The presentation of CST may be acute or sub-acute. Most patients show symptoms of fever, headache, exophthalmia, periorbital edema and sometimes with chemosis. Most of the patients usually have external ophthalmoplegia, which results from the venous congestion of eye tissues, inflammation of body organ including extra-ocular muscle and/or cranial nerves III, IV and VI [7]. Also, the patient may present with eyelid erythema, autonomic nervous system dysfunction, papilledema (optic nerve swelling) pupillary defects and changes in sensory nerve distribution particularly in the ophthalmic or maxillary trigeminal region [7] [8]. Although vision loss may be rare since the orbital nerve is located externally to cavernous sinus, it can develop through other pathophysiological mechanisms such as internal carotid artery occlusion (ICA), ophthalmic (central) retinal arteries obstructions, orbital congestion and arteritis [7]. If not diagnosed early , CST which affects one eye may spread to the other within 24-48 hours [9].

• Fever

  Drowsiness, high-grade fever, severe headache, left ocular pain with marked periorbital swelling, and paralysis of extraocular eye movements developed. [ncbi.nlm.nih.gov]

  Symptoms and signs include pain, proptosis, ophthalmoplegia, vision loss, papilledema, and fever. Diagnosis is confirmed by CT or MRI. Treatment is with IV antibiotics. Complications are common, and prognosis is poor. [merckmanuals.com]

• Chills

   Pyrexia  Rapid, weak, thready pulse  Chills and sweats  Delirium - meningitis supervenes terminally  Septic emboli to various other parts of body. 15.  Proptosis (first oedema & chemosis)  Oedema of eyelids and bridge of nose  Dilatation and [slideshare.net]

  A day after, he started having high-grade fever, not associated with chills or rigors. This was followed by progressive swelling of the upper and lower lids of the left eye for 3 days. [ijo.in]

  These complications can include: meningitis – an infection of the outer protective layer of the brain that can cause symptoms such as a stiff neck, mental confusion and sensitivity to light sepsis or blood poisoning – this can cause symptoms such as chills [nhsdirect.wales.nhs.uk]

  They include chills, fever, shock, delirium, and coma. Causes Most cases of septic cavernous sinus thrombosis (CST) are due to an acute infection in an otherwise healthy individual. [emedicine.medscape.com]

• Rigor

  A day after, he started having high-grade fever, not associated with chills or rigors. This was followed by progressive swelling of the upper and lower lids of the left eye for 3 days. [ijo.in]

  A day after, she started having high-grade fever associated with chills or rigors. This was followed by progressive swelling and redness of both eyelids in the right eye with proptosis and opthalmoplegia developing subsequently. [ispub.com]

  Less common symptoms may include rigors, stiff neck, facial numbness, confusion, seizures, stroke symptoms, or coma. [ncbi.nlm.nih.gov]

• Nausea

  She developed watery rhinorrhea, progressive headache, fever, nausea, vomiting, and left proptosis with blurred vision, and was admitted to hospital 3 days after injury. [ncbi.nlm.nih.gov]

  These are generally mild and can include diarrhoea, nausea and a skin rash. Anticoagulants You may also be given a medication called heparin to help dissolve the clot and prevent further clots. [nhs.uk]

  The headaches are sharp shooting and severe in nature accompanied by fever and nausea. As the sinus lies proximal to few cranial nerves, neurological disturbances may be experienced. [healthtipsandguides.net]

• Vomiting

  She developed watery rhinorrhea, progressive headache, fever, nausea, vomiting, and left proptosis with blurred vision, and was admitted to hospital 3 days after injury. [ncbi.nlm.nih.gov]

  Anti Arrhythmics, Antibiotic Duration, Anti-Emetic, Antihistamine, Antiseptic, Ants, Apologizing to Patients, Arrhythmia, Arthritis, Auricular Hematoma, Azithromycin, Back Pain, Bactrim, Bees, Beta Agonist, Beta-HCG, Biceps Tendon Rupture, Bilious Vomiting [hippoed.com]

  Other signs/symptoms include evidence of intracranial hypertension (vomiting, papilledema, visual disturbances), neurologic deficits, seizures, and coma. [shmabstracts.com]

