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Author: Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR, LRCP, Chairman of Medical Imaging, Professor of Radiology, NGHA, King Fahad National Guard Hospital, King Abdulaziz Medical City, Riyadh, Saudi Arabia

Ali Nawaz Khan is a member of the following medical societies:
American Institute of Ultrasound in Medicine, Radiological Society of North America, Royal College of Physicians, Royal College of Physicians and Surgeons of the United States, Royal College of Radiologists, and Royal College of Surgeons of England

Coauthor(s): Muthusamy Chandramohan, MBBS, DMRD, FRCR, Consultant Radiologist, Bradford Teaching Hospitals, UK; Ian Turnbull, MD, Lecturer, Department of Radiology, University of Manchester; Consulting Neuroradiologist, Hope Hospital, Salford, Manchester and North Manchester Hospital; Sumaira MacDonald, MBChB, PhD, MRCP, FRCR, Lecturer, Sheffield University Medical School; Endovascular Fellow, Sheffield Vascular Institute

Editors: Amilcare Gentili, MD, Clinical Professor of Radiology, University of California at San Diego; Consulting Staff, Department of Radiology, Thornton Hospital; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; Wilfred CG Peh, MD, MBBS, FRCP(Glasg), FRCP(Edin), FRCR, MHSM, Clinical Professor, Faculty of Medicine, National University of Singapore; Senior Consultant Radiologist, Programme Office, Singapore Health Services; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; Felix S Chew, MD, MBA, EdM, Professor, Department of Radiology, Vice Chairman for Radiology Informatics, Section Head of Musculoskeletal Radiology, University of Washington

Author and Editor Disclosure

Synonyms and related keywords: neurotrophic joint, neuropathic joint disease, neuroarthropathy, Charcot joint disease, arthropathy, neuropathic osteoarthropathy, destruction of articular surfaces, dense subchondral bones, joint debris, joint deformity, dislocation, hypertrophic neuropathic osteoarthropathy, atrophic neuropathic osteoarthropathy, disorganized joints

Background

Neuropathic osteoarthropathy can be defined as bone and joint changes that occur secondary to loss of sensation and that accompany a variety of disorders. Charcot first described the relationship between loss of sensation and arthropathy in 1868.

The radiographic changes include destruction of articular surfaces, opaque subchondral bones, joint debris, deformity, and dislocation. Neuropathic arthropathy poses a special problem in imaging when it is associated with a soft tissue infection.1, 2, 3, 4, 5, 6, 7

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Pathophysiology

The pathophysiology of neuropathic arthropathy is debatable. The general consensus is that the loss of proprioception and deep sensation leads to recurrent trauma, which ultimately leads to progressive destruction, degeneration, and disorganization of the joint. Another theory postulates that neurally mediated vascular reflex results in hyperemia, which can cause osteoclastic bone resorption.

Causes of neuropathic arthropathy include the following:

One of the joint manifestations of leprosy are the signs of Charcot's disease. Charcot's disease of leprosy advances despite treatment.9

Neuropathic osteoarthropathy can be classified into hypertrophic and atrophic types. Hypertrophic changes predominate in the upper motor neuron lesions, and atrophic changes occur in peripheral nerve injuries. The early stage of osteoarthritis simulates neuropathic osteoarthropathy, both radiologically and pathologically.

Progressive joint effusion, fracture, fragmentation, and subluxation should raise the suspicion of neuroarthropathy. In the advanced stage, abnormal findings on radiographs include subchondral sclerosis, osteophytosis, subluxation, and soft tissue swelling. Long-standing neuroarthropathy is characterized by disorganization of joints. The finding of considerable amounts of cartilaginous and osseous debris within the synovial membrane (termed detritic synovitis) should alert the pathologist that the changes may represent a neuropathic joint. Other causes of detritic synovitis include osteonecrosis, calcium pyrophosphate dihydrate crystal deposition disease, psoriatic arthritis, osteoarthritis, and osteolysis with detritic synovitis.

Frequency

United States

The overall incidence in the United States appears to be the same as that found internationally. Approximately 15% of patients with diabetes appear to have neuropathic arthropathy.

International

Neuropathic arthropathy is seen in 10-20% of patients with tabes dorsalis and in 20-25% of patients with syringomyelia.

