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
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-

J. A. Rubano et al. / Open Journal of Internal Medicine 2 (2012) 27-30 28
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 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-
529
[1] Nacir, B. and Cebeci, S.A. (2009) Neuropathic arthropa-
thy progressing with multiple joint involvement in the
upper extremity due to syringomyelia and type I arnold
ch iari malformation. Rheumatology International, 30, 979-
983. doi:10.1007/s00296-009-1013-5 [12] Garg, R.K. and Kar, A.M. (2008) Charcot shoulder in
syringomyelia. Internal Medicine Journal, 38, 868-870.
doi:10.1111/j.1445-5994.2008.01784.x
[2] Brower, A.C. and Allman R.M. (1981) Pathogenesis of
the neurotrophic joint: Neurotraumatic vs. neurovascular.
Radiology, 139, 349-354.