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Neurology Research

Research Overview

My research focuses on acquired brain injury in newborn infants. I am particularly interested in hypoxic-ischemic brain injury, involving a lack of oxygen and blood flow to the brain; the treatment of seizures in term newborns; and periventricular leukomalacia (injury to the white matter of the brain), intraventricular hemorrhage (bleeding into the ventricles of the brain) and hydrocephalus in preterm newborns. The broad goal of my research is to understand the causes of these brain injuries and to detect them at their earliest onset in order to develop and test neuroprotective therapies that prevent or minimize brain injury.

A current focus is improving the treatment and long-term outcomes of newborns with hypoxia-ischemia. Term age newborns with this condition can have serious long-term disabilities such as cerebral palsy and intellectual and visual disabilities resulting from brain injury. I am the Principal Investigator of a National Institutes of Health-funded clinical trial that is testing bumetanide for newborn seizures caused by hypoxia-ischemia. This is the first randomized, double-blind controlled trial of a new seizure medicine to be tested in newborns in decades, and the first to test a medicine that works specifically in the newborn brain, based on research conducted in animals. Results from this trial will be used to design larger multicenter trials of new medicines to treat newborn seizures and potentially to improve the long-term outcomes of these newborns.

Related studies are seeking to determine which newborns are most likely to develop seizures that are hard to control, the outcome of seizures and newer, more sensitive techniques to measure levels of bumetanide (or other seizure medications) in the blood and spinal fluid using very small volumes of these fluids.

In addition, I am collaborating with other investigators to study aspects of hypoxic-ischemic brain injury in term newborns. With colleagues in the Neonatal Intensive Care Unit at Boston Children's Hospital, I developed the induced hypothermia protocol used to treat these newborns to prevent or minimize brain damage from hypoxia-ischemia. Our studies include evaluation of the safety and efficacy of therapeutic hypothermia; use of advanced imaging to improve understanding of the causes, timing and prediction of long-term outcome; and evaluating the effects of treatment on the newborns' long-term neurodevelopmental outcomes.

I am also leading a project investigating the characteristics of cerebral visual impairment caused by white-matter injury to the brains of children born prematurely. Visual problems in these newborns are related to injury to the brain's visual centers, rather than eye disease. The visual perceptual problems can lead to other problems, such as learning difficulties in school and difficulties with orientation and mobility. Relatively little is known about these types of visual disorders. Our study is one of the first to look at the relationship between magnetic resonance imaging (MRI) evidence of brain injury and visual impairments detected by sophisticated tests of visual acuity and perception.

Research Background

Janet Soul received her MD from McGill University Faculty of Medicine. She completed an internship and residency at Boston City Hospital and fellowships in neurology and neonatal neurology at Boston Children's Hospital.

 

