Charcot Patients Research Articles

The Footprint of Mortality: Outcome Analysis in Charcot Neuroarthropathy Patients Who Underwent Multiple Surgical Procedures

Category: Midfoot/Forefoot; Diabetes Introduction/Purpose: Charcot neuroarthropathy (CN) is a progressive degenerative disease that most commonly manifests in the foot and ankle as a result of peripheral neuroarthropathy. Primary treatment is typically management of disease progression, however, surgical procedures including arthrodesis, exostectomy, and amputation may be indicated for more refractory cases. Our prior research analyzed a subset of the current sample to evaluate patients who underwent multiple surgical procedures to manage their CN, identifying amputation to be associated with the highest all-cause mortality rate. The purpose of this study is to analyze demographic data and mortality rates from a larger sample of patients with an emphasis on the mortality associated with procedure order and type in patients who underwent multiple procedures in the management of their CN. Methods: Following IRB approval, a database of all patients at a single institution from 1/1/2000 to 1/31/2022 with CPT and ICD codes indicating a diagnosis of Charcot foot of the lower extremity who underwent amputation, exostectomy, and/or arthrodesis was created from the electronic health record. Only patients who underwent multiple procedures in the treatment of their CN were included in the study. Amputation was further classified as major (transmetatarsal amputation or above) or minor (below the metatarsal level or a single toe at the metatarsal level). Demographics including age, sex, race, and insurance status were recorded in addition to all-cause mortality rates for each procedure type and all-cause mortality rates relative to procedure order. Descriptive statistics and chi-square tests for homogeneity were conducted for analysis. One patient, identified as an outlier, had 13 procedures, and was excluded so as to not distort the statistical analysis. Results: A total of 700 individual patients who underwent at least 2 procedures were included in this study, with a total of 1902 procedures performed of which 363, 651, 459, and 429 were completed for major amputation, minor amputation, exostectomy, and arthrodesis respectively. Figure 1A describes the baseline characteristics of patients who underwent each procedure. The all- cause mortality rate remained the lowest in arthrodesis patients, regardless of the order in which it was performed. Furthermore, patients who underwent either arthrodesis or exostectomy at any point in their procedure sequence had an absolute risk reduction in all-cause mortality of 42.5% and 21.1% respectively, while both amputation groups had an absolute risk increase in all- cause mortality of 46.0% (minor) and 48.3% (major). Conclusion: For patients who underwent multiple procedures to manage their CN, those who underwent arthrodesis at any point during their procedure sequence showed the trend of having the lowest all-cause mortality rates (Figure 1D). This may indicate that early anatomic correction through arthrodesis could lead to improved mortality in Charcot patients. Figure 1E describes the significantly increased (p < 0.001) mortality rates associated with both amputation groups, which further highlights the importance of early intervention and management of disease progression. Future research should aim to develop surgical treatment guidelines based on disease progression to continue to minimize mortality rates.

Charcot neuroarthropathy in a non-diabetic patient with renal failure: A case study

Charcot Neuroarthropathy (CN), a limb threatening disease, has previously been documented and studied extensively in the diabetic population. Within this population most individuals who suffer from CN also have documented peripheral neuropathy secondary to their diabetes. While many patients with CN are diabetic, there remains a small population of non-diabetic patients. Etiology in these non-diabetic cases has been attributed to other causes of neuroarthropathy such as leprosy, spina bifida, rheumatoid arthritis, glucocorticoid use, and simultaneous pancreas-kidney transplantation. Non-diabetic individuals are reported mainly in case studies and remain an enigma in the Charcot population. The purpose of this case study is to document a non-diabetic patient with end stage renal disease suffering from CN. In an extensive literature review no such case study has been documented in recent history. Although kidney failure has been noted in many Charcot patients, the correlation remains understudied. The Charcot event in this case was monitored through serial radiographs and treated conservatively. Corresponding bloodwork from periods of prolonged hospitalization due to unrelated coinciding events confirm normal serum glucose measurements and monitor the status of renal failure. Although this patient does not represent the majority of patients who suffer from CN, much remains to be learned from the study of outlying cases like this one.

Can Sociodemographic Factors be Used to Help Predict Outcomes in Charcot Neuroarthropathy?

Category: Diabetes; Other Introduction/Purpose: The diabetic Charcot foot, or Charcot neuroarthropathy, is a devastating condition that arises secondary to longstanding diabetes, peripheral neuropathy, and trauma. One of the many challenges associated with the Charcot patient is the lack of data exploring factors that may predict long-term outcomes. Therefore, the purpose of this study was to evaluate how certain sociodemographic factors may influence mortality and the need to undergo lower extremity amputation in patients with Charcot. Methods: Following institutional board approval, all patients from 2015-2021 with a diagnosis of Charcot Foot were queried using hospital electronic medical records. Demographics collected included sex, age, race, and insurance coverage. Outcomes recorded were the need to undergo major amputation and mortality rate. Statistical analysis was then run to determine if sex, age, race, and insurance coverage was associated with increased risk of needing a major amputation or death. Results: From 2015-2021, 80 Charcot patients with a mean age of 60 (Range, 84-32) were identified. Of these patients, 58 were male, 26 were female, 71 were white, 3 were African American, and 6 were identified as other. In our cohort, 47 patients had government funded insurance and 33 had private insurance. Amputation occurred in 22 patients and death in 15. Government funded insurance (RR: 9.8, 95% CI:1.4-71.1, P = 0.0236) and age over 65 was associated with an increased risk of death (RR: 2.5, 95% CI: 1.02 to 6.17; P = 0.044). No statistically significant increased risk of death or amputation was found in white, African American, male, or female patients. Government insurance was also not associated with an increased risk for amputation (Table 1). Conclusion: Charcot Neuroarthropathy is associated with high rates of morbidity and mortality. In our cohort, there was an increased risk of mortality in patients with government funded insurance and patients over the age of 65. Further investigation exploring the role of sociodemographic factors is warranted.

