BACKGROUND: Acquired neuromyotonia can occur in patients with thymoma, alone or in association with myasthenia gravis (MG), but the clinic-prognostic significance of such comorbidity is largely unknown. We investigated clinic-pathologic features, along with the occurrence of neuromyotonia as predictors of tumor recurrence in patients with thymoma-associated myasthenia.
METHODS: We retrospectively studied 268 patients with thymomatous MG. Patients with symptoms of spontaneous muscle overactivity were selected for autoantibody testing using immunohistology for neuronal cell-surface proteins and cell-based assays for CASPR2, LGI1, Glycine receptor, and Netrin-1 receptors antibodies. Neuromyotonia was diagnosed according to the presence of typical electromyography (EMG) abnormalities and/or autoantibodies against LGI1/CASPR2.
RESULTS: Overall, 33/268 (12%) MG patients had a thymoma recurrence. Five/268 (2%) had neuromyotonia, 4 with typical autoantibodies, including LGI1 (n=1), CASPR2 (n=1), or both (n=2). Three patients had Netrin-1 receptors antibodies, 2 with neuromyotonia and concomitant CASPR+LGI1 antibodies, and 1 with spontaneous muscle overactivity without EMG evidence of neuromyotonia. Thymoma recurrence was more frequent in those with (4/5, 80%) than 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, CI:4.71-370.58).
CONCLUSIONS: De novo occurrence of neuromyotonia in MG patients with previous thymomas is a rare event and may herald tumor recurrence. Neuronal autoantibodies can be helpful to assess the diagnosis. These observations provide pragmatic risk stratification for tumour vigilance in patients with thymomatous MG. This article is protected by copyright. All rights reserved.