Biomarkers for Early Detection of Charcot Arthropathy: A Prospective Study on Type 2 Diabetes Patients with Severe Neuropathy.

BACKGROUND: Charcot arthropathy (CA) is a progressive noninfectious inflammatory disease that causes irreversible destruction to pedal architecture in diabetic neuropathy (DN) patients. The debilitating prognosis demands early detection to prevent the development and progression of this disorder. Dysregulated and persistent production of inflammatory cytokines is reported as the key element in initiating osteoclastogenesis in CA. The study analyzed the potential association of markers of inflammation and bone turnover of prediagnostic serum samples on CA. METHODS: Seventy-one type 2 severe DN patients were selected based on inclusion-exclusion criteria. Serum samples of interleukin 6 (IL-6), osteoprotegerin (OPG), bone alkaline phosphatase (BALP), and C-reactive protein (CRP) were analyzed. These patients were followed for the development of symptoms of CA for 12 months. In the year of monitoring, 7 patients developed CA (group 1), whereas the remaining 64 patients did not develop CA (group 2). RESULTS: The rate of development of CA in patients with severe DN was 9.8%. In this group, significantly increased median values of HbA1c (group 2: 8.00 [7.00-9.00], group 1: 10.00 [9.25-11.50], P = .013); IL-6 (group 2: 1.21 [0.72-2.16], group 1: 11.08 [6.65-63.64], P = .008); and CRP (group 2: 1.25 [0.78-3.20], group 1: 3.31 [1.18-41.33], P = .041) were found. The receiver operating characteristic analysis showed that IL-6 was more strongly associated with the onset of CA (IL-6: area under the curve = 0.808; P = .008) than CRP. Cut-off values of ≥6.6 for IL-6 show potential to rule out CA in high-risk patients, with a positive predictive value of 26.1%, a negative predictive value of 97.9%, a sensitivity of 85.7%, and a specificity of 73.4%. CONCLUSION: In our study population, we found that an exacerbated inflammatory state, reflected by IL-6 values, generally occurred in DN patients before the clinical detection of CA. LEVEL OF EVIDENCE: Level II, prospective comparative study.

Management of Infections and Osteomyelitis in Patients With Charcot Foot Arthropathy.

There is growing interest in performing reconstruction of deformities associated with Charcot foot arthropathy. At least half of the patients undergoing this reconstruction will have chronic wounds and osteomyelitis overlying the deformity. It is important to provide orthopaedic surgeons with tools for making the diagnosis of osteomyelitis in this patient population and creating a strategy for treatment.

Early Diagnosis of Late-Onset Below-Level Neuropathic Pain in an 83 Year-Old Incomplete Tetraplegic Patient: A Charcot Spinal Neuro-Arthropathy Case Report.

BACKGROUND Charcot spine (CS), also called neuropathic arthropathy, appears to be triggered by damage to the nervous system (either central or peripheral) impairing proprioception and pain/temperature sensation in the vertebral column. Therefore, the defense mechanisms of altered joints lead to a progressive degeneration of the vertebral joint and surrounding ligaments, which can provoke major spinal instability. Beyond the sensory aspects, mechanic factors are identified as risk factors. While its etiology and pathophysiology remain contested, CS represents a rare and difficult pathology to diagnose at an early stage, owing to its nonspecific clinical symptoms. The diagnosis of CS is probably still underestimated and often occurs only quite late in the disease course. CASE REPORT An 83-year-old male patient who had a history of a post-traumatic tetraplegia was diagnosed with CS after 3 years, after describing a recent progressive worsening of neuropathic pain. The diagnosis was earlier than the majority of cases described in the literature. Indeed, in a recent review, the mean time lag between the onset of neurological impairment and the diagnosis of CS was 17.3±10.8 years. CONCLUSIONS This case report demonstrates the benefits of early diagnosis of CS when confronted by the clinical and radiological criteria. Therefore, it seems important to be able to evoke this neuropathic spinal arthropathy sufficiently in time to prevent its disabling consequences in patients with spinal cord injury, in terms of quality of life and independence.