Education

Undergraduate School

McGill University
Montreal, Quebec Canada

Medical School

McGill University
Montreal, Quebec Canada

Residency

Pediatrics Boston City Hospital
Boston MA

Fellowship

Neurology & Neonatal Neurology Boston Children's Hospital
Boston MA

Publications

  1. Data Collection Variability Across Neonatal Hypoxic-Ischemic Encephalopathy Registries. J Pediatr. 2025 Jan 23; 114476. View Abstract
  2. Neonatal Seizures and Associated Neurobehavioral Profiles in Preschool Age Children. Pediatr Neurol. 2025 Feb; 163:76-81. View Abstract
  3. Sleep Disorders Five Years After Acute Provoked Neonatal Seizures. J Pediatr. 2024 Nov 17; 278:114412. View Abstract
  4. Life After Neonatal Seizures: Characterizing the Longitudinal Parent Experience. Pediatr Neurol. 2024 Dec; 161:76-83. View Abstract
  5. Practice Variations for Therapeutic Hypothermia in Neonates with Hypoxic-ischemic Encephalopathy: An International Survey. J Pediatr. 2024 Nov; 274:114181. View Abstract
  6. Proceedings of the 15th International Newborn Brain Conference: Neonatal Neurocritical Care, seizures, and continuous aEEG and /or EEG monitoring. J Neonatal Perinatal Med. 2024; 17(3):S345-S392. View Abstract
  7. The importance of not increasing confusion around neonatal encephalopathy and hypoxic-ischemic encephalopathy. Pediatr Res. 2024 Mar; 95(4):871-872. View Abstract
  8. Neuroprotective therapies in the NICU in preterm infants: present and future (Neonatal Neurocritical Care Series). Pediatr Res. 2024 Apr; 95(5):1224-1236. View Abstract
  9. Establishing a regional registry for neonatal encephalopathy: impact on identification of gaps in practice. Pediatr Res. 2024 Jan; 95(1):213-222. View Abstract
  10. Association of cerebral metabolic rate following therapeutic hypothermia with 18-month neurodevelopmental outcomes after neonatal hypoxic ischemic encephalopathy. EBioMedicine. 2023 Aug; 94:104673. View Abstract
  11. Abnormal development of transient fetal zones in mild isolated fetal ventriculomegaly. Cereb Cortex. 2023 02 07; 33(4):1130-1139. View Abstract
  12. Effect of neonatal seizure burden and etiology on the long-term outcome: data from a randomized, controlled trial. Ann Child Neurol Soc. 2023 Mar; 1(1):53-65. View Abstract
  13. Feeding and developmental outcomes after neonatal seizures-A prospective observational study. Ann Child Neurol Soc. 2023 Sep; 1(3):209-217. View Abstract
  14. Neuroprotective therapies in the NICU in term infants: present and future. Pediatr Res. 2023 Jun; 93(7):1819-1827. View Abstract
  15. Seizure Burden, EEG, and Outcome in Neonates With Acute Intracranial Infections: A Prospective Multicenter Cohort Study. Pediatr Neurol. 2022 12; 137:54-61. View Abstract
  16. Continuous EEG monitoring still recommended for neonatal seizure management: commentary on NEST trial. Pediatr Res. 2023 02; 93(3):469-470. View Abstract
  17. Fetal Brain Volume Predicts Neurodevelopment in Congenital Heart Disease. Circulation. 2022 04 12; 145(15):1108-1119. View Abstract
  18. Impact of COVID-19 Pandemic on Developmental Service Delivery in Children With a History of Neonatal Seizures. Pediatr Neurol. 2022 04; 129:14-18. View Abstract
  19. Proceedings of the 13th International Newborn Brain Conference: Neonatal Neurocritical Care, Seizures, and Continuous EEG monitoring. J Neonatal Perinatal Med. 2022; 15(2):467-485. View Abstract
  20. Parent Mental Health and Family Coping over Two Years after the Birth of a Child with Acute Neonatal Seizures. Children (Basel). 2021 Dec 22; 9(1). View Abstract
  21. Seizure Severity and Treatment Response in Newborn Infants with Seizures Attributed to Intracranial Hemorrhage. J Pediatr. 2022 Mar; 242:121-128.e1. View Abstract
