Paraneoplastic limbic encephalitis associated with lung cancer

Abstract

Paraneoplastic limbic encephalitis (PLE) is a rare autoimmune neurological syndrome observed in lung cancer patients. We retrospectively investigated the clinical characteristics, treatment responses, and prognoses in 16 PLE patients who were subsequently diagnosed with lung cancer. Fifteen patients initially presented with disturbance of consciousness, 13 with disorientation, and 12 with seizures. Thirteen patients had autoantibodies, including eight with gamma aminobutyric acid B receptor (GABA_BR) antibodies and eight with Hu antibodies. PET-CT revealed lung neoplasms in 13 patients, nine of whom exhibited abnormal metabolic activity in the temporal lobe and hippocampus. Fifteen cases were confirmed as limited-stage small cell lung cancer and one as stage IV large cell neuroendocrine carcinoma. Eleven patients received immunomodulatory therapy, and four showed neurological improvement, who all had antibodies against GABA_BR. Fifteen patients received chemotherapy, of which 14 maintained or improved their PLE status. The overall cancer response rate was 75%, and two-year overall survival was 74.7%. Our results suggest patients with GABA_B encephalitis might respond better to immunotherapy than the classical PLE patients with anti-Hu antibodies. Anti-cancer treatment could further improve neurological symptoms. Lung cancer patients with PLE, especially those in limited stage, might have better outcome due to earlier diagnosis and prompt anti-cancer treatment.

Figure-1

PET-CT and MRI images for two cases. Case 1: 71-year-old female (A) PET-CT showed enhanced metabolism in the bilateral mesial temporal lobe and insula (arrows), and MRI T2 showed high signal in the same location (circles). Case 2: 54-year-old male (B) PET-CT showed abnormal metabolism in the left temporal lobe (arrows), while MRI was normal.

Figure-2

Contrast-enhanced CT and PET-CT images from a 54-year-old male patient. PET-CT showed a soft tissue mass in the inferior lobe of the right lung with abnormal metabolism (arrows), which was not evident on CT scan.

Figure-3

Neurological improvement and long-term survival in PLE patients with lung cancer. (A) Relationship between neurological symptom improvement and PLE-related treatment. (B) Long-term survival of PLE patients since LE symptom onset. IVIg, intravenous immunoglobulin; LE, limbic encephalitis; VATS, video-assisted thoracoscopic surgery.