Orbital apex syndrome
Steven Yeh and Rod Foroozan
Purpose of review
Visual loss from optic neuropathy and ophthalmoplegiainvolving multiple cranial nerves are the hallmarks of an orbitalapex syndrome. Historically, the terms superior orbital fissure,orbital apex, and cavernous sinus have been used to define theanatomic locations of a disease process. However, thediagnostic evaluation and management is similar for each ofthese entities. The authors reviewed the literature on thediagnosis and evaluation of disorders involving the orbital apex.Recent findings
High-resolution MRI is the preferred modality for evaluatingmost lesions involving the orbital apex. CT is a useful tool inthe setting of trauma, to evaluate bone involvement, or whenMRI is contraindicated. Although laboratory studies may beuseful adjuncts in the diagnostic evaluation of lesions involvingthe orbital apex, surgical biopsy is often required for definitivediagnosis.Summary
Orbital apex syndromes may result from a variety ofinflammatory, infectious, neoplastic, iatrogenic/traumatic, andvascular conditions. A detailed history with review of systemsis important in narrowing the differential diagnosis.Management is directed at the underlying cause and may beguided by surgical biopsy. Corticosteroids may be useful if aninflammatory etiology is suspected, but should be used withcaution.
Keywords
orbital apex, superior orbital fissure, cavernous sinus,Tolosa–Hunt syndrome, magnetic resonance imaging
Curr Opin Ophthalmol 15:490–498. © 2004 Lippincott Williams & Wilkins.
IntroductionAn orbital apex syndrome (OAS) has been described pre-
viously as a syndrome involving damage to the oculomo-
tor nerve (III), trochlear nerve (IV), abducens nerve (VI),
and ophthalmic branch of the trigeminal nerve (V1) in
association with optic nerve dysfunction. The cavernous
sinus syndrome (CSS) may include the features of an
OAS with added involvement of the maxillary branch of
the trigeminal nerve (V2) and oculosympathetic fibers
(Fig. 1) [1]. Cavernous sinus lesions are also more com-
monly bilateral.
The term superior orbital fissure syndrome (SOFS) or
Rochon–Duvigneaud syndrome is often applied to le-
sions located immediately anterior to the orbital apex,
including the structures exiting the annulus of Zinn and
often those external to the annulus (Fig. 2) [2]. In this
clinical setting, multiple cranial nerve palsies may be
seen in the absence of optic nerve pathology.
The superior orbital fissure, orbital apex, and cavernous
sinus are all contiguous, and although these terms define
the precise anatomic locations of a disease process, the
etiologies of these syndromes are similar. In some in-
stances, patients who have features of a SOFS may sub-
sequently develop orbital apex and cavernous sinus pa-
thology. Thus, we have chosen to discuss these entities
together under the heading of OAS. We present a diag-
nostic algorithm to evaluate an OAS and review recent
literature on the diagnosis and treatment of these disor-
ders.
Symptoms and signsVisual loss and ophthalmoplegia are often the initial
manifestations of an OAS. Thus, the ophthalmologist
may be the first physician consulted by a patient with an
OAS.
Periorbital or facial pain may reflect involvement of the
ophthalmic (V1) or maxillary (V2) branch of the trigemi-
nal nerve. Periorbital pain is one of the diagnostic criteria
for Tolosa–Hunt syndrome (THS), an idiopathic inflam-
matory syndrome of the orbital apex. However, the ab-
sence of pain does not exclude a process within the or-
bital apex. It is important to test the periorbital skin and
the corneal reflexes to detect asymmetry in sensation.
Infectious, inflammatory, and neoplastic conditions may
be associated with proptosis. Vascular causes of a CSS,
Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine,Houston, Texas, USA
Correspondence to Rod Foroozan, MD, Cullen Eye Institute, Baylor College ofMedicine, 6565 Fannin NC-205, Houston, TX 77030, USATel: 713 798 4884; fax: 713 798 8739; e-mail: [email protected]
The authors have no proprietary interest in any contents in this manuscript.
Supported in part by an unrestricted grant from the Research to PreventBlindness, Inc., New York, New York.
Current Opinion in Ophthalmology 2004, 15:490–498
Abbreviations
CSS cavernous sinus syndromeOAS orbital apex syndromeSOFS superior orbital fissure syndromeTHS Tolosa–Hunt syndrome
© 2004 Lippincott Williams & Wilkins1040-8738
490
such as a carotid–cavernous fistula, classically are associ-
ated with pulsatile proptosis.
