Symptoms in hEDS Patients with Reduced Orthostatic Cerebral Blood Flow Velocity and Small Fiber Neuropathy
Patients with hypermobile Ehlers-Danlos syndrome who exhibit reduced orthostatic cerebral blood flow velocity and small fiber neuropathy report a constellation of orthostatic, pain, autonomic, and gastrointestinal symptoms, with orthostatic dizziness being the most directly correlated with cerebrovascular dysregulation.
Orthostatic and Cerebrovascular Symptoms
- Orthostatic dizziness is the hallmark symptom directly correlated with reduced orthostatic cerebral blood flow velocity, which occurs in 79% of hEDS patients 1
- Lightheadedness upon standing is a primary manifestation of cerebral hypoperfusion 2
- Blurred vision occurs as a consequence of inadequate cerebral perfusion during postural changes 2
- Generalized weakness accompanies orthostatic intolerance in this population 2
- Palpitations and tremulousness are common autonomic manifestations 2
Pain and Sensory Symptoms
- Neuropathic pain is nearly universal, with all but one patient in studied cohorts reporting pain consistent with small fiber neuropathy 3
- Pain intensity ranges from moderate (NRS ≥4) to severe (NRS ≥7), with the majority experiencing severe pain 3
- Patients report 7 or more symptoms on the Small Fiber Neuropathy Symptoms Inventory Questionnaire 3
- Both proximal and distal body regions are affected, reflecting the generalized distribution of nerve fiber loss rather than a typical length-dependent pattern 4
- Thermal and tactile hypesthesia (reduced sensation) occurs throughout the body 4
- Chronic widespread pain is a defining feature, present in over 90% of patients 1
Autonomic Dysfunction Symptoms
- Widespread but mild autonomic failure is present in 90% of hEDS patients 1
- Orthostatic sudomotor symptoms (abnormal sweating patterns with position changes) occur in over 90% 1
- Vasomotor symptoms (abnormal blood vessel responses) affect over 90% of patients 1
- Cognitive dysfunction accompanies autonomic dysregulation 2
- Bladder dysfunction is not uncommon in this population 2
Gastrointestinal Symptoms
- Gastrointestinal symptoms occur in over 90% of hEDS patients and are more severe in those with concomitant POTS 1, 2
- Nausea is one of the most predictive symptoms of abnormal GI motility 2
- Abdominal pain is highly prevalent and predictive of dysmotility 2
- Early satiety frequently occurs 2
- Vomiting, diarrhea, bloating, and severe constipation are common manifestations 2
- These symptoms may be attributable to visceral hypersensitivity and/or dysmotility 2
Specific Orthostatic Syndromes Identified
The head-up tilt testing in this population reveals distinct patterns:
- Postural tachycardia syndrome (POTS) occurs in 33% of hEDS patients with these features 1
- Hypocapnic cerebral hypoperfusion is present in 22% 1
- Orthostatic cerebral hypoperfusion syndrome affects 18% 1
- Neurogenic orthostatic hypotension occurs in 9% 1
Important Clinical Considerations
The combination of reduced orthostatic cerebral blood flow velocity and small fiber neuropathy creates a dual mechanism for symptom generation: cerebrovascular dysregulation causes orthostatic symptoms while small fiber neuropathy contributes to pain, sensory disturbances, and autonomic dysfunction 1, 4. The small fiber neuropathy in hEDS is generalized rather than length-dependent, explaining why patients report symptoms in both proximal and distal body regions 4. This differs from typical diabetic or other metabolic neuropathies that follow a stocking-glove distribution.
Patients with dysautonomia show both A-delta and C-fiber impairment, while those without dysautonomia may only exhibit A-delta fiber loss 5. This suggests a spectrum of small fiber involvement that correlates with the severity of autonomic symptoms.
The prevalence of small fiber neuropathy using combined structural and functional criteria reaches 82% in hEDS patients 1, making it an extremely common feature that contributes substantially to the symptom burden alongside cerebrovascular dysregulation.