Pain of Ocular and Periocular Origin

Steven D. Waldman, in Pain Management, 2007

The Cavernous Sinus Syndromes

The cavernous sinus syndromes are a heterogeneous groups of diseases that have in common
their ability to produce ocular and periocular pain as well as a variety of neurologic symptoms,
including ophthalmoplegia, pupillary abnormalities, orbital and conjunctival congestion,
proptosis, and, if severe, visual loss.35 Also known as the parasellar syndromes, the evaluation of
all patients suffering from cavernous sinus syndrome should include including a complete blood
cell count and determination of erythrocyte sedimentation rate, glucose level, Lyme disease titer,
rapid plasma reagin, antinuclear antibody, HIV titer, and thyroid function. MRI of the brain,
sinuses, cavernous sinus, and orbit is also indicated as is MR angiography of the carotid artery.
Diseases comprising the cavernous sinus syndrome include cavernous sinus aneurysms, carotid-
cavernous sinus fistulas, tumors, and cavernous sinus thrombosis, as well as the idiopathic
inflammatory syndromes involving the cavernous sinus (e.g., Tolosa-Hunt syndrome).36,37 Each
is briefly discussed individually.

Cavernous Sinus Aneurysms

Aneurysms of the carotid artery as it passes through the cavernous sinus can cause all of the
symptoms associated with cavernous sinus syndrome. Unlike intracranial aneurysms, which
carry the risk of intracranial hemorrhage, unruptured carotid artery aneurysms in this region
create symptoms by pressure on the various neural structures in proximity to the aneurysm.
When the aneurysm ruptures, a direct carotid artery-cavernous sinus fistula results (Fig. 49-16).
Such fistulas can cause only limited symptoms or can result in massive neurologic dysfunction.
A loud carotid and ocular bruit is often present. Treatment with endovascular occlusion has been
attempted with some success.38

Cavernous Sinus Tumors

Tumors involving the cavernous sinus can be either primary or metastatic in origin. Primary
tumors including meningiomas and neurofibromas are the most common primary tumors seen
involving the cavernous sinus.39 Metastatic breast, prostate, lung, and craniopharyngeal tumors
can also involve the cavernous sinus, often with disastrous results (Fig. 49-17).40 Occasionally,
large pituitary tumors may extend into the cavernous sinus (Fig. 49-18). Symptoms associated
with tumors of this region will vary with the neurologic structures affected as the tumor grows
and the onset of symptoms can be either acute or insidious. Treatment is primarily limited to
palliative radiotherapy, and the results in most cases are poor at best, with the type of tumor the
major determinant of outcome. The exception to this rule is endocrine-responsive pituitary
tumors, which often respond to anti-endocrine drug therapy.

Carotid-Cavernous Fistulas
Fistulas between the carotid artery and the cavernous sinus can be the result of either a rupture of
a preexisting carotid artery aneurysm or direct trauma to the carotid artery and cavernous sinus
(Fig. 49-19).41 Direct fistulas between the carotid artery and the cavernous sinus occur when a
carotid artery aneurysm ruptures directly into the cavernous sinus or trauma to the region
damages the artery. The onset of symptoms is immediate and often quite severe. Misdiagnosis is
common, and prognosis if untreated is poor. A loud carotid and ocular bruit is often present. The
patient may report hearing “water running” in the head. Indirect aneurysms between branches of
the internal or external carotid arteries tend to be less symptomatic. Both types of fistulas can be
treated by endovascular occlusion techniques and carotid artery ligation.

Cavernous Sinus Thrombosis

A common sequela to periorbital or frontal and/or maxillary sinusitis in the preantibiotic era,
cavernous sinus thrombosis is now primarily seen in patients who are immunocompromised
(e.g., HIV-infected patients).42 The patient with an infectious etiology to cavernous sinus
thrombosis will appear septic, and the nidus of the infection may be clinically evident. Severe
ocular and retro-ocular pain is often the first symptom, followed by diplopia and ptosis.
Ophthalmoplegia and signs of meningeal irritation may also be present. Immediate treatment
with antibiotics and corticosteroids combined with surgical drainage of any abscess formation is
crucial to avoid blindness or, in some cases, death.

Head and neck

S. Jacob MBBS MS (Anatomy), in Human Anatomy, 2008

The cavernous sinus

The cavernous sinus (Figs 7.59–7.61), one on each side, situated on the body of the sphenoid
bone, extends from the superior orbital fissure to the apex of the petrous temporal bone.
Medially, the cavernous sinus is related to the pituitary gland and the sphenoid sinus. Laterally, it
is related to the temporal lobe of the brain. The internal carotid artery and the abducens nerve
pass through the cavernous sinus. On its lateral wall from above downwards lie the oculomotor,
trochlear and ophthalmic nerves (Fig. 7.60). The maxillary division of the trigeminal goes
through the lower part of the lateral wall or just outside the sinus. The endothelial lining
separates these structures from the cavity of the sinus.

