Myasthenia Gravis
By Dr. Waqar Ali
https://next.amboss.com/us/article/DR016f?q=myasthenia+gravis
Table of Contents
- General Points
- Normal Neuromuscular Junction
- Pathology in Myasthenia
- Muscles Affected
- Types of MG
- Signs & Symptoms
- Diagnostic Tests
- Single Fiber EMG
- Other Tests
- Treatment
- Myasthenic Crisis
- Prognosis
General Points
- It mostly occurs in adults (any age group). Very rare in children
- Muscle may be normal at rest but weakens when it becomes active and contracts repeatedly (fluctuating weakness)
- There is no muscle damage
- It is a slowly progressive disease
- With treatment, almost normal survival
- Some complications can be fatal (discussed in Myasthenic Crisis section)
Normal Neuromuscular Junction
- Acetylcholine (ACh) released from the nerve
- Stimulates the ACh receptors on the skeletal muscle
- Skeletal muscle contracts
- Acetylcholine then destroyed by cholin-esterase enzyme
(look at the circled areas only)
Pathology in Myasthenia
- It is a disorder of the neuromuscular junction of skeletal muscles
- It is an autoimmune disease
- Antibodies are formed which block & destroy the acetylcholine receptors
Result: ACh cannot stimulate the muscles → leads to weak muscle contraction (muscle weakness)
Summary
MG is an autoimmune disease, characterized by weak contraction of the skeletal muscles. This is due to blockage of ACh receptors on the muscles (by antibodies).
Muscles Affected
Any skeletal muscle can be affected, but most commonly affected are:
Commonly Affected Muscles
- Ocular muscles (levator, intraocular recti)
- Muscles of swallowing (pharyngeal muscles)
- Muscles of mastication (chewing)
Other Muscles That May Be Affected
- Limb muscles
- Respiratory muscles
What Is NOT Affected
- Smooth muscles
- Reflexes
- Sensory system
Types of MG
Ocular MG
(Only eye muscles)
Generalized MG
(Generalized muscles)
Key Points:
- Ocular MG is more common
- In some patients, ocular myasthenia can progress into generalized MG over time
Signs & Symptoms
Important Note: Signs & symptoms of Myasthenia worsen as the day passes (more in afternoon or evening) & with continuous muscle activity.
1. Ocular Myasthenia
Leads to:
- a. Ptosis (can be unilateral or bilateral)
- b. Diplopia (due to paralysis of eye muscles)
Which muscles are affected?
These features worsen after continuous reading, staring or looking up (muscles get tired)
⚠️ PUPILS ARE NOT AFFECTED
2. Pharyngeal Muscles
Weakness leads to difficulty in swallowing
3. Muscles of Mastication (Chewing)
Weakness leads to difficulty in chewing food. Gets worse as the person continues the meal.
4. Respiratory Muscles
- Not commonly affected on a daily basis
- Can be affected in an acute worsening of myasthenia (myasthenic crisis)
- This may lead to respiratory failure & requires mechanical ventilation
5. Limb Muscles
a. Weakness of upper limb muscles → difficulty in raising the arms or keeping them up
b. Weakness of hand muscles → leads to writing difficulty. Hand writing is affected
c. Weakness of lower limbs → difficulty in walking, rising up from a chair, climbing DARAJ
6. Facial Muscles
Weakness leads to a “masked face” (no expressions)
Summary of Affected Systems
In summary, signs & symptoms are due to involvement of:
- Eyes ✓
- Pharyngeal muscles ✓
- Chewing muscles ✓
- Upper limb ✓
- Hands ✓
- Lower limbs ✓
- Respiratory muscles ✓
- Face muscles ✓
Diagnostic Tests
1. Physical Exam Testing
- Ask the patient to look up continuously → ptosis occurs due to muscle fatigue
- Ice test: Apply ice to the ptosis → ptosis improves (ice inhibits cholinesterase)
2. Blood Tests
- Testing for ACh receptor antibodies
- Some patients have anti-MuSK antibodies also (muscle specific kinase)
3. Single Fiber EMG (Electromyography) Z
- Most sensitive test for diagnosis
- Affected muscle is stimulated continuously by electrode → action potential recorded
- Shows gradual decrease in activity of the muscle (fatigue)
Note: The diagnosis is often made by doing both antibodies plus EMG.
Single Fiber EMG
SF-EMG vs 30G CNE
Selectivity Explained
Gradually Decreasing Action Potential
Normal
Myasthenia gravis
time of nerve stimulation
Other Tests
(Not for diagnosis — for monitoring and associated conditions)
1. CT Chest
- To look for thymus enlargement (thymoma)
- Present in some patients
2. Pulmonary Function Tests (PFTs)
- Should be done at regular intervals
- For early detection of respiratory muscle weakness
Treatment
1. Cholinesterase Inhibitors Z
- First line treatment
- Neostigmine, pyridostigmine
- They inhibit cholinesterase, so acetylcholine is not destroyed
- Provide symptomatic relief, no improvement in prognosis
2. Steroids
- Used if cholinesterase inhibitors don’t work
3. Immunosuppressants
- Example: Azathioprine
- Used if first-line treatment not working
4. Thymectomy
based on age, 60 if above, remove - less than 60 only remove if there is thymoma
- If thymoma MOJOOD, thymectomy in every patient
- If no thymoma, then thymectomy only if patient more than 60 years old
Myasthenic Crisis
Patients can develop an acute worsening of weakness, especially respiratory muscles. This is called Myasthenic Crisis. It needs emergent treatment, because it can cause respiratory failure.
Factors Which Can Precipitate Crisis
- Any infection
- Many medicines (aminoglycosides, beta blockers)
- Physical stress like surgery, body trauma
- Non-compliance with medications
Treatment of Crisis Z
- Ventilatory support
- Plasmapheresis (to quickly remove the antibodies)
- i.v. Immunoglobulins ( to quickly neutralise the antibodies)
(Immunoglobulins are “antibodies” destroying the myasthenia antibodies)
ITP / GBS
Prognosis
- With treatment, prognosis is generally good with good quality of life
- Regular follow-up is essential (LAAZIM), to detect any respiratory muscle involvement
LAST SLIDE IS VERY IMPORTANT
meci