Reduced Hippocampal Volumes in Children with History of Hypoxic Ischemic Encephalopathy after Therapeutic Hypothermia.

Hypoxic ischemic encephalopathy (HIE) remains a significant cause of disability despite treatment with therapeutic hypothermia (TH). Many survive with more subtle deficits that affect daily functioning and school performance. We have previously shown an early indication of hippocampal changes in infants with HIE despite TH. The aim of this study was to evaluate the hippocampal volume via MRI and memory function at 5 years of age. A cohort of children followed from birth returned for a 5-year follow-up (n = 10 HIE treated with TH, n = 8 healthy controls). The children underwent brain MRI and neurodevelopmental testing to assess their brain volume, general development, and memory function. Children with HIE had smaller hippocampal volumes than the controls despite no differences in the total brain volume (p = 0.02). Children with HIE generally scored within the average range on developmental testing. Though there was no difference in the memory scores between these groups, there was a positive within-group correlation between the hippocampal volume and memory scores in children with HIE (sentence recall r = 0.66, p = 0.038). There was no relationship between newborn memory function and 5-year hippocampal size. Children with HIE treated with TH experienced significant and lasting changes to the hippocampus despite improvements in survival and severe disability. Future studies should target diminishing injury to the hippocampus to improve overall outcomes.

Safety and Feasibility of Transcranial Magnetic Stimulation as an Exploratory Assessment of Corticospinal Connectivity in Infants After Perinatal Brain Injury: An Observational Study.

BACKGROUND: Perinatal brain injuries often impact the corticospinal system, leading to motor impairment and cerebral palsy. Although transcranial magnetic stimulation (TMS) has been widely used to study corticospinal connectivity in adults and older children, similar studies of young infants are limited. OBJECTIVES: The objective was to establish the safety and feasibility of advanced TMS assessments of the corticospinal connectivity of young infants with perinatal brain injury. DESIGN: This was a pilot, cross-sectional study of 3- to 12-month-old (corrected age) infants with perinatal stroke or intracranial hemorrhage. METHODS: Six participants (2 term, 4 preterm) were assessed with stereotactic neuronavigation-guided TMS. Single-pulse TMS was applied to each hemisphere and responses were recorded simultaneously from both upper limbs. During data collection, vital signs and stress responses were measured to assess safety. Developmental motor outcomes were evaluated using the General Movements Assessment and Bayley Scales of Infant and Toddler Development (3rd edition). A clinical diagnosis of cerebral palsy was recorded, if available. RESULTS: No adverse events occurred during TMS testing. All sessions were well tolerated. Contralateral motor evoked responses were detected in 4 of 6 participants. Both contralateral and ipsilateral responses were observed in 2 of 6 participants. LIMITATIONS: TMS responses were not obtained in all participants. This could be related to the location of brain injury or developmental stage of the corticospinal system controlling the wrist flexor muscle group from which responses were recorded. CONCLUSIONS: This study provides a summary of the framework for performing novel TMS assessments in infants with perinatal brain injury. Implementing this approach to measure corticospinal connectivity in hypothesis-driven studies in young infants appears to be justified. Such studies could inform the characterization of corticospinal development and the neural mechanisms driving recovery following early interventions.

Motor Evoked Potentials as Potential Biomarkers of Early Atypical Corticospinal Tract Development in Infants with Perinatal Stroke.

Diagnosis of cerebral palsy (CP) after perinatal stroke is often delayed beyond infancy, a period of rapid neuromotor development with heightened potential for rehabilitation. This study sought to assess whether the presence or absence of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) could be an early biomarker of atypical development within the first year of life. In 10 infants with perinatal stroke, motor outcome was assessed with a standardized movement assessment. Single-pulse TMS was utilized to assess presence of MEPs. Younger infants (3-6 months CA, n = 5, 4/5 (80%)) were more likely to present with an MEP from the more-affected hemisphere (MAH) compared to older infants (7-12 months CA, n = 5, 0/5, (0%)) (p = 0.048). Atypical movement was demonstrated in the majority of infants with an absent MEP from the MAH (5/6, 83%) compared to those with a present MEP (1/4, 25%) (p = 0.191). We found that age influences the ability to elicit an MEP from the MAH, and motor outcome may be related to MAH MEP absence. Assessment of MEPs in conjunction with current practice of neuroimaging and motor assessments could promote early detection and intervention in infants at risk of CP.

Preserved speed of processing and memory in infants with a history of moderate neonatal encephalopathy treated with therapeutic hypothermia.

OBJECTIVE: Survivors of neonatal encephalopathy (NE) are at risk for impaired cognition. The objective of this study was to assess speed of processing (SOP) and memory in infants with moderate NE. STUDY DESIGN: Sample consisted of 17 infants with NE and 23 healthy controls. Visual-evoked potentials (VEP) were assessed at 8 months to assess SOP. Memory was assessed at 12 months using elicited imitation (EI). Memory and SOP had previously been assessed in this cohort in the newborn period. RESULTS: Infants with NE had similar SOP and EI performance as controls. Newborn SOP correlated with 8-month SOP in infants with NE, however, neonatal ERP memory measures were not correlated with EI performance at 12 months. CONCLUSIONS: Infants with moderate NE treated with TH show preserved memory and SOP through 12 months. Early behavioral and electrophysiologic assessments of memory and SOP provide insight into developing cognitive functions in this risk group.