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Young woman presents with painful ophthalmoplegia in left eye
Review of systems revealed non-resolving purulent nasal discharge, tooth pain and persistent headaches with neck pain.
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A 20-year-old woman presented to Tufts New England Eye Center with 1 day of progressively worsening left eyelid swelling and pain with eye movement. Symptoms initially began 10 days before presentation with purulent nasal discharge, which was diagnosed by an outside hospital as viral sinusitis and treated with a short course of oral methylprednisolone and fluticasone nasal spray. Three days later, she developed tooth pain and dysphagia, followed by severe headaches, for which she returned to the emergency room. She was diagnosed with migraine headache exacerbation and discharged on a “migraine cocktail” consisting of sumatriptan, aspirin/acetaminophen/butalbital and verapamil. Her migraine symptoms never fully resolved, and she began to feel increasingly lethargic. The day before presentation, she developed fever, neck pain and left eye pain. Her left eye pain was worse with movement and associated with redness, photophobia and blurred vision. She also reported intermittent diplopia and inability to close the left eye fully.
The patient’s only ocular history was high myopia for which she wore glasses. She denied contact lens use. She had a medical history significant for migraine headaches, asthma and seasonal allergies. Her medications included albuterol as needed, montelukast, cetirizine, methylprednisolone, sumatriptan, aspirin/acetaminophen/butalbital and verapamil. She had no known drug allergies. She was a full-time college student who commuted from home. She denied smoking and use of alcohol or drugs. Family history was significant only for asthma in her mother.
The patient’s initial vital signs included temperature of 39°C, heart rate of 102 bpm to 144 bpm, blood pressure of 94/70 and respiratory rate of 25 breaths per minute, saturating 100% on room air. Initial lab work revealed a WBC of 30, ESR of 80, CRP of 402 and lactate of 3.6. Bedside exam revealed 20/20 vision bilaterally at near with glasses. Color plates were 10/10 bilaterally. The right pupil was round and reactive to light without afferent pupillary defect. The left pupil was sluggish without an afferent pupillary defect. The right extraocular muscles had –2 deficit in abduction and –1 deficit in adduction, elevation and depression. The left extraocular muscles had –4 deficit in abduction, adduction, elevation and depression. The patient had left ptosis and hypoesthesia in the V2 distribution. She had trace edema of right upper and lower lids and 3+ edema of left upper and lower lids. There was 4 mm relative proptosis of the left eye with significant lagophthalmos (Figure 1).
Source: Huan Meng Mills, MD, and Alison Callahan, MD
IOP was 18 mm Hg on the right and 26 mm Hg on the left. The right eye was white and quiet, while the left eye had 3+ bullous chemosis with 3+ conjunctival injection. Corkscrew vessels were absent from both eyes. Dilated fundus exam was within normal limits in both eyes with healthy-appearing optic nerves, vessels and retinas.
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Left painful ophthalmoplegia
The differential diagnosis for this patient includes cavernous sinus thrombosis, orbital cellulitis, subperiosteal abscess, orbital apex syndrome and carotid-cavernous fistula. The key clinical clue for locating the lesion in this case is V2 hypoesthesia. This finding in the setting of acute-onset left ophthalmoplegia, pain with extraocular movement, elevated IOP, proptosis and chemosis puts cavernous sinus thrombosis highest on the differential diagnosis. Orbital cellulitis with or without a subperiosteal abscess also presents with pain on extraocular movement, chemosis and conjunctival injection but is not usually associated with ophthalmoplegia or elevated IOP, and is anatomically distinct from the path of cranial nerve V2. Orbital apex syndrome can also cause ophthalmoplegia but is less likely because of the preserved optic nerve function as measured by visual acuity, color vision and pupils. As with orbital cellulitis, orbital apex syndrome is also anatomically distinct from cranial nerve V2. A carotid-cavernous fistula can certainly present with left proptosis and elevated IOP, but the lack of corkscrew vessels or history of trauma makes this less likely. Lastly, meningitis should be ruled out with lumbar puncture because of the headache, neck stiffness and lethargy symptoms; however, meningitis alone is unlikely to cause complete unilateral ophthalmoplegia with proptosis.
Workup and management
There were several concerning findings on this patient’s initial examination that warranted prompt intervention. Tachycardia, tachypnea and hypotension in the setting of an elevated WBC of 30 may indicate sepsis. While she did not require pressor support, abnormal vital signs combined with an abnormal neurological examination warranted admission to the intensive care unit for close monitoring. Blood cultures were obtained immediately, and the patient was started on empiric broad-spectrum antibiotics including vancomycin, ceftriaxone and metronidazole within the hour. Sinus cultures and sputum cultures were also obtained, and a lumbar puncture was performed to rule out meningitis. She underwent an urgent CT of the head and orbits with and without contrast, which revealed extensive frontal, maxillary, ethmoid and sphenoid sinus opacification in addition to dilated right and left ophthalmic veins (Figure 2). Given the abnormal CT, she also underwent urgent MRI/MRV of the head and orbits with and without gadolinium (Figure 3), which revealed filling defects in bilateral ophthalmic veins and bilateral confluent areas of hypoenhancement with restricted diffusion consistent with cavernous sinus thrombosis.
