Tumors or chronic inflammatory lesions of the occipital condyle may cause occipital pain associated with an ipsilateral hypoglossal nerve injury (occipital condyle syndrome). We describe a young woman with recurrent otitis media and occipital condyle syndrome associated with a limited form of Wegener’s disease

Biller, José

Ersahin, Cagatay H.

Hornik, Alejandro

Kadanoff, Ruth

Rodriguez-Porcel, Federico

English

PubMed

Alejandro Hornik

Federico Rodriguez-Porcel

Cagatay H. Ersahin

Ruth Kadanoff

José Biller

Frontiers - Publisher Connector

CPC ARTICLE
published: 12 April 2012
doi: 10.3389/fneur.2012.00053
Wegener’s disease presenting with occipital
condyle syndrome
Alejandro Hornik , Federico Rodriguez-Porcel , Cagatay H. Ersahin, Ruth Kadanoff and José Biller*
Department of Neurology, Loyola University Medical Center, Stritch School of Medicine, Maywood, IL, USA
Edited by:
Richard Mayeux, Columbia University,
USA
Reviewed by:
Kevin N. Sheth, University of
Maryland School of Medicine, USA
Valentina Garibotto, Geneva
University and Geneva University
Hospital, Switzerland
*Correspondence:
José Biller , Department of Neurology,
Loyola University Medical Center,
Stritch School of Medicine, 2160
South, 1st Avenue, Building 105,
Room 2700, Maywood, IL 60153,
USA.
e-mail: jbiller@lumc.edu
Tumors or chronic inﬂammatory lesions of the occipital condyle may cause occipital pain
associated with an ipsilateral hypoglossal nerve injury (occipital condyle syndrome). We
describe a young woman with recurrent otitis media and occipital condyle syndrome
associated with a limited form of Wegener’s disease.
Keywords:Wegener’s disease, occipital condyle syndrome, hypoglossal nerve paralysis
A 47-year-old woman had a 2-week history of “troubles handling
food inside her mouth” resulting in a 7-pound weight loss. Few
days prior to this complaint, the patient experienced continuous,
“ice-pick-like” pains on the right occipital area radiating to the
right temporal area. The pain improved by turning her head to the
right and worsened by head turning to the left. Past medical his-
tory was remarkable for a 6-month history of recurrent bilateral
otitis media requiring bilateral myringotomies, and one episode
of transient right lid drooping. Pertinent ﬁndings on neurologi-
cal examination included dysarthric speech, right nasolabial fold
ﬂattening, and right hemilingual atrophy with fasciculations.
Initial complete blood count (CBC), complete metabolic pro-
ﬁle (CMP), activated partial thromboplastin time (aPTT), inter-
national normalized ratio (INR), and prothrombin time (PT)
were unremarkable. Erythrocyte sedimentation rate (ESR) was
29mm/h and C-reactive protein (CRP) was 0.4mg/dl. MRI of
the brain with gadolinium showed diffuse enhancement of the
nasopharynx, petrous apices, and prevertebral soft tissues with
extension to themedialmargins of the carotid artery spaces,medial
pterygoid muscles, and dura at the level of the pre-medullary
cistern (Figure 1). CT of the neck with contrast failed to iden-
tify any lesion in the nasopharynx. CT of the chest, abdomen,
and pelvis showed bilateral pulmonary nodules with irregular
margins (Figure 2). A percutaneous transthoracic biopsy of the
dominant lung nodule, showed changes consistent with a non-
caseating granulomatous reaction (Figure 3). Cerebrospinal ﬂuid
(CSF) analysis showed a protein of 70mg/dl, no red blood cells
(RBCs), 1 white blood cell (WBC), and a glucose of 53mg/dl (55%
of serum glucose). Cytology was negative for malignancy. CSF
acetylcholinesterase (ACE), PCR for Epstein Barr virus, Varicella
Zoster virus, Herpes Simplex virus type 1 and 2, JC virus as well as
antibodies againstBorrelia Burgdorferi,Arbovirus, andCoccidioides
were unremarkable. HIV 1 and 2 antibodies, serum rheumatoid
factor,ACE, rapid plasma regain (RPR), carcinoembryonic antigen
(CEA), Lyme antibodies, beta 2 glycoprotein antibodies (IgG and
IgM), cardiolipin antibodies (IgG and IgM), Aspergillus, Coccid-
ioides, and perinuclear-Anti neutrophil cytoplasmic antibody (P-
