ACP medicine, 3rd Edition

Infectious Disease

Bacterial Infections of the Central Nervous System

Jan V. Hirschmann MD

Professor of Medicine

University of Washington School of Medicine; Assistant Chief, Medical Service, Puget Sound Veterans Affairs Medical Center

The author has no commercial relationships with manufacturers of products or providers of services discussed in this chapter.

January 2006

Several barriers protect the central nervous system from bacterial infection. Considerable force is necessary to breach the skull and allow ingress of organisms into the brain or its coverings. Tight junctions between cells in the cerebral vasculature form the blood-brain barrier, limiting access by blood-borne pathogens. The vertebrae and the dura mater enveloping the spinal cord present strong defenses against incursions by microbes from contiguous areas.

Nevertheless, bacteria occasionally overwhelm or bypass these barriers, resulting in CNS infections. They usually arrive by one of three routes: (1) penetration as a result of trauma or surgery, (2) migration from an adjacent site of infection or colonization, or (3) hematogenous spread from another, often distant, location. The major bacterial infections that result are meningitis, brain abscess, epidural abscess, subdural empyema, and septic thrombophlebitis of the cerebral veins.

Acute Bacterial Meningitis

EPIDEMIOLOGY AND ETIOLOGY

Because vaccination has markedly decreased childhood Haemophilus influenzae type b infections, acute bacterial meningitis, previously most common in children, has become predominantly a disease of adults.1 Bacterial meningitis may occur in otherwise healthy persons, but it usually afflicts those with significant underlying disorders, such as hypogammaglobulinemia, sickle cell anemia, alcoholism, cirrhosis, and concurrent infections of the ears, paranasal sinuses, lungs, or cardiac valves.2 Patients with HIV disease have a substantially increased risk of bacterial meningitis, usually when their CD4+ T cell count is less than 200/mm3. The most common organism is Streptococcus pneumoniae; bacteremia is nearly always present.3 Patients with a splenectomy or poor splenic function may develop overwhelming sepsis, often including meningitis, from encapsulated bacteria, primarily S. pneumoniae. Deficiencies of some complement components increase susceptibility to infections with Neisseria meningitidis, and head trauma that disrupts the dura mater can lead to meningitis, usually from S. pneumoniae. Meningitis that occurs as a complication of neutropenia or cranial surgery is most commonly caused by gram-negative bacilli [see Table 1]. A viral upper respiratory tract infection may predispose to meningitis by allowing bacteria that are colonizing the respiratory tract, especially N. meningitidis, to enter the bloodstream and invade the meninges.

Table 1 Causes of Bacterial Meningitis in Adults1,2

Organism

Approximate Frequency

Streptococcus pneumoniae

40%–60%

Neisseria meningitidis

15%–25%

Listeria monocytogenes

10%–15%

Haemophilus influenzae

5%–10%

Other

5%–20%

Culture negative

10%–15%

  1. pneumoniaecauses approximately 40% to 60% of adult cases of bacterial meningitis in the United States; these cases often occur secondary to bacteremic pneumococcal pneumonia. Other major organisms in community-acquired cases are N. meningitidis, primarily in young adults; Listeria monocytogenes, especially in immunocompromised or elderly hosts; H. influenzae; and group B streptococci (S. agalactiae). Usually, the organisms reach the meninges through bacteremia from a mucosal site or a distant infection. Occasionally, the bacteria enter the subarachnoid space from adjacent infectious foci or through direct inoculation via trauma, surgery, or invasive medical procedures, such as lumbar puncture.

DIAGNOSIS

Clinical Features

The duration of symptoms before patients seek medical attention varies from less than 24 hours to more than 1 week. A prodrome resembling a viral upper respiratory tract infection may occur; it is characterized by sore throat, rhinorrhea, and nasal congestion, sometimes accompanied by myalgias. The most common features of bacterial meningitis are headache, fever, nuchal rigidity, and neurologic findings. Less than half of patients have the classic triad of fever, neck stiffness, and a change in mental status; however, almost all have at least two of the four manifestations of headache, fever, neck stiffness, and altered mental status.4 Fever is present in approximately 95% of patients and typically lasts 4 to 8 days after appropriate therapy has begun.2,5,6 Stiff neck is apparent in about 90% of patients. Two physical findings that, like nuchal rigidity, arise from meningeal irritation and the neuromuscular response to it are the Kernig sign (when the hip is flexed at 90°, attempted extension of the knee meets resistance at 135°) and the Brudzinski sign (passive flexion of the neck causes knee and hip flexion).7 Mental changes ranging from lethargy to confusion, stupor, and coma occur in about 80% of patients, somewhat more frequently in the elderly. Seizures, either focal or generalized, occur in about 10% to 30% of patients, usually within 24 hours of admission. Many such seizures arise from alcohol withdrawal. Focal neurologic findings other than seizures develop in about 30% of patients. They include cranial nerve palsies, aphasia, and hemiparesis as a consequence of infection-induced vasculitis or pressure of purulent exudate on neurologic structures. Papilledema occurs only occasionally; its absence does not exclude significantly increased intracranial pressure.

Laboratory Findings

Most patients with acute bacterial meningitis have leukocytosis, and some have hyponatremia, presumably because of inappropriate secretion of antidiuretic hormone. Blood cultures, which are positive in approximately 50% to 60% of cases, are always indicated. The most important diagnostic procedure is a lumbar puncture to obtain cerebrospinal fluid to determine the white cell count and differential, to measure protein and glucose levels, and for culture and Gram stain.

Clinicians commonly obtain a CT scan before doing a lumbar puncture, on the basis of two beliefs: that brain herniation is a frequent risk in meningitis and that CT scans can accurately predict its development. Neither belief is correct. Herniation occurs in approximately 1% of patients with bacterial meningitis,2 sometimes without a preceding lumbar puncture.8 CT scans are often normal in those who later experience brain herniation, and most patients who develop this complication have focal neurologic findings before the lumbar puncture that suggest that herniation has already begun: dilated, fixed pupils; Cheyne-Stokes respiration; decerebrate posturing; hemiplegia; and coma.8In addition to focal 2neurologic deficits and abnormal level of consciousness, findings that justify performing CT before lumbar puncture include the following: immune compromise; a history of CNS disease (e.g., mass lesion, stroke, or focal infection); papilledema (although the presence of venous pulsations suggests that the patient does not have increased intracranial pressure); and seizures within 1 week before presentation (some experts will not perform a lumbar puncture in patients with prolonged seizures and will delay lumbar puncture for 30 minutes in patients who have experienced short, convulsive seizures).9 In the absence of such findings in patients with suspected bacterial meningitis, clinicians should not delay lumbar puncture to obtain a CT scan [see Figure 1].

 

Figure 1. Management of Suspected Bacterial Meningitis

Management of adult patients with suspected bacterial meningitis.9 (CSF—cerebrospinal fluid; LP—lumbar puncture)

In approximately 90% of patients, the opening pressure is above 180 mm H2O; in 20%, it is above 400 mm H2O; and in about 5%, it is above 500 mm H2O. The CSF protein level exceeds 40 mg/dl in approximately 85%, and the glucose level is below 40 mg/dl in about 60%.2When bacterial meningitis develops in patients with diabetes and hyperglycemia, the CSF glucose level may be normal, but the ratio of CSF glucose to blood glucose in these patients is usually less than 0.31.10 The CSF white cell count is greater than 100/mm3 in about 90% of patients and exceeds 1,000/mm3 in 15% to 20%. Neutrophils nearly always predominate, constituting at least 80% of cells in 80% to 90% of patients. Occasionally, lymphocytes constitute the majority, especially when the white cell count is very low; lymphocytes constitute the majority in about 25% of patients with meningitis caused by L. monocytogenes.11 Several conditions can cause neutrophilia with low CSF glucose levels and can mimic acute bacterial meningitis [see Table 2].

