Myopathy Flashcards
What is a myopathy?
A primary disorder of muscle with gradual onset symmetrical weakness
What may myopathy be confused with?
Neuropathy
What features are more in favour of a myopathy than neuropathy?
Gradual onset of symmetrical proximal weakness
Specific muscle groups affected
Preserved tendon reflexes
No paraesthesia or bladder problems
What does rapid onset muscle weakness suggest?
Drug, toxic or metabolic myopathy
What does excess fatigability suggest?
Myasthenia
What does spontaneous pain at rest with local tenderness suggest?
Inflammatory myopathies
What does pain on exercise suggest?
Ischaemia or metabolic myopathy - McArdle’s disease
What do firm muscles suggest?
Infiltration of fat or connective tissue - pseudo hypertrophic muscular dystrophy (Duchenne’s)
What investigations should be ordered when considering myopathies?
CK ESR AST LDH EMG Muscle biopsy Genetic testing Systemic causes tests such as TSH
What are muscular dystrophies?
Group of genetic diseases with progressive degeneration and weakness of specific muscle groups
Primary abnormality may be in the muscle membrane
What is the commonest muscular dystrophy?
Duchenne’s muscular dystrophy
How does Duchenne’s present?
Clumsy walking at age 4yo Difficulty standing Respiratory failure Pseudohypertrophy of the calves Serum CK >40fold
Describe the genetics and pathogenesis of Duchenne’s
X linked recessive condition
Partial deletions or duplications in dystrophin (stabilises muscle fibres) gene - renders it non functional
Describe the treatment of Duchenne’s
No specific treatment
Home ventilation improves prognosis
What is the prognosis of Duchenne’s
20years
Describe Becker’s muscular dystrophy
Presents similarly to Duchenne’s but at a later age and with a better prognosis
Describe the genetics and pathogenesis of Becker’s
X linked recessive
Partial deletions or duplications in dystrophin rendering it hypo-functional
Describe the genetics and pathogenesis of facioscapulohumeral muscular dystrophy (FSHD)
Two types Autosomal dominant condition Chromosome 4 DUX4 (transcriptional activator) gene Either partial deletions (type 1) or hypomethylation (type 2) of D4Z4 releasing normal repression of DUX4 expression
Describe facioscapulohumeral (FSHD) muscular dystrophy
Onset 12-14yo
Inability to puff out cheeks and difficulty in raising arms above head
Weakness of face, shoulders, upper arms, foot drop, scapular winging, scoliosis, anterior axillary folds and horizontal clavicles
Describe the prognosis of FSHD
<20% need a wheelchair by age 40
What are myotonic disorders
Cause tonic muscle spasm (myotonia) and demonstrate long chains of central nuclei within muscle fibres on histology
What is the commonest myotonic disorder?
Myotonic dystrophy
Describe myotonic dystrophy
Genetically heterogenous (autosomal dominant)
2 types - DM1 is most common and more severe
Both show abnormal trinucleotide repeat expansions in regulatory (non-coding) genetic regions
Presents 20-40yo
Distal weakness, weak sternocleidomastoids, myotonia, facial weakness and muscle wasting.
Cataracts, male frontal baldness, diabetes, testis/ovary atrophy, cardiomyopathy and decreased cognition
Which drug may help with disabling myotonia?
Mexiletine
What is the chief example of inflammatory myopathy?
Inclusion body myositis
Describe how inclusion body myositis presents
Age >50yo
Weakness in quadriceps, finger flexors and pharyngeal muscles
Ventral extremity muscles more affected than dorsal or girdle
What does histology of inclusion body myositis show?
Ringed vacuoles and intranuclear inclusions
What is McArdle’s a disorder of?
Glycogen storage
What drugs may cause myopathy?
Alcohol Statins Steroids Chloroquine Zidovudine Vincristine Cocaine
