Two otherwise healthy young brothers present with intermittent claudication, just a coincidence?

Abstract

Popliteal artery entrapment syndrome (PAES) is a recognised cause of lower limb peripheral arterial disease in young adults. We describe the cases of two otherwise healthy brothers who presented with the condition 5 years apart. The first brother, who is also the first author of this case report, presented aged 19 with worsening, right-sided, exercise-induced lower leg pain and transient foot pallor. Imaging confirmed PAES and irreversible localised arterial damage. Surgery was performed to release the entrapment and resect the section of diseased artery. The limb was revascularised using an autologous interposition saphenous vein graft. The second brother began experiencing left-sided, exercise-induced lower leg pain aged 24. Again, imaging revealed PAES and irreversible arterial damage. A similar revascularisation procedure was performed. Both siblings fully recovered and are symptom free. Arterial duplex scans have confirmed patent grafts. A correlation in siblings has only been reported in the literature five times previously.

Background

Peripheral arterial disease is generally associated with older patients who have cardiovascular risk factors. Despite this, it is important for clinicians to appreciate that conditions exist, which can cause peripheral arterial disease in younger patients who do not fit the typical atherosclerotic profile. Popliteal artery entrapment syndrome (PAES) is one such condition; it is therefore an important differential to consider when confronted with a young patient complaining of exercise-induced lower leg pain or any other signs and symptoms of lower limb peripheral arterial insufficiency. It is caused by external compression of the popliteal artery by musculotendinous structures within the popliteal fossa.¹ Left untreated, it can lead to loss of limb.^{1 2} If the condition is identified early, surgical release of the entrapment is the only intervention required.³ This is preferable to grafting or bypass procedures, which have higher complication rates and whose long-term success is not well understood.⁴ To our knowledge, PAES occurring in siblings has only been reported in the literature five times previously.^5–9

This case report highlights the importance of considering PAES when assessing young patients with exercise-induced lower leg pain and/or peripheral arterial insufficiency and adds another familial case to the literature.

Case presentation

Case 1

A previously fit and well 19-year-old Caucasian man presented to the accident and emergency department with worsening right-sided calf pain for 3 weeks. The pain was a dull ache, brought on by walking and relieved by rest. There was no history of trauma. The patient also described two recent episodes of right foot numbness and pallor, both following long walks in cold conditions. The second of these episodes took over 2 hours to resolve. He was a non-smoker. There was no history of intravenous drug use or excessive alcohol consumption. There was no significant family history. The contralateral limb was asymptomatic. On examination, the right foot was cool and pale. There was a weak right popliteal and posterior tibial pulse and an absent right dorsalis pedis pulse. His cardiovascular system was otherwise normal.

Case 2

A 24-year-old Caucasian man, the older sibling of the patient in case 1, was referred to the vascular surgery clinic by his general practitioner with left-sided, exercise-induced calf pain. His symptoms had been progressing in severity over 10 months. He had a claudication distance of 200 m. He had no previous medical or surgical history and was a non-smoker. The contralateral limb was asymptomatic. On examination, his left foot appeared well perfused, but there were no pulses palpable distal to the popliteal pulse. Again, his cardiovascular system was otherwise normal.

The similarities and differences in presenting features in each case are illustrated in figure 1.

Figure 1.

Table comparing presenting features in each case.

Investigations

Case 1

Routine blood tests were normal. MRI was performed. This revealed a stenosis of the right popliteal artery (figure 2) with poststenotic dilatation (figure 3). The stenosis appeared to be caused by an aberrant lateral origin of the medial head of gastrocnemius exerting pressure on the popliteal artery. The contralateral limb was anatomically normal.

Figure 2.

Axial MRI of the patient in case 1 demonstrating stenosis of the right popliteal artery. The stenois appearing to be caused by an aberrant lateral origin of the medial head of gastrocnemius.

Figure 3.

Axial MRI demonstrating poststenotic aneurysm of the right popliteal artery of the patient in case 1.

Case 2

Routine blood tests were normal. Ankle–Brachial Pressure Index (ABPI) scores were 0.55 and 0.86 for the left dorsalis pedis and posterior tibial, respectively. Magnetic resonance angiography was performed which demonstrated stenosis of the left popliteal artery (figure 4). Again, the medial head of gastrocnemius had an abnormal lateral origin. This caused distortion and stenosis of the popliteal artery by pulling it medially. As in case 1, the contralateral limb was anatomically normal. An arterial duplex scan was also performed which confirmed left popliteal pathology and noted extensive collateral activity around the knee.

