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A Closer Look At Preoperative Imaging Options To Differentiate Acute Charcot Neuroarthropathy From Acute Osteomyelitis
Charcot neuroarthropathy (CN) of the lower extremity is a devastating and debilitating pathology, posing several challenges for the foot and ankle surgeon. First described in the literature more than 150 years ago, W.R. Jordan became the first, in 1936, to describe its association with diabetes and peripheral neuropathy.1 Charcot neuroarthropathy is a progressive condition characterized by joint destruction, pathological fractures, and severe deformity.2 Management of this disease process includes early detection, stabilization/offloading of the affected extremity, and prevention of the destruction of the pedal architecture. If allowed to continue through its natural clinical course, progressive destruction of normal joint alignment, coupled with peripheral neuropathy, produces osseous prominences complicated by plantar ulcerations, leading to chronic or recurrent soft tissue infection osteomyelitis, and potential need for amputation.2,3 In addition, the presentation of the affected extremity with increased warmth, edema, and erythema contributes to its difficulty in distinguishing from infection, gout, deep vein thrombosis, and trauma leading to misdiagnosis and delay in early treatment.4 The goals in treating CN are to create a stable plantigrade foot, free of ulceration, and amenable to shoe gear or a brace. However, these goals are not always achievable with conservative treatment of immobilization/offloading in the presence of significant deformity, leading to a high propensity of infection due to ulceration and difficulty in finding accommodative footwear. In these cases, surgical reconstruction of the foot is often required to restore function and decrease the risk of amputation secondary to ulceration and infection.5-7 When a Charcot foot presents with a current or history of ulceration, osteomyelitis must be considered in the case workup. Traditional imaging of plain radiographs, magnetic resonance imaging (MRI), computed tomography (CT) imaging, and routine bone scans can be quite challenging to differentiate between CN with and without osteomyelitis.
Although studies show MRI is a gold standard imaging modality in diagnosing osteomyelitis in the diabetic foot, limitations occur in the setting of evolving neuropathic osteoarthropathy, which may cause false-positive results.8 However, there are studies available describing a bone scan combining a traditional indium-111 bone scan with a technetium-99 sulfur colloid scan. Studies have shown an improved diagnostic accuracy with this combined study with high sensitivity (92 percent) and specificity (100 percent) in distinguishing Charcot neuroarthropathy alone from Charcot with osteomyelitis.9 This article provides an overview of combined In-111/sulfur colloid bone scintigraphy as an alternative tool in the surgical workup of Charcot reconstruction when underlying superimposed osteomyelitis is suspected.
Overview And Mechanism Of White Blood Cell-Labeled/Bone Marrow Scintigram
When preoperatively planning for surgical intervention in Charcot reconstruction, differentiating between CN with or without bone infection is paramount in helping to dictate treatment. The basis for combined studies propagates from a synergistic effect Tc-99m has on In-111. Indium-111 WBC is a radiotracer used to delineate white blood cell (WBC) accumulation but lacks structural detail to the images,10 Technetium-99 sulfur colloid is a gamma-emitting colloid, which is phagocytized by the reticuloendothelial system and concentrated in the liver, spleen, and bone marrow, allowing structural location.11 Thus, the combined imaging technique utilizes the structural information provided by Tc-99m for plotting out locations of WBC accumulation as identified by the In-111.
The concept of combined studies dates to investigators studying WBC imaging and bone marrow scintigraphy in non-infectious conditions. These studies resulted in nearly identical patterns of distributions of the two radiotracers regardless of alterations in the marrow, but in the setting of infection, the distributions were different.12,13 Thus, the basis for this combined study is determined on the fact that WBCs and sulfur colloid accumulates in bone marrow regardless of their location, but in the setting of acute infection, only WBCs will be present as sulfur colloid is inhibited by the infectious process.
A positive study for acute osteomyelitis occurs when there is an increased uptake in the area of concern for the WBC image without corresponding activity at the same site on the sulfur colloid image, known as discordance as the two images are spatially incongruent.14 This result occurs as the infectious process develops in the bone with bacteria and inflammatory cell proliferation, predominantly neutrophils, accounting for increased uptake on the WBC images. As the acutely infected bone begins to undergo necrosis and abscess formation, subsequent marrow edema and vascular congestion ensue, leading to increased intraosseous pressure, small vessel thrombosis, decreased oxygen tension, and low pH evolving to suppression/destruction of bone marrow phagocytes, subsequently progressing to sulfur colloid uptake to not occur.15,16 Whereas when any other pattern is present, the study is negative for acute osteomyelitis, known as concordance, as the images are spatially congruent.