  22. Characteristics of Neonates with Cardiopulmonary Disease Who Experience Seizures: A Multicenter Study. J Pediatr. 2022 03; 242:63-73. View Abstract
  23. Treatment of Neonatal Seizures: Comparison of Treatment Pathways From 11 Neonatal Intensive Care Units. Pediatr Neurol. 2022 03; 128:67-74. View Abstract
  24. Training in neonatal neurocritical care: a proposal for a hybrid model of competence by design and time-based methods. Pediatr Res. 2024 Sep; 96(4):1013-1020. View Abstract
  25. Management of seizures in neonates with neonatal encephalopathy treated with hypothermia. Semin Fetal Neonatal Med. 2021 08; 26(4):101279. View Abstract
  26. Family-Centered Care for Children and Families Impacted by Neonatal Seizures: Advice From Parents. Pediatr Neurol. 2021 11; 124:26-32. View Abstract
  27. Early-life epilepsy after acute symptomatic neonatal seizures: A prospective multicenter study. Epilepsia. 2021 08; 62(8):1871-1882. View Abstract
  28. Safety of Early Discontinuation of Antiseizure Medication After Acute Symptomatic Neonatal Seizures. JAMA Neurol. 2021 07 01; 78(7):817-825. View Abstract
  29. Seizure Control in Neonates Undergoing Screening vs Confirmatory EEG Monitoring. Neurology. 2021 08 10; 97(6):e587-e596. View Abstract
  30. A Pilot Randomized, Controlled, Double-Blind Trial of Bumetanide to Treat Neonatal Seizures. Ann Neurol. 2021 02; 89(2):327-340. View Abstract
  31. Fetal magnetic resonance imaging: supratentorial brain malformations. Pediatr Radiol. 2020 12; 50(13):1934-1947. View Abstract
  32. Regional Brain Growth Trajectories in Fetuses with Congenital Heart Disease. Ann Neurol. 2021 01; 89(1):143-157. View Abstract
  33. Predicting Autism Spectrum Disorder in Very Preterm Infants. Pediatrics. 2020 10; 146(4). View Abstract
  34. Characterization of Death in Infants With Neonatal Seizures. Pediatr Neurol. 2020 12; 113:21-25. View Abstract
  35. Parent experience of caring for neonates with seizures. Arch Dis Child Fetal Neonatal Ed. 2020 Nov; 105(6):634-639. View Abstract
  36. Associations between Infant and Parent Characteristics and Measures of Family Well-Being in Neonates with Seizures: A Cohort Study. J Pediatr. 2020 06; 221:64-71.e4. View Abstract
  37. Early exit from neonatal therapeutic hypothermia: A single institution experience using MRI to guide decision-making. J Neonatal Perinatal Med. 2020; 13(4):441-447. View Abstract
  38. Neonatal seizures: Case definition & guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine. 2019 12 10; 37(52):7596-7609. View Abstract
  39. Expanding the phenotypic spectrum of Mabry Syndrome with novel PIGO gene variants associated with hyperphosphatasia, intractable epilepsy, and complex gastrointestinal and urogenital malformations. Eur J Med Genet. 2020 Apr; 63(4):103802. View Abstract
  40. Abnormalities in cerebral hemodynamics and changes with surgical intervention in neonates with congenital heart disease. J Thorac Cardiovasc Surg. 2020 05; 159(5):2012-2021. View Abstract
  41. Seizure Prediction Models in the Neonatal Intensive Care Unit. J Clin Neurophysiol. 2019 May; 36(3):186-194. View Abstract
  42. Pharmacologic Prevention and Treatment of Neonatal Brain Injury. Clin Perinatol. 2019 06; 46(2):311-325. View Abstract
  43. Correction to: De novo and inherited TCF20 pathogenic variants are associated with intellectual disability, dysmorphic features, hypotonia, and neurological impairments with similarities to Smith-Magenis syndrome. Genome Med. 2019 03 25; 11(1):16. View Abstract
  44. De novo and inherited TCF20 pathogenic variants are associated with intellectual disability, dysmorphic features, hypotonia, and neurological impairments with similarities to Smith-Magenis syndrome. Genome Med. 2019 02 28; 11(1):12. View Abstract
