Paraneoplastic optic neuritis, vitritis (cancer related)

[Mike Bartolatz]

Original Articles
Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP-5-IgG
Shelley A. Cross, MD 1 *, Diva R. Salomao, MD 2, Joseph E. Parisi, MD 1 2, Thomas J. Kryzer, AS 2 3, Elizabeth A. Bradley, MD 4, Jonathan A. Mines, MD 5, Byron L. Lam, MD 6, Vanda A. Lennon, MD, PhD 1 2 3
1Department of Neurology, Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, MN
2Laboratory Medicine and Pathology, Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, MN
3Immunology, Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, MN
4Ophthalmology, Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, MN
5Bay Area Retinal Consultants, Clearwater, FL
6Bascom Palmer Eye Institute, Miami, FL

email: Shelley A. Cross (lennon.vanda@mayo.edu)

*Correspondence to Shelley A. Cross, Mayo Clinic, Neuroimmunology Laboratory, Guggenheim Building, Room 828, 200 First Street SW, Rochester, MN 55905

Funded by:
Mayo Clinic Cancer Center

Abstract
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



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Received: 8 November 2002; Revised: 13 February 2003; Accepted: 14 February 2003
Digital Object Identifier (DOI)

10.1002/ana.10587 About DOI