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Myasthenia Gravis (MG)

Myasthenia Gravis (MG)

Myasthenia Gravis is a chronic neuromuscular disorder that leads to weakness and abnormally rapid exhaustion of voluntary skeletal muscle. It is considered to be an autoimmune disease because the immune system is attacked by the body and its targets are acetylcholine receptors, a substance that acts as a neurotransmitter in neuromuscular synapses, where the nerves are connected to the muscles. It is normally stored in small vesicles at the nerve endings and is released when a nerve pulse reaches these points. It then forms a bridge between its receptors and muscle and initiates some chemical reactions that lead to muscle contraction.

MG leads to the production of autoantibodies that abnormally attack these receptors by reducing their number and then decreases muscle contraction capacity.

 

The production of these antibodies has been found to involve the thymus gland, a small gland below the chest. Normally, this gland secretes hormones that affect the transmission of signals to neuromuscular synapses and is involved in the normal functioning of the immune system. It is large in infancy and reaches the maximum in puberty, where it is then shrinking and has little functionality.

In patients with MG, however, it is abnormally large in size and in most cases presents abnormalities and develops tumors (thymomas), which are usually benign.

All of the above cause the weakness and exhaustion of the muscles. It is rarely fatal, although it can become threatening if the muscles involved in the breathing are affected. Affects 50-200: 1,000,000 people worldwide.

 

Symptoms

Their onset may be sudden, with generalized and severe muscle weakness, but often the first symptoms vary and are subtle, which may delay the diagnosis. It affects people of all ages, although it is more common in women, ages 20-40, and in men it is mainly in their 40-60.

The rest of the  symptoms are caused by the muscular weakness of the voluntary muscles.

Often, there is firstly a weakness in the eye muscles, with ptosis of eyelids (1 or even 2 eyelids) and / or diplopia. In addition, there are symptoms of inability to swallow, chew, talk, breathing difficulty, influence on facial muscles or limb movement. They include severe exhaustion, unbalanced gait, upper limb weakness and in the palms and fingers.

 

Muscular weakness can develop within a few days or weeks or remain on the same level for a long time. Its severity varies from person to person or even to the same person per periods. It tends to worsen with exercise, with the coexistence of other diseases and towards the end of the day. Symptoms are more intense and serious during menstruation and pregnancy.

 

Diagnosis

It is done by a neurologist or special physician with a personal history and clinical examination that includes three basic tests, electromyography (EMG), intravenous administration of tensilon, a substance that blocks the decomposition of acetylcholine and temporarily increases its levels in the neuromuscular junction. Patients have a temporary neutralization of weakness, and immunological blood tests to find antibodies against acetylcholine receptors. Ice tests can be performed on the eyelids to detect their fall, as well as magnetic and CT scans to control the thyroid gland and the brain.

 

Management

There is still no cure, but avoiding anything that can cause a crunch, taking medication, surgical removal of the throat and plasmapheresis are helpful in managing the symptoms.

In particular, common stimuli that can cause a crisis are: fatigue - burnout, anxiety, infections, some medications, surgeons.

Medication involves the administration of anti-cholinesterase or cholinesterase inhibitors, which improve the transmission of neuromuscular pulses and contribute to the proper functioning of the muscles by improving muscle weakness. A representative drug is pyridostigmine (Mestinon). Immunosuppressants such as Azathioprine (Imuran) and mainly steroids such as prednisone are also being administered.

Surgical removal of the thymus gland has been shown to lead to remission of symptoms and plasmapheresis is performed to remove antibodies from the plasma, especially in cases of symptoms exacerbation or before surgical removal of the thymus.

 

Information about clinical trials conducted globally: https://www.centerwatch.com/clinical-trials/listings/condition/104/myast... and https://clinicaltrials.gov/ct2/home

 

References

  • Muscular Dystrophy Canada, Myasthenia Gravis, http://muscle.ca/wp-content/uploads/2012/11/425E_Myasthenia_Gravis_2007.pdf
  • NORD (National Organization for Rare Disorders), Rare diseases, https://rarediseases.org/rare-diseases/
  • Vanessa S. Boyce, Lorne M. Mendell, Neurotrophins and spinal circuit function, Frontiers in Neural Circuits, Frontiers Media S.A., 2014.
  • Tai H, Cui L, Guan Y, Liu M, Li X, Huang Y, Yuan J, Shen D, Li D and Zhai F, Amyotrophic Lateral Sclerosis and Myasthenia Gravis Overlap Syndrome: A Review of Two Cases and the Associated Literature. Front. Neurol, 2017, 8, 218.

Muscular Dystrophy Association