Myasthenia gravis Flashcards
what is myasthenia gravis
Thomas Willis first described MG in 1683. The term Myasthenia is derived from Greek and means ‘Weak muscle’.
Acquired auto-immune disorder affecting neuromuscular transmission (similar to MS)
Excessive fatigue of striated muscle
Longer term permanent denervation and muscle weakness
what is the incidence of myasthenia gravis
incidence= 5/7 per 100, 000
more commonly affects woman but men are increasingly more affected
very variable- complete remisiion in 18% of patients
can be 40 years between first signs and next epsidode
what is the aetiology of myasthenia
Auto-immune disease
Antibodies to nicotinic ACh receptors reduce post synaptic receptors by:
- degrading receptor protein
- directly blocking receptor sites
- destroying receptor sites
What proteins aren’t found in MG
Muscle specific KINASE
MuSK protein (not found in ocular MG)- can also lead to neuro-transmission problems at the neuro-muscular junction
LIPOPROTEIN RECEPTOR RELATED PROTEIN 4 (LRP4)
can be found in MG and ocular MG
why do you get muscle fatigue in ach
ACh continues to be released from pre-synaptic membrane until supplies diminished, resulting in muscle fatigue
Blood findings in MG patients
85% of MG patients have nicotinic ACh receptorantibodies circulating in blood
Post synaptic membrane of neuromuscular junction is less folded in MG patients and synaptic space is wider
Enlarged thymus gland - antigen antibody reaction between endplate protein and thymus epithelial cells
What is the function of the thymus glans
Major role in babies and children up to puberty, then shrinks in size
programmes abcs into attacking and invading foreign cells such as viruses
important in normal development. response development
What is the role of the thymus gland in MG
Thymus gland enlarged in approx 75% of cases (thymomas in some patients, especially over 40 years of age)
Thymus removal cures 35% and improves a further 33% of MG patients
Thymectomy even effective in cases of non-thymomatous MG, with remission rate higher than for non-surgical treatment (Cataneo et al. 2018)
Removal advocated in MG patients between 10 - 40 years of age within 3 years of disease onset
Classifying MG
classified by paediatric populations and adult populations
Paediatric - neonatal, congenital and juvenile
Adult - ocular
- mild/moderate
- acute fulminating
- late severe
Grades of MG
Grade I
- restricted to EOM only
Grade IIa
- mild general disease
Grade IIb
- moderate general disease
Grade III
- severe general disease
Grade 5
- myasthenia crisis
Drugs related to mg
Following D-penicillamine for rheumatoid arthritis
Some antibiotics, cardiovascular agents, anti-depressants, sedatives, anaesthetics can induce or aggravate the condition
What muscle groups are affected
EOM - diplopia and ptosis are the presenting features in 50% of cases and will be present in 90% of patients
Bulbar muscles - innervated by V,VII, IX,X,XI cranial nerves
Limb/trunk muscles - 15-20% start with arm or leg weakness- weakness of intercostal muscles causes breathing problems
Natural history of MG
Variable disease, affecting individuals very differently (sometimes mimics other disease)
If onset initially in EOM prognosis better than if in limbs
Disease may peak 2-5 years from onset then improve
Periods of remission quite common
MG 50 times more common in Grave’s disease patients
Myasthenia crisis
Classed as a Medical Emergency
It is when intercostal muscles are affected and MG patient is unable to breathe without a ventilator
15-20% of generalised MG patients will have at least one myasthenic crisis
50% no known cause, others triggered by stress, infection, surgery or drug sensitivity
EOMs affected in MG
EOM highly innervated with densely concentrated receptors. Small reduction in ACh receptors and ACh levels quickly results in fatigue
Increased sensitivity of EOM neuromuscular junctions
Specific antibodies directed at specific sites on EOM
Ocular MG can mimic
its hard to siagnose
Any pupil sparing painless eye movement problem- unilateral or bilateral III,IV, VI nerve palsy- isolated muscle palsy(IR)- gaze palsy, INO, One and a half syndrome
Extremely variable - may change muscles from one visit to the next – HARD TO DIAGNOSE!!
Diplopia and Ptosis presenting features in 75% of cases
10-16% of all MG confined to eyes
If no spread to other muscle groups within 2 years of onset it is unlikely ever to do so
Clinical features of ocular MG
Ptosis can be unilateral or asymmetrical bilateral. It may increase on least affected side if examiner holds most affected lid. It also may cause fine fluttering lid movements. Also, the patient may use the brow to lift their lid or adopt an AHP (upper eyelid fold may be reduced/ absent)
Afternoon ectropion
Cogan’s lid twitch - lid twitches upwards and overshoots before settling, on moving from depression to normal
Lids forced open easily (weak orbicularis)
Lids separate slightly on voluntary closure (‘peek’ sign)
Nystagmoid jerks of upper lid (rare)
Lid abnormalities in MG
Cogan’s lid twitch
Lids forced open easily (weak orbicularis)
Lids separate slightly on voluntary closure (‘peek’ sign)
Ptosis
CT scan findings in MG
Thymic Abnormalities: Enlarged thymus gland, thymoma (tumor of the thymus), or thymic hyperplasia.
Thymic Masses: Presence of thymic masses or thymic tumors that can be associated with Myasthenia Gravis.
Thymic Hyperplasia: Increased size or abnormal growth of the thymus gland.
Mediastinal Abnormalities: Abnormalities in the mediastinum, such as lymphadenopathy or other masses.
Other findings: In some cases, CT scans may reveal abnormalities in the chest or neck region that could be related to Myasthenia Gravis.
How is MG diagnosed - 3 tests
Tensilon test
- 10Mg injected intravenously (2Mg initially followed by rest)
- Intravenous atropine (0.6Mg) if side effects occur
- improvement in 1 minute, lasts for 5 minutes
Positive response diagnostic, but negative response cannot exclude diagnosis
BLOOD TEST FOR Ach- Blood test for ACh receptor site antibodies. Presence suggests MG highly probable
Absence cannot exclude disease
Anti MuSK antibody test- present in about 50% of those who don’t show ACh receptor site antibodies. Absence doesn’t exclude MG
General treatment of MG
Long acting anticholinesterase drugs (pyridostigmine - Mestinon)
Immunosuppressive agents (azathioprine, cyclosporine) and or systemic steroids
Plasmapheresis
Intravenous immunoglobulin
Thymectomy (not for ocular MG) appears effective in the treatment of non-thymomatous MG (Cataneo et al. 2018)
Ocular MG management
Plotting course of disease / serial record
Prisms or occlusion to make patient comfortable
Ptosis props, if helpful
Botulinum toxin A injection
Strabismus surgery if situation really stable
Drugs aggravating MG
Following D-penicillamine for rheumatoid arthritis. Some antibiotics, cardiovascular agents, anti-depressants, sedatives, anaesthetics can induce or aggravate the condition
Further diagnostic tests
Sleep test- - improvement after 30 minutes in darkened room. Symptoms reappear 1-5 minutes after waking
Ice pack test- ptosis may improve on cooling
Repetitive nerve stimulation
Saccadic velocity measurement
EMG
