Perinatal Stroke: Understanding Brain Reorganization

September 5, 2022 updated by: University of Minnesota

Perinatal Stroke: Understanding Brain Reorganization Through Infant Neuroimaging and Neuromodulation

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.

Study Overview

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 Type

Observational

Enrollment (Actual)

20

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 months to 5 years (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
All Infants
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.
Anatomical and Diffusion Tensor Imaging Analysis.
Assessment of brain (cortical) excitability
Spontaneous movement assessment of infant while lying in unperturbed state.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cortical Excitability MEP Amplitude (µV)
Time Frame: 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).

2 hours
Cortical Excitability Percentage of Maximum
Time Frame: 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.

2 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
General Movement Assessment
Time Frame: 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.
15 minutes
Adverse Events
Time Frame: 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.

2 days
Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT)
Time Frame: 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.

15 minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 1, 2016

Primary Completion (ACTUAL)

July 31, 2021

Study Completion (ACTUAL)

July 31, 2022

Study Registration Dates

First Submitted

February 19, 2016

First Submitted That Met QC Criteria

April 14, 2016

First Posted (ESTIMATE)

April 19, 2016

Study Record Updates

Last Update Posted (ACTUAL)

September 19, 2022

Last Update Submitted That Met QC Criteria

September 5, 2022

Last Verified

September 1, 2022

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Stroke

Clinical Trials on Magnetic Resonance Imaging

3
Subscribe