Charcot Neuroarthropathy is Associated with Higher Rates of Phantom Limb after Major Amputation

Category: Diabetes; Trauma Introduction/Purpose: Phantom limb is a complication associated with lower extremity amputation. However, its rate in patients with Charcot Neuroarthropathy that undergo major amputation is not well-described. Moreover, there is limited research exploring outcomes of patients with Charcot Neuroarthropathy that require amputation. Therefore, the purpose of this cohort study was to determine if patients with Charcot Neuroarthropathy that undergo major amputation had an increased rate of phantom limb compared to patients that underwent amputation without a coexisting diagnosis of Charcot. Methods: Using ICD and CPT codes, an online research database was used to identify patients that underwent a major lower extremity amputation. For the purposes of our study, we defined a major amputation as a below-knee amputation (BKA). Patients were then separated into two groups. Group A consisted of patients that underwent BKA and also had a coded diagnosis of Charcot Neuroarthropathy. Group B consisted of patients that underwent BKA and lacked a diagnosis of Charcot. Statistical analysis was then run to determine the relative risk of developing phantom limb in patients that underwent BKA with a diagnosis of Charcot Neuroarthropathy compared to those without the diagnosis. Demographic data of the cohort was also collected. Results: From 2012-2022, a total of 11,374 patients underwent a BKA. Of these patients, 804 also had a diagnosis of Charcot Neuroarthropathy (Group A) and 10,570 did not (Group B). The rate of phantom limb in Charcot patients was 23.1% (186/804). The rate of phantom limb in patients without Charcot Foot was 19.5% (2063/10570). Patients with Charcot Neuroarthropathy that underwent a BKA had an increased risk of developing phantom limb compared to patients that underwent a BKA without Charcot (RR: 1.2, 95% CI: 1.039-1.352). Conclusion: Phantom limb is a serious complication following major amputation. Our results indicate that patients with a coexisting diagnosis of Charcot Neuroarthropathy that go on to require BKA may have an increased risk of developing phantom limb. Furthermore, our study adds to the limited research on outcomes of patients with Charcot Neuroarthropathy.

Combined Internal and External Fixation for Charcot Neuro Arthropathy: 1 Year Results

Category: Diabetes Introduction/Purpose: Complex foot and ankle deformities secondary to charcot neuroarthropathy continue to represent a significant challenge and management quandary. This is due to the combination of medical co-morbidities, peripheral neuropathy, immune compromise, and micro/macro vascular issues in addition to the surgical challenge of wide area of injury, progressive deformity and bone resorption. The technique of 'superconstructs' have been proposed as a method of combating these challenges with deformity correction achieved through fusion out with the zone of injury and fixation in unaffected 'normal' bone. We present here the outcomes of this technique at one year using internal fixation alone, external fixation alone and the novel technique of combined internal and external fixation using combined internal and external fixation internal/ external fixation only at one year. Methods: Retrospective two-surgeon case series with all cases jointly operated upon. Cases identified from a locally held charcot patient registry. Patients undergoing charcot foot and ankle reconstruction from 2017 to 2020 included. No exclusion criteria outlined. Patient demographics and comorbidities were collected, pre-op radiological markers (meary's angle) measured and repeated at 6-12 /52 and 1 year. Patient outcomes were recorded of ulcer recurrence, limb salvage, pain score, stable heel, able to ambulate, need for revision surgery, fusion and surgical complications. Proms are awaited for all patients. Results: 19 cases from 18 patients undergoing reconstruction identified. 18 cases were included for analysis. Fourteen patients were broadsky 1, one broadsky 2, one broadsky 3 and two broadsky 4. 3 patients had internal fixation, 5 external fixation and 10 combined internal and external fixation. Limb salvage was 94% with one amputation. Mortality rate was nil. All patients reported improved pain scores, a stable heel and were ambulating. No recurrence of ulceration reported and no prolonged antibiotic use. Mearys angle improved in all groups: Internal fixation pre-op -9.6o, post op 2.6o and 1 year -1o, external fixation pre-op -20o, post op -6o and 1 year -12o, IF + EF pre-op -24.6o, post op 1.2o and 1 year -2.3o. Fusion rate was 100% with average time to fusion 154 days and a range of 360 - 52. Complications of 2 tibial fractures and metalwork removal with delayed wound healing were noted. Conclusion: The outcome of all three methods is positive with 94% limb salvage, 100% fusion / ambulation/ improved pain and ulcer free at 1 year. Mearys angle is improved at one year however there is a loss of correction noted with external fixation alone. These results are encouraging and support the use of combined internal and external fixation in these complex cases. The added benefit of this technique of maintaining ambulation, avoiding the complications of nonweightbearing all whilst maintaining the structure of the reconstructed foot are promising. The complications reported were in the first 3 patient and represent a learning curve.