In addition to an ophthalmology consult, the ENT, neurosurgery and infectious disease services were consulted. The patient was taken to the operating room for functional endoscopic sinus surgery and tooth extraction by ENT to control the infectious source. She was started on systemic anticoagulation immediately after surgery. Blood and sinus cultures taken in the operating room subsequently grew pansensitive 3+ Streptococcusconstellatus. The patient was started on brimonidine in the left eye three times a day for elevated IOP and frequent lubrication because of her lagophthalmos.
Discussion
The anatomy of the cavernous sinus is unique, and lesions in this special location can affect all three cranial nerves responsible for eye movement: oculomotor nerve (CN III), trochlear nerve (CN IV) and abducens nerve (CN VI). In addition, the ophthalmic (V1) and maxillary (V2) nerves also travel through the cavernous sinus, and lesions can lead to hypoesthesia in their respective distributions. The most common clinical manifestations of cavernous sinus thrombosis are fever (94%), ptosis/proptosis/chemosis (95%), ophthalmoplegia (88%) and periorbital swelling (73%). Less common clinical symptoms include pupil abnormalities (32%), decreased visual acuity (22%) and diplopia (12%).
Cavernous sinus thrombosis is rare, with only a few hundred case reports in the literature. The estimated annual incidence is approximately one per 100,000 per year. The largest review analyzed 96 cases over 40 years from 1940 to 1984. Due to its infrequency, all studies are retrospective, and there are no prospective studies regarding the treatment of cavernous sinus thrombosis. The most common source of infection is sinusitis, dental infection, otitis media, facial cellulitis or abscess, periorbital and orbital cellulitis, and tonsillitis. The veins in the central triangle of the face are valveless, thus making them especially vulnerable to retrograde spread of infection and subsequent septic cavernous thrombosis. The most common organisms associated with cavernous sinus thrombosis are Staphylococcus, Streptococcus, Pneumococcus, gram-negative bacilli and rarely fungal cases such as Aspergillus and mucormycosis.
MRI and MRV of the brain and orbits with and without gadolinium is the preferred imaging study, but CT scan with and without contrast is often done first due to more widespread availability and accessibility. It is important to indicate the suspected location of the lesion to the radiologist when ordering the examination, as findings may be subtle.
In addition to antibiotics, drainage of the infective source and anticoagulation are two cornerstones of treatment for cavernous sinus thrombosis. ENT should be involved early to expedite sinus drainage as needed. Due to its proximity to the cavernous sinus, the sphenoid sinus is especially important to drain if involved to prevent spread of infection. Anticoagulation is also indicated in all causes of confirmed cavernous sinus thrombosis in which there is no evidence of intracranial hemorrhage to prevent extension of the thrombosis and limit septic emboli. In terms of choice of anticoagulation, novel anticoagulation agents such as rivaroxaban, a factor Xa inhibitor, have been shown to be non-inferior to enoxaparin and warfarin. Patients are often started on a heparin drip or enoxaparin injections in the acute setting and transitioned to either warfarin or a novel anticoagulation agent on discharge to be continued for a minimum of 6 months. There is no standard course for how long patients should be treated with antibiotics, but it is generally agreed upon that patients should be treated for a minimum of 2 weeks beyond clinical resolution of symptoms. Some studies show that for MRSA central nervous system (CNS) infections, linezolid may have better CNS penetration than the more commonly used vancomycin. Linezolid has approximately 70% CNS penetration whereas vancomycin only has 20% to 50% penetration. Corticosteroids are occasionally used to decrease intracranial inflammation and edema in patients who are already on appropriate antibiotics, but their use is controversial and not routinely recommended.
Cavernous sinus thrombosis is associated with high mortality and morbidity. Only 40% of patients achieve full recovery without any residual neurological or ophthalmological deficits. Mortality rates are around 30%, and another 30% of patients have serious chronic sequelae such as oculomotor weakness, blindness, pituitary insufficiency and/or hemiparesis. High clinical suspicion coupled with detailed review of imaging studies is key in prompt diagnosis and treatment. A multidisciplinary team consisting of ophthalmology, ENT, neurosurgery and infectious disease is preferred for management of this complex and potentially lethal condition. Anticoagulation has been shown to be beneficial in terms of reduced mortality and morbidity, and should be initiated promptly in the absence of any contraindications.
Clinical course continued
The patient was ultimately discharged on hospital day 15, at which point ophthalmoplegia, proptosis, chemosis, ptosis and conjunctival injection resolved completely (Figure 4). She regained full extraocular motions bilaterally. At the time of discharge, she continued ceftriaxone and metronidazole IV via a PICC line for an additional 2 months. She will continue oral rivaroxaban for a total of 6 months. Repeat MRI 2 months after initial presentation revealed interval recanalization of ophthalmic vein and tributaries. The patient is doing well with no residual ophthalmologic or neurological deficits noted.
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- For more information:
- Huan Meng Mills, MD, and Alison Callahan, MD, can be reached at New England Eye Center, Tufts University School of Medicine. 800 Washington Street, Box 450, Boston, MA 02111; website: www.neec.com.
- Edited by Aubrey R. Tirpack, MD, and Astrid C. Werner, MD. They can be reached at the New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.