Myopathy

Question 1

What is a myopathy?

Answer 1

A primary disorder of muscle with gradual onset symmetrical weakness

Question 2

What may myopathy be confused with?

Answer 2

Neuropathy

Question 3

What features are more in favour of a myopathy than neuropathy?

Answer 3

Gradual onset of symmetrical proximal weakness
Specific muscle groups affected
Preserved tendon reflexes
No paraesthesia or bladder problems

Question 4

What does rapid onset muscle weakness suggest?

Answer 4

Drug, toxic or metabolic myopathy

Question 5

What does excess fatigability suggest?

Answer 5

Myasthenia

Question 6

What does spontaneous pain at rest with local tenderness suggest?

Answer 6

Inflammatory myopathies

Question 7

What does pain on exercise suggest?

Answer 7

Ischaemia or metabolic myopathy - McArdle’s disease

Question 8

What do firm muscles suggest?

Answer 8

Infiltration of fat or connective tissue - pseudo hypertrophic muscular dystrophy (Duchenne’s)

Question 9

What investigations should be ordered when considering myopathies?

Answer 9

CK
ESR
AST
LDH
EMG
Muscle biopsy
Genetic testing
Systemic causes tests such as TSH

Question 10

What are muscular dystrophies?

Answer 10

Group of genetic diseases with progressive degeneration and weakness of specific muscle groups
Primary abnormality may be in the muscle membrane

Question 11

What is the commonest muscular dystrophy?

Answer 11

Duchenne’s muscular dystrophy

Question 12

How does Duchenne’s present?

Answer 12

Clumsy walking at age 4yo
Difficulty standing
Respiratory failure
Pseudohypertrophy of the calves 
Serum CK >40fold

Question 13

Describe the genetics and pathogenesis of Duchenne’s

Answer 13

X linked recessive condition

Partial deletions or duplications in dystrophin (stabilises muscle fibres) gene - renders it non functional

Question 14

Describe the treatment of Duchenne’s

Answer 14

No specific treatment

Home ventilation improves prognosis

Question 15

What is the prognosis of Duchenne’s

Answer 15

20years

Question 16

Describe Becker’s muscular dystrophy

Answer 16

Presents similarly to Duchenne’s but at a later age and with a better prognosis

Question 17

Describe the genetics and pathogenesis of Becker’s

Answer 17

X linked recessive

Partial deletions or duplications in dystrophin rendering it hypo-functional

Question 18

Describe the genetics and pathogenesis of facioscapulohumeral muscular dystrophy (FSHD)

Answer 18

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

Question 19

Describe facioscapulohumeral (FSHD) muscular dystrophy

Answer 19

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

Question 20

Describe the prognosis of FSHD

Answer 20

<20% need a wheelchair by age 40

Question 21

What are myotonic disorders

Answer 21

Cause tonic muscle spasm (myotonia) and demonstrate long chains of central nuclei within muscle fibres on histology

Question 22

What is the commonest myotonic disorder?

Answer 22

Myotonic dystrophy

Question 23

Describe myotonic dystrophy

Answer 23

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

Question 24

Which drug may help with disabling myotonia?

Answer 24

Mexiletine

Question 25

What is the chief example of inflammatory myopathy?

Answer 25

Inclusion body myositis

Question 26

Describe how inclusion body myositis presents

Answer 26

Age >50yo
Weakness in quadriceps, finger flexors and pharyngeal muscles
Ventral extremity muscles more affected than dorsal or girdle

Question 27

What does histology of inclusion body myositis show?

Answer 27

Ringed vacuoles and intranuclear inclusions

Question 28

What is McArdle’s a disorder of?

Answer 28

Glycogen storage

Question 29

What drugs may cause myopathy?

Answer 29

Alcohol
Statins
Steroids
Chloroquine
Zidovudine
Vincristine
Cocaine