To assess for optic nerve dysfunction, measurement of
best-corrected visual acuity, examination of the pupils
for the presence of an afferent pupillary defect, and color
vision testing should be included. Visual field testing
with kinetic or static perimetry may reveal subtle visual
field deficits when visual acuity is normal. We routinely
use Humphrey automated perimetry to assess for visual
field defects.
Optic atrophy typically develops over weeks to months
in patients with an OAS. Thus, optic atrophy may or may
not be present in a patient with an OAS, and its absence
should not preclude further evaluation if other clinical
findings suggest that an optic neuropathy is present.
Diplopia may be the presenting symptom in SOFS,
OAS, or CSS. The pattern of an ocular deviation is es-
pecially important in the evaluation of a single ocular
motor nerve palsy (eg, an esotropia greater in gaze ipsi-lateral to a sixth nerve palsy or hypertropia increasing in
contralateral gaze and on ipsilateral head tilt in a fourth
nerve palsy). However, because multiple cranial nerves
may be involved, a distinct pattern may be difficult to
detect.
Several authors have reported a correlation between the
initial number of cranial nerves involved and the likeli-
hood of having a CSS. In their retrospective study of 68
patients with cranial neuropathies, CSS was found in 7 of
34 patients (18%) who presented with a cranial mono-
neuropathy and in seven of nine patients (78%) who
presented with involvement of four cranial nerves. The
oculomotor and abducens nerves were the most fre-
quently involved cranial nerves, followed by the troch-
lear nerve [3••].
CausesOrbital apex syndromes may be caused by inflammatory,
infectious, neoplastic, iatrogenic/traumatic, or vascular
processes:
Inflammatory
1. Sarcoidosis
2. Systemic lupus erythematosus
3. Churg–Strauss syndrome
4. Wegener granulomatosis
5. THS
6. Giant cell arteritis
7. Orbital inflammatory pseudotumor
8. Thyroid orbitopathy
Infectious
1. Fungi: Aspergillosis, Mucormycosis2. Bacteria: Streptococcus spp., Staphylococcus spp., Actino-
myces spp., Gram-negative bacilli, anaerobes,Mycobac-terium tuberculosis
3. Spirochetes: Treponema pallidum4. Viruses: Herpes zoster
Figure 1. Cavernous sinus and its contents
(A) Block section illustration of the cavernous sinus and it contents. (B) The duralwall of the cavernous sinus has been removed and the trigeminal nerve has beenreflected forward to reveal the venous spaces of the cavernous sinus. (C) Thecavernous sinus has been completely removed to show the intracavernoussegment of the carotid artery. The location of the cavernous sinus is indicated bythe white dotted line. ICA, internal carotid artery. (Reprinted with permission fromElsevier [1].)
Orbital apex syndrome Yeh and Foroozan 491
Neoplastic
1. Head and neck tumors: nasopharyngeal carcinoma,
adenoid cystic carcinoma, squamous cell carcinoma
2. Neural tumors: neurofibroma, meningioma, ciliary
neurinoma, schwannoma
3. Metastatic lesions: lung, breast, renal cell, malignant
melanoma
4. Hematologic: Burkitt lymphoma, non-Hodgkin lym-
phoma, leukemia
5. Perineural invasion of cutaneous malignancy
Iatrogenic/traumatic
A. Iatrogenic
1. Sinonasal surgery
2. Orbital/facial surgery
B. Traumatic
1. Penetrating injury
2. Nonpenetrating injury
3. Orbital apex fracture
4. Retained foreign body
Vascular
1. Carotid cavernous aneurysm
2. Carotid cavernous fistula
3. Cavernous sinus thrombosis
4. Sickle cell anemia
Other
A. Mucocele
The incidence of each cause differs depending on the
source of the report. In a retrospective review of 151
lesions causing a CSS, tumors were the most frequent
cause (45 patients, 30%). When surgical causes were in-
cluded with trauma, an iatrogenic/traumatic etiology (53
patients, 35%) was the most common cause. Self-limited
inflammation was the third most frequent cause (34 pa-
tients, 23%), whereas vascular causes, infections, and
other causes constituted the remaining 12% of CSS [4].
