2d:I[856015,["/_next/static/immutable/chunks/1xzisbplk9czp.js","/_next/static/immutable/chunks/3j2i1faptc_-9.js","/_next/static/immutable/chunks/0fma7nlq6immz.js","/_next/static/immutable/chunks/08tq8rmv423j5.js","/_next/static/immutable/chunks/1chr5wkk3j58k.js","/_next/static/immutable/chunks/37kmmh_zm4dov.js","/_next/static/immutable/chunks/311zvdjfxff-f.js","/_next/static/immutable/chunks/1a_hqhrsle_n_.js"],"default"] 2e:T7f19,

Summary Table

Category	Details
Risk Factors	Neonates, elderly, immunocompromised (HIV, asplenia, complement deficiency), crowded living (dormitories, military barracks), unvaccinated, recent neurosurgery, cochlear implants, CSF leak, contiguous infection (sinusitis, otitis media)
Etiology	Bacterial: age-dependent organisms (see below). Viral: enteroviruses most common. Fungal: Cryptococcus neoformans in immunocompromised. TB: Mycobacterium tuberculosis in endemic regions
Patient Presentation	Headache, fever, neck stiffness (classic triad). Neonates: irritability, poor feeding, bulging fontanelle, hypothermia or fever. Elderly: altered mental status may be the only finding
Classic Physical Exam	Nuchal rigidity, positive Kernig sign (pain on knee extension with hip flexed), positive Brudzinski sign (involuntary hip flexion on passive neck flexion), petechial/purpuric rash (Neisseria meningitidis), bulging fontanelle (neonates)
Key Diagnostic Results	Lumbar puncture with CSF analysis is the cornerstone. Bacterial: elevated WBC (neutrophil-predominant), elevated protein, low glucose. Viral: lymphocytic pleocytosis, normal glucose, mildly elevated protein
Management	Empiric IV antibiotics immediately (do not delay for imaging). Dexamethasone before or with the first dose of antibiotics for suspected Streptococcus pneumoniae. Chemoprophylaxis for close contacts of N. meningitidis
Keywords	"Worst headache," "neck stiffness," "petechial rash," "bulging fontanelle," "kernig/brudzinski positive," "CSF with neutrophilic pleocytosis," "college dormitory," "waterhouse-friderichsen"

1. Pathophysiology

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.

2. Classification and Clinical Manifestation

By Etiology and Typical Presentation

Type	Onset	Fever	Headache	Meningismus	Mental Status	Distinguishing Features
Bacterial	Acute (hours to 1-2 days)	High-grade	Severe	Prominent	Often altered	Petechial rash (meningococcal), rapid deterioration, toxic appearance
Viral (Aseptic)	Acute to subacute	Low to moderate	Moderate	Mild to moderate	Usually preserved	Often preceded by URI or GI symptoms, self-limited course
Fungal (Cryptococcal)	Subacute to chronic (weeks)	Low-grade or absent	Insidious, progressive	Variable, often mild	Subtle changes	Immunocompromised host (HIV, transplant), elevated opening pressure on LP
Tuberculous	Chronic (weeks to months)	Low-grade, persistent	Progressive	Variable	Progressive decline	Basilar meningitis pattern, cranial nerve palsies, history of TB exposure or endemic region

Age-Based Bacterial Organisms

Age Group	Organisms	High-Yield Notes
Neonates (0-28 days)	Group B Streptococcus (GBS), Escherichia coli (K1 capsule), Listeria monocytogenes	Vertical transmission from maternal vaginal flora. Listeria from unpasteurized dairy. Empiric: ampicillin + gentamicin (or ampicillin + cefotaxime)
Infants/Children (1 mo - 18 yr)	Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae type b (if unvaccinated)	N. meningitidis in adolescents in dormitories. Vaccination has reduced H. influenzae dramatically
Adults (18-50 yr)	S. pneumoniae (most common), N. meningitidis	Empiric: vancomycin + third-generation cephalosporin (ceftriaxone or cefotaxime)
Elderly (>50 yr) and Immunocompromised	S. pneumoniae, Listeria monocytogenes, gram-negative bacilli	Must add ampicillin to cover Listeria. This is one of the most tested points
Post-neurosurgery / CSF shunt	Staphylococcus aureus, Staphylococcus epidermidis, gram-negative bacilli (including Pseudomonas)	Empiric: vancomycin + cefepime (or ceftazidime or meropenem for anti-pseudomonal coverage)