Combined WBC-marrow scintigraphy can be performed in various ways, which can vary from one institution to another. In general, the In-111/sulfur colloid exam consists of a two-day process. The cells are labeled and reinjected on the first day, with imaging performed on the second day approximately twenty-four hours post-injection. The sulfur colloid imaging is typically performed simultaneously with WBC imaging.17
Discussion
Charcot neuropathy is a devastating and intricate pathology to treat. When Charcot ensues concomitantly with possible acute osteomyelitis, proper peri-operative workup must be performed consisting of advanced imaging to appropriately modify and tailor the treatment protocol to address the presence of infection.
Although useful for musculoskeletal infection in general, the value of MRI for Charcot superimposed with osteomyelitis is suboptimal due to its high sensitivity and low specificity. Other imaging modalities have been suggested, such as using three-phase bone scintigraphy. However, it has been found to not reliably distinguish between osteomyelitis and the neuropathic joint because extensive bony remodeling is present in both conditions.10,18-21
WBC labeled bone scans have historically been shown to be problematic in the diagnosis of osteomyelitis in the neuropathic foot and ankle. Although reported in the past to help discriminate between neuropathic joint and osteomyelitis, uptake of labeled leukocytes in the uninfected Charcot joint has been reported as well.10,18,22
After the first decade of life, and by young adulthood, hematopoietically active marrow is confined to the medullae of centrally located bone.23-25 Palestro and colleagues report that uptake of labeled leukocytes in the neuropathic foot in the absence of infection reflects, at least in part, hematopoietically active marrow. Having hematopoietically active marrow in the distal lower extremity is unusual but may be a sequela of the arthropathy itself. Conversion of fatty marrow into hematopoietically active marrow in induced arthritis of the distal extremities has been observed in rats, and it is speculated that this enhanced myelopoiesis may be due to increased cytokine activity.18,26-27
Generalized and localized expansion of hematopoietically active marrow may produce unusual activity patterns, in terms of both intensity and distribution, on WBC images. Because labeled WBCs usually accumulate in the bone marrow and the distribution of marrow can vary dramatically from one individual to another, a logical method for distinguishing infection from marrow is to combine WBC imaging with bone marrow scintigraphy. This technique is reliable, assuming that both radiotracers accumulate in the marrow, whereas only WBCs accumulate in infection.15,23
There are limitations and pitfalls associated with combining indium-111 leukocyte labeled and Tc99 sulfur colloid bone scans. One way this combined study could be limited is with a lack of WBC migration to the site of infection. In this situation, marrow imaging will not contribute additional information.23,28 Also, animal study data have suggested that marrow imaging becomes photopenic within about one week after the onset of osteomyelitis. Although this has not been proven, further studies with human data are needed to indicate how soon after the onset of osteomyelitis, photopenia occurs on marrow imaging. Thus, caution of this combination study should be considered in the acute setting of infection.23,29 Lymph node activity can additionally confound image interpretation by producing incongruent WBC/marrow images. Finally, Tc99 sulfur colloid that is improperly prepared or is more than about two hours old degrades image quality, potentially causing erroneous conclusions.23
In Conclusion
Based on the literature, foot and ankle surgeons should consider combined WBC/sulfur colloid bone scintigraphy as an alternative tool in the surgical workup of Charcot reconstruction when underlying superimposed osteomyelitis is suspected. However, it is advisable that one also perform the gold standard bone biopsy and culture, as the combined imaging modality studies have their limitations. More literature is necessary to diagnose Charcot neuropathy when there is an underlying concern for osteomyelitis.
Dr. Bergen is a third-year resident at St. Mary’s General Hospital in Passaic, NJ.
Dr. Saleh is an Associate of the American College of Foot and Ankle Surgeons and is in practice in Lyndhurst, NJ.
Dr. Malik is a second-year resident at St. Mary’s General Hospital in Passaic, NJ
Dr. Subik is a Fellow of the American College of Foot and Ankle Surgeons, Director of the North Jersey Reconstructive Foot and Ankle Fellowship in Lyndhurst, NJ and Director of the Podiatric Residency program at St. Mary’s General Hospital in Passaic, NJ.
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