Dopamine Treatment in Children With Cerebral Palsy With Dystonia- A Double Blind Controlled Study

Overview

Background: Cerebral palsy (CP) is the main cause of childhood immobility and is defined as a non progressive injury to the developing central nervous system in children younger than 3 years, resulting in neurological and musculoskeletal abnormalities. The main pathophysiological causes are encephalopathy of prematurity (periventricular leukomalacia) hypoxic ischemic encephalopathy. Infections, infracts and migration defects are other less common causes of CP. The brain injury leads to functional motor impairment impacting on daily activities commonly manifests as a movement disorder: pyramidal, leading to spasticity and extra-pyramidal leading to dystonia and chorea. In most cases extensive brain injury causes a mixed movement disorder. Dystonia is defined as involuntary muscle contractions causing twisting and abnormal postures. While the neurological underpinnings of CP remain unknown, a link between low dopamine and increased acetylcholine release has recently been reported in dystonia. Dopamine is considered the first line of treatment in children with dystonia and CP followed by anticholiergic treatment with trihexphenidyl. The recommendation of dopaminergic treatment is based on need to rule out dopamine-responsive-dystonia, a rare genetic disorder, and on single case study reporting improvement in CP. A double blind study support or refute the use of dopamine treatment for dystonic CP was never reported. Working hypothesis and Aims: In children with CP due to a clear underlying pathology, dopamine treatment will not improve daily function. Methods: the investigators will perform a double blinded randomized controlled crossover study. 50 children ages 4-18 years with a clear pathophysiological cause for CP will be enrolled. Each child will receive dopamine and placebo treatment for 2 weeks with a 2 week washout interval. Participants will be randomized into 2 groups; one will receive placebo followed by dopamine and the other vice versa. The primary outcome measure, goal-attainment-scale, and secondary outcome functional measures (such as box and blocks, 9 hole pegs, pronation/ supination, finger sequencing) will be assessed at the beginning and end of each treatment as well as parent questionnaires regarding satisfaction and side effects. Expected results: No functional improvement with dopamine treatment compared to placebo. Importance: supplying sufficient data to support or refute the use of dopamine treatment for dystonic CP. Probable implications to Medicine: this may lead to a change in medical treatment guidelines for children with CP.