Myasthenia Gravis

Myasthenia Gravis



Definition of Myasthenia Gravis

Myasthenia gravis is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatigability. Myasthenia Gravis occurs in all races, both genders, and at any age. MG is not thought to be directly inherited nor is it contagious. It does occasionally occur in more than one member of the same family.

Cause of Myasthenia Gravis

Myasthenic cause is unknown. The disease is more common in women than in men. Most are found between the ages of 20-40. Causes and exacerbates disease, infectious diseases, and pregnancy include excessive physical strain. Miyastenili patients with central nervous system disorders found a significant structural investigations. However, adipose tissue is almost always replaced by muscle disorder, muscle fibers are seen.

Risk Factors for Myasthenia Gravis

More common in women than in men between 20 and 40 ages.

Signs and Symptoms of Myasthenia Gravis 

The hallmark of myasthenia gravis is fatigability. Muscles become progressively weaker during periods of activity and improve after periods of rest. Muscles that control eye and eyelid movement, facial expressions, chewing, talking, and swallowingare especially susceptible. The muscles that control breathing and neck and limb movements can also be affected. Often, the physical examination yields results within normal limits.

The onset of the disorder can be sudden. Often symptoms are intermittent. The diagnosis of myasthenia gravis may be delayed if the symptoms are subtle or variable.

In most cases, the first noticeable symptom is weakness of the eye muscles. In others, difficulty in swallowing and slurred speech may be the first signs. The degree of muscle weakness involved in MG varies greatly among patients, ranging from a localized form that is limited to eye muscles (ocular myasthenia), to a severe and generalized form in which many muscles – sometimes including those that control breathing – are affected. Symptoms, which vary in type and severity, may include asymmetrical ptosis (a drooping of one or both eyelids), diplopia (double vision) due to weakness of the muscles that control eye movements, an unstable or waddling gait, weakness in arms, hands, fingers, legs, and neck, a change in facial expression, dysphagia (difficulty in swallowing), shortness of breath and dysarthria (impaired speech, often nasal due to weakness of the velar muscles).

In myasthenic crisis a paralysis of the respiratory muscles occurs, necessitating assisted ventilation to sustain life. In patients whose respiratory muscles are already weak, crises may be triggered by infection, fever, an adverse reaction to medication, or emotional stress. Since the heart muscle is only regulated by the autonomic nervous system, it is generally unaffected by MG.

Diagnosis of Myasthenia Gravis

MG can be a difficult diagnosis, as the symptoms can be subtle and hard to distinguish from both normal variants and other neurological disorders. A thorough physical examination can reveal easy fatigability, with the weakness improving after rest and worsening again on repeat of the exertion testing. A good response to medication can also be considered a sign of autoimmune pathology.

Physical Examination

Muscle fatigability can be tested for many muscles. A thorough investigation includes:

  • looking upward and sidewards for 30 seconds: ptosis and diplopia
  • looking at the feet while lying on the back for 60 seconds
  • keeping the arms stretched forward for 60 seconds
  • ten deep knee bends
  • walking 30 steps on both the toes and the heels
  • five situps, lying down and sitting up completely
  • “Peek sign”: after complete initial apposition of the lid margins, they quickly (within 30 seconds) start to separate and the sclera starts to show

Blood Tests

If the diagnosis is suspected, serology can be performed in a blood test to identify certain antibodies:

  • One test is for antibodies against the acetylcholine receptor. The test has a reasonable sensitivity of 80–96%, but in MG limited to the eye muscles (ocular myasthenia) the sensitivity falls to 50% (negative in up to 50% who have MG).
  • A proportion of the patients without antibodies against the acetylcholine receptor have antibodies against the MuSK protein.
  • In specific situations (decreased reflexes which increase on facilitation, coexisting autonomic features, suspected presence of neoplasm, especially of the lung, presence of increment or facilitation on repetitive EMG testing) testing is performed for Lambert-Eaton syndrome, in which other antibodies (against a voltage-gated calcium channel) can be found.

Electrodiagnostics

Muscle fibers of patients with MG are easily fatigued, and thus do not respond as well as muscles in healthy individuals to repeated stimulation. By stimulating a nerve-muscle motor unit with short sequences of rapid, regular electrical impulses, before and after exercising the motor unit, the fatiguability of the muscle can be measured. This is called the repetitive nerve stimulation test. In single fiber electromyography (SFEMG), which is considered to be the most sensitive (although not the most specific) test for MG, a thin needle electrode is inserted into different areas of a particular muscle to record the action potentials from several samplings of different individual muscle fibers. Two muscle fibers belonging to the same motor unit are identified and the temporal variability in their firing patterns are measured. Frequency and proportion of particular abnormal action potential patterns, “jitter” and “blocking,” are diagnostic. Jitter refers to the abnormal variation in the time interval between action potentials of adjacent muscle fibers in the same motor unit. Blocking refers to the failure of nerve impulses to elicit action potentials in adjacent muscle fibers of the same motor unit.

Ice Test

Applying ice to weak muscle groups characteristically leads to improvement in strength of those muscles. Applying ice for 5 minutes to the muscles reportedly has a sensitivity and specificity of 76.9% and 98.3%, respectively, for the identification of MG. It is thought that acetylcholinesterase is inhibited at the lower temperature and that this is the basis for this diagnostic test.

 Imagin

A chest X-ray is frequently performed; it may point towards alternative diagnoses (e.g. Lambert-Eaton syndrome due to a lung tumor) and comorbidity. It may also identify widening of the mediastinum suggestive ofthymoma, but computed tomography (CT) or magnetic resonance imaging (MRI) are more sensitive ways to identify thymomas, and are generally done for this reason. MRI of the cranium and orbits may also be performed to exclude compressive and inflammatory lesions of the cranial nerves and ocular muscles.

Pulmonary Function Test

Spirometry (lung function testing) may be performed to assess respiratory function if there are concerns about breathing adequacy. The forced vital capacity may be monitored at intervals to detect increasing muscular weakness. Acutely, negative inspiratory force may be used to determine adequacy of ventilation. Severe myasthenia may cause respiratory failure due to exhaustion of the respiratory muscles.

Pathological Findings

Muscle biopsy is only performed if the diagnosis remains in doubt and clinical suspicion of MG persists. Immunofluorescence shows IgG antibodies on the neuromuscular junction. (The antibody which causes myasthenia gravis does not fluoresce, but rather a secondary antibody directed against it.) Muscle electron microscopy shows receptor infolding and loss of the tips of the folds, together with widening of the synaptic clefts. Both these techniques are currently used for research rather than diagnostically.

Prevention of Myasthenia Gravis

Myasthenia gravis cannot be prevented, but avoiding the following triggers may help patients prevent exacerbation:

  • Emotional stress
  • Exposure to extreme temperatures
  • Fever
  • Illness (e.g., respiratory infection, pneumonia, tooth abscess)
  • Low levels of potassium in the blood (hypokalemia; caused by diuretics, frequent vomiting)
  • Medications (e.g., muscle relaxants, anticonvulsants, certain antibiotics)
  • Overexertion

Treatment Of Myasthenia Gravis

 Derivative of cortisone in two days at the most common treatment prednisone 60-70 mg as a single dose is given. The first 7-10 days of treatment, rather worsen symptoms has been reported, patients are recommended to start the treatment in the hospital and possible breathing difficulties need to be monitored carefully.