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Muscle disease for physios
May 2014
Categories of muscle disease
• Congenital
– muscular dystrophy, congenital myopathy
– Mitochondrial
– Metabolic
– Channelopathy
• Inflammatory
– polymyositis
– Degenerative eg inclusion body myopathy
– Iatrogenic eg drugs, statins
• Function – watch how they walk into clinic/get
out of their seat etc before actual assessment
– Limb girdle type of pattern? (waddling gait;
lordosis)
– Facial weakness? Droopy eyelid?
– Foot drop?
– Odd shoulders?
– Scoliosis/other spinal deformity?
– Small stature? Dysmorphic? Hearing aids?
– Walking aids, Wheelchair?
• Alteration in function
– Difficulty getting up and out of chairs/sofas/cars
– Difficulty rising from a squat
– Climbing stairs/holding onto bannisters
– Reaching out for shelves; raising arms; hairdrying;
shaving
– Difficulty opening jars; picking objects; doing
buttons
– Slapping feet
Muscle pain
• Myalgia (flu-like) – myositis, Vitamin D def,
fibromyalgia/PMR
• Cramp
• Contracture (cramp but muscle goes rock
hard)
• Myotonia (muscle stiffness) look for grip and
percussion myotonia
• Muscle pain with focal swelling
(myositis/metabolic)
Contractures
• Progressive fibrosis of muscle + weakness of
antagonistic muscles = muscle shortening and
inability to passively stretch to normal length
• Sometimes pathognomic of certain disease
Contractures are typical especially in Lamin A/C mutations (LGMD)
and Bethlem myopathy (congenital myopathy with collagen 6 mutations)
Skeleton – look for rigid spine
Emery-Dreifuss
Selenoprotein
Scapular winging in
FSH muscular dystrophy
But other LGMDs can give you scapular winging
Muscle weakness
• Distribution
– Axial (do they have a dropped head? Do they have
a bent spine – camptocormia?)
– Limbs
– Face
– Eyes
– Bulbar
Anaesthetic complications
• Patient should wear Medic-Alert
bracelet
• Anaesthetist should be informed of
condition and long-acting
neuromuscular blocking agents should
be avoided
Dystrophinopathies
• Duchenne (DMD): Commonest childhood
muscular dystrophy
• 1:3500 male births
• Becker (BMD): 1:18,000 male births
• X-linked recessive
• Females not generally affected, but some
may have abnormalities on clinical exam, or
nonprogressive myopathy, or manifesting
carriers (skewed inactivation of X
chromosome and higher proportion of
defective gene producing mutant protein)
Origin of DMD
• 1/3 previous family history
• 2/3 no family history
• In the latter, mother is an undiagnosed carrier
(33%)
• Or mutation occurred in ovum producing the son
with DMD (germ line mutation) (66%)
• Once the diagnosis is made, genetic counselling
should be offered to the family especially
maternal female relatives who are likely to be
carriers
Molecular genetics
• Dystrophin is a large protein
• Gives structural integrity to the
sarcolemma and prevents contractioninduced damage
• Links intracellular cytoskeleton to the
extracellular matrix
• Gene lies on X chromosome, at Xp21
• Large gene – 2500 kb long, >70 exons
Clinical manifestations
• Progressive weakness and wasting of mainly
proximal muscles first, distal muscles later
• Girdle muscles affected first
• Calf pseudohypertrophy (fat replacement)
• Abnormal gait in the child, frequent falls
• Waddling gait because of involvement of hip
abductors and more lordotic because of
weakness of hip extensors
Calf pseudohypertrophy
Increasing lordosis
Course of disease
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Progressive weakness and wasting
Worse after period of inactivity/bedrest
Kyphoscoliosis (spinal surgery and bracing)
Wheelchair bound
Frequent respiratory infections
Respiratory muscle weakness (non-invasive
ventilation)
• Contractures (may need releasing)
Cardiac manifestations
• Conduction defects
• Congestive heart failure often in terminal
stages when respiratory failure develops
• Beta-blockers and ACEI
• Important to monitor female carriers (even in
absence of limb muscle involvement)
Intellectual impairment
• Not progressive
• IQ at least one SD below normal
• Minor cerebral atrophy
Becker MD
• Milder version of DMD
• Phenotype more variable
• Onset between 5 and 15 years but may present
in their 30s or 40s
• Similar distribution of muscle weakness
• Contractures and spinal deformity almost never
• Dilated cardiomyopathy even when weakness is
mild
• Intellectual impairment less common
Diagnosis
• Clinical features + High CK
• Muscle biopsy – frequently not
required/done
• Genetic analysis (detects
deletions/duplications in 70% of DMD and
80% of BMD)
Treatment options and trials
• Corticosteroids: improvement in muscle strength
in 11% and improved functional activity (climb
stairs faster)
• Viral vector delivery of dystrophin cDNA (AAV
safer)
• Exon skipping
Females
• Females not generally affected, but some
may have abnormalities on clinical exam,
or nonprogressive myopathy
• Can be manifesting carriers (skewed
inactivation of X chromosome and higher
proportion of defective gene producing
mutant protein)
• Large calves
• May have proximal muscle weakness
• May have cardiomyopathy
Facioscapulohumeral MD
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Age of onset of symptoms: 7 to 30 years
Can present much later
Autosomal dominant inheritance
Signs can be subtle and asymmetric
Facial weakness often detected first
Unable to close eyes tightly/bury
eyelashes
• Transverse smile
• Unable to whistle
Progression
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Facial weakness first
Foot dorsiflexors
Abdominal muscles
Shoulder girdle and humeral muscles
Pelvic girdle and proximal lower limb muscles
later
• 20% are wheelchair dependent by age 40
Odd shoulder contour
High-riding scapulae
Scapular winging
Weakness of shoulder girdle
develops first.
