Neuro: Myasthenia Gravis and LEMS Flashcards

1
Q

What is Myasthenia Gravis?

A

Myasthenia graves is an autoimmune condition that causes muscle weakness that gets progressively worse with activity and improves with rest.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

At what ages do men tend to be affected by myasthenia gravis?

A

Men over 60 (60-80s)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

At what ages do women tend to be affected by myasthenia gravis?

A

Women under 40, 20s-30s

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What type of tumour is particularly associated with Myasthenia Gravis?

A

Thymoma
There is a strong link between thymoma (tumours of the thymus gland) and myasthenia gravis. 10-20% of patients with myasthenia gravis have a thymoma. 20-40% of patients with a thymoma develop myasthenia gravis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How does a muscle contraction occur?

A

Motor nerves communicate with muscles at neuromuscular junctions.
Axons of motor nerves are situated across a synapse from the post synaptic membrane on the muscle cell
Axons release a neurotransmitter (acetylcholine) from the pre-synaptic membrane
Ach travels across the synapse and attaches to the receptors on the post-synaptic membrane, stimulation the receptors, and this signal leads to muscle contraction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the pathophysiology of Myasthenia Gravis (majority of cases)?

A

Immune system produced acetylcholine receptor antibodies
These bind to the postsynaptic neurotransmitter junction receptors, blocking them and preventing acetylcholine from being able to stimulate the receptor and rigger a muscle contraction
As the receptors are used more during physical activity more of them become blocked up hence less effective stimulation with increased activity hence more muscle weakness occurs on activity
These antibodies also activate the complement system within the neuromuscular junction, leading to damage to cells at the postsynaptic membrane, further worsening the symptoms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the two other antibodies which cause 15% of MG cases?

A

Antibodies against muscle-specific kinase and antibodies against low-density lipoprotein receptor-related protein 4
MuSK and LPR4 are important proteins for the creation and organisation of the acetylcholine receptor, so their destruction leads to inadqeuete acetylcholine receptors.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How does Myasthenia Gravis present?

A

Symptoms anywhere from mild to life threatening in severity
Symptoms minimal in morning and worsening towards the end of the day and with activity
Extraocular symptoms are usually the intital presenations
Proximal muscles and small muscles of head and neck most effected, leading to:
Diplopia
Pstosis
Weakness in facial movement
Slurred speech
Fatigue in jaw when chewing
Progressive weakness with repetitive movements
Difficulty swallowing
Thymic hyperplasia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How can you elicit fatiguability in the muscles of a patient with Myasthenia Gravis?

A

Repeated blinking to exaccerbate ptosis
Prolonged upward gazing will exacerbate diplopia on further eye movement testing
Repeated abduction of on arm 20 times will results in unilateral weakness when comparing both sides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How might you assess lung function in a patient with myasthenia gravis?

A

Test forced vital capacity (FVC)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What scar in particular might be seen on patient with Myasthenia Gravis?

A

Thymectomy scar

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How can Myasthenia Gravis be diagnosed?

A

Diagnosis can be made testing directly for the relevant antibodies:

  • Acetylcholine receptor (ACh-R) antibodies (85% of patients)
  • Muscle-specific kinase (MuSK) antibodies (10% of patients)
  • LRP4 (low-density lipoprotein receptor-related protein 4) antibodies (less than 5%)
  • A CT or MRI of the thymus gland is used to look for a thymoma.

The edrophonium test can be helpful where there is doubt about the diagnosis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the edrophonium test and how is it used to diagnose MG?

