Hypermobile Ehlers-Danlos Syndrome: Cerebrovascular, Autonomic and Neuropathic Features

Background

Hypermobile Ehlers-Danlos syndrome (hEDS) affects multiple systems, but comprehensive evaluations of a larger sample of hEDS patients are lacking. The objective of this study was to describe cerebrovascular, autonomic, and neuropathic features of hEDS.

Methods

This retrospective case-control study was conducted at Brigham and Women’s Faulkner Hospital between 2016-2023. Data from hEDS patients who completed autonomic testing and skin biopsies were analyzed. Outcome measures include validated surveys (Survey of Autonomic Functions, Neuropathy Total Symptom Score-6 (SAS)) and autonomic function testing (Valsalva maneuver, deep breathing, head-up tilt and sudomotor), cerebrovascular (cerebral blood flow velocity (CBFv) in the middle cerebral artery), respiratory (capnography), and neuropathic (skin biopsies for assessment of small fiber neuropathy) testing and inflammatory/ autoimmune markers.

Results

Total 270 hEDS patients were analyzed and compared to 29 healthy controls. Common hEDS complaints (prevalence > 90% ) were orthostatic sudomotor, vasomotor, gastrointestinal, and pain. Orthostatic cerebral blood flow velocity was reduced in 79% of hEDS and correlated with orthostatic dizziness. The head-up tilt test revealed postural tachycardia syndrome (prevalence 33%), hypocapnic cerebral hypoperfusion (22%), orthostatic cerebral hypoperfusion syndrome (18%), and neurogenic orthostatic hypotension (9%). Widespread but mild autonomic failure was present in 90% of hEDS patients on autonomic testing. Small fiber neuropathy using structural criteria was detected in 64%, and using combined structural and functional criteria in 82%.

Conclusions

This study provided evidence of cerebrovascular dysregulation with reduced orthostatic cerebral blood flow velocity associated with symptoms of cerebral hypoperfusion, frequent small fiber neuropathy, and widespread but mild autonomic failure in hEDS.