Table 2 Causes of Neutrophilia with Low Glucose Levels in the CSF

 

Infectious Cause

Noninfectious Cause

Common

Bacterial meningitis

Uncommon

Viral meningitis* (in very early phase only)
Certain parameningeal infections
   Subdural empyema* (usually produces lymphocytic-normal glucose profile)
   ?Early brain abscess at bacterial cerebritis stage*
   Cerebral abscess with leakage or rupture into ventricle
Embolic cerebral infarction* (bacterial endocarditis)
Amebic meningoencephalitis
Tuberculous meningitis (only very early in the disease and only in a small percentage of cases)
Acute hemorrhagic leukoencephalitis

Chemical meningitis
   Exogenous (e.g., contrast media, detergents used in cleaning needles)
   Endogenous (release of material into CSF from tumors: dermoids, craniopharyngiomas)
Unsual diseases*
   Initial phase of Mollaret meningitis
   Behçet syndrome
Hypersensitivity meningitis
   Drug-induced* (sulfonamides, tolmetin, ibuprofen, isoniazid)

*Glucose level in CSF usually normal.

Gram stain is positive in approximately 60% to 90% of patients, indicating a concentration of bacteria exceeding 105 organisms/ml. Misinterpretation may occur, especially through mistaking pneumococci for Listeria. In listerial meningitis, the Gram stain is positive in only 30% of cases.12

The CSF culture is positive in approximately 80% of patients. Previous oral antibiotic therapy has little effect on the WBC or differential cell counts, protein level, or glucose level, but it decreases the number of positive Gram stains by about 20% and the number of positive cultures by about 30%.13 The effect of parenteral therapy is presumably much greater, especially if given more than a few hours before the lumbar puncture. In patients with negative Gram stains and cultures, latex agglutination tests of the CSF are highly specific for H. influenzae type b, meningococci, and pneumococci, but their sensitivity ranges from 50% to 80%.

Imaging Studies

Imaging techniques are ordinarily unnecessary in bacterial meningitis unless specific complications are suspected. The subarachnoid space may be distended on CT or MRI studies; however, this finding is often difficult to interpret in adults, in whom a degree of brain atrophy is common—especially in the elderly. Several days after infection, meningeal enhancement may occur after contrast injection because of meningeal inflammation and vascular congestion. Enhancement of areas in the cerebral cortex usually indicates brain infarction from occlusion of inflamed vessels. Brain edema may occur because of disturbed cerebrovascular autoregulation, dural sinus thrombophlebitis, leakage of fluid from damaged vessels, or cytotoxic edema from injured brain cells. Communicating or noncommunicating hydrocephalus occasionally develops because inflammation obstructs the normal flow of CSF, either at the arachnoid granulations where it is absorbed or at the sites where it leaves the ventricles.

TREATMENT

Intravenous Antibiotics

The most important therapeutic maneuver is prompt initiation of intravenous antibiotics after lumbar puncture, because delay in beginning treatment increases the mortality [see Tables 3 and 4].14 In the rare situation in which lumbar puncture is justifiably postponed—for example, when signs of brain herniation are present (see above)—blood cultures should be obtained and antibiotics begun, even though they may reduce the yield of the subsequent CSF Gram stain and culture. The antimicrobial agent chosen should be bactericidal against the suspected pathogens and should achieve good CSF levels. In a Danish study, ceftriaxone plus penicillin was an appropriate choice for empirical treatment in 97% of the adult patients with bacterial meningitis in the study population.15

Table 3 Empirical Antibiotic Therapy for Purulent Meningitis in Adults9

Patient Factor

Common Bacterial Pathogens

Antibiotic

Age 2–50 yr

Neisseria meningitidis, Streptococcus pneumoniae

Vancomycin plus a third-generation cephalosporin*; consider adding rifampin if dexamethasone is given

Age > 50 yr

S. pneumoniae, N. meningitidis, Listeria monocytogenes, aerobic gram-negative bacilli

Vancomycin plus ampicillin plus a third-generation cephalosporin*; consider adding rifampin if dexamethasone is given

Basilar skull fracture

S. pneumoniae, Haemophilus influenzae,group A β-hemolytic streptococci

Vancomycin plus a third-generation cephalosporin*

Penetrating head trauma

Staphylococcus aureus, coagulase-negative staphylococci, especially S. epidermidis;aerobic gram-negative bacilli, includingPseudomonas aeruginosa

Vancomycin plus cefepime, vancomycin plus ceftazidime, or vancomycin plus meropenem

Postneurosurgery

Aerobic gram-negative bacilli, including P. aeruginosa; S. aureus; coagulase-negative staphylococci, especially S. epidermidis

Vancomycin plus cefepime, vancomycin plus ceftazidime, or vancomycin plus meropenem

CSF shunt

Coagulase-negative staphylococci, especiallyS. epidermidis; S. aureus; aerobic gram-negative bacilli, including P. aeruginosa; Propionibacterium acnes

Vancomycin plus cefepime, vancomycin plus ceftazidime, or vancomycin plus meropenem

*Ceftriaxone or cefotaxime.
CSF—cerebrospinal fluid

Table 4 Antibiotic Therapy for Bacterial Meningitis in Adults9

Organism

Antibiotic

Dosage

Alternative Antibiotic

Streptococcus pneumoniae

 

 

 

   Penicillin MIC < 0.1 µg/ml

Penicillin G

4 million U I.V. q. 4 hr

Third-generation cephalosporin* or chloramphenicol, 1 g I.V. q. 6 hr

   or

 

 

Ampicillin

2 g I.V. q. 4 hr

 

   Penicillin MIC 0.1–1.0 µg/ml

Ceftriaxone

2 g I.V. q. 12 hr

Cefepime, 2 g I.V. q. 8 hr, or meropenem, 2 g I.V. q. 8 hr

   Penicillin MIC > 1.0 µg/ml

Vancomycin

30–45 mg/kg I.V.

Fluoroquinolone

   plus

 

 

third-generation cephalosporin*

 

 

Cefotaxime or ceftriaxone MIC > 1 µg/ml

Vancomycin

30–45 mg/kg I.V.

Fluoroquinolone

   plus

 

 

third-generation cephalosporin*

 

 

Neisseria meningitidis

 

 

 

  Penicillin MIC < 0.1 µg/ml

Penicillin G

4 million U I.V. q. 4 hr

Third-generation cephalosporin* or chloramphenicol, 1 g I.V. q. 6 hr

   or

 

 

Ampicillin

2 g I.V. q. 4 hr

 

  Penicillin MIC 0.1–1.0 µg/ml

Third-generation cephalosporin*

 

Chloramphenicol, 1 g I.V. q. 6 hr, fluoroquinolone, meropenem, 2 g I.V. q. 8 hr

Listeria monocytogenes

Ampicillin§

2 g I.V. q. 4 hr

Trimethoprim (TMP)-sulfamethoxazole (SMX): 10–20 mg/kg TMP, 50–100 mg/kg SMX q.d. in two to four divided doses; or meropenem, 2 g I.V. q. 8 hr

   or

 

 

Penicillin G§

4 million U I.V. q. 4 hr

 

Haemophilus influenzae

 

 

 

  β-Lactamase negative

Ampicillin

2 g I.V. q. 4 hr

Third-generation cephalosporin*; cefepime, 2 g I.V. q. 8 hr; chloramphenicol, 1 g I.V. q. 6 hr or fluoroquinolone

