Pathophysiology

presentation on
Myasthenia gravis

Prepared By:-
Pradip Patel
Shivcharan Mandal
Sukesh Kumar Yadav
Myasthenia gravis
 Myasthenia gravis is an autoimmune disorder affecting about 1 in
10,000 population and it is more common in women.
 This is condition characterized by progressive fatigable weakness,
particularly of the ocular, neck, facial and bulbar muscle.
 This is due to the inability of neuromuscular junction to transmit
impulses from nerve to the muscle.
 It is serious and sometimes a fetal disease.
 Ocular myasthenia is more common in males, involves weakness
of eye muscles and eyelids, and may include swallowing
difficulties and slurred speech.
Causes of Myasthenia gravis
 Myasthenia gravis is an autoimmune disease.
 The body develops antibodies against its own acetylcholine
receptors.
 These antibodies destroy the acetylcholine receptors or binds on it.
 So though the acetylcholine release is normal, it cannot act
because of destruction of receptors or occupied of receptors. And
cannot show their effect.
 This results in weakness and easy fatigability on repeated activity,
with recovery after rest.
 The eyelid, external ocular, facial and pharyngeal muscles are
generally involved first.
pathophysiology
 Due to auto-immune response

Development of auto-antibodies

Antibodies attack Acetylcholine (Ach) receptors

at the motor end plate

Act against the nicotinic acetylcholine receptor

Impaired the ability of acetylcholine to bind on

receptors

Resulting in voluntary muscle weakness that escalates with

continued activity
Symptoms of Myasthenia gravis
 Because of the defective neuromuscular activity, the muscular
contraction is very slow and weak.
 When repeated contractions of muscles are attempted by the
patients fatigue occurs quickly.
 The cardinal symptoms is
• Fatigue weakness of muscles.
• Movement is initially strong but rapidly weakens as muscles use
continues.
• Weakness of oculomotor muscles may mimic a central eye
movement disorder.
• Weakness of chewing, swallowing, speaking or limb movements.
 In severe conditions there is paralysis of muscles. The patient dies
mostly due to the paralysis of respiratory muscles.
 Fluctuation weakness increasing through the day and relieved
by rest.

The major Sings and Symptoms are:

 Diplopia : Double vision- Single object seen as two
 Ptosis : Dropping of the eyelids or moving out of place
 Snarling Expression
 Dysphagia : Difficulty in swallowing
 Nasal speech
 Proximal limb weakness, rarely distal
 Respiratory muscle weakness
Types of Myasthenia gravis
Neonatal : In 12% of the pregnancies with a mother with Myasthenia
gravis, she passes the antibodies to the infant through the placenta,
causing neonatal Myasthenia gravis.
The symptoms will start in the first two days and disappear within a few
weeks after birth. With the mother, it is not uncommon for the symptoms to
even improve during pregnancy, but they might worsen after labor.
Congenital : Children of healthy mother can very rarely, develop
myasthenia symptoms beginning at birth, Congenital myasthenia
syndrome or CMS. Other than myasthenia gravis, CMS is not caused by an
autoimmune process, but due to synaptic malformation, which in turn
caused by genetic mutations. Thus CMS is a hereditary disease. More than
11 different mutations have been identified, and the inheritance pattern is
typically autosomal recessive.
Juvenile : Myasthenia occurring in childhood, but after the peripartum
period.
Classification of Myasthenia gravis
Class I : Any eye muscle weakness, possible ptosis, no other
evidence of muscle weakness
Class II : Eye muscle weakness of any severity, mild weakness of
other muscles.
Class III : Eye muscle weakness of any severity, moderate
weakness of other muscles.
Class IV : Eye muscle weakness of any severity, severe weakness
of other muscles.
Class V : Intubation needed to maintain airway
Diagnosis
 Physical examination
 Blood tests
 Neurophysiology
 Edrophonium test
 Imaging techniques
 Pulmonary function tests
Physical examination
Blood Tests
 Detection of Acetylcholine receptor antibodies.
• Sensitivity of 80-96%
• 50 % of patients with only ocular disease may lack in these
antibodies
 Antibodies against voltage gated calcium channels to differentiate
from of Lambert-Eaton Myasthenia Syndrome (LEMS).

Neurophysiology
 Repetitive nerve stimulation test.
 electromyography
Imaging
 Chest X-Ray
• Detection of thymoma.
• To detect lung cancer for alternative diagnosis
i.e. Lambert-Eaton Syndrome.
 CT-Scan
 MRI Scan

Pulmonary Function Tests

 Forced Vital Capacity is monitored to detect any gradual loss of
respiratory functions.
 Negative inspiratory force is useful to detect adequacy of ventilation.
Management and Treatment
 The principles of treatment are:-
• To maximize the activity of acetylcholine at remaining receptors
in the neuromuscular junctions.
• To limit or abolish the immunological attack or motor end plates.
 The most commonly used anticholinesterase drug is pyridostigmine
which is given orally in a dosage of 30-120mg, action start in 30-60
minutes & effect lasts 4-6 hours.
(Caution for cholinergic crises.)
 Immunological treatment of myasthenia gravis:
Thymectomy : The surgical removal of thymus.
Plasma exchange : Plasmapheresis
• Filter out the antibodies from blood
• Effect lasts only for few weeks.
Intravenous immunoglobulin :
• Provides body with antibodies
• Binds to circulating antibodies
Corticosteroid treatment :
• Significance improvement is often seen after a decreased
antibody titer which is usually 1-4 months
Immunosuppressant treatment :
Azathioprine : 2.5mg/kg daily, (other are Cyclosporine, Mycophenolate)
 Behavior Modifications
 Diet
• Thickened liquids are preferred, when dysphagia arises to
contract the ear of aspiration.
• Asparagus should be taken as it contains steroid-like substance
 Activity
• Patients should be as active as possible but should take rest in
between.
• Yoga exercises to stretch the weakened muscles should be done.
• This not only strengthens the muscles but also provides oxygen &
removes carbon dioxide from them.
Reference
1. A text book of BIOCHEMISTRY, PATHOLOGY & MICROBIOLOGY
By Birendra Kumar Yadav & Dhan Bahadur Bohara

2. Essential of MEDICAL PHARMACOLOGY

By KD Tripathi

3. Images from Internet

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