Longitudinal MRI brain volume changes over one year in children with mucopolysaccharidosis types IIIA and IIIB.

OBJECTIVE: To quantify changes in segmented brain volumes over 12 months in children with mucopolysaccharidosis types IIIA and IIIB (MPS IIIA and IIIB). METHODS: In order to establish suitable outcome measures for clinical trials, twenty-five children greater than 2 years of age were enrolled in a prospective natural history study of MPS IIIA and IIIB at Nationwide Children's Hospital. Data from sedated non-contrast brain 3 T MRIs and neuropsychological measures were reviewed from the baseline visit and at 12-month follow-up. No intervention beyond standard clinical care was provided. Age- and sex-matched controls were gathered from the National Institute of Mental Health Data Archive. Automated brain volume segmentation with longitudinal processing was performed using FreeSurfer. RESULTS: Of the 25 subjects enrolled with MPS III, 17 children (4 females, 13 males) completed at least one MRI with interpretable volumetric data. The ages ranged from 2.8 to 13.7 years old (average 7.2 years old) at enrollment, including 8 with MPS IIIA and 9 with MPS IIIB. At baseline, individuals with MPS III demonstrated reduced cerebral white matter and corpus callosum volumes, but greater volumes of the lateral ventricles, cerebellar cortex, and cerebellar white matter compared to controls. Among the 13 individuals with MPS III with two interpretable MRIs, there were annualized losses or plateaus in supratentorial brain tissue volumes (cerebral cortex -42.10 ± 18.52 cm3/year [mean ± SD], cerebral white matter -4.37 ± 11.82 cm3/year, subcortical gray matter -6.54 ± 3.63 cm3/year, corpus callosum -0.18 ± 0.62 cm3/yr) and in cerebellar cortex (-0.49 ± 12.57 cm3/year), with a compensatory increase in lateral ventricular volume (7.17 ± 6.79 cm3/year). Reductions in the cerebral cortex and subcortical gray matter were more striking in individuals younger than 8 years of age. Greater cerebral cortex volume was associated with higher fine and gross motor functioning on the Mullen Scales of Early Learning, while greater subcortical gray matter volume was associated with higher nonverbal functioning on the Leiter International Performance Scale. Larger cerebellar cortex was associated with higher receptive language performance on the Mullen, but greater cerebellar white matter correlated with worse adaptive functioning on the Vineland Adaptive Behavioral Scales and visual problem-solving on the Mullen. CONCLUSIONS: Loss or plateauing of supratentorial brain tissue volumes may serve as longitudinal biomarkers of MPS III age-related disease progression compared to age-related growth in typically developing controls. Abnormally increased cerebellar white matter in MPS III, and its association with worse performance on neuropsychological measures, suggest the possibility of pathophysiological mechanisms distinct from neurodegeneration-associated atrophy that warrant further investigation.

Image-guided percutaneous removal of ballistic foreign bodies secondary to air gun injuries.

BACKGROUND: Ballistic injuries with retained foreign bodies from air guns is a relatively common problem, particularly in children and adolescents. If not removed in a timely fashion, the foreign bodies can result in complications, including pain and infection. Diagnostic methods to identify the presence of the foreign body run the entire gamut of radiology, particularly radiography, ultrasound (US) and computed tomography (CT). Removal of the foreign bodies can be performed by primary care, emergency, surgical, and radiologic clinicians, with or without imaging guidance. OBJECTIVE: To evaluate the modalities of radiologic detection and the experience of image-guided ballistic foreign body removal related to air gun injuries within the interventional radiology department of a large pediatric hospital. MATERIALS AND METHODS: A database of more than 1,000 foreign bodies that were removed with imaging guidance by the interventional radiologists at our institution was searched for ballistic foreign bodies from air guns. The location, dimensions, diagnostic modality, duration, complications and imaging modality used for removal were recorded. In addition, the use of sedation and anesthesia required for the procedures was also recorded. RESULTS: Sixty-one patients with ballistic foreign bodies were identified. All foreign bodies were metallic BBs or pellets. The age of the patients ranged from 5 to 20 years. The initial diagnostic modality to detect the foreign bodies was primarily radiography. The primary modality to assist in removal was US, closely followed by fluoroscopy. For the procedure, 32.7% of the patients required some level of sedation. Only two patients had an active infection at the time of the removal. The foreign bodies were primarily in the soft tissues; however, successful removal was also performed from intraosseous, intraglandular and intratendinous locations. All cases resulted in successful removal without complications. CONCLUSION: Image-guided removal of ballistic foreign bodies secondary to air guns is a very effective procedure that can obviate the need for open surgical procedures in children.