  β-Lactamase positive

Third-generation cephalosporin*

 

Cefepime, 2 g I.V. q. 8 hr; chloramphenicol, 1 g I.V. q. 6 hr; or fluoroquinolone

Group BStreptococcus(S. agalactiae)

Ampicillin§

2 g I.V. q. 4 hr

Third-generation cephalosporin*

   or

 

 

Penicillin G§

4 million U I.V. q. 4 hr

 

Escherichia coli, Klebsiella, Proteus, and other enteric gram-negative bacilli

Third-generation cephalosporin*

 

Aztreonam, 2 g q. 6–8 hr; fluoroquinolone; meropenem, 2 g I.V. q. 8 hr; TMP-SMX: 10–20 mg/kg TMP, 50–100 mg/kg SMX, q.d. in two to four divided doses; or ampicillin, 2 g I.V. q. 4 hr

Pseudomonas aeruginosa

Cefepime§

2 g I.V. q. 8 hr

Aztreonam, 2 g q. 6–8 hr§; ciprofloxacin, 400 mg q. 8–12 hr§; or meropenem, 2 g I.V. q. 8 hr§

   or

 

 

Ceftazidime§

2 g I.V. q. 8 hr

 

Staphylococcus aureus

 

 

 

Methicillin sensitive

Nafcillin

1.5–2 g I.V. q. 4 hr

Vancomycin, 30–45 mg/kg I.V., or meropenem, 2 g I.V. q. 8 hr

   or

 

 

Oxacillin

1.5–2 g I.V. q. 4 hr

 

Methicillin resistant

Vancomycin||

30–45 mg/kg I.V.

TMP-SMX: 10–20 mg/kg TMP, 50–100 mg/kg SMX, q.d. in two to four divided doses; or linezolid, 600 mg I.V. q. 12 hr

Staphylococcus epidermidis

Vancomycin||

30–45 mg/kg I.V.

Linezolid, 600 mg I.V. q. 12 hr

Enterococcus species

 

 

 

  Ampicillin susceptible

Ampicillin

2 g I.V. q. 4 hr

 

  plus

 

 

Gentamicin

2 mg/kg first dose I.V., then 1.7 mg/kg I.V. q. 8 hr with normal renal function (or 4–8 mg q.d. intrathecally)

 

30–45 mg/kg I.V.

 

Ampicillin resistant

Vancomycin

2 mg/kg first dose I.V., then 1.7 mg/kg I.V. q. 8 hr with normal renal function (or 4–8 mg q.d. intrathecally)

 

   plus

 

 

Gentamicin

 

Ampicillin and vancomycin resistant

Linezolid

600 mg I.V. q. 12 hr

 

*Ceftriaxone, 2 g I.V. q. 12 hr, or cefotaxime, 2 g q. 4–6 hr.
Gatifloxacin, 400 mg I.V. q.d., or moxifloxacin, 400 mg I.V. q.d.
Consider adding rifampin, 600 mg q.d., if the ceftriaxone MIC is > 2 µg/ml.
§Consider adding an aminoglycoside.
||Consider adding rifampin, 600 mg q.d.
MIC—minimum inhibitory concentration

The findings on CSF Gram stain may help guide the choice of antibiotic; when the stain is negative, however, ceftriaxone (2 g I.V. every 12 hours, or 4 g I.V. every 24 hours) is a good choice in adults.15 Ceftriaxone provides coverage for meningococci, H. influenzae, group B streptococci, and S. pneumoniae, including many penicillin-resistant strains. In a Danish study, ceftriaxone plus penicillin was an appropriate choice for empirical treatment in 97% of the adult patients with bacterial meningitis in the study population.16

With suspected high-level penicillin resistance, use of vancomycin (2 g every 12 hours) is prudent until culture and susceptibility test results are available. If Gram stain of the CSF is negative or if a distinction between pneumococci and Listeria is uncertain, the patient should receive, in addition, ampicillin at a dosage of 2 g every 4 hours to treat possible L. monocytogenes infection.

Although controlled studies have not delineated the optimal length of antibiotic therapy, the duration is usually 7 days for H. influenzae and 10 to 14 days for most other organisms. For meningococcal disease, treatment for 4 to 5 days is of proven efficacy, and in one study, 3 days of treatment with intravenous benzylpenicillin was effective.17

Repeat lumbar puncture during or after therapy is usually unnecessary unless treatment seems to be failing.

Systemic Corticosteroids

In adults with acute pneumococcal meningitis, adjuvant treatment with dexamethasone has been shown to lower the risk of an unfavorable outcome and to lower mortality, without increasing the likelihood of gastrointestinal bleeding.18,19 Consequently, guidelines from the Infectious Diseases Society of America recommend that adults with suspected or proven pneumococcal meningitis receive adjunctive dexamethasone.9 The dosage is 0.15 mg/kg every 6 hours for 2 to 4 days, with the first dose given 10 to 20 minutes before or at least concomitant with the first dose of antibiotics. Dexamethasone should be continued only if the CSF Gram stain reveals gram-positive diplococci or if blood or CSF cultures are positive for S. pneumoniae. Dexamethasone treatment is unlikely to improve the outcome in adult patients who have already received antimicrobial therapy and hence should not be used in this circumstance.

COMPLICATIONS

Many complications may occur in meningitis patients, including secondary nosocomial infections, systemic venous thromboembolism, and adverse effects from the medications administered. The most common systemic complications occur from the initial infection, however, and include septic shock, disseminated intravascular coagulation, and the acute respiratory distress syndrome.20 The most frequent neurologic complications other than seizures and altered mentation are cerebral edema, hydrocephalus, and cerebrovascular complications.21

In bacterial meningitis, the internal carotid, basilar, and vertebral arteries and their branches lie within a purulent subarachnoid exudate, which can provoke vascular inflammation and constriction. Smaller arteries may demonstrate vessel wall irregularities, occlusion, narrowing, or widening. Thrombosis of the superior sagittal sinus or the cortical veins can occur. These abnormalities may cause discrete areas of brain damage—which is evidenced by focal neurologic findings—or increased intracranial pressure that is produced by leakage of cerebral vessels (vasogenic edema), swelling of damaged neurons (cytotoxic edema), or increased blood volume that occurs when sinus venous thrombosis impedes drainage of blood from the brain.

PROGNOSIS

The mortality associated with meningitis is approximately 10% in meningococcal infections and is typically 20% to 30% in meningitis caused by other organisms. Factors associated with poorer prognoses include infection with S. pneumoniae, advanced age (> 60 years), onset of seizures during the first 24 hours after infection, hypotension, and coma or obtundation on hospital admission.4,22 Most survivors recover completely. Approximately 30% of patients with pneumococcal meningitis have moderate to severe sequelae, including dementia, seizures, hearing loss, and gait disturbances; about 20% have mild problems, such as dizziness, slightly impaired memory, headaches, and phonophobia.23

Bacterial Meningitis in Special Circumstances

POSTTRAUMATIC BACTERIAL MENINGITIS

Epidemiology and Etiology

Bacterial meningitis develops in about 1% of persons who receive medical attention for blunt cranial injuries, most commonly from motor vehicle accidents.24 At risk are those in whom the force of impact fractures the base of the skull, tearing the dura mater, the underlying arachnoid, and adjacent soft tissues. The trauma, however, need not be severe: coma or retrograde amnesia is absent or brief in 30% to 40% of cases.

The most common cause of posttraumatic meningitis is S. pneumoniae, which accounts for about 65% of cases. In the remainder of cases, the causes are primarily other streptococci, H. influenzae, meningococci, and Staphylococcus aureus. Enteric gram-negative bacilli are rare causes, except in patients who have previously received antimicrobial therapy.

