Neuropathic arthropathy of the shoulder: Two cases of syringomyelia with cocaine use

doi:10.4236/ojim.2012.21006

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Open Journal of Internal Medicine, 2012, 2, 27-30 OJIM

http://dx.doi.org/10.4236/ojim.2012.21006 Published Online March 2012 (http://www.SciRP.org/journal/ojim/)

Neuropathic arthropathy of the should er: Tw o cas es of

syringomyelia with cocaine use

Jerry A. Rubano, Suleman Bhana, Dodji Modjinou, Colette R. J. Pameijer, Heidi Roppelt

Divisions of Surgical Oncology/Upper Gastrointestinal Surgery and Rheumatology, Stony Brook University Hospital, New York, USA

Email: [email protected]

Received 3 August 2011; revised 6 December 2011; accepted 29 January 2012

ABSTRACT

Neuropathic arthropathy (NA) is a progressive, de-

generative disorder associated with decreased sensory

innervation of the involved joints. The shoulder joint

is an uncommon presentation for NA, although sy-

ringomyelia is the most common cause for this joint.

Two cases are presented of NA of the shoulder, with

both patients having a history of syringomyelia and

cocaine use. In both cases a work up for malignancy

was negative, but imaging was consistent with NA.

Although syringomyelia has been linked with this

presentation in prior publications, the role of co-

caine use may not be incidental, with complex bio-

chemical interactions in bone metabolism. Cocaine

has been shown to involve the Leptin, Neuromedin U

(NmU), Cocaine and amphetamine-regulated tran-

script (CART), and Receptor activator of nuclear

factor kappa-B ligand (RANKL) pathways of bone

remodeling. Treatment can be challenging, involving

concurrent use of pharmacotherapy, surgical correc-

tion, and protective br acing.

Keywords: Neuropathic Arthropathy; Charco t;

Syringomyelia; Cocaine; RANKL

1. INTRODUCTION

Neuropathic arthropathy (NA), also known as Charcot

Joint, is a progressive, degenerative disord er that is asso-

ciated with decreased sensory innervation of the involved

joints. Charcot Joint is most commonly associated with

diabetes mellitus (DM), syringomyelia, and tabes dor-

salis. In patients presenting with shoulder involvement,

syringomyelia is the most common association [1].

Herein we present two cases of advanced Charcot Joint

and their associated radiologic findings.

2. CASE REPORT 1

A 44 year old male patient, with history of cocaine use,

was admitted through our Emergency Department with a

complaint of right shoulder swelling and pain. He de-

scribed an acute change in the right shoulder, moderate

shoulder pain and paresthesias of the right hand. His

symptoms progressed over one week’s time, prompting

his visit to the Emergency Room. His past medical his-

tory is significant for T3-11 syrinx, myxopapillary epen-

dymoma resection, and multiple neurosurgical proce-

dures. He was dependent on crutches for ambulation.

On examination, there was noted to be deformity of

the right shoulder and bicep with significant swelling,

and limited abduction and extension of the right shoulder.

Sensation was diminished as compared to the left.

Strength was graded as 4/5 for the shoulder joint as well

as for grip. Right upper extremity reflexes could not be

elicited. Joint position was preserved.

There was significant sclerosis of the right humeral

head with soft tissue swelling noted on radiographs of

the right shoulder. CT revealed right humeral sclerosis,

with several heterogeneous masses extending over the

region of the pectoralis, with the largest mass noted in

the right bicep. MRI revealed fractures of the proximal

humerus with erosion of the glenoid, as well as fracture

of the coracoid process. There were significant inflam-

matory changes with soft tissue swelling. All images,

therefore, were compatible with some destructive lesion

involving the humeral head, with associated pathologic

fractures with s i gni f i cant fluid c ol l e ct i on.

A CT-guided biopsy was obtained, which was non-

diagnostic. The patient was therefore brought to the op-

erating room for open biopsy, with multiple specimens

obtained. Pathology revealed no evidence of malignancy.

3. CASE REPORT 2

A 55 year old female patient, also with a history of co-

caine, presented to our Emergency Department with a

complaint of chest pain as well as right shoulder pain.