[Progress in clinical diagnosis and treatment of diabetic Charcot neuroarthropathy of foot and ankle].

Objective: To summarize the progress of clinical diagnosis and treatment of diabetic Charcot neuroarthropathy (CNO) of foot and ankle to provide reference for clinical treatment. Methods: The research literature on diabetic CNO of foot and ankle at home and abroad was widely reviewed, and the stages and classification criteria of CNO were summarized, and the treatment methods at different stages of the disease course were summarized. Results: CNO is a rapidly destructive disease of bone and joint caused by peripheral neuropathy, which leads to the formation of local deformities and stress ulcers due to bone and joint destruction and protective sensory loss, which eventually leads to disability and even life-threatening. At present, the modified Eichenholtz stage is a commonly used staging criteria for CNO of foot and ankle, which is divided into 4 stages by clinical and imaging manifestations. The classification mainly adopts the modified Brodsky classification, which is divided into 6 types according to the anatomical structure. The treatment of diabetic CNO of foot and ankle needs to be considered in combination with disease stage, blood glucose, comorbidities, local soft tissue conditions, degree of bone and joint destruction, and whether ulcers and infections are present. Conservative treatment is mainly used in the active phase and surgery in the stable phase. Conclusion: The formulation of individualized and stepped treatment regimens can help improve the effectiveness of diabetic CNO of foot and ankle. However, there is still a lack of definitive clinical evidence to guide the treatment of active and stable phases, and further research is needed.

Charcot arthropathy outcomes after early referral to a regional tertiary care foot clinic.

BACKGROUND: Community physicians may not encounter Charcot arthropathy frequently, and its symptoms and signs may be nonspecific. Patients often have a delay of several months before receiving a formal diagnosis and referral for specialty care. However, limited Canadian data are available. We evaluated the clinical history, treatment and outcomes of patients treated for Charcot arthropathy after prompt referral and diagnosis. METHODS: We performed a retrospective chart review of 76 patients with diabetes (78 feet) who received nonoperative treatment for Charcot arthropathy in a specialty foot clinic between Jan. 20, 2009, and Mar. 26, 2018. Patients were referred to the foot clinic by community physicians for evaluation or were pre-existing patients at the foot clinic with new-onset Charcot arthropathy. RESULTS: Of the 78 feet included in our analyses, 52 feet (67%) were evaluated initially by a community physician and referred to the foot clinic, where they were seen within 3 ± 5 weeks. The remaining 26 feet (33%) were already being treated at the foot clinic. Most feet had swelling, erythema, warmth, a palpable pulse and loss of protective sensation. Ulcers were present initially in 23 feet (29%). Sixty-four feet (82%) with Charcot arthropathy were in Eichenholtz classification stage 1 and most had midfoot involvement. Nonoperative treatment included total contact casting (60 feet, 77%). Mean duration of nonoperative treatment until resolution for 55 feet (71%) was 6 ± 5 months. Surgery was performed on 20 feet (26%) for the treatment of infection and recurrent ulcer associated with deformity, including 6 (8%) lower limb amputations. CONCLUSION: Charcot arthropathy may resolve in most feet with early referral and nonoperative treatment, but remains a limb-threatening condition.

Total knee arthroplasty for neuropathic arthropathy in a patient with leprosy.

