Is Blood Flow A Significant Factor In Patients With Charcot Neuroarthropathy?

There is a prevailing perception that patients with Charcot neuroarthropathy are distinctly different from other patients who present with other diabetes-related foot problems. Specifically, in comparison to patients with diabetes who do not have Charcot foot/ankle deformities, some believe Charcot patients have a “normal vascular exam.”¹ Not only do some physicians believe patients with Charcot neuropathy have normal blood flow but some consider increased local blood flow to be a hallmark of Charcot neuroarthropathy.

Diabetic foot wounds are a very challenging problem but when one considers the subset of patients who have a Charcot deformity, the problems only seem to be magnified. Charcot neuropathy remains a poorly understood pathophysiologic process. Risk factors associated with soft tissue defects in patients with diabetes include neuropathy, diminished blood flow and local trauma.²

While it is generally accepted that altered blood flow is a significant part of the etiology for most diabetic foot wounds, researchers believe the opposite to be true in patients with Charcot neuropathy.^3,4 Wukich and colleagues presented a series of patients with Charcot neuropathy who did not have significant peripheral vascular disease (PVD).⁵ In their population of Charcot patients, the need for revascularization was reduced by 82 percent in comparison to those with diabetes only. Indeed, there is a general perception that patients with Charcot not only have normal blood flow but actually have augmented blood flow due to the inflammatory nature of Charcot neuropathy.¹

We challenge the assertion that vascular disease is minimal in patients with Charcot. Accordingly, with this article, we would like to review our experience with Charcot neuropathy, determine if revascularization is necessary and see if staging of Charcot disease is a factor in revascularization.

What One Unpublished Study Reveals

The primary goal with our unpublished study was to see if patients who have been diagnosed with Charcot neuropathy and have abnormal bedside Doppler exams also have any clinically significant PVD. The secondary goal was to look for identifiable patterns of vascular disease within this patient group. We reviewed the charts of all patients with abnormalities noted on bedside exam.  

A retrospective chart review of surgical patients over the last 12 months identified 34 patients with abnormal bedside Doppler exams. The mean age of the patients was 55 years old and 64.7 percent were men. Among those patients, 79.4 percent had unilateral disease with 53 percent involving the left foot and 26.5 percent involving the right foot. Bilateral disease was present in seven of these patients.

We then stratified patients by Eichenholtz’s PVD classification.¹ Thirteen of the 34 patients had stage I PVD, 16 patients had stage II PVD and three patients had stage III PVD. Within each stage, 46 percent of stage I patients, 18.7 percent of stage II patients and 50 percent of stage III patients had severe PVD.

We sent all patients with abnormal Doppler signals for additional vascular evaluation. We measured the ankle brachial index (ABI) in 29 patients and also obtained toe pressure measurements in 76 percent of the 34 patients. This was due to limitations in interrupting ABI results with the most common reasons being non-compressible vessels and falsely elevated results. Based on the outcome of the non-invasive studies, 16 patients went on to have arteriograms. Twenty-two of the 34 patients had clinically significant PVD. Ultimately, seven patients needed intervention, five of the seven patients had an endovascular procedure and two patients needed vascular bypass. We identified the location of vascular obstruction in all patients. Eighteen patients suffered from multi-level disease while only one patient had a single lesion. The most commonly involved vessels were the anterior tibial and dorsalis pedis arteries.

Further Insights On The Impact Of Charcot Neuropathy

Diabetes is a worldwide epidemic affecting over 30 million people in the United States alone.⁶ An estimated 1 to 7.5 percent of all patients with diabetes will also develop Charcot neuropathy. Given Charcot’s clinical similarities to osteomyelitis, there is a perception that this incidence is underestimated due to misdiagnosis in early stages.

The hallmark of all patients with diabetes is hyperglycemia. It is well established that the longer the patient’s blood glucose levels are elevated, the more destructive diabetes can be. We know that persistently elevated blood glucose levels have significant deleterious effects on both nerves and blood vessels. The mechanism by which this happens is partially understood. Authors have shown that continually elevated levels of blood glucose levels contribute to endothelial cell dysfunction and smooth cell abnormalities.⁶ Additionally, we see decreases in endothelium-derived vasodilators that lead to vasoconstriction, increased atrial stiffness and, ultimately, endothial dysfunction.⁷

Further, hyperglycemia is associated with an increase in thromboxane A2 levels.⁸ Thromboxane is a potent vasoconstrictor and can cause platelet aggregation. The net result is an increased risk for plasma hypercoagulability and clotting. We also know patients with diabetic foot ulcers have higher pro-inflammatory markers, such as adiponectin, resistin and interleukin-6 levels, in comparison to patients without ulcers.⁹

It would be nonsensical to assume that the presence of hyperglycemia in patients with Charcot neuropathy would not affect blood vessels in the same way that it affects patients with diabetes who do not have Charcot neuropathy. Therefore, we should expect patients with Charcot to experience peripheral vascular disease at the same rate as patients with diabetes alone.

