Functional magnetic resonance angiography in the diagnosis of iliac artery endofibrosis in an endurance runner

Abstract

A 45-year-old woman was presented with a 2-year history of left lower limb claudication symptoms occurring only during long-distance running. Multimodal imaging with exercise duplex ultrasonography and magnetic resonance angiogram confirmed the presence of flow-limiting stenoses in the left external iliac artery consistent with a diagnosis of left external iliac artery endofibrosis. She successfully underwent a left external iliac endarterectomy with vein patch repair and returned to full physical activity soon after. A year following full recovery from her original operation, she presented with similar symptoms on the right side and was managed in a similar manner. This report illustrates an unusual case of bilateral iliac artery endofibrosis occurring in an older endurance runner. We also present a novel diagnostic modality of pre-exercise and postexercise magnetic resonance angiography for iliac endofibrosis.

Background

Iliac artery endofibrosis is a rare condition that predominantly affects young endurance cyclists, presenting with symptoms of lower limb arterial insufficiency at near-maximal exertion for prolonged periods of time. We report an unusual case of bilateral iliac artery endofibrosis occurring in an older endurance runner. This condition may be under-recognised in elite athletes, especially outside the competitive cycling demographic.

Case presentation

A 45-year-old woman running coach presented with symptoms of left thigh fatigue and weakness on exertion over the past 2 years. She was also an endurance runner who frequently ran in excess of 90 km per week. Symptoms only occurred after a 5–10 min period of near-maximal exertion during long-distance running, and were relieved entirely by rest. Symptoms were not present at rest or during low-level activity and did not impact her activities of daily living. She had no significant cardiovascular history and does not smoke. Clinical examination was grossly unremarkable and she had palpable pedal pulses bilaterally.

Prior to specialist referral, she had seen multiple healthcare professionals who were unable to explain her symptoms. She had conducted research into her own symptoms and subsequently requested a referral from her general practitioner for lower limb ultrasonography to investigate the diagnosis of iliac endofibrosis.

Investigations

Ankle-brachial index (ABI) was normal at rest, but there was a relative decrease in left external iliac artery diameter postexercise from 8 to 3 mm (10 min at average 9.5 km/hour until symptoms appeared) (figure 1). This was further investigated and confirmed with pre-exercise and postexercise magnetic resonance angiogram (MRA) with gadolinium contrast. The MRA protocol used was axial proton density and T2-weighted sequences with and without fat suppression and volumetric contrast-enhanced MRA pre-exercise and postexercise. MRA at rest demonstrated no major abnormalities or vascular compression. The patient was then asked to run briskly until symptom onset, after which a postexercise MRA was performed within 5 min. This showed two flow-limiting stenoses within the left external iliac artery (figure 2). The dynamic changes to arterial diameter and flow demonstrated by ultrasonography and MRA combined with the history of endurance sport were in keeping with a diagnosis of iliac artery endofibrosis.

Figure 1.

Ultrasound imaging demonstrating a functional stenosis of the left external iliac artery. Pre-exercise greyscale (top left) and colour duplex (top right) of the left external iliac artery. Functional stenosis of the left external iliac artery after exercise stimulus is seen on both greyscale (middle left) and colour duplex (middle right). Note the aliasing on colour duplex. The associated Doppler waveform of the functional stenosis (bottom) showing blood flow velocity of 427 cm s⁻¹. Note the aliasing and spectral broadening suggestive of poststenotic turbulence.

Figure 2.

Pre-exercise (left) and postexercise (right) MRA of the left external iliac artery demonstrating functional stenosis. On the pre-exercise MRA, pelvic vasculature is grossly normal past the common iliac artery bifurcation, but following a period of near-maximal exertion, two stenotic areas within the left external iliac artery can be identified. No significant iliac vessel elongation or tortuosity is noted. MRA, magnetic resonance angiogram.

Differential diagnosis

Given the patient’s lack of risk factors for atherosclerotic disease and a full complement of lower limb pulses at rest, it was important to evaluate non-atherosclerotic causes of claudication. These included muscular pathology, osteo-articulatory pathology and lumbar vertebral pathology. Furthermore, given her age and sex, fibromuscular dysplasia was also an important differential to exclude. Mitochondrial disease, multiple sclerosis, chronic fatigue syndrome and other psychological causes for her symptoms were initially considered by the patient’s general practitioner.

Treatment

The external iliac endofibrotic lesion was treated surgically with left external iliac artery endarterectomy and vein patch repair with ipsilateral great saphenous vein. No significant tethering or elongation of the external iliac artery was noted intraoperatively. The endarterectomy involved only the visible fibrous neointimal layer covering the vessel intima. This had a glossy disorganised appearance, and was easily removed without disrupting or dissecting the intima proper. Histopathology findings were consistent with endofibrosis.

Outcome and follow-up

The patient had no postoperative complications and was commenced on aspirin for a period of 3 months. She returned to normal activity and training after 6 weeks of rest, and follow-up arterial duplex demonstrated patent iliac arteries bilaterally. She was presented approximately a year later with similar symptoms on the contralateral side and underwent similar treatment and management of this. She has recovered well from this second operation.

