INTRODUCTION — Nonatheromatous popliteal artery diseases that can cause symptoms of claudication or, rarely, limb-threatening ischemia predominantly include popliteal artery entrapment syndrome and adventitial cystic disease. Affected patients are typically younger compared with those affected by peripheral artery disease and lack typical risk factors associated with atherosclerosis.
Treatment of symptomatic patients generally requires an open surgical approach to manage the vascular abnormality, although for some patients, medical management may be an option.
The clinical features, diagnosis, and treatment of nonatheromatous popliteal artery disease are reviewed.
The clinical features, diagnosis, and management of atherosclerotic lower extremity disease are reviewed elsewhere. Popliteal artery aneurysm is also reviewed separately. (See "Overview of lower extremity peripheral artery disease" and "Clinical features and diagnosis of lower extremity peripheral artery disease" and "Management of claudication due to peripheral artery disease" and "Popliteal artery aneurysm" and "Surgical and endovascular repair of popliteal artery aneurysm".)
ANATOMIC CONSIDERATIONS — The popliteal artery is a continuation of the femoral artery as it exits the adductor canal (Hunter canal), which is the aponeurotic passageway from anterior thigh to posterior leg (figure 1). Within the popliteal fossa, the popliteal artery is the deepest structure and lies adjacent the knee joint capsule. Multiple geniculate branches provide blood supply to the knee joint (figure 2) as well as provide collateral flow to the leg during maximal knee flexion. Important muscles relevant to the pathologies discussed below (popliteal artery entrapment syndrome, adventitial cystic disease) include the popliteus muscle, which normally lies anterior to the popliteal artery, and the medial head of the gastrocnemius muscle of the calf, which lies medially in the distal portion of the popliteal space.
CLINICAL FEATURES AND DIAGNOSIS — The clinical presentation of nonatheromatous popliteal disease is primarily intermittent claudication (derived from the Latin word for limp), which is defined as a reproducible discomfort in a muscle group induced by exercise and relieved with rest. The severity of claudication symptoms depends upon the degree of obstruction, the effectiveness of the collateral circulation, and the level of exercise.
Diagnosis of vascular obstruction — Most patients with symptoms of claudication undergo noninvasive vascular testing, including physiologic testing with or without duplex ultrasound. Symptomatic patients with nonatheromatous popliteal disease often have normal ankle-brachial index values at rest but will have abnormal studies following exercise. As such, the first step in the evaluation of a patient with claudication and suspected nonatheromatous arterial disease should be exercise testing. (See "Noninvasive diagnosis of upper and lower extremity arterial disease", section on 'Exercise testing'.)
Imaging confirms vascular obstruction and etiology. (See 'Diagnostic evaluation for entrapment' below and 'Diagnostic evaluation for cystic disease' below.)
DIFFERENTIAL DIAGNOSIS — The differential diagnosis of nonatherosclerotic popliteal artery disease is primarily obstruction due to atherosclerosis (ie, peripheral artery disease [PAD]) causing claudication or other atypical symptoms. However, while PAD typically presents later in life, a subset of younger patients with more aggressive disease does exist. However, patients with PAD most often have typical risk factors for atherosclerotic disease (eg, smoking, hypertension, dyslipidemia, diabetes, chronic kidney disease), which are typically absent in those with nonatheromatous disease. (See "Clinical features and diagnosis of lower extremity peripheral artery disease".)
Nonatheromatous popliteal artery diseases often affect younger people, and the differential diagnosis is often quite broad (table 1) [1]. Claudication symptoms can frequently be mistaken for symptoms related to muscle strains or tears, stress fractures, or chronic compartment syndrome in affected younger patients [2]. In addition, patients with nonatheromatous vascular disease often have palpable pedal pulses at rest, which further confuses the issue [3]. Endofibrosis is another nonatheromatous arterial disease that affects the iliac artery related to repetitive trauma usually due to athletic activities [4].
Popliteal venous compression can coexist with nonatheromatous arterial diseases. Popliteal venous entrapment syndrome as an isolated entity is much less common compared with popliteal artery entrapment syndrome [5,6]. Other conditions that can cause lower extremity edema, which can be associated with nonatheromatous arterial diseases, include deep venous thrombosis and chronic venous insufficiency. In a young patient with unilateral swelling and no other risk factors for venous thrombosis, iliac vein obstruction should be considered. (See "Clinical manifestations and evaluation of edema in adults" and "Clinical manifestations of lower extremity chronic venous disease" and "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity" and "May-Thurner syndrome".)
