1. Clinical Manifestations

Recognizing the distinct features of meningeal irritation versus parenchymal inflammation is the first step in narrowing the differential diagnosis. Device-associated infections present a third, unique clinical picture.

1.1 Meningitic Syndrome

This syndrome results from inflammation of the meninges. While the classic triad is taught, it is not universally present.

• Classic Triad: Fever (up to 90%), neck stiffness, and altered mental status. Fewer than 50% of patients present with all three.
• Headache: Typically severe, diffuse, and associated with photophobia and phonophobia.
• Nuchal Rigidity: Resistance to passive neck flexion. Kernig’s and Brudzinski’s signs are specific but have low sensitivity.
• Seizures: Occur in approximately 20% of cases and signal a worse prognosis.

1.2 Encephalitic Syndrome

This syndrome reflects direct inflammation of the brain parenchyma, leading to more profound neurologic dysfunction.

• Altered Consciousness: The hallmark feature, ranging from mild confusion to deep coma.
• Seizures: More common than in meningitis (~33%), often with a focal onset.
• Behavioral/Psychiatric Changes: Hallucinations, personality shifts, or psychosis can be prominent, particularly with HSV involvement of the temporal lobes.
• Focal Deficits: Cranial nerve palsies, hemiparesis, or movement disorders may be present.

1.3 Device-Associated Presentations

Infections related to indwelling cerebrospinal fluid (CSF) shunts or drains have a subtle presentation.

• Clinical Signs: Fever is often absent. Look for headache, irritability, altered mentation, or signs of elevated intracranial pressure (ICP).
• CSF Profile: May show only a low-grade pleocytosis. Culture positivity despite mild symptoms is a key finding.

2. Initial Assessment and Risk Stratification

A focused history and neurologic exam are crucial to identify risk factors that inform the timing of imaging, lumbar puncture (LP), and empiric therapy.

2.1 Focused History

• Neurosurgical History: Recent surgery, head trauma, or presence of CSF devices (shunts, drains).
• Immune Status: HIV, chronic steroid use, organ transplant, or other forms of immunosuppression.
• Exposures: Tick or mosquito bites, travel to endemic regions (e.g., for Lyme disease, West Nile virus).
• Adjacent Infections: Otitis media, sinusitis, or mastoiditis can be sources of direct extension.

2.2 Neurologic Examination

• Glasgow Coma Scale (GCS): A score ≤13 indicates high risk and is an indication for CT imaging before LP.
• Signs of Elevated ICP: Look for focal neurologic deficits, papilledema on fundoscopy, or Cushing’s triad (hypertension, bradycardia, irregular respirations).
• Seizure Activity: Overt or suspected nonconvulsive seizures require urgent EEG monitoring.

3. Cerebrospinal Fluid Analysis

CSF analysis is the diagnostic cornerstone. The combination of opening pressure, cell counts, chemistry, and rapid microbiology provides a powerful diagnostic signature.

3.1 Microbiology and Molecular Diagnostics

• Gram Stain: Provides rapid guidance with 60–90% sensitivity for common bacteria.
• Culture: The gold standard, but takes 24–72 hours. For device-associated infections, hold cultures for ≥10 days to detect slow-growing organisms like C. acnes.
• Multiplex PCR: Offers high sensitivity/specificity (>95%) for key pathogens like HSV and enterovirus with a turnaround time of <6 hours. However, interpret results for low-prevalence pathogens with caution.

4. Ancillary Laboratory Testing

Serum and CSF biomarkers can supplement core CSF analyses, particularly in distinguishing bacterial from viral etiologies.

4.1 Serum Inflammatory Markers

• C-Reactive Protein (CRP): Has a high negative predictive value. A normal serum CRP makes bacterial meningitis less likely.
• Procalcitonin: A serum level >0.5 ng/mL has a specificity greater than 80% for bacterial meningitis over viral causes.

4.2 CSF Biomarkers

• CSF Lactate: A level >3.5 mmol/L strongly favors a bacterial over a viral etiology. However, its utility can be confounded by seizures, cerebral hypoxia, or recent neurosurgery.

5. Neuroimaging Modalities

Imaging is critical for identifying contraindications to LP and characterizing parenchymal involvement.

5.1 CT Head: Indications Before Lumbar Puncture

A non-contrast head CT is performed before LP to rule out a mass lesion or significant cerebral edema that could precipitate herniation. Perform CT first if any of the following high-risk features are present:

5.2 MRI Brain and EEG

• MRI Brain: The modality of choice for evaluating parenchymal disease. Look for classic patterns like medial temporal lobe FLAIR hyperintensities in HSV encephalitis or restricted diffusion (DWI) in early cerebritis or abscess.
• EEG: Essential for detecting nonconvulsive seizures, which can perpetuate neuronal injury. Periodic lateralized epileptiform discharges (PLEDs) are strongly suggestive of HSV encephalitis.

6. Classification and Prognostic Scoring

Standardized classification and scoring systems help in communicating severity, allocating resources, and predicting outcomes.

6.1 Community vs. Healthcare-Associated

• Community-Acquired: Pathogen identified within 48 hours of admission in a patient without indwelling CNS devices.
• Healthcare-Associated (HAVM): Onset >48 hours after admission, presence of a CNS device, or recent neurosurgical procedure.

6.2 Prognostic Scores

Validated scoring systems provide objective risk stratification. While several exist, they share common high-risk variables.

• Key Predictors of Poor Outcome: Low GCS at presentation (especially GCS ≤8), presence of seizures, profound hypotension requiring vasopressors, and advanced age.
• Commonly Used Scores: The Aronin Score for bacterial meningitis and the Hansen Model for encephalitis integrate these variables to estimate mortality risk.

7. Integration into Initial Management

The “golden hour” of CNS infections involves rapid risk stratification, timely diagnostics, and immediate empiric therapy. Do not delay antimicrobial therapy pending diagnostic procedures.

7.1 Empiric Therapy Triggers

• Suspected Community-Acquired Bacterial Meningitis: Vancomycin + a third-generation cephalosporin (e.g., ceftriaxone). Add ampicillin for patients at risk for Listeria (e.g., >50 years old, immunocompromised).
• Suspected Encephalitis: Add acyclovir to cover for HSV pending CSF PCR results.