Outcomes and characteristics of myasthenia gravis: A 10-year retrospective cross-sectional study at King Fahad Medical City

Discussion

The present study included 147 patients with MG. There were more female patients than male patients, and they were significantly younger than the male patients. Our results were in accordance with previous studies conducted in the same region.^4,6,16 Although MG has traditionally been considered a disease of young women (under 40 years of age), in recent years, its incidence has increased in both sexes with age.¹⁷ Currently, patients are classified into 2 groups according to the age of onset, i.e., early-onset MG (onset before 50 years) and late-onset MG (onset after 50 years).^18,19 Early-onset MG is more common in women, whereas late-onset MG is slightly more common in men.²⁰ A recent study reported that in men, MG occurs more frequently in the elderly population. In contrast, it usually occurs at a younger age in female patients.²¹

The most common weakness that the patients presented with was ocular weakness, followed by bulbar weakness. Generalized weakness was the least common. A previous studies reported ocular presentation as the most common presentation of patients with MG,^4,5 and more than 80% of the patients reporting it at presentation.^4,22

Patients with ocular and bulbar presentations were significantly older than patients with generalized presentation. Similar results were reported by De Meel et al²² who found that compared to patients with neck, limb, or respiratory involvement, patients with ocular, or bulbar, presentation were older at the time of disease onset with a higher proportion of males. In another study, about one-third of MG patients below the age of 30 years reported limb weakness as the first presentation, while 15–20% of the patients complained of weakness in the arms, hands, or legs as the first presenting symptom.²³

Antibodies against AChR were the most frequently reported autoantibodies in the population, and are commonly associated with ocular and generalized presentation. In contrast, anti-MuSK antibodies were significantly associated with bulbar presentation. Previous studies have reported anti-AChR antibodies in about 71–85% of the patients with MG^{4,6,16,21,24,25}, and 54.7-68.2% of the patients with ocular MG.^6,16,25 In agreement with our results, Guptill et al.⁷ reported that anti-MuSK antibodies were present in 17% of the patients who presented with pure bulbar weakness, in 26% of the patients who presented with oculobulbar weakness, but only in 9%,²⁵ and 20.8%⁴ of the MG patients regardless of the type. We did not observe anti-MuSK antibodies in any of the patients with ocular presentation, which is consistent with the results of previous studies.^25,26

The most common treatment modality was pyridostigmine with prednisolone, with or without azathioprine, especially in patients with ocular presentation. A relatively large number of patients with bulbar presentation required additional IVIg or treatment with a more potent immunosuppressant. A recent study reported that pyridostigmine was the most prescribed medication for almost 94% of patients with MG, followed by glucocorticoids for 61.8% and azathioprine for 60.4% of the patients.⁴ A comparable results were reported also by Alanazy,⁶ in this study patients were divided into early onset MG and late onset MG, prednisolone was prescribed for 80% and 85% respectively while pyridostigmine was prescribed for 57.3% and 80% respectively. Heterogeneity in treatment response and outcome has been reported for different types of MG, depending on the clinical presentation, autoantibody status, and presence of comorbidities.²⁵ Regardless of the autoantibody status, treatment strategies are classified into symptomatic, immunosuppressive, and antibody-depleting therapies.²⁷ Pyridostigmine is the most common symptomatic treatment used.^28,29 However, compared to patients with anti-AChR antibody-associated MG, patients with anti-MuSK antibody-associated MG do not respond as well to pyridostigmine.^30,31 In MG, glucocorticosteroids and azathioprine are the first-line drugs for immunosuppression. Other immunosuppressive drugs such as cyclosporine, methotrexate, and mycophenolate mofetil can be used in case of contraindications, intolerance, or insufficient clinical response. The IVIg and plasmapheresis can also be used in certain situations.²⁷ Prednisone was used by 43.1% of patients in a recent study, followed by azathioprine (25%), mycophenolate mofetil (7.3%), methotrexate (1.3%), plasma exchange or IVIg treatment (14.7%), and rituximab (11.6%).²⁵

In the present study 36.1% of the patients had at least one exacerbation during follow up period, and 13.6% required ICU admission. Nearly the same frequency of exacerbation and ICU admission was reported by previous studies conducted in the same region.^4,6

Most patients with ocular and bulbar presentation developed generalized weakness during follow-up. It has been reported that about two-thirds of ocular MG patients progress to generalized disease within 2–3 years of disease onset.³² In contrast, only about 10-27.6% of the patients sustain purely ocular presentation.^{5,10, 25} The onset of ptosis or diplopia as an isolated symptom was predictive of early progression, in contrast to the concurrent development of ptosis and diplopia.³³

In this study patients with generalized and ocular presentation responded well to different medical treatment modalities. It has been reported that different MG phenotypes respond differently to various treatment modalities.^13,14,34 A randomized clinical trial found that patients with pure ocular MG did not respond as well to IVIg compared to those with generalized MG.³⁵ The role of IVIg in anti-MuSK MG is not known,³⁶ it had been reported that clinical improvement is more common with plasma exchange than IVIg,³⁷ other study suggested that IVIg treatment may be an effective therapeutic option for anti-MuSK antibody-positive MG, with a potentially long-term effect.³⁸ Over 70% of the patients with generalized MG and anti-AChR antibodies appeared to improve with treatment with acetylcholinesterase inhibitors such as pyridostigmine.³⁹ However, fewer than 33% of the patients with ocular MG^34,40 and anti-MuSK MG²⁸ appeared to benefit from the same treatment. Some patients with anti-MuSK antibodies respond negatively to acetylcholinesterase inhibitors and display deteriorating clinical symptoms, including worsening of weakness, frequent cramp, and fasciculations, and decreased therapeutic responsiveness to acetylcholinesterase inhibitors^37,41,42 which may indicate an abnormal sensitivity to cholinergic agents, which limits the use of acetylcholinesterase inhibitors in this group of patients.³¹ Almost 80% of the patients with generalized MG showed remission after immunosuppressive treatment, and a similar response was observed in ocular MG patients.⁴³ In the present study, anti-MuSK antibodies were not detected in any of the patients with ocular or generalized MG, which could explain the relatively good response of these patients to treatment, as compared with patients with bulbar presentation, for whom anti-MuSK antibodies were detected in 19.1% of the patients.

Although this study had the benefit of a 10-year follow-up period and provided information on treatment response, clinical course, and potential outcomes for each subcategory of MG patients, it was limited by the small number of patients because the neuromuscular unit was a newly developed unit in our institute. A larger investigation with a large number of patients with diverse subtypes of MG is recommended.

In conclusion, MG was found to be more frequent in young female patients. Ocular weakness was the most prevalent initial symptom. During the follow-up period, the majority of patients with ocular and bulbar presentation acquired widespread weakness. The AChR autoantibody was the most commonly reported autoantibody. At the end of the follow-up period, the majority of patients with generalized, ocular, and bulbar presentations had well-controlled weakness.