A 35-year-old man with a 10-year history of generalized tonic-clonic seizures (currently on levetiracetam 1000 mg BD) presents with a 3-month history of progressive cognitive decline, personality changes, and recurrent seizures despite compliance. His wife notes he has become withdrawn, irritable, and forgetful. On examination, he has mild tremor and ataxia. MRI brain shows bilateral temporal lobe atrophy with T2/FLAIR hyperintensity in the medial temporal lobes. Serum sodium is 128 mEq/L (normal: 135–145). What is the most likely diagnosis?

Explanation

## Autoimmune Encephalitis with Seizures ### Clinical Presentation Analysis This case presents a **classic constellation** of autoimmune encephalitis: 1. **Subacute progressive cognitive decline + personality changes** over 3 months — hallmark of autoimmune encephalitis 2. **Recurrent seizures despite AED compliance** — seizures refractory to standard AEDs are a red flag for autoimmune etiology 3. **Bilateral medial temporal T2/FLAIR hyperintensity** — the radiological signature of limbic encephalitis 4. **Mild hyponatremia (Na⁺ 128 mEq/L)** — a consequence of SIADH secondary to limbic/hypothalamic inflammation, NOT the primary cause ### Why Autoimmune Encephalitis is Correct **High-Yield:** Autoimmune (limbic) encephalitis classically presents with the **triad**: - Subacute cognitive decline / amnesia - Psychiatric/behavioral changes (irritability, withdrawal) - Seizures (often temporal lobe origin, refractory) **MRI findings:** Bilateral medial temporal lobe T2/FLAIR hyperintensity is the **pathognomonic radiological pattern** of limbic encephalitis (anti-LGI1, anti-NMDAR, anti-CASPR2, anti-GABA-B, paraneoplastic). This is NOT a feature of levetiracetam-induced hyponatremia. **Hyponatremia in autoimmune encephalitis:** Anti-LGI1 encephalitis in particular is strongly associated with SIADH and hyponatremia due to hypothalamic involvement — the hyponatremia is a *consequence*, not the cause, of the encephalitis (Harrison's 21e, Ch 380). **Clinical Pearl:** A Na⁺ of 128 mEq/L alone does NOT produce bilateral medial temporal MRI changes. Osmotic demyelination from rapid correction causes pontine/extrapontine changes, not medial temporal hyperintensity. ### Why the Other Options Are Wrong | Option | Reason Incorrect | |--------|-----------------| | **A) Levetiracetam-induced PME** | Levetiracetam does NOT cause progressive myoclonic epilepsy; it is actually used to treat PME | | **C) Drug-induced hyponatremia from levetiracetam** | Levetiracetam is NOT a recognized cause of SIADH (carbamazepine and oxcarbazepine are the classic AED culprits). Hyponatremia at 128 mEq/L does not produce bilateral medial temporal MRI changes | | **D) Temporal lobe epilepsy with mesial temporal sclerosis** | MTS is typically unilateral, associated with a childhood febrile seizure history, and does NOT cause subacute cognitive/personality decline over 3 months | ### Diagnostic Approach 1. **CSF analysis:** Lymphocytic pleocytosis, elevated protein, oligoclonal bands 2. **Autoimmune antibody panel:** Anti-NMDAR, anti-LGI1, anti-CASPR2, anti-GABA-B, anti-AMPAR (serum + CSF) 3. **Paraneoplastic workup:** CT chest/abdomen/pelvis; anti-Hu, anti-Yo, anti-Ri 4. **EEG:** Temporal lobe epileptiform discharges, extreme delta brush (anti-NMDAR) 5. **Treatment:** IV methylprednisolone → IVIG → plasmapheresis; rituximab/cyclophosphamide for refractory cases **Key Point:** The combination of subacute behavioral change, refractory seizures, and **bilateral medial temporal T2/FLAIR hyperintensity** is the textbook presentation of autoimmune limbic encephalitis until proven otherwise. [cite: Harrison 21e Ch 380 — Autoimmune Encephalitis; Ropper & Samuels Adams & Victor's Principles of Neurology 11e Ch 36]