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Ipilimumab is a monoclonal antibody that prolongs survival in patients with metastatic melanoma.1 It targets the coinhibitory receptor cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 signaling induces a state of T-cell unresponsiveness, which facilitates tumor escape from immune surveillance. Blockade of CTLA-4 is believed to shift the immune status from T-cell exhaustion to a functional antitumor response. Anti-CTLA-4 therapy is associated with immune-related adverse events in 64% of patients. Autoimmunity involving the nervous system has a low incidence and manifests predominantly as peripheral inflammatory neuropathy.2 We report new-onset inflammatory CNS demyelination in an ipilimumab-treated melanoma patient (figure), confirmed by histology and associated with enhanced responses of myelin-reactive CD4+ T cells.

Objective: To present a unique case of lesions playing “Hide and Seek” with a demyelinating lesion in the brain leading to a diagnosis of adenocarcinoma of the lung. Background Paraneoplastic syndromes consisting of a focal demyelinating lesion in the brain or spinal cord are rare but have been reported in the setting of extra cerebral malignant tumors such as seminoma and adenocarcinoma of the lung. We have a unique case with a lesion in the brain leading to a diagnosis of adenocarcinoma of the lung. Design/Methods: Case report. Results: A 64-year-old African-American woman presented with right inferior quadranopsia. MRI of the brain showed a 2.2 x 2.5cm contrast enhancing left mesial temporal lesion suspicious for glioma, lymphoma or demyelinating disease. Repeat MRI, functional-MRI and MR-Spectroscopy were done for pre-surgical evaluation a month later showing the same lesion with more definitive partial ring enhancement more suggestive of demyelination. Repetitive CSF analysis showed mild pleiocytosis (≤ 25 WBC) predominantly lymphocytic(≥ 90%) with normal protein and glucose. Lyme, ACE, Viral PCR, culture, cytology and flow-cytometry for lymphoma-markers were negative. IgG index and synthesis were increased and there were 10 oligoclonal bands. Cervical and thoracic spine MRI was negative. Chest CT scan revealed an indeterminate right upper-lobe lesion. Repetitive MRI of the brain showed complete resolution of the lesion coinciding with an increase in the pulmonary lesion size. CT guided biopsy of the lung revealed invasive adenocarcinoma. Conclusions: This is a unique case with a solitary brain lesion leading to a diagnosis of adenocarcinoma of the lung leading to an early diagnosis and treatment prior to metastasis. The etiology of the demyelinating brain lesion is most likely paraneoplastic. This case emphasizes the message that in the case of a solitary intracranial lesion “think outside the brain” which can be sometimes critical in in a proper diagnosis. Disclosure: Dr. Alareddy has nothing to disclose. Dr. Aizenberg has nothing to disclose. Dr. White has nothing to disclose. Dr. Zabad has received personal compensation for activities with Teva Neuroscience, Biogen Idec, Serono, Inc., and Bayer Pharmaceuticals Corporation.