Perinatal Stroke: Understanding Brain Reorganization

Completed

• Conditions: Stroke; Hemiparesis
• Interventions: Device: Magnetic Resonance Imaging; Device: Transcranial Magnetic Stimulation; Behavioral: General Movement Assessment

• Registration Number: NCT02743728
• Lead Sponsor: University of Minnesota

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.

Study Timeline

• Study First Submitted: 2016-02-19
• Study First Submitted QC: 2016-04-14
• Study First Posted: 2016-04-19
• Study Start: 2016-05-01
• Primary Completion: 2021-07-31
• Results First Submitted: 2022-01-20
• Results First Submitted QC: 2022-04-13
• Results First Posted: 2022-04-14
• Study Completion: 2022-07-31
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-05
• Last Update Posted: 2022-09-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
All Infants	Magnetic Resonance Imaging	Each infant will receive an Magnetic Resonance Imaging, then Transcranial Magnetic Stimulation Cortical Excitability testing, and General Movement Assessment. These 3 different components of the one arm in which all infants are involved will be collectively assessed.
All Infants	Transcranial Magnetic Stimulation	Each infant will receive an Magnetic Resonance Imaging, then Transcranial Magnetic Stimulation Cortical Excitability testing, and General Movement Assessment. These 3 different components of the one arm in which all infants are involved will be collectively assessed.
All Infants	General Movement Assessment	Each infant will receive an Magnetic Resonance Imaging, then Transcranial Magnetic Stimulation Cortical Excitability testing, and General Movement Assessment. These 3 different components of the one arm in which all infants are involved will be collectively assessed.

Primary Outcome Measures

Name	Time	Method
Cortical Excitability MEP Amplitude (µV)	2 hours	Cortical excitability of ipsilesional and contralesional hemispheres assessed by transcranial magnetic stimulation (TMS) in infants with perinatal stroke.; TMS will be used to assess cortical excitability through electromagnetic depolarization of targeted cortical neurons through painless pulses delivered over the scalp. The estimated time of TMS assessment is around 2 hours during Visit 2. Outcome is reported as MEP amplitude in units of microvolts (µV).
Cortical Excitability Percentage of Maximum	2 hours	Cortical excitability of ipsilesional and contralesional hemispheres assessed by transcranial magnetic stimulation (TMS) in infants with perinatal stroke.; TMS will be used to assess cortical excitability through electromagnetic depolarization of targeted cortical neurons through painless pulses delivered over the scalp. The estimated time of TMS assessment is around 2 hours during Visit 2. The outcome of motor threshold will be reported as the percentage of maximum stimulator output.

Secondary Outcome Measures

Name	Time	Method
General Movement Assessment	15 minutes	Movement quality will be assessed by general movement assessment (GMA). GMA requires 5-10 minutes videotaping when infants are placed in spine position for scoring. Infants are scores categorically as typical (present fidgety movements) or atypical (absent, sporadic, or abnormal fidgety movements). Outcome is reported as the number of typical infants and number of atypical infants.
Adverse Events	2 days	Recording of adverse events will take place during TMS cortical mapping and MRI scanning of infants with perinatal stroke. Assessment of vital signs changes and pain/stress responses during both MRI and TMS assessment during visit 1 and visit 2.; Outcome is reported as the number of adverse events recorded.
Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT)	15 minutes	The PEDI-CAT uses Item Response Theory statistical models to estimate a child's ability from a minimal number of items. Three functional domains will be assessed. The PEDI-CAT software provides normative standard scores presented as T scores and age percentile ranges to assess daily activities, mobility, and social/cognitive function. Outcome is reported as the mean score generated by the PEDI-CAT software.; Scores are based on t-test values and do not have a unit of measure or a defined range.; Higher scores indicate greater deviation from the standardized mean score.

Trial Locations

Locations (1)

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States