myopathies

Question 1

what are the 2 main types of muscle fibres

Answer 1

Type 1– rich in myoglobin, with low metabolism (aerobic) and rich in sarcoplasm

Type 2– low in myoglobin, with high metabolism (aerobic or anaerobic) and little sarcoplasm

Question 2

clinical features of myelopathy

Answer 2

• Gradual onset
• Symmetrical, proximal weakness: difficulty combing hair, climbing stairs, getting up from chairs
• Dystrophies usually affect specific muscle groups
• Preserved tendon reflexes– usually preserved till wasting and weakness is severe – helps distinguish myopathies from LMN syndromes.
• Changes in muscle tone – may be hypotonia – secondary to muscle disease.
• Changes in muscle bulk- wasting of affected muscles is distinctive in contrast to distal wasting of most neuropathies. Enlargement of muscles may be early sign of certain dystrophies caused by fat infiltration, therby exacerbating weakness.
• Changes in muscle contractility – myotonia = persistence of contraction, often for several seconds during attempted relaxation. Found in myotonic dystrophy, paramyotonia congenita.

NB: on EMG characteristic findings consist of rhythmic discharges.

Pain – rare complaint of in primary muscle disease, except in deficiencies of certain enzymes of carbohydrate or lipid pathways or in severe inflamm myopathy (e.gpolymositis, vasculitis). It is imp to ask about a change in the colour of urine, as this may indicate myogloburia secondary to rhabdomyolysis which can occur in some metabolic disorders.

Question 3

is it myopathy/neuropathy??

Answer 3

In favour of myopathy:

• Gradual onset of symmetric proximal weakness – difficulty combing hair and climbing stairs (NB weakness is also distal in myotonic dystrophy)
• Dystrophies – usually affect specific muscle groups ( selective weakness on first presentation)
• Preserved tendon reflexes

In favour of neuropathy:

• Paraesthesia
• Bladder problems
• Distal weakness
• Rapid onset - more likely to suggest neuropathy or toxic drug or metabolic myopathy

Other features

• Spontaneous pain at rest and local tenderness occurs in inflammatory myopathies.
• Pain on exercise suggests ischaemia or metabolic myopathy (e.g. McArdle’s disease)
• Oddly firm muscles (due to fat infiltration with fat and CT) suggest pseudohypertrophicmuscular dystrophies (e.g. Duchennes)
• Fasciculations suggest anterior horn cell or root disease
• Lumps are commonly caused by haematoma, herniation of muscle through fascia and tendon rupture. Muscle tumours are rare.

Question 4

onset + fhx

Answer 4

• Onset: In childhood – delayed motor milestones
• Fx: muscle disease typically inherited
• X-linked: DMD, Becker’s, muscular dystrophy and Emery–Dreifuss dystrophy
• Autosomal dominant: facio-scapulo-humeral dystrophy, scapuloperoneal dystrophy and myotonic dystrophy
• Autosomal recessive: limb-girdle dystrophy, all deficiencies of enzymes of glycolytic and lipid metabolism
• Mitochondrial: sometimes maternal inheritance. Chronic progressive external ophthalmoplegia and Kearns–Sayre syndrome

Question 5

ix of muscle disease

Answer 5

• ESR, CK (creatine kinase), AST & LDH serum creatine phosphokinase (CPK) may be raised. -often significantly raised in many dystrophies and in inflammatory muscle disorders e.g. polymyositis.
• EMG – needle examination will reveal ‘myopathic units’ (small, short duration, spiky polyphasic units) . may be evidence of myotonic discharges in myotonias and increase in spontaneous activity (fibrillation potentials and positive sharp waves) in primary myopathies and inflamm muscle disease.
• Muscle biopsy – can yield info about fibre type (type 1 or 2), inflammation and dystrophic and histochemical changes, electron microscopy is sometimes required. (NB: use muscle biopsy only if genetic tests are non-diagnostic).
• MRI – used to demonstrate patterns of muscle involvement – can be helpful in differentiating the dystrophies and selecting a muscle to biopsy.
• Genetic testing – increasing num of hereditary myopathies can be diagnosed by a genetic test.

Question 6

define muscular dystrophy and give examples

Answer 6

• Group of genetic disease w/ progressive degeneration and weakness of specific muscle groups

1^O pathology: abnormality of muscle membrane

eg.

• DMD
• BMD
• fascioscapulohumeral MD [landouzy dejerine]
• myotonic disorders
• inflammatory myopathies
• acquired electrolyte + endocrine yopathies [acquired myopathies of late onset]
• drug induced myopathies

Question 7

DMD: define, epi, aetiology, s/s, ix, rx

Answer 7

Definition

• X-linked recessive, caused by an absence of dystrophin (connects cytoskeleton of muscle cells to the extracellular matrix through the membrane)

Epidemiology

• Commonest: 3/1000 male births
• Age of onset: ~4yrs old

Aetiology

• Genetic: X-linked recessive

Clinical assessment

• No abnormalties at birth
• Osnet: ~4 yrs old à wheelchair bound by 10yr à death ~20yr
• Proximal weakness
• Calf pseudohypertrophy: accumulation of connective tissue and fat
• Difficulty standing: gower’s sign – ‘climb’ up legs w/ hands to stand – to overcome pelvic muscle weakness
• clumsy walking: waddling gait
• Complications: Respiratory failure, arrhythmias, cardiomyopathy

