Myasthenia gravis in current status: epidemiology, types, etiology, pathophysiology, symptoms, diagnostic tests, prevention, treatment, and complications – correspondence

Abstract

Dear Editor, Myasthenia gravis (MG) is a chronic autoimmune neuromuscular condition that causes skeletal muscle weakness. These muscles control respiration as well as the movement of various body parts, such as the arms and legs. The Latin and Greek origins of the term GM translate to ‘grave, or significant, muscle weakness.’ GM has no known cure; however, with modern treatments, the majority of cases are not as severe as the name suggests. People are frequently able to maintain a relatively high quality of life while controlling symptoms thanks to the treatments that are available. The majority of people with the disorder live a normal life1. According to estimates, there are between 5 and 30 cases of MG per million person-years, and there are between 10 and 20 cases per 100,000 people. The incidence and prevalence of MG in adults and children are distributed geographically equally, and the proportion of juvenile MG cases that begin before the age of 18 is close to 10%. Its prevalence has increased in recent decades as understanding, detection, and survival rates have improved; however, this rise has not been linear. The age of onset is bimodal, with an early peak in the second to third decades affecting young women and a late peak in the sixth to eighth decades affecting men2. The most prevalent form of this neuromuscular condition is autoimmune MG. Autoimmune MG could be: (1) Ocular – weakness in the muscles that control the eyes and eyelids. You might have trouble keeping your eyes open, or your eyelids might droop. Many people have double vision. MG frequently manifests firstly as eye weakness. Within 2 years of the onset of the first symptom, over half of those with ocular MG progress to the generalized variety. (2) Generalized – muscle weakness affects the throat, face, arms, legs, and neck in addition to the eye. Speaking, swallowing, lifting your arms above your head, standing up from a sitting position, walking vast distances, and climbing stairs may all be difficult for you3. There is no known cause of MG. The thymus gland also appears to occasionally have a role in the disease, and researchers speculate that viruses or bacteria may be the cause of the autoimmune reaction. In between 10% and 15% of those with MG, a thymoma, or thymic tumor, is present. The doctor will probably advise thymus resection, chemotherapy, and radiation treatment. However, 3–8% of MG patients had autoimmune thyroid disease. The initial evaluation should include a thyroid abnormality screening. The genetic vulnerability appears to play a role in MG and other autoimmune diseases, despite the fact that MG is not hereditary4. The number of antibodies attacking the postsynaptic neuromuscular junction’s (NMJ) acetylcholine (ACh) receptor sites is attacked, damaged, and eventually drops by about 66%. By blocking ACh receptors, causing complement-mediated membrane damage, and speeding up ACh breakdown, these antibodies lessen the impact of ACh on the NMJ. The presynaptic terminal releases a normal amount of ACh, but because there are fewer receptors, the endplate potentials at the NMJ may not be strong enough to induce an action potential. Due to transmission problems, the muscles weaken. The symptoms of this muscular weakness get better with rest, but they get worse with prolonged muscle action, increasing fatigability. Smaller quantities of ACh are typically released with each subsequent impulse during sustained muscle activity, although transmission is unaffected and muscular strength is preserved. With continued muscular activation in MG, less ACh is released, which further impairs the NMJ transmission. The electrophysiologic decline observed in MG5 and the muscle fatigability are both caused by this. Eyelid drooping and/or blurred or double vision may be the first symptoms you notice because the disease most frequently affects the muscles that control eye and eyelid movement. In 1 or 2 years, the majority will develop weakness in other muscular groups. GM symptoms include eye muscle weakness, drooping eyelids, shortness of breath, blurred vision, difficulty eating, double vision, change in facial expression, difficulty speaking, walking, and lifting objects, and difficulty holding your head up. A myasthenic crisis occurs when the breathing muscles become so weak that you are unable to control them. This is an urgent medical situation, and you could need a ventilator to help you breathe. A myasthenic crisis occurs in 15–20% of persons with GM. They may be brought on by an illness, stress, a surgical procedure, or a drug reaction6. (1) Blood test: The primary test for GM is a blood test to look for an immune system-produced antibody that interferes with communication between muscles and neurons. If you have a high