Autoimmune CRMP5 neuropathy phenotype and outcome defined from 105 cases

Abstract

ObjectiveTo establish the phenotype and clinical outcomes of collapsin response-mediator protein-5 (CRMP5) autoimmune neuropathy in comparison with anti-neuronal nuclear antibody type 1 (ANNA1)–immunoglobulin G (IgG) neuropathy.MethodsPatients with CRMP5-IgG and/or ANNA1-IgGs were identified in our service-line testing, and medical records were reviewed.ResultsOne hundred five patients with CRMP5-IgG neuropathy (88% smokers; 69% having cancer, most commonly small cell lung cancer [75%]) were identified and compared to 51 patients with ANNA1-IgG neuropathy, 27 with coexisting CRMP5-IgG. Patients with CRMP5 had painful axonal polyradiculoneuropathy (65%), mostly asymmetric onset (84%), with neuropathy predating cancer diagnosis by 185 days (range 60–540 days). Most cases (79%) had moderate to severe neuropathic pain, all on neuropathic medications (median 2, range 1–4), opioids in 39%. Nerve biopsies (n = 2) showed microvascular inflammation with axonal degeneration. Compared to ANNA1 alone, CRMP5 neuropathy has a higher prevalence of pain (79% vs 46%, p = 0.008), asymmetric polyradiculoneuropathy (54% vs 12%, p < 0.001), and inflammatory spinal fluids (elevated CSF protein or nucleated cell count 92% vs 60%, p = 0.022). Cerebellar ataxia (21%), myelopathy (19%), and optic neuritis and/or retinitis (11%) were common neurologic accompaniments. CRMP5 cases had significant pain reduction by immunotherapy (p < 0.001). Specifically, high-dose corticosteroid administration was associated with improvement/stabilization in neuropathy impairment scores (p = 0.012) (Class IV). Patients with CRMP5 had better 5-year survival than patients with ANNA1 (67% vs 32%, p = 0.012).ConclusionPainful axonal asymmetric polyradiculoneuropathy is established as the major CRMP5 autoimmune neuropathy presentation and is distinguishable from other paraneoplastic neuropathies, including by ANNA1 autoimmunity. Patients with this phenotype should be prompted for CRMP5-IgG testing to assist in early cancer diagnosis.