Acute Infections of the Central Nervous System: Meningitis and Brain Abscess

Jonathan P. Moorman

Central nervous system dysfunction is common and characterized by a broad differential diagnosis. Rapid diagnosis and treatment are often necessary to prevent morbidity or mortality. Primary factors that drive the brain’s susceptibility to damage from infection are (i) inadequate room for expansion when inflammation is present, (ii) poor immune function within the blood-brain barrier, (iii) difficulty in achieving adequate antimicrobial concentrations in the cerebrospinal fluid (CSF) and parenchyma, and (iv) inability of the brain to regenerate neural tissue once cell death has occurred.

INITIAL EVALUATION

Patients with CNS infections can present with minimal signs and symptoms of CNS irritation or with obtundation and shock.
If suspicion for CNS infection is high, blood cultures should be drawn and empiric antimicrobials should be immediately administered, preferably within 1 hour of presentation and prior to lumbar puncture (LP) if any delay is expected
- The sensitivity of Gram stain and culture is decreased when antibiotics are given before LP, but the effect is small if LP is performed within 1 to 2 hours of antibiotics
- Sensitivities as high as 38% have been reported when LP was delayed for 24 hours.
Patients who have altered mental status or focal neurologic signs or seizures must undergo brain imaging prior to LP.

History and Physical Examination

A thorough history and physical examination is essential and helps to determine if the suspected infection is acute or chronic, community-acquired or nosocomial, primary or metastatic
It is common to find a history of fever, headache, stiff neck, and confusion
- frequently not all present, especially in the elderly or immunocompromised.
- review of symptoms necessary for determining the source; sinus pain, otorrhea, productive cough, abdominal pain, or dysuria may point to a primary focus of infection and help determine selection of initial antimicrobials.
Exposure to individuals with known infections suggests a common pathogen.
Past medical history alerts the clinician to underlying illnesses that may predispose to a particular CNS infection or organism
- prior CNS infections or neurosurgical procedures (Staphylococcus and aerobic gram-negative bacilli)
- immunosuppression (Toxoplasma, fungi, and mycobacteria)
- diabetes (fungi)
- head trauma (Staphylococci and Streptococci)
- alcoholism (Streptococcus pneumoniae and Listeria monocytogenes)
- when brain abscess or subdural empyema is considered, a history of chronic ear, sinus, and dental infections is supportive.
Social history should determine homelessness, ethanol or drug abuse, animal or insect exposure, employment, and HIV risk factors.
Medication list should be reviewed with special attention to new medications, as signs and symptoms of CNS infection can be mimicked by many medications.
Physical exam helps confirm the hemodynamic and neurologic stability of the patient, and helps to target suspicions about a primary source of infection.
- classically, meningitis presents with fever and headache accompanied by meningeal signs such as Kernig and Brudzinski signs. Encephalitis (covered in an accompanying chapter) is much more likely to appear with cognitive dysfunction and personality changes.
- sinus tenderness or otitis, or dental infection suggests intracranial extension from these sites.
- focal findings on auscultation of the lungs suggest pneumococcal pneumonia and meningitis.
- a new murmur accompanied by peripheral stigmata suggests endocarditis with intracranial complications.
- rash may suggest meningococcal, rickettsial, or viral etiologies, among others.

Laboratory Evaluation

If there is any question of meningitis, LP is warranted.
Computed tomography (CT) of the brain has been used to predict intracranial hypertension and the risk for brainstem herniation from LP.
- when focal neurologic signs, seizures, or signs of elevated intracranial pressure on physical examination are present, a CT scan of the brain is indicated.
- otherwise, preprocedure radiography is generally not indicated and may increase time to appropriate antibiotic therapy and increase costs of care.
- the absence of the following factors has a high negative predictive value for abnormalities on head CT: age older than 60, immunocompromised state, history of a CNS lesion such as a tumor, recent seizure, altered mental status/cognition, and focal neurologic findings.
The most common complication of LP is headache, which occurs in 10% to 30% of patients.
Spinal hematoma occurs in <1% of procedures and is almost always associated with anticoagulation or a platelet count <50,000/mL.
De novo infection resulting from LP is rare.
CSF pressure should be measured during every diagnostic LP.

