Pediatric Leigh Syndrome: Neuroimaging Features and Genetic Correlations.

The neurodiagnostic criteria of Leigh syndrome have not yet been clearly redefined based on the expanding of molecular etiologies. We aimed to analyze 20 years of clinical, genetic, and magnetic resonance studies from our Leigh syndrome cohort to provide a detailed description of central nervous system lesions in Leigh syndrome and their biological evolution in view of their genetic and clinical findings. Our study adds new neurodiagnostic insights to the current knowledge of Leigh syndrome, including association with overlapping syndromes, and the correlation of pathogenic genetic variants with neuroimaging phenotypes. ANN NEUROL 2020;88:218-232.

How to read a fetal magnetic resonance image 101.

Accurate antenatal diagnosis is essential for planning appropriate pregnancy management and improving perinatal outcomes. The provision of information vital for prognostication is a crucial component of prenatal imaging, and this can be enhanced by the use of fetal MRI. Image acquisition, interpretation and reporting of a fetal MR study can be daunting to the individual who has encountered few or none of these examinations. This article provides the radiology trainee with a general approach to interpreting a fetal MRI. The authors review the added value of prenatal MRI in the overall assessment of fetal wellbeing, discuss MRI protocols and techniques, and review the normal appearance of maternal and fetal anatomy. The paper concludes with a sample template for structured reporting, to serve as a checklist and guideline for reporting radiologists.

Congenital Zika Virus Infection Induces Severe Spinal Cord Injury.

We report 2 fatal cases of congenital Zika virus (ZIKV) infection. Brain anomalies, including atrophy of the cerebral cortex and brainstem, and cerebellar aplasia were observed. The spinal cord showed architectural distortion, severe neuronal loss, and microcalcifications. The ZIKV proteins and flavivirus-like particles were detected in cytoplasm of spinal neurons, and spinal cord samples were positive for ZIKV RNA.

Association of periventricular nodular heterotopia with posterior fossa cyst: a prenatal case series.

OBJECTIVE: The association of periventricular nodular heterotopia (PVNH) with posterior fossa cyst (PFC) is documented after birth. We report this association in a series of fetuses. METHODS: Eleven cases (7 females) of PVNH and PFC diagnosed at prenatal imaging were collected in this retrospective multicenter study. The patients were referred to tertiary centers for targeted ultrasonography (US) and Magnetic Resonance Imaging (MRI) following detection of PFC on routine US. Mutations of the filamin A gene (FLNA) were searched for (n = 6). Maternal brain MRI was performed (n = 8). Post-mortem or postnatal data were recorded. RESULTS: Targeted US was performed at a mean gestational age of 29 (range; 23-35) weeks and identified PVNH in 4 cases. At MRI, performed at a mean gestational age of 31 (range; 29-35) weeks, PVNH and PFC were visible in all cases. Those findings were confirmed by postnatal MRI (n = 3), autopsy (n = 7) and/or post-mortem MRI (n = 2) or US (n = 1). Maternal brain MRI showed PVNH in one case. A de novo FLNA mutation was found in four cases. CONCLUSION: We describe a series of PVNH and PFC in fetuses, which underlines the importance of searching for PVNH when PFC is identified at prenatal US. © 2014 John Wiley & Sons, Ltd.

Increased vertebral morphometric fracture in patients with postsurgical hypoparathyroidism despite normal bone mineral density.

BACKGROUND: The mechanism behind parathyroid hormone (PTH) activation of bone remodeling is intimately dependent on the time of exposure of bone cells to hormone levels. Sustained high PTH levels trigger catabolism, while transitory elevations induce anabolism. The effects of hypoparathyroidism (PhPT) on bone are unknown. The objective was to study the impact of PhPT on bone mineral density (BMD), on the frequency of subclinical vertebral fracture and on mandible morphometry. METHODS: The study comprised thirty-three postmenopausal women, 17 controls (CG) and 16 with PhPT (PhPTG) matched for age, weight and height. Bone mineral density (BMD) of lumbar spine, total hip and 1/3 radius, radiographic evaluation of vertebral morphometry, panoramic radiography of the mandible, and biochemical evaluation of mineral metabolism and bone remodeling were evaluated in both groups. RESULTS: There were no significant differences in lumbar spine or total hip BMD between groups. There was marked heterogeneity of lumbar spine BMD in PhPTG (high = 4, normal = 9, osteopenia = 1, and osteoporosis = 2 patients). BMD was decreased in the 1/3 radius in PhPTG P < 0.005). The PhPTG group exhibited an increased frequency of morphometric vertebral fractures and decreased mandible cortical thickness. CONCLUSION: The study suggests that vertebral fragility occurs in PhPT despite normal or even high BMD. The current results encourage further studies to evaluate the use of panoramic radiography in the identification of osteometabolic disorders, such as PhPT and the development of a more physiological treatment for PhPT.

