Myasthenia Gravis (MG) is a neuromuscular disorder characterized by weakness and fatigability of skeletal muscles. Key Concept :- It is due to the decrease in the number of available acetylcholine receptors (AchRs) at neuromuscular junctions due to antibody mediated autoimmune attack.
Highest prevalence rate is 20.4 per 100,000 population.1 Prevalence of disease is increasing since 1950s. 2,3 Improved recognition High sensitivity & specificity of the test. Longer life-span due to effective treatment More people in the ‘at risk’ group due to increased life expectancy.
Currently, there are 60,000 patients with myasthenia gravis in Unites States.2 The incidence & prevalence increases substantially after the age of 55 years.4,5 The chances of “only ocular disease” increases after the age of 55 years.6 Atypical presentation :- Weakness in the distal extremity. Different immunological & electrophysiological findings. Prevalence 7% of patients.7
Autoimmune channelopathy Genetic predisposition: HLA B8 & DR3 DR1 specific for ocular myasthenia 75% patients have abnormality of thymus 10% have thymoma.
Autoantibodies against nicotinic acetylcholinrereceptors (nAchRs) These antibodies prevent binding of Ach to its receptors Other action: Destruction of receptors By complement activation Elimination by endocytosis
AchR antigenic peptide fragment+ TCR (T- Cell receptor) Activation of T-Helper cells B- cells converts to plasma cells Production of antibodies SYMPTOMS
Fluctuation weakness increasing trough the day & relieved by rest. Extra ocular muscle weakness Present in 50% of patients initially. Present in 90% of patients during the course of disease. Disease remains ocular in 16% of patients.
Usually affects one extra ocular muscle Ptosis Not limited by innervations of one cranial nerve Limited adduction of one eye with nystagmus of the abducting eye on attempted lateral gaze Diplopia common. Sclera below limbus may be visible due to weak lower eyelid.
Weakness of intercostal muscles and diaphragm may lead to CO2 retention Weakness of pharyngeal muscles may collapse the airway. O2 saturation can be normal while CO2 is retained. So, pulse oximetry is not reliable to detect the amount of paralysis.
Palatal muscle weakness Nasal voice Nasal regurgitation Swallowing may be difficult & regurgitation of foods can occur. Coughing & choking while drinking. Limb weakness can also be present Initially proximal but may follow distal muscles also.
Hyperthyroidism Weakness may not improve simply by treatment of patients with MG; with co-existing hyperthyroidism. Rheumatoid arthritis Scleroderma Lupus
NEONATAL: In 12% of the pregnancies with a mother with MG, she passes the antibodies to the infant through the placenta, causing neonatal myasthenia gravis. The symptoms will start in the first two days and disappear within a few weeks after birth. With the mother, it is not uncommon for the symptoms to even improve during pregnancy, but they might worsen after labor. CONGENITAL: Children of a healthy mother can, very rarely, develop myasthenic symptoms beginning at birth, congenital myasthenic syndrome or CMS. Other than myasthenia gravis, CMS is not caused by an autoimmune process, but due to synaptic malformation, which in turn is caused by genetic mutations. Thus, CMS is a hereditary disease. More than 11 different mutations have been identified, and the inheritance pattern is typically autosomal recessive. JUVENILE: myasthenia occurring in childhood, but after the peripartum period
Looking upwards & sidewards for 30 seconds For diplopia & ptosis Looking at the feet while lying on the back for 30 seconds Keeping arms stretched forward for 60 seconds Ten deep knee bends Wallking 30 steps on both the toes & heels “Peek Sign” – After initial apposition of lid margins, they quickly start to separate (in 30 seconds) & the sclera start to show.
Detection of acetylcholine receptor antibodies. Sensitivity of 80-96% 50% of patients with only ocular disease may lack in these antibodies In some cases, anti-MuSK protein antibodies. Antibodies against voltage-gated calcium channels to differenciate from Lambert-Eaton Myasthenic Syndrome (LEMS).
Forced Vital Capacity is monitored to detect any gradual loss of respiratory functions. Negative inspiratory force is useful to detect adequacy of ventilation.
To detect IgG antibodies against neuromuscular junction.
Class I: Any eye muscle weakness, possible ptosis, no other evidence of muscle weakness elsewhere Class II: Eye muscle weakness of any severity, mild weakness of other muscles Class IIa: Predominantly limb or axial muscles Class IIb: Predominantly bulbar and/or respiratory muscles Class III: Eye muscle weakness of any severity, moderate weakness of other muscles Class IIIa: Predominantly limb or axial muscles Class IIIb: Predominantly bulbar and/or respiratory muscles Class IV: Eye muscle weakness of any severity, severe weakness of other muscles Class IVa: Predominantly limb or axial muscles Class IVb: Predominantly bulbar and/or respiratory muscles (Can also include feeding tube without intubation) Class V: Intubation needed to maintain airway
Pyridostigmine Bromide - Starts in 30-60 mins & effect lasts 3-6 hours Caution for cholinergic crises.
Most commonly used corticosteroid in US Significant improvement is often seen after a decreased antibody titer which is usually 1-4 months No single dose regimen is accepted Some start low and go high Others start high dose to achieve a quicker response Clearance may be decreased by estrogens or digoxin Patients taking concurrent diuretics should be monitored for hypokalemia
Drugs that alter the immune response can be used. Commonly used drugs are Azathioprine Cyclosporine Mycophenolate
Plasmapheresis Filters out the antibodies from blood Effect lasts only for a few weeks. IV immuneglogulin Provides body with antibodies Binds to circulating antibodies.
Diet Thickened liquids are preferred, when dysphagia arises to counteract the fear of aspiration. Asparagus should be taken as it contains steroid-like substance. Activity Patients should be as active as possible but should take rest in between. Yoga exercises to stretch the weakened muscles should be done. This not only strengthens the muscles but also provides oxygen & removes carbon dioxide from them.
1. Isbister CM, Mackenzie PJ, Anderson D, et al. Co-occurrence of multiple sclerosis and myasthenia gravis in British Columbia: a population-based study [abstract]. Neurology 2002;58(suppl 3):A185-A1862. Phillips LH. The epidemiology of myasthenia gravis. Ann N Y Acad Sci 2003;998:407-4123. Phillips LH, Torner JC. Epidemiologic evidence for a changing natural history of myasthenia gravis. Neurology 1996;47:1233-12384. Kalb B, Matell G, Pirskanen R, Lambe M. Epidemiology of myasthenia gravis: a population-based study in Stockholm, Sweden. Neuroepidemiology 2002;21:221-2255. Phillips LH, Torner JC, Anderson MS, et al. The epidemiology of myasthenia gravis in central and western Virginia. Neurology 1992;42:1888-18936. Jaretzke A, Barohn RJ, Ernstoff RM, et al. Myasthenia gravis. Recommendations for clinical research standards. Neurology 2000;55:16-237. Werner P, Kiechl S, Löscher S, et al. Distal myasthenia gravis: frequency and clinical course in a large prospective series. Acta Neurol Scand 2003;108:209-210