Myasthenia gravis Flashcards
Case presentation of myasthenia gravis
- Variable ptosis (unilateral/bilateral asymmetrical)
- Accentuated by sustained upgaze
- Improves following eye closure
1A. Cogan lid twitch sign - upon looking down (rested), upper eyelid overshoot before saccade back to ptotic position - Furrowing of forehead with frontalis muscle (to compensate weakness)
- Weakness of oculomotor muscles (not limited to any CN) with variable strabismus and diplopia
- Caution for pseudo-INO - Bilateral facial muscle weakness
- Lack of facial expression
- On closing eyes, eyelashes not buried
- Easily overcome eye closure with finger and thumb
- Peek sign - eye drift open to reveal sclera during eye closure
- Inflate cheek easily overcome and air readily escape through lips when cheeks squeezed
- Lips cannot easily opposed - Myasthenia snarl - upper mouth corner fails to contract
- Jaw weakness, jaw hangs open, easily closed with force
- Weakness of neck muscles, flexors > extensors
- Jaw supporting sign - hands under chin to support weak jaw and neck
- Voice weak with nasal twang
- Nasal speech with prolonged vocalisation - count 1 to 25
- Proximal weakness with fatiguability, UL > LL
- Repeated abduct and adduct shoulder 10-15 times - No wasting, DTR normal, sensation normal
Look for:
1. Thymectomy scar
2. IST - steroid side effect - purpura, cushingoid
3. Associated autoimmune disease
- Hyperthyroidism, hypothyroidism
- Diabetes
- SLE
- RA
- Pernicious anaemia
- Pemphigus
- Drug history
How would you differentiate pseudo-INO in MG to actual INO?
- Sustained lateral gaze causes medial rectus of adducting eyes fatigue, thus nystagmus coarser in abducting eye
(INO - adduction becomes normal when abducting eye is covered) - Fluttering of ptotic eyelid (lid hopping)
- Intrasaccadic fatigue:
- Saccadic slowing with repeated eye movement due to fatiguability
- Saccades increasing duration
Pathophysiology of myasthenia gravis
Autoimmune antibodies against nicotinic acetylcholine receptor (nAChR) on post-synaptic membranes of neuromuscular junction causing impaired NMJ transmission
- Complement-mediated destruction
- Complement-mediated damage and loss of normal folds of post-synaptic membrane (reduced area for insertion)
- Functional blockage of receptor
- Accelerated endocytosis and breakdown of nAChR
- Cross-linking 2 adjacent nAChRs by anti-AChR
Clinical classification of myasthenia gravis
- Ocular MG (15%) - weakness confined to eyelids and extraocular muscles
- Generalised MG (85%) - generalised weakness
What are the autoantibodies causing MG?
- Anti-AChR (80-90%)
- Anti-MuSK (10%) - previously thought seronegative
Patients with anti-MuSK are usually female with prominent neck, bulbar and respiratory weakness
What drugs may exacerbate MG?
- Penicillamine
- Aminoglycosides
- Fluoroquinolones
- Macrolides
- Beta blockers
- Calcium antagonist
- Quinine and quinidine
- Procainamide
- Lithium and magnesium
- Phenytoin
- Lignocaine
What is the potential link between rheumatoid arthritis and MG?
- Autoimmune disease association
- Penicillamine-induced MG (treatment for RA)
What other conditions present similarly to MG?
- Botulism
- Lambert-Eaton Myasthenia Syndrome (LEMS)
- Mitochondrial myopathy (CPEO)
- Miller-Fisher syndrome
- Snake bites (cobra, kraits, coral snakes)
What are the differences between MG and LEMS?
What may cause false positive tensilon test?
- Motor neuron disease
- Poliomyelitis
- LEMS
- GBS
- Myositis
- Botulism
What are the causes of false positive nAChR antibodies?
- First degree relatives of patient with MG
- Motor neuron disease
- LEMS
- Thyroid ophthalmopathy
- Autoimmune hepatitis
- Primary biliary cirrhosis
- SLE
- Rheumatoid arthritis
- Penicillamine therapy
Ice pack test
Ice pack applied to ptotic eyelid for 2-5 minutes with improvement of ptosis.
High sensitivity and specificity
However difficult to tolerate
What is Hering’s law?
When a ptotic eye lifted manually, there is no longer a requirement for excessive eyelid intervention, resulting in other eyelid becoming ptotic
Treatment of MG
- Acetylcholinesterase inhibitor - symptomatic
Side effects: muscarinic - nausea, vomiting, diarrhoea, cramps, diaphoresis, lacrimation, salivation, bronchial secretions - Immunosuppressives
- Steroids - may cause transient increase in weakness up to 15%
- Steroid sparing: azathioprine, cyclosporin, MMF - Plasma exchange - acute severe exacerbation
- Lasts 6-8 weeks - IVIG - acute severe exacerbation
- Useful in poor vascular access or septicaemia - Thymectomy
Why do we offer thymectomy to MG patients?
- T lymphocyte tolerance to auto-antigen develops in thymus
- Thymic abnormalities - hyperplasia 65%, thymoma 15%
- More severe, generalised weakness, higher autoAb titres
Thymectomy increased medication free remission
Higher probability if there is thymus hyperplasia, high AChR Ab titre and short duration of disease