Neonatal Presentation

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

Finding	Explanation
Irritability or lethargy	Non-localizing CNS sign
Poor feeding / vomiting	Raised ICP, generalized illness
Bulging fontanelle	Direct sign of increased ICP (very high-yield)
Hypothermia or temperature instability	Immature thermoregulation
Seizures	Cortical irritation from inflammation
Apnea / respiratory distress	Brainstem involvement

3. Diagnostic Workup

Test	Purpose	Key Findings
Lumbar puncture (LP) with CSF analysis	Gold standard for diagnosis	See CSF profile table below
CSF Gram stain and culture	Identify organism	Gram stain is rapid; culture is definitive. Sensitivity drops significantly if antibiotics given before LP
CSF latex agglutination / PCR	Identify organism when cultures are negative (e.g., partially treated meningitis)	Useful for N. meningitidis, S. pneumoniae, H. influenzae, GBS, E. coli
Blood cultures	Identify bacteremia (positive in 50-75% of bacterial meningitis)	Always draw before antibiotics, but do not delay antibiotics for cultures
CT head (before LP)	Rule out mass lesion / elevated ICP before LP	Only needed in selected patients (see indications below)
CSF opening pressure	Assess ICP	Elevated in bacterial and cryptococcal meningitis
CSF cryptococcal antigen (CrAg) / India ink	Diagnose cryptococcal meningitis	CrAg is more sensitive than India ink. India ink shows encapsulated budding yeast
CSF AFB stain, culture, adenosine deaminase (ADA)	Diagnose TB meningitis	AFB smear has low sensitivity. Culture takes weeks. Elevated ADA supports diagnosis
Procalcitonin / CRP (serum)	Distinguish bacterial from viral	Elevated procalcitonin strongly favors bacterial etiology

CSF Profile Comparison

Parameter	Normal	Bacterial	Viral	Fungal / TB
Opening pressure	10-20 cm H2O	Elevated (>30)	Normal to mildly elevated	Elevated (especially cryptococcal)
WBC count	0-5 cells/microL	>1000 (often thousands)	10-500	10-500
WBC differential	--	Neutrophil predominant (>80%)	Lymphocyte predominant	Lymphocyte predominant
Protein	15-45 mg/dL	Markedly elevated (>250)	Mildly elevated (50-200)	Elevated (100-500)
Glucose	40-70 mg/dL (or >60% serum)	Low (<40 or <40% serum glucose)	Normal	Low
Gram stain	No organisms	Positive in 60-90%	Negative	Negative (India ink for Crypto)

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.

4. Management and Treatment

Age Group	Empiric Regimen	Rationale
Neonates (0-28 days)	Ampicillin (for GBS and Listeria) + Cefotaxime (for gram-negatives) OR Ampicillin + Gentamicin	Cefotaxime preferred over ceftriaxone in neonates (ceftriaxone displaces bilirubin from albumin, risking kernicterus)
Infants 1-23 months	Vancomycin + third-generation cephalosporin (ceftriaxone 50 mg/kg IV q12h or cefotaxime)	Vancomycin added for resistant pneumococcus
Children and Adults (2-50 yr)	Vancomycin (15-20 mg/kg IV q8-12h) + Ceftriaxone (2 g IV q12h)	Standard of care for community-acquired bacterial meningitis
Adults >50 yr, immunocompromised, or alcoholics	Vancomycin + Ceftriaxone + Ampicillin (2 g IV q4h)	Ampicillin added to cover Listeria monocytogenes (this is extremely high-yield)
Post-neurosurgery / CSF shunt	Vancomycin + Cefepime (or ceftazidime or meropenem)	Anti-pseudomonal and anti-staphylococcal coverage needed

Adjunctive Dexamethasone

Detail	Recommendation
Indication	Suspected or proven bacterial meningitis in adults and children >6 weeks old, particularly when S. pneumoniae is suspected
Dose (Adults)	0.15 mg/kg IV every 6 hours for 4 days
Dose (Children)	0.15 mg/kg IV every 6 hours for 2-4 days
Timing	Must be given before or simultaneously with the first dose of antibiotics. Giving it after antibiotics are started provides no benefit
Mechanism	Reduces the inflammatory surge caused by bacterial lysis after antibiotics. Decreases mortality and neurological sequelae (especially hearing loss)
When NOT to use	Neonates, viral meningitis, fungal meningitis. Evidence is strongest for pneumococcal meningitis; benefit in meningococcal disease is less clear