SHH desmoplastic/nodular medulloblastoma and Gorlin syndrome in the setting of Down syndrome: case report, molecular profiling, and review of the literature.

INTRODUCTION: Individuals with Down syndrome (DS) have an increased risk of acute leukemia compared to a markedly decreased incidence of solid tumors. Medulloblastoma, the most common malignant brain tumor of childhood, is particularly rare in the DS population, with only one published case. As demonstrated in a mouse model, DS is associated with cerebellar hypoplasia and a decreased number of cerebellar granule neuron progenitor cells (CGNPs) in the external granule cell layer (EGL). Treatment of these mice with sonic hedgehog signaling pathway (Shh) agonists promote normalization of CGNPs and improved cognitive functioning. CASE REPORT: We describe a 21-month-old male with DS and concurrent desmoplastic/nodular medulloblastoma (DNMB)-a tumor derived from Shh dysregulation and over-activation of CGNPs. Molecular profiling further classified the tumor into the new consensus SHH molecular subgroup. Additional testing revealed a de novo heterozygous germ line mutation in the PTCH1 gene encoding a tumor suppressor protein in the Shh pathway. DISCUSSION: The developmental failure of CGNPs in DS patients offers a plausible explanation for the rarity of medulloblastoma in this population. Conversely, patients with PTCH1 germline mutations experience Shh overstimulation resulting in Gorlin (Nevoid Basal Cell Carcinoma) syndrome and an increased incidence of malignant transformation of CGNPs leading to medulloblastoma formation. This represents the first documented report of an individual with DS simultaneously carrying PTCH1 germline mutation. CONCLUSION: We have observed a highly unusual circumstance in which the PTCH1 mutation appears to "trump" the effects of DS in causation of Shh-activated medulloblastoma.

The diagnostic role for susceptibility-weighted MRI during sporadic hemiplegic migraine.

BACKGROUND: Hemiplegic migraine is a rare form of migraine with aura that includes motor weakness. Diagnosis during the first episode can be difficult to make and costly, especially with the sporadic form. CASES: Our study evaluates the ictal magnetic resonance imaging (MRI) features of four sequential pediatric patients during a first-time, sporadic hemiplegic migraine. Susceptibility-weighted imaging (SWI) revealed cerebral venous prominence and increased magnetic susceptibility affecting brain regions that corresponded with each patient's neurologic deficits. Repeat MRI (performed in three patients) following migraine recovery demonstrated resolution of all susceptibility abnormalities. CONCLUSION: When combined with conventional MRI sequences, SWI has diagnostic value in the acute setting of motor weakness and with clinical features consistent with hemiplegic migraine. The sequence may help to further characterize ictal cerebral blood flow changes during the hemiplegic migraine aura.

Increasing Engagement of Imaging Professionals in Quality Improvement Using an Encounter-specific Quality-reporting Tool.

The involvement of pediatric imaging professionals in quality improvement (QI) in our department was low, with few available informatics tools to report issues or suggest improvement opportunities in a timely and efficient manner. We aimed to increase QI engagement in radiology by creating a real-time, encounter-specific reporting tool embedded into the clinical imaging workflow. Methods: A multidisciplinary team outlined requirements for a new electronic quality-reporting tool, including point-of-care access during imaging workflow and simultaneous automatic capture of encounter-specific clinical information from the hospital information system. Information system experts created a user-friendly interface for categories based on stages of imaging workflow (Planning, Acquisition, Processing, Interpretation, Communication, and Data Collection). Team members trained all department staff. Quality coordinators sorted entries and monitored personnel engagement for two 36-week periods: immediately after launch and 3 years later. Descriptive statistics were used to analyze proposed and completed QI projects during these periods. Results: There were 1,498 entries during the first 36 weeks. Ninety-three percent of radiologists and 56% of technologists participated. Three years later, there were 1,251 entries in 36 weeks. Data collection entries for established QI projects increased from 380 (25%) to 487(39%). The engagement continued among radiologists but decreased among technologists over time. Submissions for QI projects increased from baseline. The project completion rate increased. Conclusion: We created a QI reporting tool embedded into the clinical imaging workflow, which improved the participation of our imaging professionals and increased the number of completed QI projects.

