Muscle disorders Flashcards
What kind of bacterium is Clostridium botulinum?
gram positive anaerobic bacillus
How does Clostridium botulinum cause disease?
Produces botulinum toxin, a neurotoxin which irreversibly blocks the release of acetylcholine from vesicles into the synaptic cleft of neuromuscular junction
What are the features of Clostridium botulinum?
o patient usually fully conscious with no sensory disturbance
o flaccid paralysis
o diplopia (double vision)
o ataxia (loss of full control of body movements)
o bulbar palsy
What is Bulbar palsy?
Range of different signs and symptoms linked to impairment of function of the cranial nerves IX, X, XI, XII
Treatment for Clostridium botulinum?
Botulism antitoxin and supportive care
Lambert - Eaton myasthenic syndrome
A rare autoimmune disorder of the neuromuscular junction.
It is a miscommunication between the nerve cell and the muscles that lead to the gradual onset of muscle weakness.
Lambert - Eaton myasthenic syndrome features
o repeated muscle contractions lead to increased muscle strength
o limb-girdle weakness (affects lower limbs first)
o hyporeflexia
o autonomic symptoms: dry mouth, impotence, difficulty micturating
What is Lambert - Eaton myasthenic syndrome associated with?
Associated with small cell lung cancer and to a lesser extent breast and ovarian cancer.
What is the pathophysiology of Lambert - Eaton myasthenic syndrome?
Caused by an auto antibodies directed against presynaptic voltage-gated calcium channels in the peripheral nervous system.
What is the management for Lambert - Eaton myasthenic syndrome?
Treatment of underlying cancer
Immunosuppression, for example with prednisolone and/or azathioprine
Myasthenia Gravis
An autoimmune disorder resulting in insufficient functioning acetylcholine receptors.
Antibodies to acetylcholine receptors are seen in 85-90% of cases
Myasthenia Gravis features
Muscle fatigability - muscles become progressively weaker during periods of activity and slowly improve after periods of rest
o extraocular muscle weakness: diplopia
o proximal muscle weakness: face, neck, limb girdle
o ptosis
o dysphagia
What conditions are associated with Myasthenia Gravis?
o thymomas in 15%
o autoimmune disorders: pernicious anaemia, autoimmune thyroid disorders, rheumatoid, SLE
o thymic hyperplasia in 50-70%
What investigations are done for Myasthenia Gravis?
o Single fibre electromyography
o CT thorax to exclude thymoma
o CK normal
o autoantibodies
What is the management for Myasthenia Gravis?
Acetylcholinesterase inhibitors - pyridostigmine is first line
Immunosuppression - prednisolone initially
Thymectomy
What is the management for Myasthenic crisis?
Plasmapheresis
What is Myotonia?
Failure of muscle relaxation after use
MRC Muscle Power Grading
0 – no movement at all
1 - flicker of movement when attempting to contract muscle
2 – some muscle movement if gravity removed but none against gravity
3 - movement against gravity but not against resistance
4 – movement against resistance but not full strength
5 – normal strength
Polymyositis
Inflammatory disorder causing symmetrical, proximal muscle weakness
Thought to be a T-cell mediated cytotoxic process directed against muscle fibres
Dermatomyositis
A variant of the disease polymyositis where skin manifestations are prominent, for example a purple (heliotrope) rash on the cheeks and eyelids
Features of Polymyositis
o proximal muscle weakness +/- tenderness
o Raynaud’s
o respiratory muscle weakness
o interstitial lung disease: e.g. fibrosing alveolitis or organising pneumonia
o dysphagia, dysphonia
What antibodies are seen in Polymyositis?
anti-Jo-1 antibodies
Screening is usually done after a diagnosis of dermatomyositis, why?
Dermatomyositis is associated with an underlying malignancy (typically ovarian, breast and lung cancer, found in 20-25%
What are the skin lesions found in dermatomyoitis?
o macular rash over back and shoulder
o heliotrope rash in the periorbital region
o Gottron’s papules - roughened red papules over extensor surfaces of fingers
o ‘mechanic’s hands’: extremely dry and scaly hands with linear ‘cracks’
What antibodies are seen in dermatomyositis?
