Neuromuscular Diseases - Myasthenia Gravis Flashcards
What features may present in a patient with Myasthenia Gravis
Slurred speech and difficulty swallowing
Getting worse in the evenings
Difficulty moving heavy objects - Muscle weakness
Double Vision
Ophthalmoplegia (paralysis or weakness in one or more eye muscles) and Ptosis (drooping of upper eyelid)
Subtypes of MG
ACHr MA - 80% prevalence
MUSK MA - 4% prevalence
LRP4 MA - 2% prevalence
Seronegative MA - 5% prevalence
LEMS - 4% prevalence
Investigations for MG
Electromyography (EMG) and nerve conduction studies (NCS)
Blood test
CT thorax
Ice-pack test (cold ice pack applied over patients eye with ptosis for 2 mins, is there improvement after)
What neruotransmitter is used in the Neuromuscular junction?
Acetylcholine
What are the two peaks in the onset of MG and how are they different?
Juvenile peak at 30 years of age predominatly affecting females - more common in east asia
Late-onset peak at 70-80 years of age, predominantly affecting males
Describe peripheral tolerance of self reactive t cells
Self-reactive T cells evade central tolerance and escape the thymus.
Then they can bind with tissues cells or APCs lacking B7 which leads to anergy of the cell. They can also bind to APCs and be clonally deleted (apoptosis) through ligation of Fas.
Tregs also factor in and supress autoreactive tcell immune response
Describe how anti-ACHr antibodies lead to deficient NMJ transmission in MG
Binding of autoantibodies to acetylcholine receptor lead to increased internalisation and degradation of the receptor.
Antibody binding can also block ACh-AChR binding and induce complement activation, leading to deposition of MAC and damage of postsynaptic membrane.
Describe how anti-MuSKs antibodies lead to deficient MNJ transmission
Binding of antibody interfere with MuSK-LRP4 complex , inhibiting its phosphorylation and recruitment of downstream kinases. The result of this is a reduction on acetylcholine receptor clustering on the post synaptic membrane.
What is the diagnostic pathway for MG diagnoses?
Assay for Anti-ACHr and Anti-MuSK antibodies - seropositive = MG
EMG repetitive stimulation - decreased = MG
Single fibre EMG - increased jitter = MG
Acetylcholine inhibitor test - improvement = MG probable
Assessment of ocular MG - Yes - MG probable
If MG is probable - further testing done through CT or MRI for thymus screening
What is a myasthenic crisis?
A medical emergency that occurs when the muscles that control breathing weaken to the point where individuals require a ventilator
What are the treatments used for MG?
Corticosteroids + non-steroidal immunosuppressants (to reduce b cell/t cell proliferation or activation)
First line of treatment for MG
Acetylcholinesterase inhibitor and thymectomy (if early onset or thymoma)
First line of treatment in Myasthenic Crisis
Intensive care (Ventilator), IVIg or plasma exchange with treatment of infection and other precipitating events
What is thymectomy and why is it used?
Removal of the thymus gland, to reduce the production of autoantibodies and lessen the need for immunosuppressive medications
What is Lambert-Eaton Myasthenic syndrome (LEMS)?
A disease that closely mimics myasthenic gravis, but targets the Voltage gated calcium channels on the presynaptic membrane, preventing vesicle fusion with the presynapse and release of ACh.