A

Patients are given an IV dose of edrophonium chloride (or neostigmine)
Normally cholinesterase enzymes in the neuromuscular junction break down acetylcholine, but these are blocked by the edrophonium test
The weakness is therefore relieved temporarily

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Treatment options for Myasthenia Gravis

A

Reversible acetylcholinesterase inhibitors (usually pyridostigmine (oral) or neostigmine (oral and IV preperations)) increases the amount of acetylcholine in the neuromuscular junction and improve symptoms

Immunosuppression (e.g. prednisolone or azathioprine) suppresses the production of antibodies

Thymectomy can improve symptoms even in patients without a thymoma

Rituximab is a monoclonal antibody that targets B cells and reduces the production of antibodies. It is available on the NHS if standard treatment is not effective

IV immunoglobulin (acute decline or crisis, pts will respons in just over a week)
Plasmapherisis - removes AChR antibodies and short-term improvement - used in myasthenic crisis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is Myasthenic crisis and its management?

A

Myasthenic crisis is a severe complication of myasthenia gravis. It can be life threatening. It causes an acute worsening of symptoms, often triggered by another illness such as a respiratory tract infection. This can lead to respiratory failure as a result of weakness in the muscle of respiration.

Presentation: slack facial muscles, weak neck, drooling, nasal speech, general weakness, unsafe swallow

Mx:

Patients may require non-invasive ventilation with BiPAP or full intubation and ventilation.

Medical treatment of myasthenic crisis is with immunomodulatory therapies such as IV immunoglobulins and plasma exchange.
Admission to ITU
Measure FVC as often as every two hours
Avoid exarrebating drugs (aminoglycosides, muscle relazents, lithium, phenytoin, betablockers CCB, statins, antihistamines, anticholinergics,Mg, IV contrast)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How would you investigate myasthenia gravis?

A

Serum antibodies: anti-Ach receptor (90% generalised MG 50% ocular MG)
MuSK antibodies - found in a small percentage of patients
Thyroid function and thyroid autoantibodies
EMG
Thymus scanning - CT chest
Electro diagnostics - repetitive nerve stimulation
Orthoptic investigations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the basic physiological steps behind sight?

A

Light enters eye
Focusing (cornea and lens)
Signal transfuction (retina)
Processing (optic nerve, tracts and cotrex)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the role of the retina?

A

Signal transduction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What structures are responsible for processing in sight?

A

Optic nerve
Optic Tracts
Optic cortex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What structures of the eye are responsible for cornea and lens?

A

Focusing cornea and lens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is cataract?

A

Condition in chich the lens of the eye (responsible for focusing) becomes progressively opaque, resulting in blurred vision

Opacity or reduction in clarity of the crystaline lens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Symptoms of cataract?

A

Slowly progressive visual loss or blurring
Glare
Reduced colour sensitivity
Reduced night vision
Double vision

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Causes of cataract?

A

Congenital
Age
Drugs - systemic steroids or steroid eye drops
Systemic disease - diabetes, down’s syndrome
Other ocular disease - uveitis
Trauma

24
Q

How is cataract managed surgically?

A

Phaco and IOL

Lens extraction by phacoemulsification (ultrasound energy)
Intraocular lens implant

Day case - LA

25
Q

Outline steps in phaco and IOL?

A

Incision to open cornea
Capsulorhexis - open front surface of lens
Hydrodissection -seperate lens from capsule
Lens fragmentation - break up and aspirate lens
Irrigation and aspiration - clean up capsule
Lens implantation

26
Q

Potential complications of pahco and IOL to manage cataract?

A

Per-operative: Posterior capsular rupture and vitreous loss
Early post-op: Infection - endophthalmitis
Late post-op: Posterior capsule opacification

27
Q

What is posterior capsule opascification?

A

Build up of debris on the capsule, may follow phacoemulsification (cataract) and IOL (intraocular lens)

Treated by YAG laster

28
Q

What is glaucoma?

A

Optic neuorpathy with characteristic visual field defects and optic nerve head changes

Optic nerve fibres progresively damaged

29
Q

What is the most clearly definied risk factor for glaucoma?

A

Raised IOP

30
Q

What should you look for when assesing the optic nerve on fundoscopy?