Investigation

• ↑↑CK: >40 fold 10 000 U/L
• EMG: myopathic
• Muscle biopsy: fatty infiltration and absence of staining for dystrophin
• DNA diagnosis: carrier status

Treatment

• No cure
• supportive: home ventilation improves prognosis
• steroids: short term
• Genetic counselling: vital

Prognosis

• some survive > 20yrs

Question 8

BMD: define, epi, aetiology, s/s, prog

Answer 8

Definition

• X-linked recessive condition - partially functioning dystrophin

Epidemiology

• 0.3/1000 male births

Aetiology

• Genetic: X-linked recessive

Clinical assessment

• Presents later: 1^st decade of life
• less severe: cramps associated with exercise
• complications: cardiomyopathy (maybe worse than skeletal weakness) – predisposes to arrhythmias

Prognosis

• has better prognosis

Question 9

fascioscapulohumeral MD [landouzy dejerine]

Answer 9

Epidemiology

• Almost as common as DMD

Aetiology

• Genetic: AD inheritance

Clinical assessment

• Presentation
• Onset @ 12-14yrs
• Difficulty puffing cheeks and raising arms above head
• Signs
• Weakness of face, shoulders and upper arms (often asymmetric w/ deltoids spared)
• Winging of scapula
• Scoliosis
• Foot drop

Prognosis

• <20% need wheelchair by 20yrs

Question 10

myotonic disorders- definition, epi, aetiology, s/s, ix, mx, prog

Answer 10

Definition

• Muscle disease associated w/ tonic muscle spasm (myotonia)

Epidemiology

• common adult muscle disease: prevalence of 1 in 7000 UK
• Age of onset: 25 yrs

Aetiology

• Genetic: AD inheritance - Cl^-channelopathy

Clinical assessment

• Face
• Facial weakness and muscle wasting: myopathic face - long haggard appearance
• weak sternocleidomastoid
• ptosis
• Dysarthria: myotonia of tongue and pharynx
• Hands
• Wasting and weakness of distal muscles + areflexia → wrist drop
• Myotonia: slow relaxation
  
  • E.g. inability to release hand after shake
• Percussion myotonia: percuss thenar eminence→ involuntary thumb flexion
• Other
• ↓ cognition
• Male Frontal balding
• Cataracts
• Cardiomyopathy, tachy- / brad-arrhythmias
• Testicular/ovary atrophy
• DM

Investigation

• Histology: long chains of central nuclei w/i muscle fibres

Management

• No Rx for weakness
• Mexiletine, Phenytoin, acetazolamide - may improve myotonia
• genetic counselling

Prognosis

• Most die in middle-age of intercurrent illness

Question 11

inflammatory myopathies

Answer 11

Definition

• Conditions in which there is inflammation within the muscle

Types

• Inclusion body myositis
• Polymyositis and Dermatomyositis (rheumatology): associated w/ connective tissue disease or underlying carcinoma

Epidemiology

• Polymyositis and Dermatomyositis:
• Presents: 40-50s
• W>M
• Inclusion body myositis
• Common
• Present: >50

Clinical assessment

• Polymyositis and Dermatomyositis:
• Motor: proximal weakness – difficulty getting of chairs, climbing stairs
• Pain/tenderness: <50%
• Associated skin changes: Dermatomyositis (rheumatology)
• Inclusion body myositis
• Motor: weakness:
  
  • Quadriceps: difficulty climbing stairs
  • Flexor muscles of forearm and hand: difficulty holding onto objects
  • Pharyngeal muscles:

Investigation

• Polymyositis and Dermatomyositis:
• Bloods:
  
  • ESR ↑
  • CK ↑↑
  • Serology: ab – Anti-Jo, ANA, RF, ENAs
• EMG: myopathic, fibrillations
• Muscle biopsy: muscle fibre necrosis w/ inflammatory infiltrates
• CXR: Ca
• Inclusion body myositis
• Muscle biopsy + histology: ringed vacuoles

Management

• Polymyositis and Dermatomyositis:
• Corticosteroid
• Immunosuppressant: azathioprine, cyclophosphamide
• IV Ig: severe Dermatomyositis
• Surgery: associated Ca
• Recovery: 10% - remainder varying disability
• Inclusion body myositis
• Nothing effective

Question 12

Acquired electrolyte and endocrine myopathies(acquired myopathies of late onset) - define, aetiology, s/s, ix, mx

Answer 12

Definition

• Myopathies usually part of systemic disease

Aetiology

• Hyperthyroidism
• Cushing’s
• Malignancy
• ↓ K
• ↑/↓Ca²⁺

Clinical assessment

• Weakness: proximal
• Thyrotoxicosis:
• > shoulder than pelvic girdle
• brisk reflexes
• fasciculation and atrophy
• Cushing’s syndrome: proximal myopathies - long term steroid use
• Hypokalaemia: proximal myopathy - painless
• Vitamin D deficiency: Proximal muscle pain and wasting

Investigation

• Bloods:
• TFTs
• Cortisol
• Alpha foetal protein
• Ca²⁺

Management

• Reversal:
• tx primary condition
• removal of drug

Question 13

drug induced myopathies- aetiology + mx

Answer 13

Aetiology

• EtOH
• Statins: asymptomatic ↑ CK à pain overt myopathy
• Steroids: drug induced myopathy
• chloroquine: dose-related vacuolar myopathy associated with proximal weakness
• Zidovudine (HIV infection): proximal myopathies
• vincristine
• cocaine

Management

• Stop offending stug