Charcot Neuroarthropathy Theories

• Charcot Neuroarthropathy has various pathogenesis theories to consider

Neurotraumatic Theory

• Proposed by Volkman and Virchow as a German theory
• Loss of protective sensation leads to repetitive microtrauma in the insensate limb
• Normal fracture healing is inhibited
• The insensate foot is prone to repetitive, unrecognized trauma

Neurovascular Theory

• Referred to as French Theory
• Increased blood flow occurs in the region of destruction
• Sympathetic failure causes a hyper-vascular reflex, leading to vasodilation
• Increased monocytes/osteoclasts accelerate bone resorption, resulting in osteopenia
• Bone scans show increased uptake in Charcot arthropathy, possibly due to sympathetic denervation or local inflammatory processes
• Considers whether sympathetic failure is due to neuropathy

Molecular Level: Inflammation

• RANK-L (Receptor Activator of Nuclear Factor Kappa-B Ligand) activates the RANK receptor on osteoclast cells, leading to bone osteolysis
• Induces osteoclastic precursor cells to differentiate into mature osteoclasts
• OPG (Osteoprotegerin) acts as a decoy receptor for RANK-L and prevents RANK effects
• Compromised balance between pro- and anti-inflammatory cytokines contributes to Charcot
• Increased TNF-alpha, IL-1, and IL-6 are pro-inflammatory cytokines
• Decreased IL-4 & IL-10 are anti-inflammatory cytokines
• The cytokine pathway that causes vascular calcification causes RANKL/OPG

Cellular Level: Neuropathy

• Neuropathy involves CGRP (Calcitonin Gene-Related Peptide) secreted from nerve terminals
  • Antagonizes the synthesis of RANKL
  • Stimulates cell proliferation, synthesis of collagen, growth factors, and cytokines
  • Increases osteoblastic activity
  • Inhibits pro-inflammatory cytokine production and increases IL-10 by monocytes

Hyperglycemia

• Advanced glycation end products trigger RANK/RANKL
• Decreased NO production
• Increased ROS (Reactive Oxygen Species)
• NO has an inhibitory effect on osteoclastic activity
• Animal studies showed NO induced apoptosis of pre-osteoclasts
• Decreased NO in Charcot patients diminishes the suppression of osteoclastic activity

Autonomic Neuropathy

• Arterio-venous shunting is a normal physiologic response for thermoregulation
• Unregulated shunts are a result of autonomic neuropathy
• Increased venous pressure
• Increased fluid filtration through capillary leakage, leading to deep tissue edema
• Increased intra-compartmental pressure
• Compromised microcirculation leads to deep tissue ischemia
• Impaired tensile strength and stability of tendons, joints, and ligaments.

Causes of Neuropathy

• Spinal cord injuries, traumatic injuries, and peripheral nerve injuries are potential causes
• Syphilis and infections like leprosy
• Myelomeningocele can lead to neuropathy
• Disorders of neurological structures (Syringomyelia, Spina bifida) and neurodegenerative disorders like alcoholic neuropathy
• Vitamin deficiency and steroid intake
• Other neurological disorders (Congenital insensitivity to pain syndrome) and heavy metal poisoning
• Trauma induces 25-53% of Charcot cases

Trauma

• Lack of immobilization flares the inflammatory cycle with continued ambulation
• Fractured foot bone is broken down
• Uninterrupted maturation of osteoclasts occurs
• Repetitive trauma increases the expression of RANKL and osteolysis
  • Stimulates pro-inflammatory cytokines (TNF-α, interleukin-1)
  • Leads to the synthesis of nuclear transcription factor and increased RANKL

Other Forms of Trauma

• Osteomyelitis complicates 1/3 of Diabetic Foot Infections (DFI) and intensifies the pro-inflammatory cascade
• Local foot surgery accounts for 4% of acute Charcot cases in a retrospective study, emphasizing immobilization, bed rest, and casting

Clinical Presentation and Diagnosis

• A high index of suspicion is critical for early detection
• Pain sensation can occur even in an insensate limb
  • 75% of Charcot patients with neuropathy experience pain, and 22% remember a specific trauma
• Often misdiagnosed
• Common misdiagnoses include sprain, osteomyelitis, Sudek's atrophy, deep venous thrombosis, cellulitis, and rheumatoid arthritis
• 25% of cases were initially misdiagnosed after clinical and radiographic exams