Mortality/Morbidity

Mortality and morbidity are related to the disease process, the cause of the disease, and the related complications. Morbidity is worsened by the development of soft tissue infection and osteomyelitis.

Race

Diabetes-related neuroarthropathy appears to be more common in the Western population, whereas neuroarthropathy associated with infection, such as in tabes and leprosy, is common in developing countries. No racial predilection has been documented in steroid-induced neuropathic osteoarthropathy.

Sex

In general, no sex predilection has been recorded; however, neuroarthropathy related to connective tissue disorders, such as scleroderma, appears to be more common in females. Neuroarthropathy related to alcoholism and trauma is more common in males.

Age

Neuropathic arthropathy related to diabetes, syphilis, leprosy, and connective tissue disorders is more common in the elderly population. Neuroarthropathy related to asymbolia, spina bifida, and spinal trauma is more common in young individuals. Sensory impairment associated with spina bifida and myelomeningocele is the most frequent cause of neuropathic arthropathy in childhood.

Clinical Details

Joint changes usually precede neurologic deficit. The affected joint is usually swollen and warm but is not painful. Pain may be noted at presentation in one third of patients, but the response to deep pain and proprioception may be reduced.

Preferred Examination

Radiography may be the only imaging required. In the appropriate clinical setting, a fairly accurate diagnosis can be achieved. The roles of ultrasonography and CT are limited. Ultrasonography and CT can be helpful in identifying any local collection, and they can be used to guide aspiration cytology. The role of MRI and radionuclide scanning is to differentiate soft tissue infection from osteomyelitis.10, 11

Limitations of Techniques

Radiographic findings in the early stages may simulate osteoarthritis. Radiographs may not demonstrate findings that help in diagnosing osteomyelitis in neuropathic joints, which is a common problem.

The roles of ultrasonography and CT are limited. Ultrasonography can be used to identify any local collection when infection occurs and to guide aspiration for cytologic analysis; however, it provides no further information regarding the integrity of underlying bone. Although CT may be helpful in evaluating cortical destruction, sequestra, and intraosseous gas, these changes are not specific for neuropathic arthropathy.

The role of MRI and radionuclide scanning is to differentiate soft tissue infection from osteomyelitis. Bone marrow edema is nonspecific and has several causes; therefore, differentiating bone marrow edema from neuropathic arthropathy may not be possible on the basis of MRI findings alone. Similarly, enhanced bone activity on radionuclide scans is a nonspecific finding and may occur with several neoplastic, inflammatory, and degenerative processes.



Calcium Pyrophosphate Deposition Disease
Osteoarthritis, Primary

Other Problems to Be Considered

Osteoarthritis
Calcium pyrophosphate dihydrate crystal deposition disease
Osteonecrosis
Posttraumatic osteoarthritis
Infection
Alkaptonuria

In the early stage, neuropathic arthropathy can simulate osteoarthritis. Bone fragmentation and collapse are seen in osteonecrosis, posttraumatic osteoarthritis, intra-articular steroid injection, infection, and alkaptonuria.



Findings

  • Radiographic findings in the early stage are as follows:
    • Persistent or progressive joint effusion
    • Narrowing of the joint space
    • Soft tissue calcification
    • Minimal subluxation
    • Preservation of bone density unless infected
    • Fragmentation of eburnated subchondral bone
  • Radiographic findings in the late stage are as follows:
    • Destruction of articular surfaces
    • Subchondral sclerosis
    • Osteophytosis
    • Intra-articular loose bodies (bag of bones)
    • Subluxation
    • Lisfranc fracture/dislocation of midtarsal bones
    • Rapid bone resorption demonstrating pencil-in-a-cup deformity
  • Radiographic findings of the complications of septic arthritis are as follows:
    • Osteomyelitis
    • Bone ankylosis

Radiologic features of neuropathic arthropathy are the same irrespective of the etiology and distribution (see Images 1-8, 10-13). Distribution of joint disease varies depending on the etiology. In diabetic neuropathy, common sites of involvement are the metatarsophalangeal, tarsometatarsal, and intertarsal joints. In syringomyelia, neuropathic changes are relatively more common in the shoulder joint, followed by the elbow and wrist. The lower extremities can also be affected in syringomyelia. Changes in the spine are most characteristic in the cervical region.