• Chemosis

  A 56-year-old woman was admitted because of a high fever, right ptosis, chemosis, proptosis and ocular muscle palsy. Cranial MRI revealed a cavernous sinus thrombosis and a subarachnoid abscess. [ncbi.nlm.nih.gov]

  Case report A 33-year-old female visited our hospital for severe, right-sided, temporal headache, chemosis, periorbital edema, and proptosis. [head-face-med.biomedcentral.com]

• Eye Pain

  When to see your GP Contact your GP if you experience a persistent and severe headache you haven't had before, or if you develop eye pain or swelling of one or both eyes. [nhs.uk]

  Call your health care provider right away if you have: Bulging of your eyes Drooping eyelids Eye pain Inability to move your eye in any particular direction Vision loss Durand ML. Periocular infections. In: Bennett JE, Dolin R, Blaser MJ, eds. [nlm.nih.gov]

  Calling your health care provider Call your doctor right away if you have: Bulging of your eyes Drooping eyelids Eye pain Inability to move your eye in any particular direction Vision loss [coordinatedhealth.com]

  You may experience: swelling and bulging of the eyes – this usually starts in one eye and spreads to the other eye soon after red eyes eye pain – which can be severe vision problems – such as double vision or blurred vision difficulty moving the eyes [nhsdirect.wales.nhs.uk]

• Diplopia

  Cavernous sinus tumors Acute or slowly progressive ophthalmoplegia is the dominant presentation, with diplopia being the most common symptom. At times, painful diplopia is present. Usually the patient has a preceding history of cancer. [emedicine.com]

  A previously healthy 14-year-old boy developed headache, stiff neck, fever, diplopia, right proptosis, and right complete sixth and partial third cranial nerve palsies. Orbital CT showed features of pansinusitis and orbital fat stranding. [ncbi.nlm.nih.gov]

• Periorbital Edema

  A 33-year-old female visited our hospital for severe, right-sided, temporal headache, chemosis, periorbital edema, and proptosis. [ncbi.nlm.nih.gov]

  Case report A 33-year-old female visited our hospital for severe, right-sided, temporal headache, chemosis, periorbital edema, and proptosis. [head-face-med.biomedcentral.com]

  Headache is the most common presentation symptom and usually precedes fevers, periorbital edema, and cranial nerve signs. [emedicine.medscape.com]

  His exam was significant for profound bilateral periorbital edema with significant chemosis, drainage, and overlying erythema. (Figure 1.) The right eye was impossible to examine because of significant swelling. [journals.lww.com]

  Classic presentations are abrupt onset of unilateral periorbital edema, headache, photophobia, and bulging of the eye (proptosis).Other common signs and symptoms include: Ptosis, chemosis, cranial nerve palsies (III, IV, V, VI). [en.wikipedia.org]

• Retinal Hemorrhage

  hemorrhages, retinal venous congestion, and loud ocular and cranial bruit Indirect: Similar signs and symptoms of lesser severity; occasionally, isolated ophthalmoplegia, particularly if the fistula drains posteriorly Cavernous sinus thrombosis Generally [emedicine.com]

  On admis-sion, he showed mild external ophthalmoplegia and clinical evidence of intraorbital congestion (choked disc, retinal vein thrombosis, retinal hemorrhage) on the left side. [webview.isho.jp]

   Proptosis (first oedema & chemosis)  Oedema of eyelids and bridge of nose  Dilatation and tortuosity of retinal veins  Retinal hemorrhages  Involvement of the contralateral eye – (48 hours)  When pterygoid plexus is occluded along with sinus, [slideshare.net]

  Papilledema, retinal hemorrhages, and decreased visual acuity and blindness may occur from venous congestion within the retina. Fever, tachycardia and sepsis may be present. Headache with nuchal rigidity may occur. [en.wikipedia.org]

  These include periorbital edema (initially unilateral but typically bilateral), lid erythema, chemosis, ptosis, proptosis (due to impaired venous drainage of orbit), restricted or painful eye movement, and less commonly papilledema, retinal hemorrhages [ncbi.nlm.nih.gov]

• Epistaxis

  Elder Abuse, Elderly, Emergency Care, Emergency Department, Emergency Department Recidivism, Emergency Department Visit, Emergent Surgical Conditions, Employment, EM/Surgery, endocrine, endometriosis, ENT (systems based), Envenomation, Epidemiology, epistaxis [hippoed.com]

