Myopathy Flashcards
What is myopathy?
Primary disorder of muscle with gradual onset of symmetrical weakness
What characteristics point towards myopathy?
Gradual onset of symmetrical proximal weakness- difficulty combing hair, climbing stairs Specific muscle groups affected Preserved tendon reflexes No paraesthesia or bladder problems No fasiculations
What would a rapid onset of symptoms suggest?
A toxic, drug or metabolic myopathy
What does spontaneous pain at rest and local tenderness suggest?
Inflammatory myopathy
What does pain on exercise suggest?
Ischaemia or metabolic myopathy
What does oddly firm muscles (due to infiltrations with fat or CT) suggest?
Pseudohypertrophic muscular dystrophies
What types of myopathic disorders are there?
Inflammatory myopathies Muscular dystrophies Myotonic disorders Congenital myopathies Metabolic myopathies Endocrine myopathies Drug induced/toxic
What are muscular dystrophies?
A group of genetic diseases with progressive degeneration and weakness of specific muscle groups. The primary abnormality is in the muscle membrane.
There may be unusually firm muscles - fat and CT infiltration
In muscular dystrophies, what can be found on histology?
Marked variation in size of individual muscle fibres
What is the most common type of muscular dystrophy?
Duchenne’s muscular dystrophy
In Duchenne’s MD, progressive proximal muscle weakness occurs from what age?
Approximately 4 years old
Does Duchenne’s MD usually affect males or females?
Male
The disorder is x linked recessive
2/3 cases inherited from mother, 1/3 due to new mutation
Duchenne’s is caused by a mutation to the gene for the protein…
Dystrophin - important in maintaining muscle fibre cell membrane
How does Duchenne’s typically present?
Clumsy walking Difficulty standing Waddling gait Respiratory failure - weak diaphragm Scoliosis Dilated cardiomyopathy Arrhythmias
What is Gower’s sign (seen in Duchenne’s MD) ?
Child uses arms to stand up from squatted position
What percentage of patients with Duchenne’s muscular dystrophy have intellectual impairment?
30%
In Duchenne’s muscular dystrophy, pseudohypertrophy can occur especially in the…
Claves
Muscle loss typically occurs where first (in Duchenne’s muscular dystrophy)?
In the thighs and pelvis followed by the arms
Most people with Duchenne’s muscular dystrophy are unable to walk by what age ?
12
Why might affected muscles look larger in Duchenne’s?
Increased fat content
Those with Duchenne’s muscular dystrophy have a high level of what in their blood?
Creatine kinase - more than 40x normal
Is there any specific treatment for Duchenne’s muscular dystrophy?
No
Physical therapy, braces, corrective surgery may help with symptoms
Glucocorticoids can help to slow degeneration
Those with weakness of breathing muscles in Duchenne’s may require…
Assisted ventilation
What is Becker’s muscular dystrophy?
Presents similarly to Duchenne’s but with milder symptoms, later stage and with better prognosis
What is the average life expectancy for someone with Duchenne’s?
26
Does Becker’s muscular dystrophy involve dystrophin gene mutation (similarly to Duchenne’s)?
Yes = dystrophinopathies
No dystrophin - nonsense or frameshift mutation (Duchenne’s)
Misshapen protein -missense mutation (Becker)
Duchenne’s and Becker’s muscular distrophy are x linked recessive disorders. Why can females be manifesting carriers ie show symptoms?
In females only 1 X chromosome gets expressed and the other is inactivated (random) in cell. Would expect half of female cells to have functioning dystrophin gene and half to have defective. These people are typically asymptomatic. If more cells end up with the defective gene, they can be manifesting characters.
Is dystrophin expressed in heart muscle?
Yes
What investigations can be done to diagnose Duchenne’s or Becker’s?
High CK
Mutations in dystrophin - DNA test
Muscle biopsy - stain for dystrophin
What is facioscapulohumoral muscular dystrophy?
A disorder characterised by muscle weakness and wasting. Gets its name from muscles that are affected most often - face, around shoulder blades and upper arms.
When do the signs and symptoms of FSHD usually appear?
12-14
Although onset and severity can vary widely
How does FSHD typically first present?
Inability to puff out cheeks (facial muscles)
Difficulty raising arms over head
What signs are normally present indicating FSHD?
Weak muscles around eyes prevent them closing fully e.g when asleep Ironed out expression of face Scapula winging Foot drop Scoliosis Horizontal clavicles
What is the inheritance pattern of FSHD?
Autosomal dominant
What are myotonic disorders?
They cause tonic muscle spasms (myotonia) and demonstrate long chains of central nuclei within muscle fibres in histology.
The commonest = myotonic dystrophy - has 2 major forms
What are the 2 main types of myotonic dystrophy?
DM1
DM2
What does myotonia mean?
Prolonged muscle contracture; not able to relax muscle at will
What is the inheritance pattern of myotonic dystrophy?
Autosomal dominant
What causes DM1?
A trinucleotide repeat disorder - CTG repeat at the end of DMPK (dystrophia myotonica-Protein Kinase) gene on chromosome 19
What causes DM2?
A repeat expansion of the ZNF9 gene on chromosome 3
Which is commoner and more severe, DM1 or DM2?
DM1
How does DM1 typically present?
Between 20-40 years old Distal weakness(hand/ foot drop) Weak sternomastoids Myotonia - tonic spasms of muscle Facial weakness and muscle wasting give a long, haggard appearance
How is DM2 different from DM1 (in terms of weakness)?
DM2 proximal weakness more prominent
What are some general features of myotonic dystrophy?
Myotonia Weakness of arms and legs Mild mental impairment Diabetes mellitus Testicular atrophy Cardiac involvement - heart block, cardiomyopathy Dysphagia Cataracts Male frontal balding
What is an example of a metabolic myopathy?
McArdle’s disease - glycogen storage disorder
How does McArdle’s disease present?
Muscle pain and weakness after exercise
Acquired myopathies of late onset are often part of systemic disease for example…
Hyperthyroidism
Malignancy
Cushing’s
Hypo and hypercalcaemia
What drugs can cause myopathy?
Alcohol Statins Steroids Chloroquine Vincristine Cocaine
What are some example of inflammatory myopathies?
Inclusion body myosoitis
Polymyositis
Dermatomyositis
Describe polymyositis and dermatomyositis
Rare conditions characterised by insidious onset of progressive, symmetrical, proximal muscle weakness
Autoimmune mediated striated muscle inflammation (myositis)
Associated with myalgia and arthralgia
Muscle weakness may cause dysphagia, dysphonia and respiratory weakness
What is dermatomyositis?
Myositis plus skin signs
When considering myopathy, what tests should be done?
ESR, CK, AST, LDH - may be raised EMG Tests relevant to systemic cause e.g TFT Muscle biopsy Genetic testing