Patients with leprosy are known to tend to develop neuropathic arthropathy, known as Charcot joint. There are no case reports of total knee arthroplasty (TKA) in patients with leprosy with polyarticular neuropathic arthropathy, and the results are unknown. In this study, we report a case of TKA in a patient with leprosy with polyarticular neuropathic arthropathy and discuss its outcomes and indications. Right TKA using the NexGen Legacy Constrained Condylar Knee implant was performed in a 62-year-old man with neuropathic arthropathy in multiple joints with clinical symptoms, particularly in the right knee. Seven years post-operation, the American Knee Society Score-knee and -function, which represent knee function and activities of daily living on a scale of 100 points, were significantly improved compared with preoperative values, from 30 to 99 points and 0 to 60 points, respectively. Indications for arthroplasty for neuropathic arthropathy should be carefully considered in each individual case. In this case, the patient had neuropathic arthropathy in multiple joints; however, TKA was performed because recovery of function in the right knee was expected to significantly improve the patient's activities of daily living, and a good mid-term clinical outcome was achieved. Therefore, indications for arthroplasty should be considered in patients with systemic neuropathic arthropathy such as leprosy, and with accurate assessment and appropriate implant selection, good long-term outcomes may be expected.

Charcot neuroarthropathy versus osteomyelitis: a case series.

INTRODUCTION: Patients with diabetes and peripheral neuropathy have a 25% risk of developing a foot ulcer, and these can lead to soft tissue infections that worsen and result in osteomyelitis. While Charcot neuroarthropathy is not as common as osteomyelitis, it is often misdiagnosed as osteomyelitis. CASE REPORTS: Three patients presented with diabetes, neuropathy, and foot ulcers. They underwent prophylactic surgery but later developed swelling at the surgical sites. Radiographs showed fragmentations that caused concern about osteomyelitis. The authors maintained diagnoses of Charcot neuroarthropathy and treated the patients with immobilization and offloading. All patients resolved the fragmentations without antibiotics or surgery. CONCLUSION: While Charcot neuroarthropathy and osteomyelitis have similar signs and symptoms, understanding the similarities and differences between the conditions can aid providers in appropriate wound management.

Failure of internal fixation for ankle joint Charcot neuroarthropathy with beta(2)-microglobulin amyloidosis: a case report.

Charcot neuroarthropathy (CN) is a serious diabetic complication with a poor prognosis and a high rate of misdiagnosis. Furthermore, beta(2)-microglobulin amyloidosis (Abeta2M) makes the diagnosis and therapy more difficult and complex. This case report highlights the pathophysiology, clinical evaluation, treatment, and prevention of the major diabetic complications associated with CN and Abeta2M that cause poor quality of life, limit the patient's ability to walk independently, and are directly or indirectly linked with a high risk for lower limb amputation. Ankle CN was discovered in a 36-year-old single female with a history of type 1 diabetes mellitus and diabetic nephropathy. We performed early internal fixation. However, because she lived alone and needed hemodialysis three times a week, wearing a brace and non-weight-bearing were extremely inconvenient. Furthermore, she did not experience any pain and only some edema; thus, she proceeded to bear weight ahead of schedule without authorization. Due to the premature weight-bearing and poor compliance, the patient suffered severe bone resorption and infection and eventually had to undergo amputation. Abeta2M was suggested by bone pathological sections. We present a case of failed internal fixation of ankle CN with Abeta2M, emphasizing the importance of social factors and postoperative management.

No Difference in Risk of Amputation or Frequency of Surgical Interventions Between Patients With Diabetic and Nondiabetic Charcot Arthropathy.