Workflow Interruptions and Effect on Study Interpretation Efficiency.

BACKGROUND: Interruptions have been shown to adversely impact efficiency, accuracy, and patient safety. OBJECTIVE: To analyze the frequency and types of interruptions and effect on report interpretation efficiency. MATERIALS AND METHODS: A business process improvement team was consulted to make detailed recordings of the activities of the radiologists. Activities were categorized as interpreting studies, active interruptions initiated by the radiologist, and passive interruptions initiated by an external source. RESULTS: Thirteen board-certified, pediatric radiologists were observed for 61 hours. Radiologists spent 52% of their time interpreting studies, 29% on active interruptions, and 18% on passive interruptions. Approximately 50% of non-interpretive time involved in-person conversations or consults and 16% involved phone calls of which 67% were incoming. The longest time period without an interruption was 20 minutes. 85% of the time, an interruption came within 3 minutes of beginning an interpretation and lasted 1 minute or less 70% of the time. Interruptions increased the time a radiologist needed to read a study by 1 minute for radiographs, 2 minutes for ultrasounds, 6 minutes for CTs, and 10 minutes for magnetic resonance imaging. CONCLUSION: Total interruption time nearly equaled the total time interpreting studies for radiologists, and interruptions decreased efficiency and increased report interpretation times for all modalities studied. This study highlights the type and extent of interruptions in radiology and examines the effect on report interpretation times. With the frequency of interruptions and impact on efficiency, there is a need to dedicate resources to manage the radiologist workflow. Strategic interventions may ultimately improve outcomes, efficiency, and the overall work environment.

Sex Differences in the Outcomes of Mild Traumatic Brain Injury in Children Presenting to the Emergency Department.

Sex differences after concussion have been studied largely in high school and college athletes, often without reference to comparison groups without concussion. This study sought to evaluate sex differences in outcomes among all children and adolescents presenting to the Emergency Department (ED) for either mild traumatic brain injury (TBI) or orthopedic injury (OI), regardless of mechanism of injury. The study involved a concurrent cohort, prospective study design with longitudinal follow-up. Participants were eight to 16 years old with mild TBI (n = 143) or OI (n = 73). They were recruited and completed an initial assessment at EDs at two children's hospitals. They returned for a post-acute assessment within two weeks of injury and for follow-up assessments at three and six months. Outcomes included child and parent proxy ratings of somatic and cognitive symptoms, and standardized tests of cognitive functioning and balance. Sex did not moderate group differences in balance, fluid or crystallized cognitive ability, or child or parent proxy ratings of somatic or cognitive symptoms. Both parents and children reported more somatic symptoms in girls than boys, but in both groups. Compared with the OI group, the mild TBI group showed significantly lower fluid cognitive ability at the post-acute assessment and significantly higher somatic and cognitive symptoms according to both child and parent proxy ratings across the first two weeks post-injury. The results suggest that sex does not moderate the outcomes of mild TBI in a pediatric ED population. Previous research pointing to sex differences after concussion may reflect the lack of comparison groups, as well as a focus on adolescents and young adults and sport-related concussion. Future research should investigate whether sex moderates the outcomes of pediatric mild TBI in adolescents but not in pre-adolescent children.

Social determinants of participant recruitment and retention in a prospective cohort study of pediatric mild traumatic brain injury.