SPECIFIC SYNDROMES — While symptoms of ischemia and the general approach to evaluation are similar for nonatherosclerotic popliteal disease, treatment and prognosis are specific to each
syndrome. The most common nonatheromatous popliteal artery diseases, popliteal artery entrapment syndrome and adventitial cystic disease, are reviewed in detail below; other less common etiologies are briefly listed with links to separate topic reviews. (See 'Other nonatheromatous popliteal diseases' below.)
Popliteal artery entrapment syndrome — Popliteal artery entrapment syndrome (PAES) is a condition in which there is an abnormal anatomic relationship between the neurovascular structure of the popliteal fossa and nearby musculotendinous structures. Popliteal artery entrapment is the most common form, and popliteal artery compression by one of the calf muscles can reduce blood flow to the leg, causing ischemic symptoms. Symptoms of PAES are usually chronic, but acute limb ischemia (ALI) can also occur. Much less commonly, the popliteal vein is compressed, which can lead to popliteal vein entrapment syndrome (PVES) manifesting as chronic leg edema [5,6].
PAES is an overall rare condition, but its prevalence has increased in recent years likely because of increased awareness in the medical community. The overall prevalence of PAES is estimated to range from 0.17 to 3.5 percent of the general population [7].
Types: congenital versus acquired — PAES can occur as either a congenital or acquired condition. In the congenital form (types I to VI), one of the calf muscles develops in an abnormal position during fetal development, resulting in displacement or compression of the popliteal artery. In the acquired form of PAES (types F), one of the calf muscles becomes enlarged, resulting in compression of the popliteal artery. The acquired form is commonly referred to as functional PAES.
Several scales have been used to describe PAES based on the relationship of the medial head of the gastrocnemius muscle (MGH) with the course of the vascular structures, predominantly the popliteal artery [1,8-11]. The Popliteal Vascular Entrapment Forum described a classification system consisting of six congenital forms of PAES as well as the acquired form:
●Type I: An aberrant medial course of the popliteal artery around a normally positioned MGH.
●Type II: The popliteal artery courses more inferolaterally than normal due to an abnormal lateral attachment of the MGH to the femur.
●Type III: The popliteal artery is in its normal position but is encircled by an aberrant accessory muscle slip from the MGH.
●Type IV: The popliteal artery is in its normal position but is encircled by the popliteus muscle or a fibrous band.
●Type V: Primarily venous entrapment.
●Type VI: Other variants.
●Type F: The popliteal artery is in its normal position but is entrapped by a hypertrophied gastrocnemius muscle, resulting in a functional entrapment syndrome.
Presentation — Patients with PAES are typically young and male without atherosclerotic risk factors such as smoking, hypertension, hypercholesterolemia, and diabetes [12]. Based on a systemic review published in 2021, the mean age at time of PAES diagnosis was 32 years, and 83 percent of affected patients were male [8].
Individuals with PAES can be asymptomatic or symptomatic. Asymptomatic PAES has an estimated prevalence ranging from 25 to 80 percent [8,13]. Many cases are bilateral, although the exact prevalence of bilateral PAES is unknown (25 to 83 percent in the available literature [14-16]).
Symptomatic patients typically complain of classic intermittent claudication related to arterial compression, but other symptoms such as paresthesias related to tibial nerve compression or swelling related to vein compression (grade V PAES) can also occur [15]. In a study of 88 limbs with PAES treated over 10 years, claudication was the main presenting symptom in 79.5 percent of cases [14]. ALI occurs in approximately 11 percent of patients [15].