level of these antibodies, you are likely to have GM. However, not all patients with the illness will have a high level of antibodies, especially if it mainly affects the eye muscles (ocular myasthenia). If the blood test’s outcome is normal but your symptoms persist or worsen, it could be necessary to repeat it later. (2) Nerve tests: The doctor may recommend an electrical test of your nerves and muscles if your blood test results are normal but you still may have GM. In order to monitor the electrical activity in your muscles during these tests, also known as electromyography, tiny needles are inserted into them. Typically, the needles are placed near the eyes, on the forehead, or maybe in the arms. Electrical recordings can reveal whether MG is present if there is a disruption in the signals that the nerves send to the muscles. (3) Scans: To determine if your thymus gland has developed incorrectly or excessively, you may also undergo a computed tomography scan or MRI of your chest (a thymoma). The immune system includes the thymus gland, a tiny gland in the chest. GM is directly related to issues with the gland. To be sure that a brain issue is not the source of your symptoms, an MRI brain scan may occasionally be performed. (4) Edrophonium test: If the source of your symptoms is still unclear, the doctor might advise an edrophonium test. It entails receiving an injection of the drug edrophonium chloride. After the injection, if your muscle strength suddenly but briefly improves, you most likely have GM. However, these days, it is uncommon to perform this test due to the possibility that it could result in potentially harmful side effects like a slowed heartbeat and breathing difficulties. Only when absolutely essential and in a hospital setting, where any side effects can be easily treated, is it performed7. MG cannot be stopped. However, a person can act to stop a symptom flare-up or stop consequences from occurring. These include maintaining good cleanliness to prevent infections and swiftly treating them when they do. Avoiding excessive heat and overexertion is also a good idea. The frequency and severity of symptoms can also be decreased with effective stress management8. Treatment options include (1) Medication – steroids, immunosuppressive medications, anticholinesterase medications, and anticholinesterase drugs may be administered. (2) Thymectomy – the thymus gland is surgically removed in this procedure. The thymectomy may or may not alleviate symptoms because the thymus gland’s function in GM is not completely known. But in more than 70% of those without thymic cancer, it lessens symptoms, maybe by changing how the immune system reacts. Plasmapheresis is a process that replenishes blood with normal antibodies from donor blood after removing aberrant antibodies from the blood. Immunoglobulin is a blood component that aids in reducing immune system assaults on the neurological system. It is administered intravenously9. GM complications can sometimes be fatal, but they can also be managed. (1) Myasthenic crisis: When the muscles that control breathing become too weak to function, myasthenic crisis, a potentially fatal condition, develops. Both emergency medical care and mechanical breathing assistance are required. People can regain independent breathing with the aid of medications and blood-filtering procedures. (2) Thymus gland tumors: The immune system-related thymus gland, located under the breastbone, has tumors in some GM patients. The majority of these thymomas, or tumors, are not cancerous (malignant). (3) Additional disorders: The following conditions are more prevalent in people with GM: (a) An under or hyperactive thyroid – located in the neck, the thyroid gland secretes hormones that control your metabolism. You may struggle with colds, weight gain, and other problems if your thyroid is underactive. In addition to other problems, an overactive thyroid can make it harder to handle the heat and induce weight loss. (b) Autoimmune disorders – people with GM may be more susceptible to autoimmune disorders like lupus or rheumatoid arthritis10. Here, we have covered the following topics: epidemiology, types, etiology, pathophysiology, symptoms, diagnostic procedures, prevention, treatment, and complications of GM. Ethical approval None. Sources of funding None. Authors’ contribution M.M.R.: conceptualization, writing – original draft preparation, and supervision; M.R.I.: writing and editing. All authors have reviewed and approved the final version of the manuscript prior to submission. Conflicts of interest disclosure The authors declare no conflicts of interest. Research registration unique identifying number (UIN) None. Guarantor I, Md. Mominur Rahman (corresponding author) take full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish. Data availability All data are available within the manuscript.

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