A retrospective review of 130 published cases of SOFS
identified an inflammatory etiology in 45 of 63 patients
(71%) in whom a neuroradiologic evaluation was pur-
sued. Neoplastic causes and hematoma were each found
in 5 of 63 patients (8%). The causes of SOFS were un-
identified in 8 of 63 patients (13%) [5].
Inflammatory
Inflammatory disease within the orbital apex may pre-
sent as painful ophthalmoplegia with or without associ-
ated optic neuropathy (Fig. 3). Typically, the onset of
symptoms is abrupt with progression over days to weeks.
Associated conditions include Wegener granulomatosis
[6], sarcoidosis [7], systemic lupus erythematosus [8],
and Churg–Strauss syndrome [9]. Giant cell arteritis may
also rarely mimic an OAS and present with periorbital
pain and ophthalmoplegia [10•].
Both the systemic form of Wegener granulomatosis, with
pulmonary and renal involvement, and its limited form
may involve the cavernous sinus. Seizures and CSS were
reported in a patient with antineutrophil cytoplasmic an-
tibody-associated vasculitis in the limited form of Wege-
ner granulomatosis. In this patient, enhancing lesions of
the cavernous sinus and thickened pachymeninges were
observed [6].
Although patients with neurosarcoidosis often have other
systemic manifestations, CSS has been reported as the
only manifestation of this inflammatory condition [7]. In
this patient, laboratory testing revealed an elevated
erythrocyte sedimentation rate and a normal serum an-
giotensin-converting enzyme, chest radiograph, and gal-
lium scan. Definitive diagnosis was made by cavernous
sinus biopsy, which revealed noncaseating granulomas
with multinucleated giant cells.
Churg–Strauss syndrome may also cause a CSS, with one
recent report in the literature [9]. This patient, with a
history of asthma, developed severe headaches, progres-
sive left-sided ophthalmoplegia, and visual loss. Labora-
tory studies revealed eosinophilia, an elevated erythro-
cyte sedimentation rate, and an elevated perinuclear
antineutrophil cytoplasmic antibody level. MRI showed
enhancement involving the left superior orbital fissure,
cavernous sinus, and dura of the temporal base.
The THS refers to a condition of unknown cause involv-
ing painful ophthalmoplegia resulting from granuloma-
Figure 2. Right superior orbital fissure viewed anteriorly
Reprinted with permission from Elsevier [2].
492 Neuro-ophthalmology
tous inflammation within the cavernous sinus or orbital
apex [11,12]. In 2004, the International Headache Soci-
ety defined the diagnostic criteria of THS to include
episodes of unilateral orbital pain persisting for weeks if
untreated; associated paralysis of one or more of the
third, fourth, or sixth cranial nerves; and/or demonstra-
tion of a granuloma by MRI or biopsy [13••]. Cranial
nerve paresis typically coincides with the onset of pain or
follows it within a period of as long as 2 weeks, and pain
or paresis resolves within 72 hours after adequate corti-
costeroid therapy. THS is diagnosed according to Inter-
national Headache Society criteria only after exclusion of
other causative lesions [13••]. The pain is often de-
scribed as a “gnawing” or “boring” sensation and may
precede or occur with ophthalmoplegia. Oculosympa-
thetic nerve fibers adjacent to the internal carotid artery
may also be involved in THS. THS may have a relapsing
and remitting course; however, residual neurologic defi-
cits may persist after remission [2,14]. Some authors have
suggested that other causative conditions should be ex-
cluded using blood and cerebrospinal fluid examination
and possible biopsy if positive findings are seen on MRI
or CT. They recommend that follow-up examinations
must then be performed for at least 2 years before the
diagnosis of THS is made [15]. Neuroimaging may not
be specific for THS, because meningioma, lymphoma,
and sarcoidosis may have identical signal intensities on
T1- and T2-weighted MRI [16].
Infectious
Infectious diseases involving the central nervous system,
paranasal sinuses (Fig. 4), and periorbital structures may
lead to an OAS. These include fungal organisms such as
Mucormycosis [17,18] and Aspergillosis [19,20], bacteria[21–23,24•,25–29], and syphilis [30]. Early identification
of an infectious cause is paramount, because failure to
recognize these conditions may be fatal.
