Is postural orthostatic tachycardia syndrome (POTS) a central nervous system disorder?

Postural orthostatic tachycardia syndrome (POTS), a disorder of the autonomic nervous system characterized by a rise in heart rate of at least 30 bpm from supine to standing position, has been traditionally viewed as a dysfunction of the peripheral nervous system. However, recent studies and evidence from overlapping conditions suggest that in addition to being considered a disorder of the peripheral nervous system, POTS should be viewed also as a central nervous system (CNS) disorder given (1) significant CNS symptom burden in patients with POTS; (2) structural and functional differences found on neuroimaging in patients with POTS and other forms of orthostatic intolerance; (3) evidence of cerebral hypoperfusion and possible alteration in cerebrospinal fluid volume, and (4) positive response to medications targeting the CNS and non-pharmacologic CNS therapies. This review outlines existing evidence of POTS as a CNS disorder and proposes a hypothetical model combining key mechanisms in the pathophysiology of POTS. Redefining POTS as a CNS disorder can lead to new possibilities in pharmacotherapy and non-pharmacologic therapeutic interventions in patents affected by this disabling syndrome.