital horn posterior to the thalami and inferior to the superior margins of the thalami. Intraclass correlation coefficients (ICCs) were used to evaluate inter-rater reliability, and Pearson correlation coefficients and Bland-Altman plots were applied to assess agreement between US and other two modalities. RESULTS: Sixty-three paired US and MR/CT exams were assessed for agreement between US-FOR and MR/CT-FOR measurements. ICC showed an excellent inter-rater reliability for US-FOR (ICC = 0.99, p < 0.001) and MR/CT-FOR (ICC = 0.99, p < 0.001) measurements. The mean (range) values based on US-FOR showed a slight overestimation in comparison with MR/CT-FOR (0.51 [0.36-0.68] vs. 0.46 [0.34-0.64]). The Pearson correlation coefficient showed high cross-modality agreement for the FOR index (r = 0.83, p < 0.001). The Bland-Altman plot showed excellent concordance between US-FOR and MR/CT-FOR with a bias of 0.05 (95% CI: -0.03 to 0.13). CONCLUSION: US-FOR in the coronal plane is a comparable tool for evaluating ventriculomegaly in Chiari II patients when compared with MR/CT-FOR, even in the context of colpocephaly.

Advanced Ultrasound Techniques for Differentiation of Benign Versus Malignant Thyroid Nodules: A Review.

ABSTRACT: Grayscale ultrasound (US) is decisive in stratifying which thyroid nodules benefit from fine-needle aspiration to evaluate for malignancy. Unfortunately, a significant percentage of nodules remain indeterminate.Herein, we review the clinical considerations and diagnostic accuracy of advanced US, Doppler US, contrast-enhanced US, and US elastography techniques in the evaluation of indeterminate nodules.We conclude that these techniques may be used in combination with grayscale US to improve the assessment of lesion vascularity and tissue property.

Cerebral Pulsed Arterial Spin Labeling Perfusion Weighted Imaging Predicts Language and Motor Outcomes in Neonatal Hypoxic-Ischemic Encephalopathy.

Rationale and Objectives: To compare cerebral pulsed arterial spin labeling (PASL) perfusion among controls, hypoxic ischemic encephalopathy (HIE) neonates with normal conventional MRI(HIE/MRI⊕), and HIE neonates with abnormal conventional MRI(HIE/MRI⊖). To create a predictive machine learning model of neurodevelopmental outcomes using cerebral PASL perfusion. Materials and Methods: A total of 73 full-term neonates were evaluated. The cerebral perfusion values were compared by permutation test to identify brain regions with significant perfusion changes among 18 controls, 40 HIE/MRI⊖ patients, and 15 HIE/MRI⊕ patients. A machine learning model was developed to predict neurodevelopmental outcomes using the averaged perfusion in those identified brain regions. Results: Significantly decreased PASL perfusion in HIE/MRI⊖ group, when compared with controls, were found in the anterior corona radiata, caudate, superior frontal gyrus, precentral gyrus. Both significantly increased and decreased cerebral perfusion changes were detected in HIE/MRI⊕ group, when compared with HIE/MRI⊖ group. There were no significant perfusion differences in the cerebellum, brainstem and deep structures of thalamus, putamen, and globus pallidus among the three groups. The machine learning model demonstrated significant correlation (p < 0.05) in predicting language(r = 0.48) and motor(r = 0.57) outcomes in HIE/MRI⊖ patients, and predicting language(r = 0.76), and motor(r = 0.53) outcomes in an additional group combining HIE/MRI⊖ and HIE/MRI⊕. Conclusion: Perfusion MRI can play an essential role in detecting HIE regardless of findings on conventional MRI and predicting language and motor outcomes in HIE survivors. The perfusion changes may also reveal important insights into the reperfusion response and intrinsic autoregulatory mechanisms. Our results suggest that perfusion imaging may be a useful adjunct to conventional MRI in the evaluation of HIE in clinical practice.

Emerging Roles of PET/MR in the Pediatric Hospital.

