• Miller, Steven P.

    Titles
    Affiliate Investigator, BC Children's Hospital
    Head, Division of Neurology, The Hospital for Sick Children
    Bloorview Children's Hospital Foundation Chair in Paediatric Neuroscience
    Senior Scientist, Neuroscience & Mental Health
    Professor, Department of Paediatrics, University of Toronto

    Affiliate Professor, Department of Pediatrics, University of British Columbia


    Degrees / Designations

    MDCM FRCPC

    Primary Area of Research
    Secondary Area(s) of Research
    Phone
    416-813-6659
    Fax
    416-813-6334
    Lab Phone
    Mailing Address
    Division of Neurology
    The Hospital for Sick Children

    555 University Avenue
    Toronto, ON M5G 1X8


    Affiliate Websites
    Research Areas
  • Brain development and injury in the newborn
  • Advanced magnetic resonance (MR) techniques, such as MR imaging, MR spectroscopy, and diffusion tensor imaging
  • Bedside brain monitoring, such as amplitude integrated EEG and near infra-red spectroscopy
Summary

The focus of the neonatal neurology research group is to better understand brain development and injury in the newborn. Using advanced magnetic resonance (MR) techniques and bedside brain monitoring we study how white matter injury and systemic illness affects brain development in critically ill newborns. A better understanding of the factors that impact brain development and injury will allow us to directly improve the neurodevelopmental outcome of high-risk newborns.

Neurodevelopmental impairments are common in newborns delivered prior to term age and in newborns with heart birth defects, and result in a large burden of long-term disability. White matter injury, abnormal brain development and systemic illness are interrelated abnormalities that commonly follow preterm birth or heart birth defects, with focal non-cystic white matter injury being the characteristic pattern of brain injury. Though focal non-cystic white matter injury is associated with diffuse abnormalities of motor and cognitive function, how this happens is unknown. Systemic illness (e.g. infection) and therapy (e.g. steroids) may also be associated with diffuse abnormalities of motor and cognitive function.

Current Projects

Advances in magnetic resonance (MR) technology allow for brain development and injury to be studied safely in critically ill newborns. MR imaging (MRI) is a sensitive tool to measure brain structure and injury. In particular, deformation morphometry, diffusion tensor imaging, and MR spectroscopic imaging, can be used to quantify brain structure, microstructure and metabolism. Using advanced magnetic resonance (MR) techniques, as well as bedside brain monitoring, such as amplitude integrated EEG and near infra-red spectroscopy, we study brain development and injury in vulnerable populations of newborns.

Abnormal brain development and injury in premature newborns

In 2003 in British Columbia, more than 5% of all newborns were born prematurely and/or at low birth weight. These children are at very high risk for developmental delays: 5-10% of low birth-weight children exhibit major motor deficits and 25-50% exhibit significant developmental and visual deficits. The most important brain pathology associated with these deficits is injury to the white matter. Our study is characterizing the consequences of abnormal brain development and white matter injury in the premature newborn, including how delayed brain development results in impaired motor and cognitive function. This study builds on our earlier observations that: 1) brain injury in premature newborns is safely detected with MRI before term-equivalent age; 2) focal non-cystic white matter injury is the characteristic pattern of injury in the premature newborn; 3) early brain injury is associated with adverse early neurodevelopmental outcome; and 4) brain injury in the immature brain impairs subsequent brain development.

Brain Injury in Newborns with Congenital Heart Disease

Developmental deficits in children with congenital heart disease are a serious problem and may be seen in more than one third of affected newborns. However, the reasons for these developmental deficits remain unknown and may occur prior to, during or following their cardiac surgery. In this study we are investigating the timing and severity of brain injury in newborns with congenital heart disease using advanced MR imaging techniques in utero, shortly before open-heart surgery and again soon after surgery. As newborns with congenital heart disease, like premature newborns, are also specifically vulnerable to white matter injury, studying these two populations allows us to explore shared mechanisms of white matter injury. Knowing the mechanisms and timing of brain injury in newborns with heart disease will be important for the rational design of studies to evaluate emerging strategies to protect the developing brain from injury.

Many physicians consider brain injury to be the major remaining challenge in caring for critically ill newborns. The ability of advanced MR brain imaging techniques to detect which newborns have abnormalities of the brain will help parents and physicians better care for these critically ill infants. The longer-term goal of my research program will be to test new strategies to prevent brain injury in the human newborn. The advanced MR techniques I am applying in this research program provide us with powerful surrogate markers of brain injury that will allow us to monitor the effect of novel strategies to protect the brain from injury.

Selected Publications

Chau V, Brant R, Poskitt KJ, Tam EW, Synnes A, Miller SP. Postnatal Infection is Associated with Widespread Abnormalities of Brain Development in Premature Newborns. Pediatr Res 2012; 71(3):274-9.
 
Brummelte S, Grunau RE, Chau V, Poskitt KJ, Brant R, Vinall J, Gover A, Synnes AR, Miller SP. Procedural Pain and Brain Development in Premature Newborns. Ann Neurol 2012; 71(3):385-96.

Tam EW, Chau V, Ferriero DM, Barkovich AJ, Poskitt KJ, Studholme C, Fok ED, Grunau RE, Glidden DV, Miller SP. Preterm Cerebellar Growth Impairment After Postnatal Exposure to Glucocorticoids. Sci Transl Med. 2011; 3(105):105ra105.

