Baby Brain Recovery Study
- Conditions
- Perinatal Stroke
- Interventions
- Device: Magnetic Resonance ImagingBehavioral: Behavioral AssessmentsDevice: Non invasive Transcranial Magnetic Stimulation
- Registration Number
- NCT05013736
- Lead Sponsor
- University of Wisconsin, Madison
- Brief Summary
This study will be a longitudinal multiple-visit observational study, done to identify possible bioindicators of recovery and repair of motor corticospinal pathways which may be targeted by future interventions in infants with perinatal stroke.
65 participants will be recruited and complete 1 visit at time point 1 (0-2 months), and 2 visits at each timepoints 2-5 with windows of +- 4 weeks (3-6 months, 12 months, 18 months and 24 months). Visits will consist of Magnetic Resonance Imaging (MRI) assessment during the child's natural sleep, Transcranial Magnetic Stimulation (TMS), and Motor Behavioral Assessments.
- Detailed Description
Perinatal stroke has disabling consequences; 50-75% of individuals will develop life-long motor impairment, and 10-60% will also have cognitive deficits. These deficits lead to challenges in the school and home environments, with decreased likelihood of employment and independence and increased caregiver burden. Additionally, perinatal stroke is one of the primary causes of cerebral palsy (CP), a chronic and disabling neurological condition affecting motor function.
The first two years of life constitute a critical period of brain development and heightened neuroplasticity. There is now a consensus that, due to brain plasticity and rapid development, providing an early intervention may result in optimal recovery and lower costs of care. Unfortunately, researchers still have only limited understanding of how the brain develops after perinatal stroke and as a result CP diagnoses are typically not made until two years of age. There is an urgent need for very early diagnosis, prognosis and understanding of mechanisms in order to develop novel early interventions to improve outcomes in perinatal stroke with resultant CP.
Integrating study team's experience in studying and caring for this vulnerable infant stroke population, they propose to use non-invasive brain stimulation, neuroimaging, and behavioral assessments to analyze associations between development patterns, especially in the CST, and potential diagnosis of CP.
Specific aims of this study are:
* Aim 1. Map the presence and excitability of corticospinal pathways.
* Aim 2. Map the structural integrity and connectivity of corticospinal pathways.
* Aim 3. Compare motor outcomes from clinical behavioral assessments against corticospinal tract excitability and integrity.
* Aim 4. Identify the association between brain white-matter connectivity and general movements.
* Aim 5. Identify the association between corticospinal circuitry and general movements.
Protocol Amendment approved on 10/22/2021 removes TMS intervention and outcomes, adds a study time point at 0-2 months, and lowers the eligibility age to term.
Protocol Amendment approved on 12/21/2021 adds the TMS intervention back.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 65
- Infants with corrected gestational age between term age and 24 months of age at study enrollment
- Radiologically-confirmed acute unilateral or bilateral brain lesions, including perinatal stroke, neonatal hemorrhagic or thrombotic stroke, involving the motor cortex and/or subcortical structures, and intracranial hemorrhage, involving the motor cortex and/or subcortical white matter, periventricular leukomalacia, and hypoxic-ischemic encephalopathy (HIE)
- English-speaking parent/legal guardian (able to provide consent)
Main
- Other neurologic disorders unrelated to perinatal stroke/brain bleed/HIE
- Metabolic disorders
- Disorders of Cellular Migration and Proliferation
- Acquired Traumatic Brain Injury
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Infants Magnetic Resonance Imaging Pre-term and term born infants with corrected gestational age between term age and 24 months with radiologically-confirmed acute unilateral or bilateral brain lesions, including perinatal stroke, neonatal hemorrhagic or thrombotic stroke, involving the motor cortex and/or subcortical structures, and intracranial hemorrhage, involving the motor cortex and/or subcortical white matter, or periventricular leukomalacia. Parents/legal guardians able to attend study visits at the University of Wisconsin-Madison. Infants Non invasive Transcranial Magnetic Stimulation Pre-term and term born infants with corrected gestational age between term age and 24 months with radiologically-confirmed acute unilateral or bilateral brain lesions, including perinatal stroke, neonatal hemorrhagic or thrombotic stroke, involving the motor cortex and/or subcortical structures, and intracranial hemorrhage, involving the motor cortex and/or subcortical white matter, or periventricular leukomalacia. Parents/legal guardians able to attend study visits at the University of Wisconsin-Madison. Infants Behavioral Assessments Pre-term and term born infants with corrected gestational age between term age and 24 months with radiologically-confirmed acute unilateral or bilateral brain lesions, including perinatal stroke, neonatal hemorrhagic or thrombotic stroke, involving the motor cortex and/or subcortical structures, and intracranial hemorrhage, involving the motor cortex and/or subcortical white matter, or periventricular leukomalacia. Parents/legal guardians able to attend study visits at the University of Wisconsin-Madison.
