Septic cavernous sinus thrombosis secondary to acute bacterial sinusitis: A retrospective study of seven cases Franklin Lizé, M.D., Benjamin Verillaud, M.D., Pierre Vironneau, M.D., Jean-Philippe Blancal, M.D., Jean-Pierre Guichard, M.D., Romain Kania, Ph.D., and Philippe Herman, Ph.D.

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ABSTRACT

Background: Septic cavernous sinus thrombosis (SCST) is a rare but severe complication of acute bacterial sinusitis. Evaluations of advances in imaging techniques as well as in medical and surgical treatment are hampered by the lack of recent studies. Objective: We aim to report our experience in the management of SCST in patients with acute bacterial sphenoid sinusitis over the past 10 years and to discuss the initial work-up and treatment strategies. Methods: We performed a retrospective study of patients admitted for SCST related to acute sinusitis at a tertiary care center between 2003 and 2013. Clinical charts were reviewed for demographics, clinical presentations, imaging and microbiologic findings, medical and surgical treatments, and outcomes. Results: Seven patients were treated for SCST. Sphenoid sinus was involved in all cases. The most frequent presenting signs included headache (100%), cranial nerve impairment (86%), fever (71%), and orbital symptoms (71%). Diagnosis was confirmed by a cerebral contrast-enhanced CT scan in all cases. Four patients (57%) had an additional intracranial complication. The average time between clinical onset and diagnosis was 13.7 days. All patients were treated by high-dose i.v. antibiotics, anticoagulation therapy, and surgical endoscopic drainage of the infected sinuses. This treatment strategy resulted in a mortality rate of 0%, but four out of the seven patients developed transient or permanent neurologic deficits, including one with permanent unilateral visual loss. Conclusion: The combination of high-dose i.v. antibiotics, anticoagulation therapy, and endoscopic drainage of the infected paranasal sinus is an effective strategy for the treatment of SCST, but long-term sequelae remain frequent. (Am J Rhinol Allergy 29, e7–e12, 2015; doi: 10.2500/ajra.2015.29.4127)

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eptic cavernous sinus thrombosis (SCST) is a severe complication of acute sinusitis (especially sphenoid and ethmoid sinusitis), which accounts for 8%–16% of all intracranial complications.1–3 Mortality rates of 14%–79% have been reported.2–6 However, these figures should be considered with caution, because many of the patients were treated more than 20–30 years ago. Advances in the radiologic assessment as well as in the medical and surgical treatments seem to have improved the global prognosis of SCST.1,7 The aim of this work was to report our experience in the management of SCST, based on a series of seven patients treated over the past 10 years at a tertiary care center. We focused on the presenting signs and radiologic and microbiologic findings. We also discussed the treatment strategies, particularly with respect to antibiotics, anticoagulation therapy and surgical treatment.

PATIENTS AND METHODS

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This was a retrospective study based on patients diagnosed with SCST secondary to acute bacterial sinusitis who were treated at our institution between January 2003 and December 2013. These patients were identified from a local database. All patients underwent high-resolution contrast-enhanced computed tomography (CT) scan, including the preadministration of a contrast agent followed by reinjection, or a late venous-phase acquisition. The CT scan with injection was preceded by an injection-free examination centered on the paranasal sinuses to look for a sinus infection. Magnetic resonance imaging (MRI) was performed when an additional intracranial complication was found by CT scan, with the next sequences focused on the cavernous sinus: T1 weighting without and with i.v. contrast material, T2 weighting, and fluid attenuated inversion recovery. Clinical charts were reviewed for demographics, previous history of rhinosinusitis, presenting symptoms and signs, radiologic findings,

Department of Otorhinolaryngology, Head and Neck Surgery, Lariboisie`re Hospital, Paris VII University, Paris, France The authors have no conflicts of interest to declare pertaining to this article Address correspondence to Franklin Lizé, M.D., Service ORL, Hôpital Lariboisie`re, 2 rue Ambroise Paré, 75010 Paris, France E-mail address: [email protected] Copyright © 2015, OceanSide Publications, Inc., U.S.A.

