Dystonia in Ehlers-Danlos Syndrome (EDS)

Dystonia, a movement disorder characterized by involuntary muscle contractions, is a frequently overlooked complication in people with Ehlers-Danlos Syndrome (EDS). Dystonia can manifest as repetitive twisting, tremors, or abnormal postures that result from these uncontrolled muscle movements. While dystonia is common in the general population, its prevalence in EDS, particularly in the hypermobile type (hEDS), is higher than typically recognized. This association is likely due to the connective tissue abnormalities present in EDS, which can lead to joint instability, poor proprioception (the body's ability to sense movement and positioning), and muscle overcompensation.

How Dystonia Manifests in EDS

In individuals with EDS, dystonia presents in several forms:

• Focal dystonia: This type affects a specific part of the body, such as the neck (cervical dystonia), jaw (oromandibular dystonia), or limbs. Focal dystonia is common in EDS, and the spasms it causes can lead to further joint instability and dislocations.
• Generalized dystonia: This more severe form affects multiple muscle groups across the body. In generalized dystonia, patients may experience twisting movements that involve the arms, legs, and torso, making daily activities challenging.
• Dopa-responsive dystonia (DRD): A subtype of dystonia, DRD is a genetic form that responds to the dopamine precursor medication Levodopa. Although rare, DRD can appear in EDS patients and typically presents with symptoms in childhood, such as walking difficulties and abnormal postures in the lower body​​.

The frequent overlap of joint instability and muscle weakness in EDS often leads to muscle overcompensation, where muscles tighten excessively in an attempt to stabilize loose joints. Over time, this leads to the chronic involuntary contractions seen in dystonia. For example, cervical dystonia (involving the neck muscles) is often reported in EDS patients due to the instability in the upper cervical spine. This is particularly important as it not only causes painful spasms but can also lead to issues like vertebral artery compression and restricted blood flow, further exacerbating neurological symptoms​.

Causes of Dystonia in EDS

Dystonia in EDS is multifactorial, influenced by the connective tissue defects that define the syndrome. These include:

1. Proprioceptive dysfunction: Proprioception is critical for coordinated muscle movements, as it allows the body to sense and adjust to its positioning. In EDS, where joint hypermobility is prevalent, the connective tissue is too lax, reducing the efficiency of proprioceptors. This can cause muscles to overreact to minor stimuli, triggering dystonic movements​.
2. Muscle fatigue and instability: The loose ligaments and hypermobile joints in EDS force muscles to work harder to maintain stability. This constant overuse can lead to muscle fatigue, which, in turn, makes the muscles more susceptible to involuntary contractions​​.
3. Autonomic dysfunction and dysautonomia: Many individuals with EDS also experience dysautonomia, a disorder of the autonomic nervous system that controls involuntary body functions like heart rate and digestion. Dysautonomia can worsen dystonia by further complicating the body’s ability to regulate muscle control​​.

It is also believed that central nervous system dysfunction plays a role in EDS-related dystonia. Although EDS is not typically associated with significant brain abnormalities, the combination of proprioceptive deficits and autonomic dysfunction may impair the brain’s control over motor function, leading to dystonic episodes​.

Dystonic Storms: A Severe Complication

In some cases, EDS patients may experience dystonic storms (also called status dystonicus), which are severe, life-threatening episodes of sustained muscle contractions. These episodes can last for hours or days, involving intense muscle spasms, rapid breathing (tachypnea), and abnormal heart rhythms (tachycardia). Dystonic storms can result in respiratory failure, particularly if the muscles of the diaphragm or chest are involved​.

A 2021 case series highlighted the link between upper cervical instability and dystonic storms in hEDS patients. This study demonstrated how certain neck movements, which compressed the vertebral or carotid arteries, caused intermittent cerebral ischemia (restricted blood flow to the brain), leading to dystonic storms. Treating the underlying cervical instability using regenerative therapies like prolotherapy was effective in stabilizing the cervical spine and resolving the dystonic symptoms​.

Diagnosis of Dystonia in EDS

Diagnosing dystonia in EDS is often challenging due to the overlapping symptoms of EDS and the lack of clear neurological findings. Brain MRIs and EEGs (electroencephalograms) often appear normal in these patients, leading to misdiagnoses of psychogenic movement disorders. However, functional movement disorder (FMD) is increasingly recognized as a subtype of dystonia seen in EDS. In a 2022 study, many EDS patients were diagnosed with FMD, where dystonia was the most common movement disorder phenotype​.

This overlap with functional neurological conditions adds complexity to diagnosing dystonia in EDS. However, clinicians must be aware of the possibility of dystonia in EDS patients, especially in those presenting with muscle spasms, unusual posture changes, or abnormal tremors.

Treatment of Dystonia in EDS

Effective treatment for dystonia in EDS involves a combination of medical therapies, physical therapies, and interventions targeting the underlying cause of joint instability and muscle dysfunction.

