MYASTHENIA GRAVIS

DEFINITION
• Myasthenia gravis (MG) is a neuromuscular
disorder characterized by weakness and
fatigability of skeletal muscles due to decrease in
the number of available acetylcholine receptors
(AChRs) at neuromuscular junctions due to an
antibody-mediated autoimmune attack.
 Pathophysiology
• In MG, antibodies are directed toward the
acetylcholine receptor at the neuromuscular
junction of skeletal muscles
• Results in:
– Decreased number of nicotinic acetylcholine
receptors at the motor end-plate
– Reduced postsynaptic membrane folds
– Widened synaptic cleft
 Pathophysiology
– Anti-AChR antibody is found in 80-90% of
patients with MG
– dysfunction of the thymus gland
– The immune response to exogenous infectious
antigens
 PATHOPHYSIOLOGY
Destruction of AchR

Specific Anti AchR antibodies

Auto immune response mediated

• Endocytosis of receptor
• Blocks active site that normally binds to
Ach
• Damage to postsynaptic membrane
 CLINICAL FEATURES
• Fluctuating weakness increased by exertion

• Extraocular muscle weakness

• Head extension and flexion weakness

• No deficit in sensory, reflex, or cerebellar

functioning
• Progression of disease
– Mild to more severe over weeks to months
 - Facial muscle weakness
– Bulbar muscle weakness
– Limb muscle weakness
– Respiratory weakness
– Ocular muscle weakness
• Ptosis
• Diplopiae
• Snarling expression and weakness
of chewing
• Nasal timbre
• Dysarthria
• Aspiration
 CLINICAL FEATURES
• Respiratory muscle weakness
– Weakness of the intercostal muscles and the
diaghram may result in CO2 retention due to
hypoventilation
• MYASTHENIC CRISIS
– Weakness of pharyngeal muscles may collapse
the upper airway
Laboratory testing

Anti AChR radioimmunoassay

MUSK antibodies test
Nerve conduction study
 Clinical test
Anti cholinestrase test

Edrophonium 2mg

Clinical improvement

Yes No

Test positive Clinical improvement

Edrophonium 8mg iv
Yes No

Test positive Test negative

 Edrophonium (Tensilon test)
• Adverse effects
– bradycardia
– atrioventricular (AV) block
– atrial fibrillation
– cardiac arrest
 DD
• Drug-induced myasthenia
• Lambert-Eaton myasthenic syndrome (LEMS)
• Hyperthyroidism
• Botulism
• Intracranial mass lesions
• Progressive external ophthalmoplegia.
• Treatment with penicillamine (used for scleroderma or
rheumatoid arthritis) may result in true autoimmune MG.
 TREATMENT

• Anticholinesterase medications
• Immunosuppressive agents
• Thymectomy and
• Plasmapheresis or intravenous immunoglobulin
(IVIg)
Anticholinesterase Medications

• Pyridostigmine is the most widely used

anticholinesterase drug .

• 30-60mg three to four times a day.

 THYMECTOMY

• 85% of patients experience improvement after

thymectomy.
• Hence prefered in pt.s between age group of
puberty and 55yrs.
 IMMUNOSUPRESSION

• Glucocorticoids ( 15-25mg/day)
• Mycophenolate mofetil
• Azathioprine
• Cyclosporine
• Tacrolimus
• Cyclophosphamide
 Plasmapheresis
• Plasmapheresis has been used therapeutically in
MG.
• Plasma, which contains the pathogenic antibodies,
is mechanically separated from the blood cells,
which are returned to the patient.
• A course of five exchanges (3–4 L per exchange)
is generally administered over a 10- to 14-day
period.
• Plasmapheresis produces a short-term reduction in
anti-AChR antibodies, with clinical improvement
in many patients.
 Intravenous Immunoglobulin
• The indications for the use of IVIg are the same as those
for plasma exchange

• To produce rapid improvement to help the patient through

a difficult period of myasthenic weakness.

• The usual dose is 2 g/kg, which is typically administered

over 5 days .

•
• If tolerated, the course of IVIg can be shortened to
administer the entire dose over a 3-day period.

• Improvement occurs in ~70% of patients,

beginning during treatment, or week to month.
 COMPLICATIONS
• Respiratory failure – Myasthenic Crisis
• Dysphagia
• aspiration pneumonia
• dehydration
• decubitus ulcers
• Complications secondary to drug treatment
 MYASTHENIC CRISIS
• An exacerbation of weakness, usually with
respiratory failure, sufficient to endanger life.
• Caused due to disease exacerbation or inadequate
drug therapy
• 10% of MG pts
• Bulbar and respiratory muscle weakness are more
prone.
• Develops rapidly and unexpectedly
• Must be differentiated from Cholinergic crisis by
Tensilon test
• The myasthenic patient with fever and early
infection should be treated like other
immunocompromised patients

• Early and effective antibiotic therapy, respiratory

assistance is essential.

• Plasmapheresis or IVIg is frequently helpful in

hastening recovery.
 DRUGS TO BE AVOIDED

• Drugs That May Exacerbate    

• Aminoglycosides: e.g., streptomycin, tobramycin,
kanamycin  
• Quinolones: e.g., ciprofloxacin, levofloxacin,
ofloxacin, gatifloxacin 
•  Macrolides: e.g., erythromycin, azithromycin,
• Nondepolarizing muscle relaxants for surgery 
  
D-Tubocurarine (curare), pancuronium,
vecuronium, atracurium
• Beta-blocking agents  
 Propranalol, atenolol, metoprolol

• Local anesthetics and related agents   

Procaine, xylocaine in large   
• Procainamide (for arrhythmias)
• Botulinum toxin   
Botox exacerbates weakness
• Quinine derivatives  
Quinine, quinidine, chloroquine, mefloquine
(Lariam)
• Magnesium  
• Decreases ACh release
• Penicillamine   
May cause MG
• Drugs with Important Interactions in MG 
Cyclosporine
 MANAGEMENT
• ED Management
– O2
– Endotracheal intubation
– neostigmine - 0.5 to 2 mg im / sc,
- 15 mg po.
– High dose steroid therapy
– AchE inhibitors
– Neurologist consultation
– Plasmapharesis and IV Ig therapy
Thank You