A 35-year-old man from Lucknow presents with a 14-day history of high-grade fever (39.5–40.5°C), severe headache, and delirium. He is drowsy and disoriented. On examination, he has a temperature of 40°C, pulse 96/min, blood pressure 110/70 mmHg, and hepatosplenomegaly. There is no neck stiffness. Urine culture is negative. Blood culture grows Salmonella typhi. A lumbar puncture is performed: CSF is clear, glucose 35 mg/dL (serum glucose 120 mg/dL), protein 120 mg/dL, cell count 80 cells/mm³ (60% lymphocytes), and Gram stain is negative. What is the most likely diagnosis?

Explanation

## Typhoid Encephalopathy vs. Meningitis **Key Point:** Typhoid fever can cause CNS complications, but true meningitis (bacterial invasion of meninges) is rare. The more common presentation is **typhoid encephalopathy** — a toxic metabolic encephalopathy without meningeal inflammation. ### Differential: CSF Findings in CNS Infections | Feature | Typhoid Encephalopathy | Bacterial Meningitis | TB Meningitis | Viral Meningitis | |---------|------------------------|----------------------|---------------|------------------| | **Glucose (CSF:serum ratio)** | Normal or mildly ↓ (>40% of serum) | ↓↓ (<40% of serum) | ↓↓↓ (<20% of serum) | Normal or mildly ↓ | | **Protein** | Normal to mildly ↑ (40–100 mg/dL) | ↑↑ (100–500 mg/dL) | ↑↑↑ (100–500 mg/dL) | Mildly ↑ (50–100 mg/dL) | | **Cell count** | <100 cells/mm³ | 100–10,000 cells/mm³ | 10–500 cells/mm³ | 10–1,000 cells/mm³ | | **Cell type** | Lymphocytes | PMN (early), then lymphocytes | Lymphocytes | Lymphocytes | | **Gram stain** | Negative | Often positive | Negative | Negative | | **Culture** | Negative | Positive (50–80%) | Positive (10–20%) | Negative | | **Blood culture** | Positive (S. typhi) | Positive (meningococcus, pneumococcus) | Negative | Negative | ### Analysis of This Case - **CSF glucose 35 mg/dL with serum glucose 120 mg/dL** → ratio = 29% (mildly low, NOT severely low) - **Protein 120 mg/dL** → mildly elevated - **Cell count 80 cells/mm³ with lymphocytic predominance** → minimal pleocytosis - **Gram stain negative, culture negative** → no organism isolated - **Blood culture positive for S. typhi** → confirms typhoid - **No neck stiffness** → argues against meningitis - **Delirium and drowsiness** → encephalopathy (toxic-metabolic) **High-Yield:** In typhoid encephalopathy, CSF is **normal or near-normal**; in meningitis, CSF is **markedly abnormal** with high cellularity and low glucose. This case has borderline CSF changes consistent with toxic encephalopathy, NOT meningitis. ### Pathophysiology of Typhoid Encephalopathy 1. **Toxic metabolic encephalopathy** from high bacterial endotoxin load 2. **Cerebral edema** from systemic inflammation 3. **Altered mental status, delirium, coma** without meningeal invasion 4. CSF remains relatively normal (no organism, minimal cells) **Clinical Pearl:** True S. typhi meningitis is rare (<1% of typhoid cases). When CNS symptoms occur, they are usually due to encephalopathy, not meningitis. Encephalopathy is a sign of severe typhoid and carries high mortality if untreated. **Mnemonic: ENCEPHALOPATHY vs. MENINGITIS** — **E**ncephalopathy = **E**ndotoxin toxicity (CSF normal), **M**eningitis = **M**eningeal invasion (CSF abnormal).