Introduction

Ehlers-Danlos syndrome (EDS) is an umbrella term for a mixed group of 13 connective tissue disorders.¹ Connective tissues play a big role in our bodies, with the primary function to connect, protect, and support the structure of other tissues and organs. Connective tissues include cartilage, blood, fat (adipose tissue), tendons, and ligaments.² In EDS, the production, processing, or structure of collagen or other proteins that interact with collagen is disrupted.¹

The type of EDS is mostly diagnosed in the clinic following a classification system published by the EDS International Consortium. It is also helpful to get genetic testing done to confirm exactly which type of EDS the patient has.³ 

The three most common forms of EDS are: classical EDS (cEDS), vascular EDS (vEDS), and hypermobile EDS (hEDS). While each type has its own unique combination of symptoms, most people with EDS experience hypermobility of the joints, stretchy skin, and easy bruising.⁴ 

Neurological involvement in EDS

The understanding of the EDS symptoms has changed significantly since it was first identified in the early 20th century.¹ Recently, there has been more focus on how EDS affects the nervous system. While the disease does not directly affect the nerves and the brain, connective tissues are still important for the support of other parts of the body, so issues here can lead to neurological symptoms.⁵

Many patients with EDS experience neck and back problems due to their weak ligaments, as well as chronic headaches. Sometimes, more complex neurological conditions can develop, such as tethered cord syndrome (TCS) and Chiari malformations (CM).⁶

Being aware of these challenges can allow both patients and healthcare providers to manage the symptoms and improve quality of life.

Headaches

Among individuals with EDS, headaches are the most commonly reported neurological symptoms. People with vEDS and cEDS have an extra risk of developing sudden, severe headaches, mainly because their vessels are more fragile and blood flow can be unpredictable. There is also evidence that spontaneous headaches can occur due to cerebrospinal fluid (CSF) leaks, which is more common in patients with EDS.⁵ These headaches are often caused by a combination of a few factors, including poor blood flow to the brain, high blood pressure, and hypermobility of the neck joints. 

The type and severity of headaches can vary a lot between patients. Research shows that migraines are more common in patients with EDS and even higher in EDS patients assigned female at birth (AFAB). Other types of headaches, such as tension-type headaches, temple headaches, and cervicogenic headaches, have also been reported.⁶

Tethered cord syndrome

Tethered cord syndrome (TCS) is a condition experienced by patients with EDS, especially those with the hypermobile type, seen in almost 7% of cases.⁶ In TCS, the spinal cord becomes incorrectly attached to the surrounding tissue, which limits movement. Typically, the spinal cord is attached to a fibrous band of connective tissue called the filum terminale (FT) interna to the coccyx. This allows protection of the nerves in the spinal cord from stretching and damage. However, in TCS, the makeup of connective tissue in the FT is abnormally rigid, stretching the nerves during movement.⁷ 

EDS patients with TCS commonly suffer from leg and back pain, leg weakness or numbness, as well as less common bladder and bowel issues. These symptoms may worsen with activity or as children grow due to extra strain on the spinal cord.⁶

TCS is often diagnosed using magnetic resonance imaging (MRI), which can show abnormalities in the FT. However, diagnosis of TCS can be tricky, as there are other neurological disorders showing similar symptoms.⁷  

Chiari malformations

Chiari malformations (CM) are a condition in which the lower parts of the brain, called the cerebellar tonsils, push down on the base of the skull. This can cause pressure on the brainstem and spinal cord, blocking the flow of the cerebrospinal fluid (CSF).⁸ There are several different types of CM; type I is the most commonly seen in EDS patients, especially those with hEDS.

For the diagnosis of CM, doctors usually use an MRI to check if any brain tissue is blocking the fluid flow, and conduct neurological scans to evaluate the severity of the condition.⁸

Overlap and compounding effects

These neurological symptoms on their own might seem manageable. However, it is really common for patients with EDS to experience more than one neurological symptom, such as headaches, TCS, and CM, all at once. When these conditions overlap, they might actually make each other worse. For example, someone with both brain pressure from CM and spinal pressure from TCS might experience severe headaches. This mix of symptoms can be confusing for both the patient and the doctors to navigate, making diagnosis even trickier.⁷

That is why multidisciplinary care, where neurology, neurosurgery, genetic screening, and physical rehabilitation are brought together, is so important for the proper diagnosis and treatment tailored to a person's unique needs.

Conclusion

People with EDS often face a cluster of neurological issues, including headaches, TCS, and CM. The overlap of these conditions is common, often causing other complications and making the disease even harder to manage. 

As these symptoms can become so similar, having specialists who understand the way EDS affects connective tissue and how this relates to neurological problems can make a huge difference in accurate diagnosis and effective care. 

Summary

EDS is a connective tissue disorder caused by problems in the collagen structure and function, covering 13 different subtypes. Collagen is crucial for the structure and stability of many organs and body parts, such as skin, joints, and blood vessels. Because of this, patients with EDS can experience a wide array of problems throughout their bodies. 

For a long time, neurological symptoms of EDS were not focused on much, as they do not directly damage the nerves. However, recent research into the neurological complications associated with EDS has shown that the connective tissue weakness around the base of the skull and the neck can lead to a variety of problems. The fragile tissues can cause spinal instability, abnormal spinal fluid and blood flow. This abnormal flow can lead to headaches or migraines.

More severe neurological conditions, such as TCS and CM, may also be present. TCS is caused by an abnormally attached spinal cord to the surrounding tissue, and it can cause numbness and weakness in the legs, which can get worse with activity. CM, on the other hand, are caused by brain tissue moving downwards, disrupting the spinal fluid flow to the brain. 

Many people with EDS experience more than one of these conditions, making symptoms more severe and diagnosis more challenging. That is why it is crucial for patients with EDS to get multidisciplinary care, which involves neurology, neurosurgery, genetics, and rehabilitation. Having specialists who truly understand EDS, especially its neurological effects, can make a big difference in helping patients to improve their quality of life.