She was admitted to evaluate acute coronary syndrome

(ACS). Her past medical history is significant for uncon-

trolled DM, Hepatitis C, sickle cell trait, asthma, pan-

creatitis and chronic pain, with a history of a right hu-

OPEN ACCESS

J. A. Rubano et al. / Open Journal of Internal Medicine 2 (2012) 27-30

meral bony lesion, that was biopsied several years earlier

at another hospital. Once ACS was ruled out, the patient

began to focus her complaints more on her right shoulder

pain. The patient denies any history of trau ma to the right

upper extremity. Review of her hospital records revealed

some evidence of bony destruction of the right humerus

from ten years earlier.

On examination, the patient was noted to have an ob-

vious deformity of her right upper extremity, with an

apparent area of swelling extending from approximately

the right shoulder to the distal asp ect of the right deltoid.

Range of motion was grossly limited, especially involv-

ing abduction, and extension. She also had grossly di-

minished strength to 3/5 for both flexion and extension.

Sensation was grossly diminished when compared to the

left.

Chest x-ray showed destruction of the right humeral

head and anterior glenoid. CT revealed an expansile right

axillary soft tissue mass with adjacent bony destruction,

most consistent with a neoplasm. The prior biopsy report

was obtained, and demonstrated a low grade spindle cell

neoplasm most consistent with a low grade neoplasm of

the bone. Given this history, her physical exam and ra-

diographic findings, it was arranged for an open bone

biopsy. Destruction of the osseous structures and joint

was obvious. Multiple samples were sent to pathology,

with no evidence of malignancy.

Based upon the pathologic results, as well as the

clinical picture of the patient, it was determined she was

likely suffering from neuropathic arthropathy. An MRI of

the cervical spine was obtained, which revealed a syrinx

extending from approximately C1 throu gh T2, with glio-

sis at the C2-3 level.

4. DISCUSSION

4.1. Background/History

Neuropathic arthropathy (NA), also known as Charcot

Joint, is associated with d ecreased sensory innervation of

the involved joints. Although Mitchell was the first to

describe this entity in 1 831, Charcot brought attention to

the disorder in 1868 [2].

4.2. Theories of Pathogenesis

Both Charcot and Mitch ell speculated th at the changes in

the involved joint were secondary to damage in the tro-

phic centers of the central nervous system (CNS), later

known as the French Theory. Shortly thereafter, the

German theory, proposed by both Volkmann and Vir-

chow contend ed that NA was the result of multiple years

of repeated, insensible trauma results in total joint de-

struction [2]. This theory has limitations , as NA is known

to develop in bedridden patients, with no history of

trauma. In addition, the neurotraumatic theory proposes

that when the CNS is damaged, the joint exceeds the safe

limits of normal range of motion due to decreased pro-

prioception, resulting in the aforementioned repeated

microtrauma, similar to the German theory, and ulti-

mately total joint destruction [2]. The neurovascular the-

ory holds that CNS damage results in a loss of vascular

reflex, which produces locally increased blood flow, with

bone resorption due to increased osteoclast activity. Al-

though not perfor med in the two cases above, this can be

correlated with increased uptake in nuclear bone scans

and angiography demonstrating hypervascularity of the

joint [2].

4.3. Clinical Features

NA has been reported to occur with a variety of diseases

including: diabetes, tabes dorsalis, leprosy, syringomye-

lia, poliomyelitis, rheumatoid arthritis, multiple sclero sis,

congenital neuropathy, traumatic injury, iatrogenic

causes, and tertiary syphilis [3]. Both upper motor neu-

ron (UMN) and lower motor neuron (LMN) lesions can

potentiate sensory impairment an d lead to NA [1].

The majority of cases of NA are seen in patients with

underlying DM, usually accompanying peripheral neu-

ropathy [4], and a painless monoarthritis. Currently,

prevalence of NA is estimated to range from 0.08% in

the general diabetic population to 13% in high-risk dia-

betic patients [4]. The development of arthropathy in this

subset of patients with diabetes is likely multifactorial

with a complex interaction between mechanical and vas-

cular factors, vasomotor changes, and cytokine related

changes to osteoclastic activity [5].

