Publications by authors named "Matthew T Whitehead"

80 Publications

Review of Multi-Modal Imaging in Urea Cycle Disorders: The Old, the New, the Borrowed, and the Blue.

Front Neurol 2021 28;12:632307. Epub 2021 Apr 28.

Division of Neurogenetics and Neurodevelopmental Pediatrics, Department of Neurology, Children's National Hospital, George Washington University School of Medicine, Washington, DC, United States.

The urea cycle disorders (UCD) are rare genetic disorder due to a deficiency of one of six enzymes or two transport proteins that act to remove waste nitrogen in form of ammonia from the body. In this review, we focus on neuroimaging studies in OTCD and Arginase deficiency, two of the UCD we have extensively studied. Ornithine transcarbamylase deficiency (OTCD) is the most common of these, and X-linked. Hyperammonemia (HA) in OTCD is due to deficient protein handling. Cognitive impairments and neurobehavioral disorders have emerged as the major sequelae in Arginase deficiency and OTCD, especially in relation to executive function and working memory, impacting pre-frontal cortex (PFC). Clinical management focuses on neuroprotection from HA, as well as neurotoxicity from other known and yet unclassified metabolites. Prevention and mitigation of neurological injury is a major challenge and research focus. Given the impact of HA on neurocognitive function of UCD, neuroimaging modalities, especially multi-modality imaging platforms, can bring a wealth of information to understand the neurocognitive function and biomarkers. Such information can further improve clinical decision making, and result in better therapeutic interventions. investigations of the affected brain using multimodal neuroimaging combined with clinical and behavioral phenotyping hold promise. MR Spectroscopy has already proven as a tool to study biochemical aberrations such as elevated glutamine surrounding HA as well as to diagnose partial UCD. Functional Near Infrared Spectroscopy (fNIRS), which assesses local changes in cerebral hemodynamic levels of cortical regions, is emerging as a non-invasive technique and will serve as a surrogate to fMRI with better portability. Here we review two decades of our research using non-invasive imaging and how it has contributed to an understanding of the cognitive effects of this group of genetic conditions.
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http://dx.doi.org/10.3389/fneur.2021.632307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113618PMC
April 2021

ACR Appropriateness Criteria® Seizures-Child.

J Am Coll Radiol 2021 May;18(5S):S199-S211

Specialty Chair, Riley Hospital for Children Indiana University, Indianapolis, Indiana.

In children, seizures represent an extremely heterogeneous group of medical conditions ranging from benign cases, such as a simple febrile seizure, to life-threatening situations, such as status epilepticus. Underlying causes of seizures also represent a wide range of pathologies from idiopathic cases, usually genetic, to a variety of acute and chronic intracranial or systemic abnormalities. This document discusses appropriate utilization of neuroimaging tests in a child with seizures. The clinical scenarios in this document take into consideration different circumstances at the time of a child's presentation including the patient's age, precipitating event (if any), and clinical and electroencephalogram findings and include neonatal seizures, simple and complex febrile seizures, post-traumatic seizures, focal seizures, primary generalized seizures in a neurologically normal child, and generalized seizures in neurologically abnormal child. This practical approach aims to guide clinicians in clinical decision-making and to help identify efficient and appropriate imaging workup. 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.
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http://dx.doi.org/10.1016/j.jacr.2021.02.020DOI Listing
May 2021

Integrating neuroimaging biomarkers into the multicentre, high-dose erythropoietin for asphyxia and encephalopathy (HEAL) trial: rationale, protocol and harmonisation.

BMJ Open 2021 04 22;11(4):e043852. Epub 2021 Apr 22.

Department of Biostatistics, University of Washington, Seattle, Washington, USA.

Introduction: MRI and MR spectroscopy (MRS) provide early biomarkers of brain injury and treatment response in neonates with hypoxic-ischaemic encephalopathy). Still, there are challenges to incorporating neuroimaging biomarkers into multisite randomised controlled trials. In this paper, we provide the rationale for incorporating MRI and MRS biomarkers into the multisite, phase III high-dose erythropoietin for asphyxia and encephalopathy (HEAL) Trial, the MRI/S protocol and describe the strategies used for harmonisation across multiple MRI platforms.

Methods And Analysis: Neonates with moderate or severe encephalopathy enrolled in the multisite HEAL trial undergo MRI and MRS between 96 and 144 hours of age using standardised neuroimaging protocols. MRI and MRS data are processed centrally and used to determine a brain injury score and quantitative measures of lactate and n-acetylaspartate. Harmonisation is achieved through standardisation-thereby reducing intrasite and intersite variance, real-time quality assurance monitoring and phantom scans.

Ethics And Dissemination: IRB approval was obtained at each participating site and written consent obtained from parents prior to participation in HEAL. Additional oversight is provided by an National Institutes of Health-appointed data safety monitoring board and medical monitor.

Trial Registration Number: NCT02811263; Pre-result.
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http://dx.doi.org/10.1136/bmjopen-2020-043852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070884PMC
April 2021

Taenia-tela choroidea complex and choroid plexus location help distinguish Dandy-Walker malformation and Blake pouch cysts.

Pediatr Radiol 2021 Mar 30. Epub 2021 Mar 30.

Prenatal Pediatrics Institute, Children's National Hospital, Washington, DC, USA.

Background: Dandy-Walker malformation and Blake pouch cysts can have overlapping imaging features. The choroid plexus and associated taenia-tela choroidea complex are displaced inferolaterally in Dandy-Walker malformation and below the vermis in Blake pouch cysts.

