Parameningeal Infections (other than brain abscess)

Table II.

Sinus involved	Predisposition	Microbiology	Signs/symptoms
Cavernous sinus	SinusitisSoft tissue infections of middle third of face (orbital cellulitis)Dental abscesses	Staphylococcus aureus (60–70%)StreptococciAnaerobes	Periorbital edema, headache, photophobia, diplopia, proptosis, chemosis, extraocular muscle weakness, papilledemaFindings spread to contralateral side in 24–48 hours
Lateral (transverse) sinus	Otitis mediaMastoiditis	Gram-negative bacilli (Escherichia coli)Anaerobes including Fusobacterium and Bacteroides speciesStreptococciHaemophilus influenzaeStaphylococci	Headache, otalgia, high fever, and occiput swelling and tenderness (Griesinger sign)Less common photophobia, diplopia, or unilateral nuchal rigidity
Superior sagittal sinus	Scalp traumaUpper face infectionPost-bacterial meningitis or subdural and epidural space infection	Staphylococci StreptococciAnaerobes	Altered mental status, papilledema, nuchal rigidity, seizures, motor weakness
Inferior petrosal sinus	Otitis mediaMastoiditis	Gram-negative bacilli Anaerobes StreptococciHaemophilus influenzaeStaphylococci	Gradenigo syndrome of ipsilateral facial pain and lateral rectus weakness

• Cavernous sinus thrombosis: the majority of patients experience fever and periorbital edema, and headache is common. Vision loss, diplopia, proptosis, and chemosis may develop. Papilledema is present in 65% of cases and drowsiness or change in mental status may accompany increased intracranial pressure. Cranial nerve VI traverses the lumen of the cavernous sinus and a lateral gaze palsy may be present as an early diagnostic clue. If left untreated, within 48 hours of the initial periorbitial edema, infection may spread to the contralateral sinus.

• Lateral sinus thrombosis: symptom onset may be more gradual than cavernous sinus thrombosis and is marked by headache, otalgia, high fever, and mastoid swelling and tenderness. The posterior auricular swelling and pain, present in 50% of cases, has been termed Griesinger sign. Photophobia, nuchal rigidity, vomiting, and vertigo are not uncommon. Of note, the nuchal rigidity tends to be unilateral with negative Kernig and Brudzinski signs. In a case series of children with lateral sinus thrombosis, 54% had diplopia.

• Superior sagittal sinus thrombosis: abnormal mental status, nuchal rigidity, and papilledema predominate and given that most cases are secondary to bacterial meningitis, the onset may be rapid. Seizures can be observed.

• Inferior petrosal sinus thrombosis: may present with Gradenigo syndrome of ipsilateral facial pain and lateral rectus weakness.

How did the patient develop a parameningeal infection? What was the primary source from which the infection spread?

• Subdural empyema: infection of the subdural space occurs following sinusitis by spread through valveless emissary veins with or without associated thrombophlebitis, or by extension of an epidural abscess nearby a site of osteomyelitis of the skull. When secondary to meningitis the initial predisposition is likely a sterile subdural effusion that becomes secondarily infected. Following widespread vaccination for Haemophilus influenza type b, incidence of subdural empyema secondary to bacterial meningitis in infants and children has decreased dramatically.

• Cranial epidural abscess: once the almost exclusive sequelae of sinusitis, otitis media, or mastoiditis, cranial epidural abscesses are now often secondary to neurosurgical complications. Less invasive procedures, such as fetal scalp monitoring and halo pin placement have also been reported as etiologies. An accompanying subdural empyema may be present.

• Suppurative intracranial thrombophlebitis: may arise from the intracranial veins or venous sinuses, or as a consequence of spread from paranasal sinusitis, otitis media, mastoiditis, dental abscess, orbital cellulitis, or infection of the scalp or face. Conditions that may predispose to a suppurative thrombosis of the venous sinuses are those associated with hyperviscosity or hypercoagulability such as pregnancy, intravascular volume depletion, oral contraceptive use, malignancy, systemic lupus erythematosus or the more specific presence of antiphospholipid antibodies or deficiencies in antithrombin III, and protein C or S.

Which individuals are of greater risk of developing a parameningeal infection?

