Myasthenia Gravis Flashcards
Definition of Myasthenia Gravis
- Autoimmune condition with Ab targeting the _____________________
- Resulting in painless muscle weakness that WORSENS w/ activity & IMPROVES w/ rest
- Typically, will lead to early morning asymptomatic phase
- With increasing weakness through the day
- Also, typically FATIGABLE, _________ (some days not as bad as others), and ___________ (with rest)
- Weakness experienced once number of receptors is <30%
Epidemiology: 2 peaks
- 20-30y female
- > 50y male
post-synaptic ACh receptors of NMJ;
VARIABLE;
REVERSIBLE
[Lambert-Eaton syndrome]
Myasthenic disorder associated with malignancies such as ____________________
- Important to detect due to risk of malignancy; need to investigate for malignancy after diagnosis
- Detectable lung tumours may be found 2-4 years after the development of LES
Affects proximal (especially ______________) and truncal musculature
Rarely affects bulbar muscles
Improves with _______________ (vs fatigable muscles in MG) – aka less weak + reflexes reappear
Caused by antibodies to ___________________
small cell carcinoma of lung;
pelvic girdle and thigh;
sustained exercise;
voltage-gated calcium channels
What is the MG Foundation of America grading of MG?
Grade 1: ocular MG
- Anything that involves non-ocular muscles = generalised MG
Grade 2: mild weakness affecting muscles other than ocular muscles (+/- ocular!)
- 2A: limb and axial muscles
- 2B: respiratory and bulbar muscles
Grade 3: moderate weakness (3A, 3B)
Grade 4: severe weakenss (4A, 4B)
Grade 5: intubation required
What are the symptoms of myasthenia gravis?
Extraocular muscles (often first symptoms): ptosis, diplopia. Pure ocular MG are rare (20%), but most generalised MG will have Ocular involvement (70% of all MG pts)
Facial muscles: facial droop
Bulbar muscles: dysarthria, difficulty swallowing (isolated involvement in 20%)
Limb muscles: generalised weakness or reduced exercise tolerance
Truncal muscles: respiratory failure (1%); neck weakness (causing drooped head syndrome)
- Both neck flexors and extensors + diaphragm are considered TRUNCAL muscles.
- Hence a bedside test to assess MG severity will be to assess neck flexion + extension
What is myasthenic crisis?
Weakness from myasthenia gravis severe enough to necessitate intubation or delay extubation following surgery – aka stage 5
What are the precipitants of myasthenic crisis?
Non-compliance to medications
Infections (take extra precaution in event of infection)
Emotions (avoid feeling too stressed)
Drugs
- Antibiotics: aminoglycosides, tetracyclines, macrolides, fluoroquinolones
- CVS: beta blockers, CCB (verapamil)
- Others: chloroquine, quinidine, procainamide, Li, Mg, prednisolone, quinine, penicillamine
Cholinergic crisis
- Caused by excess of cholinesterase inhibitors (neostigmine, physostigmine) given as part of treatment for MG
- Neostigmine and Physostigmines are __________________
- Mainly aimed to work on muscarinic receptors of ANS 🡪 causing DUMBBELLSS syndrome (or SLUDGEM BRH) which stands for ________________________
- Will work on NMJ as well at very high doses 🡪 but risk causing depolarising block! 🡪 ________________-!
reversible Cholinesterase Inhibitors;
diarrhoea, urination, miosis, bradycardia, bronchospasm, emesis, lacrimation, lethargy, salivation, seizures;
Flaccid Paralysis
What are the salient questions to ask in a history for myasthenia gravis?
- Eyelid dropping
- Diplopia
- Fatigable Mastication
- Dysphagia
- Proximal limb fatigability – difficulty climbing stairs
- Weakness in neck flexion
What are the ddx for occular myasthenia gravis?
Thyroid opthalmopathy – aka thyroid eye disease
Chronic progressive external opthalmoplegia (Kearns-Sayre syndrome)
Myotonic dystrophy and oculopharyngeal muscular dystrophy
Brainstem and motor cranial nerve pathology
What are the ddx for generalised myasthenia gravis?
