Myasthenia Gravis and Lambert Eaton

Myasthenia gravis

Myasthenia gravis (literally "serious muscle-weakness") 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, inhibiting the stimulative effect of the neurotransmitter acetylcholine. Myasthenia is treated medically with cholinesterase inhibitors or immunosuppressants, and, in selected cases, thymectomy. At 200–400 cases per million it is one of the less common autoimmune disorders.

Signs and symptoms

Ptosis of the left eye.

The hallmark of myasthenia gravis is fatiguability. Muscles become progressively weaker during periods of activity and improve after periods of rest. Muscles that control eye and eyelid movement, facial expression, chewing, talking, and swallowing are especially susceptible. The muscles that control breathing and neck and limb movements can also be affected. Often the physical examination is within normal limits.^[3]

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, limited to eye muscles (ocular myasthenia), to a severe or 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, 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.^[4] Since the heart muscle is stimulated differently, it is never affected by MG.

Diagnosis

Myasthenia 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 fatiguability, with the weakness improving after rest and worsening again on repeat of the exertion testing. Applying ice to weak muscle groups characteristically leads to improvement in strength of those muscles. Additional tests are often performed, as mentioned below. Furthermore, 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
• 10 deep knee bends
• walking 30 steps on both the toes and the heels
• 5 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 test may be negative in up to 50% of the cases.

• 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, co-existing 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.

electromyography, which is considered to be the most sensitive (although not the most specific) test for MG

Edrophonium test

Tensilon test

Imaging

A chest CT-scan showing a thymoma (red circle).

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

Pulmonary function test

Restrictive pattern on spirometry

Associations

Myasthenia Gravis is associated with various autoimmune diseases, including:

• Thyroid diseases, including Hashimoto's thyroiditis and Graves' disease
• Diabetes mellitus type 1
• Rheumatoid arthritis
• Lupus, and
• Demyelinating CNS diseases