Diagnostic evaluation for entrapment — PAES should be considered in patients with clinical symptoms consistent with compression of the neurovascular structures of the popliteal fossa (predominantly arterial compression), particularly in otherwise healthy young male patients with claudication who do not smoke. Multiple studies are often performed to establish this often missed and difficult diagnosis. Based on a systemic review of PAES, digital subtraction angiography (DSA) was the most commonly used imaging modality in the diagnostic workup (28 percent of cases), followed by ankle-brachial index (ABI) measurements (18 percent), computed tomographic (CT) angiography (12 percent) or magnetic resonance (MR) angiography (12 percent), duplex ultrasound (10 percent), exercise ABIs (4 percent), and other modalities (4 percent) [8]. On average, patients undergo three investigations prior to confirming the diagnosis of PAES [8].
In the younger patient with claudication symptoms suspicious for PAES, resting ABIs are usually normal, but during exercise values decrease as the popliteal artery is compressed by the aberrant calf musculature. While exercise ABIs are traditionally measured before and after walking on a treadmill with a slight incline, the diagnosis of PAES may be better evaluated before and after the patient performs forceful plantarflexion. An average force of plantarflexion between 0 and 70 percent of maximum has been shown to be maximally sensitive and specific for diagnosing PAES [1]. Forceful plantarflexion is used as a provocative maneuver for making the diagnosis with ABI as well as other imaging modalities.
Vascular imaging with provocative maneuvers — Duplex ultrasound can be used to establish a diagnosis of PAES. When the patient is positioned supine with the legs straight, popliteal artery velocities should be normal. However, after exercise or with provocative maneuvers (ie, forceful plantarflexion), flow velocities in the popliteal artery will increase as the popliteal artery is compressed.
Cross-sectional imaging using CT or MR angiography show the anatomic relationship neurovascular structures in the popliteal fossa to the gastrocnemius muscle. Dynamic CT and MR angiography are particularly helpful for diagnosing functional PAES in which the anatomy is normal, but gastrocnemius hypotrophy causes compression during exercise. Dynamic angiography involves taking images first in the static position and then again following a series of provocative maneuvers. In general, MR angiography provides better resolution of muscle anatomy compared with CT angiography, but is more time consuming to obtain. By contrast, CT angiography is convenient and can be obtained quickly, but involves radiation exposure and the use of iodinated contrast.
If the diagnosis of PAES is not confirmed using one of the above studies, DSA can be performed and is best accomplished by obtaining angiographic images with the patient in a static supine position, and then again following forceful plantarflexion as described above. When performed with provocative maneuvers, DSA is highly sensitive (97 to 100 percent) for making the diagnosis of PAES [8].
Management approach
Asymptomatic patients — For patients with asymptomatic popliteal entrapment syndromes, no intervention is necessary. PAES may be present based on imaging studies, but if it is not associated with symptoms, there is no indication for repair. Similarly, in patients with evidence of venous or nerve compression who are not symptomatic, no specific treatment is needed.
Symptomatic patients
●Congenital PAES – For patients with symptomatic congenital PAES (types I to VI), open surgery is the mainstay of treatment. Only a few small studies describe outcomes for conservatively managed patients with symptomatic congenital PAES. Of these, symptom resolution was described in a small number of patients with moderate symptoms following discontinuation of an extreme exercise program [14].
●Functional PAES – For patients with functional PAES (type F), intervention is indicated for those with lifestyle-limiting symptoms. Because patients who come to medical attention tend to be young and often involved in extreme exercise or athletics, lifestyle-limiting symptoms often include those that affect athletic activities. Decompressive surgery has been the mainstay of treatment for functional PAES, but series describing the use of botulinum toxin A injections as an alternative noninvasive treatment have been favorable [17,18]. The authors of a systemic review have suggested that patients with functional PAES and normal-appearing popliteal vasculature on CT or MR angiography can be reasonably treated with a trial of botulinum toxin A [15]. If symptoms improve following injection, the diagnosis of functional PAES is confirmed. If the symptoms recur, the patients can either undergo a repeat botulinum toxin A injection or proceed with surgical decompression.
Surgery for popliteal artery entrapment — Treatment of PAES involves open surgical decompression of the popliteal space with or without arterial reconstruction depending on the condition of the vasculature. Surgical decompression is usually achieved by performing a musculotendinous division to release the entrapment.
While endovascular techniques are often the preferred initial treatment for lower extremity revascularization related to peripheral artery disease (PAD), because of the associated anatomic abnormalities with PAES, endovascular therapy is not commonplace except perhaps in the form of catheter-directed thrombolysis for patients presenting with ALI [14,19]. (See "Intra-arterial thrombolytic therapy for the management of acute limb ischemia".)