Pathogenesis

The dural rent resulting from blunt cranial trauma creates a fistula between the subarachnoid space and the nasal cavity, paranasal sinuses, or ear. The most common site for these abnormal communications is the cribriform plate; the disruptions are multiple, however, in about 40% of cases. When these rents are large, they are evident as CSF rhinorrhea; smaller leaks may go unrecognized, and drainage may be delayed or intermittent when tissue occludes the dural laceration. When trauma weakens but does not tear the dura, CSF rhinorrhea may begin abruptly after sudden increases in cerebrospinal pressure from coughing, sneezing, or straining. When the dural fistula occurs in the middle cranial fossa because of a fractured temporal bone, CSF may exit through the ear canal (if the tympanic membrane ruptures) or drain into the pharynx through the eustachian tube and go unrecognized. Evidence of basilar skull fractures may appear shortly after the injury as periorbital bruising, anosmia, hemotympanum, bloody ear drainage, or Battle sign (ecchymoses behind the ear).

Diagnosis

Clinical features

The usual clinical features of bacterial meningitis, including fever, headache, and stiff neck, are present in posttraumatic meningitis. Mortality is comparatively low (10%), however, perhaps because the fistula allows drainage of CSF (relieving intracranial hypertension) or because many patients with cranial trauma are young and otherwise healthy. The interval between blunt cranial injury and meningitis is usually less than 1 month, but infection may occur years later; when evaluating patients with unexplained meningitis, clinicians should therefore ask about any significant head trauma, even if such trauma occurred in the remote past.

Recognition of CSF rhinorrhea or otorrhea allows a diagnosis of a dural fistula. The discharge often increases with sudden movement, lowering of the head, performance of the Valsalva maneuver, or jugular vein compression. Unlike normal nasal secretions, the CSF fluid is not sticky, does not stiffen a handkerchief on drying, may taste salty, and has a glucose level greater than 30 mg/dl in the absence of infection. The most sensitive and specific way to identify CSF is by detection of a β2-transferrin found only in that body fluid.25

Imaging studies

Several techniques help localize the leak of CSF. CT scans may demonstrate the fistula site by disclosing sinus fractures, displaced bony fragments, or intracranial air (pneumocephalus). Radionuclide-labeled albumin and various dyes injected in the subarachnoid space may leak into the middle and superior meatus of the nose and become detectable on cotton pledgets placed in these locations. Magnetic resonance cisternography, a noninvasive and rapid procedure, seems highly accurate in detecting fistulas.25 This technology relies on the fact that CSF gives a high signal on T2-weighted images: demonstration of a continuous high signal through the cribriform plate or the paranasal sinuses that is similar to the signal given by the CSF in the basal cisterns indicates a dural fistula.

Treatment

Because many dural fistulas resolve spontaneously, repair is usually unnecessary unless problems persist for 2 to 3 weeks after the injury. Patients with facial fractures or meningitis are exceptions. Those with fracture sites accessible through the nose typically undergo transnasal closure with fibrin glue, fascia lata, or local flaps. Otherwise, intracranial repair is required. Recurrences may develop if the dural fistula remains uncorrected. Vancomycin plus a third-generation cephalosporin (e.g., ceftriaxone or cefotaxime) is a good antibiotic choice for bacterial meningitis after closed head trauma when the CSF Gram stain is negative. A randomized trial of patients with acute traumatic pneumocephalus after mild head injury found that ceftriaxone was not effective in preventing meningitis in these patients.26

RECURRENT BACTERIAL MENINGITIS NOT CAUSED BY TRAUMA

Although a dural fistula created by blunt cranial trauma is the most common cause of recurrent bacterial meningitis, seemingly spontaneous leaks of CSF occasionally occur; most of these probably arise from a congenital or acquired weakness in the dura. Defects of the skull or of the floor of the middle cranial fossa are other potential sources of recurrent meningitis, as are bony complications from chronic ear infections. Congenital malformations can lead to dermal sinus tracts, often associated with intradural dermoid tumors, that connect the skin to the CSF. They commonly occur at the lumbodorsal spine but may be present anywhere along the midline. Abnormalities at the cutaneous exit site can include small tufts of hair, a nevus, or a dimple from which purulent drainage may emanate. Other conditions associated with recurrent bacterial meningitis are hypogammaglobulinemia, asplenia, and deficiencies of certain components of complement, which especially predispose to meningococcal meningitis [see Table 5].

Table 5 Causes of Recurrent Meningitis

Bacterial Meningitis*

   Predisposing anatomic defects

      Congenital: meningomyeloceles, dermal sinuses

      Traumatic: skull fractures through cribriform plate or petrous ridge

      Postoperative: craniotomy, transsphenoidal hypophysectomy

      Tumors: direct invasion through the dura

      Empty sella syndrome

   Parameningeal infections*

      Mastoiditis, sinusitis, osteomyelitis of skull

   Immunologic defects*

      Immunoglobulin deficiencies: congenital or acquired (e.g., myeloma)

      Asplenic state: splenectomy or functional asplenia (e.g., sickle cell anemia)

      Complement deficiencies: C6, C7, or C8 deficiency

Endogenous Chemical Meningitis

   Tumors

      Craniopharyngioma, epidermoid cyst

Unusual Nonbacterial Recurrent Meningitides

   Mollaret meningitis

   Behçet syndrome

   Drug hypersensitivity

      Sulfonamides, ibuprofen

   Systemic lupus erythematosus

   Uveoencephalitides (Vogt-Koyanagi syndrome, Harada syndrome)

*Neutrophilic CSF pleocytosis.
Either neutrophilic or lymphocytic CSF pleocytosis.
Lymphocytic CSF pleocytosis.

CEREBROSPINAL FLUID SHUNT INFECTIONS

CSF shunts, used to relieve hydrocephalus, usually consist of a ventricular catheter; a pressure-regulating valve and reservoir, commonly placed just outside the skull; and distal tubing that drains the CSF, most often into the peritoneum but sometimes into the right atrium, pleura, or other sites.

Etiology

Mechanisms of infection of CSF shunts include implantation of microbes during shunt insertion, entry through a break in the overlying skin, hematogenous dissemination from a distant site, and retrograde spread of organisms from the distal end (in the peritoneum or another body cavity).27 The most common origin is contamination of the device by skin flora at the time of surgery. Most infections become apparent within a few weeks of the shunt's insertion. Entry of microbes into the shunt from overlying skin is probably the next most frequent cause of infection. Retrograde and hematogenous infections seem to be rare except in the case of ventriculoatrial shunts, in which the distal end lies within the bloodstream.

The bacteriology of CSF shunt infections reflects the probable cutaneous source of infection in most cases. The most common isolates are staphylococci, with coagulase-negative species accounting for approximately 50% to 60% of cases and S. aureus for approximately 20%. Streptococci, anaerobes, diphtheroids, and polymicrobial infections, primarily from these and other cutaneous species, constitute most of the remaining cases. About 10% of isolates are gram-negative bacilli, and about 5% are the same organisms that commonly cause community-acquired meningitis in patients without shunts: pneumococci, meningococci, and H. influenzae.

