Neurotrophic Arthritis

Published on 11/04/2015 by admin

Filed under Orthopaedics

Last modified 22/04/2025

Print this page

This article have been viewed 3314 times

CHAPTER 79 Neurotrophic Arthritis

J. Clarke Stevens

INTRODUCTION

As noted in prior editions of this book, little has occurred in recent years to change the fact that neurotrophic arthritis of the elbow is distinctly unusual, and poorly understood and treated. Although a large number of causes of neurotrophic arthritis are recognized (Box 79-1), diagnosis is made simpler by the fact that only five or six of these causes affect the upper extremity joints, and only three occur with any frequency at all. In fact, a Medline literature search has revealed that only two case reports have appeared in the literature since 1996.^48,^69,⁷³ In this section, the causes and pathogenesis of neurogenic arthropathy of the elbow are discussed, along with laboratory investigations and differential diagnosis. Arthropathy of lower limb joints and the spine will not be considered, but references cited in Box 79-1 are provided to direct the interested reader to other sources of information. A recent excellent review of the subject is available.⁵⁶

BOX 79-1 Etiology of Neurogenic Arthropathy

I. Brain

A. Congenital indifference (asymbolia) to pain ^29,^50,⁵⁸

B. “Stoic” individual ³⁷

C. Functional abnormality of enkephalins, endorphins, or opiate receptors?²⁴

IV. Corticosteroids–Charcot-like neuropathy ^2,^13,^25,⁶³

PATHOGENESIS

Debate about the pathogenesis of neurotrophic arthritis began with Charcot’s paper in 1868,¹⁴ and today our understanding of the pathophysiology remains incomplete. Charcot, observing the posterior column demyelination of tabes dorsalis, suggested the loss of a trophic function protecting joints as a pathophysiologic mechanism. This view was soon challenged by those who believed that the disorder resulted from trauma. A major advance in our understanding followed the often-quoted work of Eloesser,²⁶ who sectioned the posterior roots of the hindlimb of cats. Deafferentation combined with thermocautery of the joint cartilage led to the rapid development of neurogenic arthropathy, bone fractures, and dislocations, emphasizing the role of insensitivity and trauma. The results of chemical analysis and tests of bone strength and elasticity were normal–evidence against Charcot’s view that the joints and bones wasted from an abnormality of trophic nerves. The roles of insensitivity, activity, and trauma were further emphasized by Corbin and Hinsey,¹⁹ who found that cats with loss of sensation developed a Charcot joint only if they were allowed to roam freely in the cage, whereas those kept in a restricted space did not. These researchers were impressed by the importance of proprioceptive loss, which allowed an abnormal range of joint movement. It is also recognized that limbs rendered immobile by spasticity rarely develop an arthropathy. An important observation of Harris and Brand³⁶ was that joint breakdown in the neuropathy of leprosy can be minimized or prevented by proper protection. Johnson³⁷ emphasized the importance of unrecognized and untreated fractures, especially stress fractures, in the development of neurogenic arthropathy.

LOSS OF NOCICEPTION

The most widely held view on the pathogenesis of Charcot joints, then, involves a loss of protective joint nociception and position sense that subjects the joint to repeated trauma that is not recognized by the affected individual. The neurologically normal patient with an injured joint presents quickly with development of pain and loss of function, leading to immobilization and the search for appropriate medical treatment. In the neurologically impaired person, on the other hand, unrecognized injury is untreated and leads to a vicious circle of compounding injuries. This explanation is intuitively reasonable, particularly in the presence of severe superficial and deep loss of pain perception. It is more difficult to invoke when joint destruction evolves, but sensory loss is minimal or difficult to demonstrate. For example, the author has studied patients with subclinical inherited neuropathy with severe neurotrophic arthropathy of various joints and recurring fractures who had no sensory symptoms or findings on clinical examination.²⁴ Even with sophisticated tests, including computer-assisted sensory examination, periosteal nociception, and morphometric and graded teased fiber evaluation of cutaneous nerves, only a mild neuropathic abnormality was found. Methods of measuring joint capsule and articular bone pain perception are not available; however, cortical bone is known to contain both unmyelinated and myelinated fibers, and presumably some of these subserve nociception.¹⁸ Joint capsules, particularly in their external layers, contain several types of formed corpuscles and naked nerve endings. Synovium has not been observed to contain nerve endings. Although pain sense is carried by both small myelinated and unmyelinated fibers, the relative importance of these two systems in normal protective joint sensation is unknown. In those puzzling patients in whom sensation appears to be normal, a new method of measuring joint pain perception or afferent nerve fiber activity is needed.

