Perinatal Stroke: Understanding Brain Reorganization

NCT02743728 | Completed Results

• 1 other identifier: PT-2015-23643
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Stroke; Hemiparesis

Keywords

perinatal stroke; transcranial magnetic stimulation; magnetic resonance imaging; diffusion tensor imaging; non-invasive brain stimulation; infant

Outcome Measures

Primary Outcomes (2)

• Cortical Excitability MEP Amplitude (µV)

  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

  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 Outcomes (3)

• General Movement Assessment

  15 minutes

• Adverse Events

  2 days

• Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT)

  15 minutes

Study Arms (1)

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.

Device: Magnetic Resonance Imaging; Device: Transcranial Magnetic Stimulation; Behavioral: General Movement Assessment

Interventions

Magnetic Resonance Imaging DEVICE

Anatomical and Diffusion Tensor Imaging Analysis.

All Infants

Transcranial Magnetic Stimulation DEVICE

Assessment of brain (cortical) excitability

All Infants

General Movement Assessment BEHAVIORAL

Spontaneous movement assessment of infant while lying in unperturbed state.

All Infants

Eligibility Criteria

• Age: 3 Months - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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
• \- Previous participation in pilot study
• \- Lack of wireless internet access or computer to participate in virtual Zoom call

Sponsors & Collaborators

• University of Minnesota: lead
• Cerebral Palsy Alliance: collaborator
• American Academy of Cerebral Palsy and Developmental Medicine: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (13)

• 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.

  PMID: 25444092 BACKGROUND

• 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.

  PMID: 11706088 BACKGROUND

• 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.

  PMID: 25577180 BACKGROUND

• 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.

  PMID: 8865616 BACKGROUND

• 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.

  PMID: 15856440 BACKGROUND

• 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.

  PMID: 10611120 BACKGROUND

• 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.

  PMID: 17444535 BACKGROUND

• 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.

  PMID: 25283350 BACKGROUND

• 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.

  PMID: 23962321 BACKGROUND

• 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.

  PMID: 18455961 BACKGROUND

• 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.

  PMID: 25439485 BACKGROUND

• 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.

  PMID: 25556004 BACKGROUND

• 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.

  PMID: 32289718 DERIVED

MeSH Terms

Conditions

Stroke; Paresis

Interventions

Magnetic Resonance Imaging; Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Magnetic Field Therapy; Therapeutics

Results Point of Contact

• Title: Dr. Bernadette Gillick
• Organization: University of Minnesota

gillick@umn.edu

612-626-5898

Study Officials

• Bernadette T Gillick, PhD, MSPT, PT

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2016
• First Posted: April 19, 2016
• Study Start: May 1, 2016
• Primary Completion: July 31, 2021
• Study Completion: July 31, 2022
• Last Updated: September 19, 2022
• Results First Posted: April 14, 2022

Record last verified: 2022-09

Locations

US (1)