Meningitis

01Pathophysiology

Meningitis is inflammation of the leptomeninges (the pia mater and arachnoid mater) and the cerebrospinal fluid occupying the subarachnoid space. Understanding the pathophysiology is essential because every symptom and lab finding traces back to this inflammatory cascade.

Bacterial meningitis begins when organisms colonize the nasopharynx and invade the bloodstream. Bacteremia allows the pathogen to cross the blood-brain barrier (BBB), which it does through several mechanisms: transcellular penetration, paracellular entry through disrupted tight junctions, or transport within infected leukocytes (the "Trojan horse" mechanism, characteristic of Listeria monocytogenes). Once inside the subarachnoid space, the bacteria multiply rapidly because the CSF is an immunologically privileged site with minimal complement, immunoglobulins, or opsonins. The host immune response paradoxically drives the damage: bacterial cell wall components (lipopolysaccharide in gram-negatives, lipoteichoic acid in gram-positives) trigger release of TNF-alpha, IL-1, and IL-6, which increases BBB permeability, causes vasogenic and cytotoxic edema, and raises intracranial pressure. This explains why patients develop headache (increased ICP), altered mental status (cerebral edema and cortical inflammation), and neck stiffness (irritation of the meninges by inflammatory exudate).

The low CSF glucose seen in bacterial meningitis occurs because bacteria consume glucose directly and because inflammation impairs the glucose transporter (GLUT1) at the BBB. Elevated CSF protein reflects BBB breakdown allowing albumin to leak into the CSF.

Viral (aseptic) meningitis follows a different course. Enteroviruses (the most common cause) reach the CNS via hematogenous spread after gastrointestinal replication. The inflammatory response is less intense, producing lymphocytic infiltration rather than neutrophilic, and the BBB remains relatively intact. This is why viral meningitis typically shows normal glucose and only mildly elevated protein, and why patients appear less toxic.

Fungal meningitis (particularly Cryptococcus) is characteristically subacute to chronic because the polysaccharide capsule of the organism suppresses the inflammatory response. Patients with advanced HIV (CD4 < 100) are at highest risk. The organism is inhaled and disseminates hematogenously.

Tuberculous meningitis develops from rupture of a subependymal caseous focus (Rich focus) into the subarachnoid space. The resulting basilar meningitis preferentially affects the base of the brain, which explains cranial nerve palsies (especially CN VI and CN VII) and the risk of communicating hydrocephalus from obstruction of CSF flow at the basal cisterns.

02Classification and Clinical Manifestation

By Etiology and Typical Presentation

Age-Based Bacterial Organisms

Neonatal Presentation

Neonates do not present with classic meningeal signs. Instead, watch for:

03Diagnostic Workup

CSF Profile Comparison

When to order a CT scan before performing LP:

This is a classic exam question. LP is safe in most patients with suspected meningitis and should not be delayed. However, CT before LP is indicated in the following situations (to rule out a mass lesion that could cause herniation):

• Immunocompromised state

• History of CNS disease (mass, stroke, focal infection)

• New-onset seizures (within one week)

• Papilledema on fundoscopy

• Altered level of consciousness

• Focal neurological deficits

The critical teaching point: if CT is needed, draw blood cultures and start empiric antibiotics BEFORE sending the patient for imaging. Never delay antibiotics to obtain a CT or LP. The sequence is: blood cultures, then antibiotics (with dexamethasone), then CT, then LP when safe.

Partially treated meningitis is a common exam scenario. When a patient has received oral antibiotics before LP (e.g., prescribed by a clinic for presumed otitis media), the CSF may show a mixed picture: partially cleared Gram stain, negative cultures, but still abnormal cell count and chemistry. In this situation, CSF PCR and latex agglutination become invaluable because they can detect bacterial antigens or DNA even after antibiotics have sterilized the culture.

04Management and Treatment

Adjunctive Dexamethasone

Chemoprophylaxis

Management of viral meningitis is supportive: analgesics, antipyretics, hydration, and rest. Most cases resolve within 7-10 days. HSV meningitis (HSV-2, associated with primary genital herpes) may warrant IV acyclovir if there is concern for encephalitis (altered mental status, focal findings, temporal lobe involvement on imaging), but isolated HSV meningitis in immunocompetent adults is often self-limited.

Management of cryptococcal meningitis follows a phased approach:

A critical point: serial LPs or a lumbar drain may be needed to manage elevated intracranial pressure in cryptococcal meningitis. Elevated opening pressure is a major cause of morbidity and mortality, and therapeutic LPs (draining enough CSF to reduce pressure by 50% or to below 20 cm H2O) should be performed daily as needed.

Management of TB meningitis: A standard four-drug anti-TB regimen (isoniazid, rifampin, pyrazinamide, ethambutol) for 2 months of intensive therapy followed by 7-10 months of continuation therapy (isoniazid + rifampin), for a total of 9-12 months. Adjunctive dexamethasone is recommended for TB meningitis across all severity grades and has been shown to reduce mortality.

05Differential Diagnosis and Distractors

06Traps and High-Yield Pearls

The single most common way students lose points on meningitis questions is delaying antibiotics. Exam vignettes are designed to test whether you will order a CT scan and wait for results before starting treatment. The correct answer is almost always: draw blood cultures, give dexamethasone and empiric antibiotics immediately, and then obtain imaging if indicated. If the question stem describes a patient with no indications for CT (no focal deficits, no seizures, no papilledema, immunocompetent, normal consciousness), the next best step is LP, not CT.

The second major trap involves age-based antibiotic selection. Any patient over 50 years old, any pregnant woman, any immunocompromised individual, or anyone with alcoholism requires ampicillin added to the empiric regimen. A vignette describing a 65-year-old with meningitis treated only with vancomycin and ceftriaxone is a setup for a question about inadequate Listeria coverage.

Another frequently tested concept is the timing of dexamethasone. Dexamethasone must be administered before or concurrently with the first antibiotic dose. If the question states that antibiotics were already started hours ago, dexamethasone is no longer beneficial, and the answer is to continue antibiotics without adding steroids.

Students also confuse early bacterial meningitis with viral meningitis. In the first 24 hours of bacterial meningitis, the CSF can sometimes show a lymphocyte predominance before shifting to neutrophils. If the clinical picture is toxic (high fever, rapid decline, hypotension), treat as bacterial regardless of initial CSF differential.

For neonatal meningitis, remember two things: (1) ceftriaxone is avoided in neonates because of the risk of biliary sludging and displacement of bilirubin from albumin, and (2) classic meningeal signs (Kernig, Brudzinski, nuchal rigidity) are unreliable in neonates because these signs depend on mature meningeal and musculoskeletal responses. A bulging fontanelle is the most important physical finding.

For cryptococcal meningitis, the most tested pearl is that India ink staining is the classic answer but CSF cryptococcal antigen (CrAg) is more sensitive and is the preferred initial diagnostic test. Also remember that elevated opening pressure is the hallmark and must be managed with serial therapeutic LPs.

The core competency being tested across all meningitis questions is your ability to integrate the patient's age, immune status, and clinical timeline into a rapid decision about empiric therapy, the appropriate use of imaging before LP, and accurate interpretation of CSF results.