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complications, medical and surgical management, and long-term outcome. The present study was approved by the local institutional review board (Comite´ Ethique et de Protection des Personnes Ile de France, Lariboisie`re Hospital, Paris VII University, Paris, France), and written consent was obtained from all patients.

RESULTS Between 2003 and 2013, seven patients (two men and five women) were treated at our institution for SCST secondary to sinusitis. The mean age at diagnosis was 35.7 years (range of 23–55 years). Only one out of seven patients had a previous history of rhinosinusitis, who had undergone a maxillary antrostomy several years before (contralateral to the SCST side). None of the patients were immunocompromised. Table 1 summarizes the main clinical and radiologic features, complications, and microbiologic findings. A sphenoid sinusitis was present in all cases, either alone (28%), or in association with a posterior ethmoid sinusitis (57%) or with ipsilateral pansinusitis (14%). All infections were evolving acutely at the time of SCST diagnosis. The most frequent presenting symptoms and signs were headache (100% of the cases), cranial nerve impairment (86%, including III, IV, VI, and V2, but also X and XII nerves), fever (71%), and orbital symptoms (71%, including chemosis, proptosis, ptosis, and visual loss). One patient also developed Horner’s syndrome, and three patients had associated neurologic symptoms (neck stiffness, altered mental status, and seizures). All patients underwent contrast-enhanced CT scan, either alone (three patients) or in combination with MRI (four patients). The main radiologic findings are summarized in Table 2. The most frequent abnormal radiologic finding was a filling defect in the opacification of the cavernous sinus (100% of the patients), followed by a lateral displacement of the lateral wall of the cavernous sinus (71%), a global expansion of the cavernous sinus (56%) (Fig. 1), and an expansion of the superior ophthalmic vein (28%). Thrombosis extended to the contralateral cavernous sinus in one patient and to the ipsilateral transverse sinus in two patients (Figs. 2 and 3).

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Table 1. Clinical presentations, imaging results and microbiological findings in patients with septic CST Case

Age/Gender Rhinosinusal History/ Underlying Condition

Clinical Signs on Admission

Patient one

26 years/F



Patient two

37 years/F



Patient three

33 years/M



Patient four

55 years/M

Patient five

23 years/F



Headache, R R III and VI chemosis, ptosis, nerve diplopia, palsies photophobia

Patient six

26 years/F



Fever, headache, seizure, altered mental status

Patient seven 50 years/F

Wellcontrolled asthma

Fever, headache, R ptosis Fever, headache, bilateral chemosis, proptosis, ophthalmoplegia Fever, headache, bilateral horizontal diplopia, L Horner’s syndrome Fever, headache, L chemosis, ptosis, proptosis, diplopia Altered mental status

Ophthalmic Complication

Imaging Findings

Other Complications

Microbiological Findings

R III nerve R sphenoiditis, R — Haemophilus palsy CST influenzae Bilateral visual Bilateral Ponto-cerebellar Staphylococcus aureus, loss, III, IV sphenoiditis, L abscess, Streptococcus and VI CST meningism, species nerve cervical palsies cellulitis Bilateral VI R sphenoiditis and Right transverse Aspergillus fumigatus nerve palsy posterior sinus ethmoiditis, thrombosis bilateral CST L visual loss, L VI nerve palsy



R pansinusitis and L ophthalmic L sphenoiditis, L vein CST thrombosis, L orbital cellulitis, L frontal extradural abscess Bilateral Mycotic sphenoiditis and aneurysm of posterior R cavernous ethmoiditis, R carotid artery CST Bilateral L transverse sphenoiditis, L sinus CST thrombosis, L middle cerebellar peduncle abscess L sphenoiditis — with fungal ball, L CST

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X

X

X

Maxillary Fever, headache, L antrostomy V2 nerve hypoesthesia



Y P Streptococcus milleri

S. aureus, Serratia marcescens

S. milleri

Buccal bacterial flora, A. fumigatus

M ⫽ male; F ⫽ female; R ⫽ right; L ⫽ left; CST ⫽ cavernous sinus thrombosis.