Preliminary Results of an Institutional Charcot Database: Risk Factors of Conversion to Operative Treatment in Charcot Arthropathy Patients

Category:Diabetes; Midfoot/Forefoot; OtherIntroduction/Purpose:Operative correction of Charcot is generally accepted for nonplantigrade deformity that cannot be accommodated with commercially available therapeutic footwear, painful 'nonunion' type pain, in addition to the accepted indications of osteomyelitis, persistent wounds, and non-braceability. Classification schemes associated with Charcot foot are primarily descriptive in nature. Scant literature has attempted to correlate characteristics of the deformity with a specific operative strategy to enable correction of the acquired deformity. Hence, the purpose of this study is to create a database that will shed light on much needed guidelines in the management of Charcot arthropathy. Among those guidelines, identifying risk factors for conversion to operative treatment of non-operative Charcot feet is essential.Methods:A query of our institution administrative database was performed based on the Charcot ICD-10 codes for reconstruction procedures between 2015 - 2018. Clinic and hospital medical records were reviewed to determine if Charcot neuropathy was diagnosed and identify treatment plan. Minimal follow up was established at 2 years. Patient must have completed all surveys in the outcomes portion during their follow up period. If bilateral patients are identified, all records will be retained, and patients will be addressed as separate sides. The primary outcome was conversion to surgery. Independent risk factors analyzed were demographics, history of diabetes, peripheral vascular disease, use of anticoagulants, tobacco use, shoe wear, bracing, plantigrade foot, neuropathy, presence of ulcer, infection, and Brodsky classification. The data was both stored and analyzed in the REDCap electronic data capture tools hosted at our institution.Results:A total of one hundred and eighty (180) records were initially queried for. Thirty-four (34) patients met the inclusion criteria. Of the 34 patients, fourteen (41%) patients had conversion to surgery. Average age of patients who converted to surgery was 53.1 compared to patients who remained in the non-operative treatment arm (age = 66.1) (p=0.05) (Table 1). Diabetes, peripheral vascular disease, anticoagulant, and tobacco use were not found to be significant risk factors. 11 (78.6%) patients who underwent surgery had diabetes compared to 8 (40%) patients in the nonoperative arm (p=0.160). 12 (85.7%) patients in the conversion arm were diagnosed with peripheral vascular disease (p=0.184). Type of shoe wear, bracing, plantigrade foot, neuropathy, presence of ulcer, and Brodsky classification were not found to be significant risk factor.Conclusion:Identification of risk factors that lead to conversion to surgical treatment of Charcot is important. There are no well-established guidelines with regards to management or indications for surgery. This database aims to provide valuable insight into guidelines and recommendations for Charcot treatment. Preliminary results did not find independent risk factors for conversion to surgical treatment other than age. Presumably, younger patients with higher functional demands, or patients with high disease burden at younger ages are at higher risk of requiring surgical intervention. As our database expands, we will better identify risk factors and include treatment outcomes Charcot patients.

Complications from ankle arthrodesis in diabetes-related Charcot foot syndrome

IntroductionCharcot neuroarthropathy (CN) is an inflammatory arthropathy associated with bony destruction, dislocation, and deformity in patients with neuropathy. Surgical procedures involving foot and ankle in CN for deformity correction have been shown to result in high rate of complications. The purpose of this study was to compare post-operative outcomes and assess odds of complication after ankle arthrodesis among patients with diabetes-related Charcot neuroarthropathy, non-Charcot patients with diabetes, and non-Charcot patients without diabetes. MethodsThe PearlDiver Patient Records Database was queried for patients who underwent ankle fusion and maintained at least one year of post-operative follow-up. The following post-operative complications were assessed among groups: overall nonunion and amputation, one-year nonunion, amputation, and hardware removal, 90-day and 30-day surgical site infection, dehiscence, acute kidney injury, and pneumonia, and 90-day myocardial infarction and deep vein thrombosis. The odds and prevalence of each complication for each group were assessed and compared. ResultsHigher rates of amputation (OR 3.43, CI 2.89–4.06), hardware removal (OR 1.63, CI 1.45–1.83), wound dehiscence (OR 1.75, CI 1.44–2.13), acute kidney injury (OR 2.87, CI 2.32–3.54), pneumonia (OR 1.53, CI 1.13–2.07), and surgical site infection (OR 2.46, CI 2.12–2.85), were observed in patients with diabetes-related CN compared to non-Charcot patients with diabetes. In patients without CN, higher rates of nonunion (OR 1.38, CI 1.19–1.61), amputation (OR 2.26, CI 1.74–2.93), surgical site infection (OR 1.57, CI 1.30–1.90), and acute kidney injury (OR 1.57, CI 1.18–2.09) were observed in patients with diabetes compared to patients without diabetes. Time to hardware removal was significantly shorter in diabetes-related Charcot patients compared to non-Charcot patients without diabetes (368.0 ± 446.7 vs 438.5 ± 487.5 days, P < 0.001). ConclusionPatients with diabetes demonstrated increased odds of nonunion, amputation, surgical site infection, and acute kidney injury compared to patients without diabetes. In the population of patients with diabetes, odds of most of these complications were further increased with the addition of Charcot diagnosis compared to patients without diabetes. Other local and multisystemic medical conditions, including pneumonia and wound dehiscence, also demonstrated increased odds in patients of CN.Level of evidence: Cohort study; Level of evidence, 3.