1. Medications:
   • Levodopa (L-Dopa): As dystonia often involves disruptions in dopamine signaling, Levodopa can be highly effective for patients with dopa-responsive dystonia. This treatment has shown benefits in reducing muscle rigidity, improving motor function, and reducing fatigue​.
   • Botulinum toxin: Botulinum toxin (Botox) injections have been successfully used to treat focal dystonia by temporarily paralyzing the overactive muscles, relieving symptoms for several months at a time​.
   • Muscle relaxants: Medications like baclofen or benzodiazepines can help control dystonic muscle contractions in some patients. However, their long-term effectiveness varies, and they often come with significant side effects, such as sedation and dependency​.
2. Proprioceptive therapy:
   Targeted physical therapy to improve proprioception has been a cornerstone of treatment in EDS patients with dystonia. Using proprioceptive shoe inserts, specialized clothing, and balance exercises can help improve muscle coordination, reducing the severity of dystonic movements​​.
3. Prolotherapy:
   For patients with upper cervical instability, prolotherapy has emerged as a promising treatment option. This regenerative injection therapy strengthens the ligaments in the neck, stabilizing the joints and reducing the likelihood of cervical dystonia and dystonic storms​.
4. Supportive therapies:
   • Oxygen therapy has been used to alleviate muscle fatigue and reduce the severity of dystonia in some cases. This is especially beneficial for patients with dysautonomia, as improved oxygenation can enhance muscle function and decrease fatigue​.
   • Occupational therapy and lifestyle adaptations: Adjusting daily activities to avoid triggering dystonic episodes can be an important aspect of managing dystonia in EDS. Patients are often advised to limit repetitive movements and avoid positions that overstretch the joints​​.

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FAQs About Dystonia and EDS

Can Ehlers-Danlos cause dystonia?

‍Yes, dystonia is a recognized movement disorder in people with Ehlers-Danlos syndrome, particularly those with the hypermobile type (hEDS). Studies suggest that up to 75% of hEDS patients may experience some form of dystonia​​.

What is the main cause of dystonia?‍

Dystonia is typically caused by abnormal signaling in the brain's basal ganglia, which controls movement. In EDS patients, poor proprioception and muscle instability likely contribute to these abnormal signals​​.

Why does EDS cause muscle spasms?‍

EDS leads to muscle spasms and dystonia because of joint instability and abnormal connective tissue, which forces muscles to compensate excessively. This overcompensation can trigger involuntary contractions and spasms​​.

What are the neurological manifestations of Ehlers-Danlos syndrome?‍

In addition to dystonia, EDS patients may experience migraines, Chiari malformations, autonomic dysfunction (like Postural Orthostatic Tachycardia Syndrome, POTS), and small fiber neuropathy​​.

What is Ehlers-Danlos neuromuscular disease?‍

Ehlers-Danlos neuromuscular disease refers to the muscle and nerve issues caused by the connective tissue defects in EDS. These include conditions like dystonia, muscle weakness, and autonomic dysfunction​​.

Is dystonia a type of dysautonomia?‍

No, but they can occur together. Dysautonomia refers to dysfunction of the autonomic nervous system, while dystonia is a movement disorder. Both are common in EDS patients, suggesting a link​​.

Can autoimmune disease cause dystonia?‍

Yes, certain autoimmune diseases can cause dystonia by attacking parts of the brain involved in motor control. However, dystonia in EDS is more likely related to connective tissue and proprioceptive dysfunction​​.

What does a dystonic storm look like?‍

A dystonic storm, also called status dystonicus, is a severe episode of generalized dystonia involving intense, uncontrollable muscle contractions, sometimes leading to respiratory distress. It requires emergency care​​.

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References: 

1. Hamonet, Claude, and Lucette Ducret. "Dystonia in the Joint Hypermobility Syndrome (A.K.A. Ehlers-Danlos Syndrome, Hypermobility Type)." SOJ Neurology, vol. 3, no. 1, 2016, pp. 1-3.
2. Hauser, Ross, et al. "Intermittent Cerebral Ischemia as a Cause of Dystonic Storms in Hypermobile Ehlers-Danlos Syndrome with Upper Cervical Instability, and Prolotherapy as Successful Treatment: 4 Case Series." Open Journal of Clinical & Medical Case Reports, vol. 7, no. 7, 2021.
3. Margolesky, Jason, et al. "Hypermobile Ehlers-Danlos Syndrome: A Prodromal Subtype of Functional Movement Disorders?" Movement Disorders Clinical Practice, vol. 9, no. 7, 2022, pp. 956-960.
4. Hamonet, Claude, et al. "Brain Injury Unmasking Ehlers-Danlos Syndromes After Trauma: The Fiber Print." Orphanet Journal of Rare Diseases, vol. 11, 2016, p. 45.
5. Hein, Laura C., et al. "Ehlers-Danlos Syndrome: It’s Not Your Normal Hoofbeats." The Journal for Nurse Practitioners, vol. 15, no. 4, 2019, pp. 277-281.
6. Hamonet, Claude, and Lucette Ducret. "Ehlers-Danlos, Proprioception, Dystonia, Dysautonomy, L-Dopa, and Oxygenotherapy’s Efficacy." Journal of Alzheimer’s & Neurodegenerative Diseases, vol. 1, no. 1, 2019, pp. 1-11.
7. Wang, Tina J., Antonio Stecco, and Khashayar Dashtipour. "The Effect of Low Dose OnabotulinumtoxinA on Cervical Dystonia in Hypermobile Ehlers-Danlos Syndrome." Tremor and Other Hyperkinetic Movements, vol. 11, 2021, p. 42.
8. Lee, Woong-Woo, and Beom Seok Jeon. "Clinical Spectrum of Dopa-Responsive Dystonia and Related Disorders." Current Neurology and Neuroscience Reports, vol. 14, no. 5, 2014, p. 461.
9. Cariga, P., et al. "The Prevalence and Association of Neck (Coat-Hanger) Pain and Orthostatic (Postural) Hypotension in Human Spinal Cord Injury." Spinal Cord, vol. 40, 2002, pp. 77-82.

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