Figure 4.

Magnetic resonance angiography image of the lower limb vasculature of the patient in case 2. Stenosis of the left popliteal artery is demonstrated.

Differential diagnosis

The differential diagnoses for PAES vary depending on when the patient presents in the course of their condition. Those presenting early, before irreversible arterial damage has occurred, tend to present with exercise-induced lower leg pain.³ They may also report transient foot coolness and/or pallor during strenuous exercise or with the leg held in certain postures.³ In the later stages, repeated compression results in arterial wall damage; this can lead to stenosis, poststenotic dilatation and thrombus formation. The majority of these patients will present with progressive ischaemic symptoms in addition to exercise-induced lower leg pain. Some patients may present with acute ischaemia if occlusion occurs in the absence of adequate collateral formation.⁴

There will be significant overlap between the modes of presentations described above. Not all patients will fit neatly into one category; however, it is a helpful way of grouping differential diagnoses.

Exercise-induced lower leg pain is a common presenting complaint with various aetiologies; it is defined as pain between the knee and the ankle brought about by exercise.^{10 11} The vast majority of young adults will have a musculoskeletal pathology; differentials include medial tibial stress syndrome (MTSS), stress fractures, tendinopathy and chronic calf tears.¹² Unlike vascular pathologies, these conditions will cause pain and tenderness over the affected region; therefore, palpation is essential for correct diagnosis.

Although causing pain, these conditions will not cause ischaemic symptoms such as transient foot coolness, paraesthesia or pallor. Therefore, to avoid overlooking a vascular cause, these symptoms must be specifically elicited in the history and recorded as pertinent negatives if absent.

A musculoskeletal condition that can mimic PAES more closely is chronic exertional compartment syndrome (CECS). Both conditions may result in patients reporting generalised calf pain, relieved by rest and associated with foot paraesthesia and weakness.¹³ A thorough examination of peripheral pulses is essential; if absent or diminished at rest, a vascular cause should be ruled out as a priority.¹⁴ If normal, it is reasonable to refer to an orthopaedic specialist for further investigation, which should include measurement of compartment pressures.¹⁵

A table contrasting the clinical features of PAES as compared to the musculoskeletal conditions described above can be found in figure 5.¹⁶

Figure 5.

Table contrasting the clinical features of conditions causing exercise-induced lower leg pain.¹⁶

Patients who present later in the course of the disease are more likely to report ischaemic symptoms. In these cases, differential diagnoses for peripheral vascular disease in young adults must be considered. Atherosclerosis is by far the most common cause of peripheral arterial disease in the population as a whole. However, in young patients who do not fit the typical atherosclerotic profile, alternative vascular conditions must be sought. Some sources refer to this heterogeneous group of conditions as non-atherosclerotic peripheral arterial disease (NAPAD), of which PAES is one.^{17 18} Other NAPADs include thromboangiitis obliterans (Buerger’s disease), fibromuscular dysplasia and cystic adventitial disease.¹⁸

Thromboangiitis obliterans is a condition that mainly affects men between the ages of 20 and 40; it is strongly associated with heavy use of tobacco, primarily via smoking, but it has also been reported in users of smokeless tobacco products.¹⁹ It is a progressive and recurring inflammation and thrombosis of medium-sized arteries in the extremities that often presents with rest pain or tissue necrosis. Less severe cases affecting the lower limbs may present with intermittent claudication, mimicking PAES.²⁰ Unlike PAES, two or more limbs are affected in almost all cases. Enquiry about symptoms in other limbs, including the arms, may help differentiate the conditions clinically.²¹ Angiography reveals extensive arterial occlusive disease and ‘corkscrew’ collaterals.²²

Fibromuscular dysplasia is a non-inflammatory, non-atherosclerotic disease that causes abnormal growth in arterial walls.²³ It tends to affect women between the ages of 20 and 60. The condition favours the renal and carotid arteries in 75% of cases.²³ Rarely, the iliac, femoral and popliteal arteries can be affected, causing intermittent claudication.²⁴ Angiography will demonstrate a characteristic ‘beaded’ appearance of the diseased arteries.²⁵ If diagnosed, all other arteries should be screened.²⁶