Add "improving" before "detection"? PET/MR is beneficial particularly in pediatric patients who undergo recurrent imaging, such as those with cancer or chronic inflammatory disease. PET/MR has advantages compared with PET/computed tomography, including decreased radiation exposure and superior characterization of soft tissue. Ongoing challenges include reducing examination duration and costs and detection of pulmonary lesions. Accepted clinical applications of PET/MR in pediatric patients are evaluation of epileptic foci and diagnosis, staging, and follow-up of solid tumors. PET/MR also may have a role in diagnosis and management of infectious and inflammatory conditions relevant to the pediatric population, including osteomyelitis and Crohn disease.

18-F-L 3,4-Dihydroxyphenylalanine PET/Computed Tomography in the Management of Congenital Hyperinsulinism.

Congenital hyperinsulinism (HI) is the most common cause of persistent hypoglycemia in neonates and infants. Several genetic mutations have been identified and are associated with 2 distinct histopathologic forms of disease: diffuse and focal. Targeted clinical evaluation to distinguish medically treatable disease from disease requiring surgical management can prevent life-threatening complications. Detection and localization of a surgically curable focal lesion using PET imaging with 18-F-L 3,4-dihydroxyphenylalanine ([18F]-FDOPA) has become standard of care. This article provides guidelines for the selection of patients who can benefit from [18F]-FDOPA-PET/computed tomography and protocols and tips used to diagnose a focal lesion of HI.

Clinical pediatric positron emission tomography/magnetic resonance program: a guide to successful implementation.

Children with malignancies undergo recurrent imaging as part of tumor diagnosis, staging and therapy response assessment. Simultaneous positron emission tomography (PET) and magnetic resonance (MR) allows for decreased radiation exposure and acts as a one-stop shop for disease in which MR imaging is required. Nevertheless, PET/MR is still less readily available than PET/CT across institutions. This article serves as a guide to successful implementation of a clinical pediatric PET/MR program based on our extensive clinical experience. Challenges include making scanners more affordable and increasing patient throughput by decreasing total scan time. With improvements in workflow and robust acquisition protocols, PET/MR imaging is expected to play an increasingly important role in pediatric oncology.

Imaging surveillance for children with predisposition to renal tumors.

Effective surveillance is necessary for early detection of tumors in children with cancer predisposition syndromes. Instituting a surveillance regimen in children comes with practical challenges that include determining imaging modality and timing, and considering cost efficiency, accessibility, and the significant consequences of false-positive and false-negative results. To address these challenges, the American Association for Cancer Research has recently published consensus recommendations that focus on surveillance of cancer predisposition syndromes in children. This review condenses the imaging surveillance recommendations for syndromes that carry a predisposition to renal tumors in childhood, and includes summaries of the predisposition syndromes and discussion of considerations of available imaging modalities.

Whole-body magnetic resonance imaging of pediatric cancer predisposition syndromes: special considerations, challenges and perspective.

Cancer predisposition syndromes increase the incidence of tumors during childhood and are associated with significant morbidity and mortality. Imaging is paramount for ensuring early detection of neoplasms, impacting therapeutic interventions and potentially improving outcome. While conventional imaging techniques involve considerable exposure to ionizing radiation, whole-body MRI is a radiation-free modality that allows continuous imaging of the entire body and has increasingly gained relevance in the surveillance, diagnosis, staging and monitoring of pediatric patients with cancer predisposition syndromes. Nevertheless, widespread implementation of whole-body MRI faces several challenges as a screening tool. Some of these challenges include developing clinical indications, variability in protocol specifications, image interpretation as well as coding and billing practices. These factors impact disease management, patient and family experience and research collaborations. In this discussion we review the aforementioned special considerations and the potential direction that might help overcome these challenges and promote more widespread use of whole-body MRI in children with cancer predisposition syndromes.

Buckle fracture of the proximal tibia in children and frequency of association with trampoline and inflatable bouncer use.