Table 2. Imaging findings in the patients with septic cavernous sinus thrombosis Patient One

Patient Two

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Cavernous sinus filling defect partial complete Lateral wall convex bowing Cavernous sinus expansion Exophthalmos Ophthalmic vein dilatation Other

X X

X

X

Patient Three

Patient Four

X

X X

Cervical cellulitis

Patient Six

Patient Seven

X X

X

X

X

5/7 (71%)

X

X

4/7 (57%)

X X Spread of the thrombosis to the right transverse sinus

Orbital cellulitis

Four patients (57%) had further intracranial complications, including a ponto-cerebellar abscess, a frontal extradural abscess (Fig. 3), a mycotic aneurysm of the intracavernous internal carotid artery (Fig. 4), and an abscess of the left middle cerebellar peduncle (Fig. 5). Other radiologic findings included cervical cellulitis (one patient) and orbital cellulitis (one patient). All patients were treated by high-dose i.v. antibiotic therapy based on a combination of third-generation cephalosporin and metronidazole for five patients and amoxicillin-clavulanate for two patients. The mean duration of i.v. treatment was 28 days (range of 5–60 days). Five

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Patient Five

Total

7/7 (100%)

2/7 (29%) 2/7 (29%) Clival inflammation

Spread of the thrombosis to the left transverse sinus

patients were subsequently treated with oral amoxicillin-clavulanate (7–30 days). Table 3 describes the treatment and outcome for each patient. Anticoagulation therapy consisted of either unfractionated heparin or low molecular weight heparin during hospitalization, followed by the administration of a vitamin K antagonist to three patients until the complete radiologic recanalization of the cavernous sinus (confirmed by contrast-enhanced CT scan performed at one month and every two weeks thereafter if necessary). The mean duration of anticoagulation therapy was 42 days (range of 21–60 days).

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Figure 1. Computed tomography (CT) scan findings in cavernous sinus thrombosis. Axial (A) and coronal (B) contrastenhanced CT scan. Left septic cavernous sinus thrombosis (SCST) with filling defects, lateral wall convexity, and the expansion of the cavernous sinus (black arrows). Left sphenoid sinusitis.

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Figure 2. Patient number three. (A) Axial contrast-enhanced CT scan. Bilateral SCST (thin arrows) and right transverse sinus thrombosis (thick arrow) secondary to right sphenoid sinusitis. (B) Coronal T1-weighted contrast-enhanced magnetic resonance image. Bilateral SCST with the expansion of the lateral walls and intracavernous filling defect (thrombus, white thin arrows). (C) Coronal magnetic resonance venography. Right transverse sinus thrombosis with filling defect in the right transverse sinus (white thick arrow).

Surgical drainage of the infected sinuses was performed by an endoscopic approach for all patients within 24 hours after SCST diagnosis. This consisted of endoscopic sphenoidectomy and/or posterior ethmoidectomy. Two patients also underwent neurosurgical drainage for intracranial abscess, and one patient underwent endovascular occlusion of the right internal carotid artery because of a mycotic aneurysm. The average time between the first symptoms and diagnosis was 13.7 days (range of 2–20 days). Streptococcus species (43%) and Staphylococcus aureus (28%) were most commonly found in the surgical sinus samples. All bacteriologic samples remained negative for only one patient. In two patients, Aspergillus species were isolated from sinus secretions, although there was no evidence of histologic mucosal invasion. A fungus ball was found in one patient’s sphenoid sinus. None of our seven patients died during follow-up (9–49 months). Four patients (57%) developed transient or permanent neurologic deficits, including permanent ipsilateral visual loss, transient deficit

of the X and XII cranial nerves, Horner’s syndrome associated with hypoesthesia of the V2 nerve, and dysesthesia of the V2 nerve.

