NMJ conditions

Question 1

Pathophysiology and aetiology of Myasthenia Gravis

Answer 1

(1. ) Most common cause of acute fatigable, weakness affecting ocular, facial and bulbar muscles
(2. ) AI disease caused by:
- (80%) autoantibodies to Ach-R of post-synaptic mb at NMJ
- or abs against MuSK which produces a similar clinical picture
(3. ) (15%) Pts may have a benign-thymoma (this is usually atrophied in adult life)

Question 2

RF of Myasthenia Gravis

Answer 2

• <50y female predominant

- >50y male predominant

Question 3

Clinical features of Myasthenia Gravis

Answer 3

(1.) Fluctuate, Slowly increasing or relapsing muscular fatigue

(2. ) Ophthalmoplegia: Ocular weakness
- Droopy eyelids (ptosis)
- Double vision (diplopia)

(3. ) Limbs and bulbar weakness
- Affects swallowing and speech

(4. ) Fatigability is hallmark
- This is worsening weakness after prolonged and sustained muscle contraction e.g. hanging clothes after pegging 3-4 shirt and they feel like they need to relax their arms before pegging more clothes OR combing hair may require frequent rests

(5. ) Sx exacerbated by (potentially triggering myasthenic crisis):
- end of the day or after exercise is characteristic
- Pregnancy
- Infection
- Medication: gentamicin, opiates, tetracycline, quinine, Botulinum toxin, steroids, withdraw of cholinesterase inhibitors
- Stress

(6.) NOTE: Tendon reflexes and sensation are normal

Question 4

Ex of Myasthenia Gravis (5)

Answer 4

Following examinations can be done to elicit ‘fatiguability’

(1. ) Repeat blinking and this will cause weakness and ptosis
(2. ) Upward gazing will cause diplopia
(3. ) Repeated abduction of arm, will cause unilateral weakness when comparing both arms
(4. ) Ice pack test: apply for 2-5mins to eyelid and improve ptosis (due to dec Ach breakdown) Not diagnostic
(5. ) Cogan’s lid twitch
- Ask pt to gaze downward for 10–15s and then return to primary gaze.
- Cogan’s sign is present when the affected lid briefly “twitches” upward on returning to primary gaze

Question 5

Ix of Myasthenia Gravis (4)

Answer 5

(1. ) Serology: Acetylcholine receptor antibodies
- Anti-AchR +ve in 80-85%
- Anti-MuSK +ve in 10%

(2. ) Edrophonium (Tensilon test)
- Not done anymore due to dangers
- Involves IV endrophonium bromide (which blocks action of cholinesterase enzymes) so Ach levels increases and will relieve weakness and fatigue sx of MG pts

(3. ) Repetitive stimulation w/EMG
- Decremental muscle response (i.e. AP decline) to repetitive nerve stimulation

(4.) Thymus CT/MRI scan: if they have thymoma

Question 6

Mx of MG? (4)

Answer 6

(1. ) Ach-esterase inhibitor: Pyridostigmine
- Cholinergic SE: diarrhoea, colic
- Overdosage can cause ‘cholinergic crisis’ sx: Muscle fasciculation, paralysis, pallor, sweating, excessive salivation, small pupils

(2.) Steroids: Prednisolone

(3. ) Steroid sparing agents: Azathioprine, ciclosporin, methotrexate
- This is an alternative immunosuppressant that will suppress ab production
- Allows for glucocorticoid steroids dose to be reduce and help with withdrawal

(4. ) Thymectomy, considered if:
- thymoma present
- <60yrs with onset <5yrs and poor response to medical therapy

Question 7

Myasthenic crisis: What is it? Mx?

Answer 7

(1.) It is a medical emergency - life threatening weakness of respiratory muscles. MuSK +ve cases are likely to develop this.

(2. ) Comprises of one or combination of following:
- Lead to respiratory failure
- Impaired swallow
- Severe limb weakness

(3. ) Signs and Sx:
- Increasing muscle weakness + diplopia
- Quiet breathing, reduced chest expansion, tachycardia, HTN suggests hypoxia

(4. ) Mx
- Monitor Forced vital capacity, FVC
- Ventillation
- Plasma exhange and IV immunoglobulin (to removes and lowers production of ab causing this crisis)
- Idenitfy trigger e.g. infection

Question 8

Congenital myasthenic syndrome - aetiology?

Answer 8

Congenital myasthenic syndrome is not due to autoimmunity, it is due to mutations in NMJ-protein-encoding-genes: ColQ, DOK7, CHRNE

Question 9

What is Lambert Eaton Syndrome?

Answer 9

Can be autoimmune or paraneoplastic

• 50-60% of cases have underlying malignancy and Ix should involve identifying neoplasm
• AI: Ab against pre-synaptic voltage gated Ca channels –> impairing transmitter release across NMJ –> muscle weakness

Question 10

RF of Lambert Eaton Syndrome

Answer 10

• Non-cancer LEMS present at any age, associated with T1DM, thyroid disease.
• Paraneoplastic LEMS >50y, associated with SMALL CELL LUNG CANCER

Question 11

Clinical features of Lambert Eaton Syndrome

Answer 11

(1. ) Muscle weakness
(2. ) Hyporeflexia
(3. ) ANS dysfunction
- dry mouth, sphincter problems, postural hypotension, erectile dysfunction

Question 12

Dx/Ix of Lambert Eaton Syndrome (3)

Answer 12

• EMG = decremental response
• Bloods: Voltage-gated calcium-channel antibodies
• if associated with lung cancer: X-rays or a CT scan of lungs

Question 13

Tx Lambert Eaton Syndrome (3.)

Answer 13

(1. ) 3,4 diamino-pyridine: blocks K channels in the nerve terminals
(2. ) Treatment of cancer
(3. ) Steroids

Question 14

What is Neuromyotonia/Isaac’s Syndrome

Answer 14

• Due to peripheral nerve hyperexcitability
• Three types: acquired (80%), hereditary, paraneoplastic
• Autoantibodies against voltage gated K channels on nerve terminals, resulting in hyperexcitability

Question 15

Sx of Neuromyotonia/Isaac’s Syndrome

Answer 15

o	Cramps
o	Fasciculations (twitches) 
o	Hyperhidrosis (abnormal sweating) 
o	Myokymia (involuntary eyelid movement) 
o	Fatigue
o	Exercise intolerance
o	Stiffness