Neurological Disorders: Myasthenia Gravis

What is it?

Myasthenia gravis (MG) is a type of neurological disorder, and results from a dysfunction in the neuromuscular junction (NMJ) region of the nervous system. This is the area where the electrical impulses from nerve fibers enter a muscle. A Neurologist is frequently involved in the care of MG patients.

This disease results in skeletal muscle weakness, usually in a fluctuating pattern, and in severe cases respiratory paralysis (breathing difficulties) and death may occur without proper medical intervention.

More on the basics of Myasthenia Gravis

As mentioned above the problem for MG patients lies in their NMJ. Skeletal muscles are also called as voluntary muscles, as their action is under our control e.g. biceps muscle; it is used for bending the elbow as per our desire. Just for the discussion purpose, there are two more types of muscles in our body, and they are not under our control and accordingly they are called as involuntary muscles; heart and smooth muscles like gastrointestinal muscles belong to this group.

MG affects the NMJ of only voluntary or skeletal muscles, so only their function is affected; heart and smooth muscles are spared.

For a voluntary muscle to perform, the command comes from the voluntary centers in the brain. These centers are located in the region called as motor cortex that is part of a larger area of the brain called as frontal lobe. The nerve impulses (electrical signals) generated there reach the skeletal muscles in this fashion; motor cortex → sub-cortical white matter → internal capsule → brain stem → spinal cord → motor spinal roots → peripheral nerve → NMJ →muscle → and results in the muscle movement.

The NMJ is also called as a synapse (a junction between two nerve fibers or a nerve fiber and a muscle fiber). It is divided into pre-synaptic, post-synaptic and in between areas. When the nerve impulse from the brain reaches the pre-synaptic area, certain ionic movement will take place and a chemical (neuro-chemical or neurotransmitter) by name Acetylcholine (Ach) is liberated from the pre-synaptic segment. Ach passes through the synapse and reaches the post synaptic area and attaches to structures called as Ach receptors. This attachment initiates certain ionic movements again, and results in the generation of an electric potential on the muscle cell membranes which then spreads throughout the muscle and effectuate a muscle contraction.

In Myasthenia Gravis; the pre-synaptic area, the quantity and quality of Ach liberated, are all normal, but the post synaptic area is defective. The Ach receptors in this area are damaged, mediated by certain antibodies in the body (see details below)

Myasthenia Gravis is an autoimmune disorder

Normally our immune system protects us by fighting against external dangers called as antigens (infective agents like bacteria, viruses, inflammatory agents etc). Antigens are generally outside substances, and antibodies are substances produced in the body to fight against the antigens and protect us.

But under certain circumstances the immune system, instead of attacking an external threat, paradoxically attacks our own body cells. This condition is called as autoimmune disorders, and MG is an example for it. In Myasthenia Gravis certain our own antibodies, instead of helping us mount a reaction against Ach receptors at the NMJ causing reduction in the number of these receptors. Due to this even though Ach is available the electrical signals arriving from the brain towards the muscles get blocked at NMJ area and this result in weakness of these muscles. Patients with MG have a higher incidence of other autoimmune disorders like thyroiditis, lupus, rheumatoid arthritis etc.

Certain medications like penicillamine also can cause MG like syndrome. This generally should resolve on stopping the offending agent.

Who gets Myasthenia Gravis?

MG can affect almost anybody and it doesn’t respect gender, age, race, ethnicity etc. It affects women at an earlier age as compared to men in general. Highest incidence for women is around 20 to 35 years; for men around 35 to 50 years.

Neonatal myasthenia

New born infants can develop Myasthenia Gravis if their mothers had this disease. The antibodies can cross the placenta and reach the blood circulation of the baby and cause MG symptoms. This condition is called as neonatal myasthenia and it is a self limiting condition, of course baby might require treatment if symptoms are severe, until the antibodies are cleared from its blood.

Congenital myasthenia syndromes

Some children are born with pathology at NMJ area that is different from the autoimmune type of MG. They do not have any abnormal antibodies directed against the NMJ, so the defect in the NMJ is due to other reasons. Defending upon where exactly the defect present they are classified as pre-synaptic, synaptic & post-synaptic congenital myasthenic syndromes.

How does myasthenia patient present?

Muscle weakness is the hall mark symptom of MG. It is more specifically called as fatigable and fluctuating type of weakness, and is very typical for MG.

Patients with various other nerve & muscle problems can have weakness but in those patients the weakness is generally seen during rest as well, and it worsens somewhat proportionately during muscle activities.

But in Myasthenia Gravis, at least with the typical cases, the weakness during resting period is not that prominent or even may be totally absent as well as during the early part of muscle activity. But as patient continues to use the muscle, especially sustained activities, there may be dramatic development of weakness in those muscles. So the weakness is kind of fluctuating; at rest patient is better, during activities becomes weak. A patent who is watching a TV might not have any eye muscle weakness in the initial stage of watching, however after sometime may develop frank double vision.

Every person has a tendency to develop fatigue when the same muscle is used for the activity persistently. The MG patients develop muscle fatigue quicker and will develop obvious muscle weakness as compared to otherwise normal individuals who develop much less fatigue and weakness for the same duration and intensity of muscle activity. That is why the pattern of weakness in MG patients is also called as fatigable weakness.

Some typical manifestations include;

• Drooping of eyelids
• Double vision
• Difficulty with swallowing (dysphagia)
• Difficulty with speech (dysarthria)
• Difficulty with breathing (dyspnea)
• Limb muscle weakness (usually proximal like shoulder and hip areas)

MG generally starts in the eye muscles, and then spreads to other areas of the body. Some patients start with limb muscle weakness too. There are certain patients whose eye muscle weakness doesn’t progress to involve other areas of the body and this condition is called as ocular myasthenia. It is called generalized MG if the limb muscles are affected too.

Diagnosis

Once MG is suspected clinically then to confirm the diagnosis the following investigations may be required;

• Tensilon test (edrophonium test); if this is not available then Neostigmin test
• Blood test for Acetyl choline receptor antibodies
• EMG/NCS (electromyography and nerve conduction study)
• RNS (repetitive nerve stimulation test)
• SFEMG (Single fiber EMG test)
• Blood tests to look for other autoimmune disorders like lupus, rheumatoid arthritis, thyroiditis etc
• Investigations to look for thymus tumor after MG diagnosis is confirmed

Treatment

Patients are usually started with Mestinon (pyridostigmin). If thumus tumor is found it has to be treated. Steroids and other immunosuppressive agents like azathioprine, cyclosporine etc are used to suppress the autoimmune tendency and to prevent the future episodes.

Myasthenia crisis

Some patients with Myasthenia Gravis can develop severe symptoms especially breathing difficulties due to paralysis of respiratory muscles. This usually happens with patients who have severe forms of MG. Infections, stress, missing MG medications etc can precipitate it. This is a crisis situation and such patients need hospitalization and prompt treatment with immunoglobulins or plasmaphresis.



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