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Diabetes Watch

Evaluating PAD In Patients With Diabetic Charcot Neuroarthropathy

Charcot neuroarthropathy is a rare but serious complication associated with diabetes mellitus. It is a disease that affects joints and ultimately leads to their deformation and destruction. These joint and structural changes increase a patient’s risk of pedal ulceration and puts patients at risk for potential limb loss.1

Schon and colleagues found the anatomic distribution of Charcot neuroarthropathy to be 22.6 percent in the ankle, 10 percent in the hindfoot, 59.2 percent in the midfoot and 8 percent in the forefoot.2 Although Charcot neuroarthropathy’s anatomical involvement varies, it will most commonly affect the midfoot.2 These structural and destructive changes are secondary to Charcot neuroarthropathy’s strong tie to peripheral neuropathy. In comparison to a sensate foot, the risk of ulceration is seven times greater in patients with diabetic neuropathy.2

Although the true etiology of Charcot neuroarthropathy has yet to be elucidated, there is an agreed upon theory that an increased peripheral blood flow causes the leaching of minerals from the bone, which results in eventual osseous and joint breakdown. This periarticular osteopenia induced from hyperemia is theoretically a result of an autonomic-stimulated vascular reflex.3

An estimated 0.1 percent to 7.5 percent of patients living with diabetes have Charcot neuroarthropathy. In patients with Charcot neuroarthropathy, the primary surgical goal of Charcot reconstruction is to recreate a plantigrade foot, which ultimately decreases the patient’s risk for ulceration and infection. Surgical procedures include: Achilles tendon lengthening, exostectomy, osteotomies, arthrodesis and open reduction internal fixation (ORIF) techniques.4

Understanding The Connection Between Charcot And PAD

Despite the commonly accepted dogma of Charcot being associated with strong pulses and good peripheral perfusion, peripheral arterial disease (PAD) occurs in the natural history of diabetes.5 Peripheral arterial disease is the result of decreased perfusion secondary to arteriosclerotic plaques and medial artery calcifications.6,7 Worldwide, over 200 million people have PAD and in patients over the age of 70, the rate is as high as 20 percent.6

In patients with diabetes over 40 years old, the rate of PAD is twice as high as for those without diabetes.8 In patients with diabetic foot ulcers, the incidence of PAD is as high as 49 percent.9 This connection between Charcot neuroarthropathy and PAD seems contradictory.10

While it is commonly accepted that there is a connection between patients with diabetes and PAD, it is important not to ignore PAD in patients with Charcot. These patients are already at a high risk of major amputation and neglecting PAD can lead to numerous detrimental effects. As patients with diabetes advance in age, their risk for developing PAD increases as well. Without proper evaluation or detection of PAD in patients with diabetes and Charcot, patient risk for wound formation, infection and amputation increases exponentially. Despite this connection between PAD and Charcot neuroarthropathy, there is limited research available on the subject. Therefore, when considering vascular assessment in Charcot, clinicians largely depend on the literature available for patients with diabetes as a proxy.

Charcot joint destruction is a devastating and possibly limb-threatening effect of diabetes. This patient population is further complicated and amplified by the effects of PAD, which has a high prevalence in patients with diabetes. The combination of Charcot and PAD places patients at an increased risk of foot ulcerations and limb amputations. Patients with diabetes have an average life expectancy of less than three years after a below-knee amputation.11 Wukich and colleagues examined Charcot neuroarthropathy patients with abnormal clinical vascular findings, and found the rate of PAD in those patients to be 40 percent via the diagnosis of an ankle-brahcial index (ABI) of <0.9 or a toe-brachial index (TBI) of <0.7 on either extremity.12

Our unpublished research from a cohort of 284 patients with Charcot who had osseous reconstruction found a 21.8 percent rate of PAD. The patients with Charcot neuroarthropathy and PAD had significantly higher rates of complications than the Charcot patients without PAD. Patients with PAD were 2.012 times as likely to have delayed healing and 4.414 times more likely to have major lower extremity amputation post-osseous reconstruction. Due to these negative outcomes in patients with Charcot neuroarthropathy with PAD, it alerts clinicians to the need for proper vascular evaluation and possible surgical intervention.10

What Are The Most Effective Diagnostic Tools For PAD?

