Imaging challenges in Charcot’s neuroarthropathy and diabetic foot: Distinguishing infective and non-infective conditions

Pathogenesis and causes of Charcot’s neuroarthropathy

There are two main theories proposed to explain the pathogenesis of Charcot arthropathy – neurotraumatic and neurovascular [Figure 1]. In the neurotraumatic theory, the scientists – Virchow and Volkman – suggest that due to hypoesthesia, the foot is susceptible to repeated and/or acute trauma. The absence of pain and thus continued weight bearing worsens the injury, resulting in fractures and deformities.^[4] Mitchell and Charcot proposed the neurovascular theory which is based on the hypotheses that an increased blood supply to bone through arteriovenous shunting secondary to autoimmune dysfunction eventually leads to bone resorption and mechanical weakening, ultimately resulting in fractures and deformity.^[4] Other additional factors like osteopenia in type I diabetes with low body mass index^[5] predispose to significant injuries from trivial trauma. Non-enzymatic glycation of Achilles may contribute to Achilles shortening and thus, foot deformity.^[6] Recent evidence suggests that patients with Charcot arthropathy are predisposed to have a higher pro-inflammatory response.^[7] This may explain the predilection for joints held together with ligamen ts - Lisfranc and Chopart joints.^[4]

Close

Figure 1:

Pictorial representation of the two main proposed theories for the development of neuroarthropathy.

Export to PPT

While diabetes is the leading cause of CN by far, there are many other conditions which predispose to polyneuropathy. Other notable causes are:

• Alcoholic neuropathy

• Leprosy (Hansen’s disease)

• Syphilis (tabes dorsalis)

• Syringomyelia (especially upper-limb joints, but can involve the foot if the lumbosacral cord affected)

• Spinal cord injury

• Congenital insensitivity to pain

• Peripheral nerve injuries (trauma, surgery, advanced entrapment neuropathies)

• Rarer causes like - Folic acid deficiency neuropathy, multiple sclerosis, post-polio residual paralysis, Amyloid neuropathy, meningomyelocele/spina bifida.

Clinical conundrum in the diabetic patient: CN and the diabetic foot

Long-standing diabetes predisposes to Charcot foot due to peripheral neuropathy (loss of protective sensation, muscle imbalance, autonomic hyperemia) and metabolic bone weakening, which together lead to repetitive unperceived trauma, bone resorption, joint destruction, and progressive foot deformity. In addition to an increased risk of CN, diabetic individuals are prone to developing foot ulcers which are in fact more common presenting features, often leading to severe complications.^[8] More than 50% of diabetic individuals with foot ulcers present with clinical signs of infection at the initial contact, and as many as 20–60% may have underlying osteomyelitis - diabetic foot osteomyelitis (DFO).^[9] Bone infections develop due to direct contiguous spread from overlying soft tissue infection, increasing morbidity [Figure 2].^[9]

Close

Figure 2:

Pictorial flow chart of the development of diabetic foot osteomyelitis in the presence of uncontrolled hyperglycemia, worsened by coexisting neuropathy, microangiopathy, and immune dysfunction.

Export to PPT

The critical need for accurate differentiation

CN and DFO both have clinically overlapping features with significantly different treatment measures, necessitating differentiation between the two. CN represents a sterile, neuropathy-driven inflammatory and destructive process of the joints, whereas DFO is an infective condition involving the bones and joints, usually arising from a cutaneous infection or an ulcer or sinus tract. CN is managed primarily with immobilization and offloading (such as total contact casting or orthotic walkers), along with strict glycemic control and corrective surgery only in severe deformity, whereas DFO requires prolonged culture-directed antibiotics, surgical debridement or limited amputation if needed, plus wound care, offloading, and revascularization when ischemia is present.