Physical Activity Assessment in the Charcot Population

Charcot neuroarthropathy is a degenerative disorder that significantly impairs a patient's functional capacity. It has been reported that a Charcot patient's quality of life is significantly impacted by the disease state. The aim of this study is to compare measured energy expenditure to a patient's perceived quality of life and physical ability. The study enrolled 43 patients by set inclusion and exclusion criteria. Patients’ total energy expenditure was measured with doubly labeled water. The patients also completed 2 quality of life assessments: 36-Item Short Form Survey (SF-36) and International Physical Activity Questionnaire–Long Form (IPAQ-LF). The measured energy expenditure was then compared to the patient's perceived functional capacity. Scores reaching statistical significance included general health (60 ± 21; p = .011), pain (62 ± 27; p = .025), emotional (61 ± 40; p < .017), physical limitation (45 ± 39; p < .0001), and physical function (50 ± 29; p < .001). SF-36 survey variables that did not reach statistical significance included mental (73 ± 26; p = .690), energy (55 ± 21; p = .205), and social (74 ± 26; p = .105). The IPAQ-LF and physical activity level (PAL) were compared. No identified variation was noted between the 2 test methods (p = .57). The patients’ PAL was measured at 1.4 ± 0.42, which is comparable to the general population. Data from this study identify the Charcot population as comparable to the general population. The inferences taken from this study indicate that this population suffers from poor health outlooks compared with the general population but may be overestimating the level of perceived disability.

A Predictive Classification of Charcot Arthropathy of Foot and Ankle

Category:Diabetes; OtherIntroduction/Purpose:Charcot arthropathy of foot and ankle is a devastating, chronic and progressive destruction of bone and joint integrity affecting one or more joints. It is commonly associated with diabetes mellitus and is characterized by joint subluxations, dislocation, and pathological fractures in patients with peripheral neuropathy and results in a debilitating deformity, possibly leading to ulceration and amputation.Many classification systems exist for charcot arthopathy of foot and ankle. However, there is still lack of consensus regarding best classification. We are proposing a new classification for charcot arthropathy of foot and ankle based on our experience of large cohort of charcot patients. Our classification can guide treatment and prognosis of diabetic charcot arthropathy of foot and ankle, which we are following for the last decade.Methods:Patients with post-acute charcot who presented at our institution from January 2004 to October 2019 were reviewed and were further classified anatomically into Type I and Type II based on plain radiographs. Type I was characterized by charcot affection of one region. Regions were categorized anatomically as a modification of both Brodsky and Schon classifications into: ankle, Lisfranc (tarsometatarsal), naviculocuneiform, forefoot, and hindfoot which includes one of the following: talonavicular joint, calcaneocuboid joint or calcaneus. Type II was characterized by affection of more than one region like peritalar, perinavicular, transverse tarsal or any other combination. Peritalar complex involves at least two joints of the following: ankle, subtalar, and talonavicular. The perinavicular type includes talonavicular and naviculocuniform or tarsometatarsal and naviculocuniform, while the transverse tarsal involves the calcaneocuboid and talonavicu-lar. Both types were further classified into four stages according to the stability, deformity and associated mechanical ulcers. (Table 1)Results:235 patients (242 feet) were presented with diabetic charcot arthropathy. Mean age was 56 years (range 22-84). Follow- up ranged from 6 months to 10 years, with a mean of 3.3 years.Types IA and IIA were managed conservatively. All patients in Type IIB, IC, IIC, ID, IID and the majority of type IB received fusion surgery to achieve stability and correction of deformity. Stage IB ankle were fixed, while IB lisfranc were observed, and fixed if transformed to IC.Type II D had the highest complication rate in the form of: infection, nonunion, nail protrusion, implant failure, revision including exostectomy after full union and recurrence of ulcer in midfoot 3-4 years after surgery. Five patients ended up with amputation, and all were stage IID.Conclusion:For post-acute charcot, stage A have the best prognosis and can be managed conservatively provided good diabetes control.Type IB can be managed conservatively but when the ankle is affected in type IB, it is better to be elected for surgery.When charcot affects the Lisfranc joints, it is usually stable unless the lateral column is affected.All cases of type IIB, IC and IIC, ID, IID should receive surgery to achieve stability, correction of deformity and prevent complications.Mechanical ulcer (stage D) carries the worst prognosis and highest complication rate. Type IID might predict the risk of amputation

Complication Rates in Ankle and Hindfoot Charcot Arthropathy Treated with Arthrodesis