CSF analysis (please refer to the chapter on CSF Analysis for a thorough discussion):

four tubes of CSF are obtained: Tube 1 is sent for Gram stain and culture, tube 2 for protein and glucose, tube 3 for cell count and differential, and at least one additional tube is set aside for further testing as indicated
more fluid may be required, however, depending mostly on the number of cultures and DNA studies desired, and on whether cytology will be ordered.
forty milliliters can be removed safely during one procedure.

when mycobacteria or fungi infections are considerations, 10 to 20 mL may be required. In patients with potential AIDS-related diagnoses, CSF testing for cryptococcal antigen and VDRL should be considered.

Table 17-1 CSF Findings Indicative of Meningitis

Parameter	Normal CSF	Acute bacterial	Viral
Opening pressure	6-20 cm H₂O	Elevated	Often normal
CSF WBCs/mm³	0-5 (lymphocytes) Hundreds-thousands (PMNs predominate)	Few to several hundred^a (lymphocytes predominate, but early on may see PMNs)
Protein (mg/dL)	18-45	100-500 (occasionally >1,000)	Often normal or only slightly elevated
Glucose (mg/dL)	45-80, or 0.6 × serum glucose	Often 5-40, or <0.3 × serum glucose	Usually normal, can be depressed in mumps and HSV
Miscellaneous	For traumatic LP, add one WBC and 1 mg/dL protein for each 1,000 RBCs	Gram stain (+) in 60%-80% cases, some-what organism specific, and related to prior use of antimicrobials	Usually not necessary to identify specific etiology of viral meningitis
^aLymphocytes >5,000 commonly noted with lymphocytic choriomeningitis (LCM).
Adapted from Choi CK. Bacterial meningitis in aging adults. Clin Infect Dis 2001;33:1380-1385.

the results of CSF testing are used to determine whether a septic or an aseptic process is operative (Table 17-1).
results suggesting septic inflammation include an elevated CSF opening pressure, several hundred to many thousands of mostly polymorphonuclear (PMN) WBCs, protein levels generally higher than 100 mg/dL, and glucose levels of 5 to 40 mg/dL or <30% of the serum glucose.
an aseptic picture includes a normal or only slightly elevated opening pressure, several hundred cells mostly of mononuclear lineage, normal or slightly elevated protein, and a normal glucose concentration.
the CSF profile of many patients may be mixed and caused by a large group of diagnoses, including parameningeal foci, infective endocarditis, rheumatologic disorders, early aseptic meningitis, partially treated septic meningitis, medication-induced disease, and postsurgical inflammation.

Etiology and Antimicrobial Treatment of Specific CNS Syndromes

Acute Bacterial Meningitis

Fifty percent of cases of community-acquired bacterial meningitis are due to S. pneumoniae, 25% to Neisseria meningitidis, 13% to group B streptococci, 8% to L. monocytogenes, and 7% to Hemophilus influenzae.
Nosocomially acquired meningitis may also be associated with enteric gram-negative bacilli in up to 33% of cases.
Mortality rates for bacterial meningitis in adults remain at approximately 20% but rise to at least 40% among those older than age 60.
Classic presentation of bacterial meningitis is fever, headache, and meningismus, with or without altered mental status.
- a recent evidence-based review demonstrated that one of three findings—fever, neck stiffness, or altered mental status—was present in nearly all patients with the disease.
- presence of at least one of these three findings was 99% sensitive for acute bacterial meningitis; absence of all three signs has a high negative predictive value.
- Kernig and Brudzinski signs are present in 50% of adults.
A CSF WBC count of more than 3,000/mL consisting predominately of PMN cells is highly suspicious for bacterial infection
- the WBC count is higher than 2,000/mL in 38% of bacterial cases
- a low glucose is classic but occurs in only 50% of cases
- CSF/serum glucose ratio of <0.4 is 80% sensitive and 96% specific for acute bacterial meningitis (as opposed to acute viral meningitis), and a ratio of <0.25 is found in <1% of cases of viral meningitis.
- CSF protein level of more than 100 mg/dL is 82% sensitive and 98% specific for acute bacterial meningitis (as opposed to acute viral meningitis).
- Gram stain is positive in up to 85% of cases of untreated bacterial meningitis, and CSF culture is positive in up to 85% of cases.
- Blood culture identifies the causative organism in 80% to 95% of cases.
CSF bacterial antigen testing is most useful when antibiotics have been given prior to LP. Negative tests are generally not helpful, but positive tests are considered diagnostic for a particular organism.