Diagnosis and management of cavernous sinus thrombosis can be challenging, but several clinical clues can aid in a more time-efficient and cost-effective approach. This condition is rare which can delay diagnosis and be fatal due to the several important neurovascular structures that run through the cavernous sinus. This report discusses a case of cavernous sinus thrombosis in a male with substance use disorder whose signs, symptoms, and diagnostic findings were classic for the condition. Prompt recognition of these can lead to a more rapid diagnosis and early initiation of adequate treatment. There are limited evidence-based guidelines regarding diagnosis and treatment. This report will also review some of the more recent literature on the topic to aid healthcare providers in giving proper care for their patients and thereby increasing knowledge and awareness of the subject

• Cavernous Sinus Thrombosis

• Cerebral vein thrombosis

• Streptococcus

• Cavernous sinus

Spalitto D (2024) Atypical Bilateral Cavernous Sinus Thrombosis and Literature Review. JSM Clin Case Rep 12(2): 1237.

CST: Cavernous Sinus Thrombosis, CVT: CEREBRAL VEIN THROMBOSIS, CTA: Computed Tomographic Angiography, CT: Computed Tomography, NSTEMI: non ST Elevation Myocardial Infarction, PCR: polymerase chain reaction, CRP: C-reactive protein, ESR: Erythrocyte Sedimentation Rate, MRI: Magnetic Resonance Imaging.

Cavernous sinus thrombosis (CST) is a serious and potentially life-threatening condition [1]. When it was first reported in 1892, prior to introduction to antibiotics, it was almost 100% fatal [2]. CTS is characterized by a blood clot in the cavernous sinus which is in the middle cranial fossa near the pituitary gland in the brain. When a clot forms in this area it is considered an emergency, as nearly 30% of cases can be fatal [3] or can potentially cause irreversible damage to cranial nerves [4]. The sinus itself contains an array of important cranial nerves and blood vessels. A careful history and physical exam along with risk factor assessment, is important for diagnosis.

The patient was a 62-year-old male with a prior medical history significant for essential hypertension, hyperlipidemia, hypothyroidism, gastroesophageal reflux disease, and methamphetamine use.

The patient presented to the emergency department with complaints of chest pain, nausea, vomiting, fever, and chills. His chest pain had been intermittent for months, however, acutely worsened in the last few days. EKG was unremarkable except for V4, V5, and V6 minimal ST segment depression. Imaging reported pulmonary edema on chest x-ray and pleural effusion on chest computed tomographic angiography (CTA). The patient was significantly short of breath, which improved with Lasix. His lab work showed a positive troponin of 0.070ng/ml (range 0.0-0.034ng/ml). He was started on a heparin drip and was admitted to the hospital for further workup and management. He was originally admitted to the hospital for a congestive heart failure exacerbation and non-ST-elevation myocardial infarction (NSTEMI) secondary to hypertension in the setting of substance use. After further trending troponins, diuretic treatment, and imaging; the patient was diagnosed with a type two NSTEMI and diastolic heart failure exacerbation.

The patient had other symptoms upon admission including nausea, vomiting, diarrhea, chills, and subjective fever. The patient denied headaches upon admission as well as presyncope, lightheadedness, syncope, abdominal pain, and dysuria. Chest x-ray demonstrated interstitial opacities which were concerning for inflammation or infection. The patient was negative for COVID-19 and influenza. CTA chest was negative for any pulmonary embolism. Complete blood count showed mild leukocytosis with neutrophil predominance. There was concern for sepsis, and the patient was borderline hypotensive. He started to complain of a severe headache, and it was noted that he had drooping of the left eyelid with blurry vision. The patient reports he did not think these were issues at that time but states they had gotten worse. He was started on broad-spectrum antibiotics and imaging of the head, cervical spine, and orbit were ordered as well as a pneumonia PCR.

His infectious workup included lactic acidosis, elevated CRP and ESR, up trending leukocytosis with a procalcitonin of 1. His pneumonia PCR was positive for Streptococcus species and his blood cultures revealed Streptococcus anginous. The original head computed tomography (CT) was unremarkable, and CTA head showed enlarged ophthalmic veins [Figure 1].

Figure 1: CTA of the head showing enlargement of the ophthalmic veins

Further investigation with a CT venography of the head confirmed the diagnosis of bilateral cavernous sinus thrombosis [Figure 2].

Figure 2: CT venogram of the head showing dilated ophthalmic veins with diminished enhancement in both cavernous sinuses compatible with bilateral cavernous sinus thrombosis.

The radiologic read reported bilateral exophthalmos left greater than right, thrombus formation in each ophthalmic vein, bilateral cavernous sinus thrombosis, and thrombus formation in the right internal jugular vein. Ophthalmology was consulted and recommended transfer to a facility for a higher level of care. The patient had been adequately treated from a cardiac standpoint and was restarted on heparin after the thrombus was found. He was on broad-spectrum antibiotics and in stable condition. Per the ophthalmologist’s recommendation, he was transferred to a higher level of care facility.

Cavernous sinus thrombosis makes up about 1%-4% of all cerebral venous and sinus thrombosis [5]. Due to the scarcity of cases, it has been hard to estimate incidence. In general, cerebral venous thrombosis only occurs at about one per 100,000 annually [5]. The cavernous sinus is the least common location for cerebral venous thrombosis [5]. Historically, it was thought that cavernous sinus thrombosis/cerebral venous thrombosis occurs more commonly in children. Recent studies have challenged this belief. A cross-sectional study conducted in 2012 showed that the rates of these conditions can be comparable to those of bacterial meningitis and can be nearly twice as common in adults than in children [6]. This is important because the incidence of cavernous sinus thrombosis/cerebral venous thrombosis is probably higher amongst adults than previously believed. Cavernous sinus thrombosis is a very serious condition that requires immediate treatment and can be fatal in about 30% of cases, as well as lead to irreversible cranial nerve palsies and blindness [7].

