Myasthenia gravis Flashcards
Definition of Myasthenia Gravis
Myasthenia Gravis (MG) is a chronic autoimmune neuromuscular disorder characterized by weakness and rapid fatigue of voluntary muscles due to impaired communication between nerves and muscles. It occurs when antibodies block or destroy acetylcholine receptors at the neuromuscular junction (educed availability of acetylcholine at myoneural junction) preventing efficient nerve signal transmission.
Area of NS affected in MG
MG primarily affects the neuromuscular junction, where nerves communicate with skeletal muscles. While the central nervous system remains unaffected, peripheral neuromuscular transmission is impaired, leading to muscle weakness.
Epidemiology (incidence/prevalence)
- Worldwide prevalence 100-200 per million,
affecting over 700,000 worldwide - Rare incidence (10-20 per 100,000).
- Underdiagnosed?
- Two prevalence peaks:
1. second/third decade for women
2. seventh/eighth decade for men - Sex ration 3:1 female: male
- Gradual onset
Cause of MG
MG is primarily an autoimmune disorder in which the body produces antibodies that attack acetylcholine receptors or associated proteins like muscle-specific kinase (MuSK). Other potential causes include:
Thymoma or thymic hyperplasia (abnormalities of the thymus gland).
Genetic predisposition (though not directly inherited).
Course of MG
MG typically follows a relapsing-remitting pattern, with periods of worsening weakness followed by improvement.
Symptoms often progress over months to years.
Without treatment, the condition may worsen, leading to life-threatening complications like myasthenic crisis (severe respiratory muscle weakness).
Prognosis of MG
With proper treatment, most individuals can manage symptoms and lead relatively normal lives.
Some patients achieve remission, especially after thymectomy.
Untreated cases may result in significant disability and increased risk of respiratory failure.
Signs and Symptoms of MG
Muscle weakness that worsens with activity and improves with rest.
Ptosis (drooping eyelids) – common early symptom.
Diplopia (double vision) due to extraocular muscle weakness.
Dysphagia (difficulty swallowing) and dysarthria (slurred speech).
Limb weakness, typically proximal more than distal.
Respiratory muscle weakness in severe cases.
Motor Versus Sensory Involvement in MG
Motor: MG affects voluntary muscle movement, causing weakness but no loss of reflexes or muscle atrophy (except in severe, long-term cases).
Sensory: Not affected—no numbness, tingling, or pain directly caused by MG.
Subtypes of MG
Generalized Myasthenia Gravis – Affects multiple muscle groups, including limbs, bulbar, and respiratory muscles.
- early onset (40-50) associated with thymus
hyperplagia
- late onset: associated with thymus atrophy
- thymoma MG (10-15%, neoplastic -
immune response to tumour)
Ocular Myasthenia Gravis – Limited to eye muscles (ptosis and diplopia).
Seronegative Myasthenia Gravis – No detectable acetylcholine receptor or MuSK antibodies. (10-15%)
Congenital Myasthenic Syndromes – Rare, genetic forms of the disease
Diagnostic tests for MG
- Edrophonium (Tensilon) test – Temporary improvement after administration of short-acting acetylcholinesterase inhibitor.
- Ice pack test – Improvement in ptosis after cooling the eyelid.
- Electromyography (EMG) – Shows abnormal muscle response to repetitive stimulation.
- Anti-AChR and anti-MuSK antibody tests – - Detect autoantibodies.
- CT/MRI of the chest – To check for thymoma.
Medication for MG
- Acetylcholinesterase inhibitors (e.g., Mestinon) – Improve neuromuscular transmission. Provide symptomatic relief
Allow Ach to accumulate at NMJ and its effect is prolonged
Response varies across people
Adverse effects - Corticosteroids (e.g., Prednisone) – Suppress immune response. Marked improvement or complete relief of symptoms occurs in more than 75%
of patients on prednisone
Much of the improvement occurs in the first 6 to 8 weeks, but strength may
increase to total remission in the months that follow. The best responses occur in
patients with recent onset of symptoms..