Posteriorly, the sinus drains into the transverse/sigmoid sinus through superior petrosal sinus and
via the inferior petrosal sinus, passing through the jugular foramen, into the internal jugular vein.
The ophthalmic veins drain into the anterior part of the sinus. Emissary veins passing through the
foramina in the middle cranial fossa connect the cavernous sinus to the pterygoid plexus of veins
and to the facial veins. The superficial middle cerebral vein drains into the cavernous sinus from
above. The two cavernous sinuses are connected to each other by anterior and posterior
cavernous sinuses lying in front and behind the pituitary. See Clinical box 7.9
Neuro-ophthalmology of Meningiomas
Tulay Kansu, in Meningiomas, 2010

CAVERNOUS SINUS MENINGIOMAS

The cavernous sinus is a blood space containing endothelium, trabeculae, and ligaments. Each
cavernous sinus contains the internal carotid artery (and sympathetic plexus), oculomotor nerve,
trochlear nerve, abducens nerve, and the V1 to V2 branches of the trigeminal nerve.
Meningiomas arise primarily in the cavernous sinus from the meninges covering the floor of the
middle fossa in the region of the petrous apex or they involve the cavernous sinus secondarily.

The clinical picture of cavernous sinus meningiomas (CSMs) can arise from compression or
damage to one or more of the ocular motor nerves and vessels.3 Patients with cavernous sinus
tumors most frequently present with ocular motor deficits: ptosis, diplopia, anisocoria, or
complete ophthalmoplegia. The most common symptom is diplopia, resulting from paresis of the
ocular motor nerves. Damage to the oculomotor nerve within the cavernous sinus may produce a
partial or complete oculomotor nerve palsy. The pupil is usually involved in complete third nerve
palsy, and is mydriatic and not reactive to light or accommodation (Fig. 12-1). In partial third
nerve palsy, the pupil may be normal and initially may be mistaken for the ophthalmoparesis
produced by myasthenia gravis.4 If the pupil is smaller than normal, damage to the
oculosympathetic pathway should be considered. Slowly progressive compressive lesions such
as meningiomas and aneurysms may cause primary aberrant regeneration between the fibers of
the oculomotor nerve.5 The features of aberrant regeneration may be one or a combination of the
following: adduction on attempted upgaze, constriction of pupil on lateral gaze and elevation of
the upper lid on down gaze (Fig. 12-2).

Trochlear nerve paresis is often associated with other ocular motor nerve dysfunctions. When
both third and fourth cranial nerves are involved, the presence of fourth nerve palsy is detected
with the observation of internal rotation of scleral vessels during an attempt for downgaze.

Sixth nerve palsy is rarely isolated. Undiagnosed chronic isolated sixth nerve paresis or remitting
sixth nerve palsy associated with CSM were described mostly before modern imaging techniques
were available.6–8 The oculosympathetic pathway runs for a short distance with the abducens
nerve in the cavernous sinus; therefore ipsilateral postganglionic Horner syndrome may be
associated with unilateral abducens nerve paresis.1 Some patients may complain of dysesthesia
and pain in and around the eye, the orbit, or the upper face if the trigeminal nerve is involved.
Intermittent exotropia and neuroparalytic keratopathy has been reported as a rare presenting
signs of CSM.9,10 Ocular neuromyotonia is an intermittent ocular deviation due to spasm of one
or more eye muscles innervated by the same nerve and usually involves the oculomotor nerve.
Typically, spasm is triggered by sustained extremes of gaze. Although the radiotherapy remains
the most frequent cause, it has been described in patients with CSM who has not received
radiotherapy.11,12

The patient may have visual loss and visual field deficits if the optic nerve is damaged by growth
of the tumor into the orbit through the superior orbital fissure or by extension of the tumor to
involve the intracranial or intracanalicular portions of the nerve. Gaze-evoked amaurosis is a
transient monocular loss of vision occurring in a particular direction of eccentric gaze associated
with orbital tumors, optic nerve sheath meningioma, and CSM.13 Possible mechanisms for gaze
evoked amaurosis include inhibition of axonal impulses or transient optic nerve ischemia.

When cavernous sinus meningiomas compress the venous structures within that region or extend
into the orbit, mild proptosis may occur.

The decision regarding treatment is often difficult because of poor accessibility and the frequent
involvement of the cavernous carotid artery. Cranial nerve morbidity is a critical issue on the
resection of cavernous sinus meningiomas. Extraocular muscle functions may be impaired
because of cranial nerve III, IV, and VI injuries. The reported incidences of permanently
impaired extraocular muscle function developing after resection of cavernous sinus meningioma
is 14% to 58%.14–18 Initially, with the advent of skull base approaches, the authors thought that
these tumors could be removed with an acceptable cranial nerve morbidity. However, surgical
treatment of these tumors with radical excision using all the modern skull-base surgery
techniques is usually an unnecessary effort that leads to complications and decreases the quality
of life, which could have been avoided with more conservative strategies. Extraocular muscle
impairment is so disturbing that it becomes the main determining factor for the quality of life in
the postoperative period. With time, authors favored more conservative strategies with
cytoreduction of extracavernous tumor to protect brain function and to contain the tumor within
the cavernous sinus to preserve cranial nerve function.19–21 Repair of the third through sixth
cranial nerves injured during surgery can be pursued in suitable patients.22