  45. Response to antiseizure medications in neonates with acute symptomatic seizures. Epilepsia. 2019 03; 60(3):e20-e24. View Abstract
  46. Monitoring and management of brain hemodynamics and oxygenation. Handb Clin Neurol. 2019; 162:295-314. View Abstract
  47. Recommendations for the design of therapeutic trials for neonatal seizures. Pediatr Res. 2019 06; 85(7):943-954. View Abstract
  48. Advanced diffusion imaging for assessing normal white matter development in neonates and characterizing aberrant development in congenital heart disease. Neuroimage Clin. 2018; 19:360-373. View Abstract
  49. Congenital muscular dystrophy-dystroglycanopathy, type A, featuring bilateral retinal dysplasia and vertical angle kappa. J AAPOS. 2018 06; 22(3):242-244.e1. View Abstract
  50. Post-arrest therapeutic hypothermia in pediatric patients with congenital heart disease. Resuscitation. 2018 05; 126:83-89. View Abstract
  51. Acute symptomatic seizures in term neonates: Etiologies and treatments. Semin Fetal Neonatal Med. 2018 06; 23(3):183-190. View Abstract
  52. Probabilistic tractography-based thalamic parcellation in healthy newborns and newborns with congenital heart disease. J Magn Reson Imaging. 2018 06; 47(6):1626-1637. View Abstract
  53. Imaging features and prognostic factors in fetal and postnatal torcular dural sinus malformations, part II: synthesis of the literature and patient management. J Neurointerv Surg. 2018 May; 10(5):471-475. View Abstract
  54. Imaging features and prognostic factors in fetal and postnatal torcular dural sinus malformations, part I: review of experience at Boston Children's Hospital. J Neurointerv Surg. 2018 May; 10(5):467-470. View Abstract
  55. Liver Failure as the Presentation of Ornithine Transcarbamylase Deficiency in a 13-Month-Old Female. JIMD Rep. 2018; 40:17-22. View Abstract
  56. The use of phenobarbital and other anti-seizure drugs in newborns. Semin Fetal Neonatal Med. 2017 10; 22(5):321-327. View Abstract
  57. Profile of neonatal epilepsies: Characteristics of a prospective US cohort. Neurology. 2017 Aug 29; 89(9):893-899. View Abstract
  58. Seizures in Preterm Neonates: A Multicenter Observational Cohort Study. Pediatr Neurol. 2017 Jul; 72:19-24. View Abstract
  59. Electroencephalographic discontinuity during sevoflurane anesthesia in infants and children. Paediatr Anaesth. 2017 Mar; 27(3):251-262. View Abstract
  60. White Matter Volume Predicts Language Development in Congenital Heart Disease. J Pediatr. 2017 02; 181:42-48.e2. View Abstract
  61. Treatment Duration After Acute Symptomatic Seizures in Neonates: A Multicenter Cohort Study. J Pediatr. 2017 02; 181:298-301.e1. View Abstract
  62. Corrigendum to "GJC2 promoter mutations causing Pelizaeus-Merzbacher-like disease" [Mol. Genet. Metab. 111 (2014) 393-398]. Mol Genet Metab. 2016 11; 119(3):293. View Abstract
  63. Fellowship Training in the Emerging Fields of Fetal-Neonatal Neurology and Neonatal Neurocritical Care. Pediatr Neurol. 2016 10; 63:39-44.e3. View Abstract
  64. BRAT1 mutations present with a spectrum of clinical severity. Am J Med Genet A. 2016 09; 170(9):2265-73. View Abstract
  65. Contemporary Profile of Seizures in Neonates: A Prospective Cohort Study. J Pediatr. 2016 Jul; 174:98-103.e1. View Abstract
  66. Perioperative cerebral hemodynamics and oxygen metabolism in neonates with single-ventricle physiology. Biomed Opt Express. 2015 Dec 01; 6(12):4749-67. View Abstract
  67. Copy number variation plays an important role in clinical epilepsy. Ann Neurol. 2014 Jun; 75(6):943-58. View Abstract