Popliteal cystic adventitial disease (PCAD) and PAES are remarkably similar in terms of presentation and affected population (males aged 20–40).²⁷ The disease is characterised by a collection of mucinous material in the adventitia of peripheral arteries.²⁸ The popliteal artery is affected in 85% of cases.²⁹ The two conditions may sometimes be differentiated by clinical examination. In PCAD, pedal pulses often diminish on knee flexion (Ishikawa sign).²⁸ The diagnosis is confirmed by duplex ultrasound and magnetic resonance angiography demonstrating cystic compression and vessel wall pathology.²⁸

Treatment

Case 1

The patient was admitted for expedited elective surgery where he underwent a posterior approach exploration of the popliteal fossa. The medial head of gastrocnemius was identified and noted to have an abnormally lateral origin obscuring a section of the popliteal artery. The medial head was then transected exposing the popliteal artery and confirming the presence of both stenosis and poststenotic dilatation. The distal arterial tree was embolectomised with a No 3 Fogarty catheter with good results. The length of diseased artery was excised, and a long saphenous vein interposition graft was used in reverse to re-establish flow.

Case 2

The patient was admitted for expedited elective surgery where he underwent a posterior approach exploration of the popliteal fossa. Intraoperative findings confirmed a 4 cm occlusion of the popliteal artery. As in case 1, this was due to external compression from an aberrant lateral origin of the medial head of gastrocnemius. The length of diseased artery was excised, and a short saphenous vein (SSV) interposition graft was used in reverse to re-establish flow.

Outcome and follow-up

Case 1

The patient had an uneventful postoperative recovery and remains symptom free. Graft surveillance duplex scans have revealed a patent graft with good distal flow.

Case 2

The patient experienced numbness and pain in the distribution of the saphenous nerve, a recognised complication of SSV harvest. These symptoms fully resolved after 9 months. Follow-up duplex scans and magnetic resonance angiography confirmed a healthy, patent graft.

Discussion

PAES occurs due to abnormal embryological development of the structures within the popliteal fossa.³⁰ In normal subjects, the medial head of the gastrocnemius arises laterally and migrates medially to attach definitively to the posterior surface of the medial femoral condyle.¹ In the two cases described, the medial head of gastrocnemius had an aberrantly lateral origin, indicating that it did not complete its migration. Deep to the muscle, the artery is compressed. This is referred to as type II PAES; however, other variants with differing embryological chronologies have also been described.³¹ The variants are primarily classified according to the structure responsible for the arterial compression, these are summarised in figure 6.⁴

Figure 6.

Classification of PAES.⁴

Over time, repeated arterial compression can lead to stenosis, poststenotic aneurysm, thrombosis and distal embolisation.³² Progressive injury to the artery with subsequent need for amputation has been described.^{1 2 33}

In a recent systematic review of the literature, the mean age at diagnosis was reported as 32 years, with a male preponderance of 83%.⁴ The same review reported that PAES was bilateral in 38% of patients; therefore, if diagnosed unilaterally, investigation of the asymptomatic limb is essential. Athletes and soldiers appear to be disproportionally affected, the theory being that these groups experience greater muscular hypertrophy, exacerbating the condition which may otherwise have remained occult.³⁴

Clinical presentation can range from exercise-induced lower leg pain to acute limb ischaemia, depending on the degree of arterial damage that has occurred and the extent of collateral formation.^{3 4} The relatively young age at presentation generally means an absence of cardiovascular risk factors; this can lead to a vascular cause being overlooked, resulting in delayed diagnosis.³⁵ Failure to recognise the condition has led to inappropriate investigations and treatments, including cases of patients being unsuccessfully treated with four-compartment fasciotomy for presumed CECS.^{36 37}

The two cases described emphasise this variation in presentation. Case 1 presented acutely to accident and emergency with signs of limb ischaemia. Case 2 had a more indolent course, presenting with worsening claudication over 10 months to his general practitioner. Given both patients had weak or absent pedal pulses and similar intraoperative findings, the difference in presentation is probably accounted for by the fact the patient in case 2 had built up a better collateral flow.