ANCA) were negative. Serum sample for classical-antineutrophil
cytoplasmic antibody (C-ANCA) was positive. Urinalysis and
urine Histoplasma antigen were negative. AFB staining in the CSF,
blood, and lung tissue was unremarkable. A ﬂexible endoscopic
naso-pharyngo-laryngoscopy showed hypomotility of the right
true vocal cord.
The patient was started on cefepime and voriconazole. Non-
steroidal anti-inﬂammatory medications failed to relieve her
headaches. Antibiotics were discontinued after all smears and
cultures from the lung lesion, blood, urine, and CSF returned
negative. The patient received 5 days of intravenous methylpred-
nisolone followed by daily 60mg of oral prednisone. Subse-
quent serum sample for anti-proteinase 3 (APR3) was positive.
Methotrexate (MTX) and folic acid were started.
After 4 weeks of therapy with prednisone andMTX, a repeat C-
ANCA,CRP, ESR, andAPR3were found to be normal. The patient
was slowly tapered from steroids with almost immediate recur-
rence of headaches, hemilingual paresis, and dysphagia. Repeat
MRI showed a similar pattern of enhancement. Multiple biop-
sies of the right nasopharynx mucosa, right periclival area, right
descending palatine artery, skeletalmuscle of the right infratempo-
ral fossa, bone, and cartilage fragments of the maxillary, ethmoid,
and sphenoid sinus showing geographic suppurative necrosis,
focal vasculitis, and granulomatous inﬂammation (Figures 4 and
5). These ﬁndings supported the diagnosis of Wegener’s disease
(WD). Immunostains (CD20, CD3, CD5, CD56, kappa, lambda)
and Epstein–Barr virus-encoded ribonucleic acid study (EBER)
www.frontiersin.org April 2012 | Volume 3 | Article 53 | 1
Hornik et al. Occipital condyle syndrome and Wegener’s disease
FIGURE 1 | MRI (T1W with contrast) shows diffuse enhancement in the
nasopharynx, petrous apices, prevertebral soft tissues with extension
to the medial margins of the carotid spaces, medial pterygoid muscles
and dura mater at the pre-medullary cistern.
FIGURE 2 | Chest CT shows the dominant nodule located on the right
superior lobe.
FIGURE 3 | Lung fine needle aspiration shows granulomatous reaction
with epithelioid histiocytes, acute and chronic inflammation (Diff-Quik
stain, 400×).
FIGURE 4 | At low magnification, the histologic features include
”geographic” type necrosis with a basophilic appearance in right nasal
pharynx (H&E stain, 40×). Red arrow shows basophilic, “geographic”
type necrosis.
showed no evidence of sinonasal lymphoma. AFB, bacterial, and
fungal cultures were negative.
MTXwas discontinued,due to protracted nausea and vomiting,
and the patient was given on intravenous rituximab 325mg/m2. A
repeat pulse ofmethylprednisolone controlled the recurrent symp-
toms. The patient is currently free of symptoms on 20mg of pred-
nisone daily and 160/800mg of trimethoprim–sulfamethoxazole
twice daily.
DISCUSSION
The association of pain in the occipital region and ipsilateral cra-
nial nerve XII (CN XII) paresis was consistent with the occipital
Frontiers in Neurology | Neurology Education April 2012 | Volume 3 | Article 53 | 2
Hornik et al. Occipital condyle syndrome and Wegener’s disease
FIGURE 5 | Right nasal pharynx biopsy shows the inflammatory
infiltrate surrounding the blood vessels (vasculitis) and showing
angioinvasion (H&E stain, 200×). Red arrows mark the vessels
surrounded by inﬂammatory inﬁltrates.
condyle syndrome, ﬁrst identiﬁed by Greenberg et al. (1981). The
occipital condyle syndrome has been associated withmetastases to
the base of the skull and primary head and neck tumors (Green-
berg et al., 1981; Moris et al., 1998; Capobianco et al., 2002).
The largest case series ever reported about CN XII palsy indi-
cated that almost half of these cases are due to malignancies
(Keane, 1996). Our patient had many of the typical features of the
occipital condyle syndrome (Capobianco et al., 2002) including
radiation of pain to the ipsilateral temporal area, improvement
of symptoms by turning the head toward the painful side with
worsening of pain by contralateral neck rotation. Our patient
