Perinatal Stroke: Understanding Brain Reorganization

NCT ID: NCT02743728

Last Updated: 2022-09-19

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

20 participants

Study Classification

OBSERVATIONAL

Study Start Date

2016-05-01

Study Completion Date

2022-07-31

Brief Summary

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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

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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.

Conditions

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Stroke Hemiparesis

Study Design

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Observational Model Type

OTHER

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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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.

Magnetic Resonance Imaging

Intervention Type DEVICE

Anatomical and Diffusion Tensor Imaging Analysis.

Transcranial Magnetic Stimulation

Intervention Type DEVICE

Assessment of brain (cortical) excitability

General Movement Assessment

Intervention Type BEHAVIORAL

Spontaneous movement assessment of infant while lying in unperturbed state.

Interventions

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Magnetic Resonance Imaging

Anatomical and Diffusion Tensor Imaging Analysis.

Intervention Type DEVICE

Transcranial Magnetic Stimulation

Assessment of brain (cortical) excitability

Intervention Type DEVICE

General Movement Assessment

Spontaneous movement assessment of infant while lying in unperturbed state.

Intervention Type BEHAVIORAL

Eligibility Criteria

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Inclusion Criteria

* 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


\- Previous participation in pilot study

Exclusion Criteria

* 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


\- Lack of wireless internet access or computer to participate in virtual Zoom call
Minimum Eligible Age

3 Months

Maximum Eligible Age

5 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cerebral Palsy Alliance

OTHER

Sponsor Role collaborator

American Academy of Cerebral Palsy and Developmental Medicine

OTHER

Sponsor Role collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

University of Minnesota

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bernadette T Gillick, PhD, MSPT, PT

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Locations

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University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Countries

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United States

References

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Lehman LL, Rivkin MJ. Perinatal arterial ischemic stroke: presentation, risk factors, evaluation, and outcome. Pediatr Neurol. 2014 Dec;51(6):760-8. doi: 10.1016/j.pediatrneurol.2014.07.031. Epub 2014 Aug 14.

Reference Type BACKGROUND
PMID: 25444092 (View on PubMed)

Eyre JA, Taylor JP, Villagra F, Smith M, Miller S. Evidence of activity-dependent withdrawal of corticospinal projections during human development. Neurology. 2001 Nov 13;57(9):1543-54. doi: 10.1212/wnl.57.9.1543.

Reference Type BACKGROUND
PMID: 11706088 (View on PubMed)

Chen CY, Tafone S, Lo W, Heathcock JC. Perinatal stroke causes abnormal trajectory and laterality in reaching during early infancy. Res Dev Disabil. 2015 Mar;38:301-8. doi: 10.1016/j.ridd.2014.11.014. Epub 2015 Jan 9.

Reference Type BACKGROUND
PMID: 25577180 (View on PubMed)

Thelen E, Corbetta D, Spencer JP. Development of reaching during the first year: role of movement speed. J Exp Psychol Hum Percept Perform. 1996 Oct;22(5):1059-76. doi: 10.1037//0096-1523.22.5.1059.

Reference Type BACKGROUND
PMID: 8865616 (View on PubMed)

Einspieler C, Prechtl HF. Prechtl's assessment of general movements: a diagnostic tool for the functional assessment of the young nervous system. Ment Retard Dev Disabil Res Rev. 2005;11(1):61-7. doi: 10.1002/mrdd.20051.

Reference Type BACKGROUND
PMID: 15856440 (View on PubMed)

Eyre JA, Miller S, Clowry GJ, Conway EA, Watts C. Functional corticospinal projections are established prenatally in the human foetus permitting involvement in the development of spinal motor centres. Brain. 2000 Jan;123 ( Pt 1):51-64. doi: 10.1093/brain/123.1.51.

Reference Type BACKGROUND
PMID: 10611120 (View on PubMed)

Eyre JA, Smith M, Dabydeen L, Clowry GJ, Petacchi E, Battini R, Guzzetta A, Cioni G. Is hemiplegic cerebral palsy equivalent to amblyopia of the corticospinal system? Ann Neurol. 2007 Nov;62(5):493-503. doi: 10.1002/ana.21108.

Reference Type BACKGROUND
PMID: 17444535 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25283350 (View on PubMed)

Gillick BT, Krach LE, Feyma T, Rich TL, Moberg K, Thomas W, Cassidy JM, Menk J, Carey JR. Primed low-frequency repetitive transcranial magnetic stimulation and constraint-induced movement therapy in pediatric hemiparesis: a randomized controlled trial. Dev Med Child Neurol. 2014 Jan;56(1):44-52. doi: 10.1111/dmcn.12243. Epub 2013 Aug 21.

Reference Type BACKGROUND
PMID: 23962321 (View on PubMed)

Kirton A, Chen R, Friefeld S, Gunraj C, Pontigon AM, Deveber G. Contralesional repetitive transcranial magnetic stimulation for chronic hemiparesis in subcortical paediatric stroke: a randomised trial. Lancet Neurol. 2008 Jun;7(6):507-13. doi: 10.1016/S1474-4422(08)70096-6. Epub 2008 May 1.

Reference Type BACKGROUND
PMID: 18455961 (View on PubMed)

Narayana S, Rezaie R, McAfee SS, Choudhri AF, Babajani-Feremi A, Fulton S, Boop FA, Wheless JW, Papanicolaou AC. Assessing motor function in young children with transcranial magnetic stimulation. Pediatr Neurol. 2015 Jan;52(1):94-103. doi: 10.1016/j.pediatrneurol.2014.08.031. Epub 2014 Sep 18.

Reference Type BACKGROUND
PMID: 25439485 (View on PubMed)

van de Ruit M, Perenboom MJ, Grey MJ. TMS brain mapping in less than two minutes. Brain Stimul. 2015 Mar-Apr;8(2):231-9. doi: 10.1016/j.brs.2014.10.020. Epub 2014 Nov 8.

Reference Type BACKGROUND
PMID: 25556004 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32289718 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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PT-2015-23643

Identifier Type: -

Identifier Source: org_study_id

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