Category:Diabetes; Ankle; Hindfoot; OtherIntroduction/Purpose:Charcot arthropathy of the ankle and hindfoot is a progressive and destructive process that can lead to instability and ulceration resulting in significant morbidity. When indicated, the surgical goals are to restore a stable plantigrade foot, reduce the risk of ulceration, and improve function to independent ambulation. Techniques for reconstruction of the neuropathic ankle/hindfoot include external and/or internal fixation. Current literature involving small series of surgical patients has shown a high rate of limb salvage and low complication rate. Our experience has been less promising, although we believe it remains a viable option. It is our goal to report the outcomes of Charcot patients undergoing corrective ankle and hindfoot reconstruction.Methods:We retrospectively reviewed 377 patients undergoing hindfoot and ankle arthrodesis at our institution from 2006- 2017. 77 patients were identified that underwent arthrodesis for Charcot arthropathy, 51 of which met inclusion and exclusion criteria with a minimum one year follow up. 42 had internal fixation as their primary procedure (plate or nail) and 9 patients underwent external fixation with a multi-planar external fixator. Median follow up time was 4 years (IQR 2.97 years).Preoperatively, basic demographic variables, etiology of neuropathy, ulcer status, radiographic measurements, Brodsky classification, and presence of a viable talus were collected and analyzed. Postoperatively, we collected complications including infection, hardware failure, ulceration, recurrent deformity, and nonunion. Reoperation numbers and indications for reoperation were also collected. The primary outcome measure was limb salvage at final follow up. Secondary outcome measures were ambulatory and footwear/bracing status.Results:11 patients (20%) underwent amputation at final follow up and 26 (47.3%) achieved radiographic union, both of which did not vary by fixation type (p=0.67 and p=0.88). The primary reasons for amputation were persistent infection and non-union. 74.5% of patients developed a post-operative complication and 58.2% had at least one reoperation. 25.5% of patients developed a post- operative infection. Patients with a pre-operative ulceration were more likely to undergo external fixation (p=0.02), but amputation rates did not differ between groups (p>0.99). There was a trend toward increased risk of post-operative infection in the ulceration group (p=0.07). A pre-operative Meary’s angle >25° was more likely to undergo amputation (p=0.04) and less likely to achieve radiographic union (p=0.05). 75.9% of patients were ambulatory at final follow up.Conclusion:Our rates of amputation (20%), post-operative infection (25%), complications (74.5%) and non-union (52%) are higher than previously described. Previous literature has described a near 100% limb salvage rate, but in our report on a large series of Charcot patients undergoing hindfoot/ankle arthrodesis we describe an 80% limb salvage rate. Pre-operative Meary’s angle >25° was predictive of treatment failure.

İleri evre Charcot artropatisinin tedavisi için tibiokalkaneal artrodez: Diyabetes mellituslu hastaların en az 2 yıllık takibi ile klinik ve radyolojik sonuç analizi

Aim: Charcot arthropathy (CA) described by Jean-Martin Charcot is a noninfectious degenerative and destructive process of the bones, joints and soft tissues in the area of the foot and ankle which associated with peripheral neuropathy. The purpose of this study was to evaluate the outcomes of tibiocalcaneal fusion using a retrograde hind foot ankle nail fixation system in 5 Charcot patients. Material and Methods: Between 2014 and 2016, a total of 5 patients (4 women and 1 man) who underwent tibiocalcaneal arthrodesis for the treatment of advanced CA (Brodsky type 4) were evaluated. The demographic characteristics, clinical (AOFAS scores, early and late complications) and radiological (time for a union) evaluation parameters and patient satisfaction were analyzed before and after surgery. Results: The mean preoperative AOFAS score was 64.8 ± 8.55 and mean postoperative score was 82.6 ± 12.99. The difference between preoperative AOFAS and postoperative AOFAS scores were statistically significant. During the clinical and radiological follow-up; infection, implant failure, and peri-implant fractures were checked and complications were recorded. Conclusion: AOFAS scores were recorded before surgery after full weight bearing and it was found that talocalcaneal arthrodesis which was achieved with intramedullary nailing significantly increased AOFAS score compared to the preoperative AOFAS score.

Charcot Reconstruction: Outcomes in Patients With and Without Diabetes

The objective of this study is to compare risk adjusted matched cohorts of Charcot neuroarthropathy patients who underwent osseous reconstruction with and without diabetes. The 2 groups were matched based on age, body mass index, hypertension, history of end-stage renal disease, and peripheral arterial disease. Bivariate analysis was performed for preoperative infection, location of Charcot breakdown, and post reconstruction outcomes, in patients with a minimum of 1 year follow-up period. Through bivariate analysis, presence of preoperative ulceration (p = .0499) was found to be statistically more likely in the patients with diabetes; whereas, delayed osseous union (p = .0050) and return to ambulation (p ≤ .0001) was statistically more likely in patients without diabetes. The nondiabetic Charcot patients were 17.6 folds more likely to return to ambulation (odds ratio [OR] 17.6 [95% confidence interval {CI} {3.5-87.6}]), and 16.4 folds more likely to have delayed union (OR 16.4 [95% CI {1.9-139.6)]). Subanalysis compared well-controlled diabetic and nondiabetic Charcot neuroarthropathy patients for same factors. Multivariate analysis, in the subanalysis, found return to ambulation was 15.1 times likely to occur in the nondiabetic CN cohort (OR 15.1 [95% CI 1.3-175.8]) compared to the well-controlled diabetic CN cohort.