Misdiagnosis

• Sympathetic denervation, uninterrupted inflammatory response, trauma, and arterio-venous shunting cause a red, hot, and swollen foot
• The typical patient profile includes individuals aged 55-60 (mean 57) with potential bilateral involvement in 9-35% of cases and is often found in obese individuals (BMI >30) Early diagnosis of acute Charcot is critical

Identifying Early Charcot Foot Changes

• Sudden changes in foot shape, unilateral edema/erythema, deep dull arch pain in a previous neuropathic foot, and unilateral increase in skin temperature are key indicators
• Common misdiagnoses in the ER include cellulitis, DVT, trauma, and osteomyelitis vs. Charcot
• The purpose of staging is to facilitate communication, prognosticate outcomes, and facilitate treatment

Types of Classifications

• Anatomic: Sanders-Frykberg
• Pathologic: Eichenholz

Sanders-Frykberg Classification

• Pattern 1: Forefoot
• Pattern 2: Tarsometatarsal joints
• Pattern 3: Naviculocuneiform, Talonavicular, and Calcaneocuboid joints
• Pattern 4: Ankle and Subtalar joint
• Pattern 5: Calcaneus

Eichenholz Classification

• Characterized inflammatory process with edema, hyperemia, and erythema in Stage 1 (Acute) - often confused with infection
• Management focuses on patient education, Total Contact Casting (TCC), Non-Weight Bearing (NWB), and mobility aids; consolidation can occur within 12 weeks with stable status
• Stage 2 (Subacute) involves coalescence of new bone at the site of joint destruction, thus focus on patient education, prophylactic exostectomy, or osteotomy/arthrodesis if an ulcer is present or pending

Management of Charcot Foot

• Stage 3 (Chronic) is a continuation of Stage II with potential resolution of inflammation and bony consolidation, requiring similar treatments, protective shoe gear, or surgery
• Stage 0 (Added by Shibata) signifies a period of inflammation after acute trauma with normal radiographs; with the goal to arrest the process and prevent Stage 1, and consider associated injuries
• Initial management goals include achieving a stable, plantigrade, non-ulcerated foot through conservative treatments like total contact casting, crutches, or wheelchair

Non-Surgical Treatment Options

• Bisphosphonates, salmon calcitonin spray, and non-invasive bone stimulators are used
• Bisphosphonates are potent inhibitors of osteoclast activation but require considerations for renal insufficiency and potential osteonecrosis of the jaw
• Anderson et al. Study showed pamidronate bisphosphonate decreases limb temperature compared to immobilization alone

Clinical Studies on Treatments

• Intranasal Calcitonin decreases markers of bone metabolism and is used to increase vertebral bone density and has an impact on the RANKL/OPG system
• Bem et al. Study showed salmon calcitonin spray with Ca supplementation can reduce bone turnover
• The electrical bone stimulator produces bone callus through piezoelectricity and increased osteoblastic activity

Determining Weight-Bearing Safety

• The goal is to achieve chronic status while maintaining foot stability
• A dermal infrared thermometry change of less than 2 degrees C indicates progression to the intermediate/chronic stage
• Bone-specific alkaline phosphatase is a marker of bone metabolism to monitor

Lab Analysis

• ESR and CRP are acute-phase reactants that increase during inflammation but indicate neither Charcot or Osteomyelitis
• CBC, Blood culture, Glucose and Procalcitonin can be used
• CRP levels correlate to OM vs. cellulitis, reflecting the presence and intensity of the inflammatory process
• ESR is a non-specific measure of inflammation and is commonly elevated due to infection, neoplasms, or autoimmune disorders

Clinical Studies on Lab Values

• Kaleta JL et al. Study used ESR as the only lab value with a significant difference in patients with OM
• Elevated CRP and ESR values can increase the diagnostic probability of OM

Markers of Bone Metabolism

• Urinary deoxypridinoline can mark bone resorption
• Bone-specific alkaline phosphatase signals bone formation
• CROW walker, Minnesota brace, custom molded shoes, and orthoses constitute therapeutic footwear
• Additional therapeutic interventions include patient education

When To Operate

• Unstable or non-braceable foot, or failure of footwear or orthoses are cause to operate
• Surgery with external fixation can cause wound dehiscence, pin failure and pin tract infections
• Non-union/fibrous union, recurrence, and activation/progression of Charcot in the contralateral extremity are also potential surgical complications

Key Findings From Study On Surgical vs Non Surgical Treatment

• Patients with diabetic neuropathy have higher rates of post surgical complications
• Patients in surgical and non surgical groups can have similar outcomes
• Studies demonstrate that exostectomy and Arthrodesis treatments are effective and promote healing of foot ulcers