Quantitative mapping of the basal ganglia and related structures in children with dyskinetic cerebral palsy

Principal Investigator: Alexander Hoon

Cerebral palsy (CP) refers to a group of motor-impairment syndromes secondary to genetic and acquired disorders of early brain development.  When the underlying disorder affects the basal ganglia (BG) and cortico-striato-thalamic-cortical (CSTC) circuits- from etiologies including acute hypoxic ischemic encephalopathy (HIE) and genetic metabolic disorders, the clinical manifestations are often classified as dyskinetic cerebral palsy.  Currently there remains an incomplete understanding of the pathophysiology of dyskinetic CP as well as variability in treatment effects and outcome.  High resolution imaging techniques- including diffusion tensor imaging (DTI) of white matter tracts and quantitative susceptibility mapping (QSM), can provide detailed characterization of basal ganglia structure and connectivity. Taking advantage of anisotropic diffusion, DTI demonstrates brain axonal organization in detail beyond the resolution of conventional MRI.  QSM can be used to measure tissue magnetic susceptibility, which is related to tissue iron concentration, myelin and deoxyhemoglobin. High resolution QSM provides excellent tissue contrast in the basal ganglia region, showing clearly these iron-rich nuclei.

In previous research over the past decade, we have shown that there is preferential injury in sensory pathways than in descending corticospinal tracts in children born prematurely with PVL and CP, and that this injury pattern is associated with sensorimotor impairment.  This proposed quantitative BG mapping study of children with dyskinetic CP builds on our current work utilizing DTI in children with PVL and spastic diplegia.  Using a cross-sectional descriptive research design, 15 children with dyskinetic CP and 15 age-matched healthy controls 6-17 years of age born at term will be recruited for study participation.  Standardized functional motor and dystonia scales will be used to purposively recruit a diverse sample of children with dyskinetic CP.  All children will participate in a research scan including DTI, QSM and volumetric measures derived from conventional sequences.  The aim of this exploratory study is to use these advanced neuroimaging techniques to quantitatively map injury to basal ganglia (BG) and related structures in children with dyskinetic cerebral palsy (CP).

One of the recent advances in medical management for dyskinetic CP is Deep Brain Stimulation (DBS).  One of the challenges is where in the basal ganglia to place the electrodes to control the abnormal movements.  Results from this study will provide characterization of basal ganglia injury into a quantitative map, which can be used in the future to assist in the determination of electrode placement in DBS and to investigate relationships between underlying etiology and injury in the basal ganglia.  Further quantifications of these deep gray structures and their connections in children with dyskinetic cerebral palsy may help us refine the electrode targets for this therapeutic intervention and with future research, identify which children may benefit most.