Objective: To determine the normal fetal and postnatal MR appearance of the choroid plexus and taenia-tela choroidea complex, and whether their location can help distinguish Dandy-Walker malformation from Blake pouch cysts.

Materials And Methods: In this retrospective study, we evaluated brain MR exams from normal-appearing fetuses (gestational age 19-38 weeks) and infants, fetal and postnatal exams in Blake pouch cysts and Dandy-Walker malformation, and ambiguous cases equivocal for mild Dandy-Walker malformation and Blake pouch cysts. We documented choroid plexus and the taenia-tela choroidea complex location and axial and sagittal angles in each case. Then we contrasted and compared the original and updated fetal diagnoses based on taenia-tela choroidea complex and choroid plexus positions.

Results: The choroid plexus location and the taenia-tela choroidea complex location and angles varied significantly among normal exams, Blake pouch cyst exams and Dandy-Walker malformation exams (P<0.01). Dandy-Walker malformation showed inferolateral displacement of the taenia-tela choroidea complex and choroid plexus distant from the vermis. Adding the taenia-tela choroidea complex and choroid plexus into the assessment improved diagnostic accuracy, especially in ambiguous cases.

Conclusion: The location of the taenia-tela choroidea complex and choroid plexus provided additional diagnostic neuroimaging clues that could be used in conjunction with other conventional findings to distinguish Dandy-Walker malformation and Blake pouch cysts. Normal, Blake pouch cyst, and Dandy-Walker malformation cases differed with regard to taenia-tela choroidea complex and choroid plexus position. Inferolateral taenia-tela choroidea complex displacement distant from the vermian margin was characteristic of Dandy-Walker malformation.
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http://dx.doi.org/10.1007/s00247-021-04991-3DOI Listing
March 2021

Spatiotemporal distribution and age of seizure onset in a pediatric epilepsy surgery cohort with cortical dysplasia.

Epilepsy Res 2021 May 2;172:106598. Epub 2021 Mar 2.

Center for Neuroscience, Children's National Hospital, George Washington University School of Medicine, Washington DC, USA.

Objective: Focal Cortical Dysplasias (CD) are a common etiology of refractory pediatric epilepsy and are amenable to epilepsy surgery. We investigated the association of lesion volume and location to age of seizure onset among children with CD who underwent epilepsy surgery.

Methods: A retrospective study of epilepsy surgery patients with pathologically-confirmed CD. Regions of interest (ROI) determined preoperative lesion volumes on 1.5 T and 3 T T2 and SPGR MRIs, and location in 7 distributed neural networks. Descriptive and inferential statistics were used.

Results: Fifty-five patients were identified: 35 girls (56.5 %). Median age of seizure onset: 19.0 months (range 0.02 months - 16.0 years). Median age of surgery: 7.8 years (range 2.89 months - 24.45 years). CD were frontal (n = 21, 38 %); temporal (n = 15, 27 %); parietal (n = 10, 18 %); occipital (n = 3, 5%); multilobar (n = 6, 11 %). Frontal FCD had seizure onset < 1-year-old (P = 0.10); temporal lobe CD seizure onset was more likely > 5-years-old (P= 0.06). Median lesion volume for CD was 23.23 cm (range: 1.87-591.73 cm). Larger CD lesions were associated with earlier epilepsy (P = 0.01, r = -0.16). We did not find that lesions proximal to early maturing cortical regions were associated with earlier seizure onset. We found an association with CD location in the default mode network (DMN) and age onset < 5years old (P = 0.03). Age of seizure onset was negatively correlated with percent of CD overlapping motor cortex (P = 0.001, r =-0.794) but not with CD overlap of the visual cortex (P = 0.35). There was no effect of CD type on age of epilepsy onset.

Significance: Larger CD lesions are associated with earlier onset epilepsy. CD most commonly occurs within the DMN and Limbic network, and DMN is associated with seizure onset before 5-years-old. Percent of CD overlapping motor cortex correlates with earlier seizure onset. These observations may reflect patterns of brain maturation or regional differences in clinical expression of seizures.
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http://dx.doi.org/10.1016/j.eplepsyres.2021.106598DOI Listing
May 2021

Cochlear signal alterations using pseudo-color perceptual enhancement for patients with sensorineural hearing loss.

Pediatr Radiol 2021 Mar 9. Epub 2021 Mar 9.

The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.

Background: Neuroimaging detection of sensorineural hearing loss (SNHL)-related temporal bone abnormalities is limited (20-50%). We hypothesize that cochlear signal differences in gray-scale data may exceed the threshold of human eye detection. Gray-scale images can be post-processed to enhance perception of tonal difference using "pseudo-color" schemes.

Objective: To compare patients with unilateral SNHL to age-matched normal magnetic resonance imaging (MRI) exams for "labyrinthine color differences" employing pseudo-color post-processing.

Materials And Methods: The MRI database at an academic children's hospital was queried for "hearing loss." Only unilateral SNHL cases were analyzed. Sixty-nine imaging exams were reviewed. Thirteen age-matched normal MR exams in children without hearing loss were chosen for comparison. Pseudo-color was applied with post-processing assignment of specific hues to each gray-scale intensity value. Gray-scale and pseudo-color images were qualitatively evaluated for signal asymmetries by a board-certified neuroradiologist blinded to the side of SNHL.

Results: Twenty-six SNHL (mean: 7.6±3 years) and 13 normal control exams (mean: 7.3±4 years) were included. All patients had normal gray-scale cochlear signal and all controls had symmetrical pseudo-color signal. However, pseudo-color images revealed occult asymmetries localizing to the SNHL ear with lower values in 38%. Ninety-one percent of these cases showed concordance between the side of pseudo-color positivity and the side of hearing loss.