Discussion

Iliac artery endofibrosis and arterial kinking were first described in elite cyclists by Chevalier in 1986.¹ Although rare, recognition of this disease grew due to its prevalence within the cycling community. It is still, however, frequently under-recognised and under-diagnosed, with a relatively long period averaging 3 years between symptom onset and formal diagnosis.² Competitive cyclists account for more than 90% of cases of iliac artery endofibrosis, while other endurance athletes, such as triathletes and runners, account for the remainder. Onset of symptoms in the professional cyclist is typically before the age of 30 years, with the literature suggesting a strong correlation between total distance cycled and age of symptom onset. Cyclists with endofibrosis average 120 000 kilometres prior to symptom onset, with intensity of training also noted as a potential contributing risk factor. In contrast, functional arterial stenoses presenting in non-cyclists tends to develop at a significantly later age, perhaps due to a reduced burden of repetitive strain on the iliac vessels through less intensive activity and less hip hyperflexion.^3–5 These lesions are more common in men than women, and more frequently affects the left than the right side. The external iliac artery is affected in 90% of cases, with the remainder affecting either the internal or common iliac artery in equal proportion. About 15% of patients affected have bilateral lesions, as described in our case.³

Functional arterial stenoses of the iliac vessels are thought to be multifactorial. Kinking of the iliac vessel is thought to occur during strenuous lower limb activity, and has been hypothesised to be secondary to psoas muscle hypertrophy associated with vessel tethering, or anatomical elongation and tortuosity of the iliac arteries due to either congenital or acquired causes. These risk factors are recognised more frequently in competitive cyclists, and can be specifically targeted for treatment.^{2 4}

Endofibosis, on the other hand, describes a histopathologically unique neointimal lesion consisting of a loose collagenous matrix with an independent internal elastic membrane. These lesions are populated with actin-staining myofibroblasts and characteristically lack the deposited calcium and inflammatory cells that typify atheromatous plaques.⁶ As the lesions are found to be eccentric and located on the greater curvature of the vessel, it is thought that these they may originate over time as a compensatory mechanism to the adaptive hypertension and high-volume turbulent blood flow through a curved or kinked iliac artery during repeated bouts of intense exercise.⁶

In the non-cyclist minority, such as the competitive endurance runner described in this case, the burden of repetitive strain still occurs but not to the same degree as in cyclists. We hypothesise that lower-intensity endurance activities pose similar risks for the development of endofibrosis but may take a longer time course to develop, hence presenting at a later age as seen in our case. The natural history of endofibrosis is also uncertain, but the general consensus is that progression is halted with the cessation of vigorous activity. Whether these lesions may actually represent early vascular damage progressing eventually to atherosclerosis without intervention is not known.⁷

There is currently no consensus on the diagnostic criteria of iliac endofibrosis. The antecedent history of endurance sports, with symptoms of claudication on near-maximal exertion in patients who are otherwise not considered at risk for peripheral vascular disease, should raise suspicion for endofibrosis regardless of age. The optimal test to confirm this diagnosis is currently unclear, but multimodal imaging can be helpful where doubt exists.

Pre-exercise and postexercise ABIs and duplex ultrasonography are a mainstay for initial investigation and were used in this case. Most studies noted a significant drop in ankle pressure and ABI immediately following a specific cycle-ergometer-based exercise protocol.^{2 8 9} Within the first minute, postmaximal exercise ABI decrease of 0.66 or more from resting baseline has a sensitivity and specificity of 90% and 86%, respectively.⁸ As demonstrated in this case, visualising the lesion with duplex ultrasound is also possible, with myointimal thickening on ultrasound reported to have 85% sensitivity for external iliac artery endofibrosis.¹⁰ CT angiography can also be used, though mainly to rule out atherosclerotic disease and other potential causes of claudication.

MRA has been suggested in the literature as a useful adjunct for clarifying anatomy by both accurately measuring vessel length and identifying flow restriction due to vessel kinking when the patient is positioned in hip hyperflexion.¹¹ Our case presents a novel use of MRA with exercise to unequivocally visualise the functional lesion with high-resolution anatomical reconstruction. Our protocol involved sustained exercise to near-maximal exertion with MRA conducted immediately at the time point of reproduced symptoms. That MRA is a non-invasive test without ionising radiation and can be used to assess both anatomical factors and functional lesions, adding another dimension of flexibility in diagnosing iliac artery endofibrosis. This is particularly important if ABI and ultrasound findings are unremarkable or equivocal, or in cases of unusual presentations. Compared with CT angiography, it importantly avoids the use of ionising radiation in the younger population this condition typically affects.

