Rare pediatric movement disorders : clinical aspects of genotype, phenotype, and assessment

Sammanfattning: Pediatric movement disorders are defined by an impaired ability to initiate and control movements. Dystonia, one of these disorders, may cause a life-long severe motor disability. Pharmacological treatment is often insufficient, but deep brain stimulation (DBS) has turned out to be effective for some dystonia subtypes. Reliable and valid assessment tools are needed to evaluate new interventions for dystonia. The Dyskinesia Impairment Scale (DIS) is an assessment scale for dystonia and choreoathetosis, designed for children and youth with dyskinetic cerebral palsy. However, the DIS is comprehensive, and its administration and scoring times are long, and the scale is often disregarded in a clinical setting. The overall aim of this thesis was to enable and facilitate assessment of dystonia and choreoathetosis in children and young adults, and to elucidate some clinical aspects in two rare pediatric-onset dystonia disorders. Study I: This prospective long-term case series indicates that benign paroxysmal torticollis of infancy does not lead to neurological sequelae. At the last follow-up, with a mean age of 14 years, all 11 children attended regular school, and no one reported motor problems. Five had developed migraine and/or episodic syndromes that may be associated with migraine. We found no known mutations in candidate genes. Nevertheless, in the case of a severe phenotype, specifically if there are paroxysmal disorders in the family history, it may be important to follow the children longitudinally and genetic testing can be considered. Study II: This retrospective multi-center case series confirms that pallidal DBS is an effective treatment option for individuals with DYT-THAP1 dystonia. Fourteen individuals were followed for a median time of nearly five years, and at the last follow-up, median dystonia reduction was about 60% when assessed with the Burke–Fahn–Marsden Movement Scale (BFM-M). However, improvement was less obvious in the orolaryngeal and craniocervical regions; anatomical areas which are often affected by dystonia in these individuals. Study III: This cross-sectional two-center study was an instrument evaluation of the DIS for a new population; children and young adults with inherited or idiopathic dystonia. The DIS and the dystonia subscale were shown to have good-to-excellent inter-rater and test–retest reliability, whereas the choreoathetosis subscale had moderate inter-rater and excellent test–retest reliability. Concurrent validity for the dystonia subscale, when compared with the gold standard BFM-M, was good. Altogether, these results indicate that the DIS might be a valuable tool to evaluate dystonia and choreoathetosis in inherited and idiopathic dystonia. Study IV: This cross-sectional two-center study aimed to design a more clinically useful version of the DIS, the DIS-II. Scale development included an online advisory expert meeting, iterative discussions within the research team, and a Rasch measurement model analysis. With a reduced number of scoring steps, the DIS-II evaluates 60% of the items in the original DIS. The result from the Rasch analysis demonstrates evidence of construct validity of the scale. Furthermore, a high person reliability indicates that the DIS-II may separate assessed individuals into eight distinct ability levels. Altogether, this implies that the DIS-II provides valid and reliable measures for dystonia and choreoathetosis and reduces administration and scoring times in comparison with the DIS.