Conclusion: Pseudo-color perceptual image enhancement reveals intra-labyrinthine fluid alterations on MR exams in children with unilateral SNHL. Pseudo-color image enhancement techniques improve detection of cochlear pathology and could have therapeutic implications.
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http://dx.doi.org/10.1007/s00247-021-04987-zDOI Listing
March 2021

The Role of Fetal MRI for Suspected Anomalies of the Posterior Fossa.

Pediatr Neurol 2021 Apr 10;117:10-18. Epub 2021 Jan 10.

Prenatal Pediatrics Institute, Children's National Hospital, Washington, District of Columbia; Department of Neurology, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia; Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia.

Background: Posterior fossa anomalies can be diagnostic dilemmas during the fetal period. The prognosis for different diagnoses of the posterior fossa varies widely. We investigated whether fetal magnetic resonance imaging (MRI) and prenatal neurology consultation led to an alternate prognosis for fetuses referred due to concern for a fetal posterior fossa anomaly and concordance between pre- and postnatal diagnoses.

Methods: This is a retrospective study of cases referred to the Prenatal Pediatrics Institute at Children's National Hospital from January 2012 to June 2018 due to concern for posterior fossa anomaly. Each encounter was scored for change in prognosis based upon clinical and fetal MRI report. Postnatal imaging was compared with prenatal imaging when available.

Results: In total, 180 cases were referred for fetal posterior fossa anomalies based on outside obstetric ultrasound and had both fetal MRI and a neurology consultation. Fetal MRI and neurology consultation resulted in a change in fetal prognosis in 70% of cases. The most common referral diagnosis in our cohort was Dandy-Walker continuum, but it was not often confirmed by fetal MRI. In complex cases, posterior fossa diagnosis and prognosis determined by fetal MRI impacted choices regarding pregnancy management. Postnatal imaging was obtained in 57 (47%) live-born infants. Fetal and postnatal prognoses were similar in 60%.

Conclusions: Fetal diagnosis affects pregnancy management decisions. The fetal-postnatal imaging agreement of 60% highlights the conundrum of balancing the timing of fetal MRI to provide the most accurate diagnosis of the posterior fossa abnormalities in time to make pregnancy management decisions.
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http://dx.doi.org/10.1016/j.pediatrneurol.2021.01.002DOI Listing
April 2021

Prenatal diagnosis of diencephalic-mesencephalic junction dysplasia: Fetal magnetic resonance imaging phenotypes, genetic diagnoses, and outcomes.

Prenat Diagn 2021 May 26;41(6):778-790. Epub 2021 Feb 26.

Prenatal Pediatrics Institute, Children's National Hospital, Washington, District of Columbia, USA.

Objective: Report a single-center 12-year experience in the fetal diagnosis of diencephalic-mesencephalic junction dysplasia (DMJD) to expand the phenotype with Magnetic resonance imaging (MRI)-based classification, evaluate genetic etiologies, and ascertain outcomes.

Methods: Retrospective medical record and imaging review of all fetal MRI exams with DMJD were performed at our institution.

Results: Thirty-three pregnancies with fetal MRI findings of DMJD at 24 (18-37) weeks gestational age were studied; 70% were referred for fetal hydrocephalus. Three fetal MRI patterns were recognized. Type A (butterfly/hypothalamus-midbrain union) was seen in two cases (6%), Type B (partial thalamus-midbrain union) in 22 fetuses (70%), and Type C (complete/near complete midbrain-thalamic continuity) in nine fetuses (24%). L1CAM mutations were identified in four cases, and biallelic VRK1 variants in another. Among 14 live-born cases, 11 survived infancy, and 10 underwent postnatal brain MRI which confirmed the fetal MRI diagnosis in all but one case. Development was delayed in all surviving infants, most with additional neurological sequelae.

Conclusions: DMJD may be identified by prenatal MRI as early as 18 weeks gestation. We propose three distinct phenotypic forms of DMJD, Types A-C. Next-generation sequencing provides an underlying molecular diagnosis in some patients, but further studies on associated genetic diagnoses and clinical outcomes are indicated.
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http://dx.doi.org/10.1002/pd.5909DOI Listing
May 2021

Multimodal imaging in urea cycle-related neurological disease - What can imaging after hyperammonemia teach us?

Transl Sci Rare Dis 2020 Aug 3;5(1-2):87-95. Epub 2020 Aug 3.

Division of Neurogenetics and Developmental Pediatrics, Center for Neuroscience and Behavioral Medicine, Children's National Hospital, Washington, DC, USA.

Background: Urea cycle-related brain disease may take on variable neuroimaging manifestations, ranging from normal to abnormal with or without a signature appearance. In the past, we have described the usefulness of multimodal imaging in identifying biomarkers of neuronal injury in UCD patients. In this study, we report unique findings in an adolescent male with neonatal-onset OTC deficiency after an episode of hyperammonemia.

Materials And Methods: Multiplanar, multisequence MR imaging (T1WI, T2WI, T2 FLAIR, diffusion weighted images and gradient echo) of the brain was performed on seven separate occasions over the course following the acute illness; first five exams were performed within 28 days of admission and the final two exams were performed approximately 3 and 5 months later.

Results: 1.The initial MR revealed increased signal on T2WI in the basal ganglia, claustrum and frontoparietal white matter; which remained stable over time. By the 5th exam, signal changes had developed in frontal cortex; reflecting permanent injury. 2. DTI tractography of the corticospinal tracts displayed revealed diminution of the number of projectional and commissural fibers over time. 3. Blood flow measurements demonstrated hypoperfusion on the fifth exams followed by hyperperfusion on the final two studies. 4. MR spectroscopy demonstrated that glutamine was elevated during hyperammonemia with myoinositol reduction, reflecting osmotic buffering.

