Basics
Description
- Cavernous sinus syndrome comprises disease processes that localize to the cavernous sinus-a venous plexus that drains the face, mouth, tonsils, pharynx, nasal cavity, paranasal sinuses, orbit, middle ear, and parts of the cerebral cortex.
- Small lesions in this region may produce dramatic neurologic signs.
Epidemiology
Cavernous sinus syndrome is a rare but serious condition.
Pathophysiology
- The cavernous sinus is located lateral to the pituitary gland and sella turcica, superior to the sphenoid sinus, and inferior to the optic chiasm.
- Within the cavernous sinus are the carotid artery, the pericarotid sympathetic fibers, and the abducens nerve (VI); within its lateral wall are the oculomotor nerve (III), the trochlear nerve (IV), and the ophthalmic and maxillary divisions of the trigeminal nerve (V1, V2).
- Cavernous sinus syndrome is typically caused by septic or aseptic sinus thrombosis, neoplasm, or trauma. Acute obstruction by mass or thrombosis may progress rapidly if not diagnosed and treated quickly.
Etiology
- Infectious agents include Staphylococcus aureus, Streptococcus pneumoniae, Gram-negative rods, and anaerobes; Mucormycosis and Aspergillus in immunocompromised patients.
- Aseptic venous thrombosis has been associated with sickle cell anemia, trauma, dehydration, vasculitis, pregnancy, oral contraceptive use, congenital heart disease, inflammatory bowel disease, and hypercoagulable states.
- Neoplasms involving the cavernous sinus include pituitary adenomas, meningiomas, trigeminal schwannomas, craniopharyngiomas, lymphomas, neuromas, chordomas, chondrosarcomas, rhabdomyosarcomas, nasopharyngeal carcinomas, and very rarely, teratomas. Neoplasms may present with diplopia, visual field deficits, headache, or isolated cranial nerve deficits.
- The lateral extension of pituitary neoplasms into the cavernous sinus usually affects the 3rd cranial nerve, with the 4th and 6th nerves less commonly involved. Rupture of a cystic craniopharyngioma may present as acute cavernous sinus syndrome.
- Carotid-cavernous fistulas, often with a more chronic course, are direct high-flow shunts between the internal carotid artery and the cavernous sinus. Most often sequelae of trauma, they may present with a history of ocular motility deficits, arterialization of conjunctival vessels, and a bruit usually heard best over the orbit. Less commonly, rupture of a carotid cavernous aneurysm may lead to fistula formation.
- Nonspecific and idiopathic inflammation of the cavernous sinus, also called idiopathic cavernous sinusitis or Tolosa-Hunt syndrome, has been reported in patients as young as 3 ½ years. This is a diagnosis of exclusion. However, MRI may show enlargement of the affected cavernous sinus with an adjacent soft tissue mass that resolves after treatment with steroids.
Diagnosis
History
- Recent facial furuncle or cellulitis, sinusitis, dental infection, otitis, or orbital cellulitis may predispose to cavernous sinus syndrome.
- Fever, headache, eye pain, diplopia, and facial paresthesias may be present.
Physical Exam
- Conjunctival injection with lid swelling and proptosis indicates cavernous sinus venous congestion.
- Ptosis, anisocoria, ophthalmoparesis, and facial sensory changes are signs of cranial nerve involvement.
- Horner syndrome: Sympathetic nerve fibers traveling with V1 may be affected. Usually occurs in conjunction with an abducens nerve (CN VI) palsy with an inability to abduct the eye.
- Signs and symptoms begin unilaterally but may rapidly spread bilaterally.
- The optic nerve and visual acuity are spared early in cavernous sinus syndrome but can be affected as it progresses.
- Funduscopic findings include venous dilatation and hemorrhages.
- Ocular bruit may be heard in any acute cavernous sinus syndrome but especially in carotid-cavernous fistula.
- Signs of meningitis and systemic toxicity rapidly evolve if infections are untreated.
Diagnostic Tests & Interpretation
Lab
- CBC, ESR, PT/PTT, blood culture: Basic studies in any child with suspected acute cavernous sinus syndrome. Blood cultures are positive in 70% of cases of septic venous sinus thrombosis.
- Lumbar puncture should be performed if there is no contraindication and infection is suspected.
- ~35% of patients with septic cavernous sinus thrombosis have CSF findings consistent with bacterial meningitis-excess neutrophils, increased protein, and/or decreased glucose.
- Evaluation for a prothrombotic state should be considered in patients with cavernous sinus thrombosis, especially in the absence of infection or trauma. Specific labs include protein C activity, protein S activity, antithrombin III activity, factor V Leiden gene mutation, prothrombin gene mutation, anticardiolipin antibodies, β-2-glycoprotein antibodies, dilute Russell viper venom time, homocysteine, lipoprotein(a), and factor VIII activity.
- Antinuclear antibody panel, angiotensin-converting enzyme level, and HIV test should be obtained before diagnosis of Tolosa-Hunt syndrome (diagnosis of exclusion).
Imaging
Any child with proptosis, cranial nerve findings, or an ocular bruit should have an urgent MRI or CT.
- MRI, with and without gadolinium, with special attention to the cavernous sinus and parasellar region, is the imaging study of choice.
- Magnetic resonance venography may be helpful.
- CT angiography may be the preferred study to evaluate for carotid-cavernous fistula.
