Infectious Cavernous Sinus Thrombosis Presenting as Temporal Arteritis—A Case Report

Abstract

Cavernous sinus thrombosis (CST) is rare and can present with various nonspecific symptoms. The high mortality rate of this disease is largely due to delayed recognition and treatment. We report a case who presented with unrelenting headache and was diagnosed with temporal arteritis (TA) but did not respond to steroids. Imaging helped make the CST diagnosis and the patient responded well to treatment. This case reiterates the importance of early recognition and treatment of CST, and reminds physicians to include CST as an essential differential diagnosis of TA.

Introduction

Cavernous sinus thrombosis (CST) and temporal arteritis (TA) are 2 distinct disease processes. CST is a rare form of cerebral venous sinus thrombosis that is often secondary to local infections spreading to the cavernous sinuses.¹ TA, also called giant cell arteritis, is a systemic inflammatory vasculitis of medium and large-sized arteries that classically involves the temporal artery.² Early diagnosis and treatment are crucial for both conditions to achieve good outcome and minimize disability. However, overlapping symptoms between CST and TA, such as new onset headache, visual complains, elevated erythrocyte sedimentation rate (ESR) and, occasionally, jaw discomfort, can make timely diagnosis very challenging. Here we report a case who presented with symptoms suggestive of TA but was found to be infectious CST.

Case Description

66-year-old female with a history of hypertension, hypothyroidism, and migraine presented to the Emergency Department complaining of headache for 3 days. Headache was gradual onset throbbing pain in the bilateral frontotemporal regions, with radiation to the lateral and posterior neck. She denied any fever, recent infection, or vision changes. She tried ibuprofen at home without relief. Neurologic exam showed no focal findings. Head computed tomography (CT) reported no acute intracranial abnormality but failed to mention the complete opacification of the left sphenoid sinus. She received intravenous (IV) analgesics with symptom improvement and was discharged home. However, for the next 2 weeks, her headache progressively worsened and gradually spread to bilateral cheeks, jaws and shoulders. She also developed scalp tenderness, inability to adequately open her left jaw, and pain at the left temporomandibular joint (TMJ). She was seen by her primary care physician and found to have elevated ESR. TA was considered and prednisone was started at 60 mg per day, but her headache continued to worsen.

She was subsequently referred to vascular surgery for a temporal artery biopsy. She had diplopia 2 days prior to the biopsy, and on the day of biopsy she also developed right eye bulging and eyelid swelling. She was afebrile and fully orientated but lethargic. Visual fields were intact. She had bilateral incomplete horizontal gaze with mild right cranial nerve (CN) VI palsy, right eye mild ptosis with eyelid edema and conjunctiva chemosis, as well as limited range of motion at bilateral TMJs. The rest of the exam was normal. Laboratory tests revealed a leukocytosis with WBC at 27.7 x 10³/µl with 88% neutrophils, elevated serum creatinine at 2.27 mg/dl and blood urea nitrogen (BUN) at 62 mg/dl. Repeat ESR was still elevated at 56 mm/h. HIV and Lyme antibodies were negative and thyroid function was normal.

Brain and orbit magnetic resonance imaging (MRI) with and without contrast demonstrated no infarct or mass, but left sphenoid sinusitis with possible pus, right superior ophthalmic vein thrombosis (Figure 1A and D), cavernous sinus expansion and thrombosis bilaterally (Figure 1B and E), and partial thrombosis of the right upper jugular vein (Figure 1C and F). Brain MR venogram (MRV) showed no other major intracranial venous sinus thrombosis. Maxillofacial CT without contrast showed right periorbital soft tissue swelling and asymmetric right-sided exophthalmos, right superior orbit changes compatible with known superior ophthalmic vein thrombosis, and left sphenoid sinus opacification (Figure 1G and H) with thinning of the right posterior margin of the sinus which may communicate with the right cavernous sinus (Figure 1I). Partial opacifications of the right sphenoid sinus and bilateral posterior ethmoid air cells were also noted.

Figure 1.

Brain and orbit MRI demonstrated thrombosis of right superior ophthalmic vein, bilateral cavernous sinuses and right internal jugular vein with restricted diffusion in DWI (A, B and C respectively, arrows), and filling deficits in T1 with contrast (D, E and F respectively, arrows). Maxillofacial CT without contrast showed left sphenoid sinus opacification (G and H, arrows) with thinning of the right posterior margin of the sinus (I, arrow). Partial opacifications of the right sphenoid sinus were also present (G and H).

She was started on IV heparin and antibiotics for CST secondary to sinusitis. She underwent bilateral endoscopic sphenoidectomy and ethmoidectomy with polyp removal. Immediately post procedure, her headache resolved without recurrence. Right eye swelling and diplopia also resolved within 3 days of surgery. Leukocytosis and elevated creatinine gradually normalized. Temporal artery biopsy showed normal vasculature. Sphenoid sinus biopsy reported benign sinonasal mucosa with mild chronic nonspecific inflammation. IV heparin was switched to apixaban for total 3-month treatment and IV antibiotics was changed to oral form for a 14-day course. Prednisone was tapered off. She was discharged in excellent condition. She followed up with otolaryngology and neurology after discharge and had been doing well without headache recurrence.