Conclusion: This particular multimodal magnetic resonance neuroimaging showed novel, temporally specific manifestations over the disease course in OTC deficiency. This prospective imaging study expands our understanding of the effect of hyperammonemia on the structure and biochemistry of the nervous system.
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http://dx.doi.org/10.3233/TRD-200048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739971PMC
August 2020

A rare case of pediatric Tolosa-Hunt syndrome.

J AAPOS 2020 10 2;24(5):316-319. Epub 2020 Sep 2.

Department of Ophthalmology, Children's National Hospital, Washington, DC.

Tolosa-Hunt syndrome is a rare disorder characterized by granulomatous inflammation involving the cavernous sinus, superior orbital fissure, and/or orbit with no additional underlying cause. Tolosa-Hunt syndrome most often presents with painful ophthalmoplegia involving one or multiple cranial nerves. Here we report the case of an 8-year-old girl who presented, atypically, without the hallmark finding of pain. This case of pediatric Tolosa-Hunt syndrome is the only reported example to date lacking what is considered its pathognomonic feature and thus brings to light the clinical variability of this already inconspicuous disorder.
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http://dx.doi.org/10.1016/j.jaapos.2020.05.009DOI Listing
October 2020

Risk Factors for Brain Injury in Newborns Treated with Extracorporeal Membrane Oxygenation.

Am J Perinatol 2020 Jul 16. Epub 2020 Jul 16.

Division of Neonatology, Children's National Hospital, Washington, District of Columbia.

Objective:  This study aimed to assess the association of clinical risk factors with severity of magnetic resonance imaging (MRI) brain injury in neonatal extracorporeal membrane oxygenation (ECMO) patients.

Study Design:  This is a single-center retrospective study conducted at an outborn level IV neonatal intensive care unit in a free-standing academic children's hospital. Clinical and MRI data from neonates treated with ECMO between 2005 and 2015 were reviewed. MRI injury was graded by two radiologists according to a modified scoring system that assesses parenchymal injury, extra-axial hemorrhage, and cerebrospinal fluid spaces. MRI severity was classified as none (score = 0), mild/moderate (score = 1-13.5), and severe (score ≥ 14). The relationship between selected risk factors and MRI severity was assessed by Chi-square, analysis of variance, and Kruskal-Wallis tests where appropriate. Combinative predictive ability of significant risk factors was assessed by logistic regression analyses.

Results:  MRI data were assessed in 81 neonates treated with ECMO. Veno-arterial (VA) patients had more severe injury compared with veno-venous patients. There was a trend toward less severe injury over time. After controlling for covariates, duration of ECMO remained significantly associated with brain injury, and the risk for severe injury was significantly increased in patients on ECMO beyond 210 hours.

Conclusion:  Risk for brain injury is increased with VA ECMO and with longer duration of ECMO. Improvements in care may be leading to decreasing incidence of brain injury in neonatal ECMO patients.

Key Points: · Veno-arterial ECMO is associated with more brain injury by MRI compared with veno-venous ECMO.. · Longer duration of ECMO is significantly associated with severe brain injury by MRI.. · Risk for neurologic injury may be decreasing over time with advances in neonatal ECMO..
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http://dx.doi.org/10.1055/s-0040-1714208DOI Listing
July 2020

Age and Sex Influences Gamma-aminobutyric Acid Concentrations in the Developing Brain of Very Premature Infants.

Sci Rep 2020 06 29;10(1):10549. Epub 2020 Jun 29.

Center for the Developing Brain, Children's National Hospital, Washington, D.C, US.

Gamma-aminobutyric acid (GABA) and glutamate are principal neurotransmitters essential for late gestational brain development and may play an important role in prematurity-related brain injury. In vivo investigation of GABA in the preterm infant with standard proton magnetic resonance spectroscopy (H-MRS) has been limited due to its low concentrations in the developing brain, and overlap in the spectrum by other dominant metabolites. We describe early postnatal profiles of in vivo GABA and glutamate concentrations in the developing preterm brain measured by using the J-difference editing technique, Mescher-Garwood point resolved spectroscopy. We prospectively enrolled very preterm infants born ≤32 weeks gestational age and non-sedated H-MRS (echo time 68 ms, relaxation time 2000 ms, 256 signal averages) was acquired on a 3 Tesla magnetic resonance imaging scanner from a right frontal lobe voxel. Concentrations of GABA + (with macromolecules) was measured from the J-difference spectra; whereas glutamate and composite glutamate + glutamine (Glx) were measured from the unedited (OFF) spectra and reported in institutional units. We acquired 42 reliable spectra from 38 preterm infants without structural brain injury [median gestational age at birth of 28.0 (IQR 26.0, 28.9) weeks; 19 males (50%)] at a median postmenstrual age of 38.4 (range 33.4 to 46.4) weeks. With advancing post-menstrual age, the concentrations of glutamate OFF increased significantly, adjusted for co-variates (generalized estimating equation β = 0.22, p = 0.02). Advancing postnatal weeks of life at the time of imaging positively correlated with GABA + (β = 0.06, p = 0.02), glutamate OFF (β = 0.11, p = 0.02) and Glx OFF (β = 0.12, p = 0.04). Male infants had higher GABA + (1.66 ± 0.07 vs. 1.33 ± 0.11, p = 0.01) concentrations compared with female infants. For the first time, we report the early ex-utero developmental profile of in vivo GABA and glutamate stratified by age and sex in the developing brain of very preterm infants. This data may provide novel insights into the pathophysiology of neurodevelopmental disabilities reported in preterm infants even in the absence of structural brain injury.
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http://dx.doi.org/10.1038/s41598-020-67188-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324587PMC
June 2020

ACR Appropriateness Criteria® Cerebrovascular Disease-Child.