• Unilateral Facial Pain

  The symptoms of CST vary ranging from a severe headache, fever to either localized or unilateral facial pain, involving retro-orbital or frontal regions. [symptoma.com]

• Headache

  He was responsive to therapy and discharged home after his headache symptoms resolved. Seven days later, however, he presented to the emergency department with a worsening headache, progressive altered mental status, fever, and bilateral proptosis. [journals.lww.com]

  It is important to perform enhanced MRI and blood culture for patients with chronic headache related to dental treatment. [ncbi.nlm.nih.gov]

  While it's highly unlikely to be the result of cavernous sinus thrombosis, a persistent headache usually needs to be investigated. [nhs.uk]

• Meningism

  A case of cavernous sinus thrombosis is usually a complication of severe orbital cellulitis and meningitis. The authors reported a retrograde cavernous sinus thrombosis and orbital cellulitis in an immunocompetence child, due to meningitis. [ncbi.nlm.nih.gov]

• Seizure

  Altered mental status that can range from confusion to coma Bouble vision and seizures are rare. [webmd.com]

  Other signs/symptoms include evidence of intracranial hypertension (vomiting, papilledema, visual disturbances), neurologic deficits, seizures, and coma. [shmabstracts.com]

  There may be seizures and even status epilepticus. [patient.info]

  Sagittal sinus thrombosis: motor deficits, bilateral deficits, seizures Lateral sinus thrombosis: isolated intracranial hypertension Left transverse sinus thrombosis: Aphasia Deep venous sinus (straight) thrombosis: behavioural symptoms (thalamic lesions [lifeinthefastlane.com]

  A few complications associated with Cavernous Sinus Thrombosis include: Seizures Permanent loss of vision Meningitis: Infection that occurs in the outer protective layers of the brain Sepsis: Systemic spread of infection Death may occur if the condition [dovemed.com]

• Confusion

  Despite the use of the term sinus the cavernous sinuses should not be confused with the maxillary or frontal sinuses, which can be affected by sinusitis. [irishhealth.com]

  Decreased level of consciousness, confusion, seizures, and focal neurologic deficits are signs of CNS spread. [merckmanuals.com]

  […] by tearing Swelling, redness, or irritation around one or both eyes Drooping eyelids Inability to move the eye High fever Pain or numbness around the face or eyes Fatigue Vision loss or double vision Seizures Altered mental status that can range from confusion [webmd.com]

  Decreased level of consciousness, confusion, seizures, and focal neurologic deficits are signs of central nervous system (CNS) spread. [msdmanuals.com]

• Papilledema

  Symptoms and signs include pain, proptosis, ophthalmoplegia, vision loss, papilledema, and fever. Diagnosis is confirmed by CT or MRI. Treatment is with IV antibiotics. Complications are common, and prognosis is poor. [merckmanuals.com]

  Patients with severe papilledema may develop permanent vision deficits without treatment. Importantly, head CT is normal in up to 30% of cases. [shmabstracts.com]

In patients with septic CST, most clinical signs and symptoms develop rapidly and may assist in establishing the diagnosis of the condition. The onset of the disease condition may present with nonspecific features which may require optical and neurological investigations to establish the diagnosis. However, some of the common symptoms seen early in CST patient include, fever, conjunctival edema, periorbital edema, exophthalmos. These observable changes are due to venous congestion or occlusion of the sinus related to the cavernous sinus. The involvement of the cranial nerves may result into painful, external ophthalmoplegia and ptosis. Also, a mid-size mydriasis may be observed due to the relatedness of the sympathetic nervous system with the cavernous sinus resulting into internal ophthalmoplegia which causes blunted pupillary response of the patient to light. Cranial nerve (CN) VI is covered by a fibrous membrane laterally to the wall of cavernous causing CN IV to be prone to intra-cavernous pathological effect. Therefore, lateral gaze palsy development may precede ophthalmoplegia with a decrease in corneal reflex due to the position of the cranial nerve VI.