BACKGROUND: The cause of Charcot neuro-osteoarthropathy (CN) is diabetes in approximately 75% of patients. Most reports on the clinical course and complications of CN focus on diabetic CN, and reports on nondiabetic CN are scarce. No study, to our knowledge, has compared the clinical course of patients initially treated nonoperatively for diabetic and nondiabetic CN. QUESTIONS/PURPOSES: Among patients with CN, are there differences between patients with diabetes and those without in terms of (1) the frequency of major amputation as ascertained by a competing risks survivorship estimator; (2) the frequency of surgery as ascertained by a competing risks survivorship estimator; (3) frequency of reactivation, as above; or (4) other complications (contralateral CN development or ulcers)? METHODS: Between January 1, 2006, and December 31, 2018, we treated 199 patients for diabetic CN. Eleven percent (22 of 199) were lost before the minimum study follow-up of 2 years or had incomplete datasets and could not be analyzed, and another 9% (18 of 199) were excluded for other prespecified reasons, leaving 80% (159 of 199) for analysis in this retrospective study at a mean follow-up duration since diagnosis of 6 ± 4 years. During that period, we also treated 78 patients for nondiabetic Charcot arthropathy. Eighteen percent (14 of 78) were lost before the minimum study follow-up and another 5% (four of 78 patients) were excluded for other prespecified reasons, leaving 77% (60 of 78) of patients for analysis here at a mean of 5 ± 3 years. Patients with diabetic CN were younger (59 ± 11 years versus 68 ± 11 years; p < 0.01), more likely to smoke cigarettes (37% [59 of 159] versus 20% [12 of 60]; p = 0.02), and had longer follow-up (6 ± 4 years versus 5 ± 3 years; p = 0.02) than those with nondiabetic CN. Gender, BMI, overall renal failure, dialysis, and presence of peripheral arterial disease did not differ between the groups. Age difference and length of follow-up were not considered disqualifying problems because of the later onset of idiopathic neuropathy and longer available patient follow-up in patients with diabetes, because our program adheres to the follow-up recommendations suggested by the International Working Group on the Diabetic Foot. Treatment was the same in both groups and included serial total-contact casting and restricted weightbearing until CN had resolved. Then, patients subsequently transitioned to orthopaedic footwear. CN reactivation was defined as clinical signs of the recurrence of CN activity and confirmation on MRI. Group-specific risks of the frequencies of major amputation, surgery, and CN reactivation were calculated, accounting for competing events. Group comparisons and confounder analyses were conducted on these data with a Cox regression analysis. Other complications (contralateral CN development and ulcers) are described descriptively to avoid pooling of complications with varying severity, which could be misleading. RESULTS: The risk of major amputation (defined as an above-ankle amputation), estimated using a competing risks survivorship estimator, was not different between the diabetic CN group and nondiabetic CN group at 10 years (8.8% [95% confidence interval 4.2% to 15%] versus 6.9% [95% CI 0.9% to 22%]; p = 0.4) after controlling for potentially confounding variables such as smoking and peripheral artery disease. The risk of any surgery was no different between the groups as estimated by the survivorship function at 10 years (53% [95% CI 42% to 63%] versus 58% [95% CI 23% to 82%]; p = 0.3), with smoking (hazard ratio 2.4 [95% CI 1.6 to 3.6]) and peripheral artery disease (HR 2.2 [95% CI 1.4 to 3.4]) being associated with diabetic CN. Likewise, there was no between-group difference in CN reactivation at 10 years (16% [95% CI 9% to 23%] versus 11% [95% CI 4.5% to 22%]; p = 0.7) after controlling for potentially confounding variables such as smoking and peripheral artery disease. Contralateral CN occurred in 17% (27 of 159) of patients in the diabetic group and in 10% (six of 60) of those in the nondiabetic group. Ulcers occurred in 74% (117 of 159) of patients in the diabetic group and in 65% (39 of 60) of those in the nondiabetic group. CONCLUSION: Irrespective of whether the etiology of CN is diabetic or nondiabetic, our results suggest that orthopaedic surgeons should use similar nonsurgical treatments, with total-contact casting until CN activity has resolved, and then proceed with orthopaedic footwear. A high frequency of foot ulcers must be anticipated and addressed as part of the treatment approach. LEVEL OF EVIDENCE: Level III, prognostic study.

Incidence and Predictive Factors for Amputations Derived From Charcot's Neuroarthropathy in Persons With Diabetes.

