MG Flashcards
MG definition
Long-term neuromuscular junction disease that is anti-body mediated and causes fatiguable weakness
Pathophysiology of MG
Type 2 hypersensitivity autoimmune reaction:
Autoimmune attack occurs when autoantibodies form against the nicotinic acetylcholine postsynaptic receptors at the neuromuscular junction of skeletal muscles. Autoantibodies bind to nAChR receptors blocking and preventing Ach from binding to them, so muscle contraction is inhibited. AntiAch receptor antibodies can also activated the classic complement pathway (small proteins that work in an enzymatic cascade to fight of bacterial infections) - this causes inflammation and destruction of muscle cell and reduces Ach receptors on the surface. MG patients produce MUSK auto-antibodies, which activate proteins inside the muscle cell and lead to destruction of healthy cells.
Aetiology of MG
Bimodal distribution of age of onset (younger women in 20/30s and older men in 60/70s)
HLA gene and single nuclear polymorphism in various genes
The presence of other autoimmune diseases in the family and the patient
Cancer targeted therapy
Thymus may be involved - thymoma (10%) - thymic myoid cells express AchR and may possibly trigger auto-antibody synthesis but not in MUSK MG.
Hallmark sign
Fatiguable muscle weakness worse at the end of the day or after repetitive movements
Signs and symptoms
Choking/swallowing difficulty
Ptosis
Double vision (diplopia)
Speech difficulty
Breathing difficulty (respiratory dysfunction)
Cogan’s lid twitch (twitch in eyelid when opening and closing eyes)
Bulbar weakness - nasal speech
Curtis sign - lift one eye up, other comes down
Ice on eyes test - transient improvement in conduction - temperature dependent phenomenon - transient opening of the eyes
Upper limbs and proximal muscles
Head drop/neck pain (neck weakness)
Classic clinical presentations
Pure ocular MG - only eyes
Generalised MG - eyes plus another place
MG crisis - rapid deterioration due to bulbar dysfunction or respiratory failure. congenital forms of genetic abnormalities may be present. requires intubation and ventilation
Diagnosis
FVC test (MG <1)
Antibody tests (ACHR, MUSK, Thyroid) - 80% ACHR positive but only 50% in ocular MG - some antibodies yet to be discovered
+ Antibodies and clinical exam = accurate diagnosis
CT thorax - thymoma (usually benign but may be malignant, thymic hyperplasia (enlarged thymus gland) remove with surgery
EMG - decremental loss of CMAP on single-fibre test - some ESPs don’t reach the threshold to trigger an AP. Jitter on SFEMG - a delay between concurrent activation of motor fibres in the same motor unit 95% sensitive for MG
Treatment
Increase synaptic cleft Ach concentration - pyridostigmine (AchE inhibitor)
Control aberrant immune response - steroids (prednisolone)
Remove circulating antibody affect in MG crisis (IVIG or PE) - effect quick but wares off - maximise steroids too (may get steroid dip)
Thymectomy to remove thymoma
Prevent complications if on ventilation and feeding
Prognosis
Risk of iatrogenic side effects
10% brittle disease difficult to manage
90% chance of remission but can take months