A

Contour
Colour
Cup
Cup to disc ratio

31
Q

What is the most common visual field test utilised when assesing for glaucoma?

A

Humphrey visual fields

32
Q

What is arcuate scotoma and when is it seen?

A

A localized defect in the visual field bordered by an area of normal vision

Occurs in glaucoma (optic nerve damage)

33
Q

What are the stages of diabetic eye disease?

A

Background
Preproliferative
Proliferative
Maculopathy

34
Q

Myasthenia graves Orthoptic tests

A

Sustained upgrade to see if it induces Ptosis or can even be done
Elicit Cogans lid twitch,
saccades
Ice pack/sleep test for Ptosis
Peek test (or ocular is weakness)

35
Q

How can optic symptoms of myasthenia graves be managed?

A

Prisim to address diplopia
Management of occlusions

36
Q

What type of cancer is associated with neoplastic LEMS

A

SMall cell lung cancer

37
Q

Fluctuating, fatiguable, weakness of skeletal muscle, including extraocular mucles most commonly at presentation, but also bulbar involvement (dysphagia, dysphonia, dysarthria), limb weakness (proximal, symettirc) and respiratory muscle involvment at late stage - is a hallmark of what neurological condition?

A

Myasthenia Gravis

38
Q

Pattern of limb weakness in MG?

A

Proximal, symmetric

39
Q

Extraocular presentation in MG?

A

Often asymmetrical
Ptosis
DIplopia

40
Q

Exacerbating factors in myasthenia gravis?

A

Stress
Infections
Surgery
Drugs, including:
Aminoglycosides
Beta-blockers, CCBs, quinidine, procainamide
Succinylcholine
Magnesium
Ace inhibitors
These medications should be considered to be stopped if worsening symptoms

41
Q

Complications of MG resulting from treatment?

A

Acute exacerbations: myasthenic crisis - undermedication - endrophonium will improve symptoms - tachycardia, respiratory distress, mydrasis or normal pupils, hypertension, normal secretions
Overtreatment: cholinergic crisis (depolarizing muscle block - excessice stimulation of striated muscle) - overmedication - antichollinergics will improve symtpoms, brady cardia, abdominal cramps, miosis, hypotension, increased secretions

Both cause significant weakness, resp failure, unsafe swallow, generalized.

42
Q

How does a chollenergic crisis present, what causes it and how is it managed?

A

Increased seceretions
Pupil constirciton
Bradycardia
Weakness
Fasciulations
Symptoms exaggerated with tensilon test
Improvement with atropine (antichollinergic)
Hypotension

Result of overmedication (inhibition of acetylcholinesterase)
A cholinergic crisis develops as a result of overstimulation of nicotinic and muscarinic receptors at the neuromuscular junctions.

Mx: Stop pyridostigmine, administer anti-muscarinic treatments (aggresive atropine therapy)

43
Q

What is the tensilon test and how does it differential between chollenergic and myasthenic crisis?

A

Edrophonium injection administered

Muscle weakness will improve in myasthenic crisis, exaggerated in chollinergic crisis

44
Q

What is acetylcholinesterase (targeted by achetylecholinesterase inhibitors in treatment of MG)?

A

an enzyme that causes rapid hydrolysis of acetylcholine. Its action serves to stop excitation of a nerve after transmission of an impulse.

45
Q

MG vs LEMS - effect of activity, and why?

A

MG - weakness worse with activity - LEMS - improves

LEMS: Result of antibodies produced by the immune system against voltage-gated calcium channels in small cell lung cancer (SCLC) cells. After high frequency repetitive stimulation or exercise, there is increased activity in the muscle.
POST TETANIC POTENTIATION

MG: AChR antibodies produced (or muscle-specific kinase (MuSK) and antibodies against low-density lipoprotein receptor-related protein 4 (LRP4). MuSK and LRP4 and important proteins for the creation and organization of the acetylcholine receptor. Destruction of these proteins by autoantibodies leads inadequate acetylcholine receptors) - PROBLEM WITH AChR. This leads to less effective stimulation of the muscle with increased activity. There is more muscle weakness the more the muscles are used. This improves with rest as more receptors are freed up for use again.