Normocephalic Children Exposed to Maternal Zika Virus Infection Do Not Have a Higher Risk of Neurodevelopmental Abnormalities around 24 Months of Age than Unexposed Children: A Controlled Study.

Although very few controlled studies are available, in utero Zika virus (ZIKV)-exposed children are considered at risk for neurodevelopmental abnormalities. We aimed to identify whether there is an excess risk of abnormalities in non-microcephalic children born to mothers with confirmed ZIKV infection compared with ZIKV-unexposed children from the same population. In a cross-sectional study nested in two larger cohorts, we compared 324 ZIKV-exposed children with 984 unexposed controls. Outcomes were assessed using the Bayley Screening Test III applied around 24 months of age. Relative risks for classifying children as emergent or at-risk for neurodevelopmental delay in at least one of five domains were calculated, adjusting for covariates. In four of the five domains, few children were classified as emergent (4-12%) or at-risk (0.3-2.16%) but for the expressive communication domain it was higher for emergent (19.1-42.9%). ZIKV-exposed children were half as frequently classified as emergent, including after adjusting for covariates [RR = 0.52 (CI 95% 0.40; 0.66)]. However, no difference was detected in the at-risk category [RR = 0.83 (CI 95% 0.48; 1.44)]. Normocephalic children exposed to the Zika virus during pregnancy do not have a higher risk of being classified as at risk for neurodevelopmental abnormalities at two years of age.

Sepsis-Related Brain MRI Abnormalities Are Associated With Mortality and Poor Neurological Outcome in Pediatric Sepsis.

BACKGROUND: It is not known whether brain magnetic resonance imaging (MRI) abnormalities in pediatric sepsis are associated with clinical outcomes. Study objectives were to (1) determine the prevalence and type of sepsis-related neuroimaging abnormalities evident on clinically indicated brain MRI in children with sepsis and (2) test the association of these abnormalities with mortality, new disability, length of stay (LOS), and MRI indication. METHODS: Retrospective cohort study of 140 pediatric patients with sepsis and a clinically indicated brain MRI obtained within 60 days of sepsis onset at a single, large academic pediatric intensive care unit (PICU). Two radiologists systematically reviewed the first post-sepsis brain MRI and determined which abnormalities were sepsis-related. Outcomes compared in patients with versus without sepsis-related MRI abnormalities. RESULTS: PICU mortality was 7%. Thirty patients had one or more sepsis-related MRI abnormality, yielding a prevalence of 21% (95% confidence interval 15%, 28%). Among those, 53% (16 of 30) had sepsis-related white matter signal abnormalities; 53% (16 of 30) sepsis-related ischemia, infarction, or thrombosis; and 27% (eight of 30) sepsis-related posterior reversible encephalopathy. Patients with one or more sepsis-related MRI abnormality had increased mortality (17% vs 5%; P = 0.04), new neurological disability at PICU discharge (32% vs 11%; P = 0.03), and longer PICU LOS (median 18 vs 11 days; P = 0.04) compared with patients without. CONCLUSIONS: In children with sepsis and a clinically indicated brain MRI, 21% had a sepsis-related MRI abnormality. Sepsis-related MRI abnormalities were associated with increased mortality, new neurological disability, and longer PICU LOS.

Disease activity index is associated with subclinical atherosclerosis in childhood-onset systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is an independent risk factor for cardiovascular events. The present study determined the prevalence of subclinical atherosclerosis in childhood-onset SLE using the carotid intima-media thickness (CIMT) measurement and investigated associations between traditional and nontraditional risk factors for atherosclerosis, such as medications, SLE Disease Activity Index - SLEDAI-2 K and SLICC-ACR damage index and CIMT. METHODS: Cross-sectional prospective study between 2017 and 2018. CIMT was assessed by ultrasonography. Data were collected by chart review, nutritional evaluation and laboratory tests and analyzed by Fisher, Wilcoxon-Mann-Whitney tests, multiple linear and log binomial regression. RESULTS: Twenty-eight patients (mean age 13.9 years, SD 3) were enrolled. The prevalence of subclinical atherosclerosis was 32% (95% CI 14.8, 49.4). The mean CIMT was 0.43 ± 0.035 mm. The most common traditional risk factors observed were dyslipidemia (82.1%), uncontrolled hypertension (14.2%), obesity (14.3%), and poor diet (78.6%). Uncontrolled hypertension (p = 0.04), proteinuria (p = 0.02), estimated glomerular filtration rate < 75 ml /min/1.73 m2 (p = 0.02) and SLEDAI-2 K > 5 (P = 0.04) were associated with subclinical atherosclerosis. SLEDAI-2 K > 5 maintained association with CIMT after adjusting for control variables. CONCLUSION: Subclinical atherosclerosis is frequently observed in cSLE, mainly in patients with moderate to severe disease activity.