NEUROVASCULAR THEORY

With this said, there are a number of situations in which the neurotraumatic hypothesis seems inadequate for explaining joint destruction entirely, even in the neurologically impaired person, and the additional factor of a trophic vascular mechanism becomes attractive. The neurovascular theory suggests that neurologic disease triggers increased bone blood flow and active bone resorption by osteoclasts, and that fractures and joint damage follow. The arguments in favor of the hypothesis are enumerated below.

First, a proportion of patients with Charcot joints are said to have no neurologic disease when joint destruction develops, making it difficult to blame joint insensitivity. Second, there are instances in which neurotrophic joints develop in bedridden patients in whom weight bearing is impossible and repeated severe joint trauma unlikely. Third, a few patients suffer joint destruction and resorption of articular structures in a matter of weeks to a few months, making pure mechanical destruction hard to accept as the sole mechanism.¹⁸ Fourth, some neurotrophic arthropathies are associated with long bone fractures that seemingly occur spontaneously or without unusual trauma. Although histologic examination is reported to show pathologically increased vascularity, it is also a fact that acutely damaged joints become hot and swollen from increased blood flow and exudation as part of the body’s normal repair process, making pathologic vascularity difficult to prove. Hindlimb sympathectomy might be expected to increase blood flow; however, in experimental animals, at least, it does not lead to joint damage or abnormalities in the chemical composition of bone.¹⁹ It is still possible, however, that local hyperemia is exaggerated in some patients, leading to rapid bony softening and resorption, and it is not possible to discard this hypothesis out of hand (Fig. 79-1).

FIGURE 79-1 Gross resorption destruction of the elbow joint due to rheumatoid arthritis, although no hypertrophic changes are present as in the typical neurotrophic joint. This seems to represent an example of hyperemic arthropathy, one of the etiologic considerations of neurotrophic joints.

INFECTION

Although infection may coexist but cannot be offered as a cause of this problem, tuberculosis of the elbow, on the other hand, can cause resorptive and destructive changes similar to those in a neurotrophic joint (Fig. 79-2).

FIGURE 79-2 Gross destruction of an elbow joint involved with tuberculous arthritis. Note that both sides of the joint are involved. A distinction between this entity and a neurotrophic arthropathy in the early stages is complicated by the possibility that the two conditions coexist.⁴⁷

(Courtesy of Dr. Richard Marks, Cape Town, South Africa.)

ENVIRONMENT

Environmental factors can adversely add to the effect of nociceptive loss in a number of ways. Neurotrophic arthropathy is more common in weightbearing joints and in joints in men, perhaps because men often have occupations involving manual labor and physical activity. Additional factors include the presence of mental retardation, psychosis, the metabolic effect of diabetes, and rheumatoid arthritis or metabolic bone disease. The so-called stoic personality, while admitting pain, seems to be able to ignore it and continue to walk and work unimpeded. There are also those who, although experiencing considerable pain, may cling to a job out of economic necessity despite deforming arthritis.

As is being more commonly recognized today, intra-articular administration of local anesthetic is associated with chondrocyte cell death.^15,³³ For some, it is occasionally followed by rapid joint disintegration. Patients reported with this complication have not had any neurologic disease, and therefore, the joint destruction cannot be called a neurotrophic arthropathy. The interplay of multiple factors in the genesis of bone and joint complications is emphasized in Figure 79-3.