J Am Coll Radiol 2020 May;17(5S):S36-S54

Specialty Chair, Riley Hospital for Children Indiana University, Indianapolis, Indiana.

Stroke is an uncommon but an important and under-recognized cause of morbidity and mortality in children. Strokes may be due to either brain ischemia or intracranial hemorrhage. Common symptoms of pediatric acute stroke include headache, vomiting, focal weakness, numbness, visual disturbance, seizures, and altered consciousness. Most children presenting with an acute neurologic deficit do not have an acute stroke, but have symptoms due to stroke mimics which include complicated migraine, seizures with postictal paralysis, and Bell palsy. Because of frequency of stroke mimics, in children and the common lack of specificity in symptoms, the diagnosis of a true stroke may be delayed. There are a relatively large number of potential causes of stroke mimic and true stroke. Consequently, imaging plays a critical role in the assessment of children with possible stroke and especially in children who present with acute onset of stroke symptoms. 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.
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http://dx.doi.org/10.1016/j.jacr.2020.01.036DOI Listing
May 2020

ACR Appropriateness Criteria® Head Trauma-Child.

J Am Coll Radiol 2020 May;17(5S):S125-S137

Specialty Chair, Riley Hospital for Children Indiana University, Indianapolis, Indiana.

Head trauma is a frequent indication for cranial imaging in children. The majority of accidental pediatric head trauma is minor and sustained without intracranial injury. Well-validated pediatric-specific clinical decision guidelines should be used to identify very low-risk children who can safely forgo imaging. In those who require acute imaging, CT is considered the first-line imaging modality for suspected intracranial injury because of the short duration of the examination and its high sensitivity for acute hemorrhage. MRI can accurately detect traumatic complications, but often necessitates sedation in children, owing to the examination length and motion sensitivity, which limits rapid assessment. There is a paucity of literature regarding vascular injuries in pediatric blunt head trauma and imaging is typically guided by clinical suspicion. Advanced imaging techniques have the potential to identify changes that are not seen by standard imaging, but data are currently insufficient to support routine clinical use. 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.
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http://dx.doi.org/10.1016/j.jacr.2020.01.026DOI Listing
May 2020

Fetal Neuroimaging Update.

Semin Pediatr Neurol 2020 Apr 28;33:100801. Epub 2020 Feb 28.

Department of Radiology, Children's of Alabama University of Alabama at Birmingham; George Washington School of Medicine, Washington, DC. Electronic address:

Objectives: To review the current imaging techniques available for the evaluation of the fetal brain.

Findings: Ultrasound remains the initial screening modality with routine scanning typically performed at 18-20 weeks gestation. When a central nervous system (CNS) abnormality is noted by ultrasound, MRI is increasingly being used to further clarify findings. Fetal MRI has the unique ability to provide high detailed anatomical information of the entire human fetus with high contrast resolution. This technique has grown due to the development of rapid single shot image acquisition sequences, improvement of motion correction strategies and optimizing shimming techniques.

Conclusions: The assessment of fetal CNS anomalies continues to improve. Advanced MRI techniques have allowed for further delineation of CNS anomalies and have become a cornerstone in the assessment of fetal brain well-being. Those interpreting fetal studies need to be familiar with the strengths and limitations of each exam and be sensitive to the impact discussing findings can have regarding perinatal care and delivery planning. Collaboration with neurologists, neurosurgeons, geneticists, counselors, and maternal fetal specialists are key in providing the best care to the families we treat.
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http://dx.doi.org/10.1016/j.spen.2020.100801DOI Listing
April 2020

The fetal falx cerebelli.

Pediatr Radiol 2020 06 17;50(7):984-989. Epub 2020 Mar 17.

Department of Neuroradiology, Children's National Health System, 111 Michigan Ave. NW, Washington, DC, 20010, USA.

Background: The falx cerebelli is a retrocerebellar dural reflection. The MR spectrum of the fetal falx cerebelli has not been described.

Objective: To determine the prevalence of falx cerebelli abnormalities in the context of posterior fossa malformations and compare them to age-matched normal fetal MRI exams.

Materials And Methods: We reviewed all consecutive fetal MRIs performed over 1 year at a children's hospital. We assessed the falx cerebelli in each examination for location, morphology, size and number. Exams were grouped into (1) normal or non-brain/head abnormalities or (2) abnormal brain or craniofacial structures. We used chi square, linear regression and logistic regression analyses; P<0.05 was considered significant.

Results: We included 424 examinations (223 controls, 201 malformations) from 378 patients (mean gestational age 27±6 weeks). In the control group, the mean falx size was 2.6±1.2 mm (anteroposterior) × 11.0±3.2 mm (craniocaudal), with 80% retrovermian centered; the falx was linear (23%), Y-shape (15%), V-shape (22%) or U-shape (21%); it was unusually multiplicated (17%) or absent (<2%). Falx cerebellar abnormalities were more common in abnormal exams (59%; 119/201) than in normal exams (19%; 43/223) (P<0.001). The falx was abnormal with Blake pouch cysts (9/9, 100%) and rhombencephalosynapsis (3/4, 75%), absent in all Chiari II (n=9) and most Dandy-Walker malformations (5/6, 83%), commonly multiplicated in mega cisterna magna (14/22, 64%), and deviated or absent in cases with arachnoid cysts (3/3, 100%) and adhesions (4/5, 80%).

