Clinical manifestations

Presentation and course

Symptoms of intracranial epidural abscess may develop acutely. In many instances, however, symptoms may be gradual in onset and may at first be overshadowed by those of accompanying sinusitis or otitis (40; 74; 72; 67; 20; 27) or, rarely, orbital cellulitis (78). The onset of symptoms may be especially insidious in cases, complicating neurosurgical procedures (32; 12). Cases developing as a complication of sinusitis may present with swelling of the forehead caused by a collection of pus under the periosteum with accompanying osteomyelitis (Pott’s puffy tumor) (15; 30; 48; 76; 07; 13; 69; 62; 64; 39). A clue to the presence of developing epidural abscess in cases associated with known cranial infections is that the intensity of clinical signs may vary inversely with the amount of external drainage (40). Nuchal rigidity may be present in advanced cases. At times, the developing abscess may be accompanied by superficial subperiosteal infection (Pott’s puffy tumor) or edema (40; 22; 36). Headache is a common early symptom (12; 27; 36; 14). Occasionally, patients may present in atypical fashion, which was exemplified by one patient who presented profound depression and suicidal ideation (16). Later findings include focal or generalized seizures, localized neurologic deficits, alteration in mental status, and ultimately, papilledema, nausea, and vomiting as signs of increased intracranial pressure (46; 60; 24; 32; 67). Epidural abscesses near the petrous bone, affecting cranial nerves V and VI, may cause Gradenigo syndrome, characterized by unilateral facial pain and lateral rectus weakness (54). Extension of infection inward across the dura, along emissary veins, may lead to subdural empyema or, less frequently, meningitis, brain abscess, or venous sinus thrombosis. Each of these may result in the abrupt worsening of clinical signs (72).

Prognosis and complications

Otogenic or sinusitis-related intracranial epidural abscess per se is rarely fatal. The major concern in epidural abscess (and the major need for speed in diagnosis and institution of therapy) is an extension of infection into the subdural space to produce subdural empyema, a deeper extension to produce meningitis, brain abscess, or sigmoid sinus or other intracranial venous sinus thrombosis (80). Epidural abscess in the setting of cranial trauma or neurosurgical procedures frequently occurs in a setting of brain injury or manipulation and carries a worse prognosis (79).

Clinical vignette

A 25-year-old man was in excellent health, except for a history of chronic sinusitis, until 1 week before admission, when he developed nasal and sinus congestion, followed by a feeling of “sinus pressure” over his left frontal region. He treated his symptoms with acetaminophen and decongestants. Three days before admission, however, he began to develop a headache. The headache progressed over the next 2 days, accompanied by fever and chills. On the morning of admission, his headache became abruptly worse, accompanied by severe photophobia, nausea, and vomiting, followed by the onset of confusion. His wife noted that he looked “puffy” over his forehead and brought him to seek medical care. Other than the history of sinusitis, the patient had enjoyed essentially flawless health. In particular, there was no history of head trauma or previous central nervous system infections.

On examination, the patient was acutely ill and oriented but somnolent and complained of a severe frontal headache. Pulse was 120 per minute; blood pressure was 135/82, respirations were 20 per minute, and temperature was 39.8°C. A general physical examination revealed tenderness to touch over the frontal regions bilaterally. Maxillary sinuses could be transilluminated, but frontal sinuses could not. Funduscopic examination revealed sharp discs but with absent venous pulsations. The remainder of the general physical examination was otherwise normal, except for mild nuchal rigidity. Neurologic examination revealed normal cranial nerves, motor, and sensory responses. The patient could walk with support but could not stand unsupported and could not perform tandem gait. Reflexes were brisk but equal. Babinski sign was present on the right and absent on the left.

Hematocrit was 50%. White blood count was 19,500 with 80% polymorphonuclear leukocytes and 10% bands. Erythrocyte sedimentation rate was 90 mm per hour. Blood chemistries and urinalysis were normal. Contrast-enhanced head CT revealed a hypodense mass lesion with an enhancing margin anterior to the frontal lobes.

The patient was diagnosed as having an intracranial epidural abscess without evidence of an underlying subdural empyema. The patient was placed on nafcillin and metronidazole and underwent surgical drainage of the abscess. Cultures of the abscess grew out Staphylococcus aureus (minimally sensitive to nafcillin but sensitive to vancomycin) and Streptococcus milleri. The patient’s antibiotic coverage was changed to vancomycin. Antibiotics were continued for 4 weeks. Follow-up radiological studies did not show evidence of osteomyelitis. The patient recovered without neurologic deficit.

