Perinatal Stroke: Understanding Brain Reorganization

Stroke Clinical Trial

Official title:

Perinatal Stroke: Understanding Brain Reorganization Through Infant Neuroimaging and Neuromodulation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02743728
• Other study ID #: PT-2015-23643
• Status: Completed
• Start date: May 1, 2016
• Est. completion date: July 31, 2022

Study information

• Verified date: September 2022
• Source: University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: July 31, 2022
• Est. primary completion date: July 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 5 Years

Eligibility

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

Related Conditions & MeSH terms

• Hemiparesis
• Paresis
• Stroke

Intervention

Device:
• Magnetic Resonance Imaging
Anatomical and Diffusion Tensor Imaging Analysis.
• Transcranial Magnetic Stimulation
Assessment of brain (cortical) excitability

Behavioral:
• General Movement Assessment
Spontaneous movement assessment of infant while lying in unperturbed state.

Locations

Country	Name	City	State
United States	University of Minnesota	Minneapolis	Minnesota

Sponsors (4)

Lead Sponsor	Collaborator
University of Minnesota	American Academy of Cerebral Palsy and Developmental Medicine, Cerebral Palsy Alliance, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

References & Publications (12)

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View 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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	General Movement Assessment	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
Secondary	Adverse Events	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
Secondary	Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT)	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