Conclusion: Structural alterations of the falx cerebelli are more prevalent in fetuses with brain and craniofacial abnormalities. Specific changes offer clues to posterior fossa diagnoses.
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http://dx.doi.org/10.1007/s00247-020-04641-0DOI Listing
June 2020

Chordoma with lung metastases at initial presentation of a pediatric patient.

Radiol Case Rep 2020 Apr 5;15(4):382-386. Epub 2020 Feb 5.

Department of Diagnostic Imaging and Radiology, University of Missouri Hospital/ Women's and Children's Hospital, Columbia, MO, USA.

Chordomas are rare, slow growing malignant tumors derived from notochord remnants that can arise anywhere along the neuronal axis. Chordomas are particularly rare in patients under 20 years of age and tend to be intracranial in location, as opposed to sacrococcygeal in adults. Metastasis at initial presentation is uncommon in all age groups and is exceedingly rare in the absence of local recurrence of the primary tumor. We report a case of advanced clival chordoma with marked nasopharyngeal disease extension and lung metastases at the time of presentation in a pediatric patient.
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http://dx.doi.org/10.1016/j.radcr.2020.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005512PMC
April 2020

Cochlear-facial dehiscence in a pediatric patient.

Pediatr Radiol 2020 05 8;50(5):750-752. Epub 2020 Jan 8.

The George Washington School of Medicine, Washington, DC, USA.

Temporal bone dehiscence is an infrequent but clinically important phenomenon. Cochlear-facial dehiscence, the rarest type, has been described only in adults. We report cochlear-facial dehiscence in a child. Knowledge of this entity is imperative for radiologists searching for anatomical markers of inner ear pathology and for cochlear implant planning.
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http://dx.doi.org/10.1007/s00247-019-04600-4DOI Listing
May 2020

A multi-disciplinary clinic for SCN8A-related epilepsy.

Epilepsy Res 2020 01 23;159:106261. Epub 2019 Dec 23.

Children's National Medical Center, Department of Neurology, 111 Michigan Ave NW, Washington, DC, 20010, USA. Electronic address:

Objective: We endeavored to evaluate a cohort of patients diagnosed with SCN8A-related epilepsy in a multi-disciplinary clinic and to create a bio-repository.

Methods: We recruited patients with epilepsy due to SCN8A variants at Children's National Medical Center, through family organizations, or SCN8A.net. Study procedures included medical record review, review of EEG and MRI data, clinical evaluation, the Vineland Adaptive Behavior Scales, Third Edition (VABS-3), DNA extraction, and preparation of peripheral blood mononuclear cells.

Results: Seventeen patients (9 months - 19 years) completed the study. Age at seizure onset was 1 day to 4 years old (median age 4 months). Epilepsy phenotype ranged from mild epilepsy to severe developmental and epileptic encephalopathy. Medications targeting the voltage-gated sodium channel were most often effective, while levetiracetam resulted in worsening seizures and/or developmental regression in 7/16 (p < 0.05). VABS-3 scores were below age expectations for most children; older children had lower scores. Neurological examination revealed hypotonia (13), spastic quadriparesis (1), ataxia (9), dyskinesia (2)/ dystonia (7), and four non-ambulatory.

Conclusions: This is the first report of a large series of patients with epilepsy due to SCN8A variants evaluated in a single multi-disciplinary clinic. By utilizing a more comprehensive and consistent evaluation, we clarify specific seizure and epilepsy types, describe a distinct epilepsy phenotype in a patient with a nonsense variant, delineate patterns of developmental delay, language, and swallow function (specifically anomic aphasia and flaccid dysarthria), identify and characterize movement disorders, report common findings on physical exam, and demonstrate clinical worsening with levetiracetam.
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http://dx.doi.org/10.1016/j.eplepsyres.2019.106261DOI Listing
January 2020

ACR Appropriateness Criteria® Headache.

J Am Coll Radiol 2019 Nov;16(11S):S364-S377

Specialty Chair, University of California San Diego Health Center, San Diego, California.

Headache is one of the most common human afflictions. In most cases, headaches are benign and idiopathic, and resolve spontaneously or with minor therapeutic measures. Imaging is not required for many types of headaches. However, patients presenting with headaches in the setting of "red flags" such as head trauma, cancer, immunocompromised state, pregnancy, patients 50 years or older, related to activity or position, or with a corresponding neurological deficit, may benefit from CT, MRI, or noninvasive vascular imaging to identify a treatable cause. This publication addresses the initial imaging strategies for headaches associated with the following features: severe and sudden onset, optic disc edema, "red flags," migraine or tension-type, trigeminal autonomic origin, and chronic headaches with and without new or progressive features. 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.
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http://dx.doi.org/10.1016/j.jacr.2019.05.030DOI Listing
November 2019

Prevalence of pituitary cysts in children using modern magnetic resonance imaging techniques.

Pediatr Radiol 2019 12 27;49(13):1781-1787. Epub 2019 Jul 27.

Department of Diagnostic Imaging and Radiology, Children's National Medical Center, Washington, DC, USA.

Background: Pituitary pars intermedia/Rathke cleft cysts or cyst-like structures are commonly encountered in children undergoing brain magnetic resonance imaging (MRI), especially when examinations include thin-section, high-resolution sequences.

Objective: To determine the prevalence of pituitary cystic lesions in children at our institution using modern MRI technique, to assess for associated endocrinopathy and to address the need for follow-up.