Discussion

Infectious CST is thrombophlebitis in the cavernous sinus which affects the multiple structures residing in the sinus. It is an unusual complication of adjacent infection such as paranasal sinusitis, facial or periorbital cellulitis. If left untreated, it can lead to high rate of mortality and severe neurological sequalae. Thanks to effective antibiotics and surgical treatment, the prognosis of CST has improved dramatically³; however, long-term sequelae remain frequent including vision loss and CN palsy.^1,4-7

Early recognition is the key for optimal clinical outcome but remains challenging. Eye findings are characteristic for CST, including periorbital edema and pain, lid erythema, ptosis, proptosis, and ophthalmoplegia involving CN III, IV, and VI,^1,4-6 but usually occur at a later stage of the disease. In the earlier phase of the disease, CST often presents with nonspecific headache, fever, lethargy, and altered mentation.^4-6 The average time between clinical onset to diagnosis was 13.7 days in one study⁴ and more than 7 days in 2/3 patients in another study.⁶ The duration of onset-to-diagnosis is one of the significant prognostic factors.⁶

Our current case presented with unrelenting frontotemporal headache, jaw pain, scalp tenderness and shoulder pain, resembling symptoms for TA. The jaw pain and scalp tenderness may be caused by the involvement of internal jugular vein with infectious thrombophlebitis and thrombosis (Figure 1C and F), as seen in Lemierre’s syndrome.^8,9 However, jaw pain should not be mistaken for jaw claudication which refers to pain in the proximal jaw that develops only after a brief period of chewing. Jaw claudication is one of the features highly specific for TA, along with diplopia and abnormality on temporal artery examination.¹⁰ Although our case lacked these highly specific symptoms, combination of multiple less specific clinical variables, such as scalp tenderness, temporal headache, advanced age and elevated ESR, still put our patient at intermediate risk for TA according to the prediction rule of Younge et al.¹¹ Eventually, typical eye findings occurred along with unresponsiveness to steroids treatment, and CST was confirmed by neuroimaging studies. The time from symptom onset to diagnosis was 22 days in this case.

Several reports in the literature also described overlapping symptoms and early misdiagnosis between TA and CST. Eweiss et al. reported a case who presented with right-sided temporal headache and was treated with steroids for suspected TA. Unresponsive to steroid treatment, patient developed proptosis, ptosis and ophthalmoplegia in the right eye, promoting the diagnosis of CST with CT angiogram 5 days after symptoms onset. Patient responded well to antibiotics, anticoagulation and endoscopic sphenoidotomies without residue neurologic deficit.¹² On the other hand, Finsterer et al. reported one case presented with headache, fever, facial edema after influenza vaccination, and progressed to blurry vision, proptosis, pain with eye movement and right arm weakness. MRI revealed CST; however, antibiotics and anticoagulation with IV heparin were not effective. Symptoms worsened with right eye chemosis, bilateral ptosis, spontaneous nystagmus, right CN VI palsy. Cerebral angiogram showed recanalized CST, but torturous temporal artery, which along with continuous elevation of ESR and C-reactive protein, led to the suspicious of TA. Temporal artery biopsy confirmed the diagnosis and steroid therapy finally cured the patient.¹³ In addition, Gout et al. reported a case of TA with Vernet’s syndrome (simultaneous and unilateral involvement of CN IX, X, and XI) but also found to have jugular vein thrombosis extending to the lateral sinus. It was suspected that inflammatory process might have triggered a hypercoagulable state responsible for thrombosis.¹⁴

Brain MRI is the neuroimaging of choice for evaluation of new onset, atypical headache in non-emergency setting.¹⁵ Although conventional MRI is not the diagnostic tool for TA, it is the diagnostic test for CST. Specifically, when suspicious for CST, contrast-enhanced MRV and CT venogram are highly sensitive, whereas time-of-flight MRV or non-contrast CT may miss the diagnosis.¹ Hsu et al. stated that expansion of the cavernous sinus was the most common neuroimaging feature, followed by convexity of the lateral wall of the cavernous sinus and filling defect of the cavernous sinus,⁶ which is echoed by our findings (Figure 1E). Furthermore, MRI diffusion weighted imaging (DWI) can be very useful in CST diagnosis. In agreement with a previous case report,¹⁶ DWI in our case also showed restricted diffusion in the cavernous sinus (Figure 1B) as well as the superior ophthalmic vein (Figure 1A), a structure frequently involved in CST but easily missed by MRV or post-contrast CT.

Consistent with previous studies,^1,4,7,17 our case showed that the combination of early antibiotics and surgical intervention was an effective strategy for the treatment of infectious CST. As reported elsewhere,^1,12,17 steroids were not effective in CST treatment but could help in other conditions with similar presentation such as TA, Tolosa-Hunt syndrome or sarcoidosis. Although it is still contentious, most experts recommend anticoagulation in the absence of strong contraindications.^1,18 Retrospective reviews suggest a possible decrease in mortality from 40% to 14% and reduction in neurologic morbidity from 61% to 31% when anticoagulation is combined with antibiotics for infectious CST¹ and it appears to be safe.^1,3

Conclusion

Cavernous sinus thrombosis can present initially with symptoms suggestive of TA, and its typical eye findings may only occur at later stage of the disease development. Early diagnosis requires a high index of suspicion, which is critical for a favorable outcome. Due to overlapping symptoms between TA and CST, we recommend including both in the differential diagnosis for cases similar to this one. Antibiotics, anticoagulation, and urgent surgical intervention may constitute a successful regimen in treatment of CST, a potentially life-threatening condition.