Background: Prior studies have shown poor recruitment and retention of minoritized groups in clinical trials. Objective: To examine several social determinants as predictors of consent to participate and retention as part of a prospective, longitudinal cohort study of children 8-16 with either mild traumatic brain injury (mild TBI) or orthopedic injury (OI). Methods: Children and families were recruited during acute visits to emergency departments (ED) in two large children's hospitals in the midwestern United States for a prospective, longitudinal cohort study of children 8-16 with either mild TBI or OI. Results: A total of 588 (mild TBI = 307; OI = 281) eligible children were approached in the ED and 315 (mild TBI = 195; OI = 120) were consented. Children who consented did not differ significantly from those who did not consent in sex or age. Consent rates were higher among Black (60.9%) and multi-racial (76.3%) children than white (45.3%) children. Among the 315 children who consented, 217 returned for a post-acute assessment (mild TBI = 143; OI = 74), a retention rate of 68.9%. Participants who were multi-racial (96.6%) or white (79.8%) were more likely to return for the post-acute visit than those who were Black (54.3%). Conclusions: Racial differences exist in both recruitment and retention of participants in a prospective, longitudinal cohort of children with mild TBI or OI. Further work is needed to understand these differences to ensure equitable participation of minoritized groups in brain injury research.

Cognitive Outcomes in Children with Mild Traumatic Brain Injury: An Examination Using the National Institutes of Health Toolbox Cognition Battery.

This study is the first to examine cognitive outcomes after pediatric mild TBI using the National Institutes of Health Toolbox Cognition Battery (NIHTB-CB), a computerized cognitive test battery. The NIHTB-CB includes two complex measures of attention and executive function that allow differentiation of accuracy and response speed. We compared performance on the NIHTB-CB among children 8-16 years of age with mild TBI (n = 143) versus children with orthopedic injuries (OIs; n = 74) recruited in emergency departments and followed for 6 months post-injury. Mixed-model analyses showed that the mild TBI group showed significantly lower Fluid Cognition composite scores than the OI group at 10 days (group intercept, p = 0.018); the magnitude of group differences declined modestly over time (group × time interaction, p = 0.055). Effect sizes were d = 0.34 at 10 days post-injury, d = 0.27 at 3 months, and d = 0.10 at 6 months. No significant effects of group or time were found for the Crystallized Cognition composite. Analyses of Fluid Cognition subtests indicated that children with mild TBI displayed deficits for as long as 3 months on measures of attention and executive function (e.g., cognitive flexibility, inhibitory control), but not on measures of explicit memory, working memory, or processing speed. The poorer performance of the mild TBI group on measures of attention and executive function was attributable largely to slowed reaction time, not decreased accuracy. The findings suggest that children with mild TBI demonstrate persistent deficits in fluid cognition that are most apparent on tasks that combine demands for both speed and executive function.

Radiologic common data elements rates in pediatric mild traumatic brain injury.

OBJECTIVE: The nosology for classifying structural MRI findings following pediatric mild traumatic brain injury (pmTBI) remains actively debated. Radiologic common data elements (rCDE) were developed to standardize reporting in research settings. However, some rCDE are more specific to trauma (probable rCDE). Other more recently proposed rCDE have multiple etiologies (possible rCDE), and may therefore be more common in all children. Independent cohorts of patients with pmTBI and controls were therefore recruited from multiple sites (New Mexico and Ohio) to test the dual hypothesis of a higher incidence of probable rCDE (pmTBI > controls) vs similar rates of possible rCDE on structural MRI. METHODS: Patients with subacute pmTBI (n = 287), matched healthy controls (HC; n = 106), and orthopedically injured (OI; n = 71) patients underwent imaging approximately 1 week postinjury and were followed for 3-4 months. RESULTS: Probable rCDE were specific to pmTBI, occurring in 4%-5% of each sample, rates consistent with previous large-scale CT studies. In contrast, prevalence rates for incidental findings and possible rCDE were similar across groups (pmTBI vs OI vs HC). The prevalence of possible rCDE was also the only finding that varied as a function of site. Possible rCDE and incidental findings were not associated with postconcussive symptomatology or quality of life 3-4 months postinjury. CONCLUSION: Collectively, current findings question the trauma-related specificity of certain rCDE, as well how these rCDE are radiologically interpreted. Refinement of rCDE in the context of pmTBI may be warranted, especially as diagnostic schema are evolving to stratify patients with structural MRI abnormalities as having a moderate injury.