had some atypical features including absence of neck stiffness
or worsening pain by neck ﬂexion. Probably the most impor-
tant syndromatic difference in this case is related to the eti-
ology. To our knowledge, the occipital condyle syndrome has
not been previously associated to non-neoplastic etiologies such
as WD.
Wegener’s disease is a clinicopathological syndrome charac-
terized by extravascular granulomatous inﬂammation, granulo-
matous vasculitis of small size vessels, necrosis of upper and
lower respiratory tracts, and pauci-immune glomerulonephritis
(DeRemee et al., 1976; Leavitt et al., 1990). Recurrent middle ear
involvement, as in our patient, has been well documented (McCaf-
frey et al., 1980; Ridley et al., 1988). Neurologicalmanifestations in
WD include cerebral and subarachnoid hemorrhage, cerebral arte-
rial and venous thrombosis, cranial and peripheral neuropathies
(primarily mononeuritis multiplex), diabetes insipidus, retinal
vascular and optic nerve lesions, ocular myositis, orbital pseudo-
tumor, and myopathy (Drachman, 1963; Biller and Grau, 2004;
Holle andGross, 2011). A localized granulomatous involvement of
the meninges, described as chronic granulomatous pachymenin-
gitis, presents a very broad clinical spectrum including seizures,
encephalopathy and, as in the case of our patient, headaches that
only resolve with corticosteroids, meningismus, and cranial neu-
ropathies (Anderson et al., 1975; Katrib et al., 1998). In this setting,
the most common cranial nerves affected are the optic nerve
(CN II) followed by the olfactory (CN I; Nishino et al., 1993). A
presentationwithmultiple cranial neuropathies, althoughuncom-
mon, has been reported (Parker and Sobel, 1988; Fujikawa et al.,
2008). CSF analyses in these patients show lymphocytic pleocy-
tosis with high protein concentration and normal glucose level
(Reinhold-Keller et al., 2001) C-ANCA and anti PR3 are of great
diagnostic value but do not reﬂect disease activity and should
not be used to assess therapeutic response (Nowack et al., 2009).
Untreated patients with WD have a mean survival of 5months
and a 1-year mortality of 82% (Walton, 1958). In 1993, cyclophos-
phamide was the ﬁrst immunosuppressant shown to reverse the
meningeal disease (Weinberger et al., 1993). Since then, corticos-
teroids and cyclophosphamide have been documented to achieve
excellent control of disease activity (de Groot et al., 2001). Mod-
ern immunosuppressants including inﬂiximab and rituximabhave
been reported to successfullymanage refractory cases of this condi-
tion (Mukhtyar and Luqmani, 2005; Sharma et al., 2010). The use
of trimethoprim–sulfamethoxazole has been described to reduce
the incidence of relapses on patients with WD. These effect is
maximum on patient in remission who presented with limited
disease (Reinhold-Keller et al., 1996; Stegeman et al., 1996).
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Conﬂict of Interest Statement: The
authors declare that the research was
conducted in the absence of any
commercial or ﬁnancial relationships
that could be construed as a potential
conﬂict of interest.
Received: 07 February 2012; paper
pending published: 28 February 2012;
accepted: 23 March 2012; published
online: 12 April 2012.
Citation: Hornik A, Rodriguez-Porcel F,
Ersahin CH, Kadanoff R and Biller J
(2012) Wegener’s disease presenting with
occipital condyle syndrome. Front. Neur.
3:53. doi: 10.3389/fneur.2012.00053
This article was submitted to Frontiers
in Neurology Education, a specialty of
Frontiers in Neurology.
Copyright © 2012 Hornik, Rodriguez-
Porcel, Ersahin,Kadanoff andBiller .This
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Frontiers in Neurology | Neurology Education April 2012 | Volume 3 | Article 53 | 4


Wegener’s Disease Presenting with Occipital Condyle Syndrome

Jose eBiller

Alejandro eHornik

Federico eRodriguez-Porcel

Cagatay eErsahin

Ruth eKadanoff

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Wegener’s Disease Presenting with Occipital Condyle Syndrome

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