Myopathies Flashcards
Neurologic Ddx of weakness
- UMN
- LMN
- NMJ
- muscle
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
1) Duchenne
2) Becker
3) FSH
4) Myotonic
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
21 deletion
FSH assc chromosome?
Myotonic assc chromosome?
FSH- 4
Myotonic- 19
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?
-distal
Which muscular dystrophies involve the face?
- FSH, myotonic
- 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
Duchenne:
- biopsy appearance
- 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:
- waddling gait
- lumbar lordosis
- calf pseudohypertrophy
Life threatening complications of DMD (2)
+ life expectancy
- cardiomyopathy
- intestinal pseudo-obstruction
(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
Beckers:
- life expectancy
- onset
- live beyond 30 (DMD death by 20)
- Does not onset until ~12 years
- less likely to have complications outside of weakness
FSH:
- muscle groups involved
- life expectancy
- facial
- scapular
- humeral
- peroneal
-normal life expectancy
Clues to FSH on exam
- down sloping shoulders
- winged scapula
- prominent clavicles
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
MD1:
- personality
- assc findings (6)
-avoidant personality
- early cataracts
- hypersomnia
- hypogonad
- ID
- insulin resistance
- cardiac arrhythmia
What muscle groups are atrophied in MD?
- face
- neck
- finger
“Limb Girdle” refers to what part of the body?
hip and shoulders
What proteins are most common disordered in LGMD?
-sarcolemmal proteins
Typical course of LGMD
- slow
- symmetric
- proximal
What are the two types of LGMD?
- LGMD1 dominant
- LGMD2 recessive
Emery Dreiffus Types 1 and 2:
genetic defect
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:?
-ED1
Oculopharyngeal Muscular Dystrophy:
mutation
-AD mutation in PABN1 (GCG) or PABN1 (GCA)
**Gag Cough Gag or Gag Cough Aspirate
OPMD Clinical Features
- Ptosis
- EOM weakness
- Dysphagia
- Reduced Gag
Treatment OPMD
- oculoplasty
- PEG
What are the three inflammatory myopathies?
- dematomyositis
- polymyositis
- inclusion body myositis
Which inflammatory myopathy is assc with rash and responds to steroids?
DERMATOmyositis
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
- EMG
- Biopsy
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:
- dematomyositis
- polymyositis
- 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?
-dermatomyositis
(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
Polymyositis treatment
-immunosuppression
Why might dermatomyositis be more common in women?
assc with breast and gyne cancers
also lung
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?
-cardiorespiratory involvement
Inclusion Body Myositis:
muscle groups involved
finger and wrist flexors
quads
Treatment Inclusion Body Myositis
Poor response to steroids/ immunosuppression
What systems are altered in metabolic myopathies? What is the typical inheritance pattern?
glycogen metabolism
lipid metabolism
electrolyte imbalance
mitochondria
AR
What are the four glycogenoses + their assc enzymes
- McArdles (=myophosphorylase)
- Pompes (=acid maltase)
- Tauri (= PFK Def)
- Cori-Forbes (debrancher deficiency)
Two lipidoses leading to myopathies
- carnitine deficiency
- 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
- Kearns Sayre
- MERRF
- MELAS
Characteristic of weakness in glycogenoses/ lipidoses
exercise intolerance
Diagnoses of glycogenoses/ lipidoses?
- myoglobinuria following exercise
- elevated CK
- EMG myopathies featuers
- biopsy (biochemical analysis)
What are types II, III, V, VII glycogen storage diseases?
II- Pompes
III- Cori/Forbes
V- McArdles
VII- Tauri
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
2) cardiomyopathy
McArdles (V, myophosphorylase) 3 features
1) cramps
2) myoglobinuria
3) second wind phenomenon
Tauri Disease (VII, PFK Def) 2 characteristics
1) exercise intolerance
2) myoglobinuria
(true of most glycogen storage diseases….)
Lipid Storage disease:
- when are symptoms worst?
- biopsy findings?
- flares with fasting
- lipid storage vacuoles
Four features of lipid storage disease?
- proximal weakness
- swollen muscles w/ exercise
- high CK
- myoglobinuria
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?
- exercise
- cold
Mitohondrial myopathies:
- deficiency of ____
- two organ systems most effected
- inheritance pattern
- ATP
- brain, muscle
- maternal
Biopsy findings in mitochondrial myopathies
ragged red fibers
Provoked necrotizing polymyopathy is also known as?
-rhabdomyolsis with myoglobinuria
Cause of provoked necrotizing polymyopathy
crush injury
extreme exertion
Who is most susceptible to necrotizing polymyopathy?
glycogen disorders
Defect in phosphodiesterase makes patient susceptible to?
Malignant hyperthermia
What anesthetics should be avoided in RYR1 mutation?
- halothane
- succinylcholine
What are four systemic illnesses that may lead to myopathy?
- hypothyroid
- critical illness
- acromegaly
- cushings
Muscle biopsy findings in critical illness myopathy
loss of myosin
Acromegaly/ Cushings:
distribution of weakness
- proximal
* 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
1) steroids
2) statins
3) AZT
4) colchicine
5) chloroquine
6) rifampin
(Some Sucky Asians Cant Cook Rice)
++ alcohol
Why do statins lead to myopathy?
-inhibit synthesis of mevalonic acid = no coenzyme Q needed for ATP production
Myopathy type assc with AZT
mitochondrial