Tam EWY, Miller SP, Studholme C, Chau V, Glidden D, Poskitt KJ, Ferriero DM, Barkovich AJ. Differential Effects of Intraventricular Hemorrhage and White Matter Injury on Preterm Cerebellar Growth. Journal of Pediatrics. 2010 Oct 19. [Epub ahead of print]

Bonifacio SL, Glass HC, Chau V, Berman JI, Xu D, Brant R, Barkovich AJ, Poskitt KJ, Miller SP, Ferriero DM. Extreme Premature Birth is Not Associated with Impaired Development of Brain Micro¬structure. Journal of Pediatrics. 2010; 157(5):726-32.e1.

Block AJ, McQuillen PS, Chau V, Glass H, Poskitt KJ, Barkovich AJ, Esch M, Soulikias W, Azakie A, Campbell A, Miller SP. Clinically silent preoperative brain injuries do not worsen with surgery in neonates with congenital heart disease. Journal of Thoracic and Cardiovascular Surgery 2010; 140(3):550-7.

Adams E, Chau V, Poskitt KJ, Grunau RE, Synnes A, Miller SP. Tractography-Based Quantitation of Cortico¬spinal Tract Development in Premature Newborns. Journal of Pediatrics, 2010;156(6):882-8

Miller SP, Ferriero DM. From Selective Vulnerability To Connectivity: Insights From Newborn Brain Imaging. Trends Neurosci. 2009;32(9):496-505.

Chau V, Poskitt KJ, McFadden DE, Bowen-Roberts T, Synnes A, Brant R, Sargent MA, Soulikias W, Miller SP. Effect of chorioamnionitis on brain development and injury in premature newborns. Annals of Neurology 2009; 66(2):155-64.

Glass HC, Glidden D, Jeremy RJ, Barkovich AJ, Ferriero DM, Miller SP. Clinical Neonatal Seizures are Independently Associated with Outcome in Infants at Risk for Hypoxic-Ischemic Brain Injury. Journal of Pediatrics 2009; 155(3):318-23. (chosen for editorial commentary)

Tam EWY, Ferriero DM, Xu D, Berman JI, Vigneron DB, Barkovich AJ, Miller SP. Cerebellar development in the preterm neonate: effect of supratentorial brain injury. Pediatric Research 2009; 66(1):102-6.

Chau V, Poskitt KJ, Sargent MA, Lupton BA, Hill A, Roland E, Miller SP.: Comparison of computer tomography and magnetic resonance imaging scans on the third day of life in term newborns with neonatal encephalopathy. Pediatrics. 2009 Jan;123(1):319-26.

Miller SP, McQuillen PS, Hamrick S, Xu D, Glidden DV, Charlton N, Karl T, Azakie A, Ferriero DM, Barkovich AJ, Vigneron DB. Abnormal brain development in newborns with Congenital Heart Disease. New England Journal of Medicine. 2007; 357(19):1928-38.

McQuillen PS, Hamrick SEG, Perez M, Barkovich AJ, Glidden DV, Karl T, Teitel D, Miller SP. Balloon Atrial Septostomy is Associated with Preoperative Stroke in Neonates with Transposition of the Great Arteries. Circulation 2006; 113(2):280-5.

Miller SP, Ferriero DM, Leonard C, Piecuch R, Glidden DV, Partridge JC, Perez M, Mukherjee P, Vigneron DB, Barkovich AJ. Early Brain Injury in Premature Newborns Detected with MRI is Associated with Adverse Early Neurodevelopmental Outcome. Journal of Pediatrics. 2005; 147(5):609-616.

Miller SP, Ramaswamy V, Michelson D, Barkovich AJ, Holshouser B, Wycliffe N, Glidden DV, Deming D, Partridge JC, Wu YW, Ashwal S, Ferriero DM. Patterns of Brain Injury in Term Neonatal Encephalopathy. Journal of Pediatrics, 2005; 146(4): 453-60.

Grants

CIHR Operating Grant – Project: "Analgesia and sedation in the preterm neonate: brain development and outcome" (2014-2020)

Honours & Awards
Bloorview Children's Hospital Foundation Chair in Paediatric Neuroscience 2012
President Elect, Society for Pediatric Research 2012
Tier 2 Canada Research Chair in Neonatal Neuroscience - 2010-2015
Royal College Medal in Medicine, Royal College of Physicians & Surgeons of Canada 2010
Young Alumni Award, Medicine Alumni Global, McGill University Faculty of Medicine 2009
Canadian Institutes of Health Research (CIHR), Clinician Scientist (Phase 2) 2006-2011
Michael Smith Foundation for Health Research, Scholar 2006-2012  
Canadian Institutes of Health Research (CIHR), Clinician Scientist (Phase 2)
Michael Smith Foundation for Health Research, Scholar.
Council Member (Neurology), Society for Pediatric Research
Chair, Scientific Selection Committee, Child Neurology Society

 

 

Research Group Members

CFRI:
Sandy Belanger, RN – Research Nurse
Mark Chalmers – Respiratory Therapist
Janet Rigney – Research Coordinator 
Jill Vinall – Graduate student
Jill Zwicker, PhD – Postdoctoral Fellow 

Hospital for Sick Children:
Emma Duerden, PhD – Research Associate