Mucormycosis and Aspergillosis should be suspected in in-dividuals with predisposing conditions including diabe-
tes mellitus, alcoholism, hematologic malignancies, and
immunosuppression [17]. A fungal cause should be con-
sidered in any patient requiring immunomodulatory, an-
tineoplastic, or long-term corticosteroid therapy. How-
ever, Aspergillosis andMucormycosis have been reported inimmunocompetent individuals as well [20,31]. Although
fungal infections of the orbit and paranasal sinuses may
present with pain, local tissue invasion and necrosis, and
typical radiographic findings, they may also occur with-
out pain and in an insidious fashion, making the diagno-
sis more difficult. Otolaryngologic consultation may be
helpful to identify and to sample areas of tissue necrosis
if the cause of an orbital apex syndrome is unclear [18].
Tuberculosis has also been reported to cause both uni-
lateral and bilateral CSS [21]. CSS resulting from tuber-
culosis has rarely been reported in the literature, but may
occur in the absence or presence of other central nervous
system findings [22]. A cavernous sinus tuberculoma
may also occur in the absence of pulmonary findings [23].
Bacterial infection may result in cavernous sinus throm-
bosis, most commonly from contiguous spread of infec-
tions from the paranasal sinuses. Organisms most com-
monly implicated include Staphylococcus aureus,Streptococcus pneumoniae, other streptococci, Gram-
Figure 3. Axial T1-weighted MRI (left) showing contrast
enhancement within the orbital apex (larger arrow) and
cavernous sinus (smaller arrow) in a 77-year-old woman who
developed a left sixth nerve palsy and optic neuropathy
Total ophthalmoplegia developed, prompting a craniotomy and cavernous sinusbiopsy, which revealed nongranulomatous inflammatory changes. Despitecorticosteroids and the addition of other immunomodulatory agents, the patientlost vision to no light perception, and repeat neuroimaging revealed progressionof the inflammatory process (right).
Figure 4. Axial CT (left) showing opacification within the
ethmoid (larger arrow) and sphenoid (smaller arrow) sinuses
Coronal CT (right) confirms opacification within the ethmoid sinus in a43-year-old man who developed fevers, visual loss, and a sixth nerve palsy.Endoscopy revealed mucosal inflammation within the paranasal sinuses and puswithin the orbital apex. His symptoms improved after surgical drainage andtreatment with intravenous antibiotics.
Orbital apex syndrome Yeh and Foroozan 493
negative bacilli, and anaerobes [24•,25,26]. Bilateral cav-
ernous sinus involvement has also been reported in as-
sociation with central nervous system Actinomyces israelii[27,28]. A mixed infection with S. aureus and Pseudomo-nas aeruginosa has also been observed to cause an OASwith cavernous sinus thrombosis [29].
Neoplastic
The possibility of a neoplasm should be considered in
the differential diagnosis of an OAS, especially in any
patient with a known history of cancer. Primary ocular or
orbital tumors, neoplasms of the paranasal sinuses, or
central nervous system tumors may invade the orbital
apex. Metastatic disease may also involve the cavernous
sinus. Tumors that most commonly cause a CSS include
nasopharyngeal cancer, lymphoma, pituitary adenoma,
meningioma, and metastatic disease [4].
Lymphomatous infiltration of the cavernous sinus has
been reported both in pediatric [32•,33] and adult pa-
tients [34,35]. Lymphoma may be found in the paranasal
sinuses or within the cavernous sinus alone. Neural tu-
mors of the orbital apex are most commonly benign and
include meningiomas (Fig. 5), schwannomas, neurofibro-
mas, and, rarely, ciliary neurinomas [36•,37•]. These be-
nign lesions typically result in slowly developing orbital
symptoms in the absence of pain.
Local invasion of the orbital apex from adjacent head and
neck tumors has also been frequently reported in the
literature. Although patients with tumors of the head,
neck, and paranasal sinuses most frequently have other
findings, OAS has been reported as the initial sign in a
patient with maxillary sinus carcinoma [38]. Adenoid cys-
tic carcinoma [39], mucoepidermoid carcinoma [40], and
poorly differentiated squamous cell carcinoma [41] have
also presented with primary involvement of the orbital
apex.
Metastatic disease to the cavernous sinus has been re-
ported from the breast [42], lung [43], kidney [44], and
from malignant melanoma [45•]. Extramedullary hema-
topoiesis in a patient with polycythemia rubra vera
caused an OAS from compressive neuropathy. Bone mar-
row biopsy revealed myelofibrosis in this patient [46].
