Concurrence of autoimmune diseases has always been a field of interest in medicine. The discovery of a common pathway in the pathogenesis of related autoimmune diseases can guide future therapies and assist in disease mitigation. The frequency of MG along with MS and NMO is higher than the prevalence of MG in the general population based on the results of this paper and another report(12). It seems that this is not a mere coincidence, and strengthens the hypothesis that common immunopathologic mechanisms may exist.
Although there are different pathological mechanisms in MS and MG, immunologic similarities exist. Studies suggest that regulatory T cells (Treg) may have a lower suppressive function which on the one hand leads to increased pro-inflammatory cytokines such as IL-6, IL-17, IFN-g, and proliferation of antibody producing B cells, on the other. Although antibody damage to neuromuscular junction is evident, the presence of specific antibodies in the pathogenesis of MS has not been unveiled, still. However, the role of rituximab in the treatment of MS implies the role of B cells in MS.(13) In a study, decreased expression of CD72, a B cell regulatory molecule, further highlighting the importance of B cells in the pathogenesis of the two diseases. (14)
The thymus, which is the origin of T cells, is a key organ in the pathogenesis of MG. Thymectomy is a notable treatment option in patients with MG but is not a typical therapy for MS patients. However, in our population, MS attacks were either none or very few after thymectomy of patients with MG and MS. Unlike patients with concurrent MS and MG, thymectomy is proposed to be a trigger of NMO in MG patients.(15)
Matrix metalloproteinases (MMPs) also have pathogenic roles in the central nervous system diseases. MMPs 3 and 9 are common MMPs that are elevated in MG and MS relapses.
On the other hand, granulocyte-macrophage colony-stimulating-factor (GM-CSF) are pathogenic in the context of MS, whereas they have protective effects in patients with MG.(16)
Midaglia et al.(17) reported an interesting case of a 24-year-old female with MS who was being treated with alemtuzumab and subsequently developed MG. Gharagozli et al.(18) also reported a case of an interferon-beta 1b treated MS patient who developed MG later on. There is also a report of a patient with PPMS who subsequently developed MG. Similar to one of our cases with PPMS and MG, the clinical course was unfavorable with an EDSS score of 7.0. (19)
Several cases of concurrent NMO and MG have been reported suggesting a common immunopathological mechanism in the two diseases. However, the altered immune response caused by thymectomy or immunosuppressive drugs used in MG have also been put forward as triggers of NMO in MG patients. (20)
The complement system is remarkably involved in the pathogenesis of NMOSD and MG, which may be the underlying mechanism for their concurrent presentation.(21) Both MG and NMOSD are mediated by IgG1 antibodies against distinct proteins, therefore, common immunological pathways may be involved in the two diseases considering the fact that the concurrence of NMOSD and MG is relatively higher in the general population than each of the diseases alone.(22) In AChR positive MG, similar to NMO, IgG1 and IgG3 antibodies are the main pathogenic antibodies that can lead to complement activation and ultimately, complement dependent cytotoxicity. (23) In a unique study Mizrachi et al.(24) injected NMO immunoglobulins and AQP4 peptide into mice with experimental autoimmune MG (EAMG) which caused increased muscle weakness and exacerbation of EAMG.
Castro-Suarez et al.(22) reported two cases of MG who developed NMOSD later on. A 57-year-old woman developed bilateral vision loss while being treated for MG, and a 26-year-old female with tingling sensations in her upper extremities, but was not being treated for MG, although diagnosed. The latter patient underwent thymectomy at age 30 with resolution of myasthenia symptoms, and without any NMO exacerbations. Both patients were able to carry out their daily tasks independently on follow up. Akiyuki et al.(20) reported two cases of MG followed by NMO, both of which had undergone thymectomy prior to NMO diagnosis. Bates et al. (25) reported a case of a 54 year old male who was diagnosed with AQP4 and anti-MOG + NMOSD 15 years after the diagnosis of AChR positive MG and 5 years after thymectomy. This is consistent with the study that retrospectively showed that in almost 80 % of patients with concurrent NMO and MG, thymectomy preceded the diagnosis of NMO. (15) However, there is also a report of concurrent MG and NMO without thymectomy. (26)
When a patient is diagnosed with a primary CNS disease, the diagnosis of the second disease may become difficult. Based on previous studies, MG can present in patients with either NMO or MS, however, diagnosis of MG usually precedes MS, unlike NMOSD which is mainly diagnosed after MG or thymectomy.(27,28) In our study two patients with NMOSD and MG had undergone thymectomy, both of which NMOSD presented after thymectomy.