Diagnosis

Clinical features

The manifestations of CSF shunt infections differ from the usual findings of bacterial meningitis and depend on the site involved. Fever is usually present. When ventriculitis occurs, nuchal rigidity rarely develops, because infected CSF typically does not communicate from the ventricle to the meninges. Mental changes, including headache, nausea, lethargy, and confusion, are the most common abnormalities; these may result from infection in the ventricle or from increased intracranial pressure caused by obstruction of the shunt anywhere along its route. Evidence of infection over the shunt may sometimes be detected by the presence of wound dehiscence, cellulitis, or purulent drainage. When the distal end lies within the atrium, bacteremia may occur, sometimes complicated by endocarditis. In chronic bacteremia, usually caused by coagulase-negative staphylococci, renal disease (so-called shunt nephritis) produced by deposition of immune complexes in the kidney may develop. When the distal end lies in the peritoneum, infection may cause peritonitis, manifested by abdominal pain and tenderness, anorexia, and fever. Often, the infection is more insidious, with enlarging cysts developing around the end of the catheter as the inflamed peritoneum fails to absorb the CSF.

Laboratory findings

The peripheral white cell count is often normal. Blood cultures are characteristically positive in patients with infected ventriculoatrial shunts but are usually negative when the distal end lies elsewhere. The culture of CSF obtained through needle aspiration of the shunt reservoir or the culture of any fluid in contact with the shunt is the best approach to delineating the cause. The CSF will usually show pleocytosis, which is often mild, and an elevated protein level; the glucose level is typically normal or slightly decreased. Gram stain may reveal bacteria, but it is often negative.

Treatment

Treatment of shunt infections usually entails systemic antibiotics, shunt removal, and temporary placement of an external ventricular drain to control intracranial pressure (and to provide a conduit for intraventricular antibiotic administration). The systemic antimicrobials used for the treatment of shunt infections are nafcillin for susceptible strains of S. aureus and vancomycin for methicillin-resistant S. aureus and coagulase-negative staphylococci, often supplemented by oral rifampin (600 mg daily). Ceftriaxone is used for susceptible gram-negative bacilli; ceftazidime is appropriate for ceftriaxone-resistant organisms, including Pseudomonas aeruginosa. Empirical antibiotic treatment of CSF shunt infections is with vancomycin plus cefepime, ceftazidime, or meropenem. Intraventricular antibiotics are commonly employed in patients with ventriculitis (generally, vancomycin at a dosage of 10 to 20 mg daily for gram-positive organisms and gentamicin at a dosage of 4 to 8 mg daily for gram-negative bacilli). Once the infection has resolved (usually after several days), a new shunt can be inserted.

NOSOCOMIAL MENINGITIS AND MENINGITIS AFTER NEUROSURGERY

Epidemiology and Etiology

Nosocomial meningitis is quite rare except in patients who have recently undergone neurosurgery. A study of 51 hospitalized patients who underwent lumbar puncture to exclude bacterial meningitis revealed no cases, despite the presence of mental status changes in 78%, fever in 47%, and meningeal signs or headache in 22%.28 By contrast, 92% of patients with community-acquired bacterial meningitis had either meningeal signs or headache. The conclusion is that lumbar puncture can be safely withheld in most hospitalized patients who have fever and changes in mental status; the exceptions to this rule are patients who have headache or nuchal rigidity and patients who have recently undergone neurosurgery.

Even after neurosurgery, bacterial meningitis is very uncommon, especially after spinal surgery or craniotomy; it is somewhat less rare, but still unusual, after transsphenoidal procedures. During neurosurgery, bacteria most commonly enter the subarachnoid space from contiguous sites of colonization on the skin and mucous membranes. Less frequent sources or causes of infection include contaminated instruments or irrigation solutions, airborne organisms, breaches of sterile technique, and organisms from adjacent sites of suppuration. Postoperative sources are wound infections at the operative site, indwelling catheters that allow organisms to enter the ventricle or subarachnoid space, and CSF leaks. A very uncommon cause is hematogenous spread from a distant site of infection, such as the lungs or urinary tract.

Approximately one half of cases of bacterial meningitis after craniotomy or spinal surgery occur in the first postoperative week, approximately 25% in the second week, and the remainder after the second week. After transsphenoidal surgery, about 85% of cases occur in the first week. The onset of meningitis may be inconspicuous, however, because headache, nuchal rigidity, and impaired consciousness are common after cranial surgery.

Diagnosis

Clinical features

Nearly all patients with nosocomial or postneurosurgical meningitis have fever, often accompanied by worsening meningismus, deteriorating mentation, and erythema or purulence at the incision site. CSF rhinorrhea may appear in patients with dural defects.

Laboratory findings

The peripheral white cell count is usually elevated; the elevation is accompanied by neutrophilia and increased bands. Blood cultures are positive in about 30% of cases. The most important diagnostic test is sampling of the CSF, usually after obtaining a CT scan to exclude brain abscesses or other fluid collections. In most cases of postoperative meningitis, the CSF protein level is 100 to 500 mg/dl and the white cell count exceeds 1,000/mm3, with neutrophilic predominance. The CSF glucose level is decreased in 85% of cases; Gram stain discloses the responsible bacteria in 50% to 80%.

The infecting organisms are primarily gram-negative bacilli, including P. aeruginosa and species of Klebsiella and Enterobacter. In patients with ventricular drains, coagulase-negative staphylococci predominate. The bacteria isolated in meningitis after transsphenoidal surgery are more diverse, reflecting various nasal mucosal organisms—especially as altered by hospitalization and previous antimicrobial therapy. Causes include gram-negative bacilli, streptococci, staphylococci, diphtheroids, anaerobes, Haemophilus species, and, sometimes, polymicrobial isolates.

Differential Diagnosis

A confounding diagnostic problem in neurosurgical patients with a negative Gram stain is that an aseptic meningitis may develop several days after surgery, probably in response to blood in the subarachnoid space. Fever, nuchal rigidity, nausea, vomiting, and altered mentation may all occur, and the findings on lumbar puncture resemble a bacterial infection, including marked pleocytosis, neutrophilic predominance, increased protein, and, sometimes, decreased glucose. However, in one study, no patients with postneurosurgical chemical meningitis had a CSF white cell count above 7,500/mm3 or a CSF glucose level below 10 mg/dl.29

Treatment

Antimicrobial therapy should be directed by the results of CSF Gram stain and culture. For gram-negative bacilli, ceftazidime (2 g I.V. every 8 hours) is the drug of choice unless the organism is known to be susceptible to ceftriaxone. Often, ceftazidime is combined with intrathecal or intraventricular injection of gentamicin (4 to 8 mg daily). For gram-positive organisms, parenteral vancomycin, supplemented by oral or parenteral rifampin and intrathecal or intraventricular vancomycin (10 to 20 mg daily), is a good regimen. When the Gram stain is negative, a combination of ceftazidime and vancomycin is reasonable until culture results become available.

When the distinction between bacterial and aseptic meningitis is unclear, a reasonable approach is to initiate appropriate empirical antimicrobial therapy. If the cultures remain negative, it is appropriate to withdraw the antibiotics and administer systemic corticosteroids, which seem useful in this form of chemical meningitis.30

Brain Abscess

EPIDEMIOLOGY AND ETIOLOGY

Brain abscesses are about two to three times more frequent in males than in females. About 50% arise from contiguous infections, such as sinusitis and otitis media, with the organisms arriving in the brain from direct extension or retrograde spread through the venous system. Pathogens from distant areas of suppuration may reach the brain via a hematogenous route through the cerebral arteries. Occasionally, abscesses develop after penetrating trauma or surgery, with organisms directly inoculated into the cerebral tissue. In approximately 20% to 30% of brain abscesses, the source of origin is inapparent.31

Chronic otitis media is a common predisposing factor, with the abscesses most frequently forming in the temporal lobe or cerebellum. Those occurring secondary to frontal sinusitis usually develop in the frontal lobe, whereas abscesses originating from the sphenoidal sinus are typically in the temporal lobe. Hematogenous infections from distant sites are commonly multiple and most likely to cause suppuration in the territories supplied by the distal middle cerebral artery. Frequently, these arise when blood-borne organisms bypass the ordinary filtering mechanisms of the lung in such conditions as left-sided endocarditis, pulmonary infections, and right-to-left cardiac or pulmonary shunts. In patients with shunts, concurrent hypoxemia and secondary erythrocytosis may cause brain damage that predisposes them to subsequent infection. Immunocompromised patients, especially patients who have undergone bone marrow transplantation or solid organ transplantation, have an increased risk of developing brain abscesses, usually through hematogenous spread.

