Neuro - Myasthenia Gravis, Lamber-Eaton and Guillain-Barre' Syndrome Flashcards
1
Q
What is myasthenia gravis? Explain the pathophysiology
A
- Autoimmune condition that causes muscle weakness that gets progressively worse with activity and improves with rest.
- In 85% of patients, self acetylcholine receptor antibodies bind to postsynaptic neuromuscular junction receptors and block them, preventing the acetylcholine from be able to stimulate the receptor and trigger muscle contraction. As the receptors are used more during muscle activity, more of them become blocked up, leading to less effective stimulation and muscle weakness. These antibodies also activate the complement system - leads to damage to cells in post-synaptic membrane and worsens symptoms.
- 15% of cases: antibodies against muscle-specific kinase (MuSK) and abasing low-density lipoprotein receptor-related protein 4 (LRP4), which are important for creation/organisation of acetylcholine receptor.
2
Q
What are important associations/risk factors for MG?
A
- Thymoma: 20-40% of patients with thymoma develop MG
- Autoimmune disorders: pernicious anaemia, thyroid disorders, rheumatoid and SLE
3
Q
Describe the PC of a patient with MG
A
- Very variable between patients: can be subtle or life threatening.
- Weakness gets worse with muscle use and improves with rest and worst at end of day.
- Proximal muscles affected: shoulders and hips
- Extraocular muscle weakness: diplopia
- Ptosis
- Facial movement weakness, slurred speech, disarthria, dysphagia
- Shortness of breath
4
Q
Describe some examination techniques to elicit fatiguability in the muscles?
A
- Repeated blinking: exacerbates ptosis
- Prolonged upward game: will exacerbate diplopia when you test eye movements
- Repeated abduction of one arm 20 times will cause unilateral weakness when compared to other side
5
Q
What investigations should you perform if you suspect MG?
A
- Single fibre electromyography (high sensitivity - 92-100%)
- Antibodies: ACh-R ( acetylcholine receptor, 85% of patients), MuSK (muscle-specific kinase, 10%), LRP 4 (low-density lipoprotein receptor-related protein 4, less than 5%)
- Edrophonium/Tensilon test: give patients dose of IV edrophonium chloride (or neostigmine) - edrophonium blocks breakdown of acetylcholine and will temporarily relief weakness.
- CT thorax: exclude thymoma (check for thymoma scars)
- CK: will be normal
- Spirometry: if forced vital capacity is less than 1.5L, consider admitting to HDU
6
Q
What treatment options are available for MG?
A
- Reversible acetylcholinesterase inhibitors: pyridostigmine or neostigmine (increases acetylcholine in neuromuscular junction)
- Immunosuppression: prednisolone/azathioprine
- Thymectomy: can relieve sx even if don’t have thymoma
- Monoclonal antibodies: rituximab (targets B cells and reduces production of antibodies)
7
Q
What is a myasthenic crisis? How do you manage them?
A
- Severe complication of MG - can be life threatening
- Acute worsening of symptoms, often triggered by another illness (URTI) - can lead to resp failure
- Patients require NIV with bipap or full intubation/ventilation
- Use IV immunoglobulins and plasma exchange to treat the patient
8
Q
What is Lambert-Eaton myasthenic syndrome?
A
- Causes progressive muscle weakness with increased use as a result of damage to the neuromuscular junction - symptoms tend to be more insidious/less pronounced than in MG.
- Usually occurs in patients with small cell lung cancer - antibodies are produced against voltage-gated calcium channels in SCC cells. These antibodies also target and damage VGCC in the presynaptic terminals of the neuromuscular junction, which leads to decreased acetylcholine released into the synapse
9
Q
Describe the presentation of Lambert-Eaton
A
- Slow onset of symptoms
- Proximal symptoms most affected
- Intraocular muscles: diplopia
- LPS: ptosis
- Oropharyngeal muscles: slurred speech, dysphagia
- Fatiguability with paradoxical initial improvement in power after exercise, followed by sustained weakness.
- Reflexes usually absent but return following use of muscles
10
Q
How would you investigate someone for lambert-Eaton?
A
- EMG: incremental increase of compound muscle action potentials after repetitive stimulation (opposite to MG)
- ACh antibodies: negative
- VGCaC antibodies: usually positive
- Look for malignancy: eg PET scan
11
Q
How would you manage Lambert-Eaton?
A
- Diagnose and manage underlying malignancy - been on lookout for smokers and SCC
- Amifampridine: allows more ACh to be released in synapses
- Immunosuppression: pred or azathioprine
- IV IG
- Plasmapheresis
12
Q
Name some drugs which affect neuromuscular junctions (ie will precipitate MG/LES)
A
- Aminoglycosides
- Beta blockers, calcium channel blockers
- Quinine
- Procainamide
- Chloroquine, penicillamine,
- Succinylcholine
- Magnesium
- ACE inhibitors
13
Q
What is Guillain-Barre’ syndrome? Briefly explain pathophysiology
A
- Acute, symmetrical ascending weakness (and sometimes sensory sx), usually triggered by infection, associated with campylobacter jejune, cytomegalovirus and EBV
- Thought to occur due to molecular mimicry - B cells make antibodies against antigens of pathogen, which have proteins that match proteins on nerve cells. Antibodies are thought to target the myelin sheath of the motor nerve cell or nerve axon
14
Q
How will a patient with GBS present?
A
- Symmetrical ascending weakness
- Reduced reflexes
- May get peripheral loss of sensation/neuropathic pain
- May get cranial nerve involvement - eg diplopia
- Autonomic involvement: urinary retention and diarrhoea
15
Q
How do you investigate GBS?
A
- Dx is made clinically
- Nerve conduction studies: reduced signal through nerves
- LP: CSF will have raised protein with a normal white cell count and glucose
