Methotrexate Use in Generalized Autoimmune Myasthenia Gravis: A Case series

Methotrexate (MTX) is an inexpensive and well-tolerated immunosuppressive medication that is used anecdotally in autoimmune myasthenia gravis (MG). However, the efficacy in MG is unclear at this time. This retrospective analysis describes six patients with acetylcholine receptor antibody positive MG who were treated with MTX and corticosteroids. The efficacy of MTX was measured by steroid-sparing effect and the Myasthenia Gravis Foundation of America (MGFA) classification. MTX initiation was associated with a reduction in prednisone dosage in all patients. Minimal manifestation status was reached at an average duration of 10 months in 5 patients. No patients were hospitalized for myasthenia gravis exacerbations. There were no major side effects experienced with MTX use. This retrospective analysis suggests that MTX is safe and probably efficacious as a corticosteroid-sparing agent in the management of MG.

Bulbar-Predominant Weakness

A 61-year-old man sought care for recurrent episodes of dysarthria for about 1 year. This symptom was more common after prolonged speaking. Six months before his evaluation he had significant slurring of his speech after talking for 3½ hours at work about a new project. This led to emergency evaluation and his symptoms were thought to represent a transient ischemic attack; he started aspirin and a statin. The episodes continued to recur. He also experienced intermittent binocular double vision, which did not improve with new eyeglasses, and a sensation that chewing and swallowing was more effortful. He noted that his arms and legs felt “heavy” at times. All these symptoms tended to occur later in the day or after exertion. Neurologic examination was remarkable for binocular double vision with prolonged gaze upward or to the far right. He could squat and rise 5 times but with difficulty by the 5th attempt. The patient’s symptoms suggested myasthenia gravis. The differential diagnosis for autoimmune myasthenia gravis, particularly with prominent ocular and facial muscle involvement, can include central nervous system disorders, motor neuron disease, and myopathy. Serologic evaluation showed positivity for acetylcholine receptor-binding antibody and acetylcholine receptor-modulating antibody. Striated muscle antibody was also positive. Thiopurine S-methyltransferase activity was low. Repetitive stimulation studies showed a decrement in the right facial nerve, which partially improved after exercise. Routine needle examination showed motor unit variation in the right orbicularis oculi. Single-fiber electromyography showed increased jitter in the right orbicularis oculi. Chest computed tomography showed scattered tiny pulmonary nodules but no evidence of thymoma or other neoplasm. The clinical diagnosis was autoimmune generalized myasthenia gravis, seropositive for acetylcholine receptor antibody, without evident thymoma or other neoplasm. The patient was initially treated with oral pyridostigmine with some symptomatic benefit. Oral prednisone was then initiated; symptoms resolved when the dose was titrated. Calcium and vitamin D supplements, as well as Pneumocystis prophylactic therapy, were initiated concurrently. Mycophenolate mofetil was added as a steroid-sparing agent. On thoracic surgery consultation, thymectomy was recommended. Autoimmune myasthenia gravis is a disorder of impaired neuromuscular transmission caused by immunoglobulin G-mediated attack on a critical component of the acetylcholine receptor signaling complex in the muscle’s postsynaptic membrane. The most commonly identified antibodies, target the nicotinic acetylcholine receptor.

Diabetes mellitus exacerbates experimental autoimmune myasthenia gravis via modulating both adaptive and innate immunity

Background Diabetes mellitus (DM) is a common concomitant disease of late-onset myasthenia gravis (MG). However, the impacts of DM on the progression of late-onset MG were unclear. Methods In this study, we examined the immune response in experimental autoimmune myasthenia gravis (EAMG) rats with DM or not. The phenotype and function of the spleen and lymph nodes were determined by flow cytometry. The serum antibodies, Tfh cells, and germinal center B cells were determined by ELISA and flow cytometry. The roles of advanced glycation end products (AGEs) in regulating Tfh cells were further explored in vitro by co-culture assays. Results Our results indicated clinical scores of EAMG rats were worse in diabetes rats compared to control, which was due to the increased production of anti-R97–116 antibody and antibody-secreting cells. Furthermore, diabetes induced a significant upregulation of Tfh cells and the subtypes of Tfh1 and Tfh17 cells to provide assistance for antibody production. The total percentages of B cells were increased with an activated statue of improved expression of costimulatory molecules CD80 and CD86. We found CD4+ T-cell differentiation was shifted from Treg cells towards Th1/Th17 in the DM+EAMG group compared to the EAMG group. In addition, in innate immunity, diabetic EAMG rats displayed more CXCR5 expression on NK cells. However, the expression of CXCR5 on NKT cells was down-regulated with the increased percentages of NKT cells in the DM+EAMG group. Ex vivo studies further indicated that Tfh cells were upregulated by AGEs instead of hyperglycemia. The upregulation was mediated by the existence of B cells, the mechanism of which might be attributed the elevated molecule CD40 on B cells. Conclusions Diabetes promoted both adaptive and innate immunity and exacerbated clinical symptoms in EAMG rats. Considering the effect of diabetes, therapy in reducing blood glucose levels in MG patients might improve clinical efficacy through suppressing the both innate and adaptive immune responses. Additional studies are needed to confirm the effect of glucose or AGEs reduction to seek treatment for MG.

Diagnosis of Myasthenia Gravis

The diagnosis of autoimmune Myasthenia Gravis (MG) remains clinical and rests on the history and physical findings of fatigable, fluctuating muscle weakness in a specific distribution. Ancillary bedside tests and laboratory methods help confirm the synaptic disorder, define its type and severity, classify MG according to the causative antibodies, and assess the effect of treatment objectively. We present an update on the tests used in the diagnosis and follow-up of MG and the suggested approach for their application.