Myasthenia gravis Flashcards
What antibodies are associated with myasthenia gravis?
ACh receptor Ab - 80-90% sensitive MuSK Ab - positive in 40% of AChR-negative patients. - more severe weakness, particularly respiratory and proximal weakness (esp neck extension) - recognised oculobulbar form, with diplopia, ptosis, dysarthria - not purely ocular - not associated with thymic disease. LRP4 Ab - mild-moderate disease - not associated with thymic disease. Anti-striated muscle Ab - positive in 90% of thymomas Ryanodine receptor Ab - positive in 70% of thymomas with MG - marker for severe disease Titin Ab (in addition to ACh R Ab) - thymoma and late-onset MG Agrin Ab - poor sensitivity but specific for MG
What should be specifically checked for an examination?
Sustained upward gaze - weakness of eyelid elevators and oculomotor muscles
Peek sign - eyelids separate after 30sec of closing, and sclera is visible.
Dysarthria - palate weakness
Dysphonia on counting - bulbar weakness
Smiling causes snarling expression
Neck flexion weakness
Flap 1 arm then test muscle strength together - asymmetrical due to fatigue of one arm
What does EMG show?
Repetitive stimulation shows progressive decrease in amplitude of action potentials
Needle examination - motor unit potential variation and, sometimes, fibrillation potentials and myopathic changes
Single-fibre EMG - increased jitter and blocking
What other investigations should be performed in MG?
Thymoma search - CXR, chest CT or MRI
Respiratory function tests - weakness in muscles of respiration
What is myasthenic crisis and how is it treated?
Crisis involves respiratory weakness causing respiratory failure. Often caused by an infection. Treat with ABx, although aminoglycosides may worsen symptoms.
What is first line treatment for Myasthenia Gravis?
Acetylcholinesterase inhibitors - pyridostigmine
K supplements and K-sparing diuretics may improve symptoms but are rarely used
What if acetylcholinesterase inhibitors fail?
Steroids - may worsen symptoms and therefore should be monitored closely during initiation.
Immunosuppressants next line - AZA may be used as steroid-sparing agent, however should never be used as monotherapy.
Rituximab in desperate cases
What % of myasthenia gravis have isolated ocular signs?
15%
Which antibodies are implicated in isolated ocular myasthenia gravis?
ACh and LRP4 (not MuSK)
What autoimmune diseases are often associated with myasthenia gravis?
Thyroiditis (most commonly)
SLE and RA
NMO
ALS
Kv1.4 Ab in myasthenia gravis are associated with which coexisting cardiac condition?
Myocarditis
What is the most effective cholinesterase inhibitor used in myasthenia gravis?
Which subpopulation is it less effective in?
Pyridostigmine
Less effective in MuSK positive patients
What is second line Rx for myasthenia gravis?
Third? Fourth?
2nd - Prednisone + AZA
3rd - Mycophenolate (mild) or rituximab (moderate)
4th - MTX, cyclosporin, tacrolimus
How is myasthenic crisis treated?
IVIG or plasmapheresis
Which myasthenia patients should have a thymectomy?
Recommended in:
- Those with thymomas
- Early-onset myasthenia gravis
- Generalised myasthenia gravis and ACh receptor Abs. 70% of these show improvement after thymectomy.
- Seronegative MG with generalised disease and biomarkers similar to early-onset MG
Not recommended in:
- MuSK or LRP4 Ab positive
- Ocular MG
- Seronegative MG