There is no consensus on how to diagnose PAD in the diabetic population. This is due to the discrepancy in the interpretation of the validity of tests, especially in patients with diabetes. Medial artery calcinosis occurs in the natural history of diabetes and leads to inaccuracies in the diagnosis of PAD. Vessels become less compressible and rigid with medial artery calcinosis, causing lower sensitivities when palpating the pedal pulses and elevated ABI readings.13,14

The use of the TBI, rather than the ABI, may improve reliability in testing for PAD in the diabetic population.14 The theory is digital arteries are less susceptible to medial artery calcinosis than those at the level of the ankle and therefore have more accurate pressure readings in the diabetic population.14

However, there are many perspectives when dealing with the reliability of ABIs and TBIs. Wukich and colleagues advocate considering both ABIs and TBIs to improve the diagnostic accuracy of PAD in patients with diabetes. Hyun and coworkers rely solely on TBIs for the diagnosis of PAD in patients with diabetes, due to the limited predictive values of ABIs resulting from the falsely elevated ABI readings.15 Despite the theory of digital arteries being less affected by medial artery calcinosis, a study by Stoekenbroek and colleagues found the use of TBIs did not result in earlier detection of PAD in comparison to ABIs.16

Other clinicians do not rely on ABIs or TBIs for the diagnosis of PAD for these reasons. Boulton and colleagues assessed PAD with pedal pulse palpation and Doppler examination in the diabetic population.17 Dopplers utilize an audible signal to assess and classify a waveform of a vessel as opposed to evaluating its pressure in ABIs. However, Doppler examinations are not without flaws as investigators have found low accuracy in Doppler exams due to high false positive rates and low specificity.18

Due to each individual test’s shortcomings, the combination of tests allows for higher reliability in the results. The combinations of the examinations build a clinical picture of the microvascular and macrovascular circulation.
The current gold standard for defining normal macrovascular anatomy and identifying vascular pathology is contrast angiography.19 Angiography provides a map of perfusion based on the distribution of injected dye. One can assess this dye radiographically in real time. However, Hirsch and colleagues stated that due to digital contractures, the smaller distal vessels may be hard to visualize on angiography.20 Angiography is not without its detrimental effects, such as its ability to induce or worsen kidney injury, putting patients at risk for developing end-stage renal disease.19 There have also been adverse reactions in select patients who mount a cell-mediated reaction to the dye itself. Despite these setbacks, angiography remains a standard of care in the diagnosis of vascular disease.

In our unpublished research, we compared post-osseous reconstruction complication rates in patients with diabetic Charcot neuroarthropathy and PAD who were diagnosed by angiography versus those diagnosed clinically. Nineteen patients had angiography-diagnosed PAD and 40 patients had clinically diagnosed PAD. Patients with PAD diagnosed by angiography had a statistically significant higher rate of return to ambulation than those with PAD who were diagnosed clinically. We found no statistical significance between preoperative infection rates of preoperative ulcers present, preoperative soft tissue infection, preoperative osteomyelitis, delayed healing, surgical site infection, osteomyelitis, dehiscence, transfer lesion, new site of Charcot collapse, malunion/nonunion and major lower extremity amputation.

Preventing catastrophic events such as major lower extremity amputation or new sites of Charcot collapse is paramount. The results of our study give legitimacy to the prognostic findings of the clinical exams for PAD due to the ability of the exams to evaluate local tissue perfusion. Return to ambulation was the only outcome with statistical significance in our study, which indicates improved functional outcomes. With a shift in limb salvage to functional limb salvage, this outcome is crucial to a patient’s functional level with day to day activities. The main goal of limb salvage should not focus on sparing the foot but on functional outcomes.21

In our study, we hypothesized that angiography depicted macrovascular pathology whereas clinical examinations depicted both macrovascular and microvascular pathology. Angiography helps to visualize a vascular road map of known larger named vessels but it does not readily evaluate local tissue perfusion.

Key Insights On The Value Of Assessing Angiosomes

An additional method for evaluating local tissue perfusion and vascular status is the assessment of angiosomes. Clinical evaluation of angiosomes with assessment of retrograde flow is a technique to give clinicians a better picture of location perfusion. The foot and ankle are comprised of six source angiosomes, which originate at the anterior tibial, posterior tibial and peroneal arteries.

Taylor and Minabe defined an angiosome as a three-dimensional anatomical unit of tissue fed by a source artery.22 Although these dominant arteries supply differing regions of the distal leg and foot, they also have numerous artery to artery connections. This vast web of arterial connections provides a continual arterial supply to these zones, despite occlusion or vascular damage to a dominant vessel.23 The foot uses these connections to provide blood flow to various areas via retrograde flow should a direct arterial route be occluded.21

The three large arteries can be compartmentalized into further subcategories that are branches of the large arteries. The posterior tibial artery can be broken down into the medial calcaneal branch, medial plantar artery and lateral plantar artery. The peroneal artery supplies the anterolateral ankle, lateral rearfoot and the lateral calcaneal branch. The anterior tibial artery supplies the anterior ankle and the dorsalis pedis supplies the dorsum of the foot. All these branches make up the local angiosome that provides the localized network of blood flow to the soft tissue and osseous structures.23 Adjacent angiosomes are connected by their local arterial to arterial connections, also called “choke vessels,” which link angiosomes together and provide a conduit to provide blood flow to an adjacent angiosome should the latter’s source artery be compromised.24

We can clinically evaluate arterial to arterial connections to see whether an angiosome is occluded and if it is being supplied by another angiosome via retrograde flow.21 It takes an understanding of anatomy to identify which artery is the predominant supply to a region and this can happen in clinic using a Doppler instrument.

