Muscle weakness Flashcards
1
Q
Describe the potential lesion locations causing muscle weakness from spinal cord to muscle.
A
Anterior horn cell –> Spinal roots –> Ganglion –> Plexus –> Peripheral nerve (polyneuropathy) –> Peripheral nerve (mononeuropathy) –> NMJ –> Muscle
2
Q
What can cause damage to the anterior horn cell/motor neuron to produce weakness?
A
- Spinal muscular atrophy
- Infections (Polio, West Nile virus, enteroviruses)
- AML
- Progressive bulbar palsy
- Paraneoplastic syndrome
3
Q
What can cause damage to the spinal roots to produce weakness?
A
- Neurofibromatosis
- Herniated disc
- Infections
- Neoplastic
- Spinal foraminal stenosis
- Trauma
4
Q
What can cause damage to a nerve plexus to produce weakness?
A
- Acute brachial neuritis
- Autoimmune disorders
- Diabetes mellitus
- Haematoma
- Neoplasm
- Neurofibromatosis
- Traction during birth
- Trauma
5
Q
What can cause damage to peripheral nerves to produce weakness?
A
- Entrapment
- Hereditary (Charcot-Marie-Tooth disease)
- Infections (Hep C, HSV, HIV, Lyme disease etc)
- Inflammatory (CIDP, polyradiculoneuropathy, GBS)
- Ischaemia
- Diabetes
- Alcohol
- Vitamin B deficiency
- Amyloidosis
- Renal insufficiency
- Poisoning - lead, arsenic
- Porphyria
6
Q
What can cause damage to the NMJ to produce weakness?
A
- Myasthenia gravis
- Lambert-Eaton syndrome
- Congenital myasthenia (rare)
- Botulism in infants
7
Q
What can cause damage to the muscle fibres to produce weakness?
A
- Dystrophies (DMD, Becker’s, limb-girdle, fascioscapulohumeral)
- Myotonic dystrophy
- Congenital causes
- Endocrine (acromegaly, Cushing’s, hypothyroidism)
- Inflammatory (polymyositis, dermatomyositis)
- Metabolic
8
Q
What is the aetiology and pathophysiology of botulism?
A
An uncommon but lethal disease which is caused by exotoxins of the anaerobe Clostridium Botulinum –> toxin is carried to the NMJ where it binds irreversibly
9
Q
When do features of botulism begin post contamination?
A
6 hours to 8 days
- earlier onset associated with more severe features
10
Q
What are the clinical features of botulism
A
- Progressive, descending flaccid weakness
- GI disturbance
- Sore throat
- Fatigue
- Dizziness
- Paraesthesia
- Potential cranial nerve involvement
11
Q
How is botulism diagnosed?
A
- Isolating Clostridium from the stool, gastric aspirate, or wound
- Mouse bioassay –> survival of immunised mice and death of non-immunised mice when infected serum is injected
12
Q
What is the management of botulism?
A
- Respiratory care (regular FVCs)
- Toxin removal (sorbitol, avoid magnesium)
- Antitoxin (prevent further paralysis)
- Wounds: surgical debridement and benzylpenicillin + metronidazole
13
Q
What is the prevalence and incidence of myasthenia gravis?
A
Prevalence: 15 per 100,000 population
Bimodal peak in incidence: 20-30s and 60-70s
14
Q
Describe the pathophysiology of myasthenia gravis.
A
- Acetylcholine receptor antibodies (AChR-Abs) bind to ACh-Rs on the motor endplate of skeletal muscles
- Binding of AChs blocked
- Once a threshold of motor endplates is lost, the endplate potentials are reduced and fail to trigger a muscle action potential
15
Q
What are the causes of myasthenia gravis?
A
- Most cases are autoimmune (80-90%)
- Thymus abnormalities (thymic hyperplasia or thymoma)
16
Q
Which autoimmune conditions are associated with myasthenia gravis?
