Myopathies/Muscular Dystrophies Flashcards
Myopathy is a disease of _____ and _____
single muscle fiber and supporting connecting tissue
____ does not exclude myopathy
normal biopsy
When performing EMG, do on muscles with _____ weakness
mild/mod (motor 3/5)
Perform EMG on ____ side of the body
one side, biopsy will be performed on the other
What are the three main types of muscle fibers?
Ia - slow, red ox (dark, high density, smallest diameter)
IIA - intermediate (dark color, high density, large diameter)
IIB - Fast twitch (pale color, fatiguable, low density, large diameter) glycolytic
EMG assess which type of fibers?
1A - slow red oxidative fibers
Steroid myopathy affects ____ so emg will be normal
Type II
____ is the reduction in size of single muscle fiber. Caused by (4)
Atrophy
- loss of innervation
- immobilization
- intrinsic muscle disease
- excess corticosteroid use
What is fiber group typing?
loss of innervation causes dying back phenomenon with reinnervation which can cause the muscle fiber to change from Ia to IIb
_____ is a disease of a small muscle fiber that has arrest in normal maturation process.
example?
hypotrophy
congenital myopathy
such as Nemaline rod myopathy, central nuclear myopathy, fiber type disproportionate myopathy, central core myopathy
____ is increase in single fiber volume; can be normal or pathologic
Causes? (4)
Hypertrophy
- T1 increase in size with endurance training
- T2 increase in progressive resistive exercises
- anabolic steroids increase growth hormone which cause increase in T2
- Pseudohypertrophy - fat infiltration seen in DMD. Muscle volume is not increased in size.
____ is damage to connective tissue (endomysium) or muscle fiber
- examples (2)
necrosis
- rhabdomyolysis
- polymyositis
will have myoglobinuria
Regeneration depends on extent of insult as well as if supporting structures are intact (basal lamina, connective tissue)
Restorative capacity of muscle tissue with endomysium intact is pretty good.
Myopathy presents as ___ weakness and muscle ____
proximal weakness > distal weakness
muscle pain (acquired)
Muscle cramping
Myopathy on NCS:
1. Sensory NCS:
2. Motor NCS:
- Latency: _____
- Amplitude: _____
- Conduction velocity: ____
- F wave/H reflex: _____
- Normal
- Normal
- decreased
- normal
- normal
Myopathy on EMG
- insertional activity:
- spontaneous:
- voluntary activity: (5)
I: normal, increased, or decreased
S: can be normal or none
- acute: PSW/Fibs
- chronic: CRD
- Myotonia in Pompe’s disease or acid maltase deficiency
V:
- polyphasic
- increased serations
- decreased amplitudes
- short duration ****
- early recruitment (“increased”)
Why are the classic findings on EMG voluntary activity apparent?
All looks this way due to collateral sprouting and increased components of a single motor unit. Muscle fibers close together in new motor units.
- polyphasic
- increased serations
- decreased amplitudes (200-600microvolts)
- short duration ****
- early recruitment (“increased”)
what is the most consistent and most sensitive finding with myopathy on EMG?
mean duration of the potential is decreased - mean duration based off non-polyphasic potentials
How do you discern cramp vs contracture on EMG?
Cramp will have normal muscle fibers firing spontaneously and rapidly with shortening of the muscle
Contracture: silent on EMG, classic example: Mcardles disease/myophosphorylase deficiency: contractures silent on EMG
Duchenes MD:
1. ____ inheritence.
2. _____ gene
3. Incidence
4. prevalence
5. ____ are inherited
6. pathology:
- X-linked recessive inheritence
- affects short p21 locus of short arm of x-chromosome
- 1 in 2500 males
- 1 in 1800
- 2/3 are inherited
- lack of dystrophin (<10% of normal)
_____ is a protein located in skeletal, cardiac, and brain tissue that binds to the sarcolemma, providing structure and stability to the membrane. Lack of protein results in lack of integrity during contraction of muscle, which results in membrane tears. Regeneration occurs, but is futile because tears recur. Ultimately symptoms occur around age ____
dystrophin
5.
CK levels in DMD are ____ of normal
10 times greater. Aldolase levels increased.
Disease?
- clumsy walkers, difficulty with stairs, toe walking, pseudohypertrophy of calves, Gower’s sign.
stop walking by _____
Death by ____
due to ____
DMD
10-12 yoa
20 yoa
cardiac
What will you see on muscle bx for DMD
variation of muscle fiber size and splitting. some fibers are hypertrophic, some hypotrophic, some have muscle fiber splitting.
