Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP-5-IgG

• Published in: Annals of neurology Vol. 54; no. 1; pp. 38 - 50
• Main Authors: Cross, Shelley A., Salomao, Diva R., Parisi, Joseph E., Kryzer, Thomas J., Bradley, Elizabeth A., Mines, Jonathan A., Lam, Byron L., Lennon, Vanda A.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.07.2003; Willey-Liss
• Subjects: Aged; Antibodies, Monoclonal - immunology; Autoantibodies - immunology; Biological and medical sciences; Carcinoma, Small Cell - complications; Carcinoma, Small Cell - immunology; CD4 Antigens - immunology; Diagnosis, Differential; Diseases of visual field, optic nerve, optic chiasma and optic tracts; Electroretinography - methods; Female; Humans; Immunoglobulin G - immunology; Lung Neoplasms - complications; Lung Neoplasms - immunology; Male; Medical sciences; Middle Aged; Nerve Tissue Proteins - immunology; Nerve Tissue Proteins - metabolism; Neuromyelitis Optica - diagnosis; Ophthalmology; Optic Nerve - immunology; Optic Nerve - metabolism; Optic Nerve - pathology; Optic Neuritis - complications; Optic Neuritis - immunology; Optic Neuritis - metabolism; Retinitis - complications; Retinitis - diagnosis; Retinitis - immunology; Retinitis - metabolism; Human; Oligoclonal immunoglobulin; Nervous system diseases; Spinal cord; Optic nerve; Retinopathy; Autoantibody; IgG; Vitreous body; Retina; Cerebrospinal fluid; Malignant tumor; Spinal nerve; Eye disease; Cranial nerve disease; Optic nevritis; Smoker; T-Lymphocyte; Immunoblotting assay; Paraneoplastic syndrome; Optic papilla; Small cell carcinoma; Lymphocytosis
• ISSN: 0364-5134; 1531-8249
• DOI: 10.1002/ana.10587

Autoantibodies have defined two paraneoplastic visual disorders related to small‐cell lung carcinoma: retinopathy (“CAR”‐IgG [23kDa, recoverin]) and optic neuritis collapsin response‐mediated protein 5 (CRMP‐5‐IgG [62kDa]). Among 16 patients with CRMP‐5‐IgG and optic neuritis (aged 52–74 years; all smokers, 9 women), we documented coexisting retinitis in 5. None had CAR‐IgG. Fifteen had subacute vision loss, swollen optic discs, and field defects. Vascular leakage was evident at and remote from the disc; 5/5 tested had abnormal electroretinograms. Nine had striking vitreous cells. Vitrectomy showed reactive lymphocytosis (4/4), predominantly CD4+ (1/1). Most patients had multifocal neurological accompaniments. Cerebrospinal fluid contained lymphocytes (7‐32), elevated protein, multiple oligoclonal immunoglobulin bands, and CRMP‐5‐IgG. Three patients superficially resembled Devic's disease at presentation. One autopsied patient had predominantly CD8+ T lymphocytes infiltrating optic nerve and spinal cord. Eleven patients had confirmed small‐cell carcinoma; 1 had imaging evidence of lung cancer; 3 had renal or thyroid carcinoma. Full‐length CRMP‐5 protein was identified in normal retina and optic nerve by Western blot analyses. Photoreceptor cells, retinal ganglion cells, and nerve fibers exhibited CRMP‐5–specific immunoreactivity. In summary, CRMP‐5‐IgG defines a paraneoplastic ophthalmological entity of combined optic neuritis and retinitis with vitreous inflammatory cells. Positive serology obviates the need for vitreous biopsy and expedites the search for cancer. Ann Neurol 2003