Brain abscesses begin as localized—but poorly demarcated—areas of encephalitis, often called cerebritis. At this stage, tissue has not liquefied, and needle aspiration or surgery is unhelpful. Over several days, necrosis occurs, with pus forming in the center of the infection. With time, a capsule of fibrous tissue develops, delimiting the suppuration, but pus may rupture through it into the ventricle or adjacent cerebral tissue, forming satellite abscesses.

The most common organisms isolated from brain abscesses are aerobic, microaerophilic, or anaerobic streptococci; other anaerobic bacteria; staphylococci; and gram-negative bacilli (especially when the abscess arises from chronic ear infection). Common associations are Klebsiella pneumoniae and viridans streptococci in brain abscess from hematogenous spread; S. aureus, K. pneumoniae, and viridans streptococci in postneurosurgical brain abscess; viridans streptococci from paranasal sinusitis infections; and Proteus species in polymicrobial brain abscesses of otogenic origin.32 K. pneumoniae is an especially common pathogen in patients with diabetes.33

DIAGNOSIS

Clinical Features

Most patients with brain abscess have symptoms for several days to weeks before they seek medical attention. Fever is present in only about 40% to 50% of cases. The most common symptom is headache, which may be diffuse or localized to the abscess area. Other frequent findings are altered mental states, such as confusion, aberrant behavior, and somnolence; generalized or focal seizures; and specific neurologic abnormalities, depending on the abscess site. With temporal lobe involvement, contralateral sensory or motor signs, aphasia, and an upper homonymous quadrantanopia may occur. In cerebellar abscesses, ataxia in the ipsilateral extremities, nystagmus, signs of increased intracranial pressure, and ataxic gait are characteristic. Frontal lobe involvement commonly results in hemiparesis, aphasia, and impaired mentation, whereas the main finding in occipital lobe abscesses is homonymous hemianopsia. Typical features of parietal lobe abscesses include hemianesthesia, homonymous hemianopsia, neglect of one half of the body, alexia, and impaired spatial perception. Papilledema is infrequent, irrespective of the abscess site.

Laboratory Findings

Leukocytosis occurs in approximately 50% of patients, and an elevated erythrocyte sedimentation rate occurs in about 60%. Lumbar punctures are not recommended unless meningitis is strongly suspected, because of the low risk of brain herniation and the low likelihood of positive cultures. Examination of the CSF usually shows a pleocytosis with mixed neutrophils and lymphocytes, elevated protein levels, normal glucose levels, and a negative Gram stain. Blood cultures are positive in about 10% to 20% of patients.

Imaging Studies

During the cerebritis phase, CT scans show low-density abnormalities with mass effect, sometimes with patchy enhancement. On MRI, the characteristic findings are areas of low density on T1-weighted images and, on proton-density or T2-weighted images, high-intensity areas surrounded by areas of patchy enhancement with gadolinium. In a mature abscess, the CT scan shows a low-density lesion with uniform ring enhancement and a surrounding area of low density, representing cerebral edema [see Figures 2a and 2b]. On T1-weighted images, the encapsulated abscess appears as a round, low-intensity lesion with mass effect and a surrounding area of low density, signifying edema. On proton-density and T2-weighted images, the abscess has a high-intensity signal in the center and in the surrounding parenchyma as a consequence of the adjacent cerebral swelling. Ring enhancement occurs with gadolinium.

 

Figure 2a. CT Scan: Thalamic Abscess

CT scan of a 39-year-old patient reveals a large thalamic abscess. Plain scan demonstrates abscess and a surrounding zone of what may be either increased vascularity or an actual capsule formation (arrow).

 

Figure 2b. CT Scan of Thalamic Abscess with Contrast Media

Intravenous administration of contrast media enhances definition of the surrounding zone (thick arrow). A wide area of periabscess edema (thin arrow) is also evident. The mass effect can be seen clearly in the asymmetry of the ventricles.

TREATMENT AND PROGNOSIS

Most patients should undergo prompt stereotactic-guided needle aspiration of pus34 or craniotomy with excision of the abscess. If possible, antimicrobials should be withheld until a specimen is obtained, to avoid reducing the yield on cultures. Gram stain and culture determine antibiotic choice; appropriate empirical therapy that can be used until the microbiologic results become available include agents effective against anaerobes, streptococci, staphylococci, and gram-negative bacilli. A good regimen is a combination of ceftriaxone and metronidazole.35 Patients with significant cerebral edema should receive dexamethasone. Some patients may respond to antibiotic therapy alone—especially those with cerebritis only, those with numerous abscesses that are inaccessible to drainage, or those with small abscesses who have stable neurologic function.

Mortality may range from 5% to 25%. Factors associated with poor prognosis include a low Glasgow Coma Scale score, immunodeficiency, or the presence of underlying disease.36 Many patients have residual neurologic problems, most commonly focal seizures.

Spinal Epidural Abscess

PATHOGENESIS AND PATHOPHYSIOLOGY

The epidural space, an area posterolateral to the spinal cord containing fat and blood vessels, can potentially extend anteriorly to where the dura adheres to the posterior vertebral bodies. Most epidural abscesses occur in midthoracic and lumbar locations, where the space is largest. Cervical abscesses are less common, in part because the epidural space is very small in that area. Because no anatomic barriers prevent superior and inferior extension, abscesses typically involve several (an average of four) adjacent vertebral segments.37

Organisms may arrive in the epidural space from contiguous infection, especially vertebral osteomyelitis, but also from retropharyngeal, psoas, perivertebral, or perinephric abscess. All these infections are predominantly anterior to the spinal cord. Microbes also enter the epidural space as a result of penetrating trauma, surgery, and epidural catheterization for analgesic administration. Hematogenous spread may occur from distant foci of infection, including the skin and soft tissue, urinary tract, heart valves, and respiratory tract. Patients with frequent or prolonged bacteremias, such as intravenous drug users and those undergoing hemodialysis, are at increased risk.38 Diabetes mellitus, alcoholism, and underlying disease in the affected spinal area are other predisposing factors. Many patients report recent trauma near the affected location, suggesting hemorrhage at the site with subsequent bacteremic superinfection. Often, the source of infection is inapparent. Males are more frequently affected than females, for unclear reasons.

Pus and granulation tissue in the epidural space can damage the spinal cord, in part by compression, which may impede arterial flow and cause ischemia. Inflammation and increased pressure can also provoke thrombophlebitis or venous thrombosis, which can lead to cord edema and infarction.

ETIOLOGY

  1. aureusis the most common isolate from spinal epidural abscess; most of the other isolates are streptococci and gram-negative bacilli. Usually, only a single species of organism is responsible, but polymicrobial infections occur in approximately 5% to 10% of cases. In the United States, Mycobacterium tuberculosisis an occasional cause of epidural abscess. In such cases, the infection usually arises from an adjacent vertebral osteomyelitis. Patients may feel back pain for quite some time (weeks to months) before neurologic symptoms appear. Most of these patients have no evidence of pulmonary tuberculosis at the time of epidural infection.