DISCUSSION SCST has been reported to account for 8%–16% of the intracranial complications of acute sinusitis.1–3 However, the precise incidence of SCST in association with acute sinusitis is unknown. It remains a rare complication, particularly because of the widespread use of antibiotics, which began in the 1960s. Before this, most cases of SCST were caused by dental and skin infections, which are now usually treated at early stages. Acute sphenoid and ethmoid sinusitis are currently the main cause of SCST.8 We did not identify any risk factors for SCST, although other authors have reported its increased incidence in patients with chronic rhinosinusitis or diabetes.6,8 The clinical features of SCST in our seven patients were in accordance with most previous studies. The main symptoms that should alert the practitioner are high and fluctuating fever, unusual severe

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Figure 3. Patient number four. Axial contrast-enhanced CT scan. (A) Left ophthalmic vein thrombosis secondary to left SCST extension. Enhancing wall, expansion, and nonopacification of the lumen. Left-sided exophthalmos. (B) Left frontal extradural abscess.

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Figure 4. Patient number five. (A) Coronal T2-weighted image and (B) axial Time-Of-Flight MR image. Mycotic aneurysm of the right carotid artery (white arrow) inside of the SCST. (C) Arteriography of the right internal carotid artery. Opacification of a mycotic aneurysm at the beginning of the intracavernous portion of the internal carotid artery (black arrow).

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frontal and retro-orbital headaches that steadily increase in severity despite the use of painkillers, and orbital symptoms such as chemosis, proptosis, ptosis, and ophthalmoplegia.5,8 Cranial nerve impairment is initially present in 88% of patients.8 Visual loss may be due to corneal ulceration, ophthalmic arterial occlusion, venous embolism, ischemia of the optic nerve, or to an intraorbital compression. Persistent blindness affects 8%–16% of patients.5 Neck stiffness has been reported in up to 40% of cases.8 Other neurologic symptoms, such as altered mental status, seizures, and focal neurologic deficits, are usually related to other intracranial complications. Bilateral cases exist but are not common (one patient in our study), when cavernous sinus thrombosis spreads to the contralateral side via the intercavernous sinuses.9,10 Contrast-enhanced CT scan is the primary radiologic examination used for the early diagnosis of SCST, with direct radiologic findings including confluent areas of nonopacification in the cavernous sinus, convex bowing of the cavernous sinus lateral wall, the expansion of the cavernous sinus, and asymmetry between the two sides of the cavernous sinus. MRI remains a second-line examination for SCST diagnosis, which typically shows the loss of the T1 heterogeneity of

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the cavernous signal, which is replaced by an iso- or hyperintense homogenous T1 signal.11 The most specific indirect imaging finding is thrombosis in the superior ophthalmic vein, which appears expanded. There may be other indirect signs, such as thrombosis of the superior petrosal sinus or the inferior petrosal sinus or thrombosis of the spheno-parietal sinus, an expansion of the inferior ophthalmic vein, exophthalmos, or dural enhancement next to the lateral edge of the cavernous sinus.11 Bone sequence sinus CT scan allows for the identification of the infected sinus, and can also show calcifications suggesting fungal sinusitis, anatomic variations, or physical or traumatic bone defects in the sphenoid or the maxillary sinus posterior wall.12 The treatment of SCST complicating acute bacterial sinusitis relies on: 1) High-dose i.v. antibiotic therapy directed against S. aureus, grampositive organisms, and anaerobes. However, its duration remains controversial and depends on the microbiologic findings and associated intracranial complications. In our opinion, antifungal therapy is not necessary in cases in which the fungus is only detected in the lumen of the sinus but not in the mucosal samples. 2) Surgical drainage of the infected sinuses, usually performed through an endoscopic approach. Although there is no consensus on

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Figure 5. Patient number six. (A) Contrast-enhanced CT scan and (B) T1weighted MR image with gadolinium. Cerebellar abscess (white thick arrow) secondary to SCST and left transverse sinus thrombosis.