Patients with PAES who are treated for ALI will still require surgical decompression following restoration of flow to address their anatomic abnormalities. There is currently no role for an endovascular-only intervention for the management of PAES.
A posterior [11,20-24] or a medial approach [14,25,26] for surgical decompression of PAES can be used. There are no objective benefits of one approach over another, although studies performing both tend to describe using the posterior approach for decompression alone and the medial approach for cases when arterial reconstruction is anticipated [8].
●For the posterior approach, either a longitudinal or S-shaped incision is made on the posterior knee. The popliteal artery is completely exposed, releasing all musculotendinous attachments along its course. The artery is then replaced in its native (ie, orthotopic) position [24].
●For the medial approach, a longitudinal incision is made just below the knee, and the gastrocnemius and/or other musculotendinous attachments are fully divided to release the compression of the popliteal artery. If there is a popliteal artery stenosis due to long-term trauma to the vessel, arterial reconstruction is indicated. Sometimes this will be anticipated preoperatively based on cross-sectional or angiographic imaging. If it is unclear, intraoperative duplex ultrasound can be helpful to assess for stenosis in the affected segment following decompression. As with any lower extremity bypass, autogenous conduit using great saphenous vein is preferred whenever possible.
Outcomes following surgical decompression of PAES are generally favorable. Successful resolution of symptoms occurs in 77 percent of cases. Complications following surgery for PAES are generally related to arterial reconstruction, which occurs in a median of 27.5 percent of cases [8]. Other complications include deep vein thrombosis (11 percent), wound seroma (4.6 percent), and wound infection or hematoma (3 percent) [8].
Adventitial cystic disease — Adventitial cystic disease (ACD) is a condition of unknown etiology that results in cysts containing gelatinous mucoid material located between the adventitial and medial layers of the artery, causing luminal stenosis or occlusion [27]. The cysts are usually unilocular, lack a cellular lining, and contain hyaluronic acid, protein, and proteoglycans [28,29].
Anatomic locations — ACD was first identified in 1946 in the external iliac artery of a 40-year-old man presenting with claudication [30]. It has subsequently been described in other locations, most commonly within the popliteal artery, the superficial femoral artery, and nearly all other arteries of the thigh. It has also been described in arteries of the upper extremity, most commonly in the distal upper extremity arteries. ACD has also been described in several lower extremity venous locations (eg, common femoral vein, great saphenous vein).
Pathogenesis — Given the rarity of ACD, the pathogenesis has not been fully elucidated and is still debated. There are four main hypotheses to explain the origin of ACD:
●Cyst formation is in response to a synovial fluid that has leaked from the joint space into neighboring arterial (or venous) adventitia [31]. While trauma may cause the joint capsule defect, it is presumed that it is the exudation of synovial fluid that results in the pathology. This connection has purportedly been identified on various imaging modalities in patients with adventitial cystic disease, including CT and MR imaging and arthrogram of involved joints [32,33]. However, the cysts contain hyaluronic acid and protein as well as proteoglycans without lubricating ability, suggesting ganglionic origin as opposed to synovial origin [28,29].
●Cysts form from primary adventitial degeneration following repetitive trauma. Given the common location of these lesions near joints, the presumed flexion/extension results in the pathologic changes due to recurring stretching of the adventitia.
●A developmental abnormality results in mucin secreting mesenchymal cells placed within the adventitia during embryogenesis [34]. Due to an unknown trigger later in life, these cells begin secreting mucin, resulting in the pathologic changes.
●Adventitial cysts form in response to a systemic connective tissue disorder [35]. However, this has not been clinically demonstrated, as most patients with ACD do not consistently show signs of systemic illness.
Cystic disease presentations — The overall incidence is unknown; however, among patients presenting with claudication, it is estimated to be present in 1 of 1200 [35]. ACD occurs more commonly in males than females (4:1 ratio), and while it can occur in older patients and pediatric populations, ACD is typically diagnosed in the fourth or fifth decade of life [36]. In most patients, a single vessel is affected, although multiple artery ACD has been described [37].