BACKGROUND: Proximal tibial buckle fractures are often called "trampoline fractures," but mechanisms are more varied. OBJECTIVE: To assess the frequency of trampoline or bouncer etiology among children with buckle fracture of the proximal tibia, characterizing demographics, alternative etiologies, and fracture patterns. MATERIALS AND METHODS: We performed retrospective chart review of mechanisms, age and gender of children with radiographs interpreted as proximal tibial buckle fracture between 2010 and 2016. Two pediatric radiologists assessed presence of cortical impaction, cortical break, increased anterior scoop deformity, and oblique extension of fracture toward the physis. We studied the associations among demographics, etiology and fracture appearance using analysis of variance and chi-square/Fisher exact tests. RESULTS: We identified 145 exams interpreted as proximal tibial buckle fracture (median age 34 months, 64% girls). Bouncing surface was the most common mechanism (44%), and 80% of those cases reported multiple people on the bouncing surface. Falls were the second most common mechanism (30%). Children injured while bouncing were older (median 41 months) than others (median 21 months, P<0.005) and more likely to have oblique extension of fracture toward the physis (P<0.05). Buckle deformity was associated with a younger age (F=8.67; P<0.01), while oblique extension to the physis and concurrent fibula fracture were associated with older age (F=18.62, P<0.001; and F=8.02, P<0.01, respectively). CONCLUSION: Trampoline use was the most common single mechanism of injury in children with proximal tibial fracture interpreted as buckle deformity. However, non-bouncing mechanisms were overall more common and occurred in a younger age group at risk for "toddler fractures."

Bedside contrast-enhanced ultrasound diagnosing cessation of cerebral circulation in a neonate: A novel bedside diagnostic tool.

Imaging diagnosis of brain death is performed with either four-vessel cerebral angiography or radionuclide cerebral blood flow studies. Unfortunately, timely performance of either study at a critically ill period is not only cumbersome but not feasible in many cases. We present a case of a 6-month-old male three hours status post-cardiac arrest of unknown etiology who underwent contrast-enhanced ultrasound (CEUS) for diagnosis of near absent perfusion, or near brain death. The patient passed away 30 minutes after the exam and clinical diagnosis of brain death was confirmed. The case report highlights the utility of CEUS for diagnosis of brain death. This can have significant clinical implications in neonates who may not be eligible for commonly used, cumbersome radiologic studies for diagnosis of brain death.

Does non-erosive rheumatoid arthritis exist? A cross-sectional analysis and a systematic literature review.

OBJECTIVE: To evaluate the prevalence and factors associated with non-erosive rheumatoid arthritis (RA). METHODS: First, a cross-sectional analytical study was performed. Non-erosive disease, defined as the absence of any erosion on X-rays after 5 years of RA, was evaluated in 500 patients. Further and additional evaluations including ultrasonography (US) and computed tomography (CT) were performed in those patients meeting the eligibility criteria. The Spearman correlation coefficient, kappa analysis, and Kendall׳s W test were used to analyze the data. Second, a systematic literature review (SLR) was performed following the PRISMA guidelines. RESULTS: Of a total of 40 patients meeting the eligibility criteria for non-erosive RA, eight patients were confirmed to have non-erosive RA by the three methods. A positive correlation between non-erosive RA and shorter disease duration, antinuclear antibodies positivity, lower rheumatoid factor (RF) and C-reactive protein titers, lower global visual analog scale values, toxic exposures, and lower disease activity-(RAPID3) was found. In addition, an inverse correlation with anticyclic citrullinated peptide antibodies (ACPA) positivity and medication use was observed. From the SLR, it was corroborated that factors associated with this subphenotype were shorter disease duration, younger disease onset, negative ACPA and RF titers, low cytokine levels, and some genetic markers. CONCLUSION: Non-erosive RA is rare, occurring in less than 2% of cases. These findings improve on the understanding of RA patients who present without erosions and are likely to have less severe disease.