46
Q

LEMS vs MG symptoms?

A

Lambert-Eaton myasthenic syndrome has a similar set of features to myasthenia gravis.
Both causes progressive muscle weakness with increased use as a result of damage to the neuromuscular junction.
The symptoms tend to be more insidious and less pronounced in LEMS than in myasthenia gravis.

47
Q

Lambert-Eaton myasthenic syndrome (LEMS) pathophysiology?

A

Lambert-Eaton syndrome typically occurs in patients with small-cell lung cancer.
It is a result of antibodies produced by the immune system against voltage-gated calcium channels in small cell lung cancer (SCLC) cells.
These antibodies also target and damage voltage-gated calcium channels in the presynaptic terminals of the neuromuscular junction where motor nerves communicate with muscle cells.
These voltage-gated calcium channels are responsible for assisting in the release of acetylcholine into the synapse of the neuromuscular junction.
This acetylcholine then binds to the acetylcholine receptors and stimulates a muscle contraction.
When these channels are destroyed, less acetylcholine is released into the synapse.

48
Q

Presentation of LEMS?

A

The symptoms of Lambert-Eaton syndrome tend to develop slowly.
The proximal muscles are most notably affected, causing proximal muscle weakness.
It most notably presents with PROXIMAL LEG MUSCLE WEAKNESS (vs initial extraoccular weakness in MG)
It can also affect the intraocular muscles causing double vision (diplopia), the levator muscles in the eyelid causing eyelid drooping (ptosis) and the oropharyngeal muscles causing slurred speech and swallowing problems (dysphagia).
Patients may also experience dry mouth, blurred vision, impotence and dizziness due to autonomic dysfunction.

Patients with Lambert-Eaton have REDUCED TENDON REFLEXES
A notable finding is that these reflexes become TEMPORARIOY NORMAL for a short period following a period of strong muscle contraction - POST TETANIC POTENTIATION

49
Q

LEMS: management

A

It is important to diagnose and manage any underlying malignancy. In older smokers with symptoms of Lambert-Eaton syndrome consider investigating for small cell lung cancer.

AMIFAMPRIDINE allows more acetylcholine to be released in the neuromuscular junction synapses.
It works by blocking voltage-gated potassium channels in the presynaptic cells, which in turn prolongs the depolarization of the cell membrane and assists calcium channels in carrying out their action. This improves symptoms in Lambert-Eaton syndrome.

Other options:

Immunosuppressants (e.g. prednisolone or azathioprine)
IV immunoglobulins
Plasmapheresis

50
Q

LEMS diagnosis?**

A

Diagnosis of Lambert-Eaton myasthenic syndrome (LEMS) is supported by electrophysiological and serological tests.
Cancer is found either at disease onset or subsequently in 40% to 54% of patients with cancer-associated LEMS (CA-LEMS); small cell lung cancer (SCLC) is the most commonly associated cancer.

51
Q

Sensory and reflexes in MG

A

No sensory or reflex loss

52
Q

Autoimmune disorders associated with MG?

A

Thyroiditis
Graves
RA
SLE
Pernicious anaemia

53
Q

Muscle atrophy in MG?

A

Rare but possible

54
Q

When might the tensilon test give a false positive?

A

MND

Also gives 10 percent false negative

55
Q

Bedside spirometry in MG.

A

FVC
If falling rapidly or FVC< 20ml/kg review as may need
ventilation
Blood gases raised C02 decreasing 02 acidosis late manifestations of type I respiratory failure

56
Q

Thymic hyperplasia vs tumour in MG

A

Hyperplasia - cannot be identified by ct, early onset, less common in occular presenation
Tumour - later onset, rarely seronegative, worse prognosis