Patients with lower extremity ACD most commonly present with unilateral intermittent claudication [38]. Because the most common location for the lesion is the popliteal artery, the calf is the most commonly affected muscle group; the right and left lower extremity are affected with similar frequency [36]. As compared with PAD, however, patients with ACD and claudication frequently have prolonged post-exercise recovery time before pain resolution and may report a waxing and waning of symptoms due to fluctuating amounts of cyst content present at any given time.
Patients can also present with ALI, pain, paresthesias, or a palpable tissue masses [38].
Venous ACD most commonly present with limb swelling resulting from venous compression from the cystic mass. The cystic structures may be mistaken for venous thrombus, although venous compression can also result in DVT [39-41].
Diagnostic evaluation for cystic disease — While ACD is a rare cause of unilateral lower extremity arterial symptoms, it should be considered in any patient lacking typical cardiovascular risk factors but presenting with claudication symptoms, particularly in younger patients.
The pulse examination is variable depending on the severity of the compression by the cystic lesions; the patient can have normal, diminished, or no distal pulses. The "Ishikawa sign" may be present, which is a palpable pedal pulse that is lost with passive flexion of the knee or exercise [42]. This sign may be also noted during ABI determination.
Vascular imaging can demonstrate the cystic lesion(s) of the affected artery and the severity of any associated stenosis or complete occlusion [38].
●In the hands of experienced sonographers, ACD lesions are noted as anechoic or hypoechoic masses (black) arising from the arterial wall that have smooth contours and compress the lumen of the vessel to varying degrees [43]. This compression is concentric, resulting in an "hourglass" appearance. Duplex ultrasound may demonstrate elevated peak systolic velocities at the point of maximal compression.
●CT angiography typically demonstrates hypodense lesions within the artery wall, and MR angiography shows homogenous low signal intensity on T1-weighted images and high signal intensity on T2-weighted images, and both modalities may reveal connections with adjacent joint capsules.
●DSA alone may demonstrate a stenotic lesion but cannot provide a specific diagnosis of ACD [44]. However, if performed, the classic "scimitar sign" with contrast filling the narrowed vessel in a curvilinear manner due to the eccentric lesion compression may raise suspicion for the diagnosis, which requires ultrasound or cross-sectional imaging to confirm.
Treatment for cystic disease — Given its rarity, the natural history of untreated ACD has not been fully elucidated. However, treatment of symptomatic patients is warranted to prevent progression to a fixed lesion or to prevent limb-threatening ischemia due to thrombosis of the stenotic segment of the artery.
Popliteal adventitial cyst — Several treatments have been described to treat popliteal ACD, including aspiration of the cyst contents or cyst resection without or with vascular reconstruction (eg, interposition graft, bypass). Patients undergoing cyst resection are less likely to have recurrence compared with cyst aspiration. Vascular reconstruction has excellent long-term patency. Endovascular treatment is not typically performed given risk of recurrence with angioplasty alone, as well as the common location of ACD lesions at flexion points, which preclude long-term durability with stent placement; however, endovascular intervention has been described successfully for some anatomic locations such as ACD involving the external iliac arteries [45].
The goal of cyst aspiration is to reduce the severity of compression and can be performed via an open surgical approach or percutaneously using image guidance (ultrasound or CT). Technically, the procedure can be challenging given the location of the cyst surrounded within the popliteal space. In addition, given the multilocular nature of the cysts and the thickness of the contents, evacuation is often incomplete, leading to high rates of recurrence (up to 40 percent) or inadequate relief of symptoms [38]. In general, this technique is reserved for patients who are not surgical candidates.
Surgical management of ACD involves cyst resection with or without vascular reconstruction, either using an interposition graft or saphenous vein bypass graft. The surgical approach depends upon the extent of the cystic changes. The popliteal artery is typically exposed from a posterior approach. A short interposition saphenous vein graft is typically all that is required after excision of the cyst from the affected artery [46].
Other nonatheromatous popliteal diseases — Other nonatheromatous diseases that can affect the popliteal artery and cause ischemic lower extremity symptoms include the following [47,48]:
●Fibromuscular dysplasia – Fibromuscular dysplasia (FMD) most commonly affects the renal arteries and extracranial cerebrovascular arteries, but it can affect the popliteal artery, leading to ischemic symptoms due to embolism or related to formation of popliteal aneurysm. (See "Clinical manifestations and diagnosis of fibromuscular dysplasia" and "Popliteal artery aneurysm".)