Generalised non-specific fatigue
MND – eg. ALS
Lambert-Eaton myasthenic syndrome (LEMS)
Miller-Fisher/pharyngeal-cervical-brachial variants of GBS because MFS will lead to early involvement of ophthalmoplegia and CN involvement
Botulism
Penicillamine induced MG
Congenital myasthenic syndromes
What would you inspect for on general inspection in a patient with MG?
Mask like facies with ptosis (+/- furrowing of forehead musculature to compensate for ptosis)
Look for malar rash of SLE
Management issues
- Presence of NG tube: suggest swallowing impairment
- Thymectomy scar on chest
- Presence of plasmapheresis line
What would you examine for in a MG’s patient’s eyes?
Ptosis with fatigability 🡪 after extensive upward stare (during eye exam!)
Variable strabismus and diplopia that occurs after sustained gaze
(Examine pupil to ensure isolated ptosis not related to III palsy or Horner’s)
Look for TED (thyroid eye disease): association with hyperthyroidism
Look for anaemia: association with pernicious anaemia
What would you examine for in a MG’s patient’s face?
VII function test – show me your teeth.
Speech assessment – yeeee or count from 1 to 20; listen from progressively worsening nasal voice (bulbar palsy) and hypophonia.
Masseter weakness but pterygoids normal
What would you examine for in a MG’s patient’s neck?
Test neck flexion and extension – assess strength and fatigability 🡪 good surrogate for diaphragm function!
What would you examine for in a MG’s patient’s upper limbs?
Deep tendon reflexes – normal (vs reduced in Lambert-Eaton or Miller-Fisher)
Normal sensation
Fatigability with weakness
- Test muscle strength (eg. abduction)
- Repeat after getting patient to use the muscle 20 times (flap your arms up and down)
- RA/SLE features in joints
What are the conditions is MG associated with?
Endocrine – Thyroid disease, DM, Pernicious anaemia
CTD – RA, SLE, polymyositis
Thymus (75% of cases)
- 15% thymoma
- 85% thymic hyperplasia
What are the investigations performed for MG?
Icepack test
Tensilon test
- Only in patients with obvious ptosis/ opthalmoparesis, such that improvement can be easily observed
- 1ml edrophonium (10mg/ml) is drawn up and given via IV starting with 1mg and progressively increasing every minute up to 10mg
Serologic testing
- AChR Ab
- Anti-muscle specific kinase (Anti-MuSK) Ab (positive when AChR Ab is negative)
- Anti-striated muscle Ab
- FBC: rule out infective exacerbation
Electrophysiology
- Repetitive nerve stimulation test (RNS)
- Single fibre nerve EMG
CXR
- Thymus (appears as anterior mediastinal mass)
- Aspiration pneumonia
CT thorax – review thymus for thymoma
What is the conservative management of MG?
Patient education – including triggers and what to do in event of exacerbation / myasthenic crisis
Allied health – ST for swallowing impairment, PT/OT for mobility issues
What is the medical management of MG?
AChE inhibitors
- Symptomatic management
- Slows down degradation of ACh in the synaptic cleft, allowing for prolonged effect of ACh and thus a variable improvement in strength
- Pyridostigmine: drug of choice in maintenance therapy
- Neostigmine: alternative to pyridostigmine
- Edrophonium: mainly used in diagnostic workup
Chronic immunomodulatory drugs
- Steroids (prednisolone): fastest onset of effect
- Other agents: Azathioprine, MMF, Cyclosporine. Usually added if not responsive to steroids or unable to tolerate steroids (DM, advanced age)
- Rapid immunotherapy: Plasmapheresis, IVIG
What are the side effects of AchE inhibitors?
- Risk of cholinergic crisis
- Cholinergic effects to a milder degree; mostly GIT (abdominal cramping and diarrhoea)
- Mitigated with anti-muscarinic (sparing nicotinic receptors at NMJ): glycopyrrolate, propantheline, hyoscyamine sulfate
What are the indications of immunotherapy?
- Myasthenic crisis
- Preoperatively before thymectomy/other surgery
- As a bridge to slower acting immunotherapy
- Periodically to maintain remission in patients with MG that is not well controlled despite use of chronic immunomodulating drugs
What are the indications of thymectomy?
Thymoma – need to remove malignant thymus
Thymic hyperplasia – preferred given the long-term benefits (twice as likely to achieve remission); not recommended in elderly >60yo