Incidence and Demographics of Pediatric Intracranial Hypertension.

OBJECTIVE: We analyzed the incidence and demographic features of pediatric intracranial hypertension. METHODS: Inpatient and outpatient encounters of children aged 18 years or younger who were diagnosed with primary (idiopathic) or secondary intracranial hypertension between January 2010 and December 2013 were identified. Data were collected from a subspecialty clinic devoted to intracranial hypertension and the sole children's hospital in a large Midwestern city of the United States. Estimated incidence rates were calculated based on the number of newly diagnosed patients in our hospital's primary service area, which includes seven central Ohio counties. Sex, race, body mass index, socioeconomic status, and geographic distribution were also noted. RESULTS: A total of 74 pediatric patients were diagnosed with intracranial hypertension (49 primary/idiopathic and 25 secondary) between January 2010 and December 2013. Using census data, we determined the pediatric population in our service area during the four-year period. The Ohio Hospital Association's database indicated that 92.3% of patients aged 0 to 17 years residing in the region sought care at our institution. By combining these data, we calculated an annual incidence of primary and secondary intracranial hypertension of 0.63 and 0.32 per 100,000 children, respectively. CONCLUSIONS: The estimated annual incidence of pediatric primary intracranial hypertension in our seven county service area in central Ohio is similar to previous pediatric reports from other countries and is 67% of that reported in the US adult population.

ACR Appropriateness Criteria® Back Pain-Child.

It is now generally accepted that nontraumatic back pain in the pediatric population is common. The presence of isolated back pain in a child has previously been an indication for imaging; however, recently a more conservative approach has been suggested using clinical criteria. The presence of constant pain, night pain, and radicular pain, alone or in combination, lasting for 4 weeks or more, constitute clinical red flags that should prompt further imaging. Without these clinical red flags, imaging is likely not indicated. Exceptions include an abnormal neurologic examination or clinical and laboratory findings suggesting an infectious or neoplastic etiology, and when present should prompt immediate imaging. Initial imaging should consist of spine radiographs limited to area of interest, with spine MRI without contrast to evaluate further if needed. CT of the spine, limited to area of interest, and Tc-99m bone scan whole body with single-photon emission computed tomography may be useful in some patients. The addition of intravenous contrast is also recommended for evaluation of a potential neoplastic or infectious process. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Ultrasound-Guided Transgluteal Percutaneous Nephrolithotomy for a Patient with Complex Urogenital Reconstruction and Ectopic Kidney.

BACKGROUND AND PURPOSE: Pediatric patients with urolithiasis and complex reconstructed genitourinary anatomy pose a significant surgical challenge. We describe a technique utilized to treat an obstructing calculus in the ectopic kidney of a patient with a history of cloacal exstrophy, bladder augmentation, Monti catheterizable channel, and reconstructed abdominal wall. Case and Technique: A 5-year-old female with a history of cloacal exstrophy, pelvic kidney, and reconstructed urologic and abdominal wall anatomy presented after prior shockwave lithotripsy with an obstructing ureteropelvic junction calculus with signs of sepsis. Because of the patient's previous abdominal wall reconstruction with polytetrafluoroethylene mesh and the location of her pelvic kidney, traditional methods of percutaneous nephrostomy tube placement could not be performed. Transgluteal percutaneous nephrostomy tube was placed by interventional radiology. Subsequently, a percutaneous nephrolithotomy (PCNL) was performed through this tract. CONCLUSIONS: Transgluteal PCNL is a feasible option in children with complex congenital genitourinary anomalies with a history of reconstructed anatomy.

Social competence following neonatal and childhood stroke.