ANA positive antibodies
Inclusion body myositis (IBM)
An inflammatory and degenerative muscle disease that causes painless weakening of muscle.
IBM gets worse slowly and is sometimes misdiagnosed as treatment-resistant polymyositis,
Myotonic Dystrophy
An inherited myopathy with features developing at around 20-30 years old. It affects skeletal, cardiac and smooth muscle.
What are the two types of Myotonic dystrophy?
DM1 and DM2.
What is the inheritance of Myotonic dystrophy?
Autosomal dominant - a trinucleotide repeat disorder
CTG repeat at the end of the DMPK (Dystrophia Myotonica-Protein Kinase) gene on chromosome 19
What are the features of DM1?
Distal weakness more prominent
What are the features of DM2?
Proximal weakness more prominent
What are the general features of Myotonic Dystrophy?
o myotonic facies (long, 'haggard' appearance) o frontal balding o bilateral ptosis o cataracts o dysarthria
What are the less common features of Myotonic dystrophy?
o myotonia (tonic spasm of muscle)
o weakness of arms and legs (distal initially)
o mild mental impairment
o diabetes mellitus
o testicular atrophy
o cardiac involvement: heart block, cardiomyopathy
o dysphagia
How are Dystrophinopathies (muscular dystrophies) inherited?
X-linked recessive - due to mutation in the gene encoding dystrophin, dystrophin gene on Xp21
Duchenne muscular dystrophy
A frameshift mutation resulting in one or both of the binding sites are lost leading to a severe form
Becker muscular dystrophy
A non-frameshift insertion in the dystrophin gene resulting in both binding sites being preserved leading to a milder form
What are the two types of muscular dystrophies?
Duchenne muscular dystrophy
Becker muscular dystrophy
What are the signs of Duchenne muscular dystrophy?
o progressive proximal muscle weakness from 5 years
o calf pseudohypertrophy
o Gower’s sign: child uses arms to stand up from a squatted position
o 30% of patients have intellectual impairment
What are the signs of Becker muscular dystrophy?
Develops after the age of 10 years - milder form of muscular dystrophy
Intellectual impairment much less common
Rhabdomyolysis
Damaged skeletal muscle breaks down rapidly
What are the features of Rhabdomyolysis?
o acute kidney injury with disproportionately raised creatinine
o elevated creatine kinase (CK)
o myoglobinuria
o hypocalcaemia (myoglobin binds calcium)
o elevated phosphate (released from myocytes)
o hyperkalaemia (may develop before renal failure)
o metabolic acidosis
What are the causes of Rhabdomyolysis?
o seizures
o collapse/coma (e.g. elderly patients collapses at home, found 8 hours later)
o ecstasy
o crush injury
o McArdle’s syndrome
o drugs: statins (especially if co-prescribed with clarithromycin)
What drugs cause Rhabdomyolysis?
statins (especially if co-prescribed with clarithromycin)
What is the management of rhabdomyolysis?
IV fluids to maintain good urine output
Urinary alkalinization is sometimes used
What is Spinal muscular atrophy?
Group of hereditary diseases that progressively destroys motor neurons—nerve cells in the brain stem and spinal cord that control essential skeletal muscle activity such as speaking, walking, breathing, and swallowing, leading to muscle weakness and atrophy.
How is Spinal muscular atrophy inherited?
Autosomal recessive inheritance
What is the role of the (SMN1) gene?
Produces the survival motor neuron (SMN) protein which maintains the health and normal function of motor neurons.
What are the features of Spinal muscular atrophy?
Muscle weakness and wasting
Proximal skeletal muscles
Respiratory muscles
Loss of anterior horn cells
What gene is affected in Spinal muscular atrophy?
defects in both copies of the survival motor neuron 1 gene (SMN1) on chromosome 5q.