Biological basis

Etiology and pathogenesis

Causative infectious agents. The causative agents of intracranial epidural abscess are similar to those associated with subdural empyema and brain abscess. Aerobic, microaerophilic, and anaerobic streptococci, including Streptococcus anginosus and Streptococcus milleri, are common in epidural abscesses associated with sinusitis or otitis (10; 05; 67; 20; 31). Multiple additional organisms, including Bacteroides species and enteric bacteria such as Escherichia coli, Proteus species, or Pseudomonas species may also be present in this setting (85; 05; 33). Streptococcus pneumoniae may be a causative agent in children with otitis or mastoiditis. Staphylococcus aureus is the most common organism in cases associated with cranial trauma or surgical procedures (74; 20). Fusobacterial infections have been increasingly associated with childhood intracranial epidural abscess in the setting of otogenic, sinus, or orbital infections and may result in venous sinus thrombosis or Lemierre syndrome involving internal jugular vein thrombosis and resultant septic emboli (66; 37).

Isolated cases have been associated with Campylobacter fetus (82), with Mycobacterium tuberculosis in patients with AIDS (Gettler and Sadr 1993; 70), with Eikenella sinusitis (02), and with infections with Salmonella (68), Aspergillus (34; 52), Mucor (Rhizopus) (57), or Blastomyces (08; 19). Salmonella sp. may produce osteomyelitis in patients with sickle cell anemia and may cause intracranial epidural abscess in that setting (17). Multiple organisms may be present, in particular in cases secondary to sinusitis or otitis.

Pathogenesis. The cranial dura forms both the outermost layer of the meninges and the innermost layer of the cranial periosteum. This thick membrane tightly adheres to the overlying skull so that infections arising at the interface between the dura and skull tend to be sharply circumscribed (11; 12). An epidural abscess is most commonly a complication of sinusitis, otitis, or mastoiditis (25; 29; 23). The infection may arise directly from cranial osteomyelitis or may result from septic thrombophlebitis of the emissary veins that link the venous drainage of the sinuses, middle ear, and mastoid with the deep cerebral venous system (72; 12). In rare instances, septic thrombosis of these small vessels may result in a venous epidural hemorrhage rather than an epidural abscess (06; 83).

Epidemiology

Epidural abscess represents an extremely rare complication of a common disorder – frontal sinusitis or, more rarely, otitis or mastoiditis. In an older series by Harris and colleagues, intracranial epidural abscesses constituted approximately 10% of all infections of the epidural space and were the third most common intracranial space-occupying infection, following brain abscess and subdural empyema (33). In a retrospective study, Gallagher and colleagues found epidural abscess to be the most common suppurative intracranial complication of sinusitis (25). Germiller and colleagues, in a study of 25 children and adolescents, found epidural abscess to be the most common intracranial complication of sinusitis, followed by subdural empyema, meningoencephalitis, brain abscess, and dural sinus thrombosis (27). Dubey and colleagues, in a study from New Guinea, found that the condition represented 21% of cases of intracranial suppuration following otitis (21). Intracranial epidural abscess, although uncommon below the age of 12 years, may occur in children as an initially silent complication of mastoiditis (09; 29). Interestingly, a report describes two children who developed epidural abscess during therapy with the tumor necrosis factor alpha inhibitor adalimumab (47). Intracranial epidural abscess may also occur as a rare complication of intranasal cocaine abuse (63). Although Pott’s puffy tumor is characteristically more common in the young (particularly males), a study by Nguyen and colleagues found a mean age of 42 years (58). Additionally, a retrospective literature review by Sideris and colleagues covering the period from 1983 to 2022 identified 125 adult patients (94 males, 31 females) with a mean age of 45 years (71). In this study, risk factors for Pott’s puffy tumor included head trauma, neurosurgical or sinus operations, immunosuppression, diabetes mellitus, cocaine use, and dental infections (71). In the past several years, an increase in intracranial infections has been observed in association with epidemic SARS-CoV-2 (COVID-19) infection (03).

Prevention

Sinusitis, in particular involving the frontal sinuses, is the major risk factor for developing an intracranial epidural abscess outside of hospital settings. A much smaller number of cases are associated with otitis media or mastoiditis (25; 29; 41; 31). Occasionally, epidural abscesses arise following cranial trauma or surgery involving the skull, sinuses, middle ear, or mastoid (49; 12; 42). Prior craniotomy is the major risk factor for hospital-acquired intracranial epidural abscess and is the most common risk factor overall in some series (38). Epidural abscess following surgery may be associated with a foreign body such as a graft, dural substitute, or skull penetration by neurosurgical stabilizing devices (49; 12). Development of the abscess may occur months to years after the associated surgery or trauma. Rarely, the condition may complicate orbital cellulitis (48), furunculosis (56), dental infection, or acupuncture (65; 84). In infants, epidural abscess may occur as a complication of scalp vein catheters (50).

Differential diagnosis

Confusing conditions

Early symptoms of intracranial epidural abscess may be nonspecific and may be masked by those of severe sinusitis, otitis, or mastoiditis (12; 27). The symptoms of the abscess itself (focal pain followed by generalized headache, followed by signs of increased intracranial pressure) may suggest brain abscess or, particularly in rapidly developing cases, subdural empyema (72; 61).