Iatrogenic/traumatic
Iatrogenic causes of an OAS have been reported follow-
ing sinonasal and periorbital surgical procedures. An
OAS has been reported after ethmoidal artery ligation for
recurrent epistaxis [47•], intranasal ethmoidectomy for
nasal polyposis [48], and septorhinoplasty [49]. Optic
neuropathy during sinus surgery may occur from direct or
indirect injury to the optic nerve or its blood supply [50].
OAS has been observed after both penetrating and blunt
orbital trauma [51]. Penetrating trauma leading to OAS is
rare in the absence of a bony fracture; however, an OAS
has been reported secondary to a retained intraorbital
foreign body without bone involvement. Although de-
layed onset of neurologic symptoms is rare after an acute
traumatic injury, symptoms of a SOFS were delayed for
72 hours in a patient with a retained foreign body within
the orbit and cavernous sinus [52].
Vascular
Vascular causes of CSS include cavernous carotid aneu-
rysms, carotid–cavernous fistulas, and cavernous sinus
thrombosis. Cavernous carotid aneurysms may cause a
unilateral or bilateral cavernous sinus syndrome via com-
pression of adjacent cranial nerves [4,53•]. A carotid–
cavernous fistula may cause pulsatile proptosis, severe
conjunctival injection, and glaucoma from elevated epi-
scleral venous pressure. A history of head trauma is often
elicited; however, carotid–cavernous fistulas may also oc-
cur spontaneously and have been observed in patients
with longstanding hypertension or connective tissue dis-
orders such as Ehlers–Danlos syndrome [54,55••]. Septic
thrombosis of the cavernous sinus may occur in the set-
ting of systemic or, more commonly, periorbital infec-
tions [56,57], but aseptic cavernous sinus thromboses
have also been noted [58]. Cavernous sinus thrombosis
may be visualized on contrast-enhanced high-resolution
CT or with MRI. Typical findings include filling defects
Figure 5. Axial T1-weighted MRI showing an enhancing lesion
within the left cavernous sinus and orbital apex (larger arrow)
and involvement of the meninges around the left temporal
lobe (smaller arrow) in a 50-year-old woman with a left third
nerve palsy and optic neuropathy
Neurosurgical resection confirmed that the lesion was a meningioma.
494 Neuro-ophthalmology
within the cavernous sinus and expansion of tributary
veins and venous sinuses [59].
Evaluation and managementNeuroimaging should be performed in a patient with
findings consistent with an OAS (Fig. 6). High-resolution
(1.5-T magnet or greater) MRI is the preferred imaging
modality in the evaluation of most patients with an OAS.
To evaluate the orbital apex and cavernous sinus, we
perform MRI of the brain and orbits with contrast and fat
suppression sequences. The 3-T MRI has been found to
be superior to the standard 1- to 1.5-T MRI magnet to
define parasellar anatomy and to diagnose tumor inva-
sion of the cavernous sinus [60••].
Figure 6. Evaluation and management of a patient with an orbital apex syndrome
Orbital apex syndrome Yeh and Foroozan 495
CT also plays an important role in the setting of trauma
or in patients who are suspected of having magnetic for-
eign bodies, surgical clips, or who have other contraindi-
cations to MRI. CT is superior to MRI for the depiction
of bony anatomy and is especially helpful if an orbital
apex fracture is suspected clinically [61].
If a vascular lesion of the cavernous sinus is suspected,
magnetic resonance angiography (MRA) or CT angiog-
raphy may be helpful. If the index of suspicion remains
high despite negative neuroimaging studies, cerebral an-
giography may be necessary.
Laboratory testing for inflammation and infection (eg,erythrocyte sedimentation rate, complete blood count
with differential, rapid plasma reagin, microhemaggluti-
nation assay for antibody to Treponema pallidum, angio-tensin-converting enzyme, perinuclear antineutrophil
cytoplasmic antibody, cytoplasmic antineutrophil cyto-
plasmic antibody, antinuclear antibody, purified protein
derivative, chest radiography, HIV, lumbar puncture)
should also be considered if the clinical findings are sug-
gestive of these processes.
