Ch 5 - EDX: Myopathies Flashcards
What is dystrophin?
Protein found in the sacrolemma of normal muscle that provides mechanical support and structural integrity for the muscle membrane cytoskeleton
What does mutation of dystrophin lead to?
Muscle fiber necrosis. Patients present with clinical symptoms of myalgias, fatigue, and weakness.
What is myotonia?
Painless delayed relaxation of skeletal muscles following a voluntary contraction
What can exacerbate myotonia?
Cold
Dilantin
Procainamide
Calcium channel blockers
What is Arthrogryposis?
Fixed deformity of the extremities due to intrauterine hypomobility, myopathy, muscular dystophy or oligohydraminos
What is seen on NCS in myopathy?
SNAP: Normal
CMAP: Dec amp with significant muscle fiber atrophy. Normal latencies and conduction velocities
What is seen on EMG in myopathy?
Low amp
Short duration
Polyphasic MUAP with early recruitment
Resting activity depends on d/o
What is Quantitative EMG used for?
Detailed measurement of MUAPs and waveform duration using 20 MUAPs on screen set with a trigger and delay line
What causes short duration small amplitude (SDSA) MUAPs on EMG?
Classic polyphasic potentials are due to loss of muscle fibers
What causes long duration large amplitude (LDLA) MUAPs on EMG?
Polyphasic potentials are due to collateral sprouting
What causes long duration unstable MUAPs on EMG?
These variable amplitude potentials are due to blocking of immature NMJs, which are formed at the beginning of collateral sprouting
What can be demonstrated on single fiber EMG in myopathy?
Increased jitter, FD, and blocking
Which disorders have type I fiber atrophy on muscle biopsy?
- Myotonic dystrophy
- Nemaline rod myopathy
- Fiber type disproportion
Which disorders have type II fiber atrophy on muscle biopsy?
- Steroid myopathy
- Myasthenia gravis
- Deconditioning
What is the inheritance pattern of Duchenne Muscular Dystrophy?
X-linked recessive (xp21), spontaneous
What is the onset of Duchenne Muscular Dystrophy?
3 to 5 years old
What is the course of Duchenne Muscular Dystrophy?
Severely progressive (death by 20s)
What is the clinical presentation of Duchenne Muscular Dystrophy?
Proximal muscle weakness Inc lumbar lordosis Scoliosis Calf pseudohypertrophy Possible MR Toe walking <5 years Clumsy running <7 years WC by 12 yo Contractures: ITB first, Achilles tendon Gower's sign
What is seen on muscle biopsy in Duchenne Muscular Dystrophy?
No dystrophin
Internal nuclei variation in fiber size
What are seen on labs in Duchenne Muscular Dystrophy?
Increased CPK and aldolase
When should surgery be done for scoliosis in Duchenne Muscular Dystrophy?
Before the vital
capacity is below 35% (usually due to a curve of >30°).
What is the inheritance pattern of Beck Muscular Dystrophy?
X-linked recessive
What is the onset of Becker Muscular Dystrophy?
Adulthood
What is the course of Becker Muscular Dystrophy?
Slowly progressive
What is the clinical presentation of Becker Muscular Dystrophy?
- Proximal weakness
- Calf pseudohypertrophy
- Cardiomyopathy
- Less mental retardation than DMD
What is seen on muscle biopsy of Becker Muscular Dystrophy?
Decreased dystrophin
15% to 85%
What is seen in labwork in Becker Muscular Dystrophy?
Increased CPK
What is the inheritance pattern of Myotonic dystrophy?
Autosomal dominant
What is the onset of Myotonic dystrophy?
Infancy
What is the clinical presentation of Myotonic dystrophy?
Distal > proximal myotonia with sustained grip Hatchet face Frontal balding Poor vision/Ptosis Hypertrichosis Impotence MR Cardiac/Endocrine ABN
Describe the appearance of hatchet face.
Wasting of the temporalis and
masseter
What are clinical features specific to Congenital myotonic dystrophy?
“Shark mouth” appearance
Facial diplegia
Possible club foot
What is seen on muscle biopsy in Myotonic Dystrophy?
Type I fiber atrophy
Type II hypertrophy
No dystrophin involvement
What medications can be used in treatment of Myotonic Dystrophy?
Procainamide
Dilantin
Quinine
(PDQ)
What is inheritance pattern and onset of Central Core Disease?
Autosomal dominant
Infancy
What is clinical presentation of Central Core Disease?
- Floppy infant/hypotonia
- Proximal weakness
- Congenital hip dislocation
- Delayed milestones
- Associated with malignant hyperthermia
What is seen on muscle biopsy in Central Core Disease?
Central cores in Type I fibers
Absent mitochondria
What is the inheritance pattern and onset of Nemaline Rod Myopathy?
Autosomal dominant/ Recessive
Infancy
What is clinical presentation of Nemaline Rod Myopathy?
- Floppy infant/hypotonia
- Diffuse weakness
- Facial involvement
- Narrowed long face
- High arched palate
- Foot drop
What is the typical cause of death in Nemaline Rod Myopathy?
Respiratory failure
What is seen on muscle biopsy in Nemaline Rod Myopathy?
Rod-shaped bodies on Gomori trichrome stain
What is the inheritance pattern and onset of Centronuclear myotubular myopathy?
X-linked recessive
Infancy
What is the clinical presentation of Centronuclear myotubular myopathy?
Floppy infant/hypotonia • Ptosis • Extra ocular muscle involvement • Facial diplegia • Dysphagia • Respiratory insufficiency
What is seen on muscle biopsy in Centronuclear myotubular myopathy?
Central location of fiber nuclei, forming chains
What is the inheritance pattern and onset of Fiber Type Disproportion?
Variable inheritance
Infancy
What is the clinical presentation of Fiber Type Disproportion?