Perhaps the confusion centers around the fact that patients who suffer from Charcot neuropathy may present for care earlier in the course of their disease. As a result, we are potentially seeing patients with Charcot neuropathy and foot problems presenting years before patients with diabetes alone present for treatment. Regardless, we believe the incidence of PVD in patients with Charcot is high enough that one should perform a detailed vascular assessment prior to any surgery, especially if the patients present with non-healing wounds. Pre-surgical revascularization was necessary in 20 percent of our patients with Charcot neuroarthropathy. We also found vascular augmentation was necessary despite non-invasive studies in some cases not being consistent with critical limb ischemia, a finding Hafner and coworkers previously suggested.¹⁰

While this study had a limited number of patients, the findings suggest that PVD is still a concern for patients with Charcot deformities. We did see PVD evident in patients presenting within all stages of the Eichenholtz scale but further study is necessary to determine if there is any correlation to PVD. What is clear from the results of this study is that once one determines a patient has an abnormal bedside Doppler exam, at least 20 percent of patients may need revascularization and in the Stage III group, 50 percent required revascularization.

In Conclusion

With the well-known risk of PVD in patients with diabetes, one must perform routine vascular exams during normal evaluation. This study has shown a large percentage of patients with Charcot neuropathy and abnormal bedside Doppler have clinically significant vascular disease. Despite the common belief that patients with Charcot do not have blood flow problems, we believe that all patients with diabetes need thorough vascular evaluation, including those with Charcot neuropathy. In addition, revascularization may be necessary prior to any surgical intervention as others have previously advocated.¹¹

We recommend conducting further studies to determine the true rate of PVD in patients with Charcot neuropathy. A nationwide Charcot database would be helpful in this regard.

Dr. Mancoll is in private practice at Mancoll Cosmetic and Plastic Surgery in Virginia Beach, Va.

Mr. Webb is a graduate of Norfolk State University and an incoming first-year student at the Barry University School of Podiatric Medicine.

Dr. Grant is a Fellow of the American College of Foot and Ankle Surgeons, and is board-certified by the American Board of Podiatric Surgery. He is an instructor in the Department of Surgery at Eastern Virginia Medical School and is in private practice in Virginia Beach, Va.

References
1.     Wheeless CR. Charcot changes in the diabetic foot and ankle. Wheeless Textbook of Orthopaedics. Available at www.Wheelessonline.com/ortho/charcot .
2.     Mills JL. Lower Limb ischemia in patients with diabetic foot ulcers and gangrene: recognition, anatomic patterns and revascularization strategies. Diabetes Metab Res Rev. 2016; 32(Suppl 1):239-45.
3.     Naka KK, Papathanassiou K, Bechlioulis A, et al. Determinants of vascular function in patient with type 2 diabetes. Cardiovasc Diabetol. 2012; 11:127.
4.     Palena LM, Brocco E, Ninkovic S, et al. Ischemic Charcot foot: different disease with different treatment? Cardiovasc Surg (Torino). 2013; 54(5):561-6.
5.     Wukich DK, Raspovic KM, Suder NC. Prevalence of peripheral arterial disease in patients with diabetic Charcot neuroarthropathy. J Foot Ankle Surg. 2016; 55(4):727-31.
6.     Huysman E, Mathieu C. Diabetes and peripheral vascular disease. Acta Chir Belg. 2009; 109(5):587-94.
7.     Bruno RM, Penno G, Daniele G, et al. Type 2 diabetes mellitus worsens arterial stiffness in hypertensive patients through endothelial dysfunction. Diabetologia. 2012; 55(6):1847-55.
8.     Clayton W, Elasy T. A review of the pathophysiology, classification, and treatment of foot ulcers in diabetic patients. Clin Diabetes. 2009; 27(2):52-58.
9.     Tuttolomondo A, La Placa S, Di Raimondo D, et al. Adiponection, resistin and il-6 plasma levels in subjects with diabetic foot and possible correlations with clinical variables and cardiovascular co-morbidity. Cardiovasc Diabetol. 2010; 9:50.
10.     Hafner J, Schaad I, Schneider E, Seifert B, Burg G, Cassina PC. Leg ulcers in peripheral arterial disease (arterial leg ulcers): impaired wound healing above the threshold of chronic critical limb ischemia. J Am Acard Dermatol. 2000; 43(6):1001-8.
11.     Aust MC, Spies M, Guggenhein M, et al. Lower limb revascularization preceding surgical wound coverage-an interdisciplinary algorithm for chronic wound closure. J Plast Resconstr Aesthet Surg. 2008; 61(8):925–33.
12.     Castronuovo JJ, Adera HM, Smiell JM, Price RM. Skin perfusion pressure measurement is valuable in the diagnosis of critical limb ischemia. J Vasc Surg. 1997; 26(4):629-37.
13.     Jansen RB, Christensen TM, Bulow J, et al. Bone mineral density and markers of bone turnover and inflammation in diabetes patients with or without a Charcot foot: an 8.5-year prospective case-control study. J Diabetes Complications. 2018; 32(2):164–70.