Cavernous sinus thrombosis typically presents with severe headache, tearing, swelling/irritation around one or both eyes, drooping eyelids, inability to move eyes, high fever, fatigue, vision loss, seizures, or altered mental status [8]. Ocular symptoms commonly occur first due to the presence of several cranial nerves that run through the cavernous sinus with the sixth cranial nerve most frequently affected [4]. The ideal diagnostic test is either a contrast-enhanced CT or an magnetic resonance imaging (MRI) of the head, although a non-contrast CT is typically ordered first [8]. A non-contrast CT may show subtle abnormalities like dilation of the ophthalmic veins or exophthalmos and a contrast- enhanced MRI would show the bulging of the cavernous sinus, increased dural enhancement, and absent flow [8]. The most sensitive test of choice would be the CT or MR venogram [8]. The venography allows for visualization of significant findings such as carotid artery narrowing, carotid wall enhancement cerebral infarcts, meningitis, or hemorrhages.

The most common causes of cavernous sinus thrombosis are typically due to aseptic or infectious pathology. Sinusitis, otitis, odontogenic sources, facial or orbital cellulitis/abscesses, or mastoiditis are examples of infectious causes [1,4,8]. One study suggested the most common cause was sinusitis of the sphenoid sinus [4]. Most of the infectious causes stem from the “Danger Triangle of the face”, which is from the corners of the mouth to the bridge of the nose. Staphylococcus aureus accounts for nearly 67% of the cases [8] and is said to be the most common cause [9]. This condition can occur postoperatively or due to trauma however, this occurs less commonly.

Due to the scarcity of the disease, there has been no guideline- directed treatment algorithm. There are also no random controlled trials to guide treatment. Literature frequently discusses antibiotics, steroids, and anticoagulation, but there is limited research on interventional therapies. Studies show that antibiotics and anticoagulation are beneficial however steroids are of equivocal benefit. Most experts currently recommend antibiotic therapy with an agent that covers methicillin- resistant Staphylococcus, a third-generation cephalosporin, and metronidazole with consideration for antifungal treatment [8,9]. There are no current recommended surgical interventions, however source control is needed. If there is an abscess or infected bone then source control should be attempted with removal of bone from infected area.

Evidence regarding steroid use has not reported any improvements. Steroids might decrease inflammation and vasogenic edema however has not demonstrated efficacy [9].

Anticoagulation is recommended in the absence of strong contraindications. Anticoagulation treatment should be extended several weeks to months. It has been documented retrospectively that mortality decreases from 40% to 14% with the use of unfractionated weight heparin (UFWH), and a reduction in morbidity from 61% to 31% when anticoagulation is combined with antibiotics [8]. The European Federation of Neurological Societies mentions that three months of anticoagulation in secondary cerebral venous and sinus thrombosis should be efficient to decrease the risk of further injury. There are risks and benefits to anticoagulation. The benefits would be to stop the progression of thrombosis and prevent clot propagation, but the risk would be intracranial bleeding [9]. Currently, it is suggested that the reduced mortality and morbidity benefit outweighs the risk.

Antibiotics decreases the risk of mortality, and with the advancement in technology paired with increased awareness, the diagnosis of cavernous sinus thrombosis has become more frequent. Further investigation is warranted to discover finer treatment algorithms or modalities to provide better quality care and decrease the mortality rate. This case was unique in that the patient did not have any of the classic causes like orbital trauma, infections in the danger triangle, or recent surgical intervention. This stresses the importance of increased awareness, diligent physical exams, and recognition of early symptoms, which can lead to rapid diagnosis and early treatment.

1. Saposnik G, Barinagarrementeria F, Brown DR, Bushnell CD, Cucchiara B, Cushman M, et al. Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011; 42: 1158-1192.
2. Clifford-Jones RE, Ellis CJ, Stevens JM, Turner A. Cavernous sinus thrombosis.J Neurol Neurosurg Psychiatry. 1982; 45: 1092-1097.
3. Ebright JR, Pace MT, Niazi AF. Septic Thrombosis of the Cavernous Sinuses. Arch Intern Med. 2001; 161: 2671-2676.
4. Van Der Poel NA, Mourits MP, de Win MML, Coutinho JM, Dikkers FG. Prognosis of septic cavernous sinus thrombosis remarkably improved: a case series of 12 patients and literature review. Eur Arch Otorhinolaryngol. 2018; 275: 2387-2395.
5. Coutinho JM, Zuurbier SM, Aramideh M, Stam J. The incidence of cerebral venous thrombosis: a cross-sectional study. Stroke. 2012; 43: 3375-3377.
6. Absoud M, Hikmet F, Dey P, Joffe M, Thambapillai E. Bilateral Cavernous Sinus Thrombosis Complicating Sinusitis. J R Soc Med. 2006; 99: 474-476.
7. Shrma R, Bessman E. Cavernous Sinus Thrombosis Treatment and Management. Medscape - Drugs and Diseases. 2018.
8. Plewa MC, Tadi P, Gupta M. Cavernous Sinus Thrombosis. In. StatPearls, Treasure Island (FL). StatPearls Publishing. 2023.
9. Weerasinghe D. Christian LJ. Septic Cavernous Sinus Thrombosis: Case Report and Review of the Literature. Neuroophthalmology. 2016; 40: 263-276.