Clinical study of immunological and electrophysiological profile of patients with myasthenia gravis at a super-speciality hospital

 

 

Abstract              Background: Myasthenia gravis (MG) is an autoimmune disorder in which antibodies bind to acetylcholine receptors or related molecules in the postsynaptic membrane at the neuromuscular junction. The diagnosis of myasthenia gravis is confirmed by the combination of history and physical signs and a positive test for specific autoantibodies with supportive evidence of electrophysiological studies. Present study was aimed to study immunological and electrophysiological profile of patients with myasthenia gravis at a superspeciality hospital. Material and Methods: The present study was single-center, prospective observational study, conducted in patients >18 years of age, either gender with Diagnosis of myasthenia gravis. Results: A total of 77 Myasthenia patients from 26-86 years of age were observed during the study. Mean age of study population was 54.8 years. 48 (62.3%) are males and females contribute 29 (37.7%) patients. Ocular onset presentation was noted in 68 (88.3%) patients. Most common clinical feature was Ptosis (96.1%), dysphagia (49.3%) and diplopia (44.1%). AChR positive was observed in 70(90.9%), MuSK positive was observed in 2 (2.6%) patients. Myasthenic Crisis was observed in 15(19.5%) patients, most common cause of crisis was Infection in 6(40%). 2 (13.3%) patients of myasthenia crisis were managed with non-invasive mode of ventilation and rest of patients required invasive mode of ventilation. Among the patients with myasthenic crisis 14(93.7%) of them recovered and One mortality was noted. Conclusion: Most common mode of onset of presentation was ocular, most common clinical feature was ptosis in our study. AChR antibodies were positive in nearly 91% of the patients in our study. RNS was positive in 84% of the patients.

Keywords: myasthenia gravis, ptosis, AChR antibodies, thymoma

 

INTRODUCTION

Myasthenia gravis (MG) is an autoimmune disorder in which antibodies bind to acetylcholine receptors or related molecules in the postsynaptic membrane at the neuromuscular junction. The antibodies induce weakness of skeletal muscles, which is the sole disease manifestation of MG.^1,2,3 With an annual incidence of 8 to 10 cases per 1 million people and with a prevalence of 150 to 250 cases per 1 million.⁴ Myasthenia gravis is the major diseases that affect the neuromuscular junction. The Lambert– Eaton myasthenic syndrome and neuromyotonia are other rare NMJ disorders which are presynaptic autoantibody disorders characterized by skeletal-muscle dysfunction.⁵ Congenital myasthenic syndromes and toxin-induced conditions (e.g., botulism) can also affect the neuromuscular junction and leads to muscle weakness. The diagnosis of myasthenia gravis is confirmed by the combination of history and physical signs and a positive test for specific autoantibodies with supportive evidence of electrophysiological studies.⁶ The primary goals of the treatment of patients with MG is to improve symptoms and to prevent generalization in case of focal onset of MG. First-line symptomatic treatment is with acetylcholinesterase (AChE) inhibitors, with pyridostigmine being the most widely used drug.⁷ AChE inhibitors alone are frequently insufficient, and oral corticosteroids are required in most cases to improve the symptoms. Steroid-sparing drugs, such as azathioprine, Mycophenolate mofetil, cyclosporine and methotrexate are also treatment options to alleviate the symptoms and/or reduce corticosteroids use.⁸ Present study was aimed to study immunological and electrophysiological profile of patients with myasthenia gravis at a superspeciality hospital.

              

MATERIAL AND METHODS

The present study was single-center, prospective observational study, conducted at Department of Neurology, Sri Ramachandra Medical College And Research Institute, Chennai. Study duration was of 2 years (January 2017 to December 2018)

INCLUSION CRITERIA: Patients >18 years of age, either gender with Diagnosis of myasthenia gravis.

EXCLUSION CRITERIA: Patients with less than 18 yrs. of age. Patients with congenital, steroid and inflammatory myopathies and stroke. Patients with history of exposure to toxins like botulin, organophosphates, black widow spider venom and snake venom. Patients not willing to be included in the study

Once identified as a study participant, based on the inclusion and exclusion criteria, a detailed history of every patient was taken after obtaining a written consent. They were then subjected to a detailed clinical examination and the observations were carefully noted. Then Classified into subgroups of Myasthenia and then subjected into AChR Antibodies by RIA if negative then subjected to MuSK Antibodies. Repetitive nerve stimulation is done in Orbicularis Oculi, Nasalis, Abductor pollicis brevis, Abductor digiti minimi where 10% decremental response is considered diagnosis and less than !0% is normal. CT Thorax is done for Thymoma. Outcome measures that were noted for patients were patients with Subgroups of MG, clinical and Electrophysiological profile of patients, clinical profile of patients with Myasthenic crisis and outcome of patients. The analysis was done using Microsoft Office Excel 2013. Statistical analysis was done using descriptive statistics. The quantitative data was represented as their mean ± SD. Categorical and nominal data is expressed in proportions and percentage.

