Neuroimaging and movement assessment for early detection of cerebral palsy

Abstract

Cerebral palsy (CP), often caused by early brain injury such as perinatal stroke or brain bleed, has lifelong impact on function and participation. Early identification of at-risk infants and access to rehabilitation interventions are critical to improve long-term outcomes. Recent clinical guidelines highlight the importance of key evidence-based assessments for early detection of CP. Neuroimaging can identify injury patterns that are associated with increased risk of CP. Movement assessments, including the General Movements Assessment (GMA) and Hammersmith Infant Neurological Examination (HINE), provide information about neuromotor development. As these evidence-based assessments are increasingly integrated into clinical settings, the subsequent real-world impact on diagnosis and intervention access timelines in varied clinical populations needs to be assessed. Furthermore, while the GMA has very high sensitivity and specificity to predict CP, the neurological correlates of the spontaneous (general) movements which it assesses are poorly understood. This limits the interpretation and use of the GMA to guide prognosis and early intervention strategies. To address these research gaps, this dissertation aimed to assess 1) the impact of evidence-based infant assessments on diagnostic timeline and intervention access and 2) brain connectivity related to early spontaneous motor patterns in infants with perinatal brain injury. For Aim 1, I assessed the relationships between early evidence-based assessments, diagnosis timeline, and rehabilitation intervention access in a population of children with CP who were seen between 2010 and 2022 at the University of Wisconsin Waisman Center Newborn Follow Up Clinic. I found that CP-specific assessments were increasingly integrated after the publication of early detection guidelines by Novak et al. in 2017. Age at CP first mention (high risk for CP) decreased over time, though age at diagnosis remained similar. Infants who received multiple evidence-based assessments were diagnosed at a younger age. Ninety-eight percent of children were referred to rehabilitation therapies prior to or at the time of CP diagnosis. Changes in referral practices were observed between outpatient therapies and early intervention over time, with referrals to outpatient therapies occurring at earlier ages in more recent years. In Aim 2, I investigated white matter pathways using diffusion-weighted MRI and looked for differences in white matter connectivity among infants with typical and atypical general movements on the GMA. With tract-based spatial statistics analysis, I found differences in white matter integrity among groups in several white matter pathways. I additionally used tractography to compare diffusion parameters in individual tracts between infants with and without typical general movements. In most tracts, diffusion parameters did not differ significantly between groups. Metrics of tract integrity in the corticospinal tract tended to have greater asymmetries between hemispheres in infants with asymmetries in their spontaneous movements. An exploratory longitudinal analysis showed that infants with poor repertoire general movements who developed absent fidgety movements had lower tract integrity in the CST than those who developed normal fidgety movements. Results from this study indicated that white-matter integrity across many brain regions may be implicated in general movements. However, existing research supports the likelihood of additional changes in gray matter and brainstem regions that were not detected in this analysis. This work adds to our understanding of the real-world use and rationale for neuroimaging and spontaneous motor assessment for early detection of CP. Future work in this field will support early detection and diagnosis efforts and promote advanced understanding of developmental trajectories in infants with perinatal brain injury, which may facilitate more timely and targeted early rehabilitation interventions and improved outcomes.