The sequential spread of the disease to both eyes usually indicates CST although, previously observed signs and symptoms may assist in establishing the diagnosis. These include identification of the primary route of infection, sepsis, visual defect, pupillary dysfunction and features of meningismus (photophobia and nuchal rigidity). The ophthalmoscopy examination may reveal papilloedema, retinal vein dilatation, hyperesthesia or hypoaesthesia in the arrangement of ophthalmic nerve including the maxillary. Most often, these features are not common in periorbital and orbital cellulitis, which are often misdiagnosed as CST. 50% of the affected population develop visual loss due to corneal ulceration resulting from proptosis, papilloedema, and corneal reflex loss. Also, occlusion or obstruction of the internal carotid artery, ophthalmic artery, central retinal artery, orbit cavity congestion or embolism may cause impaired vision. The seizure usually occurs as a complication of septic CST due to intracranial suppuration. Rarely, patients with septic CST can manifest milder symptoms, with gradual cranial nerve dysfunction and reduced clinical manifestation of sepsis or ocular defects. A unilateral isolated form of lateral gaze palsy is usually the initial sign of subacute septic CST which may later transform into the bilateral form. The mechanism behind these presentation shows that a slow progressive destruction of the cavernous sinus results in an increased compensation during rapid venous occlusion. The previous study postulated this phenomenon when there is an infection spread into the cavernous sinus through retrograde pathway such as otogenic infection which is commonly seen before the development of antibiotics [9].The pattern of disease development in aseptic CST is similar to the acute septic form but may be slower and less complex. Although, it may sometimes be difficult to differentiate between septic and subacute, aseptic CST, however, the most clinical feature of sepsis and primary infection are not commonly seen. Most often, aseptic CST is usually related to known predisposing factors which include, hypercoagulability syndrome, sinus surgery history, and neoplasms.

Septic CST may be diagnosed adequately with clinical findings, however, when there is co-existence of other diseases such as meningitis or orbital infections, the clinical details may not be appropriately analyzed [9]. Therefore, the patient with sepsis and manifestations of focal neurological dysfunction or orbital symptoms urgently needs an immediate contrast computed tomography (CT scan) and/or magnetic resonance imaging (MRI) to identify the location of the infection. Both CT scan and skull MRI techniques are the primary radiological technique used to establish the diagnosis of CST. Also, they may be used in assessing the etiological cause and the disease pathology. However, both techniques are not totally sensitive and specific for septic CST. MRI technique particularly MRV (venography) is usually adapted for CST diagnosis and can be used to detect all the stages in thrombus formation. There are contradicting views in the early detection of clot development in dural (cerebral or cranial) sinuses. Some studies reported CT scan has higher sensitivity compared to MRI in the early detection of clot formation in the cavernous sinuses [10], while MRI is better in other types of the cranial sinuses. MRI may also be useful for diagnosing CST in cases where CT scan is not efficient, analyzing complications that involve pituitary gland or spread of infection to the brain. Angiography may also be required. In the recent diagnosis of septic CST, conventional imaging methods such as venography and cerebral angiography are limited in use with a report of severe complications in their choice. Also, use of normal x-ray method (mastoid and sinus plain films, sinus tomograms) has reduced following the use of CT scan and MRI.

Routine laboratory investigations may be done as part of the diagnostic plan. A marked leukocytosis is usually observed in complete blood cell count (CBC) during septic disease. Also, the result of CBC may help to evaluate the factors that may influence the disease condition. These include polycythemia, thrombocytopenia, (which may be indicative of thrombotic thrombocytopenic purpura). Leukocytosis could assist in differentiating septic CST from the aseptic form. The causative bacteria establishing infection may be isolated from the primary infective site including exudate samples and blood culture method. Cerebrospinal fluid (CSF) samples may be collected by lumbar puncture (LP) to differentiate between peri-orbital cellulitis and septic CST. The increase in inflammatory cells are commonly seen in about 75% cases of affected patient with septic CST and sometimes, CSF culture may help to identify the infecting microorganism.

Clinical assessment of hypercoagulable syndrome may include antiphospholipid syndrome test, quantify the level of antiphospholipid or anticardiolipin antibodies in the blood. Other tests may also be done to determine the cause of the hypercoagulable states. These include factor V protein, antithrombin III, protein C and S estimation. Hemoglobin electrophoresis may be useful to identify patients blood genotype in order to rule out sickle cell disease.