Charcot’s neuroarthropathy

CN can present either acutely or as a chronic condition with both the phases often overlapping [Figure 3]. Acute CN typically presents with the sudden onset of swelling, erythema, warmth, and edema of the foot or ankle, often following trivial trauma. Despite the striking inflammatory appearance, patients usually report little or no pain due to underlying neuropathy. The marked local hyperemia and temperature rise frequently mimic cellulitis, deep vein thrombosis, or gout, leading to misdiagnosis in the early stage. In contrast, chronic CN is characterized by longstanding, progressive deformity of the foot or ankle, most classically the development of a “rocker-bottom” foot due to collapse of the midfoot arch. These patients generally remain painless but demonstrate joint instability, malalignment, and abnormal weight-bearing with varus or valgus deformities. Chronic pressure overload results in recurrent plantar ulcers, callus formation, and a predisposition to secondary infections, which further complicate the clinical picture.^[18]

Close

Figure 3:

Comparative analysis of clinical features of Charcot neuroarthropathy and osteomyelitis. CN: Charcot neuroarthropathy, OM: Osteomyelitis, CRP: C-Reactive protein, ESR: Erythrocyte sedimentation rate, and WBC: White Blood Cell count, WB: Weight-bearing, DVT: Deep vein thrombosis, d/d: Differential diagnoses.

Export to PPT

Acute CN: Radiologically silent stage of disease

Acute CN presents with clinically active inflammation corresponding to stages 0, 1, and 2 of the modified Eichenholtz classification [Figure 4].^[20] Stage 0 which is negative on radiographs represents an early stage of CN. MRI is useful in early stages to identify bone marrow edema and changes in the Lisfranc ligament which eventually lead to midfoot collapse.^[21] Stage 3 of Eichenholtz classification represents the chronic, coalescent stage of inactivity and residual deformity [Figure 5].

Close

Figure 4:

Modified Eichenholtz classification correlating clinical findings with radiograph.

Export to PPT

Close

Figure 5:

Clinical stages of Charcot neuroarthropathy.

Export to PPT

The most commonly used anatomical classification is described by Sanders and Frykberg - Pattern 1 involves the phalanges, interphalangeal, and the metatarsophalangeal joints; pattern 2 involves the tarsometatarsal (TMT); pattern 3 involves the cuneonavicular, talonavicular, and calcaneocuboid articulations; pattern 4 involves the talocrural joint; and pattern 5 involves the posterior calcaneum. Clinically pattern 2 followed by 3 is the most common [Figure 6].^[22]

Close

Figure 6:

Pictorial representation of the 5 zones of involvement of the foot in neuroarthropathy as described by Sanders and Frykberg.

Export to PPT

Conventional radiographs

Radiographs are the first choice of investigation of CN with demineralization being the earliest marker of neuropathic osteoarthropathy and flattening of the metatarsal head favors diabetic neuroarthropathy.^[21] Lack of soft tissue involvement in the presence of midfoot subchondral or periarticular changes with polyarticular distribution indicates diabetic neuroarthropathy.^[24]

Acute and chronic CN

Weight-bearing serial radiographs are the mainstay of radiographic evaluation of CN to rule out progressive foot collapse. Typical measurements acquired on radiographs include^[10] Meary’s angle [Figure 7], cuboid height [Figure 8], calcaneal pitch [Figure 9], and oblique radiographs add value in assessing the 3^rd–5^th TMT joints [Figure 10].

Close

Figure 7:

Meary’s angle: Angle (white) between the line originating from the center of the body of the talus (thin red line), bisecting the talar neck and head, and the line through the longitudinal axis of the 1^st metatarsal (thick red line) with 0° being normal.

Export to PPT

Close

Figure 8:

Cuboid height: Distance perpendicular from the plantar cuboid (yellow double headed arrow) to a line drawn from the plantar surface of the calcaneal tuberosity to the plantar aspect of the 5^th metatarsal head (red line). 2.2 cm above the line is the mean normal value.

