A 62 year old woman with a history of left ventricular outflow tract obstruction presented with acute onset of shortness of breath and flash pulmonary edema. She was gently diuresed with improvement, and on the following day was noted to be agitated and paranoid with hallucinations. Further history was taken from her daughter who described a four month period of declining ability to perform activities of daily living, worsening short term memory loss and behavioral changes including paranoia and agitation. Work up for reversible causes of dementia was initiated and the patient’s TSH, B12, HIV, RPR, computed tomography (CT) of the head without contrast, and magnetic resonance imaging (MRI) of the brain with and without contrast were all found to be within normal limits. Lumbar puncture demonstrated normal levels of red blood cells, white blood cells, glucose and protein, but was positive for oligoclonal bands as was the serum. Several days later the patient complained of shortness of breath. CT of the chest with contrast was performed which demonstrated a 5.8 cm left mediastinal mass with regional lymph node spread concerning for malignancy. Biopsy demonstrated small cell lung cancer. Anti-Hu antibody testing of the serum was positive. A diagnosis of small cell lung cancer (SCLC) with paraneoplastic limbic encephalitis was made. She was initiated on chemotherapy with cisplatin and etoposide followed by intravenous immunoglobulin (IVIG) and prednisone. Within several weeks she demonstrated significant improvement of her agitation and paranoia.
Paraneoplastic encephalitis is an inflammatory disorder of the central nervous system that is associated with a distant malignancy. Paraneoplastic encephalitis commonly presents as limbic encephalitis (PLE) which is characterized by mood and behavioral changes and short term memory loss. In PLE, cerebral spinal fluid is positive for inflammatory markers but demonstrates negative cytology. MRI frequently demonstrates temporal lobe abnormalities, though the MRI was normal in this patient. The majority of patients with PLE have antineuronal antibodies, of which anti-Hu antibody (also known as antineuronal nuclear antibody, type 1) is very common. Any patient presenting with limbic encephalitis should be considered for imaging to rule out underlying SCLC and anti-Hu is particularly strongly correlated with SCLC. The mainstay of treatment for PLE is treatment of the underlying malignancy. Although no randomized trials have been performed, immunosuppressive therapy with IVIG or corticosteroids is often used. There is a highly variable response to treatment and this patient has shown a favorable early response, though relapses are possible.
Paraneoplastic encephalitis should be considered in patients with rapidly progressive dementia and is often the presenting symptom of an underlying malignancy that has not yet been diagnosed.