Myasthenia Gravis Flashcards
What is myasthenia gravis?
Myasthenia gravis (MG) is a long-term neuromuscular autoimmune disease that leads to varying degrees of skeletal muscle weakness
The most commonly affected muscles are those of the eyes, face, and swallowing
What is the characteristic pathological sign of myasthenia graves?
Myasthenia gravis is characterised by IgG1-dominant antibodies against the post-synaptic acetylcholine receptor (AChR-Ab), or against a receptor-associated protein called muscle-specific tyrosine kinase (MuSK-Ab)
Most cases are due to immunoglobulin G1 (IgG1) and IgG3 antibodies that attack AChR in the postsynaptic membrane, causing complement-mediated damage and muscle weakness
When is the typical onset of myasthenia gravis?
Women under 40, men over 60
What is the clinical presentation of myasthenia gravis?
The initial, main symptom in MG is painless weakness of specific muscles, not fatigue
The muscle weakness becomes progressively worse during periods of physical activity and improves after periods of rest. Typically, the weakness and fatigue are worse toward the end of the day. MG generally starts with ocular (eye) weakness; it might then progress to a more severe generalised form, characterised by weakness in the extremities or in muscles that govern basic life functions
What is the initial symptom of myasthenia gravis?
In about two-thirds of individuals, the initial symptom of MG is related to the muscles around the eye: eyelid drooping and double vision
What are the two types of myasthenia gravis?
Ocular
Generalised
Ocular usually progresses to generalised
How does myasthenia gravis progress?
Starts with eye, often progresses to swallowing and speaking, then head and neck weakness
The muscles that control breathing and limb movements can also be affected; rarely do these present as the first symptoms of MG, but develop over months to years
What is the prognosis for myasthenia gravis?
The prognosis of people with MG is generally good, as is quality of life, given very good treatment
Monitoring of a person with MG is very important, as at least 20% of people diagnosed with it will experience a myasthenic crisis within two years of their diagnosis, requiring rapid medical intervention
What haplotype is associated with increased susceptibility to myasthenia gravis?
Human leukocyte antigen haplotypes
Relatives of people with myasthenia gravis have a higher percentage of other immune disorders
How does the thymus relate to myasthenia gravis?
The thymus gland cells form part of the body’s immune system. In those with myasthenia gravis, the thymus gland is large and abnormal. It sometimes contains clusters of immune cells that indicate lymphoid hyperplasia, and the thymus gland may give wrong instructions to immune cells
Which proteins do antibodies in myasthenia gravis attack?
nicotinic acetylcholine receptor, or a related protein called MuSK, a muscle-specific kinase
How would you diagnose myasthenia gravis?
Serum anti-acetylcholine receptor (ACh-R) antibody testing is the first-line investigation for non-urgent patients
Muscle fatigue after exercise (For example, getting the patient to count up to 50. As the patient nears 50 their voice becomes less audible as they are fatiguing.)
Droop of the upper eyelids is typical with weakness of external ocular muscles producing diplopia
How would you differentiate MS from myasthenia gravis?
Hyperreflexia and extensor plantar response can be seen in MS, which help differentiate it from MG.
What condition is indicated in a positive Babinksi sign?
MS
How would you differentiate MND from myasthenia gravis?
MND usually features of lower motor neurone (LMN) disease with wasting and fasciculation are present
How would you differentiate between MND and MS?
Hyperreflexia and extensor plantar response can be seen in MS
MND usually features of lower motor neurone (LMN) disease with wasting and fasciculation are present
What are the different types of myasthenia gravis?
The antibody specificity: acetylcholine; muscle-specific receptor tyrosine kinase (MuSK); low-density lipoprotein receptor-related protein 4 (LRP4), or seronegative.
Thymus histology: thymitis, thymoma, or atrophy.
Age at onset: child, or aged less than or more than 50 years.
Type of course: ocular or generalised.
What is the main epidemiological group for seronegative myasthenia gravis?
They are predominantly female, tend to be aged under 40 years
How quickly does myasthenia gravis progress?
The most typical pattern is for disease to spread from mild to moderate or severe over the course of weeks or months, although sometimes the disease can remain restricted to the external ocular muscles and eyelids for years
Disease is confined to the ocular muscles in only around 15% of patients.
What is a myasthenic crisis?
Worsening muscle weakness resulting in respiratory failure that requires intubation and mechanical ventilation
What drugs can aggravate myasthenia gravis?
Antibiotics
Beta blockers
Anti-arrhythmic drugs
Neuromuscular blocking agents
How would you manage myasthenia gravis?
Symptomatic treatment with acetylcholinesterase inhibition (Pyridostigmine) is usually combined with immunosuppression
For patients who do not adequately respond to symptomatic therapy, corticosteroids, azathioprine and thymectomy are first-line immunosuppressive treatments
In myasthenia gravis, who would benefit from a thymectomy?
Thymectomy is important if a thymoma is present but may be beneficial even without one.
What is Lambert Eaton syndrome?
Autoantibodies against the pre-synaptic calcium channels
What is the presentation of Lambert Eaton syndrome?
Proximal muscle weakness that IMPROVES with with use (compared to myasthenia graves which gets worse with use)
How would you manage Lambert Eaton syndrome?
Treat underlying cancer
Immunosuppression
IV Ig plasma exchange
What cancer can cause Lambert Eaton syndrorme?
Small cell lung cancer