Any suspicion of vascular compromise should prompt urgent referral to a vascular surgeon. If PAES is considered, bedside tests can be used to further investigate, for example, handheld Doppler and ABPI measurement. In equivocal cases, handheld Doppler in the stress position (maximal plantar flexion) may demonstrate reduced or absent flow and a corresponding reduction in the ABPI, which may also be reduced following exercise.³⁷

Those patients in whom the diagnosis is suspected, either from positive bedside tests or clinical examination, should go on to have formal imaging. There remains a lack of consensus as to the most appropriate modality; duplex ultrasonography, conventional angiography, CT angiography and magnetic resonance angiography have all been used, often in combination.³⁸ Local resources and experience play a role in decision making. Magnetic resonance angiography is gaining favour as it provides good anatomical detail of the soft tissues, as well as demonstrating arterial patency.⁴

Early in the course of the disease or in less severe cases, the artery can appear patent at rest. In these situations, imaging can be performed while in the stress position. This serves to replicate any transient occlusion caused by contraction of the gastrocnemius muscle during exercise. However, dynamic occlusion can occur in patients with normal popliteal anatomy; therefore, this method can produce false positives.³⁹

If PAES is diagnosed, surgical exploration of the popliteal fossa is required. If arterial damage has not yet ensued, resection of the causative anomalous muscle or fibrous tissue will suffice. In cases where there is local damage to the artery, resection of the diseased segment is also required. Revascularisation with reverse saphenous vein interposition is the generally preferred method. Graft patency at 5 years has been shown to be around 75%, although further research on long-term outcomes is required.⁴⁰

There are five other reported occurrences of familial PAES.^5–9 Despite the fact that the condition has an embryological basis and is often bilateral, a genetic link has yet to be established. However, as well as highlighting the importance of considering vascular pathologies in young patients with exercise-induced leg pain, this case reminds clinicians that enquiring about family history is good practice in any consultation. It may just provide a clue to clinching a challenging diagnosis.

Patient perspective.

Case 1

• A quirk of this particular case report is that the patient in case 1 is also the first author. I will therefore write this section from my perspective as the patient.

• My symptoms began before I had started medical school meaning I had little insight as to what could be causing them. I first noticed an issue with my right calf when playing football aged 16. It would often be the first muscle to cramp up at the end of a strenuous game but I thought nothing more of it. Aged 18 I went on holiday to New Zealand during their winter. Whilst walking in cold temperatures I noticed that my right foot would become numb, cold and pale, in addition to my calf cramping. It was during the second and more severe of these episodes that I began to become particularly concerned and attended the accident and emergency department. Initially the doctors I saw seemed a little perplexed, they admitted they were not used to seeing these symptoms in such a young patient and I was referred to the vascular surgeons. A decision was made the following day to perform an MRI scan and the diagnosis was quickly made. The diagnosis was explained to me and I was relieved, I had worried that the issue may involve my whole cardiovascular system.

• The focus then moved to whether I should have surgery in New Zealand or be repatriated back to the UK. After careful consideration and discussion with family I decided to fly home, self-administering subcutaneous enoxaparin to reduce the risk of further clots.

• The day after arriving home I had surgery and made a rapid and full recovery.

Case 2

• My symptoms began around 4 years after my brother’s, however cramping was the predominant symptom for me. In hindsight I could have made the connection to my brother earlier but I thought it was too much of a coincidence to have the same condition when we were told it was not hereditary. I was less fortunate than my brother in that I experienced numbness and pins and needles in my foot following surgery for around a year, this was quite frustrating as I was unable to wear certain shoes or do certain activities. Thankfully my symptoms have now fully resolved and I have had no further issues.

Learning points.

• Always ask about symptoms and signs of vascular insufficiency when taking a history from young patients with exercise-induced lower leg pain.

• Always remember to palpate distal pulses when examining a patient complaining of exercise-induced lower leg pain or signs and symptoms of vascular insufficiency. Any suspicion of vascular involvement should prompt referral to a vascular surgeon for formal imaging of the vascular tree.

• Early diagnosis of popliteal artery entrapment syndrome (PAES) before irreversible arterial damage has occurred could save a patient from major vascular surgery and potentially limb amputation.

• Family history may provide a clue to diagnosis even in conditions that do not yet have an established familial component. It is always worth asking.