The main therapeutic approach for managing cavernous sinus thrombosis is by prompt and adequate antibiotic administration. Although the common bacteria causing infection in CST is usually S aureus, broad-spectrum antibiotics which are effective for both gram-positive and gram-negative including anaerobes should be administered before the culture result. Treatment with empiric antibiotic drugs includes penicillin (penicillinase-resistant type) with cephalosporin (3rd and 4th generation preferably). In the case of suspected anaerobic infection of the teeth, selected antibiotics may be administered against the anaerobes. Intravenously administered antibiotics for about 3-4 weeks is usually recommended. There are contradicting views on the use of anticoagulation for cavernous sinus thrombosis treatment. Because of the low prevalence of this condition, there are no current drug trials for the use of anticoagulation in CST. Previous studies revealed a reduction in the mortality rate and clot development by anticoagulation. Few shreds of evidence showed that anticoagulant used as drugs in treating coagulopathy disorder is safe and also effective in treating the patient with sinus thrombosis [11]. It is therefore recommended that anti coagulopathy is treated with heparin in other to prevent thrombosis development and subsequent increase in the septic emboli incidence.

A study review reported that a low-molecular-weight type of heparin (LMWH) are more effective than unfractionated heparin (UFH) in the treatment of the condition [12]. There is contraindication in the use of heparin for CST patient with other diseases. These include intracerebral hemorrhage and another hemorrhagic diathesis. Thrombolytics may be experimentally administered to treat CST patients locally particularly for severe refractory cases. Also, adjunct therapy of corticosteroids may be used to subside inflammation, edema and in CST cases which may result in pituitary insufficiency so as to prevent adrenal complication. This should be administered after antibiotic therapy. Also, drugs such as dexamethasone or hydrocortisone may be recommended. Most often, the effectiveness of surgical technique involving the cavernous sinus is unknown. The primary route of infection can be superficially drained in cases such as sphenoid sinusitis and facial abscess. Early identification of infected sphenoid sinus is usually important in order to inhibit the transmission of infection to the cavernous sinus. Adequate provision and medical care must be provided for CST patient requiring drainage including appropriate antibiotic regimen particularly if surgery is required.

The mortality rate is 30% in affected patients and about 50% among those having an underlying sphenoid sinusitis. Also, more than 30% of the affected individual may develop severe sequelae [6], such as ophthalmoplegia, sight loss, pituitary incapability and physical disability resulting in stroke, which sometimes may be permanent.

Cavernous sinuses are thick-walled sinuses, situated at the base of the skull draining venous blood directly from the facial veins. CST condition is a very rare complication commonly associated with facial infections [2], including the nasal furuncles which are responsible for 50% of all cases. Other causes include sphenoidal (ethmoidal) sinusitis and dental infections which account for 30% and 10% cases respectively. Most frequently, the main pathogens are bacteria such as staphylococcus aureus, and streptococcus spp. Also, in cases where the underlying infection results from infected tooth or sinusitis, anaerobic bacteria may be the causative agent. Other types of intracranial septic thromboses may develop but are rarer than CST. These include thrombosis of the lateral sinus (associated with mastoiditis) and superior sagittal sinus. Sagittal sinus thromboses are usually caused by bacterial meningitis.

The incidence of cavernous sinus thrombosis is generally low, with only a few reported cases in the medical publications. There is no age difference among the affected patients. The majority of the mentioned cases are not recent, mostly before the development of newly effective therapeutic agent. CST rarely occurs, with an approximate value of 4.5 cases in 1,000,000 population per year [3]. Among the types of dural venous sinus thrombosis, it is responsible for <1.5% of known cases. The mortality rate associated with this condition was close to 100% before the development of newly, effective antibiotics. However, following the development of improved or better approach, the mortality rate has reduced below 30%. Most often, patient death caused by CST is usually due to sepsis and infection of the central nervous system (CNS). Also, the morbidity is still high and full recovery is uncommon. About 18% of the affected patients permanently develop varying degree of visual defect, while 50% have cranial nerve abnormalities. The mortality or morbidity rates may partially be due to delay in establishing diagnosis thereby hindering prompt surgical drainage and proper drug administration.