• Subdural empyema: accounting for 15 to 20% of all intracranial infections, subdural empyema is the most common intracranial infection associated with sinusitis. Concomitant brain abscess is present in 9 to 17% of cases of subdural empyema. While initial infection of the paranasal sinuses is present in up to 80% of cases, additional causes include meningitis, otitis media, postneurosurgery, or in other posttraumatic settings of penetrating head trauma or pre-existing subdural hematoma.

• Cranial epidural abscess: patients with untreated sinusitis, otitis media, or mastoiditis are at risk for cranial epidural abscesses, as well as those having had neurosurgery or other less invasive procedures such as fetal scalp monitoring and halo pin placement. Concomitant brain abscess is present in 6 to 22% of patients who have an epidural abscess.

• Suppurative thrombophlebitis: most commonly, cavernous sinus thrombosis is secondary to infection of the frontal, ethmoid, or sphenoid sinuses, but can be observed with dental abscesses, orbital cellulitis, or infections of the middle third of the face. Lateral sinus thrombosis can be observed in the presence of both acute and chronic otitis media, whereas infection of the inferior and superior petrosal sinuses may arise from otitis media or mastoiditis. Lateral sinus thrombosis is more common in children and can be a devastating complication. The superior sagittal sinus may become infected following trauma to the scalp, after another infection of the subdural or epidural space, or after bacterial meningitis.

Beware: there are other diseases that can mimic parameningeal infection:

The following diseases can mimic parameningeal infection:

• brain abscess

• bacterial meningitis

• intracranial bleed

• ischemic stroke

• noninfectious space occupying lesion (e.g. tumor, particularly in an immunocompromised host)

What laboratory studies should you order and what should you expect to find?

Results consistent with the diagnosis

• Subural empyema/cranial epidural abscess: lumbar puncture is contraindicated given the risk of cerebral herniation, and cerebrospinal fluid (CSF) cultures are routinely negative unless complicated by bacterial meningitis.

• Suppurative thrombophlebitis: laboratory findings may be nonspecific. Lumbar puncture results are more characteristic of a parameningeal focus with mild pleocytosis that can be neutrophilic or mixed, and elevated CSF protein. In superior sagittal thrombophlebitis secondary to bacterial meningitis, CSF Gram stain and culture can be diagnostic. Blood cultures should be drawn prior to administration of broad spectrum antibiotics in all cases of suspected suppurative venous thrombosis and may be positive in patients with a more fulminant presentation.

Results that confirm the diagnosis

• Abscess/drainage culture:material obtained at the time of surgery that was cultured for aerobic/anaerobic bacteria and fungi is diagnostic. Histopathologic staining of infected tissue may be additionally confirmatory.

What imaging studies will be helpful in making or excluding the diagnosis of parameningeal infection?

Neuroimaging is the diagnostic modality of choice for suspected parameningeal infection

• Subdural empyema: neuroimaging is the diagnostic procedure of choice for subdural empyema given the high degree of sensitivity and for means of planning surgical intervention. Contrast-enhanced computed tomography (CT) or MRI can identify a crescent-shaped or elliptical area of hypodensity adjacent to the falx cerebri or beneath the cranial vault. Imaging may reveal loculations within the hypodensity or associated mass effect. Edema related mass effect includes displacement of midline structures, effacement of basilar cisterns, and flattening of cortical sulci. MRI has greater sensitivity for smaller subdural empyema, and for locations at the base of the brain, the posterior fossa and along the falx cerebri. Both imaging modalities will detect sinusitis and otitis, but MRI is preferred if spinal subdural empyema is a consideration. $$$–$$$$

• Cranial epidural abscess: similar to subdural epyema, a contrast-enhanced CT scan or MRI are essential to the diagnosis of cranial epidural abscess and MRI is the preferred modality. MRI can distinguish lentiform or crescentic collections overlying the cerebral convexity or within the interhemispheric fissure. Compared with CT scans, MRI can better differentiate sterile postsurgical effusions and hematomas. $$$$

