Abstract Background AMPA receptor encephalitis is an uncommon cause of paraneoplastic limbic encephalitis. While classically presenting with short-term memory loss, confusion, and behavioral change, it may manifest atypically (e.g., psychosis or hyponatremia), delaying diagnosis and treatment. Outcomes appear less favorable than with other autoimmune encephalitides, and prognosis hinges on early immunotherapy and identification of an underlying tumor. Here we present a rare case of AMPA-R positive encephalitis presenting as acute metabolic encephalopathy and hyponatremia associated with small cell lung cancer. Case 71-year-old female patient with history of type 2 diabetes mellitus, COPD, tobacco abuse presented with change in mental status. She was found to have UTI and severe hyponatremia, however despite treatment symptoms did not improve. Extensive workup was done including Electroencephalography (EEG) which was negative for seizures, MRI brain showing abnormal signal in the medial temporal lobes and the hippocampus, left right and lumbar puncture which came positive for human herpes virus 6, treated empirically with IV acyclovir and subsequently oral valganciclovir after discharge. Despite completing antiviral treatment, she had worsened cognitive impairment, behavioral change, and confusion. Repeat MRI of the brain showed white matter abnormalities similar to prior. CSF analysis returned positive for AMPA receptor antibodies, and she was readmitted for IV steroid therapy and plasma exchange. Mentation stablilized but short-term memory deficits persisted. CT chest imaging was evident of 5 mm pulmonary nodule, subsequently PET scan showed increased uptake within the right hilum, biopsy returned positive for small cell lung cancer. Patient was started on chemo-radiation. Although her cognition deteriorated over a short period, interval MRIs (Figure 1 showing pretreatment limbic flair changes on Left and post treatment on right) improved and were no longer consistent with active encephalitis. Conclusion 1. AMPA-R antibody positive paraneoplastic limbic encephalitis is a rare and challenging diagnosis. It can be particularly difficult to manage, with progressive cognitive decline posing a significant concern. In patients with compatible clinical features and mesial temporal MRI changes, early AMPAR antibody testing should be pursued to expedite immunotherapy.2. Thorough malignancy screening is essential, as tumor association classically small cell lung cancer but also reported with breast cancer, malignant thymoma, and ovarian teratoma helps guide management and can markedly influence outcomes.3. Prompt immunotherapy (e.g., steroids, plasma exchange, IVIG) with early and aggressive oncologic treatment offer the best chance of recovery and reduced relapse risk. Limited reports suggest tumor-associated cases may respond better to first line regimens than non-paraneoplastic cases. This abstract is funded by: None
Asif et al. (2026) studied this question.