As demonstrated by both of our patients, NA can also

be associated with syringomyelia [1,6], of which 20% to

25% of patients with syringomyelia developing NA, with

a predilection for upper extremity joints [3]. An uncom-

mon process, syringomyelia is characterized by a longi-

tudinal cavitatio n of the spinal cord, leading to the loss of

pain and sensory innervation of the involved joint, pre-

disposing the patient to the development of NA. The

involvement of a single join t helps categorize this arthri-

tis in the group of monoarthropathies. The clinician

should keep in mind that the differential diagnosis for a

monoarthopathy is diverse, and appropriate history and

examination is needed to distinguish (see Table 1).

4.4. Role of Cocaine

Of interest both patients reported in this series had a his-

tory of cocaine use. Whether cocaine use has contributed

to the unusual findings in these two cases is unclear. It

has been well documented that cocaine use can cause

clinically significant vasospasm and ischemia [7]. It may

be possible that a similar vaso-occulusive process can

J. A. Rubano et al. / Open Journal of Internal Medicine 2 (2012) 27-30 29

Table 1. The differential diagnosis of acute monoarthropathies.

Adapted from Kelley’s Textbook of Rheumatology 8th ed. 2008 [3]

 Acute Monoarthritis:

o Infectious Arthritis

o Crystal-induced Arthritis

 Other Causes of Acute Monoarthritis:

o Patients without Syste mic Manifestations:

 Juvenile Idopathic Arthritis

 Rheumatoid Arthritis

 SeronegativeSpondyloarthropathies

 Neuropathic Arthropathy

 Hemarthroses

 Lyme Arthritis

o Patients with Signs of Systemic Illness:

 Enteropathic Arthritis

 Systemic Autoimmune Disease

potentiate neurovascular derangement, changes to blood

flow, and eventual increased local osteoclast activity. In

addition, cocaine’s role as a neuropeptide, particularly in

the regulation of Neuromedin U (NmU) may contribute

to NA [8].

NmU is a is a neuropeptide found in the brain of hu-

mans and other mammals, with a number of diverse

functions including bone growth and hormone release [1].

Recombinant NmU receptors have been found to in-

crease the internal calcium concentration [9]. Previous

work has shown that neuronal control of bone remodel-

ing is mediated by leptin, and that leptin inhibits bone

formation [10]. Like leptin, NmU is an anorexigenic

neuropeptide that acts downstream and independently of

leptin to regulate bone formation [10]. NmU-deficient

(Nnm-/-) mice have high bone mass owing to an increase

in bone formation (both trabecular and cortical bone)

compared to Wild-Type (WT) mice [10,11].

NmU has been shown to modulate bone remodeling

through a mechanism known as the molecular clock. In

the hypothalamus, NmU stimulates the sympathetic ner-

vous system, leading to an ti-osteogen ic activities without

affecting bone resorption [10]. Sympathetic signaling in

osteoblasts is gated by transcriptional factors referred to

as the molecular clock (MC) [11]. MC genes are media-

tors of the inhibition of bone formation by leptin. These

genes contribute to daily variation in bone marrow pro-

liferation. Taken together, NmU, acting through the CNS

affects the negative regulator of bone remodeling via

leptin, that is, the MC in bon e. One can infer th at cocain e,

therefore, as a sympathomimetic agent acting via NmU

and through the CNS, can affect the MC in bone remod-

eling. In addition to bone formation, sympathetic signal-

ing also regulates bone resorption. For example, Isopro-

terenol, a surrogate of sympathetic signaling, increases

expression of Receptor activator of nuclear factor kappa-

B ligand (RANKL) in osteoblasts, which results in the

activation of osteoclastogenesis [11].

Besides NmU, leptin is reported to interact with other

various hypothalamic neuropeptides, such as cocaine and

amphetamine-regulated transcript (CART) and neu-

ropeptide Y, all of which may modulate the effects of

leptin on bone [11]. CART is a central mediator of

leptin’s action on bone resorption, and CART’s expres-

sion is increased in NmU-/- mice as compared to WT,

suggesting a protective activity of CART on bone resorp-

tion [10]. Thus, through CART, leptin leads to inhibition

of bone resorption by decreased RANKL expression.

Indeed, mice lacking CART have low bone mass due to

an increase in bone resorption stimulated by RANKL

[11].