• Suppurative thrombophlebitis: a contrast-enhanced CT scan may demonstrate an empty delta sign of darkened thrombus in the vessel lumen surrounded by enhancement of the surrounding wall. MRI may demonstrate adjacent areas of cerebral edema, and an acute thrombus appears isointense on T1-weighted images and hypointense on T2-weighted images with absence of the flow void signal. Magnetic resonance venography (MRV) is more sensitive than contrast-enhanced CT or MRI and can demonstrate loss of signal followed by absence of flow within the thrombosed sinus. However, MRV is usually performed in conjunction with contrast-enhanced CT or MRI in order to better visualize the paranasal sinuses, and evaluate for subdural or epidural infection and cerebral infarction. $$$–$$$$

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What consult service or services would be helpful for making the diagnosis and assisting with treatment?

If you decide the patient has a parameningeal infection, what therapies should you initiate immediately?

General treatment approach

• Subdural empyema: optimal approach involves surgical drainage by bur hole or open craniotomy and empiric parenteral antibiotic therapy. Drainage allows relief of mass effect and the ability to obtain aerobic and anerobic bacterial cultures of purulent material that will ultimately guide antibiotic choice.

• Cranial epidural abscess: as with subdural empyema, a combined medical and surgical approach is necessary for the treatment of cranial epidural abscess. Given the more indolent nature of cranial epidural abscesses and the likelihood of encountering a more thickened and tenacious purulence, open craniotomy or craniectomy is preferred over bur hole placement.

• Suppurative thrombophlebitis: surgery is often required and targeted at draining the initial source and this is particularly the case for cavernous sinus thrombosis secondary to paranasal sinusitis. Mastoidectomy is often performed for suppurative lateral sinus thrombosis if mastoiditis is present. Anticoagulation is recommended if central venous thrombosis is truly aseptic but remains controversial in suppurative thrombophlebitis with greatest risk being intracranial hemorrhage.

Principles of anti-infective therapy: initial Gram stain and culture of the aspirated pus will guide final antibiotic choice. Parenteral antibiotics are continued for 3 to 6 weeks depending upon clinical resolution and the need for repeat surgical drainage or exploration. Given the increase in methicillin-resistant Staphylococcus aureus and the finding of coagulase negative staphylococci in up to 5% of cases of subdural empyema, vancomycin is typically added to the combination of a third generation cephalosporin and metronidazole for community acquired subdural empyema and cranial epidural abscess. In the postneurosurgery setting, a cephalosporin with coverage of Pseudomonas aeruginosa or meropenem is preferred. Given the spectrum of anaerobic activity of meropenem when used, metronidazole is not required. Empiric regimens are detailed below.

1. Anti-infective agents

If I am not sure what pathogen is causing the infection what anti-infective should I order?

• Community acquired subdural empyema or cranial epidural abscess: we recommend a third generation cephalosporin such as cefotaxime 3 to 4g every 8 hours, or ceftriaxone 2g every 12 hours plus metronidazole at 7.5mg/kg (usually 500mg) every 6 hours plus vancomycin at 15 to 20mg every 12 hours.

• Postneurosurgery or penetrating trauma: we recommend an anti-pseudomonal cephalosporin such as cefepime at 2g every 8 hours or ceftazidime at 2g every 8 hours plus metronidazole at 7.5mg/kg (usually 500mg) every 6 hours plus vancomycin at 15 to 20mg/kg every 12 hours. Alternatively, meropenem at 2g every 8 hours can be substituted for the anti-pseudomonal cephalosporin and metronidazole.

• Suppurative thrombophlebitis: bacterial pathogens are similar to those observed with community acquired subdural empyema and cranial epidural abscess, but overall staphyloccoci are more prevalent and particularly so for suppurative cavernous sinus thrombosis; therefore, empiric therapy should always include vancomycin. We recommend a third generation cephalosporin such as cefotaxime 3 to 4g every 8 hours, or ceftriaxone 2g every 12 hours plus metronidazole at 7.5mg/kg (usually 500mg) every 6 hours plus vancomycin at 15 to 20mg every 12 hours, until cultures and susceptibility can guide therapy.

Pathogen-specific treatments for intracranial infection are summarized in Table I. Certain species are unlikely to be involved in isolated subdural empyema or cranial epidural abscess, but rather may be observed with associated brain abscess.