Neurological Considerations in hEDS

While hypermobile Ehlers-Danlos (hEDS) is often recognized for causing joint hypermobility, fragile skin, and frequent injuries, it also affects the nervous system in ways that are often underdiagnosed or misunderstood. These neurological effects can be caused directly by changes in connective tissue or may result from how hEDS interacts with other body systems. This article explores both well-established and emerging information about how hEDS influences the brain, spine, nerves, and related functions.

Prevalence of Neurological Conditions in hEDS

Empirical data on the prevalence of specific neurological and neuropsychiatric disorders in hEDS is limited, but several patterns are supported by the medical literature.

• Neurodegenerative Diseases

  • No evidence of increased rates of Alzheimer's, Parkinson's, Amyotrophic Lateral Sclerosis (ALS), or multiple sclerosis (MS) in hEDS.

  • These conditions are not listed as comorbidities in large hEDS studies or reviews.

• Headache Disorders

  • Migraine affects up to 75% of individuals with hEDS.

  • Occurs earlier and more frequently than in the general population.

  • Tension-type headaches are also more common.

  • No increase in cluster headaches has been observed.

• Seizure Disorders

  • General evidence: There is no robust evidence that individuals with hEDS are at increased overall risk for epilepsy or febrile seizures compared to the general population.

  • When it does occur: Epilepsy is recognized in EDS, particularly in the presence of brain malformations such as periventricular heterotopia (a condition where clusters of brain cells form in the wrong place near the ventricles) or polymicrogyria (a brain malformation with too many small folds on the surface). Both focal and generalized seizures have been reported.

  • Cohort data: In one clinical series of 42 EDS patients with epilepsy, 45% had focal seizures and 55% had generalized epilepsy. Focal seizures often presented with temporo-parieto-occipital auras (early seizure symptoms from the back and side parts of the brain, often affecting vision or sensation) and epileptiform EEG findings (abnormal brain wave patterns typical of epilepsy).

  • Prognosis: Patients without brain lesions frequently achieved seizure freedom with AED monotherapy (a single drug treatment). Those with cortical malformations often required polytherapy (treatment with multiple drugs) and had a less favorable prognosis, with many remaining on medication after five years.

  • Other factors: Chiari malformation, craniocervical instability, and intracranial pressure disorders can mimic or complicate seizure presentations.

  • Familial cases: Epilepsy has been reported to co-segregate in some EDS families, particularly in vascular EDS with COL3A1 mutations.

  • Medication considerations: Standard AEDs are typically effective. No AEDs are contraindicated solely because of hEDS, but side effects may be heightened by autonomic dysfunction (problems in the body’s automatic systems such as heart rate, blood pressure, and digestion) or GI absorption issues (difficulty absorbing medications through the digestive tract).

• Neurodevelopmental and Psychiatric Conditions

  • Autism spectrum disorder (ASD) and ADHD are clearly more common. The psychological and functional impacts of ADHD and autism are discussed further on the Psychological Impacts page.

  • Tourette syndrome may be more frequent, though prevalence is not well quantified.

• Infectious or Inflammatory Conditions

  • No evidence for increased meningitis, encephalitis, or Guillain-Barré syndrome.

• Cerebrovascular Disease

  • Stroke and TIA (transient ischemic attack) are not reported as more common in hEDS.

  • These are more relevant in vascular EDS.

• Neuromuscular Disorders

  • Small fiber neuropathy (damage to small pain and temperature nerves, causing burning or tingling sensations) is common, with biopsy-confirmed rates up to 61%.

  • Myasthenia gravis is not increased in hEDS.

• Movement Disorders

  • Dystonia (involuntary muscle contractions causing twisting or abnormal posture) is reported more frequently in hEDS.

  • Essential tremor does not appear to be increased.

  • Tics and Tourette syndrome

    • Tourette syndrome may be more frequent, though robust data are lacking.

    • Case reports and reviews suggest motor and vocal tics are more common in EDS and related hypermobility disorders than in the general population.

    • Tics often coexist with ADHD, autism, or seizures, and individual patients with EDS have been documented with comorbid epilepsy and Tourette syndrome.

    • Proposed mechanisms include extracellular matrix dysfunction affecting brain development, abnormal cortico-basal ganglia-thalamic circuits, and autonomic dysregulation.

Summary

Migraine, small fiber neuropathy, dystonia, ASD, and ADHD are empirically increased in hEDS, while most other major neurological diseases are not.

Neurological Comorbidities in hEDS

Several neurological conditions are more common in hEDS, while others occur at similar rates to the general population. Migraine and tension-type headaches are clearly increased, often beginning earlier and occurring more frequently. Small fiber neuropathy is common and contributes to chronic pain. Dystonia is reported more often, though the exact mechanism is unclear.

Epilepsy is not increased overall, but when present, it usually occurs alongside brain malformations; both focal and generalized seizures have been documented, with prognosis depending on the presence of structural lesions.

Tics and Tourette syndrome may also be more frequent in hEDS, often overlapping with ADHD, autism, or seizures, though robust prevalence data are lacking.

