Hemiparesis, Stroke
Conditions
Keywords
perinatal stroke, transcranial magnetic stimulation, magnetic resonance imaging, diffusion tensor imaging, non-invasive brain stimulation, infant
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.
Interventions
DEVICEMagnetic Resonance Imaging
Anatomical and Diffusion Tensor Imaging Analysis.
DEVICETranscranial Magnetic Stimulation
Assessment of brain (cortical) excitability
BEHAVIORALGeneral Movement Assessment
Spontaneous movement assessment of infant while lying in unperturbed state.
Sponsors
Cerebral Palsy Alliance
American Academy of Cerebral Palsy and Developmental Medicine
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of Minnesota
Study design
Observational model
OTHER
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
3 Months to 5 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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: Anatomical and Diffusion Tensor Imaging Analysis.
Transcranial Magnetic Stimulation: Assessment of brain (cortical) excitability
General Movement Assessment: Spontaneous movement assessment of infant while lying in unperturbed state. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | All Infants | — |
|---|---|---|
| Age, Categorical <=18 years | 20 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 0 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 20 participants | — |
| Sex: Female, Male Female | 6 Participants | — |
| Sex: Female, Male Male | 14 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 13 |
| other Total, other adverse events | 0 / 13 |
| serious Total, serious adverse events | 0 / 13 |
Outcome results
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).
Time frame: 2 hours
Population: Of the 20 enrolled infants, 11 infants participated in TMS. 3 of the 11 infants participated in TMS sessions at two different timepoints; therefore, 14 datasets for TMS outcome measures (MEP amplitude (Outcome 1), Resting Motor Threshold (Outcome 2) were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Infants | Cortical Excitability MEP Amplitude (µV) | 325 µV |
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.
Time frame: 2 hours
Population: Of the 20 enrolled infants, 11 infants participated in TMS. 3 of the 11 infants participated in TMS sessions at two different timepoints; therefore, 14 datasets for TMS outcome measures (MEP amplitude (Outcome 1), Resting Motor Threshold (Outcome 2) were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Infants | Cortical Excitability Percentage of Maximum | 70 %MSO |
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.
Time frame: 2 days
Population: Of the 20 enrolled infants, 13 infants participated in either MRI or TMS (during which adverse events were recorded).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Infants | Adverse Events | 0 # Adverse Events |
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.
Time frame: 15 minutes
Population: Of the 20 enrolled infants, 12 were able to complete the General Movements Assessment (GMA). The GMA was only completed if infants were between 3-5 months of age at the time of enrollment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Infants | General Movement Assessment | Typical | 8 Participants |
| All Infants | General Movement Assessment | Atypical | 4 Participants |
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.
Time frame: 15 minutes
Population: Of the 20 enrolled infants, 6 infants participated in remote follow-up and were assessed with the PEDI-CAT.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| All Infants | Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) | Daily Activities | 46 normative age percentiles |
| All Infants | Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) | Mobility | 42 normative age percentiles |
| All Infants | Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) | Social/Cognitive | 38 normative age percentiles |