An observational study in Perinatal Stroke, sponsored by University of Wisconsin, Madison. Recruiting at 1 site in United States. Open to participants aged 0 Years to 24 Months. Per ClinicalTrials.gov, last updated 2026-09-18.
Sponsored by University of Wisconsin, Madison · Observational
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.
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:
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.
261 studies on the registry are indexed under Hypoxia-Ischemia, Brain; 95 are open to participants now.
This study's planned enrollment of 65 is below the median of 100 across 92 observational studies indexed under Hypoxia-Ischemia, Brain.
Browse Hypoxia-Ischemia, Brain studies →University of Wisconsin, Madison is the lead sponsor of 1,188 studies on the registry; 181 are open to participants now.
Of its 157 completed or terminated interventional studies of FDA-regulated products, 118 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
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 and infants able to attend study visits at the University of Wisconsin-Madison.
Main Inclusion Criteria:
Main Exclusion Criteria:
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.
Device: Magnetic Resonance Imaging · Behavioral: Behavioral Assessments · Device: Non invasive Transcranial Magnetic Stimulation
3 Tesla Discovery MR750 MRI scanner (GE Healthcare, Waukesha, WI) will be used to perform structural imaging, diffusion MRI, relaxometry and microstructural imaging. The exact scan length and parameters of each scan type (T1, T2, DWI) will be set for this study to optimize the quality of data and decrease the length of scanning session for each type of scan. All of the imaging methods have been previously implemented at UW-Madison. Each sequence will take approximately 5-10 minutes.
Also known as: MRI
The behavioral assessments (GMA: General Movements Assessment; HINE: Hammersmith Infant Neurological Examination; Baby Observation of Selective Control AppRaisal (BabyOSCAR); Bayley-4 / Bayley Scales of Infant and Toddler Development 4th ed; Pediatric Evaluation of Disability Inventory -Computer Adaptive Test (PEDI-CAT)) are infant and age-specific and will be administered by trained pediatric occupational and physical therapists.
TMS will be used to assess cortical excitability and circuitry (not as a neuromodulation intervention). Single-pulse TMS (Magstim 200², Magstim, UK) with a scalp surface coil will be used to assess how the brain is developing and how connected the tract is, between the brain and a target muscle on the arm. 10-20 TMS stimulation pulses will be delivered at a range of stimulation intensities (50-100%) increasing by 5% maximal stimulator output (MSO) at each stage. After this assessment, a brief assessment of peripheral nerve excitability will be performed. Peripheral stimulation will begin at 40% MSO. Stimulation intensity will be adjusted in increments of 5% until motor responses are evident on the EMG. Once motor responses are identified, 10 pulses will be delivered at the stimulation intensity that produced the response. In sum, around 150 stimulation pulses per hemisphere of brain stimulation and 22-60 pulses of peripheral stimulation are expected for TMS assessment of each infant.
Also known as: TMS
Change in Cortical excitability measured as presence/absence of motor evoked potentials (MEP)
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).
Time frame: 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months
Change in Cortical excitability measured by intensity of motor threshold (MT)
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.
Time frame: 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months
Change in Mean Fractional Anisotropy (FA) within the CST
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 scans
Time frame: 1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months
Behavioral assessments: General Movements Assessment (GMA) reported on binary (Y/N) scale
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".
Time frame: 1 ±1 month
Behavioral assessments: General Movements Assessment (GMA) reported on binary (Y/N) scale
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".
Time frame: 3 ±1 months
Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) global score
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.
Time frame: 1 ±1 month
Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) global score
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.
Time frame: 3-6 months (one visit in this time frame)
Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) global score
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.
Time frame: 12±1 months
Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) global score
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.
Time frame: 18±1 months
Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) global score
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.
Time frame: 24±1 months
Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) Asymmetry Scores
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.
Time frame: data collected at 1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months
Behavioral assessments: Bayley Scales of Infant and Toddler Development Test, 4th edition (Bayley-4) score
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.
Time frame: 3-6 months (one visit in this time frame)
Behavioral assessments: Bayley Scales of Infant and Toddler Development Test, 4th edition (Bayley-4) score
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.
Time frame: 12±1 months
Behavioral assessments: Bayley Scales of Infant and Toddler Development Test, 4th edition (Bayley-IV) score
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.
Time frame: 18±1 months
Behavioral assessments: Bayley Scales of Infant and Toddler Development Test, 4th edition (Bayley-4) score
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.
Time frame: 24±1 months
Baby Observation of Selective Control AppRaisal (Baby OSCAR)
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.
Time frame: 1±1 month
Baby Observation of Selective Control AppRaisal (Baby OSCAR)
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.
Time frame: 3-6 months (one visit in this time frame)
Change in Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT)
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.
Time frame: 1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months
Change in blood pressure
Time frame: 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
Time frame: 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
Time frame: 1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months
Change in body temperature
Time frame: 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
Respiration rate will be measured as breaths/minute.
Time frame: 1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months
Plan to share: Yes — Individual participant data collected during the trial will be shared after deidentification.
Supporting information: Study protocol, Statistical analysis plan
Time frame: Beginning 3 months after publication of primary outcomes, and ending 5 years after that date
Access criteria: Data will be shared with the researchers whose proposed use of the data is for independent verification of study outcomes or to conduct subsequent clinical research. Data sharing will be approved by an independent review committee identified for this purpose. Proposals should be directed to bgillick@wisc.edu. If approved after review by regulatory counsel, requestors will enter into a formal data sharing agreement. Data will be shared via encrypted single-user file transmission protocol.
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