A 28-year-old woman from rural Maharashtra presents to the emergency department with a 2-hour history of continuous seizure activity. She had her first unprovoked seizure 6 months ago, followed by 3 more episodes over the past month. On examination, she is post-ictal, with a temperature of 38.5°C, neck stiffness, and photophobia. CT head shows no acute abnormality. Lumbar puncture reveals CSF with 120 cells/μL (90% lymphocytes), protein 85 mg/dL, glucose 45 mg/dL (serum glucose 110 mg/dL), and negative Gram stain. She is started on lorazepam, phenytoin, and empiric ceftriaxone + acyclovir. Over the next 48 hours, seizures recur despite therapeutic phenytoin levels. What is the most likely diagnosis?

Explanation

## Clinical Diagnosis: Tuberculous Meningitis (TBM) with Secondary Epilepsy ### Key Diagnostic Features **CSF Profile Consistent with TBM:** - Lymphocytic pleocytosis (90% lymphocytes) with moderate cell count (120/μL) - Elevated protein (85 mg/dL) — typically 100–500 mg/dL in TBM - Low glucose with low CSF:serum glucose ratio (45:110 ≈ 0.41) — **hallmark of TBM** (ratio <0.5) - Negative Gram stain — rules out acute bacterial meningitis **Clinical Context:** - **Rural Maharashtra** — endemic region for tuberculosis - **Recurrent seizures over 6 months** — suggests chronic meningitis rather than acute viral encephalitis - **Fever + neck stiffness + photophobia** — meningeal signs - **Seizures persist despite therapeutic phenytoin** — indicates ongoing CNS inflammation from TBM, not primary epilepsy ### Why TBM Causes Refractory Seizures **Key Point:** Seizures in TBM occur in 10–30% of cases due to: 1. Basilar meningitis causing vasculitis → ischemic stroke 2. Tuberculomas (mass lesions) → focal seizures 3. Hydrocephalus and raised intracranial pressure 4. Cortical inflammation These mechanisms cause **secondary epilepsy** that is often **refractory to standard anticonvulsants** until the underlying TB is treated. ### Management Implications **High-Yield:** The seizures will NOT resolve with phenytoin/levetiracetam alone. TBM requires: - Anti-tuberculous therapy (HRZE for 2 months, then HR for 7 months) - Corticosteroids (dexamethasone 0.3 mg/kg/day × 6–8 weeks) — reduces inflammation, vasculitis, and seizure recurrence - Anticonvulsants as adjunctive therapy **Clinical Pearl:** CSF glucose <40 mg/dL with lymphocytic pleocytosis is **highly specific for TBM** in India; viral encephalitis typically has normal or mildly low glucose. ### Mnemonic: CSF Profile in Meningitis **"VBAT"** — Viral, Bacterial, Aseptic, Tuberculous - **Viral:** lymphocytes, normal glucose, normal protein - **Bacterial:** PMNs, LOW glucose, HIGH protein, positive Gram stain - **Tuberculous:** lymphocytes, **VERY LOW glucose (<40)**, **VERY HIGH protein (100–500)**, negative Gram stain - **Aseptic (viral):** lymphocytes, normal glucose, mildly elevated protein [cite:Harrison 21e Ch 380]