Paraneoplastic limbic encephalitis associated with lung cancer

Kaini Shen,Minjiang Chen,Jing Zhao,Mengzhao Wang,Longyun Li,Yan Xu,Wei Zhong,Hongzhi Guan

doi:10.1038/s41598-018-25294-y

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 (GABABR) 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 GABABR. 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 GABAB 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.

Highlights

Paraneoplastic limbic encephalitis (PLE) is a rare neurological syndrome associated with cancer, and selectively affects limbic system structures, including the hippocampus, hypothalamus, and amygdala
The current study investigated clinical characteristics, autoantibody profiles, responses to treatment, and prognoses in 16 patients with LE who were later diagnosed with lung cancer
gamma aminobutyric acid B receptor (GABABR) antibodies were found in both cerebrospinal fluid (CSF) and serum samples in seven patients, and solely in serum in one patient

Summary

Introduction

Paraneoplastic limbic encephalitis (PLE) is a rare neurological syndrome associated with cancer, and selectively affects limbic system structures, including the hippocampus, hypothalamus, and amygdala. PLE is an immune-mediated response associated with anti-neuronal antibodies. Classical limbic encephalitis (LE) with temporal lobe seizures is associated with onconeural antibodies directed against intracellular antigens, including anti-Hu2, anti-Ma23, anti-amphiphysin, and anti-CRMP52,4. PLE treatment options include immunotherapy and anti-cancer therapy[6]. Immunomodulators, such as steroids and intravenous immunoglobulin (IVIg), have been used to treat all types of LE with variable results. Anti-cancer treatment is often not recommended in PLE patients, due to severe PLE-associated neurological symptoms (seizures, dementia, status epilepticus, etc.). Few studies have focused on treatment responses and prognoses in PLE patients with lung cancer. The current study investigated clinical characteristics, autoantibody profiles, responses to treatment, and prognoses in 16 patients with LE who were later diagnosed with lung cancer. Anti-GABABR in serum Anti-Hu in serum Anti-amphiphysin in serum Anti-GM1 in serum Anti-Yo in serum Anti-GABABR in CSF Anti-Hu in CSF Abnormal pressure Lymphocytic pleocytosis

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Results

Conclusion