Gamma-knife radiosurgery was found to be an effective low morbidity–related tool for the
treatment of cavernous sinus meningioma.23 Although it cannot eradicate the neoplasm, it makes
a favorable change in its natural history and helps clinical healing or stabilization of the
symptoms. From a clinical perspective, the authors indicated stable or improved neurologic
status in more than 90% of cases.24–27 Postoperative cranial nerve palsies are extremely rare (0%
to 1% post-radiosurgery cranial nerve palsy).25,26 However, radiation sensitivity of the optic
apparatus is one of the radiosurgery-limiting issues in the management of cavernous sinus
meningiomas. Duma and colleagues28 reported 2 of 34 patients with radiation-induced
neuropathy after radiosurgery. Removing the extracavernous part near the optic nerves also may
eliminate this problem; a distance may be maintained between the radiated tumor margin and the
closest optical anatomic structure to preserve optic nerve function.

The prognosis for vision depends on the extent of compression on optic nerves. Removal of
compressing part of tumor may help; however, ischemia to the optic nerve is also an issue in this
regard. Delayed ischemic optic neuropathy in two cases after surgery on skull-base meningiomas
have been reported and successfully treated with nimodipine and rheologic therapy.29 In addition,
some patients may experience spontaneous regression of symptoms and signs.30,3
Shaffrey, Mark & Dolenc, Vinko & Lanzino, Giuseppe & Wolcott, W.Putnam & Shaffrey, Christopher.
(1999). Invasion of the internal carotid artery by cavernous sinus meningiomas. Surgical neurology. 52.
167-71. 10.1016/S0090-3019(99)00092-0.

Meningiomas are the most common tumor involving the cavernous sinus. Although these tumors have
been known to invade adjacent structures such as bone, soft tissue, and brain, invasion of the internal
carotid artery (ICA) by meningiomas has only been recognized recently. The authors evaluate the extent
of carotid wall involvement in nine patients with cavernous sinus meningiomas encasing the ICA who
underwent en bloc resection of the cavernous sinus.

The en bloc tumor-ICA specimens were fixed in formalin, embedded in paraffin, and sectioned on a
rotary microtome. Hematoxylin and eosin, EVG, and HVG stains were performed and evaluated by light
microscopy.

There were four males and five females with a mean age of 47 years. Eight patients had not undergone
previous surgery, whereas one patient had been operated on before. In this latter case, however, the
cavernous sinus was not entered during the first operation. In all patients, stenosis of the ICA was
confirmed by preoperative angiography and/or magnetic resonance imaging (MRI). In seven cases, the
tumors were excised en bloc along with the stenotic ICA segment. A petrous-to-supraclinoid ICA bypass
was performed in these seven patients. In two cases, the tumor was excised with the stenotic artery, but
no bypass was performed. The final pathological diagnosis was meningothelial meningioma. In all cases
tumor cells were found in the adventitia of the cavernous carotid with stenosis of the arterial lumen.
Compression and/or obliteration of the vasa vasorum within the adventia was noted in all specimens. In
four cases, the tumor was found to have invaded the external elastic lamina. In two instances the
external elastic lamina was disrupted and the tumor focally extended into the media.

These findings suggest that in the case of cavernous sinus meningiomas with encasement and stenosis
of the intracavernous ICA, invasion of the vessel wall has occurred. The effect of these findings on the
management of cavernous sinus meningiomas and the involved ICA is discussed.

Our aim was to review the imaging findings of relatively common lesions involving the
cavernous sinus (CS), such as neoplastic, inflammatory, and vascular ones. The most common
are neurogenic tumors and cavernoma. Tumors of the nasopharynx, skull base, and sphenoid
sinus may extend to the CS as can perineural and hematogenous metastases. Inflammatory,
infective, and granulomatous lesions show linear or nodular enhancement of the meninges of the
CS but often have nonspecific MR imaging features. In many of these cases, involvement
elsewhere suggests the diagnosis. MR imaging is sensitive for detecting vascular lesions such as
carotid cavernous fistulas, aneurysms, and thromboses.

The cavernous sinus (CS) contains vital neurovascular structures that may be affected by
vascular, neoplastic, infective, and infiltrative lesions arising in the CS proper or via extension
from adjacent intra- and extracranial regions. Patients with CS syndrome usually present with
paresis of 1 or more cranial nerves (III−VI), which may be associated with painful
ophthalmoplegia. The clinician needs to know the type of CS lesion, its relationship to crucial
neurovascular structures, and its extension into the surrounding tissues. These findings are
essential for deciding therapeutic modalities such as microsurgery, radiation therapy, or medical
treatment as well as for appropriate planning of surgery or radiation therapy.1–8 Because the MR
imaging features of many of these lesions overlap and are often nonspecific, we will emphasize
those features that allow one to formulate a reasonable differential diagnosis.