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.

Tubulinopathies.

Mutations causing dysfunction of the tubulins and microtubule-associated proteins, otherwise known as tubulinopathies, are a group of recently described entities, that lead to complex brain malformations. An understanding of the fundamental principles of operation of the cytoskeleton and compounds in particular microtubules, actin, and microtubule-associated proteins, can assist in the interpretation of the imaging findings of tubulinopathies. Somewhat consistent morphological imaging patterns have been described in tubulinopathies such as dysmorphic basal ganglia-the hallmark (found in 75% of cases), callosal dysgenesis, cerebellar hypoplasia/dysplasia, and cortical malformations, most notably lissencephaly. Recognizing the common imaging phenotypes present in tubulinopathies can prove invaluable in directing the genetic workup for a patient with brain malformations.

Comparison between Graf method and pubo-femoral distance in neutral and flexion positions to diagnose developmental dysplasia of the hip.

PURPOSES: To evaluate whether the pubo-femoral distance (PFD) can be used as an accurate screening test to diagnose developmental dysplasia of the hip (DDH) in an at-risk population compared with the Graf method. Second, to determine whether PFD assessment is feasible and reproducible regardless of the observer's experience. MATERIALS AND METHODS: IRB approved this retrospective single-institution study. Written informed consent was waived. Between January 2010 and March 2012, 116 neonates at risk for DDH were included. Infants' hips were distributed into two groups according to recommendation for treatment: non-dysplastic (ND; Graf I/IIA; 211 hips; 69 females/37 males) and dysplastic hip (DH; Graf IIB/IIC/III/D/IV; 21 hips; 8 females/3 males). One resident and one experienced radiologist reviewed ultrasonography images performed in the fourth week. To compare the groups, Student's t and Mann-Whitney tests for normally and non-normally distributed covariates were performed. Accuracy of PFD to diagnose DDH was calculated. Intraclass correlation coefficient (ICC) was calculated to assess inter-observer agreement. RESULTS: Mean PFDs of ND group were 3.09mm at neutral position and 3.64mm with the hip flexed. Mean PFDs of DH group were 6.29mm and 7.59mm, respectively. Sensitivity, specificity, and accuracy of PFD were 94.4%, 93.4%, and 97.2% (cut-off=4.6mm) at neutral position and 94.4%, 89.0%, and 95.5% (cut-off=4.9mm) with hip flexed. ICCs were 0.852 and 0.864, respectively. CONCLUSIONS: PFD is comparable with Graf method, enabling physicians to differentiate patients who should undergo treatment from those who should not. PFD can be used as a screening tool for diagnosing DDH with high accuracy, even by inexperienced radiologists.

Evolving concepts in breast lobular neoplasia and invasive lobular carcinoma, and their impact on imaging methods.

Invasive lobular carcinoma (ILC) and lobular neoplasia (LN) are two distinct conditions that still pose challenges regarding to their classification, diagnosis and management. Although they share similar cellular characteristics, such as discohesive neoplastic cells and absence of e-cadherin staining, they represent completely different conditions. LN encompasses atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS), which are currently considered risk factors and non-obligatory precursors of breast neoplasia. These lesions are diagnosed as incidental findings in percutaneous biopsies or appear as non-specific clusters of punctate calcifications in mammograms. ILC is the second most common breast malignancy and has typical histological features, such as infiltrative growth and low desmoplasia. These histological features are reflected in imaging findings and constitute the reasons for typical subtle mammographic features of ILC, as architectural distortion or focal asymmetries. Ultrasonography (US) may detect almost 75 % of the ILCs missed by mammography and represents the modality of choice for guiding biopsies. Magnetic resonance imaging (MRI) exhibits a high sensitivity for the diagnosis of ILC and for detecting synchronous lesions. Teaching Points • LN includes ALH and LCIS, risk factors and non-obligatory precursors of breast cancer.• Absence of e-cadherin staining is crucial for differentiation among ductal and lobular lesions. • ILC has typical histological features, such as infiltrative growth and low desmoplasia. • Mammographic features of ILC are often subtle and reflect the histological features. • MRI exhibits a high sensitivity for the diagnosis of ILC and for detecting synchronous lesions.