A 27-year-old woman arrived at the emergency room late at night, her face crumpled in pain. She reported feeling sick this morning and vomiting, but that didn’t strike her as unusual as her young children have had stomach flu the last few days. Since then, she has had severe and acute neck and head pain in the occipital-cervical area that has intensified throughout the day, along with dizziness. There were no neurological deficits noted by the ED doctor. This patient reported that her only medication was a birth control pill, and her medical history is significant for a third-trimester uterine rupture and an ankle sprain resulting in a ruptured tendon in her late teens. She says her OB-GYN suggested following up with a geneticist, but life got in the way, and she never did. The patient then vomited again, her hand flying to the back of her neck as the pain increased. Before she is even completely settled in the exam room, the attending physician was already ordering imaging and contacting the neurologist at a larger facility that can provide a higher level of care to set up a transfer. The critical care neurology team diagnosed her with an acute vertebral arterial dissection there. The patient was subsequently treated with anticoagulants and had an excellent prognosis. She did follow up with a geneticist, who diagnosed her with Ehlers-Danlos syndrome (EDS).
What is Ehlers-Danlos syndrome (EDS)?
Like other connective tissue disorders, Ehlers-Danlos syndrome is rare, affecting approximately 1 in 5,000. The vascular subtype, or Ehlers-Danlos type IV, is even rarer, with 1 person in 200,000 diagnosed.[i] It is caused by a defect in the COL3A1 gene, which affects the fibrillar collagen found in connective tissues such as the skin, uterus, intestines, and vascular system. This defect leads to the weakening of these systems, leading to rupture, aneurysms, and other catastrophic events. While the threat of abdominal and brain aneurysms remains the most visible, there are several other conditions that, while rare in the general population, are more commonly observed in those with EDS type IV.
Spontaneous vertebral artery dissection often presents as acute and severe head and neck pain and may include impaired coordination, weakness, visual loss, or aphasia. The tear is flap-like in the inner lining of the vertebral artery and then causes a blood clot which thickens the arterial wall and causes decreased blood flow. It is often related to trauma but can happen spontaneously, especially in the EDS population. Vertebral artery dissection can be either extracranial, involving the distal segment near the atlas and axis, or intracranial, associated with subarachnoid hemorrhage and poorer outcomes. The initial test of choice is a CTA which can more easily identify irregularities or thickening of the arterial wall but may not show a dissection. An MRI may also detect the initial flap, but a cerebral angiogram should be done if possible. Treatment is generally anticoagulants to prevent further blood clots or stroke unless subarachnoid hemorrhage is present. While 10% of patients with a vertebral arterial dissection will die before treatment, the prognosis for those that survive the initial dissection is very good, with 80% of patients achieving a full recovery.[ii]
Carotid-cavernous fistulas are another rare but well-known complication of vascular EDS. The fistula is an irregular connection between either the internal or external carotid artery and the cavernous sinus vein. The arterial blood is then pushed into the low-pressure cavernous sinus, which in turn impinges the blood from draining from the eye. Patients may present with eye redness and loss of vision, eye bulging, or eye pain, particularly if trauma has recently occurred. Patients often may hear a “whooshing” or audible hum while experiencing a carotid-cavernous fistula. Diagnosis is based on imaging; the gold standard is a cerebral angiogram. Treatment depends on whether the fistula is low or high flow, with non-traumatic fistulas generally being low. 20-60% of low-flow carotid-cavernous fistulas may actually close over time by themselves.[iii] Surgical intervention such as clipping or suturing the fistula is possible in some cases, but the preferred and first-line treatment is endovascular intervention. The fistula may be embolized with coils or stented with a graft. The endovascular intervention has been found to have an 80% cure rate.[iv] While carotid-cavernous fistula may not be life-threatening, it can destroy the patient’s eyesight. Early detection and treatment will lead to significantly better outcomes.
When assessing a patient with a connective tissue disorder, the clinician should have a high suspicion of serious conditions for all complaints, no matter how low acuity the initial presentation may appear. A simple neck ache may be a vertebral artery dissection, while eye redness and pain may be a carotid-cavernous fistula. A thorough history and physical examination are important, especially as many patients may be unaware that they have a connective tissue disorder. A history of organ ruptures, frequent sprains or tendon tears, and a family history of aneurysms or sudden death should cause the clinician to consider that the patient may have undiagnosed Ehlers-Danlos syndrome. It is important for clinicians to thoroughly assess every single patient they treat, regardless of the primary complaint.
[i] Germain, D.P. Ehlers-Danlos syndrome type IV. Orphanet J Rare Dis 2, 32 (2007). https://doi.org/10.1186/1750-1172-2-32
Urasyanandana K,Songsang D,Aurboonyawat T,Chankaew E,Withayasuk P,Churojana A, Treatment outcomes in cerebral artery dissection and literature review. Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences. 2018 Jun
[iii] Ellis JA, Goldstein H, Connolly ES, Meyers PM. Carotid-cavernous fistulas. Neurosurg Focus. 2012 May;32(5):E9).
[iv] (Gemmete JJ, Ansari SA, Gandhi DM. Endovascular techniques for treatment of carotid-cavernous fistula. J Neuroophthalmol. 2009 Mar;29(1):62-71.).
Sara Gruver, MS.Ed, FP-C, is a critical care paramedic with Erway Ambulance Service in Elmira, NY, and holds a master’s degree in education. In her spare time, she is pursuing a second master’s degree in EMS paramedicine from Creighton University and is an EMS consultant and educator with Medivation, LLC. Sara writes and speaks about topics ranging from autism and patients with developmental disabilities to innovative EMS education and retention in emergency services. She is also married to Rob, also a paramedic, and they have three children.