Materials And Methods: We retrospectively reviewed 232 consecutive 1.5- and 3-T brain MRIs in children ages 0-18 years (mean: 8.3±5.3 years). We evaluated 3-D volumetric T1 spoiled gradient echo (SPGR) and axial T2-weighted sequences. Pituitary glands were evaluated for the presence, size and signal characteristics of cysts. Cyst volumes were measured in three orthogonal planes. Endocrine abnormalities were documented from the medical record.

Results: Pituitary cysts were present in 57.7% of children (n=134), with a mean linear measurement of 3.6±1.17 mm (range: 0.4 to 12.3 mm). The overwhelming majority of cysts were hyopointense on T1-W images (n=121, 90%) and isointense on T2-W images relative to the adenohypophysis (n=106, 79%). T1 hyperintense and T2 hypointense signals were present in a minority, 6.7% and 8%, respectively. Most cysts were occult on post-contrast T1-W images (n=24, 77%). Endocrine abnormalities were present in 2/134 (1.5%) of children with cysts (these were unrelated to the pituitary gland) versus 1/98 (1%) children without cysts (P=0.7).

Conclusion: More often than not, pituitary cysts/cyst-like structures can be found incidentally in children using modern MRI techniques. Follow-up is not typically required if there are no associated symptoms or excessive size.
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http://dx.doi.org/10.1007/s00247-019-04479-1DOI Listing
December 2019

"Laser and the Tuber": thermal dynamic and volumetric factors influencing seizure outcomes in pediatric subjects with tuberous sclerosis undergoing stereoencephalography-directed laser ablation of tubers.

Childs Nerv Syst 2019 08 17;35(8):1333-1340. Epub 2019 Jun 17.

Department of Neurosurgery, Children's National Medical Center, Washington, DC, USA.

Purpose: Tuberous sclerosis (TSC) is a well-known cause of medically refractory epilepsy (MRE). Stereoencephalography-directed magnetic resonance-guided laser interstitial thermal therapy (SEEG-directed MRgLITT) is an emerging minimally invasive technique that appears aptly suited for the surgical management of TSC. Our aims are to present our experiences with patients who had undergone SEEG-directed MRgLITT to identify and treat cortical tubers responsible for clinical seizures and to perform an in-depth analysis of volumetric and thermal dynamic factors that may be related to seizure outcomes.

Methods: We studied all pediatric patients with MRE due to TSC who underwent SEEG-directed MRgLITT, investigating seizure outcomes in relation to thermal dynamic and volumetric factors.

Results: Eight cortical tubers from three pediatric patients were analyzed. Two of three patients had Engel I outcomes at last follow-up (median 18 months). Average A/T (ablation volume/tuber volume) ratio for Engel I outcomes was 1.28 (variance, 0.16) and 0.84 (variance, < 0.01) for all other outcomes (P = 0.035). There was a moderate positive correlation when comparing ablation energy to ablation volume (R = 0.65) in cortical tuber tissue. When the calcified tuber is excluded, the correlation is stronger (R = 0.77). Thus, the calculated energy needed to ablate 1 cm of cortical tuber tissue is 1263.6 J (calcified tuber) or 1089.5 J (non-calcified tuber).

Conclusions: SEEG-directed MRgLITT appears to be a safe and effective technique in the management of pediatric patients with MRE due to TSC. The A/T ratio may be a useful indicator in predicting seizure outcomes.
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http://dx.doi.org/10.1007/s00381-019-04255-4DOI Listing
August 2019

ACR Appropriateness Criteria Ataxia.

J Am Coll Radiol 2019 May;16(5S):S44-S56

Specialty Chair, Emory University, Atlanta, Georgia.

Ataxia can result from an abnormality in the cerebellum, spinal cord, peripheral nerves, and/or vestibular system. Pathology involving the brain, such as infarct or hydrocephalus, can also present with ataxia as part of the symptom constitution, or result in symptoms that mimic ataxia. Clinical evaluation by history and careful neurological examination is important to help with lesion localization, and helps determine where imaging should be focused. In the setting of trauma with the area of suspicion in the brain, a head CT without intravenous contrast is the preferred initial imaging choice. If vascular injury is suspected, CTA of the neck can be helpful. When the area of suspicion is in the spine, CT or MRI of the spine can be considered to assess for bony or soft-tissue injury, respectively. In the setting of ataxia unrelated to recent trauma, MRI is the preferred imaging modality, tailored to assess the brain or spine depending on the area of suspected pathology. The use of intravenous contrast is generally helpful. 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.
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http://dx.doi.org/10.1016/j.jacr.2019.02.021DOI Listing
May 2019

ACR Appropriateness Criteria Thyroid Disease.

J Am Coll Radiol 2019 May;16(5S):S300-S314

Specialty Chair, Emory University, Atlanta, Georgia.

There are a wide variety of diseases that affect the thyroid gland ranging from hyperplastic to neoplastic, autoimmune, or inflammatory. They can present with functional abnormality or a palpable structural change. Imaging has a key role in diagnosing and characterizing the thyroid finding for management. Imaging is also essential in the management of thyroid cancer. 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.
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http://dx.doi.org/10.1016/j.jacr.2019.02.004DOI Listing
May 2019

ACR Appropriateness Criteria Suspected Spine Trauma-Child.

J Am Coll Radiol 2019 May;16(5S):S286-S299

Specialty Chair, Riley Hospital for Children Indiana University, Indianapolis, Indiana.

