Tremor and myoclonus: clinical, neurophysiological and neuroimaging phenotypes in children and adolescents

Tremor, defined as an involuntary rhythmic oscillatory movement, and myoclonus, characterized by brief, jerk-like movements, are distinct hyperkinetic movement disorders. Despite differences in their pathophysiology and clinical management, tremor and myoclonus are often confused due to their potentially similar presentations. Tremor and myoclonus are considered uncommon in children and adolescents, and few studies have investigated their causes and clinical features in the pediatric population. Therefore, the spectrum of clinical features and underlying causes of tremor and myoclonus in young patients remains only partially understood. Additionally, classification systems for tremor and myoclonus are largely based on adult-onset conditions, and their clinical applicability in children and adolescents has not yet been tested. The aim of this thesis is to dissect the phenotype of tremor and myoclonus in children and adolescents. By assessing a large cohort of patients with childhood-onset tremor and myoclonus, including the collection of clinical, neurophysiological and neuroimaging data, this project aims to address currently unanswered questions about these disorders in children. First, through a deep analysis of a large pediatric cohort, we tested whether the latest classification of tremor syndromes is applicable to childhood-onset tremor, analyzing specific peculiarities and diagnostic uncertainties. Second, we investigated the clinical phenotype of essential tremor in children, examining its neurophysiological features. Third, we explored whether co-occurring subtle neurological abnormalities in patients with essential tremor ("essential tremor plus") are associated with identifiable anatomical differences in brain volumetry. Fourth, we assessed the role of combined EEG-polymyography in the diagnosis of tremor and myoclonus, evaluating its utility in refining clinical diagnoses. Finally, we investigated the neurophysiological features of myoclonus in a cohort of affected children, focusing on the accuracy of polymyographic recordings in differentiating myoclonus subtypes.