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
Investigations for Myasthenia Gravis
- AchR antibody, Anti-MusK
- CT thorax - thymoma
- Electromyography TRO myopathy
- Nerve conduction study TRO neuropathy
- Repetitive nerve stimulation (RNS)
- Previously Tensilon test, ice pack test (superceded by RNS)