When a specific cause cannot be determined, the pri-
mary management options in a patient with an OAS in-
clude observation, an empiric trial of corticosteroids, and
surgical biopsy. In the absence of systemic signs of in-
fection and when inflammatory disease is likely, we offer
corticosteroids and a period of close observation. If visual
loss or ophthalmoplegia progresses, repeat neuroimaging
and a biopsy are then pursued. Neurosurgical, otolaryn-
gologic, and radiologic consultation may be warranted if
a cavernous sinus or paranasal sinus lesion is accessible
for surgical biopsy [62••]. Internal medicine or neuro-
logic consultation may also be sought when clinical cir-
cumstances suggest a systemic or neurologic process.
Management of an OAS is aimed at the underlying
cause. The distinction between inflammation, infection,
and neoplasia is often difficult, and all may respond ini-
tially to corticosteroids. Judicious use of corticosteroids is
recommended, because the presence of an occult infec-
tion, especially fungal disease, may result in severe mor-
bidity or mortality. Methotrexate [63] and azathioprine
[64] have provided clinical benefit in a limited number of
patients with THS. Radiotherapy also has reportedly al-
leviated symptoms of THS in one patient refractory to
immunosuppressive therapy and in another patient who
became steroid dependent [65]. Following traumatic or
iatrogenic operative injury, corticosteroids may be insti-
tuted while surgical intervention is considered.
ConclusionOASs represent a heterogeneous group of disorders that
result from a number of etiologies. A systemic disease (ie,
infection, neoplasm, autoimmune condition) may pre-
cede the OAS, and a thorough history with review of
systems may offer diagnostic clues; however, an OAS
may also be isolated and herald a systemic process. Neu-
roimaging, preferably with MRI, can confirm the clinical
findings of an OAS and identify sites that may be
sampled if the diagnosis remains unclear.
Treatment is directed at the underlying cause and may
require neurosurgical, otolaryngologic, neurologic, or
medical consultation. Corticosteroids may be helpful if
an inflammatory cause for an OAS is suspected, but
should be used judiciously, particularly if an infectious
etiology is being considered.
References and recommended reading
Papers of particular interest, published within the annual period of review,are highlighted as:
• Of special interest
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Ophthalmol 2004, 49:231–236.This is a case report and literature review of Burkitt lymphoma presenting withbilateral cavernous sinus lesions. A 9-year-old boy presented with left-sided tooth-ache, headache, and, subsequently, vertical diplopia. Examination revealed a thirdnerve palsy, and cranial MRI showed bilateral cavernous sinus lesions. Blood smearand bone marrow biopsy revealed Burkitt lymphoma, which was treated with che-motherapy.
33 Kalina P, Black K, Woldenberg R: Burkitt’s lymphoma of the skull base pre-senting as cavernous sinus syndrome in early childhood. Pediatr Radiol 1996,26:416–417.
34 Rubin MM, Sanfilippo RJ: Lymphoma of the paranasal sinuses presenting ascavernous sinus syndrome. J Oral Maxillofac Surg 1992, 50:749–751.
35 Julien J, Ferrer X, Drouillard J, et al.: Cavernous sinus syndrome due to lym-phoma. J Neurol Neurosurg Psychiatry 1984, 47:558–560.
•36 Schick U, Bleyen J, Hassler W: Treatment of orbital schwannomas and neu-
rofibromas. Br J Neurosurg 2003, 17:541–545.The authors discuss their treatment of five orbital peripheral nerve tumors. Twocases, both schwannomas, involved the orbital apex and superior orbital fissure.Their surgical management is outlined.
•37 Vassilikos C, Pepe P, Christopoulos C: Ciliary neurinoma: a very rare intraor-
bital extraocular tumor causing orbital apex syndrome. Plast Reconstr Surg2003, 112:1504–1505.
This is a case report of a 75-year-old woman who presented with a 1-month historyof decreased vision, diplopia, retroorbital pain, and exophthalmos. CT and MRIrevealed a 12 × 16-mm mass involving the orbital apex. The mass was surgicallyremoved and pathology revealed a benign ciliary neurinoma. The patient’s painresolved and visual acuity was partially restored.
38 Srinivasan S, Fern AI, Wilson K: Orbital apex syndrome as a presenting signof maxillary sinus carcinoma. Eye 2001, 15:343–345.