Chemoprophylaxis

Organism	Who Receives Prophylaxis	Regimen
*N. meningitidis*	Close contacts (household members, daycare contacts, anyone exposed to respiratory secretions, healthcare workers who performed mouth-to-mouth or unprotected intubation)	Rifampin 600 mg PO q12h x 4 doses (2 days), OR Ciprofloxacin 500 mg PO single dose (adults), OR Ceftriaxone 250 mg IM single dose (preferred in pregnancy)
H. influenzae type b	Household contacts if any member is <4 years old and incompletely vaccinated, or if an immunocompromised individual is present	Rifampin 20 mg/kg/day (max 600 mg) PO once daily x 4 days

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:

Phase	Regimen	Duration
Induction	Amphotericin B (0.7-1.0 mg/kg/day IV) + Flucytosine (100 mg/kg/day PO divided q6h)	At least 2 weeks
Consolidation	Fluconazole 400 mg/day PO	8 weeks
Maintenance	Fluconazole 200 mg/day PO	At least 1 year (until immune reconstitution in HIV patients)

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.

5. Differential Diagnosis and Distractors

Differential	Why It Is Similar	Key Discriminator
Subarachnoid hemorrhage (SAH)	Sudden severe headache, neck stiffness, photophobia, and altered mental status overlap with meningitis	SAH presents with "thunderclap" headache (maximal intensity at onset). CSF in SAH shows xanthochromia and RBCs (not WBCs). CT head without contrast is the initial study and shows hyperdensity in the subarachnoid space
Encephalitis (HSV)	Fever, headache, altered mental status. HSV encephalitis can present with meningeal signs	Encephalitis features focal neurological deficits (personality changes, aphasia, seizures, temporal lobe signs). MRI shows temporal lobe involvement. CSF may show lymphocytic pleocytosis (similar to viral meningitis) but the clinical picture is dominated by parenchymal, not meningeal, disease
Brain abscess	Fever, headache, focal deficits, and elevated ICP can mimic meningitis	Brain abscess presents with focal neurological signs and ring-enhancing lesion on CT/MRI. LP is contraindicated due to herniation risk
Subdural empyema	Post-sinusitis or post-otitis infection with fever, headache, meningismus, and focal deficits	CT/MRI shows a crescent-shaped extra-axial collection. This is a neurosurgical emergency requiring drainage, not just antibiotics
Drug-induced aseptic meningitis	CSF shows lymphocytic pleocytosis with sterile cultures, mimicking viral meningitis	History of culprit medications: NSAIDs (especially ibuprofen), IV immunoglobulin, trimethoprim-sulfamethoxazole, isoniazid. Resolves upon discontinuation
Autoimmune / Lupus meningitis	Sterile lymphocytic meningitis in a patient with SLE	Look for other lupus features (rash, arthritis, serositis, renal involvement). ANA and anti-dsDNA positive. Responds to immunosuppressive therapy
Carcinomatous meningitis (leptomeningeal metastasis)	Chronic headache, cranial nerve palsies, elevated CSF protein, low glucose (mimics TB/fungal meningitis)	History of known malignancy (breast, lung, melanoma, lymphoma). CSF cytology reveals malignant cells. Multiple cranial neuropathies are common

6. Traps 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.

1e:["$","$L2d",null,{"article":{"id":"810748a3-8be5-4349-bd05-12d17be69e13","title":"Meningitis","content":"$2e","category":"Neurologi","created_at":"2026-08-07T12:32:52.253427+00:00","status":"published","subcategory":null},"questionCount":1,"sections":[{"id":"section-pathophysiology","num":"01","title":"Pathophysiology"},{"id":"section-classification-and-clinical-manifestation","num":"02","title":"Classification and Clinical Manifestation"},{"id":"section-diagnostic-workup","num":"03","title":"Diagnostic Workup"},{"id":"section-management-and-treatment","num":"04","title":"Management and Treatment"},{"id":"section-differential-diagnosis-and-distractors","num":"05","title":"Differential Diagnosis and Distractors"},{"id":"section-traps-and-high-yield-pearls","num":"06","title":"Traps and High-Yield Pearls"}],"hasSummaryTable":true}]