A
- Thyroiditis
- Graves’ disease
- Rheumatoid arthritis
- SLE
- Pernicious anaemia
- Addison’s disease
- Vitiligo
- NMO
17
Q
What are the clinical subtypes of myasthenia gravis?
A
- Generalised MG: affects multiple muscle groups
- Ocular MG: weakness limited to eyelids and extraocular muscles
18
Q
What are the antibody subtypes of myasthenia gravis?
A
- MG with AChR-Abs (80-90%)
- MG with Anti-MuSK (4%)
- MG with Anti-LRP4 (2%)
- Seronegative MG
19
Q
What is the hallmark feature of myasthenia gravis?
A
Fluctuating, fatiguable weakness
- Symptoms worse at end of the day or following exercise
20
Q
What are the ocular features of MG?
A
- Diplopia
- Ptosis (enhanced on prolonged upward gaze)
- Weak eye movements (unusual pattern of weakness that does not correlate to a single nerve/muscle)
- Pupillary sparing
21
Q
What are the ‘generalised’ features of MG?
A
- Bulbar muscles: fatiguable chewing, dysarthria, dysphagia
- Facial muscles: expressionless face, poor smile/myasthenic sneer
- Neck muscles: ‘dropped-head syndrome, unable to withstand resistance against forehead
- Limbs: mainly proximal, and arms affected more than legs
- Respiratory muscles: can be serious and lead to life-threatening respiratory failure
22
Q
What investigations should be performed for MG?
A
- Serological (AChR Ab, MuSK, LRP4)
- EMG
- Examination of thymus
- TFTs
- Ice- pack test
- Rheumatological screen (ANA,ENA, CCP, RF)
- Edrophonium (tensilon) test –> no longer done in clinical practice
23
Q
Describe the ice pack test in the diagnosis of myasthenia gravis.
A
- Relies on the principal that NMJ transmission is better at lower temperatures
- Apply an ice pack a closed eyelid
- In patients with MG there should be an improvement in ptosis
24
Q
Describe the edrophonium (tensilon) test in the diagnosis of myasthenia gravis.
A
- Infusion of acetylcholine esterase inhibitor to look for a brief improvement in symptoms
25
Describe the appearance of MG on EMG.
Repeated nerve stimulation will result in a progressive decline in waveform amplitude, suggesting fatiguability
26
What is the differential diagnoses of generalised MG?
- Lambert-Eaton syndrome
- Botulism
- Drug-induced myasthenia (penicillamine)
- Congenital myasthenic syndrome
- Inflammatory myopathies
- MND (bulbar onset)
27
What is the differential diagnoses of ocular MG?
- Disinsertion syndrome
- Thyroid ophthalmopathy
- Mitochondrial disease
- Intracranial mass lesion
- Wernicke's encephalopathy
- Oculopharyngeal muscular dystrophy
28
What is the management of MG?
- Pyridostigmine (15mg QDS for 2-4 days then titrate up to 300mg/day)
- If no response: prednisolone (10mg in generalised MG and 5mg in ocular MG)
- Thymectomy if suitable
29
What is the definition of myasthenic crisis?
Worsening of weakness/myasthenia symptoms that required respiratory support
30
What are the precipitants of myasthenic crisis?
- Warm weather
- Stress
- Surgery, infections, intercurrent illness, comorbidities
- Pregnancy
- Medication
31
What is the pharmacological management of a myasthenic crisis?
- IVIG
- Plasma exchange
- Corticosteroids
- Avoid pyridostigmine (respiratory secretions and risk of aspiration)
32
What are the causes of Lambert-Eaton syndrome?
- Small cell lung cancer (60%)
| - Autoimmune (40%)
33
Describe the pathophysiology of Lambert-Eaton syndrome.
- Antibodies are produced against voltage-gated calcium channels
- Voltage-gated calcium channels in the presynaptic terminals of the NMJ are damaged
- Therefore less acetylcholine can be released into the synapse to stimulate muscle contraction
34
What are the clinical features of Lambert-Eaton syndrome?