FIGURE 79-3 Schematic representation of the interrelationship between the etiology and pathophysiology of neurotrophic arthropathy.²⁴

CONDITIONS CAUSING NEUROTROPHIC ARTHROPATHY OF THE ELBOW

SYRINGOMYELIA

In contrast to tabes dorsalis, 80% of the joints involved in syringomyelia are in the upper extremities.³⁰ It is estimated that approximately 25% of these affected joints will develop joint breakdown. Neuropathic disease involves the shoulder most commonly, followed by the elbow and wrist. Degenerative changes in the cervical spine are not uncommon. The process evolves gradually with paresthesias of the hands, followed by progressive weakness and wasting of the small hand muscles and then atrophy of arm and shoulder muscles. Loss of pain and temperature sense affects the arms and upperthoracic segments, often in a cape distribution. As the syrinx enlarges, long tract signs appear, and a Horner syndrome is noted. The Arnold-Chiari malformation is commonly associated and is related to the development of syringomyelia.

Post-traumatic syringohydromyelia presenting as a neuropathic arthropathy of the elbow and of the shoulder has been reported.⁵¹ Morrey has seen one additional instance of an acquired neurotrophic elbow joint after injury to the cervical spine (Fig. 79-4). The mechan-ism is also presumably that of a traumatic syringohydromyelia.

FIGURE 79-4 A brachial plexus injury occurred in a 47-year-old man in 1986. Five years later, instability and effusion were noted in the ipsilateral elbow (A). Rapid destruction occurred in the next 3 months (B).

Electromyography and somatosensory evoked potentials can indicate the presence of a spinal cord lesion and the need for an imaging study.⁷⁰ Radiographic examination of the cervical spine may show widening of the spinal canal, but the diagnostic procedure of choice is magnetic resonance imaging, which demonstrates both the syrinx and any associated malformation.⁴¹ Computed tomography with metrizamide contrast enhancement of the cerebrospinal fluid may also demonstrate spinal cord enlargement and cavitations in some instances.

Elbow arthropathy may follow neurologic symptoms but is sometimes a presenting complaint.⁴ A history of trauma is usually lacking. Joint swelling due to effusion may be marked, and pain is experienced in some cases. Atrophic changes in the bone, particularly of the shoulder, are more common than in tabes dorsalis.⁶⁷ Although extremely rapid destruction of the shoulder may occur with resorption of the humeral head, the elbow seems less likely to be affected in this fashion.^51,⁶⁸

The radiograph of the elbow shows resorption of bone ends and often of the entire joint (Fig. 79-5). Reparative callus is evident, along with gross deformity and instability. The youngest patient documented with elbow involvement was recently reported related to a myelomeningocele.⁷³

FIGURE 79-5 Gross destruction of an elbow joint in a patient with syringomyelia.

DIABETES MELLITUS

Today the rate of diabetes mellitus as the leading cause of neurotrophic arthropathy in the lower extremity is well recognized. The arthropathy usually develops in diabetics who have had the disease for some time and who have suffered the additional complication of a symmetrical sensorimotor polyneuropathy. In diabetic “pseudotabes,” severe sensory and autonomic impairment leads to an ataxic gait, pupillary abnormalities, neurogenic bladder, and lightning pains reminiscent of tabes dorsalis. Diabetic arthropathy affects primarily the joints of the feet, with less frequent involvement of the ankles and knees.^6,^17,^46,^52,⁵⁹ The distal predominance of the arthropathy is in keeping with the stocking pattern of sensory loss, which is maximal in the feet. Bony abnormalities in the upper extremities of diabetics are uncommon, but involvement of the shoulder, elbow, and wrist has been recorded.²⁸ Campbell and Feldman¹¹ presented a radiograph of the elbow in a 59-year-old patient that showed marked disorganization of the joint with destruction of the articular surfaces, numerous bone fragments, and periosteal new bone formation typical of a Charcot joint.