After locating the artery with the Doppler, you can identify the direction of flow by causing selective occlusion, both proximally or distally to the artery, with your finger. The Doppler evaluates the quality of flow to the area, whether it is triphasic, biphasic or monophasic, as well as antegrade or retrograde flow. Occluding an artery to identify its flow pattern will tell us if a segment of tissue is dependent on inflow from another major artery via a choke vessel/arterial-arterial connection.21 Any disruption of that connection will place the soft tissue benefiting from that connection at risk. For surgical patients with diabetes and PAD who have rest pain or foot ulcerations, this clinical assessment can aid in incision placement as well as assist vascular surgeons with bypass planning based on which angiosomes are compromised, resulting in local ischemia. Berceli and coworkers found that 15 percent of bypasses fail to heal pedal wounds because they fail to revascularize the affected angiosome.25

Comparing Endovascular Therapy With Surgical Bypass

When faced with a compromised blood supply, doing proper arterial mapping is crucial in incision placement and wound management. Although Doppler examination helps identify the flow patterns of the lower extremity, vascular surgeons can employ angiography to identify the main vascular flow and collateralization, and perform necessary intervention. In patients with non-palpable pulses and monophasic Doppler ultrasound, clinicians should refer the patient for angiography with possible intervention prior to proceeding with definitive surgical correction.

Endovascular therapy and surgical bypass treatments are two techniques for restoring blood flow in patients with PAD or critical limb ischemia (CLI). While authors have promoted bypass for its long-term patency and effects, research has also shown that bypass increases patient morbidity and hospital resources.26 However, in comparison to angioplasty with or without stenting, bypass has lower procedural morbidity, lower mortality, is faster and preserves vascular collateralization.27

Endovascular treatments have become the first line of interventional therapy in patients with PAD, in comparison to the bypass. Endovascular treatment is now one of the first choices in CLI cases involving vasculature at the below knee level.26 Endovascular treatment in patients with diabetes has a lower complication rate and does not require general anesthesia, which benefits patients with higher comorbid diseases.26,27 In one study, percutaneous transluminal angioplasty was able to increase TcPO2 in patients one month postoperatively.25 A study by Lida and colleagues found 68 percent of patients with CLI and diabetes had limb preservation following endovascular therapy at the two-year mark.28 Ferraresi and coworkers found a limb preservation rate of 93 percent at a mean follow-up of 1,048 days after infrapopliteal angioplasty in patients with diabetes.29

However, even with advancement in vascular intervention, patients who receive bypasses fail to heal 15 percent of lower extremity wounds.25 Failure may be multifactorial, such as improper wound care or biomechanical instability, but part of it may be due to inadequate revascularization to the ischemic area.30 Failure to obtain revascularization to the direct source artery of a particular angiosome decreases healing rates in comparison to revascularizing the other major arteries depending on arterial to arterial connections.Intervention is optimal when direct revascularization to the vessel feeding the occluded angiosome is possible.

Final Thoughts

Patients with Charcot neuroarthropathy become severely debilitated by the biomechanical changes associated with the disease. As Charcot neuroarthropathy progresses and osseous and joint destruction occur, these patients are at an increased risk of ulceration and risk of limb loss.4 While evaluating these patients for surgical correction, it is important to consider the patient as a whole and his or her associated comorbidities. Peripheral arterial disease, in patients with Charcot, often occurs due to the natural progression of diabetes.

As clinicians, we understand the importance of assessing for PAD but there is currently not a consensus of how to diagnosis it in the clinical setting. Using clinical techniques such as palpable pulses, Doppler, ABI and TBI provide a basis of patient vascular status. The overall reliability of these studies decreases by the tunica media calcinosis that occurs naturally with diabetes.13,18 Clinical evaluation of angiosome flow via Doppler exam helps identify the source artery to local tissue. Noninvasive evaluation in conjunction with angiography allows the physician an in-depth clinical picture of a patient’s vascular status. These assessments will allow physicians to evaluate for local tissue perfusion and give them insight into the need for vascular intervention, proper surgical incision placement and preventing ischemic events postoperatively. 

Dr. Cates is a third-year podiatric surgery resident at MedStar Georgetown University Hospital in Washington, DC.

Dr. Salerno is a second-year podiatric surgery resident at MedStar Georgetown University Hospital in Washington, DC.

Dr. Lavery is a board-certified podiatrist and Professor of Plastic Surgery, Orthopaedic Surgery, and Physical Medicine & Rehabilitation at UT Southwestern Medical Center. He is also the Medical Director of UT Southwestern’s Comprehensive Wound Care Center and Director of the Amputation Prevention Program at Parkland Memorial Hospital in Dallas.

Dr. Kim is a Professor in the Department of Plastic Surgery at MedStar Georgetown University Hospital in Washington, DC. He is a Fellow of the American College of Foot and Ankle Surgeons.

References

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By Nicole K. Cates, DPM, Nicholas Salerno, DPM, Lawrence L. Lavery, DPM, MPH, and Paul J. Kim, DPM, MS
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