Myasthenia Gravis – Causes And Symptoms
Myasthenia gravis is an autoimmune disease that affects 5 in 100,000 individuals and is more common in women, sex ratio being 2/1 for women. The disease has two peaks of incidence: between 20 and 30 years and a second peak between 50 and 70 years. Excepting congenital form, onset in adolescence is rare.
Myasthenia Gravis Causes
Myasthenia gravis is an immunologically mediated disease in which antibodies are directed against the acetylcholine receptor, causing disturbances in the functionality of acetylcholine receptors and in neuromuscular transmission, leading to muscle fatigue. Anti-acetylcholine antibodies are considered essential in the development of the disease.
Anti-acetylcholine antibodies levels are increased in 80% -90% of patients with myasthenia gravis, while 10% -20% of patients do not present elevated levels of these antibodies.
Increased levels of anti-acetylcholine antibodies are correlated with disease severity. The form of disease with ocular onset is correlated with low levels of these antibodies.
Anti-acetylcholine antibodies are highly specific for the disease and essential for diagnosis. Their biological significance is not fully known, but it is considered that they may not be the only causative factors of the disease, knowing that are absent in 10% of patients with myasthenia gravis and in 40% of patients with ocular form of the disease anti-acetylcholine antibodies are not present.
The mechanism by which anti-acetylcholine antibodies produce the disease is not fully known. In myasthenia gravis, there is a reduction in the number of acethilcholine receptors available at the muscle endplate and flattening of the postsynaptic folds. Due to this events, even if a normal amount of acethylcholine is released, fewer endplate potentials will be produced, being insufficient to generate an action potential. The result of this process is inefficient neuromuscular transmission, explaining the muscle fatigue seen in myasthenia gravis patients.
Myasthenia gravis symptoms appear when the number of acethlycoline receptors is reduced to approximately 30% of normal. Due to the fact that cholinergic receptors of cardiac muscle have a different antigenicity than skeletal muscle, cardiac symptoms are not specific for the disease.
The decrease in the number of acethylcoholine receptors is the result of an autoimmune process that produce anti-acthylcholine antibodies against this receptors, causing an increase turnover of actehylcholine receptors.
Stimulus for anti-acetylcholine antibodies formation is uncertain, but however, the thymus seems to have an important role because most patients with myasthenia gravis present a thymic abnormality in the form of thymoma or thymic hyperplasia. Thymoma is detected in 9% -16% of patients and between 47% -81% of patients have thymic hyperplasia.
Autoimmune mechanism of the disease is supported by the fact that myasthenia gravis is frequently associated with other autoimmune diseases such as rheumatoid arthritis, lupus, polymyositis and autoimmune thyroiditis.
Myasthenia Gravis Symptoms
Myasthenia gravis is a neuromuscular disorder characterized by excessive fatigue of skeletal muscle at normal physical activity. The characteristics of the disease are:
- Deficits restoration at rest;
- Diurnal fluctuation of symptoms;
- Affecting a certain muscle group;
- Evolution with intermittent remissions.
Muscle fatigue can become pseudo-paralytic, with transient paresis which improve at rest and anticholinesterase medication. The two important clinical aspects of myasthenia gravis are distribution and fluctuation character of muscle fatigue. Muscle fatigue is more pronounced in the second part of the day.
There are two clinical forms, cephalic or superior form and generalized form. In most cases, the disease begins at the cephalic muscles, especially in the eye muscles, and for 15% of patients symptoms are limited to this level (ocular myasthenia). Bulbar muscles is then affected and generally within about three years disease spreads to other muscle groups.
Onset is usually insidious over 4-6 months, with a slowly progressive symptomatology, that is affecting, over time, all muscle groups. There are forms of disease with rapid evolution, within a few days with respiratory failure, which occurs most often after a respiratory infection or psychological trauma. The disease can also debut in pregnancy.
Symptoms may be exaggerated after administration of certain drugs: nondepolarizing skeletal muscle relaxants, quinidine, procainamide, benzodiazepines, beta blockers, corticosteroids, etc..
Hypocalcemia, hypokalemia, hypothyroidism and hyperthyroidism can aggravate the symptoms.
Superior or cephalic form of myasthenia gravis
Ocular symptoms occur at onset in 50% of cases and in evolution are present in over 90% of patients. Most commonly occurs palpebral ptosis and diplopia. Palpebral ptosis is bilateral, unequal, alternate, asymmetric and is caused by upper eyelid levator muscle weakness. Diplopia and strabismus, with limited eye movements, are caused by extrinsic eye muscle weakness. Symptoms are more pronounced in the second part of the day.
Bulbar or facial form of myasthenia gravis
Facial muscles involved in chewing, swallowing and speaking are affected in 80% of cases. Approximately 60% of patients can not smile and thus appear myasthenic snarf, in which the upper lip rises vertical (horizontal laughter). Myasthenic facies is characterized by a tired expressions, poor gestures, with tight lips, half-closed eyes and the disappearance of physiological folds. Nasal twang to the voice and nasal regurgitation of food,especially liquids, appear due to palatal muscle weakness. Chewing may become difficult and severe jaw weakness may cause the jaw to hang open (the patient may support his chin with the hand ). Fluid aspiration may occur, causing coughing or choking while drinking. Tongue mobility disorders occur rarely and may cause the appearance of furcus myasthenicus (three longitudinal grooves on the tongue surface). Fasciculations are not characteristic for the disease.
Severe symptoms of bulbar form may announces, or sometimes may accompany, the appearance of myasthenic crisis.
Generalized form of myasthenia gravis
In generalized form, first are affected neck muscles, then in evolution are affected proximal limb muscles and finally back muscles. Muscle fatigue occur at a minor physical effort. Weakness is most often in proximal limb muscle, patient being unable to stand up from a chair and to raise his arms above his head. Over time, most affected muscles may suffer atrophies. In severe cases of myasthenia gravis, diaphragm and intercostal muscles may be affected.
Generally, pain is not characteristic for myasthenia gravis and if pain occurs is due to extreme muscle fatigue of neck, back and trunk muscles.
The evolution of the disease is different, depending on the affected muscles, severity of the disease and age of onset. The disease is often unpredictable, with remission, but there is the possibility of rapid decompensations, with the occurrence of acute respiratory failure. Decompensation of a patient with myasthenia gravis occurs due to infection, high temperature environment, surgery, trauma and stress. In the first years after onset, decompensations are more frequent.