Novel FEMASK-score, a histopathologic assessment for destructive Charcot neuropathic arthropathy, reveals intraneural vasculopathy and correlates with progression and best treatment

BackgroundCharcot neuropathic arthropathy is a debilitating, rapidly destructive degenerative joint disease that occurs in diabetic, neuropathic midfoot. Clinicoradiologic assessment for Charcot neuropathic arthropathy previously relied on Eichenholtz stage. There is limited histopathologic data on this entity. We wanted to independently develop a histopathologic scoring system for Charcot neuropathic arthropathy. DesignRetrieval of surgical pathology midfoot specimens from Charcot patients (2012–2019) were analyzed to evaluate joint soft tissue and bone. Considering progression from large (≥half 40× hpf) to small (<half 40× hpf) periarticular bone fragments to resolution, we devised and applied a Charcot neuropathic arthropathy novel FEMASK-score (named after coauthors: Fanburg-Smith, Frauenhoffer, Flemming, Fritsche, Elfar, Murie, Aynardi, Stauch, Smith, King, and Klein): 0 (initial) = the observed intraneural arteriolosclerosis in all diabetic neuropathic patient specimens (not observed in other diabetic nerves); and finally scored with the most destruction observed: 1 = large bone fragments without host histiocytic response; 2 = mixed bone fragments with host histiocytic response; 3 = small minute bone spicules resorption to fibrosis. Eichenholtz stage and outcome were then compared. ResultsForty-eight cases of Charcot neuropathic arthropathy included 34 males and 14 females, mean age 60.3 and age range 28–83 years, with clinical diabetes mellitus (predominantly Type II) and longstanding neuropathy. Elevated HbA1C, Eichenholtz stage, American Society of Anesthesia score, and Charlson comorbidity index indicated initial clinical amputation. Pathologic specimens varied from fixation tissue to amputation. In addition to neurotraumatic, neurovascular and inflammatory findings, a distinctive intraneural hyalinized arteriolosclerosis was observed. FEMASK-scores: 1 = 10%, 2 = 58%, and 3 = 32%. Score comparisons were 98% accurate compared with Eichenholtz and 98% reproducible among pathologists. FEMASK 2 and 3 correlate with clinical need for amputation. ConclusionsOur novel Charcot neuropathic arthropathy FEMASK-score classification, derived from the largest cohort of diabetic neuropathic specimens, is reproducible, explains pathophysiologic progression of destructive phase of Charcot, correlates with Eichenholtz, and predicts progression to or clinical need for amputation. The unique intraneural vasculopathy observed contributes to Charcot neuropathic arthropathy etiology.

Charcot Foot and the Osteoclast: More Than Just Cytokines

Category:Basic Sciences/BiologicsIntroduction/Purpose:Charcot foot is a serious complication of diabetes present in up to 13% carrying with high morbidity (dislocations, fractures, deformities) and up to 14% mortality. In Charcot, osteoclasts are found in increased numbers and with increased activity3,4 while C-telopeptide of type I collagen (CTX) is upregulated as opposed to ALP suggesting this is indeed an osteoclast and not an osteoblast disease.Methods:The scientific literature was reviewed to identify relevant osteoclastic activators and their role in the hyper activated state. We will also show videos of our current micromanipulation research techniques used to study osteoclast inhibitors in the lab.Results:The blood of Charcot patients is different at the nano level. Micro-nano-particles are extracellular vesicles derived from cells into plasma. Microparticles are found in increased quantity in Charcot;which contain more cytokines; known osteoclast activators. MicroRNAs – Epigenetic changes also are in Charcot; 16 different circulating microRNA known osteoclast activators are associated with Charcot. Advanced glycation end products (AGE). The hyperglycemic state in Charcot is a driving force in pathogenesis. AGEs are normal proteins turned dud after hyperglycemic induced glycation, a post translational modification which is irreversible affects both intracellular and extracellular proteins. AGEs may bind receptor RAGE, increasing osteoclast activity . RANKL is the main osteoclast differentiator and activator. RANKL has been the target of osteoclast control almost since it was found in 1998 .Conclusion:Charcot mediated bony destruction and remodeling; both of which are mediated by the osteoclast has traditionally had a tremendous cytokine focus. Our review suggests the mechanism for modifying a Charcot response on a local and systemic level. It is interesting to note that osteoclast inhibitors Denosumab, Bisphosphonates, Calcitonin and osteoblcast activators rPTH are not completely effective in switching off the Charcot response, implying there is a far more complex interaction between the inflammatory response, osteoclastic stimulators and osteoblastic inhibitors.

Outcomes of Hindfoot and Ankle Arthrodesis in Neuropathic Patients

Category:Ankle Arthritis, Diabetes, HindfootIntroduction/Purpose:Charcot neuropathy of the ankle and hindfoot is a progressive and destructive process that can lead to instability and ulceration resulting in significant morbidity which can end with amputation. The foot and ankle surgeon’s aim is to reconstruct the high risk foot with the creation of a stable plantigrade foot, while reducing the risk of ulceration and allowing the patient to mobilize in commercially available footwear. There are numerous techniques for the reconstruction of the neuropathic hindfoot, but the most utilized of these include multiplanar external fixation or internal fixation with a plate or intramedullary nail. It is our goal to further elucidate outcomes of Charcot patients undergoing corrective ankle and hindfoot fusion comparing internal versus external fixation.Methods:We retrospectively collected 377 patients undergoing hindfoot and ankle arthrodesis at our institution from 2006- 2017. 77 patients were identified that underwent arthrodesis for Charcot arthropathy, 56 of which met our inclusion and exclusion criteria. This included 47 who had internal fixation as their primary procedure and 9 patients who underwent external fixation with a multi-planar external fixator. Our median follow up time was 3.4 years (IQR .5 to 12.9). Preoperatively we collected basic demographic variables, reasons for neuropathy, and ulcer status. Postoperatively we collected complications including infection, hardware failure, ulceration, recurrent deformity, and radiographic outcomes including union and hardware backout. Reoperation numbers and indications were also collected. Our primary outcome was limb salvage at final follow up.Secondarily, we collected final ambulatory and footwear status.Results:The limb salvage rate was 82% with 10 patients undergoing amputation, which did not vary between groups (p=.99). The primary reasons for amputation were persistent infection (4 of 10) and nonunion (4 of 10). Thirteen (24%) patients developed an infection. The median number of reoperations per patient was 1 (IQR 0-2) with the patients who underwent amputation undergoing a median of 2 (IQR 2-4) reoperations. The rate of union was 54%, occurring at a median of 26.5 (IQR 12-47) months. 44% (4/9) of patients in the external fixation group had a preoperative ulceration versus 19% (9/47) of the patients in the internal fixation group (p=.19). Preoperative ulceration was not a risk factor for amputation. Forty-two (75%) patients were ambulatory at final follow up.Conclusion:We report on the single largest series of Charcot patients undergoing hindfoot and ankle arthrodesis. The surgical management of this population has a high rate of complications with infection and reoperation being common. Despite a high nonunion rate most patients are able to ambulate in a brace or orthotic. Limb salvage can be expected with either internal or external fixation techniques.

