Flashcards in Myopathies Deck (86):
Neurologic Ddx of weakness
Three major groups of myopathies
1) muscular dystrophies
2) inflammatory myopathies
3) metabolic myopathies
What are "dystrophic" features of muscles?
1) fiber splitting
2) increased CT
Five major muscular dystrophies
5) Limb Girdle
Two minor muscular dystrophies
1) Emery Dreifuss
2) Oculo-pharyngeal muscular dystrophy
What are the inheritance patterns of the major muscular dystrophies?
Duchenne and Becker- XR
FSH and myotonic- AD
Limb Girdle- Can be AD vs AR on multiple chromosomes
Duchenne/ Becker chromosome
FSH assc chromosome?
Myotonic assc chromosome?
When do the major muscular dystrophies onset?
Duchenne and Becker: early (5-10 years old)
Others: 10-30 years of age
Where is primary weakness in Duchenne/ Beckers?
pelvic region first
Where is primary weakness in Myotonic dystrophy?
Which muscular dystrophies involve the face?
-Later in disease Duchenne, Becker
-None in limb girdle
What EKG abnormality is seen in muscular dystrophies? Which major dystrophy is an exception?
Deep narrow Q waves in L precordial leads
(except FSH which has normal EKG)
Which of the muscular dystrophies have elevated CK?
Duchenne, Becker, Limb Girdle
(Normal in FSH, myotonic)
-specific gene involved
-macs invade necrotic muscle fibers, missing dystrophin on stain
-dystrophin out of frame mutation
Contrast Duchenne mutation w/ Beckers
Duchenne: out of frame mutation
Beckers: in frame mutation
Classic symptomatic features of DMD:
Life threatening complications of DMD (2)
+ life expectancy
(death by cardiorespiratory failure around age 20)
Treatment for DMD
No cure, can prolong course with steroids if started at 4-7 years of age.
(stabilizes sarcolemma, increases muscle mass)
Female DMD carrier symptoms
mild compared to diseased males
-risk CVD, weakness, cognitive/behavioral issues
-myalgia, ^^CK/ aldolase are are possible
-live beyond 30 (DMD death by 20)
-Does not onset until ~12 years
-less likely to have complications outside of weakness
-muscle groups involved
-normal life expectancy
Clues to FSH on exam
-down sloping shoulders
Contrast Myotonic Dystrophy types 1 and 2
-Type 1: Distal weakness, common
-Type 2: Proximal, rare
Gene assc with MD1
CTG repeat at DMPK gene
(Cats Throw Goldfish) and (Dumb Mammals Punch Kids)
-assc findings (6)
What muscle groups are atrophied in MD?
"Limb Girdle" refers to what part of the body?
hip and shoulders
What proteins are most common disordered in LGMD?
Typical course of LGMD
What are the two types of LGMD?
Emery Dreiffus Types 1 and 2:
Type 1: Emerin mutation, Recessive
Type 2: Lamin A/C mutation, may be dominant or recessive
*alphabetic order (1 emerin --> 2 lamin)
What ED type is assc with contractures and cardiac abnormalities:?
Oculopharyngeal Muscular Dystrophy:
-AD mutation in PABN1 (GCG) or PABN1 (GCA)
**Gag Cough Gag or Gag Cough Aspirate
OPMD Clinical Features
What are the three inflammatory myopathies?
-inclusion body myositis
Which inflammatory myopathy is assc with rash and responds to steroids?
Distribution of weakness in Inflammatory myopathies:
-proximal in dermatomyositis and polymyositis
-distal and proximal/ assymetric in inclusion body
Which of the three inflammatory myopathies has an unequal sex distribution?
-Inclusion body is more common in males
-dermato and poly are either more common in female or equal (her slides are contradictory)
Which of the two inflammatory myopathies may be assc with cancer?
