Small Cell Lung Carcinoma Presenting as Collapsin Response-Mediating Protein (CRMP) -5 Paraneoplastic Optic Neuropathy

Abstract

A 77-year-old woman presenting with progressive visual loss in both eyes was found to have small cell lung cancer. Assay for collapsin response-mediating protein (CRMP) -5 was positive suggesting a paraneoplastic optic neuropathy (PON). During treatment of the small cell lung cancer, the patient died of pneumonia and autopsy disclosed neuropathologic abnormalities consistent with PON. This is only the second case of CRMP-5-confirmed PON to report neuropathologic findings.

Paraneoplastic and non-paraneoplastic retinopathy and optic neuropathy: Evaluation and management

“…At least 56 cases of PON have been reported, the vast majority associated with an underlying SCLC. 32,55,160,170,189,241,259,275,279 Other associations include Bcell lymphoma, 54,197,234 pancreatic glucagonoma, 154 neuroblastoma, 133,254 uterine sarcoma, 272 breast, 18,228 prostate, 44 nasopharyngeal, 105 bronchial, 220 papillary thyroid, 55,151 nonsmall cell lung, 21,192 and renal cell carcinomas. 55,108,268 Patients classically present with subacute, bilateral, painless vision loss that progresses over days to weeks.…”

“…55 Neuroimaging may reveal patchy, hyperintense T2 signal changes in the brain parenchyma, enhancement of the optic nerves, spinal cord abnormalities, or may be unremarkable. 55,259 Most of these patients test positive for a serum antibody to the 62-kDa neuronal antigen, collapsin response-mediating protein-5 (CRMP-5), which has also been called CV2. 107 The CSF typically reveals a lymphocytic-predominant pleocytosis, elevated protein, oligoclonal bands, and CRMP-5-IgG titers that equal or may significantly exceed serum levels.…”

Anti-Collapsing Response-Mediating Protein-5 Antibody–Positive Paraneoplastic Perioptic Neuritis without Typical Neurological Symptoms

“…To the best of our knowledge, only three anti-CRMP-5 antibody-positive PON cases with only optic neuropathy as a neurological symptom have been previously reported. 7,8,12 The visual prognoses of these cases and MRI findings varied. One case 7 suffered bilateral deterioration in light perception, and mild enhancement and enlargement were observed only in the right optic nerve on MRI.…”

“…Magnetic resonance imaging (MRI) of these cases has been reported as normal, 8,12 or involving unilateral optic nerve involvement. 7 In the following case report, we describe an anti-CRMP-5 antibodypositive PON patient without neurological symptoms who presented with bilateral perioptic neuritis.…”

“…1,2 Most PON patients exhibit many neurological symptoms, including ophthalmoplegia, cerebellar ataxia, seizures, dementia, and various sensory and/ or motor abnormalities. 1,[3][4][5] The various neurological symptoms are believed to be caused by an antitumour immune response 3,6 associated with an increased level of autoantibodies against collapsing response-mediating protein-5 (CRMP-5), 4,5,[7][8][9] which is expressed in the optic nerve, neurons of the central and peripheral nervous systems, oligodendrocytes, the cytoplasm of small cell lung carcinoma (SCLC) cells, or thymomas.- 5,6,[9][10][11] Only a few studies have reported anti-CRMP-5 antibody-positive PON cases that presented with optic neuropathy as the only clinical symptom. Magnetic resonance imaging (MRI) of these cases has been reported as normal, 8,12 or involving unilateral optic nerve involvement.…”