Bone Mineral Density in Type 2 Diabetes Patients with Charcot Arthropathy

Charcot arthropathy is one of the disabling diabetes complications. There are enigmatic areas concerning its underlying pathophysiology and risk predictors. Osteoporosis and local osteopenia have been postulated to have a role in Charcot arthropathy development, but it is still controversial. The study aims to compare bone mineral density among type 2 diabetics with and without Charcot arthropathy. Two groups with type 2 diabetes participated in this study; Group I [30] patients with Charcot arthropathy while Group II [30] patients without charcot arthropathy. All patients underwent full clinical examination and complete history taking with special emphasis on foot problems. Laboratory investigations were done that included fasting blood sugar, postprandial blood sugar, glycosylated hemoglobin, serum calcium, serum phosphorus, and alkaline phosphatase. All patients underwent MRI for both feet and dual energy X-ray absorptiometry scan of the lumbar spine and femur. The demographic data, clinical data, the presence or absence of comorbidities and bone mineral density were compared for both groups. Bone mineral density was significantly lower in Group I than Group II with median lumber T score (-0.15, 1.99 p <0.001), median Femur T score (0.050, 2.400, p <0.001). Group I showed higher propensity for hypertension, neuropathy, micro-albuminuria with peripheral arterial disease (23.33 %) compared to Group II (p <0.001). Multiple logistic regression analysis revealed that female gender and low femur bone mineral density can be risk predictors of the condition. Bone mineral density is lower in patients with Charcot arthropathy with female gender and Femur T score as risk predictors. Peripheral arterial disease shows greater incidence in Charcot patients than was previously reported.

Charcot arthropathy of the diabetic foot in a sub-Saharan tertiary hospital: a cross-sectional study

BackgroundCharcot foot arthropathy is a potentially limb-threatening condition that leads to progressive destruction of the bones and joints in the neuropathic foot. One of its main causes is diabetes mellitus whose prevalence is steadily increasing. The acute phase is often misdiagnosed thus leading to foot deformity, ulceration and increased risk of amputation. There is a paucity of literature on this condition from sub-Saharan Africa. This study aimed at determining the extent of Charcot foot arthropathy, the radiological patterns of Charcot foot arthropathy and patient’s factors associated with Charcot foot arthropathy among adult patients with longstanding diabetes in an African setting.MethodsThis was a cross-sectional study that was carried at a national referral and university teaching hospital in Kampala, Uganda. One hundred patients with longstanding diabetes mellitus were consecutively recruited. Patients with a history of having diabetes mellitus for at least seven years since diagnosis were considered to have a longstanding disease. Clinical assessment of both feet was done. Weight-bearing radiographs of the selected foot were taken and evaluated using the Sanders and Frykberg and modified Eichenholtz classifications. A blood sample was taken for glycosylated haemoglobin (HbA1c). Data were summarized using descriptive statistics and student t-test.ResultsThe proportion of Charcot foot arthropathy among patients with longstanding diabetes was 12% of which one-third (4 out of 12) were acute cases. Fifty percent of the lesions were in the forefoot and 50% in the midfoot. Seventeen percent of lesions were at the inflammatory stage of the modified Eichenholtz classification, 50% at the developmental stage, 25% at the healing stage, and 8% at the remodelling stage. An abnormal foot radiograph was significantly associated with Charcot foot arthropathy among patients with longstanding diabetes.ConclusionCharcot foot arthropathy is fairly common in patients with longstanding diabetes mellitus in these settings with one third of patients presenting in the early acute phase. An abnormal weight-bearing radiograph was an associated factor of Charcot foot arthropathy among this specific group of patients. To reduce on the morbidity and limb threatening sequelae of this condition, clinicians are therefore advised to routinely examine the feet of patients with diabetes and send those with suspicious signs and symptoms for radiographic assessment.