●Thromboangiitis obliterans (Buerger disease) – Thromboangiitis obliterans (TAO) more typically affects the small vessels of the hands and feet. Large artery involvement can occur, but when it does, it rarely occurs in the absence of small vessel occlusive disease. Cannabis can lead to a vasculitis that is clinically similar to TAO [47]. (See "Thromboangiitis obliterans (Buerger disease)" and "Cannabis use: Epidemiology, pharmacology, comorbidities, and adverse effects".)
●Medium and large vessel vasculitis – Arterial involvement occurs in 10 to 30 percent of patients with Behcet syndrome, largely related to aneurysm formation [48]. Other forms of vasculitis more typically involve the vessels of the upper extremity, but rarely the lower extremities can be involved [49]. (See "Clinical manifestations and diagnosis of Behçet syndrome", section on 'Arterial disease' and "Overview of and approach to the vasculitides in adults" and "Popliteal artery aneurysm".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acute extremity ischemia".)
SUMMARY AND RECOMMENDATIONS
●Nonatheromatous arterial diseases – Nonatheromatous popliteal artery diseases are uncommon conditions and include predominantly popliteal artery entrapment syndrome (PAES) and adventitial cystic disease (ACD). Affected patients are typically younger compared with those affected by peripheral artery disease (PAD) and lack typical risk factors associated with atherosclerosis. (See 'Clinical features and diagnosis' above.)
•Popliteal artery entrapment syndrome – Popliteal artery entrapment syndrome (PAES) is due to an abnormal anatomic relationship between the neurovascular structures of the popliteal fossa and nearby musculotendinous structures that can be congenital or acquired. PAES can be bilateral. PAES is classified based on the relationship of the medial head of the gastrocnemius muscle with the vascular structures, predominantly the popliteal artery. (See 'Popliteal artery entrapment syndrome' above.)
•Adventitial cystic disease – ACD is a condition of unknown etiology that results in cysts containing gelatinous mucoid material located between the adventitia and medial layers of the artery causing luminal stenosis or occlusion. ACD is more common in males compared with females and typically presents in the fourth or fifth decade of life. (See 'Adventitial cystic disease' above.)
●Clinical features and diagnosis – Nonatheromatous popliteal artery disease can reduce perfusion to the extremity typically causing chronic ischemic symptoms, but acute limb ischemia or other related symptoms can also occur. Patients with nonatheromatous popliteal disease predominantly present with intermittent claudication, which a reproducible discomfort in a muscle group induced by exercise and relieved with rest. Other symptoms include paresthesias, or limb swelling related to nerve or venous compression, respectively. Symptomatic patients often have normal ankle-brachial index (ABI) values at rest, but with exercise testing, ABI values markedly decrease. Vascular imaging (eg, ultrasound, cross-sectional imaging, angiography) confirms the diagnosis. (See 'Clinical features and diagnosis' above and 'Diagnostic evaluation for entrapment' above and 'Diagnostic evaluation for cystic disease' above.)
●Differential diagnosis – The differential diagnosis of nonatherosclerotic disease is primarily obstruction due to atherosclerosis (ie, PAD) causing claudication or other atypical symptoms. Because nonatheromatous popliteal artery diseases usually affects younger people, the differential diagnosis of exertional leg pain is broad (table 1). (See 'Differential diagnosis' above.)
●Treatment – Patients who are asymptomatic do not require treatment. For symptomatic patients, treatment generally requires an open surgical approach to manage the vascular abnormality, although for some patients less invasive therapy, though not endovascular therapy, may be an option (eg, botulinum toxin for PAES; cyst aspiration for ACD). Long-term patency rates following surgical management of nonatheromatous arterial disease in the absence of thrombosis are generally excellent.
•Surgical treatment of PAES involves decompression of the popliteal space with reconstruction of the artery, if damaged. (See 'Surgery for popliteal artery entrapment' above.)
•Surgical treatment of ACD involves surgical excision of the cyst and interposition grafting using saphenous vein reconstruction. (See 'Popliteal adventitial cyst' above.)