DIAGNOSIS

Clinical Features

The most common symptom of spinal epidural abscess is back pain over the infected area. It is typically persistent and unrelieved by altered position or bed rest. Localized tenderness is often present; fever is common but is not invariable. With time, patients may develop radicular pain, primarily along the route of the affected level of the spinal cord. The next stage is usually marked by muscle weakness, typically paraparesis with thoracic involvement or quadriparesis with cervical infection. At this stage, findings of upper motor neuron disease are usually predominant; such findings include spasticity, hyperreflexia, and extensor plantar responses. Bilateral sensory loss and impaired bladder and bowel function may occur. Without treatment, paralysis develops, sometimes abruptly, and is usually irreversible.

Laboratory Findings

Leukocytosis is common in patients with epidural abscess, but white cell counts may be normal, especially in patients with protracted symptoms. The erythrocyte sedimentation rate is usually elevated. A lumbar puncture is not ordinarily recommended, except when needed for myelography; however, when a lumbar puncture is performed, the specimen typically demonstrates pleocytosis of up to a few hundred cells, commonly with a mixture of lymphocytes and neutrophils. The glucose level is normal; the protein level is usually elevated, sometimes by more than 1 g/L when the spinal canal is completely blocked. Gram stain and culture of CSF are usually normal. Blood cultures, which are commonly positive in epidural abscess, are worth obtaining in all suspected cases.

Imaging Studies

When the abscess arises from vertebral osteomyelitis, plain films of the spine may demonstrate erosion of the cortical margins of the vertebrae, narrowed or obliterated intervertebral disk spaces, and bone destruction. Myelograms show evidence of blockage of CSF circulation at the level of the epidural abscess but are rarely necessary when CT or MRI scans are available. CT scans detect vertebral osteomyelitis well; characteristic findings include narrowed intervertebral disk spaces, eroded vertebral end plates, and bony destruction of the vertebral bodies. The epidural abscess is present as a low-density focal epidural mass, which may be better delineated with CT myelography. The best imaging modality, however, is MRI, which discloses a low-intensity or isointense image on T1-weighted scans (when compared with the spinal cord image) and a high signal on proton-density or T2-weighted scans. Epidural abscesses typically appear enhanced with gadolinium. Demonstration of the extent of the mass is simple on MRI with both longitudinal and transverse sections, and vertebral osteomyelitis is easily visualized as high-intensity areas on T2-weighted images.

TREATMENT

Neurosurgery

The most important element of therapy is urgent neurosurgery for removal of pus and granulation tissue—which, rather than purulent material, is sometimes the major or sole finding. Decompressive laminectomies are performed for posterior epidural abscesses, whereas more complicated anterior approaches with bone graft fusion to establish spinal stability may be necessary for ventral collections. Occasionally, patients with absent or minimal neurologic findings respond to antimicrobial therapy alone,39 but even these patients may benefit from surgery when imaging procedures show significant evidence of spinal cord compression. In such patients, the organism should be identified by blood culture or abscess aspiration, and clinicians should realize that neurologic decline may occur abruptly.39

Antimicrobial Therapy

Antimicrobial therapy alone may also be appropriate for patients who are at high surgical risk because of concurrent medical problems, for those who have very extensive spinal involvement, and for patients with paralysis that has lasted more than 48 hours, after which significant neurologic recovery is highly unlikely.

If the infecting organism is unknown, empirical antibiotic therapy should include an agent effective against gram-negative bacilli (e.g., gentamicin or a third-generation cephalosporin) plus an agent active against S. aureus (e.g., a penicillinase-resistant penicillin such as nafcillin).

When methicillin-resistant S. aureus is a possibility, vancomycin should be used. Results of microbiologic evaluation of surgical specimens or blood cultures can then dictate the appropriate choice. In general, treatment is continued for 3 to 4 weeks in the absence of vertebral osteomyelitis and continued for 6 to 8 weeks when it is present. Patients with tuberculous epidural abscesses should receive antituberculous chemotherapy for at least 6 months.

PROGNOSIS

The prognosis in spinal epidural abscess depends on several factors, the most important of which is the extent of neurologic deficiency at the time of surgery. Poor outcomes are common when paresis or, especially, paralysis is present. Other unfavorable prognostic features are advanced age (> 60 years), substantial thecal sac compression on neuroimaging, and longer duration of symptoms.40 About 40% of patients recover completely, 25% have residual weakness, 20% have permanent paralysis, and 15% die.

Subdural Empyema

PATHOGENESIS AND PATHOPHYSIOLOGY

A subdural empyema is a collection of pus between the dura mater and the underlying arachnoid. Because this space contains no septations, except where the arachnoid granules lie within the dura, purulent material easily spreads over the surface of the brain. Most cases occur as a complication of sinusitis in older children and young adults, especially males, who account for about 75% of cases.41 The frontal sinus is nearly always involved, usually along with one or more of the other paranasal sinuses. Another cause is ear infection, either otitis media or mastoiditis; in such cases, the empyema may lie below the tentorium.

In these infections, pathogens probably reach the subdural space via blood draining from the infected sites through the venous sinuses in the dura. Subsequent septic thrombophlebitis of these vessels spreads organisms into the subdural space. Direct extension from contiguous infectious foci through erosion of the bones of the sinus or the ear may also occur. Other possible sources of the organisms causing subdural empyema are bacteremic infection of a preexisting subdural hematoma and direct inoculation of microbes into the area from penetrating head trauma or intracranial surgery.

Once the subdural space is infected, pus may spread widely over the convexities of the ipsilateral cerebrum; it may also travel along the falx separating the two hemispheres. The clinical features arise from pressure exerted on the underlying brain, the systemic effects of infection, and septic thrombophlebitis that spreads to the cortical and subcortical veins, causing brain infarction or infection.

ETIOLOGY

In most cases, only one species of organism is isolated from the pus, but polymicrobial infections can occur. The usual pathogens are aerobic or anaerobic streptococci and other anaerobes, especially with infections arising from sinusitis. Staphylococci and gram-negative bacilli are common causes in postoperative infections. Approximately 20% of cultures are negative, possibly because of inadequate microbiologic techniques (especially in isolating anaerobic bacteria) or previous antimicrobial therapy.

DIAGNOSIS

Clinical Features

Many patients have had a preceding sinusitis or a nonspecific upper respiratory tract illness; in some patients, however, symptoms of subdural empyema arise suddenly. The most common features are fever, stiff neck, and headache, which can be diffuse or localized to the area of empyema or underlying sinusitis. Neurologic abnormalities are usually present, including hemiparesis, seizures, aphasia, hemianesthesia, hemianopsia, and altered mentation, such as confusion, drowsiness, disorientation, and even coma. Papilledema may occur, indicating increased intracranial pressure, which can also cause palsies of the third and sixth cranial nerves. Sinus tenderness and periorbital edema may develop, reflecting the underlying sinusitis. With infratentorial empyema, which usually originates from neglected otic infections, the clinical features include stiff neck, altered consciousness, signs of increased intracranial pressure, otorrhea, and fever.42Patients typically deteriorate rapidly.

The presence of fever, headache, nuchal rigidity, and focal neurologic signs, especially in an adolescent boy or young man with sinusitis, should strongly suggest the presence of a subdural empyema and the necessity of immediate neuroimaging with CT or, preferably, MRI.

Laboratory Findings

A peripheral leukocytosis is common. Lumbar puncture is inadvisable because of the risk of brain herniation from increased intracranial pressure, but it is often performed because the clinical features suggest acute bacterial meningitis. Fortunately, serious complications rarely occur. The opening pressure is elevated, and pleocytosis of several hundred white cells or fewer is present. There is commonly a mixture of neutrophils and lymphocytes; either may predominate, but frequently the two cell types are equal in number. The protein level is typically increased, but the glucose level is almost always normal, and both Gram stain and culture are characteristically negative.

