Muscle disease for physios May 2014. Categories of muscle disease Congenital – muscular dystrophy,...
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Transcript of Muscle disease for physios May 2014. Categories of muscle disease Congenital – muscular dystrophy,...
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)
Emery-Dreifuss
Selenoprotein
Skeleton – look for rigid spine
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 contraction-induced 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
• 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
• 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
• 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 contourHigh-riding scapulae
Scapular wingingWeakness 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• 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
LGMD 1B
• Contractures• Rigid spine• Some patients have lipodystrophy• Cardiac involvement requiring
pacemakers/ICDs• Proximal and distal muscle weakness
Rigid spine
Emery-dreifuss: typical contractures at theelbows
LGMD 2A
• 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
• 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
• Cramps• Exercise intolerance• Rhabdomyolysis• Progressive myopathy
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
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
• 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