Headaches in hEDS

Headaches are very common in individuals with hypermobile Ehlers-Danlos (hEDS), and they tend to be more frequent, severe, and disabling than in the general population. Studies suggest that 50–75% of people with hEDS experience headaches, with migraine being the most frequently reported type. The underlying causes are multifactorial, involving both structural and functional contributors.

Headache Types in hEDS

Causes of Headaches in hEDS

The causes of headache in hEDS are multifactorial and may include

• Migraine pathophysiology (how migraines develop, possibly due to nervous system changes like central sensitization—increased sensitivity to pain)

• Cervical spine instability or spondylosis (instability or degeneration in the neck portion of the spine), contributing to cervicogenic headaches (headaches originating from the neck)

• Temporomandibular joint (TMJ) dysfunction (problems in the jaw joint)

• Meningeal fragility (weakness in the membranes covering the brain and spine), predisposing to spontaneous cerebrospinal fluid (CSF) leaks (leakage of spinal fluid that reduces pressure in the brain)

• Chiari I malformation (a condition where brain tissue extends into the spinal canal) and other craniocervical anomalies (structural problems where the skull meets the spine)

• Autonomic dysfunction (impaired automatic body functions), including postural orthostatic tachycardia syndrome (POTS) (a condition where heart rate increases excessively upon standing)

• Mast cell activation disorders (immune cells release chemicals inappropriately), which may promote neuroinflammation (inflammation in the nervous system) and hypersensitivity

Symptoms

• Migraine features: unilateral (one-sided), pulsatile (throbbing) pain, photophobia (light sensitivity), phonophobia (sound sensitivity), and nausea

• Cervicogenic symptoms: neck pain, limited neck range of motion

• TMJ-related pain: facial or temple discomfort, clicking or popping of the jaw

• Orthostatic features: headache that worsens upon standing and improves when lying down—should prompt evaluation for CSF leak or dysautonomia (autonomic dysfunction)

Treatment Approaches

Empirically Supported Treatments

High-quality trials are limited, but commonly used treatments include

• Acute migraine therapy

  • Triptans: migraine-specific drugs that narrow blood vessels in the brain

  • NSAIDs: non-steroidal anti-inflammatory drugs (e.g., ibuprofen)

  • Antiemetics: medications to reduce nausea and vomiting

• Migraine prevention

  • Beta blockers: drugs that slow heart rate and reduce blood pressure

  • Tricyclic antidepressants (e.g., amitriptyline): older antidepressants used at low doses for pain

  • Antiepileptics (e.g., topiramate): seizure medications that also reduce migraine frequency

• Physical therapy

  • Targets cervical spine (neck region) and TMJ dysfunction (jaw joint issues)

  • Must be guided by therapists familiar with hEDS to prevent joint or tissue injury

• Cervicogenic headache

  • Headache caused by neck joint or muscle dysfunction

  • May respond to facet joint injections (into small spinal joints) or nerve blocks (temporary nerve numbing) in select cases

• Multidisciplinary pain management

  • CBT (Cognitive Behavioral Therapy): psychological therapy to change pain-related thoughts and behaviors

  • Biofeedback: technique to learn control over body functions like tension or heart rate

  • Patient education and coordinated care among different medical specialties

• The GeneReviews guideline recommends caution with invasive procedures (e.g., surgery, injections) due to tissue fragility in hEDS

Theoretically Supported Treatments

Though not yet supported by robust clinical trials, many clinicians consider

• Targeting central sensitization

  • Brain becomes overly sensitive to pain; treated with graded exposure (gradual activity reintroduction) and neuroplasticity methods (retraining brain responses)

• Treating autonomic dysfunction

  • Includes fluids, salt, compression garments, and beta blockers

  • Helps stabilize blood pressure and reduce symptoms like dizziness

• Stabilizing mast cell activation

  • Antihistamines: block allergic-type responses

  • Mast cell stabilizers: prevent immune cells from releasing inflammatory chemicals

These are often used together as part of a personalized, multidisciplinary approach, which is widely supported in clinical practice.

Summary of Headache Mechanisms and Treatments

Summary

Headaches are one of the most common and disabling neurological symptoms in people with hypermobile Ehlers-Danlos syndrome (hEDS), affecting up to 75% of patients. Migraines are the most frequently reported type, but other headache patterns—such as those related to neck instability, jaw dysfunction, spinal fluid leaks, or autonomic dysregulation—are also prevalent. These headaches often begin early in life and may be worsened by structural differences in the cervical spine or skull base, heightened pain sensitivity (central sensitization), or comorbid conditions like mast cell activation and postural orthostatic tachycardia syndrome (POTS).

Treatment requires a tailored, multidisciplinary approach. Common therapies include migraine medications, physical therapy targeted at neck and jaw issues, and cognitive behavioral interventions. In some cases, nerve blocks or joint injections may be appropriate, though invasive procedures must be approached cautiously due to tissue fragility in hEDS. Other supportive treatments focus on regulating the nervous and immune systems, stabilizing blood pressure, and reducing hypersensitivity. While high-quality trials are limited, combining symptom-specific treatments with whole-body strategies has shown the most promise for improving outcomes.