Choosing the appropriate imaging in children with accidental traumatic spine injuries can be challenging because the recommendations based on scientific evidence at this time differ from those applied in adults. This differentiation is due in part to differences in anatomy and physiology of the developing spine. This publication uses scientific evidence and a panel of pediatric experts to summarize best current imaging practices for children with accidental spine trauma. 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.
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http://dx.doi.org/10.1016/j.jacr.2019.02.003DOI Listing
May 2019

ACR Appropriateness Criteria Neuroendocrine Imaging.

J Am Coll Radiol 2019 May;16(5S):S161-S173

Specialty Chair, Emory University, Atlanta, Georgia.

Neuroendocrine dysfunction includes suspected hyper- and hypofunction of the pituitary gland. Causative lesions may include primary masses of the pituitary such as pituitary microadenomas and macroadenomas, as well as extrinsic masses, typically centered in the suprasellar cistern. Clinical syndromes related to hormonal dysfunction can be caused by excessive hormonal secretion or by inhibited secretion due to mass effect upon elements of the hypothalamic-pituitary axis. Additionally, complications such as hemorrhage may be seen in the setting of an underlying mass and can result in hormonal dysfunction. MRI with high-resolution protocols is the best first-line test to evaluate the sella turcica and parasellar region. CT provides complementary information regarding bony anatomy, and may be appropriate as a first-line test in certain instances, but it provides less detail and lesion characterization when compared to MRI. 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.
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http://dx.doi.org/10.1016/j.jacr.2019.02.017DOI Listing
May 2019

The effect of unilateral stroke on autonomic function in the term newborn.

Pediatr Res 2019 05 2;85(6):830-834. Epub 2019 Feb 2.

Fetal Medicine Institute, Children's National Health System, 111 Michigan Avenue NW, Washington, DC, 20010, USA.

Background: The mature cerebral cortex has a topographically organized influence on reflex autonomic centers of the brainstem and diencephalon and sympathetic activation coming primarily from the right hemisphere and parasympathetic activation from the left. In the term newborn, the maturational status of this central autonomic system remains poorly understood.

Methods: Sixteen term newborns admitted to Children's National with unilateral middle cerebral artery (MCA) strokes (n = 8 left, n = 8 right) had archived continuous electrocardiograph (EKG) signals available. We compared stroke laterality and severity with indices of autonomic function, as measured by heart rate variability. We performed both time- and frequency-domain analyses on the R-R interval (RRi) over 24h of continuous EKG data at around 7 days of age.

Results: Right MCA stroke significantly increased sympathetic tone, while left MCA stroke increased parasympathetic tone. Regardless of laterality, stroke severity was associated inversely with sympathetic tone and positively with parasympathetic tone. Surprisingly, injury to either insular region had no significant autonomic effect. Phenobarbital blood levels were positively associated with sympathetic tone and inversely related to parasympathetic tone.

Conclusion: Based on these findings, it is difficult to reconcile the functional topography of the central autonomic system in term newborns with that currently proposed for the normal mature brain. Further investigation is clearly needed.
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http://dx.doi.org/10.1038/s41390-019-0320-0DOI Listing
May 2019

ACR Appropriateness Criteria Sinusitis-Child.

J Am Coll Radiol 2018 Nov;15(11S):S403-S412

Specialty Chair, Riley Hospital for Children Indiana University, Indianapolis, Indiana.

Sinusitis is common in children that usually resolves spontaneously. Imaging is not part of the standard of care for initial diagnosis, however may be necessary in cases with persistent or chronic sinusitis to guide surgical intervention, or to rule out intracranial and vascular complications of sinusitis. Computed tomography (CT) and magnetic resonance imaging (MRI) are the leading imaging modalities. In this article, appropriateness in use of imaging modalities are discussed under common/clinically relevant scenarios. 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.
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http://dx.doi.org/10.1016/j.jacr.2018.09.029DOI Listing
November 2018

Hyponatremia: An Unusual Presentation in a Neonate With Chromosome 1q21.1 Deletion Syndrome.

Front Pediatr 2018 11;6:273. Epub 2018 Oct 11.

Department of Nephrology, Children's National Health System, Washington, DC, United States.

Chromosome 1q21.1 deletion syndrome is associated with a wide variety of clinical features including mild to moderate mental retardation, microcephaly, cardiac abnormalities, and cataracts. We report an unusual case of a premature neonate with persistent hyponatremia, markedly elevated plasma arginine vasopressin level (32.7 pg/mL), and clinical findings consistent with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The patient, who also had microcephaly and dextrocardia, was subsequently diagnosed with chromosome 1q21.1 deletion syndrome. Further evaluation revealed hypothalamic abnormalities, features not previously described with this syndrome. To our knowledge, this is the first report of SIADH associated with congenital hypothalamic anomalies in a neonate with chromosome 1q21.1 deletion syndrome. We also report our experience using tolvaptan, a vasopressin receptor antagonist, in this patient to effectively maintain eunatremia.
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http://dx.doi.org/10.3389/fped.2018.00273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193093PMC
October 2018

Acute-Onset Flaccid Hemiparesis in a 9-Year-Old Boy With Presumed Enteroviral Infection.

Pediatr Emerg Care 2018 Sep;34(9):e171-e174

From the Division of Emergency Medicine, Children's National Health System, and.

In the summer and autumn of 2014, a cluster of cases of flaccid paralysis were seen in the United States related to patients infected with enterovirus D68 (EV-D68). We present here a case of acute-onset flaccid hemiparesis in a previously healthy boy with altered mental status, hypothermia, and bowel incontinence.
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http://dx.doi.org/10.1097/PEC.0000000000001604DOI Listing
September 2018