Clinical trial NCT02743728: Perinatal Stroke: Understanding Brain Reorganization
Official title: Perinatal Stroke: Understanding Brain Reorganization Through Infant Neuroimaging and Neuromodulation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Stroke
Hemiparesis
Keywords: perinatal stroke
transcranial magnetic stimulation
magnetic resonance imaging
diffusion tensor imaging
non-invasive brain stimulation
infant
Lead sponsor: University of Minnesota
Sponsor class: OTHER
Collaborators: name: Cerebral Palsy Alliance
name: American Academy of Cerebral Palsy and Developmental Medicine
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2016-04-19
Enrollment: 20
Sex: ALL
Minimum age (years): 3
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The pilot study portion will recruit infants with unilateral perinatal stroke between 3 to 5 months of corrected age to understand their brain reorganization after stroke.

The follow-up study portion will recruit children aged 5 years or younger who have been diagnosed with perinatal stroke and who participated in the pilot study.

Brief summary: The incidence of perinatal stroke is relatively common, as high as 1 in 2,300 births, but little is known about the resulting changes in the brain that eventually manifest as cerebral palsy (CP). Motor signs that indicate the infant is beginning to develop CP often do not become evident for several months after the diagnosis of perinatal stroke which delays therapy. The main purpose of this study is to examine early brain reorganization in infants 3-12 months of age corrected for prematurity with perinatal stroke using magnetic resonance imaging (MRI) and non-invasive transcranial magnetic stimulation (TMS). In addition, the association between the brain reorganization and motor outcomes of these infant participants will be identified.

In this study, the MRI scans will include diffusion tensor imaging (DTI) - an established method used to investigate the integrity of pathways in the brain that control limb movement. Infants will be scanned during nature sleeping after feeding. The real scanning time will be less than 38 minutes. TMS is a painless, non-surgical brain stimulation device which uses principles of electromagnetic induction to excite cortical tissue from outside the skull. Using TMS as a device to modulate and examine cortical excitability in children with hemiparetic CP and in adults has been conducted previously.

In this infant study, we will assess cortical excitability from the motor cortex of both the ipsilesional and contralesional hemispheres under the guidance of a frameless stereotactic neuronavigation system. Additionally, the investigators will assess infants' movement quality using an age-appropriate standardized movement assessment. This will allow the investigators to examine the relationship between measures of motor pathway integrity and early signs of potential motor impairment. We will longitudinally follow enrolled infants, and complete repeat assessments at 12- and 24-months corrected age to assess how infants develop over time after perinatal stroke. The remote follow-up will occur at 5 years or less.

Detailed description: Understanding the early brain reorganization before the brain has not yet largely reorganized is critical for developing efficacious early intervention. As a unique aspect of investigation, this study will combine Magnetic Resonance Imaging (MRI)/ Diffusion Tensor Imaging (DTI) and TMS to provide an additional opportunity to assess both the cortical excitability and corticospinal tract (CST) integrity in infants with perinatal stroke.

Identifying the association between laboratory assessment results and developmental outcomes is also critical. This study is to use MRI/DTI and TMS to comprehensively examine both the CST integrity and cortical excitability in infants following perinatal stroke, and to identify association with motor outcome as evaluated by movement assessment.

Eligibility criteria: Inclusion Criteria for Pilot Study:

* Birth diagnosis of unilateral perinatal stroke by cranial ultrasound, computer tomography (CT) or magnetic resonance imaging (MRI)
* Corrected gestational age between 3 and 24 months of age for both infants with stroke and typically developing infants

Exclusion Criteria for Pilot Study :

* Metabolic Disorders
* Neoplasm
* Disorders of Cellular Migration and Proliferation
* Acquired Traumatic Brain Injury
* Received surgeries that may constraint current spontaneous movements
* Indwelling metal or incompatible medical devices
* Received surgeries that may constraint current spontaneous movements
* Other neurologic disorders unrelated to stroke
* Small for gestational age (SGA): Infants are smaller in size than normal for the gestational age
* Apneic episodes and syncope (known heart defects) for the safety of participants in the stud.
* Genetic disorders
* Uncontrolled seizures

Additional Inclusion Criteria for Follow-up Study:

- Previous participation in pilot study

Additional Exclusion Criteria for Follow-up Study:

- Lack of wireless internet access or computer to participate in virtual Zoom call

Primary outcomes:
measure: Cortical Excitability MEP Amplitude (µV)
timeFrame: 2 hours
measure: Cortical Excitability Percentage of Maximum
timeFrame: 2 hours
Secondary outcomes:
measure: General Movement Assessment
timeFrame: 15 minutes
measure: Adverse Events
timeFrame: 2 days
measure: Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT)
timeFrame: 15 minutes
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: Bernadette T Gillick, PhD, MSPT, PT
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Gillick BT, Krach LE, Feyma T, Rich TL, Moberg K, Menk J, Cassidy J, Kimberley T, Carey JR. Safety of primed repetitive transcranial magnetic stimulation and modified constraint-induced movement therapy in a randomized controlled trial in pediatric hemiparesis. Arch Phys Med Rehabil. 2015 Apr;96(4 Suppl):S104-13. doi: 10.1016/j.apmr.2014.09.012. Epub 2014 Oct 2.
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citation: Kowalski JL, Hickey M, Rao R, Georgieff MK, Chen M, Gillick BT. Safety of single-pulse TMS in two infants with implanted patent ductus arteriosus closure devices. Brain Stimul. 2020 May-Jun;13(3):861-862. doi: 10.1016/j.brs.2020.03.007. Epub 2020 Mar 14. No abstract available.