A 32-year-old woman with known SLE (ANA-positive, anti-dsDNA-positive, diagnosed 2 years ago) presents to the emergency department with acute onset of severe headache, confusion, and seizures. She has a fever of 38.5°C. Fundoscopy reveals cotton-wool spots and retinal hemorrhages. Lumbar puncture shows: CSF protein 120 mg/dL, glucose 58 mg/dL (serum glucose 110 mg/dL), WBC 85 cells/μL (60% lymphocytes), and negative bacterial culture and gram stain. Brain MRI shows no focal lesions. What is the most likely diagnosis?

Explanation

## Diagnosis: Lupus Cerebritis (CNS Lupus) ### Clinical Presentation of CNS Lupus **Key Point:** CNS lupus (neurolupus) occurs in 14–75% of SLE patients and can manifest as acute encephalopathy, seizures, psychosis, or meningitis. This patient presents with the acute encephalitic form. ### Diagnostic Features Present | Feature | Finding | Significance | |---------|---------|---------------| | **Neurological** | Acute seizures, confusion, headache | Typical of lupus cerebritis | | **Fever** | 38.5°C | Can occur in active CNS lupus | | **Fundoscopy** | Cotton-wool spots, retinal hemorrhages | Lupus retinopathy; vasculitis | | **CSF Analysis** | Protein 120, glucose 58, WBC 85 (lymphocytic) | Aseptic meningitis pattern | | **Cultures** | Negative bacterial and gram stain | Rules out bacterial infection | | **MRI** | No focal lesions | Excludes structural pathology; consistent with diffuse inflammation | | **SLE status** | Known ANA+, anti-dsDNA+ | Active autoimmune disease | **High-Yield:** The CSF profile in lupus meningitis is typically: - Lymphocytic pleocytosis (40–500 cells/μL) - Elevated protein (50–200 mg/dL) - Low-to-normal glucose (CSF:serum ratio <0.4) - Negative cultures (aseptic meningitis) This matches the patient's CSF findings exactly. ### Why This Is Lupus Cerebritis, Not Infection 1. **Negative cultures** — bacterial meningitis would show positive gram stain or culture 2. **Lymphocytic predominance** — bacterial meningitis typically shows neutrophilic pleocytosis 3. **Known SLE with active serology** — patient is at high risk for lupus flare 4. **Retinal findings** — cotton-wool spots and hemorrhages are consistent with lupus vasculitis, not bacterial infection 5. **Normal MRI** — rules out abscess, ventriculitis, or focal infection **Clinical Pearl:** Lupus cerebritis is a diagnosis of exclusion — infectious causes (bacterial, tuberculous, fungal, viral) must be ruled out first. However, the combination of negative cultures, lymphocytic CSF, low glucose, and known active SLE with retinal vasculitis makes lupus cerebritis the most likely diagnosis. ### Pathophysiology ```mermaid flowchart TD A[Active SLE with anti-dsDNA+]:::outcome --> B[Immune complex deposition in CNS vasculature]:::action B --> C[Vasculitis and blood-brain barrier disruption]:::action C --> D[Neuroinflammation]:::action D --> E[Seizures, encephalopathy, meningitis]:::outcome F[Lupus retinopathy] -.->|Concurrent vasculitis| E ``` **Key Point:** The presence of lupus retinopathy (cotton-wool spots, hemorrhages) suggests systemic vasculitis, which supports CNS lupus over isolated infection. ### Management Implications **High-Yield:** Treatment of lupus cerebritis requires: - High-dose corticosteroids (methylprednisolone 1 g IV daily × 3–5 days) - Immunosuppression (cyclophosphamide or mycophenolate mofetil) - Anticonvulsants for seizure control - Avoidance of antibiotics unless infection is proven **Warning:** Delaying immunosuppression while awaiting culture results can lead to irreversible neurological damage. Once infection is reasonably excluded, aggressive immunosuppression should be initiated. [cite:Harrison 21e Ch 312]