Export to PPT

Close

Figure 9:

Calcaneal pitch: Angle (white) between a line extending from the plantar aspect of the calcaneus to the plantar surface of the 5^th metatarsal head (red line) and the line extending from the most plantar portion of the calcaneal tuberosity to the most plantar portion of the anterior calcaneus (green line) with angle between 20 and 30° being normal.

Export to PPT

Close

Figure 10:

Oblique radiographs demonstrating the 3^rd to 5^th magnetic resonance imaging tarso-metatarsal joints (white encircled).

Export to PPT

In the early stage of CN (Stage 0 modified Eichenholtz), the X-ray findings may be normal or equivocal. In stage 1 (fragmentation and destruction), there is osteopenia, fragmentation of the subchondral bone, and small periarticular debris which may be distinguishable. In stage 2 (coalescence), the osteopenia may also be accompanied by early sclerosis of the bone ends, absorption of the fine debris and larger bone fragments, as well as joint subluxation and dislocation. In stage 3 (reconstruction/consolidation phase), the most marked findings will be the residual deformity (ankylosis/pseudoarthrosis) and joint remodeling. Radiographic features of acute CN include soft tissue edema, juxta-articular osteopenia, periosteal reaction and may have a background of chronic CN in the form of fracture-dislocations and joint destruction^[24] [Figure 11]. Follow-up radiographs are essential to assess for progressive foot collapse/deformity due to involvement of the TMT joints, resulting in collapse of the load-bearing longitudinal arch and cuboid, resulting in the “rocker bottom foot.” Chronic stage fits into the rule of “6 D’s” – joint distention, destruction, dislocation, disorganization, debris, and increased bone density. Forefoot “Pencil and cup”/“sucked candy” appearance is seen due to tapering of the metatarsal and phalangeal diaphysis [Figure 11].^[3]

Close

Figure 11:

Sequential radiographs and magnetic resonance imaging (MRI) of a 50-year-old diabetic male with acute on chronic Charcot’s neuroarthropathy. (a) Oblique, anteroposterior, and lateral radiographs demonstrating subchondral cystic change at the 1^st and 2^nd tarsometatarsal (TMT) joints (yellow arrows) with healed metatarsal fracture (black arrow) and evidence of the acute phase of neuroarthropathy in the form of diffuse periarticular osteopenia and subcutaneous soft tissue edema (green arrow in a). Note the cuboid height (red double arrowhead). (b) Follow-up radiograph after 1 year demonstrates progressive foot collapse (red line), worsening of TMT joint arthropathy with a sucked candy appearance at the metatarsophalangeal and TMT joints (yellow arrows). New bone formation on the dorsal aspect of the TMT joints (white arrow). (c) Corresponding MRI image shows features of acute and chronic neuroarthropathy - joint fluid with subchondral edema and cysts (yellow arrows), osteitis with corresponding hazy and reticular T1 low signal and preserved cortex suggesting edema, without osteomyelitis (blue arrows), heterogeneous Lisfranc ligament (red arrow), and new bone formation at the TMT joint (white arrow).

Export to PPT

Radiographic signs of osteomyelitis

Osteomyelitis in its early stages has only demineralization, periosteal reaction, cortical destruction, and marrow lucency [Figure 12] which becomes visible after 2–3 weeks, necessitating the utilization of advanced imaging for early identification of osteomyelitis.^[8] New bone formation, bone sclerosis, sequestrum, involucrum, and cloacae can be seen in chronic cases.

Close

Figure 12:

Radiographs of a diabetic 48-year-old with pus discharge from the tip of the second toe. (a) Lateral, oblique, and AP radiographs demonstrate osteolysis of the distal phalanx of the second digit, with tiny bony fragments, soft tissue edema, and overlying skin ulceration (red circle). Background changes of neuroarthropathy in the form of tarsometatarsal joint arthropathy with subchondral osteopenia and subcutaneous soft tissue edema can be seen (white circle) Note the reduced calcaneal pitch in the lateral foot radiograph (red line and white diamond). (b) MR images reveal moderate edema in the tip of the distal phalanx with loss of cortex at the tip (red arrows) representing Ghost sign on T1-weighted images (top left), suggestive of osteomyelitis. Background severe tarsometatarsal arthropathy characterized by subchondral edema, cystic changes, new bone formation, and overlying subcutaneous edema (white arrows).