  68. Cerebral blood flow velocity and neurodevelopmental outcome in infants undergoing surgery for congenital heart disease. Ann Thorac Surg. 2014 Jul; 98(1):125-32. View Abstract
  69. GJC2 promoter mutations causing Pelizaeus-Merzbacher-like disease. Mol Genet Metab. 2014 03; 111(3):393-398. View Abstract
  70. Cerebral oxygen metabolism in neonatal hypoxic ischemic encephalopathy during and after therapeutic hypothermia. J Cereb Blood Flow Metab. 2014 Jan; 34(1):87-94. View Abstract
  71. Near-infrared spectroscopy versus magnetic resonance imaging to study brain perfusion in newborns with hypoxic-ischemic encephalopathy treated with hypothermia. Neuroimage. 2014 Jan 15; 85 Pt 1:287-93. View Abstract
  72. Passive cooling during transport of asphyxiated term newborns. J Perinatol. 2013 Jun; 33(6):435-40. View Abstract
  73. Good outcome with early empiric treatment of neural larva migrans due to Baylisascaris procyonis. Pediatrics. 2012 Mar; 129(3):e806-11. View Abstract
  74. Brain perfusion in asphyxiated newborns treated with therapeutic hypothermia. AJNR Am J Neuroradiol. 2011 Dec; 32(11):2023-9. View Abstract
  75. Sensitive isotope dilution liquid chromatography/tandem mass spectrometry method for quantitative analysis of bumetanide in serum and brain tissue. J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Apr 15; 879(13-14):998-1002. View Abstract
  76. Early versus late MRI in asphyxiated newborns treated with hypothermia. Arch Dis Child Fetal Neonatal Ed. 2011 Jan; 96(1):F36-44. View Abstract
  77. Relationship of intraoperative cerebral oxygen saturation to neurodevelopmental outcome and brain magnetic resonance imaging at 1 year of age in infants undergoing biventricular repair. Circulation. 2010 Jul 20; 122(3):245-54. View Abstract
  78. Neurodevelopmental outcome of fetuses referred for ventriculomegaly. Ultrasound Obstet Gynecol. 2010 Apr; 35(4):405-16. View Abstract
  79. Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance. Cell. 2010 Jan 08; 140(1):74-87. View Abstract
  80. Elevated cerebral pressure passivity is associated with prematurity-related intracranial hemorrhage. Pediatrics. 2009 Jul; 124(1):302-9. View Abstract
  81. Subtle hemorrhagic brain injury is associated with neurodevelopmental impairment in infants with repaired congenital heart disease. J Thorac Cardiovasc Surg. 2009 Aug; 138(2):374-81. View Abstract
  82. Cerebral hemodynamic changes during intensive care of preterm infants. Pediatrics. 2008 Nov; 122(5):e1006-13. View Abstract
  83. Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders. J Med Genet. 2009 Apr; 46(4):242-8. View Abstract
  84. Positive screening for autism in ex-preterm infants: prevalence and risk factors. Pediatrics. 2008 Apr; 121(4):758-65. View Abstract
  85. Randomized trial of hematocrit 25% versus 35% during hypothermic cardiopulmonary bypass in infant heart surgery. J Thorac Cardiovasc Surg. 2008 Feb; 135(2):347-54, 354.e1-4. View Abstract
  86. Current definitions of hypotension do not predict abnormal cranial ultrasound findings in preterm infants. Pediatrics. 2007 Nov; 120(5):966-77. View Abstract
  87. Neurodevelopmental outcome in survivors of periventricular hemorrhagic infarction. Pediatrics. 2007 Oct; 120(4):785-92. View Abstract
  88. Does cerebellar injury in premature infants contribute to the high prevalence of long-term cognitive, learning, and behavioral disability in survivors? Pediatrics. 2007 Sep; 120(3):584-93. View Abstract
  89. Neonatal hypocalcemic seizures in siblings exposed to topiramate in utero. Pediatr Neurol. 2007 Apr; 36(4):274-6. View Abstract
  90. Fluctuating pressure-passivity is common in the cerebral circulation of sick premature infants. Pediatr Res. 2007 Apr; 61(4):467-73. View Abstract
