A 62-year-old woman with a 6-month history of progressive confusion, memory loss, and personality changes presents to neurology. She reports recent weight loss and fatigue. MRI brain shows temporal lobe atrophy with T2/FLAIR hyperintensity. Serum anti-CRMP5 (collapsin response mediator protein 5) antibodies are positive. Whole-body CT reveals a small cell lung cancer (SCLC) in the left lower lobe. Which paraneoplastic neurological syndrome is most likely?

Explanation

## Clinical Diagnosis: Paraneoplastic Limbic Encephalitis (PLE) **Key Point:** Paraneoplastic limbic encephalitis is a subacute dementia syndrome with temporal lobe involvement, strongly associated with SCLC and positive anti-CRMP5 (or anti-Hu) antibodies. ### Diagnostic Criteria Met | Feature | Finding | Relevance | | --- | --- | --- | | **Cognitive symptoms** | Progressive confusion, memory loss, personality change | Limbic system dysfunction | | **MRI findings** | Temporal lobe atrophy + T2/FLAIR hyperintensity | Inflammation/gliosis in limbic structures | | **Antibody** | Anti-CRMP5 positive | Paraneoplastic marker; associated with SCLC | | **Malignancy** | SCLC (small cell lung cancer) | Classic association with paraneoplastic syndromes | | **Timeline** | Subacute (6 months) | Consistent with immune-mediated mechanism | **High-Yield:** Anti-CRMP5 antibodies are found in ~5% of SCLC patients and strongly predict paraneoplastic neurological disease, particularly limbic encephalitis and sensory neuronopathy. ### Pathophysiology 1. SCLC tumor expresses CRMP5 antigen 2. Immune system generates anti-CRMP5 antibodies that cross-react with CNS neurons 3. CD8^+^ T-cell infiltration of hippocampus, amygdala, and temporal lobes 4. Neuronal loss → atrophy and cognitive decline **Clinical Pearl:** The **temporal lobe predominance** on MRI is the anatomical hallmark of limbic encephalitis. Patients may also develop seizures (30–40% of cases) and psychiatric symptoms (depression, anxiety, personality changes). ### Differential Features of Paraneoplastic Syndromes | Syndrome | Key Features | Antibody | Cancer | | --- | --- | --- | --- | | **Limbic encephalitis** | Temporal lobe atrophy, dementia, seizures | Anti-Hu, Anti-CRMP5 | SCLC, testicular | | **Cerebellar degeneration** | Ataxia, dysarthria, nystagmus | Anti-Yo, Anti-Hu | Ovarian, breast, SCLC | | **Opsoclonus-myoclonus** | Chaotic eye movements, myoclonus | Anti-Hu, Anti-Ri | SCLC, neuroblastoma | | **Sensory neuronopathy** | Dorsal root ganglion destruction, sensory loss | Anti-Hu, Anti-CRMP5 | SCLC | **Mnemonic: CRMP5 + SCLC + Temporal Lobe = Limbic Encephalitis (CSTLi)** ### Management - **Immunotherapy:** Intravenous immunoglobulin (IVIG), plasmapheresis, corticosteroids - **Cancer treatment:** Chemotherapy for SCLC (may improve neurological symptoms) - **Symptomatic:** Antiepileptics if seizures present - **Prognosis:** Variable; early recognition and cancer treatment improve outcomes