Export to PPT

Magnetic resonance imaging

MRI plays a central role in the evaluation of diabetic foot complications, particularly in differentiating CN from DFO. In the acute phase of CN, MRI is highly sensitive for detecting early changes such as bone marrow edema, microtrabecular fractures, and subchondral changes, which may not be visible on radiographs.^[26] MRI also demonstrates associated soft tissue edema and joint effusions, allowing for early diagnosis and intervention before significant deformity develops. Early identification of disruption of Lisfranc ligament can help in the management and prevention of longitudinal arch in early stages of the disease.^[27] In chronic CN, MRI helps delineate the extent of bony fragmentation, sclerosis, disorganization, and deformity, although marrow edema may be less pronounced.

Findings in established/Chronic CN

In the chronic stage, edema and enhancement become less pronounced. Well-marginated subchondral cysts, bone proliferation, and debris or intra-articular bodies can be seen. Overall, there is a decrease in signal intensity, consistent with osteosclerosis. Joint deformity, subluxations, and dislocations can also be identified.^[18] Soft tissue findings of neuroarthropathy are important ancillary features which come to the rescue in atypical and overlapping cases. These findings include callus formation at sites of weight-bearing with the exact location variable due to the varied biomechanics of each foot, commonly being at the base of cuboid in patients with established neuropathy.^[30] These areas of callus formation appear as T1 hypointense and T2 iso-hyperintense areas in the subcutaneous heel fat with overlying skin thickening [Figure 14].

Close

Figure 14:

(a-c) Soft tissue ancillary findings in neuroarthropathy include callus formation at sites of weight-bearing and the exact location varies due to the varied biomechanics of each foot. Note: callus formation in the form of low signal on all sequences at sites of chronic friction (white arrows in coronal T1 weighted image of the forefoot in a, coronal PD image of the forefoot in b and axial T1 weighted image of the forefoot in c).

Export to PPT

Upon ulceration, these areas begin to show T2 hyperintensity and skin irregularity with peripheral post contrast enhancement. Once infected, these can propagate infection to the underlying bone and joint. Ancillary findings of neuropathy also include diffuse atrophy of the intrinsic muscles of the foot, appearing as T1 hyperintense fat replacing the muscle fibers [Figure 15]. Diffuse subcutaneous fat edema is another finding in acute neuroarthropathy.

Close

Figure 15:

Multiplanar magnetic resonance imaging of a 32-year-old female with Charcot–Mary–Tooth disease presenting with a draining sinus on the plantar aspect of the 4^th metatarsophalangeal joint. Sagittal T1 and short tau inversion recovery images (upper row) demonstrate skin ulceration (white arrows in both lower and upper row), joint effusion (red arrows in both lower and upper row), and osteitis (blue arrows) characterized by hazy and reticular low T1 signal with interspersed areas of preserved marrow fat and high short tau inversion recovery signal. Note T1 ghost sign characterized by blurring of the plantar cortex of the metatarsal head is highly suspicious for osteomyelitis (pink arrows). In the lower row, the first image demonstrates diffuse fatty infiltration in intrinsic muscles (yellow arrow) consistent with denervation-related changes. Enhancement of reactive osteitis can be seen in the last images (blue arrow).

