Implementation of a Comprehensive Telehealth Assessment Battery for Complex Neurogenetic Disease: An Observational Study of Rapid-Onset Dystonia-Parkinsonism

ATP1A3-related syndromes represent a continuously expanding clinical spectrum and present with an extraordinarily wide range of symptoms. New phenotypes continue to emerge, posing ongoing challenges for both diagnosis and development of treatments. In this context, telemedicine offers a unique opportunity to greatly expand outreach to patients. Remote, high-resolution assessments help refine phenotypic characterization and the identification of novel and intermediate phenotypes. In this study we aimed to determine completion rates and practicality of conducting motor, speech, and neuropsychological assessments entirely via virtual visits. Although the broader recruitment included several ATP1A3-related disorders, this virtual battery was specifically developed for subjects with RDP. Participants with other ATP1A3 phenotypes enrolled in the study contributed to evaluating the overall feasibility of the workflow but were not the target population for the full battery. We recruited individuals with suspected or confirmed diagnosis of ATP1A3-related disorders, along with familial controls, from three participant clinical sites. Participants completed all study procedures through scheduled telemedicine visits using their personal devices (tablets, laptops, smartphones). A total of 59 participants were enrolled, including 46 individuals with suspected or confirmed ATP1A3 variants and 13 family member controls. Among affected patients, 18 had RDP, 12 AHC (Alternating Hemiplegia of Childhood), 4 CAPOS (Cerebellar ataxia, Areflexia, Pes cavus, Optic atrophy, Sensorineural hearing loss), 10 were categorized as "uncertain" and 2 with "mixed" phenotype (RDP/CAPOS and RDP/AHC). The virtual assessment battery included: (i) patient history questionnaire (PHQ), (ii) structured neurological examination adapted for virtual visits, (iii) speech recording, and (iv) extensive neuropsychological assessment. Feasibility was evaluated based on completion rates for each assessment component. Remote neurological, speech and neurocognitive/psychiatric assessments were completed by most participants with ATP1A3 phenotypes, with completion rates of 78% for motor examination and 87% for speech evaluation. The observed pattern of motor and speech impairments were consistent with prior in-person evaluations, supporting the validity and feasibility for both motor and nonmotor features of remote assessment in complex genetic neurological disease.