Differential Diagnosis of Central Nervous System Infections
Central nervous system (CNS) infections are life-threatening conditions that include meningitis, encephalitis, brain abscesses, and myelitis. Their etiologies span bacterial, viral, fungal, parasitic, and atypical pathogens. Early differentiation is critical for timely treatment and improved outcomes. This article outlines the clinical features, laboratory findings, and imaging characteristics of common CNS infections to guide accurate diagnosis.
1. Common CNS Infections and Pathogens
- Bacterial Meningitis
- Typical Pathogens: Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae type B.
- High-Risk Groups: Infants, elderly individuals, immunocompromised patients.
- Viral Meningitis/Encephalitis
- Common Viruses: Herpes simplex virus (HSV-1/2), enteroviruses (e.g., Coxsackievirus), varicella-zoster virus (VZV), West Nile virus.
- Tuberculous Meningitis
- Pathogen: Mycobacterium tuberculosis.
- High-Risk Groups: Patients with a history of tuberculosis or HIV/AIDS.
- Fungal Meningitis
- Typical Pathogens: Cryptococcus neoformans, Aspergillus, Candida species.
- High-Risk Groups: Organ transplant recipients, diabetics, long-term corticosteroid users.
- Parasitic Infections
- Examples: Cerebral toxoplasmosis (caused by Toxoplasma gondii), neurocysticercosis (tapeworm larvae).
- Endemic Regions: Common in tropical and subtropical areas.
2. Key Clinical Features for Differentiation
A. Bacterial Meningitis
- Acute Onset: Fever, severe headache, neck stiffness (meningismus), photophobia.
- Altered Mental Status: Confusion, lethargy, or coma in advanced cases.
- Petechial Rash: Classic sign of Neisseria meningitidis infection.
B. Viral Encephalitis
- Prodromal Symptoms: Flu-like illness (fever, fatigue) preceding neurological symptoms.
- Focal Neurological Deficits: Seizures, aphasia, or hemiparesis (common in HSV encephalitis).
- Behavioral Changes: Agitation, hallucinations, or memory loss.
C. Tuberculous Meningitis
- Subacute Progression: Symptoms develop over weeks.
- Cranial Nerve Involvement: Oculomotor or facial nerve palsies.
- Basilar Meningitis: Thick exudate at the brain base seen on imaging.
D. Fungal Meningitis
- Insidious Onset: Chronic headache, low-grade fever.
- Increased Intracranial Pressure: Papilledema, nausea, vomiting.
- Immunocompromised Clues: Concurrent pulmonary or cutaneous fungal infections.
E. Parasitic Infections
- Seizures: Common in neurocysticercosis due to cysticerci in brain parenchyma.
- Ring-Enhancing Lesions: Seen on MRI in cerebral toxoplasmosis.
3. Laboratory and Imaging Diagnostics
A. Cerebrospinal Fluid (CSF) Analysis
- Bacterial Meningitis:
- CSF Appearance: Turbid.
- Cell Count: Neutrophil predominance (>1,000 cells/μL).
- Glucose: Low (<40% of serum glucose).
- Protein: Elevated (>100 mg/dL).
- Gram Stain/Culture: Identifies pathogens.
- Viral Meningitis:
- CSF Appearance: Clear.
- Cell Count: Lymphocytic predominance (50–500 cells/μL).
- PCR Testing: Detects viral DNA/RNA (e.g., HSV, enterovirus).
- Tuberculous Meningitis:
- CSF: Lymphocytic pleocytosis, very high protein (>200 mg/dL), low glucose.
- Acid-Fast Bacilli (AFB) Stain: Low sensitivity; PCR or GeneXpert MTB/RIF® improves detection.
- Fungal Meningitis:
- India Ink Stain: Detects Cryptococcus (positive in 50–70% of cases).
- Antigen Testing: Cryptococcal antigen (CrAg) in serum or CSF.
B. Neuroimaging
- MRI vs. CT:
- MRI: Superior for detecting early encephalitis, abscesses, or meningeal enhancement.
- CT: Used initially to rule out mass lesions or hydrocephalus.
- Characteristic Findings:
- HSV Encephalitis: Temporal lobe hyperintensity on T2-weighted MRI.
- Brain Abscess: Ring-enhancing lesion with edema and restricted diffusion on DWI.
- Neurocysticercosis: Multiple cystic lesions with scolex (“dot-in-ring” sign).
4. Differential Diagnosis Pitfalls
- Autoimmune Encephalitis (e.g., anti-NMDA receptor encephalitis): Mimics viral encephalitis but lacks fever.
- Subarachnoid Hemorrhage: Sudden-onset headache; distinguished by CT or xanthochromia.
- Drug-Induced Meningitis: NSAIDs, IVIG, or antibiotics (e.g., trimethoprim-sulfamethoxazole).
5. Treatment Considerations Based on Diagnosis
- Bacterial Meningitis: Immediate empiric antibiotics (ceftriaxone + vancomycin) ± dexamethasone.
- HSV Encephalitis: High-dose intravenous acyclovir.
- Tuberculous Meningitis: Four-drug antitubercular therapy (isoniazid, rifampin, pyrazinamide, ethambutol).
- Cryptococcal Meningitis: Induction with amphotericin B + flucytosine, followed by fluconazole.
6. Prognostic Indicators
- Poor Outcomes: Delayed treatment, coma at presentation, immunocompromised status.
- Favorable Factors: Early antiviral therapy for HSV, rapid CSF sterilization in bacterial meningitis.
Conclusion
Accurate differentiation of CNS infections relies on integrating clinical presentation, CSF analysis, and neuroimaging. Rapid pathogen identification and targeted therapy are vital to reducing morbidity and mortality. Clinicians must maintain a high index of suspicion for atypical pathogens in immunocompromised patients or those with travel-related exposures.