-dermato vs poly myositis
Three tests for inflammatory myopathies:
CK findings in the three inflammatory myopathies
-^^ in dermato/polymyositis
-may or may not be elevated in inclusion body myositis
EMG/ NCS findings in inflammatory myopathies
-myopathic in all three
-also neuropathic in inclusion body
Biopsy findings for:
-inclusion body myositis
-dermatomyositis: perifasicular atrophy
-polymyositis: inflammatory (endomysial inflammation) v normal
-inclusion bodies: bodies + rimmed vacuoles
Which of the inflammatory myopathies may be seen in children?
(also seen in 40+)
-poly in adults
-inclusion body in elderly
dermato --> poly --> inclusion body
What is a sign of proximal muscle weakness?
difficult standing from seated position or trouble lifting arms above head
Why might dermatomyositis be more common in women?
assc with breast and gyne cancers
Describe dermatomyositis rash
-Grottons sign (rash at hands)
-helipotrope (rash at eyes)
-also cape like distribution rash
In addition to weakness and rash, what are features of dermatomyositis?
Inclusion Body Myositis:
muscle groups involved
finger and wrist flexors
Treatment Inclusion Body Myositis
Poor response to steroids/ immunosuppression
What systems are altered in metabolic myopathies? What is the typical inheritance pattern?
What are the four glycogenoses + their assc enzymes
-Pompes (=acid maltase)
-Tauri (= PFK Def)
-Cori-Forbes (debrancher deficiency)
Two lipidoses leading to myopathies
-carnitine palmitoyl transferase deficiency
Four Channelopathies leading to myopathies
1) hyperkalemic perioidic paralysis
2) hypokalemic PP
3) Myotonia congenita
4) Paramyotonia congenita
Three mitochondrial myopathies
Characteristic of weakness in glycogenoses/ lipidoses
Diagnoses of glycogenoses/ lipidoses?
-myoglobinuria following exercise
-EMG myopathies featuers
-biopsy (biochemical analysis)
What are types II, III, V, VII glycogen storage diseases?
PLEASE CUT MY TAG! = 2 3 5 6
Pompes (II, acid maltase) 2 characteristics
1) fixed proximal weakness
2) early cardiorespiratory insufficiency (Pompes effects the pump-heart)
Cori-Forbes (III, debrancher) 2 features
1) distal weakness
McArdles (V, myophosphorylase) 3 features
3) second wind phenomenon
Tauri Disease (VII, PFK Def) 2 characteristics
1) exercise intolerance
(true of most glycogen storage diseases....)
Lipid Storage disease:
-when are symptoms worst?
-flares with fasting
-lipid storage vacuoles
Four features of lipid storage disease?
-swollen muscles w/ exercise
Channels involved in hypokalemic and hyperkalemic periodic paralyses
-hypo: L type Ca Channel
-hyper: SCN4A (Na) Channel
Contrast weakness in hyper/hypokalemic PP:
-hypo: lasts hours- days
-hyper: relieved quickly by eating or exercise
both occur after rest following carb load or exercise
Channels involved in myotonia congenital/ paramyotonia congenital
-myotonia: CLCN1- hypertrophy
-paramyotonia: CLCN1 or SCN4A
What triggers paramyotonia congenital?
-deficiency of ____
-two organ systems most effected
Biopsy findings in mitochondrial myopathies
ragged red fibers
Provoked necrotizing polymyopathy is also known as?
-rhabdomyolsis with myoglobinuria
Cause of provoked necrotizing polymyopathy
Who is most susceptible to necrotizing polymyopathy?
Defect in phosphodiesterase makes patient susceptible to?
What anesthetics should be avoided in RYR1 mutation?
What are four systemic illnesses that may lead to myopathy?
Muscle biopsy findings in critical illness myopathy
loss of myosin
distribution of weakness
*Cushings mainly of lower extremities
Common feature of hypothyroid + critical illness myopathy
-loss of DTRs
EMG findings in myopathies
1) low amplitude
2) short duration
3) polyphasic + rapid recruitment
Six meds that cause myopathy
(Some Sucky Asians Cant Cook Rice)
Why do statins lead to myopathy?
-inhibit synthesis of mevalonic acid = no coenzyme Q needed for ATP production