TABES DORSALIS

Although syphilis used to be responsible for up to 90% of neurotrophic joints, tabes dorsalis is now a rare disease. Approximately 10% of all tabetics are said to develop a Charcot joint, the majority occurring between the ages of 40 and 60 years, approximately 20 years or more after the primary infection. In approximately 78% of cases, the lower limbs are affected,³⁰ with the knee most frequently involved. In the upper limbs, the shoulder, elbow, hands, and wrists are affected.^3,^20,^61,^66,⁶⁹ Polyarticular involvement occurs in up to 40%. Clinical features include the presence of lightning pains, neurogenicbladder disturbances, optic neuritis, and visceral crises. Most patients have pupillary abnormalities, and loss of pupillary reflexes to light (Argyll Robertson pupils) occurs in up to 62%. Vibration and position senses are reduced, and deep pain sensation may be absent. Pain perception may be delayed. Although the Venereal Disease Research Laboratory (VDRL) test may be negative, rapid plasma reagin (RPR) and fluorescent treponemal antibody absorption (FTA-ABS) test results are usually positive. Elbow movement may be restricted, or the elbow may be subluxed and hypermobile with marked instability (Fig. 79-6). Spontaneous fractures can occur. Radiographic examination may show extensive destruction of the bone ends, disintegration of the joint, abundant periosteal callus formation, valgus deformity, and free bodies in the articulation.

FIGURE 79-6 The deformity associated with this Charcot joint from tabes dorsalis is obvious by inspection, and the joint is grossly unstable.

(From Beetham, W. P., Kaye, R. L., and Polley, H. F.: Charcot’s joints. Ann. Intern. Med. 58:1002, 1963.)

CONGENITAL INDIFFERENCE AND INSENSITIVITY TO PAIN

The concept of indifference to pain implies that these patients perceive pain stimuli in a normal fashion but fail to react in the usual defensive manner, a kind of asymbolia for pain, whereas insensitivity denotes an inability to receive a painful stimulus because of a neurologic deficit. Most patients with the former disorder have not had detailed electrophysiologic, biomechanical, and pathologic examinations, and it is likely that previously reported patients have had a congenital sensory and autonomic neuropathy of type IV or V.²³ Nevertheless, occasionally patients in this group may develop a neurotrophic arthropathy or fracture that may affect the elbow.^29,^44,⁵⁸ Involvement of the elbow in Charcot-Marie-Tooth disease has also been recorded.⁸

HEREDITARY SENSORY AND AUTONOMIC NEUROPATHY TYPE II

Hereditary sensory and autonomic neuropathy type II has not been reported as a cause of neurogenic arthropathy of the elbow. The author has evaluated a remarkable patient with this disorder, who had severe acral mutilation.

Case Report

The patient was a 34-year-old white woman referred by the editor for evaluation of a left elbow effusion and flail joint. At age 2 years, she was found to have a peripheral neuropathy, and her first operation was for a bump on the foot. This was followed by approximately 100 operations on the distal extremities for nonhealing ulcers and infections. At age 18, her right leg was amputated below the knee. At about this time, she had an infection of the left foot. Eventually, a left above-knee amputation was performed when the patient was 34 years old. Beginning at age 12, she began to lose fingers to sepsis and she required distal and middle interphalangeal amputations of the hand.

Left elbow symptoms began 6 months before evaluation, when she had surgery for an olecranon bursitis and removal of loose bone fragments. This was followed by an infection that required hospitalization for 3 months.

She stated that she could feel temperature and deep pain, but was unable to appreciate textures. The hands felt swollen and ached. There was no history of diabetes or other family members with a peripheral neuropathy. The patient had an unaffected 6-year-old son.

She ambulated with a wheelchair and easily scooted along the floor and examining table or bed using her arms. The left elbow was swollen and flail. The upper forearm had migrated proximally and posteriorly in reference to the distal humerus. There were right below-knee and left above-knee amputations. On the right, there was an open draining wound of the patella and distal stump. Muscle strength was normal, but the upper extremity reflexes were absent.

Nerve conduction studies showed no response with stimulation of the superficial radial nerves bilaterally, median sensory fibers, and the lateral antebrachial cutaneous nerve. Median and radial motor nerve conduction studies were normal. The needle electrode examination showed large motor units and reduced recruitment in the abductor pollicis brevis and first dorsal interosseous muscles. The patient did not feel pain during the needle examination of the thenar muscle. These findings were consistent with a severe axonal sensorimotor peripheral neuropathy with more prominent involvement of sensory than motor fibers.

