P 72 Antibody depletion in nodo-paranodopathy: Clinical and electrophysiological long-term follow-up

Abstract

Nodo-paranodopathies are rare immune-mediated neuropathies with autoantibodies against proteins of the node of Ranvier. The antibodies cause conduction failure and a destruction of nodal architecture in vivo and in vitro. Affected patients show severe motor and sensory involvement and signs of demyelination in electroneurography, fulfilling EFNS/PNS criteria for CIDP. Response to standard treatment is poor, but good clinical response to rituximab has been reported. Little is known about long-term outcome after antibody depletion and electroneurographic follow-up. We conducted a cohort study of 7 patients with neuropathy with anti-paranodal antibodies treated at the University Hospital of Würzburg (n = 3 anti-contactin-1, n = 4 anti-Caspr-1) who showed an antibody decrease in the course of the disease either spontaneously (n = 2) or treatment-induced by B-cell depletion with Rituximab (n = 5). Antibody titers and Neurofilament Light-Chain (NfL) levels were assessed at first diagnosis/ recruitment and in follow-up serum samples by ELISA and Ella. Clinical data, scores and electrophysiological data were assessed retrospectively with a mean follow-up period of 48.6 (8-78) months and compared using paired t-test and Spearman correlation. At recruitment, mean disease duration was 43.6 (0.25-180) months. Patients showed sensorimotor tetraparesis with a mean Overall Disability Sum Score (ODSS) of 7.43 (5-10) and MRC sum score of 48.29 (40-57). The antibody titer ranged from 1:100 – 1:10,000 and did not correlate with inter-individual disease severity. Electroneurography revealed demyelinating features with highly elevated distal motor latency (dml), loss/ reduction of F-waves and reduced nerve conduction velocity, but also signs of severe, length-dependent compound motor action potential (CMAP) amplitude decrease and spontaneous activity in electromyography in 5/ 7 patients. After antibody depletion, we found a significant reduction in the Overall Disability Sum Score (ODSS, p < 0.007) and improvement in the MRC sum score. Electrophysiological demyelinating parameters improved significantly. The mean increase in tibial nerve dml correlated with the increase in MRC sum score (r = 0.922, p < 0.003). Median nerve CMAP amplitudes increased significantly (p < 0.009), with a significant negative correlation to ODSS (r = -0.7, p < 0.03). Tibial nerve CMAP on the other hand remained severely reduced. In patients with autoantibody-mediated nodo-paranodopathy, the depletion of antibodies leads to a clinical and electrophysiological improvement, even after a long disease duration. In our cohort, distal, length dependent axonal damages could not be fully reversed. Our data therefore suggest that early antibody depletion should be a main therapeutic goal in nodo-paranodopathy. Although the antibody titer cannot be used as an inter-individual indicator of disease severity, it may serve as a valuable intra-individual marker for treatment reevaluation and prognosis.