Paraneoplastic Limbic Encephalitis: A Rare Presentation of Lung Malignancy

Abstract

Introduction: Paraneoplastic limbic encephalitis (PLE) is a rare paraneoplastic syndrome associated with small cell lung cancer (SCLC). We present a case of PLE as the initial manifestation of SCLC, highlighting the importance of having a high clinical suspicion for PLE in the appropriate patient population. CASE PRESENTATION: A 62 year-old man with 50 pack-year smoking history presented with four months of short term memory impairment, headaches, weight loss, and witnessed seizure. MRI showed temporal lobe enhancement. CSF analysis was negative for infectious processes including HSV. Concern for autoimmune encephalitis prompted workup for malignancy and CT chest showed right hilar mass. Endobronchial ultrasound-guided FNA of mediastinal lymph node yielded a diagnosis of small cell carcinoma. CSF was positive for ANNA-1 at a high titer, consistent with paraneoplastic limbic encephalitis. The patient was referred for chemotherapy. DISCUSSION: Paraneoplastic limbic encephalitis (PLE) is a rare syndrome most commonly associated with lung malignancy, specifically SCLC. The diagnosis of PLE precedes the malignancy diagnosis in up to 60% of patients. The most common symptoms are non-specific and include memory loss, seizures, cognitive dysfunction, and psychiatric disturbances. 50% of patients with SCLC-related PLE have Anti-Hu (ANNA-1) antibodies. The presence of these antibodies predicts a poor neurological prognosis even with treatment of the malignancy. Conclusions: Physicians must have a high index of suspicion for PLE when patients, especially those with a significant smoking history, present with neurologic symptoms. Given the lack of specificity of the most common presenting symptoms, PLE is likely underdiagnosed. As in this case, patients may not have any respiratory symptoms, and the PLE diagnosis may precede the lung cancer diagnosis. Imaging should be considered to rule out malignancy in patients presenting with neurologic symptoms if initial workup for space occupying brain lesion and infectious encephalitis is negative. CSF antibodies such as Anti-Hu are helpful in confirming the diagnosis and aiding in prognosis. Treatment with chemotherapy may improve the neurologic symptoms, especially in those patients who are antibody negative.