Abstract
Background and purposeAcquired neuromyotonia can occur in patients with thymoma, alone or in association with myasthenia gravis (MG), but the clinical prognostic significance of such comorbidity is largely unknown. The clinico‐pathological features were investigated along with the occurrence of neuromyotonia as predictors of tumour recurrence in patients with thymoma‐associated myasthenia.MethodsA total number of 268 patients with thymomatous MG were studied retrospectively. Patients with symptoms of spontaneous muscle overactivity were selected for autoantibody testing using immunohistology for neuronal cell‐surface proteins and cell‐based assays for contactin‐associated protein 2 (CASPR2), leucine‐rich glioma inactivated 1 (LGI1), glycine receptor and Netrin‐1 receptor antibodies. Neuromyotonia was diagnosed according to the presence of typical electromyography abnormalities and/or autoantibodies against LGI1/CASPR2.ResultsOverall, 33/268 (12%) MG patients had a thymoma recurrence. Five/268 (2%) had neuromyotonia, four with typical autoantibodies, including LGI1 (n = 1), CASPR2 (n = 1) or both (n = 2). Three patients had Netrin‐1 receptor antibodies, two with neuromyotonia and concomitant CASPR2+LGI1 antibodies and one with spontaneous muscle overactivity without electromyography evidence of neuromyotonia. Thymoma recurrence was more frequent in those with (4/5, 80%) than in those without (28/263, 10%, P < 0.001) neuromyotonia. Neuromyotonia preceded the recurrence in 4/5 patients. In univariate analysis, predictors of thymoma recurrence were age at thymectomy [odds ratio (OR) 0.95, 95% confidence interval (CI) 0.93–0.97], Masaoka stage ≥IIb (OR 10.73, 95% CI 2.38–48.36) and neuromyotonia (OR 41.78, 95% CI 4.71–370.58).Conclusions De novo occurrence of neuromyotonia in MG patients with previous thymomas is a rare event and may herald tumour recurrence. Neuronal autoantibodies can be helpful to assess the diagnosis. These observations provide pragmatic risk stratification for tumour vigilance in patients with thymomatous MG.
Highlights
This study focused on the clinico-pathological and neuronal autoantibody characterization of patients with myasthenia gravis (MG), NMT and thymoma, extrapolated from a very large series of patients with MG and thymoma who, in turn, were investigated for tumour-related prognostic factors
It was confirmed that the recently identified autoantibodies to Netrin-1 receptors can be found in thymoma-associated MG with NMT/Morvan syndrome comorbidity, mainly as co-reactivities
Due to the retrospective nature of the study, a suggestive EMG was not a mandatory requirement for NMT diagnosis, which could alternatively be assessed if typical autoantibodies (CASPR2 and/or leucine-rich glioma inactivated 1 (LGI1)) were detected
Summary
Acquired neuromyotonia (NMT) is characterized by spontaneous and continuous muscle overactivity resulting from peripheral nerve hyperexcitability [1,2]. It is associated with antibodies to contactin-associated protein 2 (CASPR2), leucine-rich glioma inactivated 1 (LGI1) or both in around 40% of cases and shows good response to plasmapheresis [3,4] These antibodies target neuronal cell-surface epitopes, and they are probably pathogenic [5]. Patients with symptoms of spontaneous muscle overactivity were selected for autoantibody testing using immunohistology for neuronal cell-surface proteins and cell-based assays for contactin-associated protein 2 (CASPR2), leucine-rich glioma inactivated 1 (LGI1), glycine receptor and Netrin-1 receptor antibodies. Neuronal autoantibodies can be helpful to assess the diagnosis These observations provide pragmatic risk stratification for tumour vigilance in patients with thymomatous MG
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