Myasthenia Gravis Flashcards
Define the term Myasthenia Gravis
An autoimmune mediated disease characterised by episodic weakness of striated muscle, which is typically improved with cholinesterase-inhibiting drugs
Discuss the underlying pathological process in
Myasthenia Gravis
Production of autoimmune antibodies against muscle specific tyrosine kinase (MuSK) and acetylcholine receptors on the post synaptic membrane due to exposure to something like the herpes simplex virus - in some individuals it can be similar to the structure of the acetylcholine receptor and we have a case of molecular mimicry. The autoantibodies can either; bind to the ACh rec - activating complement and destroying the receptor
Block the ACh rec - impeding the ability of ACh to bind
And Modulating antibodies - causing endocytosis of the ACh rec from the surface of the muscle
Discuss the role of the thymus in Myasthenia Gravis
The thymus is an immune organ that usually becomes redundant as we age - in the case of Myasthenia Gravis it continues to produce faulty T cells that organise the B cells to create autoimmune antibodies against ACh
Types
Thymitis (thymus hyperplasia)
1. Women 20-40
2. ↑ B-lymphocytes in thymus
3. Medullary lymphoid follicles found in thymus
Thymoma
1. Middle aged males
2. Mixed tumour of lymphocytic and epithelial cells
Discuss the aetiology of Myasthenia Gravis
Adult MG:
aetiology is unknown but the individual has to be genetically predisposed?
1. Idiopathic
2. HLA – DR3 B8 A1
3. Herpes simplex glycoprotein D cross reactivity
Neonatal MG:
movement of anti-ahc receptors from mother to babies (this wears off after about 6 months like all the other Ab)
Congenital MG: rare autosomal recessive disorder
Describe the typical Myasthenia Gravis patient
Male
i. 40-60
ii. Thymoma
Female
i. 20-40
ii. No thymoma
List the 6 most frequently encountered symptoms and signs of MG
Ptosis, diplopia, muscle fatigue, dysarthria, dysphagia, proximal limb weakness
List 3 important findings that would enable you to exclude other pathologies
No sensory changes, no DTR loss, no muscle wasting
Describe the severe clinical manifestations of MG
a. Generalised quadraparesis (proximal mm)
b. Bulbar involvement (voice alteration, nasal regurgitation, choking, dysphagia)
c. Myasthenic crisis (Resp involvement)
Discuss ocular Myasthenia Gravis
- Ocular MG is a benign variant
- It affects 20% of MG patients
- The disease is limited to extraoccular mm
NB: Extrinsic extraocular mm are affected first in 40% of sufferers and are eventually affected in 85% of patients
Discuss the clinical course of MG
- MG is a chronic relapsing a remitting disease
- The ssx fluctuate in intensity
- symptoms progressively worsen
- in severe cases progression is rapid and death occurs in months but most patients will have a more chronic course over many years
- resp mm are usually affected in 5-20 years after onset
- main cause of death is aspiration pneumonia
- mortality rate with current medicine is 3-4%
List 4 events which cause relapses if MG
i. Pregnancy
ii. Infection
iii. Emotional disturbance
iv. Intense muscular effort
ALSO:
surgery, immunisation, medications, menstruation
Discuss the tests and procedures that are employed in the diagnosis of Myasthenia Gravis
i. Diagnosis usually takes a couple of years because all other muscle fatigue/weakness causes must be ruled out
ii. Clinical Picture, Anticholinesterase Administration, Electrophysiological studies, Serological studies, CT-scan, Thyroid tests
iii. Repetitive nerve stimulation
iv. Single fibre electromyography
Which of the tests is usually used to establish the diagnosis
Anticholinesterase Administration and serology
How is MG treated
- Anti-acetylcholinesterase drugs
- Immunosuppression with Corticosteroids: may stimulate ↑edAch receptor synthesis-Azathioprine & Cyclosporin
- Thymectomy (improved ssx in >50% of Px)
- Plasmapheresis
- IV immunoglobulin (anti-antibody)
- Rest; minimise physical exertion