The joints of the lower extremity are commonly affected in patients with tabes dorsalis. Other sites include the joints of the forefoot and midfoot and the vertebral column. The ankle and intertarsal joints are commonly involved in patients with myelomeningocele and congenital insensitivity to pain (asymbolia). The interphalangeal joints of the hands and the metatarsophalangeal joints of the feet are commonly affected in patients with leprosy. Neuropathic arthropathy associated with chronic alcoholism commonly involves the metatarsophalangeal and interphalangeal joints. The knee and ankle appear to be the predominant sites of involvement in patients with amyloidosis.

Degree of Confidence

Radiographic features found in the severe form of neuropathic arthropathy are pathognomonic, and no further imaging is necessary. Bone eburnation, fracture, subluxation, and joint disorganization can be more profound in this disorder. However, early changes may resemble osteoarthritis, and the bone collapse seen in the late stage may resemble osteonecrosis and posttraumatic osteoarthritis. Radiography is a relatively insensitive modality when used in the diagnosis of osteomyelitis.

False Positives/Negatives

Early features of neuropathic arthropathy, such as joint space narrowing, marginal osteophytosis, and subchondral sclerosis, may resemble osteoarthritis. Neuropathy-like arthropathy can be seen in patients with calcium pyrophosphate dihydrate deposition disease. Bone fragmentation and collapse are manifestations of osteonecrosis, posttraumatic osteoarthritis, intra-articular steroid arthropathy, infection, and alkaptonuria.



Findings

As with ultrasonography, CT has no significant role in the diagnosis of neuropathic arthropathy. CT may be helpful in evaluating cortical destruction, sequestra, and intraosseous gas (see Image 9).



Findings

On T1-weighted MRIs, involved joints appear diffusely swollen and demonstrate low signal intensity. The fat plane adjacent to the skin ulceration appears hypointense; when the joints are infected with a gas-producing organism, areas showing a loss of signal intensity are seen. After the intravenous administration of a gadolinium-based contrast agent, the inflammatory mass enhances and demonstrates central nonenhancing necrotic debris.

On short-tau inversion recovery (STIR) sequences, early bone infection may be evidenced by high-signal marrow edema. Later, loss of clarity of the cortical outline and cortical destruction can be identified.

Features that help differentiate spinal neuroarthropathy from disk infection include joint disorganization; facet involvement; debris; a pattern of diffuse signal intensity in the vertebral bodies; spondylolisthesis; and rim enhancement of the disk on gadolinium-enhanced MRIs.12 Features that do not help in differentiation include endplate sclerosis, erosions, osteophytes, a reduction in disk height, and paraspinal soft tissue masses.

Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have recently been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans.

As of late December 2006, the FDA had received reports of 90 such cases. Worldwide, over 200 cases have been reported, according to the FDA. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving  or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape.

Degree of Confidence

MRI plays a significant role in diagnosing complications. Findings help in assessing the extent of the disease and in determining the presence of osteomyelitis.

False Positives/Negatives

Differentiating bone changes that result from neuropathic arthropathy from those that result from infection is difficult. Bone marrow edema is a nonspecific finding that can be seen in both neuropathic arthropathy and in infection. In general, bone marrow edema found close to a skin ulceration and away from a joint suggests infection.



Findings

Ultrasonography has no role in the diagnosis of neuropathic arthropathy. Ultrasonography can be used to identify any local collection when an infection occurs, and it can be used to guide aspiration for obtaining cytologic specimens.



Findings

The role of radioisotopic studies is to detect osteomyelitis in a neuropathic joint.13 Three-phase phosphate scintigraphy has a high sensitivity (85%) but a low specificity (55%) because of bone remodeling of other causes. Studies using uptake of the gallium-67 citrate have a high false-positive rate. Scanning using indium-111–labeled leukocytes has the highest sensitivity (87%) and specificity (81%) for detecting osteomyelitis in a neuropathic foot. The role of positron emission tomography using fluorodeoxyglucose (FDG) is promising.14

One study has shown a valuable role of FDG PET in the setting of Charcot's neuroarthropathy by reliably differentiating it from osteomyelitis, both in general and when foot ulcer is present.15 In diabetic patients in the setting of concomitant foot ulcer, FDG PET accurately rules out osteomyelitis. Basu and associates estimated the sensitivity and accuracy of FDG PET in the diagnosis of Charcot's foot as 100% and 93.8%, respectively; by contrast, MRI had a sensitivity of 76.9% and an accuracy of 75%.15

Degree of Confidence

Increased uptake on radioisotope scan is seen in both neuropathic joints and in infection. Three-phase bone scan and gallium-67 scintigraphy are sensitive but not specific. Imaging using indium-111-labeled leukocytes has the highest sensitivity and specificity.