The Charcot Foot and Mortality from 2000 to 2016

Introduction: The Charcot foot is a relatively rare but serious foot complication in patients with diabetes and neuropathy. The aim was to study the mortality and compare baseline characteristics at diagnosis between Charcot patients who died or survived during follow-up. Materials and Methods: A retrospective cohort study including all patients with a Charcot diagnosis at our centre from 2000 to 2016. Poisson regression analyses were done. Results: A total of 164 patients had the diagnosis Charcot (DM146) and 52 (31.1%) died during follow-up. They lived for 1973 days (range: 219-4895) i.e., 5.4 years. Patients were followed for 1122 years in total, median 6.0 years/patient (Q1-Q3=3.2-10.0). The mortality rate was 4.6/100 person-years-at-risk. Patients who died were significantly older (61±10 vs. 54±11 years), had less often type 1 diabetes (40 (27-55) vs. 60% (50-70)), were less often non-smokers (35 (22-49) vs. 52% (42-61)), had a lower hemoglobin (7.9±1.2 vs. 8.3±0.9), a higher creatinine (114 [88-161] vs. 85 [69-109]) and were more often treated with antitrombotic agents (71 (57-83) vs. 53% (43-62)) compared to survivors. Rate ratios for death were insignificantly different among smokers and non-smokers, among patients with type 1 and 2 diabetes, among patients with a diabetes duration below or above 10 years and among patients with HbA1c above or below 60 mmol/mol-both in univariate analyses and after adjustment for age and gender. Conclusion: The mortality rate among patients with Charcot feet was 4.6%/person-years-at-risk and was not affected by diabetes type, smoking, diabetes duration or HbA1c-level. Disclosure S. Engberg: None. K. Kirketerp-Møller: None. A. Rasmussen: None.

Biomechanical simulation of the Charcot neuroarthropathic foot with plantar ulcer

Diabetic patients with long-term diabetes are mainly affected by peripheral neuropathy. This can lead to the Charcot neuropathic osteoarthropathy (CNO). The CNO results in dramatic deformities and dysfunctional foot and ankle complex. The gait and stance are modified and overloads occur because of overpressures below the bony prominences. As the neuropathy makes the region insensitive to pain, foot ulcers can appear. Currently, there is no way to predict foot ulcer resulting from the foot anatomy reconfiguration induced by CNO. The purpose of this study is to address this issue. A Type 2 CNO foot was reconstructed using the CT-scan modality and the corresponding biomechanical finite element (FE) model was created. This model includes bones as rigid bodies and represents the soft tissues of the foot as two different sub-domains. The sole of the foot model is put in contact with a virtual horizontal pedobarographic platform. The Charcot patient was asked to perform a static standing acquisition of plantar pressures using a Zebris platform. The collected pressures were applied on the FE foot sole in order to compute internal strains. Then, the foot model including gravity and contact with the virtual pedobarographic platform was used to simulate a standing position. The corresponding sole pressure and internal strains thus computed can therefore be respectively compared with the measured standing plantar pressures and with the internal strains simulated from the measured boundary conditions. The volumes and location of the largest clusters with contiguous nodes with Von Mises (VM) strains over 20% or 50% are similar (errors < 5%) between measured pressure applied and static simulations. The simulated peak pressure value is also close to the one measured with the patient in weight bearing position. The FE model of the type 2 CNO can predict, in weight bearing position, the location and the proportion of the Von Mises Strains in the soft tissue of the diabetic foot. The location is similar to the real plantar ulcer for this patient and the plantar pressure values are in accordance with the measurements. Indeed, a peak pressure value of 19.6 N/cm 2 is simulated in regard of the cuboid bone, which happens to be the actual location of the ulcer.

Role of Wnt/β-catenin and RANKL/OPG in bone healing of diabetic Charcot arthropathy patients

Background and purpose — Charcot neuropathy is characterized by bone destruction in a foot leading to deformity, instability, and risk of amputation. Little is known about the pathogenic mechanisms. We hypothesized that the bone-regulating Wnt/β-catenin and RANKL/OPG pathways have a role in Charcot arthropathy.Patients and methods — 24 consecutive Charcot patients were treated by off-loading, and monitored for 2 years by repeated foot radiography, MRI, and circulating levels of sclerostin, dickkopf-1, Wnt inhibitory factor-1, Wnt ligand-1, OPG, and RANKL. 20 neuropathic diabetic controls and 20 healthy controls served as the reference.Results — Levels of sclerostin, Dkk-1 and Wnt-1, but not of Wif-1, were significantly lower in Charcot patients than in the diabetic controls at inclusion. Dkk-1 and Wnt-1 levels responded to off-loading by increasing. Sclerostin levels were significantly higher in the diabetic controls than in the other groups whereas Wif-1 levels were significantly higher in the healthy controls than in the other groups. OPG and RANKL levels were significantly higher in the Charcot patients than in the other groups at inclusion, but decreased to the levels in healthy controls at 2 years. OPG/RANKL ratio was balanced in all groups at inclusion, and it remained balanced in Charcot patients on repeated measurement throughout the study.Interpretation — High plasma RANKL and OPG levels at diagnosis of Charcot suggest that there is high bone remodeling activity before gradually normalizing after off-loading treatment. The consistently balanced OPG/RANKL ratio in Charcot patients suggests that there is low-key net bone building activity by this pathway following diagnosis and treatment. Inter-group differences at diagnosis and changes in Wnt signaling following off-loading treatment were sufficiently large to be reflected by systemic levels, indicating that this pathway has a role in bone remodeling and bone repair activity in Charcot patients. This is of particular clinical relevance considering the recent emergence of promising drugs that target this system.