Diagnostic Procedures/Other
- Diagnosis of carotid-cavernous fistulas requires angiography.
- Nasopharyngeal biopsy and culture if Mucormycosis or Aspergillus is suspected.
Differential Diagnosis
Other disorders that may resemble cavernous sinus syndrome include the following:
- Orbital cellulitis
- Sphenoid sinusitis
- Thyroid eye disease
- Cavernous carotid aneurysm
- Orbital apex tumor
- Orbital pseudotumor
- Ocular migraine
- Ocular trauma
- Burkitt lymphoma
Alert
- Ophthalmoplegic migraine or cluster headache must be distinguished from cavernous sinus syndrome by neuroimaging studies and history.
- Proptosis does not occur in migraine or cluster headache.
- Ophthalmoplegic migraine is a diagnosis of exclusion, especially on first presentation.
- Acute infection and hemorrhage of the pituitary gland-pituitary apoplexy-may present with acute bilateral ophthalmoplegia and signs of acute pituitary insufficiency; most commonly occurs with pituitary neoplasms but may also occur in pregnant women at the time of delivery.
- Chronic granulomatous disorders such as sarcoid and tuberculosis may underlie cavernous sinus syndrome.
Treatment
First priority is to rule out septic cavernous sinus thrombosis, life-threatening infections of the face, sinuses, middle ear, teeth, and orbit.
Medication
First Line
- For septic cavernous sinus thrombosis, broad-spectrum antibiotics (including coverage of penicillinase-resistant staphylococci and anaerobes) are begun immediately. Duration of therapy is usually 2-4 weeks beyond the resolution of symptoms.
- Amphotericin B if Mucormycosis or Aspergillus is suspected
- Idiopathic cavernous sinusitis, a diagnosis of exclusion, responds to corticosteroids. Treatment should not be started until neoplasm and infection have been ruled out.
Second Line
Anticoagulation is controversial, but one study in adults found that heparin reduced morbidity from septic cavernous sinus thrombosis.
Surgery/Other Procedures
- Surgical drainage of the primary infection (i.e., sinusitis) may be indicated (avoiding surgical manipulation of the cavernous sinus itself).
- Posttraumatic carotid-cavernous fistulas rarely close spontaneously and have been treated with endoarterial balloon embolization.
Ongoing Care
- Septic cavernous sinus thrombosis may relapse or embolic abscesses may develop 2-6 weeks after therapy has been stopped.
- Repeat MRI with gadolinium should be considered, especially if symptoms recur or new symptoms develop.
- Mortality remains 13-30%, and <40% of patients recover fully from cranial nerve deficits.
- Patients with carotid-cavernous fistulas frequently have persistent cranial nerve deficits even after embolization.
- Idiopathic cavernous sinusitis responds to steroids, but relapses can be problematic. Clinical follow-up and serial MRI scans are indicated to rule out a low-grade neoplasm or fungal infection.
- Consultation with a neurooncologist and a neurosurgeon is important for suspected neoplasms or surgical lesions.
Prognosis
- Prognosis depends on the underlying cause.
- Bacterial infections usually respond if diagnosed and treated promptly.
Complications
- Vary with the cause of cavernous sinus syndrome. Septic cavernous sinus syndrome thrombosis and fungal infections may rapidly evolve to bilateral thrombosis, life-threatening sepsis, and meningitis.
- Visual impairment and cranial nerve palsies may persist.
- Mucormycosis, usually seen in patients with diabetic ketoacidosis, is especially dangerous.
- Carotid arteritis with resulting stenosis, occlusion, or embolism may occur, resulting in focal neurologic deficits.
- Aseptic cavernous sinus syndrome thrombosis may evolve to more extensive intracranial venous sinus thrombosis.
- Local spread of neoplasms will continue if not treated appropriately.
Additional Reading
- Chen CC, Chang PC, Shy CG, et al. CT angiography and MR angiography in the evaluation of carotid-cavernous sinus fistula prior to embolization: a comparison of techniques. Am J Neuroradiol. 2005;26(9):2349-2356. [View Abstract]
- Ebright JR, Pace MT, Niazi AF. Septic thrombosis of the cavernous sinuses. Arch Intern Med. 2001;161(22):2671-2676. [View Abstract]
- Lee AG, Quick SJ, Liu GT, et al. A childhood cavernous conundrum. Surv Ophthalmol. 2004;49(2):231-236. [View Abstract]
- Leiba H, Jaqqi GP, Boltshauser E, et al. Prediction of the clinical outcome of cavernous sinus lesions in children. Neuropediatrics. 2013;44(4):191-198. [View Abstract]
Codes
ICD09
- 437.6 Nonpyogenic thrombosis of intracranial venous sinus
- 747.81 Anomalies of cerebrovascular system
- 378.55 External ophthalmoplegia
ICD10
- I67.6 Nonpyogenic thrombosis of intracranial venous system
- G08 Intracranial and intraspinal phlebitis and thrombophlebitis
- H49.889 Other paralytic strabismus, unspecified eye
SNOMED
- 35386004 Cavernous sinus syndrome
- 95794005 Tolosa-Hunt syndrome
FAQ
- Q: Will my child's eye movements return to normal?
- A: In most cases, oculomotor nerves regain function as other signs improve, although they may take the longest to recover.
- Q: Can more pain medicine be given?
- A: There is often an attempt to balance side effects of sedation and hypoventilation against the need for pain control, especially when intracranial pressure is a concern.