39 McDonald HR, Char DH: Adenoid cystic carcinoma presenting as an orbitalapex syndrome. Ann Ophthalmol 1985, 17:757–759.
40 Gore HL, Corin SM, Klussmann KG, et al.: Mucoepidermoid carcinoma pre-senting as an orbital apex syndrome. Ophthalmic Surg 1992, 23:59–61.
41 Veness MJ, Biankin S: Perineural spread leading to orbital invasion from skincancer. Australas Radiol 2000, 44:296–302.
42 Ryan MW, Rassekh CH, Chaljub G: Metastatic breast carcinoma presentingas cavernous sinus syndrome. Ann Otol Rhinol Laryngol 1996, 105:666–668.
43 Auerbach DB, Bilyk JR: Lung cancer, proptosis, and decreased vision. SurvOphthalmol 1999, 43:405–412.
44 Mehelas TJ, Kosmorsky GS: Painful ophthalmoplegia syndrome secondary tometastatic renal cell carcinoma. J Neuroophthalmol 1996, 16:289–290.
•45 Harkness KA, Manford MR: Metastatic malignant melanoma presenting as a
cavernous sinus syndrome. J Neurol 2004, 251:224–225.This is a case report of a 21-year-old fair-skinned man with a 10-day history ofprogressive bifrontal headache and diplopia. Partial third, fourth, and sixth nervepalsies were observed initially, and the patient’s pupillary reaction was normal. CTof the brain and orbits was normal. Symptoms progressed to complete ptosis andophthalmoplegia with a fixed, dilated pupil. Routine blood tests and MRI of the brainand orbits with gadolinium contrast were normal at this time. Excisional biopsy oftwo skin nevi showed dysplastic nevi but no malignant features. Diagnosis of ma-lignant melanoma was made with a core biopsy of a 4.1-cm axillary lymph node.Despite whole-brain radiotherapy, the patient died 4 months after initial presenta-tion after developing multiple metastases.
46 Pless M, Rizzo JF 3rd, Shang J: Orbital apex syndrome: a rare presentation ofextramedullary hematopoiesis: case report and review of literature. J Neu-rooncol 2002, 57:37–40.
•47 Yeh S, Yen MT, Foroozan R: Orbital apex syndrome after ethmoidal artery
ligation for recurrent epistaxis. Ophthal Plast Reconstr Surg 2004, 20:392–394.
This is a case report of a 34-year-old man with severe, recurrent epistaxis whounderwent external anterior and posterior ethmoidal artery ligation on the right side.Severe visual loss from optic neuropathy and complete ophthalmoplegia devel-oped after surgery. CT revealed surgical clips within the right orbital apex. Emer-gent removal of the surgical clips and medial wall decompression were performed.Despite prompt recognition and treatment, severe visual loss and ophthalmoplegiapersisted.
48 Vassallo P, Tranfa F, Forte R, et al.: Ophthalmic complications after surgeryfor nasal and sinus polyposis. Eur J Ophthalmol 2001, 11:218–222.
49 Jaison SG, Bhatty SM, Chopra SK, et al.: Orbital apex syndrome: a rare com-plication of septorhinoplasty. Indian J Ophthalmol 1994, 42:213–214.
50 Rene C, Rose GE, Lenthall R, et al.: Major orbital complications of endo-scopic sinus surgery. Br J Ophthalmol 2001, 85:598–603.
51 Anderson RL, Panje WR, Gross CE: Optic nerve blindness following bluntforehead trauma. Ophthalmology 1982, 89:445–455.
52 Jarrahy R, Cha ST, Shahinian HK: Retained foreign body in the orbit andcavernous sinus with delayed presentation of superior orbital fissure syn-drome: case report. J Craniofac Surg 2001, 12:82–86.
•53 Atri A, Sheen V: Cavernous sinus syndrome and headache due to bilateral
carotid artery aneurysms. Arch Neurol 2003, 60:1327–1328.This is a case report of an 89-year-old woman with a history of hypertension andPaget disease who developed right-sided headache. Two years earlier she hadfallen, resulting in a fracture of her arm; weeks later, she developed pain and swell-ing in the right eye followed by numbness of the right forehead and blurred vision.Neurologic examination revealed right-sided ptosis, esotropia, complete ophthal-moplegia, and decreased sensation in the V1 and V2 dermatomes. MRI and MRangiography showed bilateral cavernous carotid aneurysms with thrombi. At-tempted endovascular occlusion of the aneurysm on the right side was unsuccess-ful.