Charcot's neuroarthropathy (CN) is the progressive destruction of the bones and joints of the feet, as a consequence of severe peripheral neuropathy, which predisposes patients to amputations. The purpose of this study was to measure the cumulative incidence of amputations resulting from CN and risk factors among amputated people with diabetes mellitus (DM). This was an epidemiological, observational, and retrospective study of 114 patients with DM who had an amputation involving the lower limbs. Data were collected from 2 specialized outpatient clinics between 2015 and 2019, including socio-demographic and clinical variables (cause of amputation: CN, peripheral arterial disease [PAD], infected ulcers, fracture, osteomyelitis, and others; body mass index [BMI]; 1 or 2 DM, time since DM diagnosis, insulin treatment, glycated hemoglobin; creatinine; smoking and drinking; systemic arterial hypertension, diabetic retinopathy, diabetic kidney disease, diabetic peripheral neuropathy, acute myocardial infarction, PAD, and stroke; characteristics of amputation [level and laterality], in addition to the specific variables related to CN [time of amputation in relation to the diagnosis of CN, diagnosis of CN in the acute phase, and treatment implemented in the acute phase]). We compared socio-demographic and clinical characteristics, including types of amputation, between patients with and without CN. Statistical analyses were performed using the 2 sample t-test or Wilcoxon-Mann-Whitney test, for quantitative variables, and the Pearson's χ2 test or Fisher's exact test for categorical variables. The investigation of the possible association of predictive factors for a CN amputation was carried out through logistic regression. The amputation caused by CN was present in 27 patients with a cumulative incidence of 23.7% in 5 years. There was a statistically significant association between BMI and the occurrence of CN (odds ratio: 1.083; 95% confidence interval: 1.001-1.173; P = .048); higher values of BMI were associated with a higher occurrence of amputations secondary from CN.

Iatrogenic Ankle Charcot Neuropathic Arthropathy after Spinal Surgery: A Case Report and Literature Review.

Charcot neuropathic arthropathy is a relatively rare, chronic disease that leads to joint destruction and reduced quality of life of patients. Early diagnosis of Charcot arthropathy is essential for a good outcome. However, the diagnosis is often based on the clinical course and longitudinal follow-up of patients is required. Charcot arthropathy is suspected in patients with suggestive symptoms and an underlying etiology. Failed spinal surgery is not a known cause of Charcot arthropathy. Herein we report a patient with ankle Charcot neuropathic arthropathy that developed after failed spinal surgery. A 58-year-old man presented to the emergency room due to painful swelling of the left ankle for 2 weeks that developed spontaneously. He underwent spinal surgery 8 years ago that was associated with nerve damage, which led to weakness of great toe extension and ankle dorsiflexion, and sensory loss below the knee. CT and T2-weighted sagittal MRI showed a fine erosive lesion, subluxation, sclerosis, fragmentation, and large bone defects. Based on the patient's history and radiological findings, Charcot arthropathy was diagnosed. However, the abnormal blood parameters, positive blood cultures, and severe pain despite the decreased sensation suggested a diagnosis of septic arthritis. Therefore, diagnostic arthroscopy was performed. The ankle joint exhibited continued destruction after the initial surgery. Consequently, several repeat surgeries were performed over the next 2 years. Despite the early diagnosis and treatment of Charcot arthropathy, the destruction of the ankle joint continued. Given the chronic disease course and poor prognosis of Charcot arthropathy, it is essential to consider this diagnosis in patients with neuropathy.

Identification of Charcot Foot: A Case Report.

Neuropathy is a painful and potentially devastating complication of diabetes mellitus affecting many patients. Neuropathy can lead to foot ulcers, infections, and subsequent amputations. Nerve damage from peripheral neuropathy may lead to Charcot neuropathic osteoarthropathy, commonly known as Charcot foot. Flesh wounds and weakened bones causing microfractures of the foot and ankle may lead to foot malformations. Early recognition and care are essential for the treatment of Charcot foot and prevention of further injury. This article discusses the use of monofilament testing for diabetic neuropathy, increasing awareness of Charcot foot, and introducing a screening algorithm for Charcot foot.

The Association of Olfactory Impairment with Charcot Neuroarthropathy and Possible Links to Causation.

