Time-of-Day and State-Dependent Variation in Movement Disorders: A Primer of Relevant Clinical Conditions

Movement disorders may vary with the time of day and with mental state. Despite hypothalamic control of biological timing, we discuss how many cell populations throughout the brain and body, including dopaminergic nuclei, likely have time-keeping functions. We provide a “primer” of movement disorders with significant variation in time or with presentation in a state of altered consciousness. Parkinsonism illustrates our overall argument. Patients with an idiopathic behavioral and motoric disorder in sleep develop a parkinsonism eventually, at a high phenotype conversion rate over roughly ten years. Diurnal variation in severity of motor manifestations happens after diagnosis of a parkinsonism, and nocturnal movements of various types also occur after diagnosis. An inflammatory or autoimmune mechanism for timing or state variability in movement disorders may be part of the pathophysiology in many Parkinsonisms, but autoimmunity as a disease mechanism becomes particularly relevant in various encephalitides associated with movement disorders. We address seven major syndromes. Further addressing temporal variability, we then discuss Willis-Ekbom (restless legs) syndrome, an akathisia that implicates both iron and dopamine. Clinically, it is a multi-faceted movement disorder associated with either recumbency or with sleep. Next, we discuss dystonias characterized specifically by variation during the day. The clinical implications of our review are several: Parkinsonism is not exclusively a motor disease; identification of movement disorders is increasingly important in encephalitic conditions; state-dependency (in altered consciousness, in repose, in sleep) and temporal variation are hallmarks of many dyskinesias. We end with observations about the relevance of time in the assessment of disordered movement.