As previously stated, cavernous sinuses are thick-walled venous pathways with the anterior end extending from the superior orbital fissure. The posterior end is attached to the petrous part of the temporal bone. Cavernous sinuses are covered in the dura between the layers of the meninges and the periosteum. Each side of the cavernous sinuses has an extension of internal carotid artery, cranial nerves III, IV, and VI. Cranial nerve IV is situated laterally to the sinus wall. The dural layers release a trabeculae support which projects the sinuses with a reticular pattern, thereby assisting in trapping foreign objects such as bacteria, thrombi, and emboli. Infections with bacteria can also stimulate thrombogenesis through released toxins or tissue damage. Thrombus growth is suggested to be a barrier preventing antibiotic penetration into the cavernous sinuses. In this situation, administration of antibiotics may not be effective in treating the patient because the thrombus clot will hinder the drug penetration from reaching the site of infection [4]. Cerebral emissary veins and the dural sinuses are usually valveless, allowing blood flow in dual directions depending on the pressure gradient of the vascular system. Therefore, infections spread into the cavernous sinuses from the nasal region, sinuses, or middle third of the face moves in an anterograde direction while dental or lateral venous sinuses, otogenic infections spread to the sinuses through retrograde direction. Generally, the mechanism of disease development can be divided into three [5]. These include thrombophlebitis caused by inflammation of the vein inflammation associated with a thrombus which spread into the cavernous sinuses. Also, it may be due to an embolization of infectious substance, which may occur following trauma, injury, abscess, or infection. Phlebothrombosis (aseptic type) resulting from thrombosis of a vein usually without inflammatory reaction is another mechanism. It is different from other types because of the absence of sepsis or a primary source of infection.

Most of the preventive approaches involve a lifestyle change. Furuncles in faces should not be forcefully removed and proper antibiotics must be administered at the appropriate regimen plan in order to avoid development of the septic form of cavernous sinus thrombosis.

Cavernous sinus thrombosis (CST) was first reported in the year 1831 by Bright as a complication resulting from infections in the epidural and subdural region. Dural sinuses are classified into three types, which include sagittal sinuses, cavernous sinuses and lateral sinuses. Lateral sinuses can be further differentiated into transverse, sigmoid or petrosal sinuses. Due to its complexity and the extensive neurovascular involvement, CST is the most severe among the classes of intracranial septic thrombosis [1]. CST usually results lately from the complications of the central facial infections or paranasal sinusitis. Other possible causes of CST may include septicemia, trauma, otitis and maxillary teeth infection. Most often, cavernous sinus thrombosis is sudden and severe in nature with high incidence of morbidity and mortality. However, recent development of new, potent antimicrobial drugs have assisted in reducing reported cases of cavernous sinus thrombosis.

Cavernous sinus thrombosis (CST) is an uncommon clinical condition caused by clot formation in cavernous sinuses. This condition may be due to bacterial infections such as those caused by S. aureus and streptococcus spp, contagious transmission of bacterial and fungal from the sinus, nasal or dental region. An immune response to the infection may result in the formation of blood clot in the sinus which if undiagnosed early or untreated may be severe. Factors such as age, gender and blood clotting disorder predispose individuals to cavernous sinus thrombosis. Pregnant women and those on contraceptives are at risk of developing the disease because of the blood clotting. Also, the disease is commonly seen among children and adolescents. Therefore, it is important to discuss various health issues with healthcare provider.

The symptoms of CST vary ranging from a severe headache, fever to either localized or unilateral facial pain, involving retro-orbital or frontal regions. Affected patient may develop a condition called ophthalmoplegia (a blunted eye papillary response to light), proptosis, and conjunctival edema. Also, the patient may have a seizure, neurologic complications (due to cranial nerve involvement), reduced facial sensation or consciousness. Optical effect may result in anisocoria, vision impairment, mydriasis, and papilledema. Following careful clinical examination of the suspected patient by the physician, the diagnosis is established after proper and adequate investigations. Various investigations may be required. These include CT scan, MRI ( sometimes venogram) and X-ray of the sinus. Patient medical history may also be requested. Other laboratory investigations such as complete blood count, bacteriological culture and blood clotting test may also assist the clinicians in establishing the right diagnosis.

The choice of treatment depends on the discretion of the physician. It is, therefore, important to discuss health challenges and self-medication is not encouraged. However, in most cases of CST, antibiotics are recommended in managing the condition. Antibiotics such as nafcillin, oxacillin, cephalosporin, metronidazole are usually administered. Also, drugs such as corticosteroids may be used to manage the patient if there are neurological involvement. Depending on the condition of the patient, surgery may be needed to effectively treat the condition.

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