DISCUSSION

Myasthenia gravis presentation can be at any age from infancy to very old age. Epidemiological studies report considerable variability in incidence and prevalence around the world While methodological differences may explain some of this variability, biological and genetic factors may also play a role.⁹ Epidemiological studies done so far showed an increasing prevalence over the past 50 years, related to an increase in the frequency of diagnosis in elderly patients, but also likely due to improved ascertainment, reduced mortality rates and an increased longevity of the population. Most of the epidemiology studies are hospital based and there are no many populations-based studies. Reported annual incidence has gradually increased from 1.4-9.1 per million in the1950s-80s to 31-39 until 24.9 per million in 2012. This increasing trend is particularly profound in the elderly due to prolongation of life expectancy. Consequently, over the past six decades, MG prevalence has risen from less than 30 per million to over 300 per million in 2014.^10,11 In present study, myasthenia was seen predominantly among males, comprising of 48 males (62.3%) and 29 females (37.7%). B S Singhal et al.,¹² study reported 73% were males and Hamid Suhail et al.,¹³ has reported around 64.4% were males in his study. But there are studies done by Aline Mansueto et al.,¹⁴ and Y Sadri et al.,¹⁵ studies who have reported myasthenia was more common in female patients. In B S Singhal et al.,¹² mean age of patients was 48 years, with male patients showing mean age of 53 and female patients of 34 years. In Y Sadri et al.,¹⁵ mean age is 47.3 years where male is 54.1 and female is 42.3. Our study and the above-mentioned studies have shown a clear trend that myasthenia tends to occur earlier in females compared to males. In our study peak age of onset for males is in 7^th decade whereas the peak age of onset for females is in 4^th decade. These findings are similar to findings reported by BS Singhal et al.,¹² and Y Sadri et al.,¹⁵ Onset of presentation in our study, Ocular onset is present in 88.3% patients, Bulbar onset in 9.1% patients and Limb onset in 2.6% patients. According Grob B et al.,¹⁶ have more than 2/3^rd had ocular presentation, 1/6^th patients had Bulbar presentation and 1/10^th had limb onset weakness. Our study showed similar results to Rajeev Ojha et al.,¹⁷ study with respect to Ptosis, dysphagia, Dysarthria and limb weakness but differs with respect to Diplopia who have reported diplopia is seen among 87% patients. Our study had concurrent results to Y Sadri et al.,¹⁵ with respect to Diplopia, Dysarthria and limb weakness but his study has shown lower incidence of ptosis and dysphagia compared to our study. In our study, Serology was found to be AChR positive in 90.9% patients, MuSK positive in 2.6% patients and Both negative in 6.5% patients. This finding is similar to results found in B S Singhal et al.,¹² Aline Mansueto et al.,¹⁴ and Y Sadri et al.,¹⁵ studies. CT Thorax in our study showed presence of Thymoma in 6.5% patients similar to Aline Mansueto et al.,¹⁴ and Y Sadri et al.,¹⁵ studies. Indian studies like B S Singhal et al.,¹² and Suhail Hamid et al.,¹³ have reported Thymoma in more than 20% patients. In our study Myasthenic Crisis is seen in 19.5% patients which is similar to J M K Murthy et al.,¹⁸ study. In our study, first presentation as Myasthenia Crisis before diagnosis of Myasthenia in 13.3% patients. Most common Precipitating factor of Crisis in our study is infection in 40%, High dose of steroids, Non-Compliance and Unknown Cause are 13.3% each, Hypokalemia, Post-Thymectomy and Drug induced are present in 6.66% each patient. As in JMK murthy et al.,¹⁸ and S Panda.,¹⁹ study where Infection is most common cause. In our study, Treatment of Crisis is IVIg in 86.66%, Plasmapheresis in 6.66% and Both in 6.66%. In Sudhir Sharma et al.,²⁰ JMK Murthy et al.,¹⁸ and S Panda et al.,¹⁹ studies where Plasmapheresis is more commonly preferred. Mean duration of ICU stay was 14.5 days and mean duration of hospitalisation was 18 days, similar findings were noted by Sudhir Sharma et al.,²⁰ JMK Murthy et al.,¹⁸ and S Panda et al.,¹⁹ In present study, recovery occurred in 93.7% patients which is similar to S Panda et al.,¹⁹ which has recovery in 91%. Present study findings differs with Sudhir Sharma et al.,²⁰ study where recovery was 70%. Respiratory infection being common precipitating factor for MC, early institution of antibiotic therapy and Prophylactic vaccination were recommended in patients with MG. Multi-Disciplinary approach such as symptomatic, immuneactive and supportive approaches to therapy have a very good effect on muscle strength, functional abilities, quality of life, and survival. Therapy should be aimed at full or nearly full pharmacologic remission.

Limitations of present study were small sample size, patients underwent a single clinical assessment and there is no long term follow up, newer antibodies or thymic antibodies were not tested and thymectomy was not done in normal or atrophied thymus in our study. We recommend larger, population-based studies for further knowledge of myasthenia gravis.

 

CONCLUSION

There was a single peak of age at onset in both males and females: in males in the seventh decade and in females in the fourth decade. Most common mode of onset of presentation is ocular onset. Most common clinical feature is ptosis in our study. AChR antibodies were positive in nearly 91% of the patients in our study. RNS was positive in 84% of the patients. It is prudent to exercise great care while withdrawing or introduction of steroids. Similar care is also necessary while introducing steroids in patients with MG.

 

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