Radiographs showed medial subluxation of the left ulna and radius, with marked destructive joint changes and osseous debris in the periarticular soft tissues (Fig. 79-7). There was marked soft tissue swelling about the elbow, especially in the region of the olecranon bursa. The findings were consistent with a neuropathic joint. Efforts to stabilize the joint failed.

FIGURE 79-7 A, Gross destruction as described in the case report. B, An effort to restore function by arthroplasty was completely unsuccessful after two procedures.

Commercial testing to define genetic abnormality is now available for many varieties of inherited neuropathy.^40a

SURGICAL DENERVATION

In recent years, there is evidence that aggressive surgical release of contracted elbow joints that causes marked stripping of the bone may cause severance of joint innervation. Two of Morrey’s patients have developed destructive resorption of the elbow after fascial arthroplasty following an aggressive surgical release of the soft tissue around the joint (Fig. 79-8).⁴⁵ Several years later, one was diagnosed with congenital indifference to pain. The other appears to have occurred possibly from the aggressive soft tissue release.

FIGURE 79-8 Traumatic arthritis of the right elbow in a 33-year-old man (A). Interposition arthroplasty was performed (B), and the joint developed aseptic resorption in less than 18 months (C).

MISCELLANEOUS

A case of idiopathic arthropathy of the elbow was reported by Meyn and Yablon ⁴³ in 1973; however, syringomyelia was not excluded because the patient refused myelography. A second example of “idiopathic” arthropathy of the elbow may also have been syringomyelia.⁵ In a poorly studied patient reported by Karten³⁸ with the CRST^* variant of systemic sclerosis and multiple neuropathic joints including the elbows, hysterical indifference to pain was suggested to be a major factor. This seems an unlikely explanation, however, because muscle weakness and atrophy and absence of deep pain were present. Another unusual patient, described by Alajouanine and Boudin,¹ had elbow arthropathy associated with distal muscular atrophy, subcutaneous and vascular calcification, and abnormal calcium and phosphorus metabolism. There were no sensory changes, and the cause of the arthropathy is obscure.

INVESTIGATION AND DIAGNOSIS

The examination of a patient with a neurotrophic arthropathy of the elbow should focus on a search for evidence of syringomyelia, diabetes, and tabes dorsalis because almost all patients will be found to harbor one of these disorders. When physical signs of these diseases are lacking, the patient should be examined carefully for evidence of pes cavus, hammer toes, enlargement of peripheral nerves, and distal sensory loss, which may suggest the presence of a peripheral neuropathy. A dissociated sensory loss is found in syringomyelia but may also be present in amyloid neuropathy, familial dysautonomia, hereditary sensory and autonomic neuropathy type II, and Tangier disease. Evidence of an autonomic neuropathy is important because small myelinated and unmyelinated pain afferents that provide joint nociception are often involved as well. Loss of sweating, orthostatic hypotension, urinary incontinence, and impotence are the most important symptoms of the autonomic dysfunction seen in a variety of small fiber neuropathies. Other neuropathies may have a more generalized sensory disturbance that affects both large and small fibers. A profound loss of pain sense, however, is not a necessary prerequisite for the development of neurogenic arthropathy, and the patient’s complaint of pain and the presence of normal or nearly normal nociception should not deter further investigation. It is often helpful to interview and examine family members, even when no apparent disease is known to kin. This is particularly necessary in patients with a peripheral neuropathy or only slight neurologic abnormalities, in whom the hereditary nature of the disorder may become evident only after intensive investigation of relatives. The clinician should also look for wasting of small hand muscles and ulnar sensory loss because the nerve may be compromised behind the medial epicondyle by the deformity associated with the Charcot joint.

Laboratory investigations that my colleagues and I have found useful in the investigation of neurogenic arthropathy, in addition to “routine tests,” are listed in Box 79-2. We have found the computer-assisted sensory examination and electromyography and nerve conduction studies helpful in detecting disease in minimally affected patients and family members. In a few patients, nerve biopsy, including teased fiber preparations, quantitative morphometry, electron microscopy, histochemistry, analysis of myelin lipids, the in vitro nerve action potential, and studies of axonal transport may be needed for complete evaluation of the specimen. The differential diagnosis of neurogenic arthropathy is listed in Box 79-3.