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: foroozan@bcm.tmc.edu

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

•• Of outstanding interest

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•32 Lee AG, Quick SJ, Liu GT, et al.: A childhood cavernous conundrum. Surv

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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