Export to PPT

Findings in DFO

Osteomyelitis on MRI is based on abnormal marrow signal with hypointensity on T1-weighted images and hyperintense signal on fluid-sensitive images with the T1 images being more predictive of true marrow infiltration [Figure 12]. Confluent pattern of hypointensity completely replacing the marrow fat favors osteomyelitis, while hazy and reticular pattern with interspersed spared marrow fat is more commonly seen in reactive edema or osteitis.^[26,31] Since DFO occurs most commonly due to contiguous spread of infection, adjacent soft tissue changes such as edema, ulcers, and sinus tracts should be closely looked for. These predominate in the forefoot, including under the heads of the first and fifth metatarsal, first phalanx, and in the hindfoot at the posterior plantar calcaneus. Subperiosteal hyperintensity (indicative of fluid or pus) is also a strong predictor of osteomyelitis [Figure 13]. Matching areas of T1 and T2 hypointensity raise suspicion of chronic or sclerosing osteomyelitis which are low-grade chronic processes of osteonecrosis, osteosclerosis and are sharply delineated from the normal marrow. The presence of T2 hyperintense patches may represent granulation tissue. Such equivocal cases warrant close follow-up for superimposed infection, true marrow edema, enhancement, and erosions.^[26]

Ghost sign has also been described in which bones with active infection disappear on T1-weighted images and reappear on T2-weighted images [Figure 16]. Contrary to this, bones destroyed by neuroarthropathy will remain the same on all pulsed sequences.^[32]

Close

Figure 16:

An example of T1 ghost sign in which bones with active infection disappear on T1-weighted images and reappear on T2-weighted images (red arrows). Note the adjacent collection (yellow arrow) and background changes of subchondral edema at the tarsometatarsal joint (white circle) in this patient with Charcot neuroarthropathy with osteomyelitis.

Export to PPT

DFO is also complicated by septic arthritis which is characterized by bony erosions, joint effusion, chondral destruction, thickened and enhancing synovium with pericapsular edema. Often, a communicating sinus tract is seen and joints adjacent to the affected joint may show reactive marrow edema. Edema extending into the subchondral bone with corresponding T1 hypointensity suggests associated osteomyelitis [Figure 15].^[26]

Management and diagnostic algorithm

The management strategies for CN and DFO differ fundamentally due to their distinct underlying pathophysiology. In CN, the primary goal is to halt inflammation and prevent further mechanical destruction through early and aggressive off-loading and immobilization, typically using a total contact cast or orthotic walker. In general, strict immobilization is observed until the acute phase subsides, followed by gradual mobilization and use of orthopedic shoes and braces. Pharmacologic agents such as anti-resorptive and anti-inflammatory agents have been tried for treatment although evidence remains limited.^[38] In the chronic phase, surgical correction is reserved for fixed deformities like rocker bottom foot and persistent instability. In contrast, the cornerstone of DFO management is infection control through targeted antimicrobial therapy combined with surgical debridement or limited amputation in cases of gangrene or sepsis. Adequate wound care, off-loading, and revascularization in patients with peripheral arterial disease are essential to promote healing. Both CN and DFO require strict glycemic control, optimization of comorbidities, and a multidisciplinary approach involving the expertise of endocrinology, orthopedics, infectious disease, podiatry, vascular surgery, and radiology. In cases where both pathologies coexist, it is pertinent to integrate both therapeutic strategies and apply a case or patient-tailored approach.

The clinicoradiological approach to diabetic foot can be summarized in Graphical Abstract. The summary of the American College of Radiology (appropriateness criteria) for CN and DFO is as follows [Table 1]^[39,40]:

• First-line imaging: Radiographs of the foot are recommended initially for all patients with suspected infection.

• MRI with and without contrast is considered the most appropriate next test for suspected osteomyelitis or soft tissue infection, given its high sensitivity and specificity.

• When MRI is inconclusive (i.e., unable to differentiate between sterile CN and DFO) or due to metallic hardware in the foot, labeled leukocyte scintigraphy (with or without SPECT/CT) of FDG/PET may be performed for detecting osteomyelitis.

• MRI remains first-line for Charcot, but nuclear medicine is strongly advised in equivocal cases.

• Monitoring Treatment Response: FDG-PET/CT and leukocyte scans may be used for assessing therapeutic response, but clinical and laboratory correlation remains essential.