- Floppy infant/hypotonia
- Hip contractures
- Hip dislocations
What is seen on muscle biopsy in Fiber Type Disproportion?
Numerous small Type I and normal to large Type II fibers
What is the etiology of Polymyositis/ Dermatomyositis?
Autoimmune
Connective tissue disorder
Infection
Cancer
What is the clinical presentation of both Polymyositis/ Dermatomyositis?
- Symmetrical proximal weakness: Hips followed by shoulders
- Neck flexion weakness
- Myalgias, dysphagia, dysphonia
What is the clinical presentation specific to Dermatomyositis?
Periorbital violet rash and edema
Gottron’s sign: Red-purple patches
over the knuckles, elbows, knees
What is seen in lab work of Polymyositis/ Dermatomyositis?
Increased CPK, ESR, aldolase, SGOT, SGPT, LDH
What is seen on muscle biopsy in Polymyositis/ Dermatomyositis?
Necrosis of the Type I and II fibers. Perifascicular atrophy
What is the inheritance pattern of Inclusion Body Myositis?
Unknown
What is the clinical presentation of Inclusion Body Myositis?
Asymmetric, slowly progressive, painless weakness in proximal and distal muscles
What is associated with Inclusion Body Myositis?
Polyneuropathy
What is the age distribution of Inclusion Body Myositis?
Adults 45 to 55 years and peaks at 70 years
What is seen in lab work of Inclusion Body Myositis?
Increase in CK muscle
What is seen on muscle biopsy in Inclusion Body Myositis?
Rimmed or cytoplasmic/ basophilic vacuoles
Eosinophilic
inclusion bodies
What is the inheritance pattern of McArdle disease (Type V metabolic myopathy)?
Autosomal recessive
Myophosphorylase deficiency
What is the onset of McArdle disease (Type V metabolic myopathy)?
<15 years of age
What is the clinical presentation of McArdle disease (Type V metabolic myopathy)?
- Exercise intolerance
- Easy fatigability
- Muscle stiffness
- Cramping
- Second-wind phenomenon
What can happen with exercise in McArdle disease (Type V metabolic myopathy)?
Strenuous exercise can precipitate myolysis (possibly cause renal failure and death)
What is the inheritance pattern of Pompe’s disease (Type III metabolic myopathy)?
Autosomal recessive
Acid maltase deficiency
What is the onset of Pompe’s disease (Type III metabolic myopathy)?
Infant to adult
What is the clinical presentation of Pompe’s disease (Type III metabolic myopathy)?
- Hypotonia
- Tongue enlargement
- Cardiomegaly
- Hepatomegaly
- Respiratory insufficiency
- Death by 2 years of age
- A milder form may affect adults
What is the inheritance pattern of Hyperkalemic Periodic Paralysis?
Autosomal dominant
Multiple secondary causes
What is the onset of Hyperkalemic Periodic Paralysis?
Childhood–second decade
What is the clinical presentation of Hyperkalemic Periodic Paralysis?
- Proximal muscle weakness
- Paresthesias of the lips and lower limbs
- Myotonia
- Attacks last 10 to 60 min
- May be aborted with exercise
- Exacerbated with cold exposure and rest following exercise
What is seen on labwork of Hyperkalemic Periodic Paralysis?
High K+ during the attack
What is the treatment of Hyperkalemic Periodic Paralysis?
High carbohydrate diet
What is the inheritance pattern of Hypokalemic Periodic Paralysis?
Autosomal dominant
Multiple secondary causes
What is the onset of Hypokalemic Periodic Paralysis?
Starts in early second decade
What is the clinical presentation of Hypokalemic Periodic Paralysis?
- Weakness starts in the legs and spreads proximally
- Attacks last 12 to 24 hours
- Myotonia seen in the eyelids
- Exacerbated with rest after exercise, stress, and a high carbohydrate diet
What is seen on labwork of Hypokalemic Periodic Paralysis?
Low potassium
Muscle biopsy normal
What is the treatment of Hypokalemic Periodic Paralysis?
K+ supplement
What are different names for Myotonia Congenita?
Thomsen’s disease
Little Hercules
What is the inheritance pattern and onset of Myotonia Congenita?
Autosomal dominant
Birth–adulthood
What is the clinical presentation of Myotonia Congenita?
- Severe spasms exacerbated by the cold
- Improves with warmth and exercise
- Muscle hypertrophy
- Myotonia
- No weakness
What are treatments for Myotonia Congenita?
Procainamide
Dilantin, quinine (PDQ)
What is the inheritance pattern and onset of Paramyotonia congenita (Eulenburg)?
Autosomal dominant
Birth–adulthood
What is the clinical presentation of Paramyotonia congenita (Eulenburg)?
- Stiffness
- Weakness
- Fatigue
- Myotonia
- Exacerbated with cold and exercise
What is the treatment of Paramyotonia congenita (Eulenburg)?
Warm extremities
What is the etiology of steroid myopathy?
Corticosteroid proteolysis effect
What is the clinical presentation of steroid myopathy?
- Proximal muscle weakness
- Risk is increased if on 30 mg / day
- Preferentially affects the hip girdle muscles
What is seen on muscle biopsy of steroid myopathy?
Type II atrophy
What is the clinical presentation of statin myopathy?
- Proximal weakness and pain
- Worse with exercise
- Lipophilic statins are more likely to produce muscular effects, than are relatively hydrophilic agents
What are lipophilic statins?
Simvastatin
Atorvastatin
Lovastatin
What are hydrophilic statins?
Pravastatin
Rosuvastatin
Fluvastatin
What are treatments of statin myopathy?
Stop statins, or stop medications that
interfere with Cy-P450: macrolide antibiotics, verapamil, diltiazem, cimetidine, etc.