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Table 3. Medical and surgical treatments and associated long-term effects in patients with septic cavernous sinus thrombosis Case

Patient one

Patient two

Patient three

Types and Durations of Intravenous Antibiotics

Types and Durations of Oral Antibiotics

Type and Duration of Anticoagulation Therapy

Amoxicillinclavulanate, 21 days Third-generation cephalosporin and metronidazole, 60 days Third-generation cephalosporin and metronidazole, 25 days Third-generation cephalosporin and metronidazole, 21 days Third-generation cephalosporin and metronidazole, 31 days Third-generation cephalosporin and metronidazole, 35 days Amoxicillinclavulanate, 5 days

Amoxicillinclavulanate, 7 days

LMWH, 21 days

Amoxicillinclavulanate, 15 days

Unfractionated heparin, 60 days

Bilateral endoscopic sphenoidectomy

Temporary XII and X nerve palsies, daily headaches

Amoxicillinclavulanate, 10 days

LMWH, 11 days; then vitamin K antagonist, 45 days

Right sphenoidectomy and ethmoidectomy

Horner’s syndrome

Amoxicillinclavulanate, 30 days

Unfractionated heparin, 21 days

Bilateral sphenoidectomy, right maxillary antrostomy, craniotomy for frontal empyema

Left blindness



LMWH, 45 days



LMWH, 30 days; then vitamin K antagonist, 30 days

Right sphenoidectomy and ethmoidectomy, endovascular occlusion of the right internal carotid artery Bilateral sphenoidectomy and ethmoidectomy, craniotomy

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Patient four

Patient five

Patient six

Patient seven

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Amoxicillinclavulanate, 15 days

LMWH, 5 days; then vitamin K antagonist, 30 days

Surgical Treatment

Long-Term Sequelae

Right endoscopic sphenoidectomy

Left sphenoidectomy and ethmoidectomy







V2 nerve hypoesthesia

LMWH ⫽ low molecular weight heparin.

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REFERENCES

this issue, surgical drainage is in our experience an effective option associated with a low morbidity rate.5,12,13 We perform this procedure as early as possible after SCST diagnosis. 3) Anticoagulation therapy. According to a review by Bhatia et al.,5 anticoagulation therapy could statistically lower mortality and morbidity rates if it is initiated within seven days of the admission of the patient to the hospital. This therapy should be given for at least three months. In our series, anticoagulation therapy was used only for a short period of time, because all patients underwent the complete recanalization of the cavernous sinus within six weeks. We observed no deaths in our study, which may have been due to the systematic early drainage of the primary infectious site and to the anticoagulation therapy. In addition, none of the patients experienced any side effects related to these treatments. However, 57% of our patients developed permanent or transient neurologic deficits. Indeed, SCST long-term morbidity rate is high: 7%–22% of partial visual loss and 8%–17% of blindness,5,8,14 up to 50% of cranial nerve deficits,15,16 seizures, neurologic deficits, pituitary failure, and incapacitating persistent headache. Mortality is higher in immunocompromised patients.6 SCST is a rare pathology that remains unfamiliar to general practitioners. Thus there is often a delay between the first SCST symptoms (five to six days after the first symptoms of sinusitis) and the onset of proper treatment. Patients have frequently received many unsuitable and ineffective treatments despite their worsening before their admission at the hospital, which seems to prove the ignorance of this severe disease.

1.

2.

3. 4. 5.

6.

7.

8. 9. 10.

11.

T 12.

CONCLUSION SCST is still considered as a severe complication of acute bacterial sinusitis. Morbidity and mortality rates seem to have decreased for the last decades, but long-term sequelae remain frequent. According to our experience of the past 11 years, a precocious diagnosis and an aggressive treatment strategy combining high-dose i.v. antibiotics, anticoagulation therapy until the radiologic recanalization of the cavernous sinus, and the early surgical endoscopic drainage of the infected sinus substantially reduce the mortality and morbidity rates of SCST.

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Septic cavernous sinus thrombosis secondary to acute bacterial sinusitis: a retrospective study of seven cases.

Septic cavernous sinus thrombosis (SCST) is a rare but severe complication of acute bacterial sinusitis. Evaluations of advances in imaging techniques...
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