Comorbidity of Ehlers-Danlos syndrome with postural tachycardia syndrome and/or cerebrospinal fluid hypovolemia

Abstract

Since around 2000, evidence has been accumulated that Ehlers-Danlos syndrome (EDS) highly co-occurs with postural tachycardia syndrome (PoTS) and/or cerebrospinal fluid (CSF) hypovolemia. The essential matters for discussion on the reason of this comorbidity is as follows: (1) The overwhelming majority cases of EDS are hypermobility type, which exhibit joint hypermobility only. (2) PoTS is characterized by excessive venous blood pooling in the lower part of the body while standing, but typical PoTS patients also exhibit emotional disturbance, e. g. anxiety and depression. Most authors have attributed such emotional disturbance to centripetal input of chronic pain into the central autonomic network (CAN). (3) Most cases of CSF hypovolemia have CSF leak, but decreased production in CSF to compensate the leak is essentially involved in the development of CSF hypovolemia. Concerning the reason of the comorbidity of EDS, PoTS and CSF hypovolemia, some authors have suggested that EDS induces PoTS or CSF hypovolemia; venous hyperextensibility may contribute to the excessive blood pooling, and fragility of the connective tissue may induce CSF leak. However, the majority cases of EDS are lacking venous hyperextensibility and tissue fragility. Recently, Sharp, Critchley, and Eccles (2021) provided a rational hypothesis for the association of EDS and PoTS; patients with both conditions have altered interoception, which produces abnormal emotion and autonomic activities in the CAN. Patients with EDS have altered input of deep sensation into the CAN persistently from periods of development. We suggest that altered interoception is underlying in EDS, PoTS, and CSF hypovolemia.