Neuromuscular Disorders + Treatments Flashcards
What are the acquired causes of myopathy?
- autoimmune
- endocrine (thyroid, PTH, Addison’s, Cushing’s)
- toxic (corticosteroids, alcohol)
- viral (HIV, HCV)
- metabolic (Ca++/K+)
- critical illness myopathy
What is dermatomyositis?
- 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
What is the treatment of dermatomyositis?
Acute treatment - steroids
Long-term immunosuppressants (methotrexate, azathioprine, mycophenolate mofetil) - started in parallel with steroids
If not tolerated: IVIG, ciclosporin
3rd line: rituximab, cyclophosphamide
What are some other causes of neuromuscular junction dysfunction?
Lambert Eaton Syndrome
Organophosphate poisoning
Botox
Congenital syndromes
What antibodies are present in most cases of mysathenia gravis?
Antibodies against ACh receptors
10-25% anti-MuSK antibodies + 5-10% double seronegative MG
What is the pathophysiology of myasthenia?
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
What are the clinical features of MG?
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
What are the investigations done for MG?
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**
How is MG managed?
- 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)
What can exacerbate MG?
Infection Stress (trauma, post-op) Withdrawal of cholinesterase inhibitors Rapid introduction of increase of steroids Electrolyte imbalance Anaemia Drugs
What is myasthenic crisis?
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
How is a myasthenic crisis managed?
IVIg
Plasma exhange
Ventilatory support
Nil by mouth + NG feeding
How can neuropathies be broadly grouped?
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
What are the most common causes of polyneuropathies?
Diabetes Vitamin deficiencies Endocrine Toxins Hereditary Infectious or inflammatory
Describe Guillain Barre syndrome
Acute inflammatory demyelinating polyradiculoneuropathy (AIDP)
- acute infectious triggers in most cases (pt reports symptoms of URTI or other infection)
What are the clinical features of GBS?
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
What are the investigations of GBS?
CSF - elevated protein NCS - demyelination (velocity decreased) Imaging - exclude structural cause CK - exclude muscle disease TFTs, K, bone - exclude metabolic cause
How is GBS treated?
- discuss with neurology
- IVIg or PLEX
- Supportive care with airway support
- MDT - months to years of recovery
- Enoxaparin - prophylactic anticoagulation
- steroids are no help
Give examples of mononeuropathies and clinical features?
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
Which areas of the brain are being degraded in MND?
Cortical pyramidal cells, cortico-spinal pathways, brainstem motor nuclei (V, VII, X, XII), anterior horn cells
Why is it important to ask for family history of any neurological condition in MND?
Genetic component - increased risk in those with FHx of MS, Parkinson’s, Alzheimer’s etc.
What are the clinical findings of MND?
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
How is MND investigated?
No single test - diagnosed with Hx, exam + progression
MRI spine - exclude other causes
NCS + EMG - exclude multifocal motor neuropathy, features suggest LMN lesion
How is MND managed?
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
What is the median survival of MND?
- 5 years
- early bulbar involvement is bad prognostic sign
- respiratory difficulties - NMRF
Describe acute neuromuscular respiratory failure.
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