  91. Patient with novel interstitial deletion of chromosome 3q13.1q13.3 and agenesis of the corpus callosum. Clin Dysmorphol. 2006 Oct; 15(4):217-220. View Abstract
  92. Characterizing the shape of anatomical structures with Poisson's equation. IEEE Trans Med Imaging. 2006 Oct; 25(10):1249-57. View Abstract
  93. Periventricular hemorrhagic infarction: risk factors and neonatal outcome. Pediatr Neurol. 2006 Aug; 35(2):85-92. View Abstract
  94. Ultrasonographic features and severity scoring of periventricular hemorrhagic infarction in relation to risk factors and outcome. Pediatrics. 2006 Jun; 117(6):2111-8. View Abstract
  95. The current etiologic profile and neurodevelopmental outcome of seizures in term newborn infants. Pediatrics. 2006 Apr; 117(4):1270-80. View Abstract
  96. Measurement of cortical thickness in 3D brain MRI data: validation of the Laplacian method. J Neuroimaging. 2006 Apr; 16(2):146-53. View Abstract
  97. Impaired trophic interactions between the cerebellum and the cerebrum among preterm infants. Pediatrics. 2005 Oct; 116(4):844-50. View Abstract
  98. Talairach-based parcellation of neonatal brain magnetic resonance imaging data: validation of a new approach. J Neuroimaging. 2005 Oct; 15(4):305-14. View Abstract
  99. Video and CD-ROM as a training tool for performing neurologic examinations of 1-year-old children in a multicenter epidemiologic study. J Child Neurol. 2005 Oct; 20(10):829-31. View Abstract
  100. Development of visual acuity in children with cerebral visual impairment. Arch Ophthalmol. 2005 Sep; 123(9):1215-20. View Abstract
  101. Late gestation cerebellar growth is rapid and impeded by premature birth. Pediatrics. 2005 Mar; 115(3):688-95. View Abstract
  102. In vivo visualization of white matter fiber tracts of preterm- and term-infant brains with diffusion tensor magnetic resonance imaging. Invest Radiol. 2005 Feb; 40(2):110-5. View Abstract
  103. Identification of pressure passive cerebral perfusion and its mediators after infant cardiac surgery. Pediatr Res. 2005 Jan; 57(1):35-41. View Abstract
  104. Hemodilution elevates cerebral blood flow and oxygen metabolism during cardiopulmonary bypass in piglets. Ann Thorac Surg. 2004 May; 77(5):1656-63; discussion 1663. View Abstract
  105. CSF removal in infantile posthemorrhagic hydrocephalus results in significant improvement in cerebral hemodynamics. Pediatr Res. 2004 May; 55(5):872-6. View Abstract
  106. An elliptic PDE approach for shape characterization. Conf Proc IEEE Eng Med Biol Soc. 2004; 2004:1521-4. View Abstract
  107. Peroneal neuropathy from ankle-foot orthoses. Pediatr Neurol. 2003 Jul; 29(1):72-4. View Abstract
  108. Time course of changes in diffusion-weighted magnetic resonance imaging in a case of neonatal encephalopathy with defined onset and duration of hypoxic-ischemic insult. Pediatrics. 2001 Nov; 108(5):1211-4. View Abstract
  109. Cerebral infarction in Menkes' disease. Pediatr Neurol. 2000 Nov; 23(5):425-8. View Abstract
  110. Noninvasive detection of changes in cerebral blood flow by near-infrared spectroscopy in a piglet model of hydrocephalus. Pediatr Res. 2000 Oct; 48(4):445-9. View Abstract
  111. New technologies in pediatric neurology. Near-infrared spectroscopy. Semin Pediatr Neurol. 1999 Jun; 6(2):101-10. View Abstract
  112. Sonographic ventriculography: a new potential use for sonographic contrast agents in neonatal hydrocephalus. AJNR Am J Neuroradiol. 1998 Nov-Dec; 19(10):1931-4. View Abstract
  113. Vestibular-contingent voluntary saccades based on cognitive estimates of remembered vestibular information. Adv Otorhinolaryngol. 1988; 41:71-5. View Abstract

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