Myasthenia gravisMys + a + sthenos = muscle without strength

Urbir SidhuMD 4

What is it?

• Myasthenia gravis is an autoimmune disease where antibodies are formed to acetylcholine receptors on motor end plates of skeletal muscle (neuromuscular junction)– Ach is produced in normal amounts, but these antibodies

prevent binding of Ach to its receptor on the motor end plate

• Due to this, End plate potential & Action potential cannot be generated, resulting in muscular weakness

What do you see?

• Severe muscle weakness especially of arms, legs, & eyes– Muscle weakness is generalized but usually

fluctuation and becoming more pronounced towards the end of the day

– Weakness most prominently affects extraocular eyes• Electromyography shows progressively weaker

contraction of muscles on repeated stimulation• Muscle histology appears normal

Epidemology

• More commonly seen in women• Affects 3 in 100,000 people• Two age peaks: 20-30 years (women) and 50-

60 years (men)• Thymic hyperplasia (65%) and thymoma (15%)

found among younger patients

Pathogenesis

• Cross-linking 2 adjacent AChRs with anti-AChR antibody, thus accelerating internalization and degradation of AChR molecules

• Causing complement-mediated destruction of junctional folds of the postsynaptic membrane

• Blocking the binding of ACh to AChR• Decreasing the number of AChRs at the NMJ by

damaging the junctional folds on the postsynaptic membrane, thereby reducing the surface area available for insertion of newly synthesized AChRs

Clinical features

– Muscle weakness that worsens with use and improves with rest

– Predominantly involves facial muscles• Ptosis• Diplopia• Decresed facial expressions• Dysphagia• Dysarthria

– Daily routines are tiring

Ptosis

Treatment• Treatment is physiological based• Symptoms improve with use of anticholinesterase agents such as

Neostigmine and Pyridostigmine– Drugs inhibit Acetyl cholinesterase – Acetylcholine remain in the synaptic cleft for longer period and in larger

amounts, prolonging the time available for Ach to activate its receptors– Enables a larger amplitude of EPP (end plate potential) which will be

able to generate muscle AP (action potential)– Better muscle contractions

• Associated with thymic hyperplasia or thymoma– Thymectomy improves symptoms

Myasthenia gravis

Before treatment After 3 days of intravenous…

Differential: Lambert-Eaton Syndrome

• Clinical condition resembles myasthenia gravis• But it is characterized by skeletal muscle

weakness• May be associated with small cell carcinoma

of lungs or any other autoimmune disorder