Myasthenia gravis overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Myasthenia gravis (literally "serious muscle-weakness"; from Greek μύς "muscle", Template:Polytonic "weakness", and Latin gravis "serious"; abbreviated MG) is a neuromuscular disease leading to fluctuating muscle weakness and fatiguability. It is an autoimmune disorder, in which weakness is caused by circulating antibodies that block acetylcholine receptors at the post-synaptic neuromuscular junction,[1] inhibiting the stimulative effect of the neurotransmitter acetylcholine. Myasthenia is treated medically with cholinesterase inhibitors or immunosuppressants and in selected cases with thymectomy. At 200-400 cases per million it is one of the less common autoimmune disorders.[1]
Historical Perspective
The first possible patient with Myasthenia gravis, Openchancanough was first described by Virginian Chroniclers in 1664. His symptoms included fatigue, heavy eyelids and weak muscle tone. In the late 1800s the name Myasthenia gravis was created and the classic symptoms of the disease were described. The autoimmune nature of this disease was first described by Simpson and Nastuck in 1959-1960. The first important step in treatment of MG occurred in 1934 by Marry Walker. She observed that the symptoms of patients with myasthenia gravis in similar to those with curare poisoning so their symptoms can improve by a cholinesterase inhibitor like physostigmine. In 1937 Blalock described an improvement in his patient after removal of the thymus and established thymectomy as one of the treatment options of MG. In 1970s the use of immunosuppressants, azathioprine and plasma exchange became more prevalent.
Classification
Myasthenia gravis may be classified into 4 sub types based on presence of autoantibodies: Pure ocular form, generalized form with anti-AChR antibodies, the forms without classical anti-AChR antibodies, neonatal MG, congenital.
Pathophysiology
Myasthenia gravis is a neuromuscular disease caused by an autoimmune reactions. The main problem in this disease is the abnormal transmission of nerve impulses to muscle fibers in NMJ. Genes involved in the pathogenesis of Myasthenia gravis include: The Major Histocompatibility Complex, the CHRNA1 Locus, the PTPN22 Gene, the FCGR2 Locus and the CTLA4 Locus.
Causes
Myasthenia gravis may be caused by thymus abnormalities, genetic and environment.
Differentiating Myasthenia Gravis from other Diseases
Differential diagnosis for Myasthenia gravis includes: Adult Botulism, infant Botulism, guillian-Barre syndrome, eaton lambert syndrome, electrolyte disturbance, organophosphate poisoning, tick paralysis, tetrodotoxin poisoning, stroke, poliomyelitis, transverse myelitis, neurosyphilis, muscular dystrophy, multiple sclerosis, amyotrophic lateral sclerosisand myositis.
Epidemiology and Demographics
The incidence of Myasthenia gravis is approximately 7-23 new cases per year. The prevalence of Myasthenia gravis is approximately 70-320 per million and increasing since 20th century. The age of onset in Myasthenia gravis follows a bimodal distribution. The early type (before age of 50) is female predominant and the late type (after age of 60) is male predominant. Between the age of 50-60 there is no significant different between male and female. Some studies demonstrated that the incidence, prevalence and the severity of this disease is higher in African/Americans.
Risk Factors
Common risk factors in the development of Myasthenia gravis are: Gender, Stress and other psychological factors.
Screening
There is insufficient evidence to recommend routine screening for Myasthenia gravis.
Natural History, Complications and Prognosis
Natural history: The age of onset before age of 50 is female predominant and after age of 60 is male predominant. Between the age of 50-60 there is no significant different between male and female. About 50 percent of patiens have ptosis and diplopia as their presenting sign. Complications: Complications from the treatment of myasthenia gravis such as: Glucocorticoids, azathioprine, cyclosporine, tacrolimus, cyclophosphamide, plasmapheresis, intravenous immune globulin and myasthenia crises (Respiratory failur) The prognosis of myasthenia gravis depends on: Disease duration at diagnosis, disease severity and the age of onset.
Diagnosis
History and Symptoms
History: Female Gender, african/Americans race, evidence of coexisting autoimmune diseases, a positive history of: Heavy eyelids and double vision , eye movement problems, Photophobia , facial weakness, tongue weakness, chewing and swallowing problems, respiratory problems, limbs muscles weakness, Fatigue and urinary incontinency. symptoms: Ptosis and diplopia, gaze paralysis, photophobia, facial weakness, orbicularis oculi weakness, tongue weakness (chewing problems and dysphagia), respiratory problems, limbs muscles weakness, fatigue and pelvic floor weakness.
Physical Examination
Physical examination of patients with myasthenia gravis is usually remarkable for: Downward lip corners and depress face, asymmetrical ptosis, incomplete eye closure, Cogan's lid twitch, peek sign, weakness of oropharyngeal muscles, respiratory muscle weakness, dropped head syndrome and proximal muscles weakness.
Laboratory Findings
Laboratory findings consistent with the diagnosis of myasthenia gravis include: Acetylcholine receptor antibodies, muSK antibodies, anti-striated muscle antibodies, antibodies to titin and other antibodies such as: antibody against LRP4 (which are IgG1)[1], cortactin (which help AChR clustering)[2], ryanodine receptor, myosin, alpha actin, rapsyn and gravin.
Electrocardiogram
There is controversy about ECG changes in MG. These changes are mostly non specific but the fact that they will regress after treatment of MG will rise this suspicion that MG causes these abnormalities. These abnormalities include arrhythmias (which can increase the risk of sudden cardiac death, Q-T prolongation, conduction disturbances and ST-T changes.
Chest X Ray
Chest X-ray scan may be helpful in the diagnosis mediastinal masses in myasthenia gravis such as thymic hyperplasia and thymoma.
CT
Findings on CT scan suggestive of MG are mostly thymic masses such as thymic hyperplasia and thymoma.
MRI
Magnetic resonance imaging (MRI) is also a more sensitive way to identify thymomas. In a case report done by Vasiliki Zouvelou and colleagues, based on MRI findings it was suggested that MG patients with anti-MuSK antibodies are more prone to have facial and bulbar muscle atrophy.
Echocardiography or Ultrasound
Some abnormalities has been reported in these patients. One of them is LV diastolic filling defects which improve with AChE inhibitors
Other Imaging Findings
Other Diagnostic Studies
Treatment
Surgery
The mainstay of surgical treatment of MG is thymectomy. Thymectomy means removing as much thymic tissue as possible. This treatment is done for patients with thymoma and even in patients without thymoma and who have generalized MG with AChR antibodies.
Medical Therapy
The mainstays of medical therapy for myasthenia gravis are: Symptomatic treatments (An oral anticholinesterase like pyridostigmine), chronic immunomodulating treatments (glucocorticoids and immunosuppressive drugs), rapid immunomodulating treatments (plasmapheresis and intravenous immune globulin).