Myasthenia gravis
Myasthenia gravis is an autoimmune disease characterized by the production of antibodies, which are directed against nicotinic acetylcholine postsynaptic receptors located at the neuromuscular junction. This leads to a gradual decrease in the number of acetylcholine receptors at the postsynaptic neuromuscular junction. There are two different variants of myasthenia gravis, which include the ocular myasthenia gravis and the generalized form of myasthenia gravis. The result of the reduction in the number of acetylcholine receptors lead to a concomitant reduction in the muscle strength (Paul, 2000). However, there is recovery of the muscle strength resting it for some time (Kulkantrakon & Jarungkiatkul, 2010), (Paul, 2000). Most commonly and severely affected are the bulbar muscles. However, some patients also have some form of generalized weakness. (Goldenberg, 2012)
. In myasthenia gravis, antibodies (Immunoglobulin G [IgG]) are developed against acetylcholine postsynaptic receptors at the neuromuscular junction of skeletal muscles. The reason for this is unknown. However, genetics have been implicated as certain genotypes are predisposed to this disorder. (Goldenberg, 2012)
The basic pathology is the gradual reduction in the amount of acetylcholine released by the presynaptic motor neurons with each propagated nerve impulse. This has been rightly termed the presynaptic rundown. In addition, as earlier stated, there is a reduction in the number of acetylcholine receptors available at the motor end plate of the muscle leading to flattening of the space that constitutes the motor end plate. This also leads to generation of fewer motor end-plate potentials even if normal amount of acetylcholine is produced and released by the presynaptic terminals. The overall effect of this is a largely inefficient neuromuscular transmission. The clinical manifestation of fatigability seen in myasthenia gravis seen in patients is because of these pathologies (Myasthenia Gravis Foundation, 2012). Generally, the patient begins to manifest clinical signs of myasthenia gravis when the number of acetylcholine receptors has been depleted to up to 30% of the usual number. It is also imperative to state that cardiomyocytes and smooth muscles do not seem to be affected by myasthenia gravis because of the different antigenicity of these types of muscles, which is different from that of skeletal muscles. The immunoglobulin-mediated destruction of the acetylcholine receptors are also complement mediated. The idea that immunogenic mechanisms are important in the development of myasthenia gravis is corroborated by the presence of other autoimmune diseases in patients with myasthenia gravis. They include systemic lupus erythematous, rheumatoid arthritis and autoimmune thyroiditis. Infants of mothers that have myasthenia gravis also transiently develop a syndrome similar to myasthenia gravis. Anti-acetylcholine receptor antibodies are also found in most patients with myasthenia gravis.
Myasthenia gravis is idiopathic in majority of patients. However, it has been confirmed that there is a derangement in immune system regulation. However, some patients do not possess anti-acetylcholine antibodies. In these patients, antibodies against muscle specific kinase have been demonstrated. Some drugs have been shown to induce or even worsen the condition. They include some antibiotics like erythromycin, ampicillin, polymyxins, ciprofloxacin, aminoglycosides to mention just a few.
Penicillamine has been shown to induce myasthenia gravis. However, discontinuation of the drug leads to complete remission with a reduction in the elevated acetylcholine receptor antibody titer in the course of the disease. Some other drugs include beta-blockers like oxprenolol and propanolol. Other drugs that have been implicated include chloroquine, prednisone, procainamide, verapamil which is a calcium channel blocker, quinidine, magnesium and lithium. Neuromuscular blockers like curare, vercuronium and pancurorium should be used with caution in patients with myasthenia gravis so that they do not cause prolonged neuromuscular blockade (Paul et al, 2001).
References
RH Paul et al (2001). “Quality of life and well-being of patients with myasthenia gravis”. Muscle Nerve. 2002 Mar: 25:466-7. Accessed on 24th February 2012 from
Myasthenia Gravis Foundation (2012). “Living with Myasthenia Gravis”. Myasthenia gravis Foundation of Illinois.
William, Goldenberg (2012). “Myasthenia Gravis”. Medscape Reference. Accessed on 24th February 2012 from
RH Paul et al (2000).”Fatigue and Its Impact on Patients with Myasthenia Gravis”. Muscle Nerve 200 sept; 23(9):1402-6 Accessed on 24th February 2012 from
Kongkiat Kulkantrakon and Wiwat Jarungkiatkul (2010). Quality of life of Myasthenia Gravis Patients. J Med Assoc Thai 2010 93(10): 1167-71 accessed on 24th February 2012 from
