1. Muscle disease for physios
May 2014

2. Categories of muscle disease
Congenital
muscular dystrophy, congenital myopathy
Mitochondrial
Metabolic
Channelopathy
Inflammatory
polymyositis
Degenerative eg inclusion body myopathy
Iatrogenic eg drugs, statins

3. 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?

4. 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

5. 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)

6. Contractures
Progressive fibrosis of muscle + weakness of antagonistic muscles = muscle shortening and inability to passively stretch to normal length
Sometimes pathognomic of certain disease

7. Contractures are typical especially in Lamin A/C mutations (LGMD)
and Bethlem myopathy (congenital myopathy with collagen 6 mutations)

8. Skeleton – look for rigid spine
Emery-Dreifuss
Selenoprotein

9. Scapular winging in FSH muscular dystrophy
But other LGMDs can give you scapular winging

10. Muscle weakness Distribution
Axial (do they have a dropped head? Do they have a bent spine – camptocormia?)
Limbs
Face
Eyes
Bulbar

11. Anaesthetic complications
Patient should wear Medic-Alert bracelet
Anaesthetist should be informed of condition and long-acting neuromuscular blocking agents should be avoided

12. 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)

13. 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

14. Molecular genetics Dystrophin is a large protein
Gives structural integrity to the sarcolemma and prevents contraction-induced damage
Links intracellular cytoskeleton to the extracellular matrix
Gene lies on X chromosome, at Xp21
Large gene – 2500 kb long, >70 exons

15. 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

16. Calf pseudohypertrophy Increasing lordosis

17. Course of disease 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)

18. 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)

19. Intellectual impairment
Not progressive
IQ at least one SD below normal
Minor cerebral atrophy

20. 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

21. Diagnosis Clinical features + High CK
Muscle biopsy – frequently not required/done
Genetic analysis (detects deletions/duplications in 70% of DMD and 80% of BMD)

22. 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

23. 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

24. Facioscapulohumeral MD
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

25. Progression 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

26. Odd shoulder contour
High-riding scapulae
Scapular winging
Weakness of shoulder girdle develops first.
Weakness of triceps/biceps and supraspinatus develops later

27. Cardiac muscle not affected
But respiratory muscle involvement is common and respiratory muscle function needs to be regularly monitored

28. 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)

29. Pain
Beyond the deformity from their periscapular and pelvic muscle weakness
Often difficult to control

30. 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

31. LGMD Autosomal dominant Autosomal recessive LGMD 2A:Calpain 3
LGMD1A: Myotilin
LGMD1B: Lamin A/C (+cardiac involvement)
LGMD1C: Caveolin 3
LGMD1D: ? Gene product (+cardiac involvement)
LGMD1E: ? Gene product
Autosomal recessive
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

32. LGMD 1B Contractures Rigid spine Some patients have lipodystrophy
Cardiac involvement requiring pacemakers/ICDs
Proximal and distal muscle weakness

33. Emery-dreifuss:
typical contractures at the
elbows
Rigid spine

34. LGMD 2A Contractures esp around calf, elbows, fingers Waddling gait
Toe-walking as a child
Leg>arms
Periscapular and quadriceps
Respiratory failure

35. 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

36. 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

38. Oculopharyngeal muscular dystrophy
Men>women
Autosomal dominant
Ptosis
Bulbar problems – may require
gastrostomy for feeding
Progressive myopathy
May develop respiratory muscle involvement

39. Metabolic myopathies Lipid storage myopathies
CPT2 deficiency
Glycogen storage disorders
McArdle’s
Mitochondrial myopathies
Syndromes
Defects in fatty acid oxidation pathways
Complex

40. Cramps
Exercise intolerance
Rhabdomyolysis
Progressive myopathy

41. Mitochondrial disorders
Multi-system disorders
Myopathy
Complex eye problems
Endocrinological problems
Hearing loss
Gastrointestinal problems
CNS problems including migraine and seizures
Learning disabilities
Short stature etc

42. Pompe’s disease Infantile onset – severe and fatal
In infants with cardiac involvement and hepatosplenomegaly
Adult-onset
Progressive myopathy
Respiratory involvement
Enzyme replacement therapy

43. Inclusion body myopathy
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

44. Quadriceps wasting
in IBM

45. Wasting of forearm flexor compartment in IBM

46. 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