- Proximal weakness around the pelvic girdle and weakness around shoulder girdle
- Weakness improves with sustained/repeated exercise
- Reflexes reappear after exercise
- Cranial nerve involvement occurs in 30% (dysphagia, dysarthria, ptosis, diplopia)
- Autonomic symptoms: dry mouth, blurred vision, impotence, dizziness
35
What investigations can be carried out for Lambert-Eaton syndrome?
- EMG
- Single fibre studies
- Imaging to detect malignancy
- Serology for autoimmune cause
- Edrophonium test (result may be +ve, but not to the same extent as in MG)
36
What is the appearance of Lambert-Eaton syndrome on EMG?
- Reduced amplitude of the compound muscle action potential (CMAP) after single supramaximal stimulus
- Increase in amplitude after exercise (post-exercise facilitation)
- Decremental response to repetitive stimulation at 3Hz and incremental response at 30Hz
37
What is the management of Lambert-Eaton syndrome?
- Diagnosis and management of malignancy
- Amifampridine
- Immunosuppression
- IVIG
- PLEX
38
What is the MOA of Amifampridine?
- Blocks voltage-gates potassium channels in the presynaptic channels
- Prolongs the depolarisation of the presynaptic membrane
- Allows calcium channels to release more acetylcholine into the synapse
39
What is the aetiology + pathophysiology of polymyositis?
- Inflammatory disorder causing symmetrical, proximal muscle weakness
- T-cell mediated cytotoxic process directed against muscle fibres
- May be idiopathic r associated with connective tissue disorders
- Associated with malignancy
40
What are the features of polymyositis?
- Proximal muscle weakness +/- tenderness
- Raynaud's
- Respiratory muscle weakness
- Interstitial lung disease (fibrosing alveolitis, pneumonia)
- Dysphagia, dysphonia
41
What investigations should be done for polymyositis?
- Creatine kinase (elevated)
- Muscle enzymes (LDH, aldolase, AST, ALT)
- EMG
- Muscle biopsy
- Anti-synthetase antibodies (Anti-Jo1 antibodies seen in diseases associated with lung involvement, Raynaud's, and fever)
42
What is the management of polymyositis?
Corticosteroids and immunosuppressants
43
What is the aetiology + pathophysiology of dermatomyositis?
- May be idiopathic or associated with connective tissue disorders or underlying malignancy
- Unknown factor activates C3 --> formation of membrane attack complex --> accumulation in capillaries --> destruction of capillary wall --> microinfarctions
44
What are the clinical features of dermatomyositis?
- Progressive proximal muscle weakness
- Heliotrope rash (purplish eyelids + potential periorbital oedema)
- Gottron papules (scaling erythema of knuckles, elbows, knees)
- Macular rash over back and shoulders
- Photosensitivity
- Raynaud's
- Interstitial lung disease
- Dysphagia, dysphonia
45
What investigations should be done for dermatomyositis?
- CT if malignancy suspected
- Creatine kinase (elevated)
- LDH, aldolase, AST, ALT
- ANA, Anti-Mi2
- Muscle biopsy
- EMG
46
What is the management of dermatomyositis?
- Corticosteroids
- Immunosuppressive agents
- IVIG
47
Describe the pathophysiology of inclusion body myositis.
Uknown factor causes myofibres to present MHCI --> CD8+ T cells gather, recognise MHCI, bind --> express perforin --> pores form on myofibre membranes --> cell degeneration
48
What are the clinical features of inclusion body myositis?
- Slowly progressive muscle weakness, sometimes asymmetric
- Muscle atrophy
- Reduced tendon reflexes
49
What investigations should be performed for inclusion body myositis?
- CK (Mild elevation/may be normal)
- Muscle biopsy
- EMG (polyphasic motor unit action potentials with small amplitude, short duration)
50
What is the management of inclusion body myositis?
- Immunosuppressive therapy
| - Physical + speech therapy
