Commentary: Progressive Encephalomyelitis with Rigidity and Myoclonus and Myasthenia Gravis Comorbid Status with Thymoma.

Abstract

The short history of leg paraesthesia and falls without loss of consciousness is suggestive of an autoimmune brainstem disorder and fairly classical for progressive encephalomyelitis with rigidity and myoclonus (PERM), often with glycine receptor (GlyR) antibodies.1, 2 In keeping with this, the case video shows bouts of painful myoclonic spasms with trunk and leg extension and arm flexion that occur spontaneously and when attempting to stand or walk.1 There seems to be also intermittent leg stiffness. The lack of tone between spasms gives an unusual appearance of “bouncy legs.” The other remarkable aspect is the reported masseter weakness. Although ptosis, diplopia, dysarthria, and dysphagia are well-recognized signs in PERM, it is more typically trismus than masseter weakness that is associated with PERM. The latter points to an additional, peripheral component. PERM and myasthenia gravis (MG) symptoms, with or without MG-associated antibodies, have been reported.2 This is not surprising given that both MG and PERM have a strong association with thymomas. Another antibody associated with thymomas is anti-Contactin-associated protein-like 2 (Caspr2), and anti-Caspr2 Morvan syndrome and MG can co-occur in patients with thymoma or thymic hyperplasia.3 Caspr2 autoimmunity can cause leg myoclonus with a similar phenomenology as observed here4 but would not feature the axial extensor spasms. The present case of PERM (with anti-GlyR) and MG (with acetylcholine receptor and titin antibodies) illustrates that sometimes central and peripheral pathologies can co-occur, just as antibodies can co-occur. Co-occurrence of antibodies can give rise to a syndromic overlap and be attributed to an autoimmune predisposition (eg, glutamic acid decarboxylase (GAD) and GlyR antibodies) or be part of paraneoplastic autoimmunity, where it may help narrowing down the list of possibly underlying malignancies—in this case a thymoma. The case also exemplifies that, treated with thymectomy and immunotherapy, such patients have a good prognosis despite the potentially life-threatening complications of PERM and MG. (1) Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique. B.B.: 1A T.O.: 1B K.O.: 1B K.D.: 1B T.N.: 1B M.A.: 1B S.K.: 1B R.W.: 1B K.N.: 1B N.H.: 1B Y.O.: 1B O.B.: 1B The authors confirm that neither informed patient consent nor the approval of an institutional review board was necessary for this work. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. This work was supported by the Japan Society for the Promotion of Science KAKENHI (Grant 19K17047) and the Brain Mapping by Integrated Neurotechnology for Disease Studies (Brain/MINDS) Beyond Program from Japan Agency for Medical Research and Development (AMED) (Grant JP20dm0307024). B.B. and O.B. did not receive funding for this work and have no conflicts of interest to report. The authors declare that there are no disclosures to report.