Neurodevelopmental conditions such as autism spectrum disorder (ASD) and ADHD are consistently more common, while most other major neurological diseases (e.g., cluster headaches, essential tremor, stroke, MS) are not elevated in hEDS.

How hEDS May Cause Neurological Illness

• Small Fiber Neuropathy (SFN)

  • Involves damage to small nerve fibers in the skin.

  • Causes widespread burning pain, tingling, and sensitivity.

  • Very common in hEDS and confirmed by skin biopsy in many patients.

• Nerve Entrapment

  • Fragile connective tissue around nerves can lead to compression.

  • Can cause localized pain, numbness, or weakness.

• Craniocervical Instability (CCI)

  • Loose ligaments at the base of the skull may allow excessive movement.

  • Can cause headaches, dizziness, weakness, and difficulty concentrating.

• Spinal and Brain Structure Issues

  • Chiari I malformation, tethered cord syndrome, and spinal fluid leaks are more common in hEDS.

  • These can lead to pressure symptoms, chronic headaches, and neurological dysfunction.

• Dysautonomia (especially POTS)

  • The autonomic nervous system, which controls involuntary body functions, can be affected.

  • POTS (Postural Orthostatic Tachycardia Syndrome) is a form of dysautonomia seen in many with hEDS.

  • Symptoms include rapid heartbeat, dizziness, fainting, fatigue, and digestive issues.

• Proprioceptive Dysfunction

  • Proprioception is the body’s sense of where its parts are in space.

  • Joint hypermobility may lead to clumsiness, balance issues, and difficulty with coordination.

How hEDS May Influence or Interact with Neurological Conditions

• Migraines and Headache Disorders

  • Often more severe and frequent.

  • May be triggered or worsened by CSF leaks or spinal instability.

• Neurodevelopmental Disorders

  • Higher rates of ADHD, autism, and sensory processing issues.

• Movement Disorders

  • Some patients experience tremors, tics, or dystonia.

• Epilepsy

  • hEDS itself does not increase risk of epilepsy.

  • Seizures can occur in hEDS patients, particularly in those with brain malformations such as periventricular heterotopia.

  • Focal seizures are most common.

  • Standard antiepileptic drugs are typically effective.

  • Coexisting structural brain problems or autonomic dysfunction can complicate management.

  • No antiepileptic medications are contraindicated solely due to hEDS.

• Psychiatric Conditions

  • Anxiety, depression, and sensory processing disorders are common.

  • Emotional and physical symptoms may cluster due to connective tissue vulnerability.

Symptoms to Watch For

• Burning, tingling, or numbness in hands and feet

• Dizziness or fainting when standing

• Chronic headaches or migraines

• Fatigue and exercise intolerance

• Sensory sensitivities (light, sound, texture)

• Memory or focus difficulties (“brain fog”)

• Poor balance or frequent clumsiness

• Motor coordination difficulties in childhood

Treatment and Management Options

• Physical Therapy

  • Gentle and individualized.

  • Emphasis on motor control and proprioception.

• Pain Management

  • May include NSAIDs, gabapentin, or antidepressants.

  • Transcutaneous Electrical Nerve Stimulation (TENS), acupuncture, and Cognitive Behavioral Therapy (CBT) are supportive options.

• Autonomic Support

  • Salt/fluid intake, compression garments, and graded exercise for POTS.

• Psychological Support

  • Therapy and social support for anxiety, depression, and trauma.

• Surgical Considerations

  • For structural anomalies like Chiari or CCI.

  • Require surgeons experienced with connective tissue fragility.

• Medication Considerations

  • No studies have identified altered pharmacokinetics, increased risk of hypersensitivity, or a need for dose adjustment of neurological medications in hEDS patients. However, as with all patients with connective tissue disorders, clinicians should be vigilant for general comorbidities (such as gastrointestinal dysmotility or autonomic dysfunction) that could theoretically influence drug absorption or tolerability, though this has not yet been empirically established.

• Epilepsy Management

  • Standard antiepileptic drugs are effective in most hEDS cases.

  • Monitor for side effects due to potential autonomic or GI issues.

  • Brain imaging may be warranted to rule out structural abnormalities.

Summary

Neurological symptoms in hypermobile Ehlers-Danlos syndrome are common, complex, and often misunderstood. They range from small nerve fiber damage and migraines to more severe structural brain and spine issues. Autonomic dysfunction, developmental disorders, and chronic pain are particularly prominent. Epilepsy can also occur in hEDS, especially in the presence of brain malformations, and may involve either focal or generalized seizures. hEDS itself does not appear to increase epilepsy risk overall, but prognosis is less favorable when cortical abnormalities are present. Tics and Tourette syndrome may also be more frequent in hEDS than in the general population, though large-scale studies are lacking.

Management strategies must be individualized and multidisciplinary, with attention to overlapping symptoms and quality of life. Future research is needed to further define the neurological profile of hEDS, clarify the prevalence of seizures and tic disorders, and develop targeted therapies..