Determining the prevalence and clinical characteristics of paediatric paroxysmal movement disorders in Ireland

Objective: Paroxysmal movement disorders (PxMD) are characterised by episodic involuntary movements and are divided into paroxysmal dyskinesias (PD) and episodic ataxias (EA). Despite existence in the medical literature since 1892, much remains unknown about PxMD including their exact prevalence in adult and paediatric populations. Notwithstanding recent increases in known genetic causes of PxMD, there is a paucity of literature on yield from genetic investigations, optimal investigation approach and treatment outcomes in children. This study set out to clinically characterise PxMD and to determine the prevalence in a paediatric population for the first time. Methods: Cross sectional cohort study across paediatric neurology services in the Republic of Ireland incorporating retrospective chart reviews (clinical presentation, treatment response, co-morbidities, genetics, neuroimaging, electrophysiology) and phone reviews with patients and families. Results: Seventy-nine cases met inclusion criteria (PD=37, EA=38, AHC=4). Point prevalence for all PxMD was 6.5 cases per 100,000 persons aged less than 18 years (PD 3/100,000, EA 3.1/100,000, AHC 0.3/100,000). Sixty-four cases were reviewed clinically (PD=33, EA=31). A cause was identified in 34% (22/64) with no difference between PD (42%,14/33) and EA (26%, 8/31) subgroups (2=1.96, p=0.162). The highest investigation yield was from single gene testing (35%, 7/20) followed by gene panels (25%, 11/44), whole genome sequencing (25%, 2/8) and whole exome sequencing (9%, 1/11). Neuroimaging performed in 73% (47/64) and EEG in 59% (38/64) did not contribute to diagnosis in any case. Variable evolution patterns were seen between disorders. In PD, 55% (18/33) resolved and 30% (10/33) improved, with medication accounting for resolution or improvement in 61% (20/33). In EA, 45% (14/31) resolved and 42% (13/31) improved, with self-resolution responsible for resolution or improvement in 48% (17/33). Conclusion: The findings of this study have added to the knowledge base of PxMD in determining the prevalence of PxMD among a paediatric population for the first time. This prevalence is higher than previously estimated in adult populations. Despite this, PxMD remain rare with an often prolonged time to diagnosis. The study has shown that current practice results in aetiology identification in only one third of patients. Encouragingly however, large proportions of PxMD patients can expect symptom improvement either with medications or self-resolution over time. Future work should centre on increased recognition of PxMD by neurologists and referring clinicians to facilitate earlier diagnosis, a new focus on the associated psychological co-morbidities, an increased emphasis on the identification of new genetic causes, and a detailed evaluation of effective existing and prospective therapies.