Weakness of triceps/biceps and
supraspinatus develops later
• Cardiac muscle not affected
• But respiratory muscle involvement is
common and respiratory muscle function
needs to be regularly monitored
• Sensorineural hearing loss (75%)
• Patients need to be asked specifically
about this
• Commoner in those who present earlier in
life
• Retinal vasculopathy (50%) (Coat’s
disease)
Pain
• Beyond the deformity from their periscapular
and pelvic muscle weakness
• Often difficult to control
Limb-girdle MD
• Marked genetic heterogeneity
• Clinically diverse with wide range of phenotypes
• Different ages of presentation, different muscle
group involvement, different grades of severity
with different rate of progression
• LGMD 1 = autosomal dominant
• LGMD 2 = autosomal recessive
• Diagnosis mostly made by protein
immunoblotting from muscle biopsies
LGMD
• Autosomal dominant
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LGMD1A: Myotilin
LGMD1B: Lamin A/C
(+cardiac involvement)
LGMD1C: Caveolin 3
LGMD1D: ? Gene product
(+cardiac involvement)
LGMD1E: ? Gene product
• Autosomal recessive
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LGMD 2A:Calpain 3
LGMD 2B: Dysferlin
LGMD 2C: Gamma-sarcoglycan
LGMD 2D: Alpha-sarcoglycan
LGMD 2E: Beta-sarcoglycan
LGMD 2F: Delta-sarcoglycan
LGMD 2G: Telethonin
LGMD 2H: TRIM32
LGMD 2I: FKRP
LGMD 2J: Titin
LGMD 2K: POMT1
LGMD 2L: ANO5
LGMD 1B
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Contractures
Rigid spine
Some patients have lipodystrophy
Cardiac involvement requiring
pacemakers/ICDs
• Proximal and distal muscle weakness
Emery-dreifuss:
typical contractures at the
elbows
Rigid spine
LGMD 2A
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Contractures esp around calf, elbows, fingers
Waddling gait
Toe-walking as a child
Leg>arms
Periscapular and quadriceps
Respiratory failure
LGMD 2L FKRP
• Proximal>distal
• Legs and arms
• Legs affecting thigh adductors, psoas and
quads
• Arms – periscapular, deltoid, biceps and
triceps
• Type 2 respiratory failure even when ambulant
• Can have calf, thigh and tongue hypertrophy
LGMD 2L ANO5
• Progressive proximal muscle weakness
• Previously can be very strong individuals
including marathon runners etc
• Can have focal atrophy of biceps and focal
hypertrophy of lateral gastrocnemius
• Can have mild distal lower limb weakness
Oculopharyngeal muscular
dystrophy
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Men>women
Autosomal dominant
Ptosis
Bulbar problems – may require
gastrostomy for feeding
• Progressive myopathy
• May develop respiratory muscle involvement
Metabolic myopathies
• Lipid storage myopathies
– CPT2 deficiency
• Glycogen storage disorders
– McArdle’s
• Mitochondrial myopathies
– Syndromes
– Defects in fatty acid oxidation pathways
– Complex
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Cramps
Exercise intolerance
Rhabdomyolysis
Progressive myopathy
Mitochondrial disorders
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Multi-system disorders
Myopathy
Complex eye problems
Endocrinological problems
Hearing loss
Gastrointestinal problems
CNS problems including migraine and seizures
Learning disabilities
Short stature etc
Pompe’s disease
• Infantile onset – severe and fatal
• In infants with cardiac involvement and
hepatosplenomegaly
• Adult-onset
• Progressive myopathy
• Respiratory involvement
• Enzyme replacement therapy
Inclusion body myopathy
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An acquired degenerative muscle condition
Slow, insiduous and progressive
Usually affects >4th decade
Fine motor tasks (eg opening bottle jars,
buttons)
• Early falls in IBM due to involvement of
quadriceps (with wasting often by time of
presentation)
• Also wasting of flexor muscle compartment of
forearm with finger flexion weakness in IBM
• Patients with IBM do not respond to
immunomodulatory treatments eg steroids
Quadriceps wasting
in IBM
Wasting of forearm flexor compartment in IBM
Prognosis
• Poor
• Develop facial weakness and problems
swallowing
• Can have neck weakness
• Often end up in wheelchair
• No cardiac complications but may require NIV
and PEG feeding