- Primary Outcome Measures
Name Time Method Change in Cortical excitability measured as presence/absence of motor evoked potentials (MEP) 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months Motor evoked potentials (MEPs) are the electrical signals recorded from the descending motor pathways or from muscles following stimulation of motor pathways within the brain.
Responses from TMS pulses will be measured by recording muscle activity, referred to as motor evoked potentials (MEP).Change in Cortical excitability measured by intensity of motor threshold (MT) 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months The MT is the minimum stimulation intensity that will elicit a consistent MEP of a pre-determined amplitude. MT and MEP are the common measures of TMS-induced excitability. Together, these measures provide information about the brain's excitability, associated with synaptic activity.
Change in Mean Fractional Anisotropy (FA) within the CST 1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months Mean Fractional Anisotropy (FA) within the CST will be used to study structural connectivity. It is a dimensionless index between 0 and 1. (0 equals no anisotropy; greater anisotropy is indicated by higher FA values approaching the maximum of 1).
N=10 infants aged 0-2 months (first timepoint) will participate in MRI scansBehavioral assessments: General Movements Assessment (GMA) reported on binary (Y/N) scale 3 ±1 months The General Movements Assessment is used to identify absent or abnormal general movements. GMA requires 5-10 minutes video taping when infants are placed in spine position for scoring.
"Absence or abnormal movements" will be reported as "Y".Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) global score 24±1 months The HINE includes three sections, the Neurological Examination, the Development of Motor Functions and the State of Behaviour. The first section evaluates cranial nerve, posture, movements, tone and reflexes. These items are not age-dependent. The second section evaluates head control, sitting, voluntary grasping, rolling, crawling and walking. The third section evaluates state of consciousness, emotional state and social orientation.
The maximum score for any one item is a score of 3 and the minimum is a score of 0. A subscore can be given for each section and the overall global score can be calculated by summing up all 26 items (range: 0-78), with higher scores indicating better neurological performance. High-risk cutoff scores for cerebral palsy are \<57 at 3 months and \<73 at 6, 9, or 12 months. See Novak et al, 2017 linked in the reference section for context.Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) Asymmetry Scores data collected at 1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months An asymmetry can also be recorded for each item, with one point maximum allotted per item, with a total score ranging from 0-26. Based on the literature regarding asymmetries, the cutoff score of \>3 asymmetries will be used for recommendation of referral to early intervention service. See article by Fehlings, 2024 for additional context.
Behavioral assessments: Bayley Scales of Infant and Toddler Development Test, 4th edition (Bayley-4) score 24±1 months Bayley-4 is a developmental test that measures cognitive, language, motor, and social-emotional domains of infants and young children between 1 and 42 months of age. A higher score generally corresponds with higher function.
Behavioral assessments: Bayley Scales of Infant and Toddler Development Test, 4th edition (Bayley-IV) score 18±1 months Bayley-4 is a developmental test that measures cognitive, language, motor, and social-emotional domains of infants and young children between 1 and 42 months of age. A higher score generally corresponds with higher function.
Baby Observation of Selective Control AppRaisal (Baby OSCAR) 3-6 months (one visit in this time frame) Baby OSCAR assessments are scored from video recordings of infant movement. Each limb is scored separately, with scores ranging 0-7 per lower limb, and 0-9 per upper limb for a total score of 0-32. Higher scores indicate better selective motor control.
Change in Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) 1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months Patient/caregiver-reported outcome measure of functional abilities and performance in children with disabilities. Scores are displayed instantly after completion of an assessment. A Detailed Score Report and a Summary Score Report are available. Normative scores are provided as age percentiles and T scores are based on a child's chronological age and intended for use by clinicians so that they may interpret a particular child's functioning relative to others of the same age. Scaled scores provide a way to look at a child's current functional skills and progress in these skills over time. Scaled scores are especially helpful in documenting improvements in functional skills for children not expected to exhibit or regain normative levels of functioning.
- Secondary Outcome Measures
Name Time Method Change in blood pressure 1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months Change in respiration rate 1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months Respiration rate will be measured as breaths/minute.
Change in body temperature 1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months Change in heart rate 1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months Change in skin integrity reported as presence/absence of skin redness/rash 1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months
Trial Locations
- Locations (1)
University of Wisconsin School of Medicine and Public Health
🇺🇸Madison, Wisconsin, United States