It is difficult to say that cocaine was primarily respon-

sible for the NA observed in the above cases, as co-

caine’s biochemical affect on the NmU-CART pathway

is paradoxical. NmU stimulates sympathetic outflow and

ultimately leads to decreased bone mass while CART,

conversely, leads to sparing of bone mass. Furthermore,

recent work shows that Leptin has a dose dependent ef-

fect: initial increases in leptin stimulate bone formation,

however higher levels result in inhibition of bon e forma-

tion [11]. Despite the complexity of this pathway, one

can say that cocaine use leads to dynamic effects on bone

remodeling.

4.5. Treatment of NA

The aim of NA treatment is to treat the underlying dis-

ease and decrease the rate of deformity to the lowest

level [1]. It entails early diagnosis, proper management,

and includes reducing further articular damage by pre-

vention of repetitive trauma when it has a traumatic/

physical etiology [12]. When present, the aspiration of

large effusions and splinting will prevent further liga-

mentous laxity. When there is synovial inflammation,

nonsteroidal anti-inflammatory drugs can be used [1].

Other therapeutic and conservative options include func-

tional orthosis, physical therapy, and bisphosphonates,

which have been found to be quite beneficial in reducing

disease activity and bone turnover [12]. However, when

these options prove not to be successful, procedural and

surgical interventions should be considered. Surgical

procedures require careful patient selection [12]. Surgical

treatment options include: prosthetic replacement, resec-

tion arthroplasty or arthrodesis [1]. Surgical treatment

options are not withou t risks due to the lack of protective

pain sensation and reflexes, the presence of osteopenic

J. A. Rubano et al. / Open Journal of Internal Medicine 2 (2012) 27-30

[3] Weissman, B.N. and Firestein (2008) Kelley’s textbook

of rheumatology. 8th Edition, W. B. Saunders Company,

New York.

bone, and the weakness of the surrounding ligamentous

and muscular tissues. The high stresses put on the im-

planted components leads to a high failure rate, in p art by

septic loosening and periprosthetic fractures [12]. De-

spite the occasional good result after surgical treatment, a

non-operative treatment with the use of braces is proba-

bly the best solution for long-term management of these

cases.

[4] Frykberg, R.G. and Belczyk, R. (2008). Epidemiology of

the charcot foot. Clinics in Podiatric Medicine and Sur-

gery, 25, 17-28. doi:10.1016/j.cpm.2007.10.001

[5] Hatzis, N. and Karr, K. (1998) Neuropathic arthropathy

of the shoulder. Journal of Bone and Joint Surgery, 80,

1314-1319.

[6] Lange, R. and Cigorra, R. (1989). Cocaine-induced coro-

nary-artery vasoconstriction. The New England Journal

of Medici ne, 321, 1557-1562.

doi:10.1056/NEJM198912073212301

5. CONCLUSION

Charcot Joint can pr esent a confusing clinical picture for

the physician. It can often present with the sudden onset

of pain in the in volved joint without trauma. Th e clinical

picture can be confusing for malignancy as well, as there

is often concern for a lytic process. Although DM is the

most common cause of NA, in cases of upper extremity

NA it is imperative to screen for the presence of syrin-

gomyelia. Other patient factors, such as cocaine use,

through complex biochemical mechanisms on bone

physiology, may potentiate the development of NA. The

radiologic findings, as outlined above, can be quite im-

pressive, demonstrating total destruction of the involved

joints and a dramatic soft tissue mass.

[7] Takeda, S. (2008) Genomic approaches to bone and joint

diseases. Control of bone remodeling by hormones and

neuronal pathways. Clinical Calcium, 18, 216-221.

[8] Brighton, P.J. and Szekeres, P.G. (2004) Signaling and

ligand binding by recombinant neuromedin U receptors:

Evidence for dual coupling to Galphaq/11 and Galphai

and an irreversible ligand-receptor interaction. Molecular

Pharmacology, 66, 1544-1556.

doi:10.1124/mol.104.002337

[9] Sato, S. and Hanada, R. (2007) Central control of bone

remodeling by neuromedin U. Nature Medicine, 13, 1234-

1240. doi:10.1038/nm1640

[10] Cirmanová, V., Bayer, M., Stárka, L. and Zajícková, K.

(2008) The effect of leptin on bone: An evolving concept

of action. Physiological Research, 57, S143-S151.

REFERENCES

[11] Ruette, P. and Stuyck, J. (2007) Neuropathic arthropathy

of the shoulder and elbow associated with syringomyelia:

A report of 3 cases. Acta Orthopaedica Belgica, 73, 525-

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