False Positives/Negatives

The incidence of false-positive results is increased because of coexisting bone remodeling.



Medical/Legal Pitfalls

  • The incidence of osteomyelitis is increased in patients with neuropathic joints, particularly in the foot. Hence, careful follow-up imaging is essential.



Media file 1:  Neuropathic arthropathy (Charcot joint). Neuropathic arthropathy of the shoulder in a patient with syringomyelia. Note the destruction of the articular surface, dislocation, and debris, which are pathognomonic for a neuropathic joint.
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Media type:  X-RAY

Media file 2:  Neuropathic arthropathy (Charcot joint). Neuropathic arthropathy in a patient with syringomyelia. Anteroposterior view of the elbow demonstrates resorption of the bone with opaque subchondral bone.
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Media type:  X-RAY

Media file 3:  Neuropathic arthropathy (Charcot joint). Lateral view of the elbow shows disorganization of the joint (same patient as in Image 2).
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Media type:  X-RAY

Media file 4:  Neuropathic arthropathy (Charcot joint). Gross disorganization of the hip joints in a patient with tabes dorsalis.
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Media type:  X-RAY

Media file 5:  Neuropathic arthropathy (Charcot joint). Charcot joint in a patient with tabes dorsalis who has dislocation, osseous fragmentation, and sclerosis. The opacities projected over the iliac blades represent intramuscular bismuth-containing injections.
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Media type:  X-RAY

Media file 6:  Neuropathic arthropathy (Charcot joint). Fragmentation and collapse of the chondral and osseous structures of both knee joints in a patient with tabes dorsalis.
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Media type:  X-RAY

Media file 7:  Neuropathic arthropathy (Charcot joint). Anteroposterior view of the foot in a patient with diabetes and neuropathic arthropathy. Note the fragmentation, collapse, and sclerosis of the intertarsal joints.
Click to see larger pictureClick to see detailView Full Size Image
Media type:  X-RAY

Media file 8:  Neuropathic arthropathy (Charcot joint). Oblique view of the foot in a patient with diabetes and neuropathic arthropathy shows destruction of the articular surface of the intertarsal joints with subchondral sclerosis (same patient as in Image 7).
Click to see larger pictureClick to see detailView Full Size Image
Media type:  X-RAY

Media file 9:  Neuropathic arthropathy (Charcot joint). CT scan of the ankle in a patient with neuropathic arthropathy. Note the destruction of the articular surface, disorganization of the joint, and fragmentation.
Click to see larger pictureClick to see detailView Full Size Image
Media type:  CT

Media file 10:  Neuropathic arthropathy (Charcot joint). Anteroposterior and oblique views of a neuropathic foot in a patient with leprosy. Note the predominant involvement of the metatarsophalangeal and interphalangeal joints with severe periostitis.
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Media type:  X-RAY

Media file 11:  Neuropathic arthropathy (Charcot joint). Neuropathic arthropathy in a patient with diabetes mellitus. Note the lateral disruption of the base of the metatarsal in relation to the tarsals, representing a Lisfranc fracture/dislocation. Note the soft tissue gas and osteomyelitis of the second and third metatarsal heads.
Click to see larger pictureClick to see detailView Full Size Image
Media type:  X-RAY

Media file 12:  Neuropathic arthropathy (Charcot joint). Lisfranc fracture/dislocation in a patient with diabetes and neuropathic arthropathy. Note the soft tissue swelling, fragmentation, sclerosis, and periostitis.
Click to see larger pictureClick to see detailView Full Size Image
Media type:  X-RAY

Media file 13:  Neuropathic arthropathy (Charcot joint). Osteolysis of the distal metatarsals and phalanges with tapering results in a pencil-like appearance in the late stage of diabetic neuropathy.
Click to see larger pictureClick to see detailView Full Size Image
Media type:  X-RAY



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Neuropathic Arthropathy (Charcot Joint) excerpt

Article Last Updated: May 27, 2008