Lesion distribution and network mapping in dyskinetic cerebral palsy

Dyskinetic cerebral palsy encompasses a group of predominantly perinatally acquired complex motor disorders that present with dystonia and/or choreoathetosis and are frequently associated with brain lesions in neuroimaging. Recently, lesion network mapping provided a tool to redefine neurological disorders as circuitopathies. Elucidating the common networks impacted by lesions in this condition could pave the way to identify new targets for neuromodulatory therapeutic approaches. In this study, we aim to assess lesion distribution in dyskinetic cerebral palsy and identify a related functional network derived from lesions. Here, we review the literature of MRI findings in dyskinetic cerebral palsy and perform literature-based lesion network mapping. Articles reporting conventional MRI findings clearly attributable to affected patients were included for review. Imaging findings and their anatomical distribution were extracted and quantified according to an established MRI classification system for cerebral palsy. Reviewed articles were searched for figures depicting lesions and these were traced onto a paediatric template. Whole-brain functional connectivity from lesions causing dyskinetic cerebral palsy was calculated using a paediatric resting-state functional MRI connectome. Individual maps were thresholded and later overlapped to derive a common network map associated with dyskinetic cerebral palsy. Results were contrasted with two control datasets for spatial specificity. Review of 48 selected articles revealed that grey matter injury predominated (51%), followed by white matter injury (28%). In 16% of cases MRI was normal. Subcortical lesions affected the thalamus, pallidum and putamen in >40% of reported patients, respectively. Figures available from 23 literature cases were used to calculate the lesion netwok map of dyskinetic cerebral palsy. The lesion-derived map revealed functional connectivity to a wide network including the brainstem, cerebellum, basal ganglia, cingulate and sensorimotor cortices. The strongest connectivity was found for the motor thalamus. This study confirms subcortical grey matter lesions as the most common MRI finding in dyskinetic cerebral palsy. The neural network identified with lesion network mapping includes areas previously implicated in hyperkinetic disorders and highlights the motor thalamus as a common network node. These results should be validated and their therapeutic implications explored in prospective trials.