Myasthenia Gravis–Associated Neuromyelitis Optica–Like Disease

Abstract

Background: Although overt involvement of the central nervous system (CNS) in myasthenia gravis (MG) is considered rare, hyperreflexia is a common and yet unexplained finding. Aquaporin 4 (AQP4), the target autoantigen in neuromyelitis optica, is expressed both in the CNS and in the neuromuscular junction.Objectives: To evaluate the prevalence of even mild CNS involvement in patients with MG and to identify features indicative of neuromyelitis optica-like disease.Design: Cohort study.Setting: Outpatient clinic.Patients: A cohort of 164 patients with MG. Methods:In 24 patients with MG, signs of CNS involvement were detected; 15 of these patients had at least 1 additional paraclinical indication of neuromyelitis opticalike disease (presence of antibodies against AQP4, pathological visual evoked potentials, or white matter lesions detected on brain and/or spinal magnetic resonance imaging scans) and fulfilled the inclusion and exclusion criteria for our study.Results: Of the 15 patients who had at least 1 additional paraclinical indication of neuromyelitis optica-like disease, 14 had abnormal visual evoked potentials, and in 6 of 9 patients in whom magnetic resonance imaging was performed, there was evidence of lesions in the white matter of the brain and/or spinal cord. Anti-AQP4 antibodies were detected in 7 patients (out of the 14 tested). Thymic enlargement (hyperplasia or thymoma) was more frequent in patients with MG who had signs of CNS involvement than in patients with MG who did not.Conclusions: The incidence of CNS involvement in MG is higher than previously reported and is expressed predominantly as a pyramidal syndrome accompanied by optical tract involvement (frequently subclinical). These features bear some resemblance to neuromyelitis optica spectrum disease, supported also by the presence of anti-AQP4 antibodies in 7 of the 14 patients tested. This association may represent a new nosological entity or may indicate that an autoimmune process targeting AQP4 is an integral part of the immunopathogenetic mechanisms in MG.

Immunopathogenesis in Myasthenia Gravis and Neuromyelitis Optica

“…In one study of 117 patients with NMOSD, comorbid MG was identified in 2% of patients, and AChR antibodies were detected in 11% of patients ( 160 ). In another study of 164 patients with MG, 10–15% of patients had CNS involvement resembling an NMO-like disease, half of whom exhibited AQP4-IgG ( 161 ). MG likely has a benign course, but CNS involvement is potentially more severe when accompanied by thymomas ( 159 , 161 ).…”

“…In another study of 164 patients with MG, 10–15% of patients had CNS involvement resembling an NMO-like disease, half of whom exhibited AQP4-IgG ( 161 ). MG likely has a benign course, but CNS involvement is potentially more severe when accompanied by thymomas ( 159 , 161 ). AChR antibodies and AQP4 antibodies may precede the onset of the relevant symptoms, and the titers of the two antibodies tend to be negatively correlated ( 159 ).…”

Regulatory T cells in multiple sclerosis and myasthenia gravis

“…In another study, MS preceded MG in five out of eight patients by 6 to 8 years [19]. Onset of MG in MS patients treated with interferon (IFN)-β and glatiramer acetate (GA) was reported in one [20], but not in another study [18]. Therefore, definitive evidence of co-morbidity between MS and MG requires further validation in large independent cohorts of patients.…”

“…Further, Tregs of these patients have numerous documented dysfunctionalities [1, 13, 27, 28]. T cells originate from the thymus, and evidence suggests the thymus as a key regulator in the pathogenesis MG, and less so in MS [18, 20, 29]. Thus, thymectomy is a treatment option from which few MS patients may benefit [30, 31].…”

Aquaporin and brain diseases

“…Regardless of the answer, the presence of anti-AQP4 IgG remains to be a powerful and useful differential diagnostic tool in the daily clinical practice [105]. However, several clinical observations have also reported patients with myasthenia gravis suffering from auto-AQP4-antibody positive serum as well [106–112]. This points out the possibility of a common autoimmune mechanism for both diseases; and further points to the involvement of AQP4 in the peripheral immune system as well.…”