Imaging Studies

CT scans may show the empyema as isodense to low-density collections over one hemisphere and in the interhemispheric space, with a contrast-enhanced rim [see Figure 3]. MRI is a more sensitive and accurate imaging technique, however, revealing the empyema as isointense masses on T1-weighted images but showing high signal on proton density or T2-weighted images. The rim may be enhanced with gadolinium.41 These imaging techniques may also demonstrate concurrent complications, which are relatively common and include brain abscess, cranial epidural abscess, cortical thrombophlebitis, and venous infarction.

 

Figure 3. CT Scan: Subdural Empyema

CT scan of a 17-year-old patient with a subdural empyema shows two loculations (arrows) that are restricted to the interhemispheric area. Contrast-enhanced margins surround the two loculations.

DIFFERENTIAL DIAGNOSIS

The differential diagnosis for subdural empyema includes bacterial meningitis, brain abscess, and encephalitis. Clinical distinction among these infections may be difficult; however, focal findings are unusual in meningitis, and a stiff neck is uncommon with brain abscesses and encephalitis.

TREATMENT

The most important therapy is removal of the subdural pus through use of multiple bur holes or craniotomy. It is unclear which method is better; the choice may depend on the location of the infection and the patient's neurologic status. With either procedure, but especially with bur holes, multiple operations are often necessary because of inadequate drainage of pus. Antibiotic therapy, usually continued for 3 to 4 weeks after surgery, can be dictated by the results of Gram stain and culture of pus. The combination of ceftriaxone and metronidazole is a reasonable empirical regimen to use until the results of the Gram stain and culture are received.

PROGNOSIS

The prognosis depends greatly on the patient's state of consciousness at the time of surgery, with worsening outcomes accompanying decreasing levels of awareness. Overall mortality is approximately 15%. Significant neurologic sequelae, such as speech abnormalities and hemiparesis, occur in approximately 15% to 20% of survivors, and seizures occur in about 30%. These problems may emerge long after the surgery.

Septic Thrombophlebitis of the Major Cerebral Veins

The dural sinuses drain blood from the brain into the jugular veins. These sinuses lack valves, allowing flow in either direction, depending on the prevailing pressure gradient. Septic thrombophlebitis of these vessels, which may result from intracranial suppuration or spread of infection from extracranial veins, causes increased intracranial pressure, focal cerebral edema, or brain infarction. Usually, the initiating site of infection is clinically obvious in the middle ear, mastoid, paranasal sinuses, or facial skin. The cavernous, lateral, and superior sagittal sinuses are the most commonly involved vessels.43

CAVERNOUS SINUS THROMBOPHLEBITIS

Cavernous sinus thrombophlebitis most frequently develops from infections in the paranasal sinuses or the facial skin, especially on the medial third near the eyes and nose. Most cases are caused by S. aureus.44 Other causative pathogens are streptococci, gram-negative bacilli, and anaerobes.

The earliest symptom is usually headache, which often precedes fever and other findings by several days. The pain typically involves areas innervated by the ophthalmic and maxillary divisions of the trigeminal nerve, which traverse the cavernous sinus. Hyperesthesia or decreased sensation may be demonstrable in the dermatomes served by these nerves. Other focal findings may arise from obstructed ophthalmic veins: unilateral chemosis, proptosis, and edema of the ipsilateral eyelids, nose, and forehead. With time, the findings become bilateral as the phlebitis extends to the opposite cavernous sinus. Compression of cranial nerves III, IV, and VI, which course through the cavernous sinus, leads to varying degrees of ophthalmoplegia. The pupils may dilate and fail to react to light. Retinal veins engorge, visual acuity may lessen, and hemorrhages and papilledema can occur. Lethargy and coma may supervene, reflecting increased intracranial pressure and neuronal damage. Occasionally, bacteremia with metastatic foci of infection develops.

LATERAL SINUS THROMBOPHLEBITIS

Lateral sinus thrombophlebitis is almost always a complication of mastoiditis. Anaerobes, staphylococci, and gram-negative bacilli, especiallyProteus organisms, are the most common isolates.

The clinical course is usually subacute, with symptoms lasting for several weeks. Earache and drainage are often the first symptoms. Persistent, severe unilateral headache, followed by nausea and vomiting, indicates the development of lateral sinus thrombophlebitis. Fever, chills, and manifestations of increased intracranial pressure, including confusion and papilledema, are commonly present. Postauricular tenderness, venous engorgement, and edema represent involvement of the mastoid emissary vein. Extension into the jugular vein may occur.

Otoscopic examination commonly reveals a perforated or inflamed tympanic membrane. Focal neurologic findings are usually absent except for unilateral sixth nerve palsy, reflecting compression of the inferior petrosal sinus.

SUPERIOR SAGITTAL SINUS THROMBOPHLEBITIS

Superior sagittal sinus thrombophlebitis complicates bacterial meningitis, paranasal sinusitis, contiguous osteomyelitis, and dural infection. The most common organisms are S. pneumoniae, other streptococci, and gram-negative bacilli. Thrombosis of only the anterior portion of the sinus is often asymptomatic, but posterior involvement causes increased intracranial pressure. The predominant feature is acute headache, often with nausea and vomiting, followed in a few days by confusion and eventually coma. Focal or generalized seizures are common, and most patients are febrile. Extension of the thrombophlebitis to cortical veins may cause infarction of the underlying cortex, producing such neurologic manifestations as focal seizures and hemiparesis.

DIAGNOSIS

With septic thrombophlebitis in any of the cerebral veins, examination of the CSF may yield normal results or may demonstrate findings consistent with a parameningeal focus of infection: increased protein level, normal glucose level, and a pleocytosis of mixed neutrophils and lymphocytes that rarely exceeds a few hundred cells. Increased opening pressure is also common in all types.

Plain films of the skull are rarely helpful except in cases of septic lateral sinus thrombosis, in which they nearly always reveal mastoiditis. Certain findings on CT scan suggest cerebral venous thrombosis, but MRI provides a much better study. Acutely thrombosed cerebral veins lack a flow void. They are isointense on T1-weighted images and hypointense on T2-weighted images. In subacute thrombosis, the methemoglobin in the veins produces areas of high intensity on both images.

TREATMENT

Management of cerebral vein thrombophlebitis includes appropriate antibiotic therapy. For each of these disorders, when the infecting organisms are unknown, a good empirical antibiotic regimen is a combination of ceftriaxone and metronidazole. With cavernous sinus thrombosis in which S. aureus is prominent, vancomycin may be added if methicillin-resistant strains are likely.

Occasionally, treatment of cerebral vein thrombophlebitis includes surgery for the areas of purulence from which the infection arose. When paranasal sinusitis is the underlying cause, drainage of the infected sinuses may be necessary to obtain a good clinical response. In lateral sinus thrombophlebitis, radical mastoidectomy and exploration over the lateral sinus are commonly performed to remove purulent material.

Other medical treatment may include mannitol and dexamethasone in superior sagittal thrombophlebitis to help relieve the severe cerebral edema that is often present. The role of anticoagulation in cerebral vein thrombophlebitis remains unsettled; it seems valuable in cavernous sinus thrombosis45 but appears potentially hazardous in superior sagittal and lateral sinus thrombophlebitis because of the frequent concurrent hemorrhagic venous cortical infarcts that it may exacerbate.

PROGNOSIS

Septic thrombophlebitis of the superior sagittal and cavernous sinuses imposes a high mortality, even with appropriate therapy; however, most patients with involvement of the lateral sinus have a good prognosis.

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Editors: Dale, David C.; Federman, Daniel D.