BACKGROUND: Charcot neuroarthropathy (CN) is a devastating complication of some diseases affecting the peripheral nervous system. Initial subjective and objective presentation of the disease can be variable. Common among all presentations seems to be uncontrolled inflammation yielding dislocations and/or fractures. The exact cause remains the subject of much debate. METHODS: Our study retrospectively looks at the function of olfactory function in consecutive patients with CN and compares the findings with a nonaffected population. The University of Pennsylvania Smell Identification Test was used to assess olfaction and document microsomia. RESULTS: Twenty consecutive patients presenting with CN demonstrated significant (P < .0001) microsomia when compared to an unaffected population with diabetes. CONCLUSIONS: Microsomia is strongly associated with CN. This finding may be correlated to voltage-gated sodium 1.7 channel impairment and appears to be a candidate precursor for the development of CN.

Diabetes Mellitus: An Overview in Relationship to Charcot Neuroarthropathy.

Diabetes mellitus with the lack of glycemic control increases risks for developing comorbidities affecting organ systems responsible for critical function. The development of diabetic neuropathy predisposes patients to the onset of Charcot neuroarthropathy (CN). There is significant complexity with treatment of diabetic-induced CN, which can have an often delayed or missed diagnosis. Supervision and treatment from trained specialists are required to provide care for this multifaceted disease process. It is essential for patients to partner with glucose control, comorbidity prevention and care, as well as lower extremity management. Ultimately, CN can result in significant lower extremity deformity placing patients at risk of limb and life.

Nondiabetic Charcot Neuroarthropathy: Evaluation and Treatment.

There are many similarities between nondiabetic and diabetic Charcot neuroarthropathy (CN) but many of the underlying causes causing nondiabetic neuropathy and CN are associated with poor bone quality. Patient workup for nondiabetic CN should include the underlying cause of the neuropathy and optimization of bony healing, such as vitamin D supplementation and bisphosphonate or calcitonin administration. Surgical reconstruction should include the most robust fixation possible, as nondiabetic patients with CN are more prone to delayed union.

Conservative Management of Charcot Neuroarthropathy.

Charcot can be a difficult clinical entity to diagnose in the acute phase, and clinicians should have a high clinical suspicion in neuropathic patients who present with erythema, edema, and warmth of the foot or ankle. Immobilization and nonweight-bearing should be immediately initiated when the diagnosis of Charcot has been made and patients should remain nonweight-bearing until the affected bones/joints have coalesced. Educating patients and managing expectations is crucial to improve compliance with the conservative treatment of Charcot and avoid the long-term sequelae including severe deformity, ulceration and infection, and amputation.

Etiology, Epidemiology, and Outcomes of Managing Charcot Arthropathy.

Surgical intervention for Charcot arthropathy is becoming more common; this is driven by an increased prevalence, better understanding of the cause, identifying patient risk factors that influence outcomes, and how to best optimize these. This article aims to summarize the cause of Charcot, look at the factors that influence the outcomes, and the financial cost of managing what is a very challenging condition.

The Shoulder Charcot Arthropathy and Secondary to Hemangioblastoma in Conus Medullari with Syringomyelia.

Charcot arthropathy of the shoulder joint is usually referred to as shoulder joint involvement of Charcot arthropathy, which is a chronic, degenerative, destructive condition resulting from decreasing or loss of sensorial innervation. To date, several reports have described the shoulder Charcot arthropathy, caused by malformations of the occipital region with syringomyelia; but nobody has reported the shoulder Charcot arthropathy secondary to hemangioblastoma in conus medullari with syringomyelia. Therefore, we report a 32-year male patient who was diagnosed with Charcot arthropathy of the shoulder joint, which was misdiagnosed as a soft tissue tumor and treated surgically. After the operation, the whole-spine MRI examination was performed as a presenting feature of hemangioblastoma in conus medullari with syringomyelia. Key Words: Arthropathy, Neurogenic, Hemangioblastoma, Syringomyelia.