Myasthenia Gravis

Fatima Riaz

The Basics
Literally means Grave Muscle Disease , is an autoimmune neuromuscular disorder leading to fluctuating muscle weakness and fatigability A relatively rare disorder of peripheral nerves in which antibodies form against acetylcholine (ACh) nicotinic postsynaptic receptors at the neuromuscular junction (NMJ). 3-30 cases per million per year Is a channelopathy

HOW & the WHO?

The exact cause is unknown. One possibility is that certain viral or bacterial proteins mimic "selfproteins" in the body (such as the ACh receptor), stimulating the immune system to unwittingly attack the self-protein. The thymus gland teaches immune cells called T-cells to recognize self from non-self. About 15 percent of people with MG have a thymic tumour, called a thymoma, and another 65 percent have overactive thymic cells, a condition called thymic hyperplasia. Damaged thymus may result in damaged T cells with the inability to differentiate self from non self. Myasthenia gravis can affect people at any age. It most commonly affects young adult women (under 40) and older men (over 60). 10% of cases has juvenile onset. People with a preexisting or inherited autoimmune disorder are more likely to develop MG.

SYMPTOMS
1.Difficulty maintaining steady gaze. Eyelid drooping-asymmetrical ptosis. Double vision-diplopia. 2.Chewing /swallowing difficulty (dysphagia), causing frequent gagging, choking, or drooling. Difficulty talking- disarthria. Facial paralysis.

3.Difficulty climbing stairs, lifting objects, or rising from a seated position. Fatigue.

4.Breathing difficulty because of weakness of the chest wall muscles.

PTOSIS

DIPLOPIA

Immunopathology of Myasthenia Gravis

IMPULSE
Nervous system transmits information as a series of nerve impulses. A nerve impulse, is the movement of an action potential as a wave through a nerve fiber. Inactive and polarized membrane is at resting potential. Depolarization: Na ions influx reverses charge Repolarization: K+ channels open,Na+ channels close and K+ rushes.

NEUROMUSCULAR JUNCTION A synapse between an axon and a muscle fibre is called neuromuscular junction. Na caused depolarization of the presynaptic membrane causing the entry of Ca+ ions. Acetylcholine released from presynaptic vesicles to the cleft.

POST SYANPSE Acetylcholine binds to nAch receptors which causes sodium influx and hence, generation of an
action potential.

Neuromuscular Junction and the Intracellular Events

AchR has 5 integral membrane subunits(2a,1b,1g,1d) surrounding a central oin channel which opens when 2 Acetylcholine molecules bind to the a proteins. Small cations move across the postsynaptic membrane and depolarise it.

Action potential moves along the length of the sarcolemma ,penetrating into the transverse tubules

Stimulates secretion of Ca+ from the sarcoplasmic reticulum

Ca+ binds to troponin C to end the troponin/tropomyosin blockade

Anti-AchR Antibody

T-cell receptor (TCR) binds to the acetylcholine receptor antigenic peptide fragment

(epitope) resting within the major histocompatibility complex of antigen presenting cells Activates B cells and promotes production of anti AchR receptive antibodies Antibodies block or destroy the nAchR and impair ability of acetylcholine to bind

Decreased numbers of functioning nAchRs therefore impairs muscular contraction

Treatment
ANTICHOLINESTERASE MEDICINES These medicines delay the breakdown of acetylcholine when it is released from the nerve endings. More acetylcholine is then available to compete with autoantibodies. The most commonly prescribed anticholinesterase medicine is called Pyridostigmine. THYMECTOMY This is an option in some cases. A thymectomy can improve symptoms in more than 7 in 10 people with Myasthenia Gravis and may even cure some. STEROID MEDICATION Steroids suppress the immune system and prevent the abnormal antibodies from being made. A low dose, often on alternate days, is usually enough for people where symptoms only affect muscles around the eye. Example would be Prednisolone IMMUNOSUPPRESSANT MEDICINES An immunosuppressant medicine such as Azothiaprine may be advised in addition to steroid medication. These medicines work by suppressing the immune system.