Myasthenia gravis

Clinic

• MG is an autoimmune disease characterized by muscle weakness and fatigue
• MG is an autoimmune disease of the neuro-muscular junction which results from antibodies that block or destroy nicotinic acetylcholine receptors (AChR) at the junction between the nerve and muscle.
• This prevents nerve impulses from triggering muscle contractions.
• The Initial / Main symptom is painless weakness of specific muscles, not fatigue.
• The muscle weakness becomes progressively worse during periods of physical activity and amel by rest.
• Typically, the weakness and fatigue agg toward the end of the day.

Sign / Symptoms

MG generally starts with ocular weakness then progress to weakness in the extremities. (Opposed to GBS which is ascending paralysis)

• Ptosis due to weakness of levator palpebrae superioris
• Diplopia due to weakness of the extraocular muscles

• Dysphagia
• Weakness of mastication
• Hanging jaw sign and as a snarling expression when attempting to smile.
• Difficulty in holding the head upright
• Dysarthria and Hypophonia (Slow / Slurred / Nasal Speech)
• Dyspnea and limb movements

Pathology

• MG is an autoimmune synaptopathy. The disorder occurs when the immune system malfunctions and generates antibodies that attack the body's tissues. The antibodies in MG attack a normal human protein, the nicotinic acetylcholine receptor, or a related protein called MuSK, a muscle-specific kinase. Other, less frequent antibodies are found against LRP4, agrin, and titin proteins.
• Human leukocyte antigen haplotypes are associated with increased susceptibility to myasthenia gravis and other autoimmune disorders. Relatives of people with myasthenia gravis have a higher percentage of other immune disorders.

• The thymus gland cells form part of the body's immune system. In those with myasthenia gravis, the thymus gland is large and abnormal. It sometimes contains clusters of immune cells that indicate lymphoid hyperplasia, and the thymus gland may give wrong instructions to immune cells.

Related disease

• Guillain-Barré syndrome
• Miller Fisher syndrome (MFS) is an immune-mediated neuropathy that involves the triad of symptoms of acute ophthalmoplegia, ataxia and areflexia, also with positive GQ1b antibody.

• Peripheral neuropathy

Note

A;though MG is very similar to GBS or LMN disease, it has completely different pathology. Neuromascular Junction is the center of MG pathology. We have no known viral infection which is related to Neuromascular Junction but there are some candidates due to the symptom of cranial nerve paralysis. As we know in MG cranial and occular nerves are more involved. So I check viruses like EBV, JE, EEE/WEE and KRU.

EBV: The thymus plays a major role in MG. Our recent finding of a persistent EBV infection in some MG thymuses. Real-time PCR for EBV genome, latent (EBER1, EBNA1, LMP1) and lytic (BZLF1) transcripts, and immunohistochemistry for LMP1 and BZLF1 proteins confirmed an active intrathymic EBV infection, further supporting the hypothesis that EBV might contribute to onset or perpetuation of the autoimmune response in MG.