54 Lach B, Nair SG, Russell NA, et al.: Spontaneous carotid–cavernous fistulaand multiple arterial dissections in type IV Ehlers–Danlos syndrome. J Neu-rosurg 1987, 66:462–467.
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••55 de Keizer R: Carotid–cavernous and orbital arteriovenous fistulas: ocular fea-
tures, diagnostic and hemodynamic considerations in relation to visual impair-ment and morbidity. Orbit 2003, 22:121–142.
This is a retrospective review of 101 cases of direct dural carotid–cavernous andorbital arteriovenous fistulas. The diagnostic triad of arterialized loops, exophthal-mos, and glaucoma are discussed. Diagnostic procedures such as ultrasound,color Doppler of the orbit and carotid systems, and MRI and MR angiography arereviewed. Management strategies including conservative therapy, balloon emboli-zation, and direct or indirect surgery are discussed. Of the 10 orbital arteriovenousshunts with signs of dural fistulas, findings spontaneously resolved in eight pa-tients, one patient required direct surgery (which was successful), and one pa-tient’s nonprogressive orbital findings persisted.
56 Tveteras K, Kristensen S, Dommerby H: Septic cavernous and lateral sinusthrombosis: modern diagnostic and therapeutic principles. J Laryngol Otol1988, 102:877–882.
57 DiNubile MJ: Septic thrombosis of the cavernous sinuses. Arch Neurol 1988,45:567–572.
58 Oliven A, Harel D, Rosenfeld T, et al.: Hypopituitarism after aseptic cavernoussinus thrombosis. Neurology 1980, 30:897–899.
59 Schuknecht B, Simmen D, Yuksel C, et al.: Tributary venosinus occlusion andseptic cavernous sinus thrombosis: CT and MR findings. AJNR Am J Neuro-radiol 1998, 19:617–626.
••60 Wolfsberger S, Ba-Ssalamah A, Pinker K, et al.: Application of three-tesla
magnetic resonance imaging for diagnosis and surgery of sellar lesions. JNeurosurg 2004, 100:278–286.
This is a study to determine the value of high-field MRI for diagnosis and surgery ofsellar lesions. High-field MR images were obtained with 3-T MRI, with emphasis on
sellar and parasellar structures in 21 patients. Three-tesla MR images were com-pared with standard 1- to 1.5-T MR images already obtained with intraoperativefindings with attention to the medial border of the cavernous sinus to assess forpossible invasion of a sellar tumor. Three-tesla MRI was superior to standard MRIfor predicting tumor invasion through the medial cavernous sinus border. Betterdelineation of the lateral sinus compartment was also observed with 3-T MRI. Iden-tification of the cavernous sinus segments of the third, fourth, fifth (V1 and V2), andsixth cranial nerves was also improved with 3-T MRI. Three-tesla MRI was found tobe superior to standard MRI for delineation of parasellar anatomy and tumor infil-tration of the cavernous sinus, and may be valuable for intraoperative navigation.
61 Unger JM: Orbital apex fractures: the contribution of computed tomography.Radiology 1984, 150:713–717.
••62 Schick U, Hassler W: Neurosurgical management of orbital inflammations
and infections. Acta Neurochir (Wien) 2004, 146:571–580.This is a retrospective review of the treatment and clinical outcomes of 22 orbitalinflammations and infections, with a subgroup involving the orbital apex. The sur-gical approach in each of these cases was determined by the anatomic location ofthe disease process within the orbit. A transantral approach was used in one pa-tient with a mucocele involving the orbital apex and maxillary sinus. A pterionalextradural approach was useful in two patients with lesions of the orbital apex. Apterional intradural operation was performed in five patients with inflammation ofthe optic canal extending into the intracranial space.
63 Smith JR, Rosenbaum JT: A role for methotrexate in the management of non-infectious orbital inflammatory disease. Br J Ophthalmol 2001, 85:1220–1224.
64 Hannerz J: Recurrent Tolosa–Hunt syndrome. Cephalalgia 1992, 12:45–51.
65 Mormont E, Laloux P, Vauthier J, et al.: Radiotherapy in a case of Tolosa–Huntsyndrome. Cephalalgia 2000, 20:931–933.
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