BACKGROUND: Social functioning encompasses a range of important skills that an individual uses to interact with the social world. Previous studies suggest that social functioning (outcomes) may be impaired after childhood stroke, but research is limited. AIMS: We examined the following: (1) the effect of ischemic stroke upon social outcomes in children; (2) the correlation of cognitive abilities and problem behaviors with social outcomes; and (3) the role of infarct characteristics as predictors of social outcomes. METHODS: We conducted an observational case-controlled study to compare children with neonatal or childhood onset stroke and controls with chronic asthma. Neurological deficits were measured with the Pediatric Stroke Outcome Measure. Cognitive abilities, problem behavior, adaptive behavior, and social outcomes were assessed with standardized measures. RESULTS: Overall stroke cases were impaired in several areas of adaptive behaviors but not in cognitive ability, problem behaviors, or social outcomes. Children with more severe neurological deficits had impairments in a range of adaptive behaviors, social adjustment, and social participation. Impaired cognitive ability and more problem behaviors correlated with impaired social adjustment, particularly in stroke cases. Larger infarcts correlated with greater neurological impairment, lower IQ, and poorer social participation. CONCLUSIONS: Stroke can result in impaired adaptive and social functioning without apparent deficits in IQ or behavior. Infarct size, residual neurological deficits, impaired cognitive ability, and problem behaviors increase the risk for poor social adjustment and participation. These findings can help the clinician anticipate impaired social functioning after pediatric stroke, which is important because age-specific treatments are available.

Outcomes in children with hemorrhagic stroke.

OBJECTIVES: To determine if a specific intracerebral hemorrhage ratio predicts poor outcome; whether predictors of outcome in adults, specifically hemorrhage location, ventricular involvement, or initial Glasgow Coma Scale score, predict outcome in childhood hemorrhagic stroke; and whether the cause of hemorrhagic stroke predicts outcome. DESIGN: Retrospective case study. SETTING A single tertiary care pediatric hospital. PARTICIPANTS: Fifty-nine cases who had nontraumatic hemorrhages. MAIN OUTCOME MEASURES: We examined whether hemorrhage volume, location, initial Glasgow Coma Scale score, or associated diagnoses predicted outcomes. We contacted survivors and parents and assessed outcomes using measures of neurological function, quality of life, and caregiver stress. RESULTS: Twenty died of the hemorrhage or associated illnesses, and we obtained follow-up on 19 survivors. Most survivors had mild to moderate neurological deficits, but many reported impaired school or physical functioning. Increasing hemorrhage volume predicted poorer neurological outcomes and poorer quality-of-life ratings among survivors. Subjects who had intracranial vascular anomalies had the best outcomes of the group. Associated diagnoses strongly predicted scores on the parent- and child-rated quality-of-life measures. In contrast to what has been reported in adult studies, initial Glasgow Coma Scale score, primary location of the hemorrhage, and ventricular hemorrhage did not significantly predict outcomes, although ventricular hemorrhage was associated with trends toward poorer outcomes. CONCLUSIONS: The mortality of hemorrhagic stroke in children is lower than that in adults. Childhood survivors tend to have mild to moderate physical deficits, but they may have significant impairment in other domains such as school functioning.

Assessment of the cerebral circulation in adults with coarctation of the aorta.

AIMS: There is a fivefold increase in the frequency of intracranial aneurysm (IA) in adults with coarctation of the aorta (CoA). Current guidelines for management of adults with CoA recommend computed tomography angiography (CTA) or magnetic resonance imaging of the intracranial vessels. However, this recommendation has not been universally accepted. The purpose of our study was to prospectively perform CTA of the intracranial vessels in adults with CoA to evaluate the prevalence and identify high-risk features of this complication. METHODS AND RESULTS: From January 2008 to February 2011, adults ≥18 years of age with CoA were prospectively enrolled in a screening program with CTA of the intracranial vessels. Analyses of prognostic variables were performed with both Fisher's exact and two sample t-test. Forty-three patients (58% female, 33.55 ± 10.21 years) with CoA completed CTA of the intracranial vessels. Five patients (11%) were found to have IA. Patients with IA were older than those without (45.6 ± 8.17 vs. 30.89 ± 7.89, P = 0.0003). There were no statistically significant differences detected between measurements of fasting lipid profiles, C-reactive protein, brain natriuretic peptide, and homocysteine levels among CoA patients with and without IA (P = not significant). CONCLUSION: Prospective screening of adults with CoA confirmed the increased prevalence of IA but also identified increased age as the sole risk factor. These data suggested that screening is justified particularly in the fourth and fifth decades of life. Further studies are required that focus on the development, natural history, and treatment of IA.