Isolated paraneoplastic optic neuropathy associated with small-cell lung cancer and anti-CV2 antibodies

Abstract

Sirs: Paraneoplastic neurological syndromes (PNS) are disorders that occur in patients with systemic cancer, which are not due to direct tumour invasion or metastasis, chemotherapy or radiotherapy-induced neurotoxicity, coagulopathy, infection or metabolic or nutritional deficits. They are mediated by immunological mechanisms related to onconeural antigens expression by cancer cells [1]. Paraneoplastic optic neuropathy is an uncommon disorder [2–8]. We describe a patient with an isolated optic neuropathy associated with small-cell lung cancer and anti-CV2 antibodies. The patient was a 64-year-old heavy-smoker male who developed painless, progressive vision loss in his left eye, with only perception of movement 5 days after onset and mild visual loss in his right eye 2 days later. General and neurological examination revealed no abnormalities. Visual acuity was 0.4 in the right eye and only movement perception in the left one; a left relative afferent pupillary defect was present. Funduscopy showed right eye papilledema, whereas the left papilla was pale. Fluorescein angiography showed vitreous turbidity and dye enhancement in both papillae; no signs of retinitis or vasculitis were found. Blood analysis, including ESR, thyroid function tests, angiotensin-converting enzyme levels, autoantibodies and tumour markers (including neuron-specific enolase), were negative. CSF showed five mononuclear cells/ mm, a protein level of 78 mg/dl and no oligoclonal bands. Cytological examination was negative. Anti-CV2 antibodies were found in serum (1/8,000) and CSF (1/400), but not in aqueous humour. Brain MRI showed no abnormalities. Visual evoked potentials showed reduced amplitudes and mildly prolonged P100 latencies. Electroretinography was normal. A thorax CT scan revealed a 3-cm cystic nodule in the right superior lobe. Video-assisted thoracoscopy with lung biopsy was done; smallcell lung cancer was diagnosed. Methylprednisolone (1 g iv. daily for 5 days) was given and chemotherapy (cisplatin plus etoposide) was started after diagnosis of limited-stage disease. Fifteen months after diagnosis visual acuity was 0.7 in both eyes and no further relapses nor new neurological symptoms or signs developed over follow-up. Anti-CV2 antibodies remained in the serum sample at the same titer of 1/8,000. We report a patient with a seven-day history of painless, progressive, asymmetric, optic neuropathy as the only manifestation of small-cell lung cancer associated with anti-CV2 antibodies. Anti-CV2 (also called CRMP5-IgG) is an IgG autoantibody specific for the 62 kDa collapsing response-mediator protein 5 (CRMP-5) [9, 10]. Both the retina and the optic nerve contain full-length CRMP-5 protein. AntiCV2/CRMP-5 antibodies are markers of paraneoplastic autoimmunity related to lung cancer (mainly small-cell type) or thymoma [9, 10]. Graus et al. [11] have recently recommended diagnostic criteria for PNS. Although optic neuropathy is not a classical syndrome, our patient fulfills criteria for PNS as a non-classical syndrome with onconeural antibodies (anti-CV2/CRMP-5) and cancer (small-cell carcinoma). Response to therapy (steroids and chemotherapy) can be interpreted as an additional data supporting the diagnosis. Optic neuropathy is an uncommon paraneoplastic manifestation of cancer. Up to date, only 42 patients with paraneoplastic optic neuropathy have been reported in the English literature. However, nearly always patients had other neurological symptoms or signs, such as neuropathy, cerebellar ataxia, dementia, other cranial nerve abnormalities, A. Ares-Luque (&) L.A. Garcia-Tunon AE B.C. Cabezas L.E. Hernandez-Echebarria AE J. Tejada Neurology Dept. Hospital de Leon C/ Altos de Nava sn. 24071 Leon, Spain Tel.: +34-98/7237400 Fax: +34-98/7240503 E-Mail: adrianares@telefonica.net