The major disadvantages of chronic corticosteroid therapy are the side effects. - Immunosuppressant drugs (such as
azathioprine) can alter the body’s immune system and reduce the production of
the antibodies that cause myasthenia gravis. - Plasma exchange (PLEX) or plasmapharesis – Used in severe exacerbations or myasthenic crisis. Blood is routed through a machine that removes the
plasma containing the harmful antibodies, and replaces it with antibody-free
plasma before returning it to your body.
Often 4-5 treatments over a two week period in hospital. - Intravenous immunoglobulin (IVIG): you are injected with normal
antibodies that change the way your immune system acts
Treatment of MG
Thymectomy – Recommended in cases with thymoma or generalized MG, often leading to symptom improvement or remission. Most favourable response 2-5 yrs post surgery
Physical therapy – Helps maintain muscle strength and function.
Lifestyle modifications – Avoiding stress, infections, and certain medications that can worsen symptoms (e.g., aminoglycoside antibiotics, beta-blockers)
MG Classification System
Osserman Classification System
Role of thymus gland in MG
- Link between MG and
thymomas (tumours of thymus
gland) - 10-20% of people with MG have
a thymoma - 20-40% of people with a
thymoma will develop MG
Quick tests for MG
- Aim to elicit fatigue
- Repeatedly blink (induce ptosis)
- Upward gaze (elicit double-vision)
- Count 1-100 (dysarthria)
- Abduct arm (unilateral weakness)
- Forced vital capacity
- Hx thymoma
Myasthenic
Crisis
Weakness from MG that is severe
enough to necessitate intubation
for ventilatory support or airway
protection.
Intubation generally indicated if
evidence of respiratory muscle
fatigue with increasing tachypnea
and declining tidal volumes,
hypoxaemia, hypercapnea, and
difficulty handling secretions.
Plasma exchange is the favoured
treatment for myasthenic crisis.
Cholinergic
Crisis
Respiratory crisis due to
overdose of
cholinesterase inhibitors
Clinical features include
sweating, constricted
pupils, excessive salivation
and muscle fasciculations
MG rating scales/outcome measures
- Myasthenia Gravis Activities of Daily Living (MG-ADL)
- Myasthenia Gravis Quality of Life 15 (
Clinical Features
Bulbar Signs: Initial sign in 15% MG population:
* Nasal regurgitation
* Difficulty masticating solids
* Weak breathy voice quality
Respiratory muscle involvement:
* Acute respiratory
symptoms- medical
emergency
Neck & limb muscle weakness
* Worse at end of day or after
exercise (fatigability
SLT Assessment in myasthenia gravis
- Observe muscle fatigue at rest and during oro-facial exam
- Check for low tone/flaccidity of oro-facial muscles
- Ensure you evaluate person over time
- Stress/Fatigue testSpeech: Count 1-100 and compare speech at
beginning and end - Swallow: Include solids in clinical or instrumental swallow evaluation to determine fatigue of masticatory muscles
Dysarthria features in MG
Flaccid dysarthria:
Hypernasality
Weak breathy voice quality
Low volume
Misarticulation
Fatigability- speech deteriorates
during conversation
Dysarthria Management in MG
- Observe the effects of medical intervention
- Educate person re causes and factors affecting speech
- Energy conservation
- Conservation strategies (rest before conversation, short sentences, take breaks, calls early in day, non-verbal options, quiet environment)
- Prostheses: ptosis props and palatal lifts
Dysphagia in MG
- Difficulty masticating solid food (muscles of
mastication) - Nasal regurgitation of fluids (VP seal)
- Weak tongue movement (lingual muscles)
- Reduced hyolaryngeal excursion (Suprahyoid
muscles) - Poor airway protection (VC adduction)
- Impaired UES tone (reduced CP tone)
- Weak cough response (expiratory muscles)
Dysphagia management in MG
- Observe effects of medical
management - Education
- Compensation- small meals
often, avoid chewy solids, smaller bolus, multiple swallows - Direct rehabilitation contraindicated
Tensilon
(Edrophonium)
Test
- Edrophonium chloride is a shortacting acetylcholinesterase inhibitor that prolongs the duration of action of acetylcholine in the NMJ
- Most reliable in people with
ptosis, nasal speech or strabismus