Management of iliac endofibrosis has not been standardised. It is generally agreed on that cessation of intense activity will halt further progress of this condition without any impact on normal activities of daily living. Unfortunately, this is often not an option for some athletes, who may depend on their activity as a source of income. There are no proven medical alternatives for managing endofibrosis and surgical therapy is the mainstay of treatment. Surgical treatment for endofibrosis, first described by Chevalier in 1985, originally involved operative resection of the diseased portion of the external iliac artery and endarterectomy of further diseased portions, with an overall effect of shortening the vessel. By doing this, the artery is released, the stenotic lesion is treated and the elongated iliac artery trimmed to reduce its propensity to kink with hip flexion.^{1 12} If vessel kinking is the primary issue, then iliac artery release has been shown to be sufficient, but this will not be the case in the presence of a haemodynamically significant intraluminal lesion.² For those with a demonstrated intraluminal lesion, endarterectomy and vein patch repair of the diseased portion of the external iliac artery is indicated, with 85% of patients resuming high-level sports after operative recovery.¹³ In some cases, a further femoral counterincision is required to extend the endarterectomy into the femoral artery to facilitate complete removal of the lesion. Our case exemplified a successful external iliac endarterectomy and vein patch repair without the need for iliac vessel resection.

Conclusion

Iliac artery endofibrosis is a rare disease seen in endurance athletes. Although most commonly diagnosed in cyclists, it is an important differential in other potentially at-risk populations as seen in our unusual case of iliac artery endofibrosis in an older marathon runner. Diagnosis of this condition is often difficult, but a suspect history in combination with exercise imaging modalities is most appropriate for demonstrating the functional lesion, especially in uncertain or unusual cases. We also describe the novel use of pre-exercise and postexercise MRA in aiding diagnosis. Further research into this condition outside the cycling community is required.

Patient’s perspective.

I was diagnosed with endofibrosis near the end of 2017, but had been experiencing symptoms for 2 years prior. Initially, I did not know what was going on, but having run since my youth and knowing my own body as a lifetime runner, I knew that something was not right. From late 2015 to 2017, I saw multiple specialists about my symptoms, including a chiropractor, physiotherapist, naturopath and sports physician. Nobody knew what was going on, and the most common diagnosis was fatigue; one was determined that the fatigue and pain were psychological. I even went to see a hypnotherapist and obviously, that didn’t help my symptoms. During this time, my sports physician had brought up alternative diagnoses, such as multiple sclerosis and mitochondrial disease, and had wanted me to get tested. Needless to say, contemplating these conditions made me much more worried and anxious. Nobody had entertained the possibility of endofibrosis.

It was only when I started conducting my own research and stumbled on a Women’s Running article by Nicola Curtis (https://www.womensrunning.com/2017/10/columns/i-defeated-iliac-artery-endofibrosis_81969) that I had that ‘Eureka’ moment. The story and symptoms of this woman were exactly what I was going through! I brought myself back to my doctor and asked specifically to be referred to the vascular lab for assessment for endofibrosis. My advice to others who might have similar symptoms is to truly listen to your body. If you think that the symptoms you’re experiencing are indicative of endofibrosis, be an advocate for yourself and don’t be afraid to request an ultrasound.

When I saw the vascular surgeon and was formally diagnosed with endofibrosis, it was a huge relief. Especially at that time, where there was so much uncertainty about what might have been going on, it was pure validation to know that it wasn’t just in my head and that there was actually something physical causing the symptoms that I was experiencing. I was excited about the possibility of reclaiming running with surgery to fix the problem.

Postsurgery, I did not run, cycle or do any vigorous exercise for 6 weeks (only leisurely walks). However, when I went for my first postop run, it was amazing, I felt light. The moment I ran up my first hill, when that pain and fatigue that had held me back for too long wasn’t there at the end of it, I knew that my body was better and the surgery worked. It felt great to be able to run again and be back in control of my own legs. The comeback path hasn’t been easy though. Having had issues with my left leg, and running with the symptoms, I had subconsciously changed my stride and put more strain onto my right leg. I developed other injuries. So, I worked with an exercise scientist and took my strength training seriously to readjust and retrain both legs to work evenly, and eventually eased back into training. When the endofibrosis came back around on the other side, I knew far quicker what needed to be done.

I am happy about having had the procedure on both sides and grateful for the opportunity to have running returned as part of my life. It has always been part of who I am and I don’t think anybody in a similar position would be satisfied with giving up the sport they love, it’s part of one’s identity. However, there are still a lot of unknowns. For example, why me and not others I know who run with greater intensity or far more kilometres? Is it my form or just bad luck? What can I do to stop this from coming back? Since I’m predominately a runner, should I also avoid cycling given that cyclists are the ones more typically affected by endofibrosis? I want to keep running for the rest of my life, and if this means doing so less intensively, or switching to shorter race distances, I have learnt to be happy with that, but there simply is a lack of quality information about what we should do after having the surgery. I hope greater awareness can be raised about this condition and that more research is conducted to give us as patients more information about this in the future.

Learning points.

• Unusual symptoms of muscle weakness and disproportional cramping pain at near-maximal exertion in an endurance athlete should raise flags for a potential functional vascular lesion.

• Iliac artery endofibrosis is most commonly diagnosed in endurance cyclists, but can occur in other endurance athletes often at a later age.

• In diagnosing iliac artery endofibrosis, multimodal exercise imaging, including the use of ultrasonography and exercise magnetic resonance angiogram, can confirm the diagnosis, especially in equivocal or atypical cases.