Neuromuscular Disorders + Treatments

Question 1

What are the acquired causes of myopathy?

Answer 1

• autoimmune
• endocrine (thyroid, PTH, Addison’s, Cushing’s)
• toxic (corticosteroids, alcohol)
• viral (HIV, HCV)
• metabolic (Ca++/K+)
• critical illness myopathy

Question 2

What is dermatomyositis?

Answer 2

• cause of inflammatory myopathy
• Signs: Gottron papules, periorbital oedema, heliotrope rash, V-sign, shawl sign, mechanic’s hands
• Acute (days) or subacute (weeks) proximal weakness + myalgia
• CK x10-50 normal
• Anti-Mi2, anti-MDA5, anti-TIF-1a/B/y
• Association with malignancies (lung, breast, ovarian, lymphoma)
• Muscle biopsy shows perifascicular atrophy, perimysial atrophy

Question 3

What is the treatment of dermatomyositis?

Answer 3

Acute treatment - steroids
Long-term immunosuppressants (methotrexate, azathioprine, mycophenolate mofetil) - started in parallel with steroids
If not tolerated: IVIG, ciclosporin
3rd line: rituximab, cyclophosphamide

Question 4

What are some other causes of neuromuscular junction dysfunction?

Answer 4

Lambert Eaton Syndrome
Organophosphate poisoning
Botox
Congenital syndromes

Question 5

What antibodies are present in most cases of mysathenia gravis?

Answer 5

Antibodies against ACh receptors

10-25% anti-MuSK antibodies + 5-10% double seronegative MG

Question 6

What is the pathophysiology of myasthenia?

Answer 6

AChR antibodies bind to and block the receptor, leading to:
1. degradation and endocytosis of ACh receptors
2. degeneration of motor end plate
Leads to reduced muscle membrane depolarisation + increase in threshold require to generate AP in muscle

Question 7

What are the clinical features of MG?

Answer 7

Fluctuating, symptoms can resolve, diurnal variation
Clinical hallmark is fatigability
Weakness of extraocular muscles: ptosis + opthalmoplegia
Weakness of neck/extension/flexion
Proximal limb weakness + finger extensor weakness
Reflexes + sensation preserved

Question 8

What are the investigations done for MG?

Answer 8

AChR antibody, MuSK antibody (tests can take 2 months)
Ice pack test (resolves ptosis due to denaturing enzymes)
Tensilon test (edrophonium IV improves muscle strength temporarily)
Exclude thymoma with CT chest
Neurophysiology - repetitive nerve stim, SFEMG**

Question 9

How is MG managed?

Answer 9

• Pyridostigmine (plus propantheline)
  inhibits ACh breakdown, increasing synaptic respone to ACh
• Steroids (immune supression)
• PLUS steroid sparing agents (azathiprine, ciclosporin, methotrexate , mycophenolate motefil)
• IVIg, PLEX
• Rituximab (strong immunosuppression)

Question 10

What can exacerbate MG?

Answer 10

Infection 
Stress (trauma, post-op)
Withdrawal of cholinesterase inhibitors 
Rapid introduction of increase of steroids
Electrolyte imbalance
Anaemia
Drugs

Question 11

What is myasthenic crisis?

Answer 11

Neurological emergency- 20% will develop
Increasing muscle weakness + diplopia
T2 respiratory failure (hypercapnia)
O2 sat + blood gases can be normal until it is too late so don’t use as a measure
Use FVC - less than 1L - requires ICU support

Question 12

How is a myasthenic crisis managed?

Answer 12

IVIg
Plasma exhange
Ventilatory support
Nil by mouth + NG feeding

Question 13

How can neuropathies be broadly grouped?

Answer 13

Demyelinating

• conduction velocity reduced, amplitude of muscle AP preserved
• secondary axonal degeneration

Axonal

• amplitude of muscle AP reduced, conduction velocity preserved
• secondary demyelination

Distinguished by nerve conduction studies

Question 14

What are the most common causes of polyneuropathies?

Answer 14

Diabetes
Vitamin deficiencies
Endocrine
Toxins
Hereditary
Infectious or inflammatory

Question 15

Describe Guillain Barre syndrome

Answer 15

Acute inflammatory demyelinating polyradiculoneuropathy (AIDP)
- acute infectious triggers in most cases (pt reports symptoms of URTI or other infection)

Question 16

What are the clinical features of GBS?

Answer 16

Progressive weakness - hours to days
Areflexia
Peak in <4 weeks
Symmetrical
Motor» sensory, with pain
Autonomic dysfunction in most cases (BP, arrhythmias, urinary retention)
Facial involvement + bulbar involvement - may need help with feeding

Question 17

What are the investigations of GBS?

Answer 17

CSF - elevated protein
NCS - demyelination (velocity decreased)
Imaging - exclude structural cause
CK - exclude muscle disease
TFTs, K, bone - exclude metabolic cause

Question 18

How is GBS treated?

Answer 18

• discuss with neurology
• IVIg or PLEX
• Supportive care with airway support
• MDT - months to years of recovery
• Enoxaparin - prophylactic anticoagulation
• steroids are no help

Question 19

Give examples of mononeuropathies and clinical features?

Answer 19

Carpal tunnel (median nerve palsy) - tingling + weakness of hands
Ulnar nerve palsy (weakness in hand, tingling of fourth + fifth finger, tender elbow)
Radial nerve palsy (wrist drop)
Common peroneal/fibular nerve palsy (foot drop)

Compression of nerves

Question 20

Which areas of the brain are being degraded in MND?

Answer 20

Cortical pyramidal cells, cortico-spinal pathways, brainstem motor nuclei (V, VII, X, XII), anterior horn cells

Question 21

Why is it important to ask for family history of any neurological condition in MND?

Answer 21

Genetic component - increased risk in those with FHx of MS, Parkinson’s, Alzheimer’s etc.

Question 22

What are the clinical findings of MND?

Answer 22

Painless, progressive weakness + wasting
Eye movements normal
Lower cranial nerves - jaw weakness, jaw jerk brisk, facial weakness, gag reduced/exaggerated, bulbar palsy, tongue fasiculations
Head drop
Limbs UMN/LMN signs e.g. weak, wasted + fasciculations but brisk reflexes
Cachexia
Sensation normal
Cognition - frontal involvement - emotional lability

Question 23

How is MND investigated?

Answer 23

No single test - diagnosed with Hx, exam + progression
MRI spine - exclude other causes
NCS + EMG - exclude multifocal motor neuropathy, features suggest LMN lesion

Question 24

How is MND managed?

Answer 24

SALT - lost speech
Nurse specialist
Gastroenterologist/dietitian - lost swallow
Non-invasive ventilation
Palliative care - symptom control
Riluzole - watch LFTs, delays onset of ventilator dependence + can extend survival slightly

Question 25

What is the median survival of MND?

Answer 25

3. 5 years
   - early bulbar involvement is bad prognostic sign
   - respiratory difficulties - NMRF

Question 26

Describe acute neuromuscular respiratory failure.

Answer 26

O2 sats + ABG normal until very late
FVC <1L

Acute: pts don’t often complain of SOB but single breath test often reveals SOB; anxiety, increased HR, accessory muscles

Acute on chronic: confusion + sedation

Top causes: GBS, MG, MND