Diagnostic workup

The possibility of intracranial epidural abscess should be kept in mind in any patient with sinusitis or otitis who develops focal pain or diffuse headache out of keeping with the severity of the infection at hand. The presence of swelling of the forehead in this setting, suggesting osteomyelitis and subperiosteal abscess (Pott’s puffy tumor), should always raise concern that infection has spread intracranially (13; 36). Fever and leukocytosis are often present but may be attributed to sinusitis or otitis. Studies in children have suggested that elevation of erythrocyte sedimentation rate and C-reactive protein may help distinguish intracranial extension of sinusitis from uncomplicated sinus infection (01). The diagnostic procedures of choice are MRI with gadolinium enhancement and, less optimally, CT with contrast (44; 81; 18; 86; 53; 42; 27; 59; 62). MRI will detect areas of loculated infection not seen on CT, but CT may provide additional information about adjacent bone (81; 42). Epidural abscesses typically appear bright on MRI diffusion-weighted images (53; 14). Patient sedation, with careful monitoring of vital signs, may be essential to achieve an adequate study. Films should be studied with care for evidence of sinusitis or otitis, osteomyelitis, and, of greatest importance, subdural empyema. Spinal fluid findings are nonspecific, and the possibility of increased intracranial pressure (in particular if subdural empyema is also present) contraindicates lumbar puncture. Material obtained at the time of surgical drainage should be submitted for both aerobic and anaerobic culture. If infection with Mycobacterium tuberculosis or fungi is suspected, material should be sent for mycobacterial and fungal culture and, if available, for polymerase chain reaction for Mycobacterium tuberculosis.

Management

Small epidural abscesses may be managed with antibiotics alone and, at times, may contain so little purulent material that attempts at surgical drainage would be unsuccessful. A report by Heran and colleagues suggests that where there is minimal extradural mass effect, sinus-related intracranial epidural abscesses in children may be successfully managed with appropriate antibiotics and, as needed, drainage of the infected sinus, without neurosurgical procedures (35; 75; 61). In the small series by Heran and colleagues, several patients worsened symptomatically during the first week but did not exhibit increased mass effect. Where antibiotic therapy alone is used, the patient will require serial imaging and careful follow-up. Larger abscesses often require both antibiotic therapy and surgical drainage. In simple cases, surgery may be confined to burr holes. In certain instances, both sinusitis and the epidural abscess have been drained using a transnasal endoscopic approach (26). Craniotomy may be required in more extensive infections, particularly if there is osteomyelitis of the overlying skull. Surgery may also be required to treat the associated sinusitis or otitis. Material obtained at surgery should be submitted for both aerobic and anaerobic culture (61).

Antibiotics used in the treatment of intracranial epidural abscess are as follows (Table 1).

Table 1. Antibiotics for Empiric Therapy of Intracranial Epidural Abscess

Controlled studies of antibiotic treatment of epidural abscess do not exist as yet. The similarity in the bacteriology of intracranial epidural abscess to those of subdural empyema and brain abscess suggests the following approach to treatment. Because many abscesses contain a mixed culture of organisms, two or more agents may be required. Initial therapy, where no information exists as to the source of infection, should consider the combined use of oxacillin, plus ceftriaxone, plus metronidazole (04; 12). Vancomycin should be used in place of oxacillin if there is any question that nafcillin-resistant Staphylococcus aureus might be present or if the patient is known to be allergic to penicillin. Ceftazidime or cefepime should be used in place of ceftriaxone if Pseudomonas aeruginosa is strongly suspected (43). Linezolid has been used in individual cases to treat central nervous system infections with methicillin-resistant S aureus and other multidrug-resistant organisms, but experience with its use in intracranial epidural abscess is lacking (45; 55). The antibiotic regimen used in a given patient may need to be revised as data become available from cultured abscess material. The length of therapy is determined by patient course and follow-up MRI or CT. In general, antibiotics should be continued for at least 4 weeks if surgery is not undertaken or 6 to 8 weeks if osteomyelitis is present. Careful follow-up of the infection by MRI or, if MRI is not available, by CT is essential if the epidural abscess is treated with antibiotics only.

Outcomes

Intracranial epidural abscess per se is rarely fatal unless the infection extends intracranially to cause subdural empyema, meningitis, brain abscess, or septic thrombosis of intracranial veins or venous sinuses. The accompanying sinusitis or otitis, along with osteomyelitis, may require surgery and prolonged antibiotic treatment.

Special considerations

Pregnancy

Incidence, clinical symptomatology, and treatment of intracranial epidural abscess in pregnancy do not differ from that seen in nonpregnant individuals.

Anesthesia

Intracranial epidural abscess is not a contraindication to the use of anesthesia. An extremely large epidural abscess or a coexisting subdural empyema may cause significant elevation in intracranial pressure. In such cases, the use of anesthetic agents such as halothane, methoxyflurane, or ketamine should be approached with caution. These agents cause intracranial vasodilatation and, thus, may further increase intracranial pressure and the risk of herniation.