Becker’s MD:
1. _____ inheritence
2. Incidence:
3. Prevalence:
4. _____ protein
5. pathology?
X-linked recessive
5/100,000
2.4/100,000
some normal dystrophin (greater than 10%)
less than normal but present
Beckers MD
- walk until ____
Mean life expect ____
Cog: ____
Cardiac ____
CK?
20 yoa
mid-30s
cognition normal
cardiac less severe
CK and aldolase 5 x greater than normal.
Facioscapulohumeral dystrophy
1. inheritence
2. incidence
3. prevalence
4. age onset:
5. lab abnormalities:
- AD
- 4 in 1 million
- 1 in 20,000
- second decade
- CK and FSH 5 x greater than normal
Disease?
- facial muscles affected. Difficulty with eye closure (bell’s phenomenon), bilateral scapular winging (one greater than the other - not symmetrical), straight clavicles, extra axial fold, cant abduct arms greater than 90 degrees. Popeye arms (small arms, large forearms, b/c affects biceps, triceps, pecs)
Hyperlordotic gait
bilateral trendelenburg gait (waddling)
facioscapulohumeral dystrophy (FSH)
Where is the genetic defect in FSH dystrophy?
long arm Ch 4 - 4g35
What is coats syndrome
severe profound sensori-neural hearing loss and retinal telengectasias along with FSH
Life expectancy in FSH dystrophy?
normal
20% become WC bound.
Limb Girdle MD
1. difficult to diagnose bc ____
2. onset:
3. inheritence?
4. men ____ women
5. CK:
- variable presentations, changes over time
- 2nd or 3rd decade with weakness
- AD or AR
- men = women
- 20-50 x normal with AR
<5 x normal with AD
Scapuloperoneal MD
1. Weakness in _____
2. ______ appearing legs
3. _____ is most commonly affected (muscle)
4. Inheritence
5. CK?
6. Symmetric?
- peroneal muscles with associated scapular weakness
- inverted wine bottle b/c thighs are big with small calves
- tib ant (foot drop)
- AD
- normal or slightly abnormal
- asymmetry possible
disease?
- bilateral ptosis, may be asymmetric. Dysphagia. Onset in 50s or later. Inhereted via AD.
occulopharyngeal muscular dystrophy
Myotonic dystrophy is also known as ____
steiners disease
In myotonic dystrophy, symptoms start ____. CK ____ early.
Begins in ____
first symptoms?
distal and progress proximally (different from other myotonias)
CK normal early then increases
adolescence to early adulthood
muscle stiffness/cramping
What is clinical myotonia?
hit with a reflex hammer and note muscle tightening/shortening with slow relax (not immediate)
What is electrical myotonia?
waxing/waning sounds like a dive bomber/motor cycle
Myotonic dystrophy:
1. Inheritence
2. Die by _____ at age ____
3. Incidence
4. Prevalence
5. Typical clinical picture
- AD
- cardiopulmonary; 50-60yoa
- 13/100,000
- 2-5/100,000
- temporal wasting, high forehead, inverted face, ptosis, inverted V palate, thin neck, frontal balding
- genetic abnormality in myotonic dystrophy
- ____ are common eye finding
- cardiac?
- Chromosome 19 (CTG repeat)
- cataracts
- conduction block, arrythmias
Name the 7 most common muscular dystrophies
- Duchennes
- Beckers
- Facioscapulohumeral
- limb-girdle
- scapuloperoneal
- oculopharyngeal
- myotonic disorders (myotonic dystrophy, non-dystrophic ((inherited and acquired)) including (a) myotonia congenita
- thompsons disease
- becker type
- autosomal w/ painful myotonic contractions
and (b) paramyotonia congenita.
Describe the different non-dystrophic inherited and acquired myotonias:
A
1.
2.
3.
B:
A Myotonia Congenita
1. Thompsons
2. Beckers
3. Autosomal w/ painful myotonic contractions
B: para-myotonia congenita
Thompsons Myotonic congenita (group of non-dystrophic inherited and acquired myotonias)
1.inheritence
2. onset at _____
3. Clinically will have ___ and ____ myotonia
4. _____ phenomenon
- AD (named after danish physician)
- 1-6 yoa
- percussion myotonia (myotonia with delayed painless muscle contraction with slow release)
- Action myotonia (shortening of the muscle with forceful activity (gripping))
- warm up - increased activity once warmed up (most other dystonias fatigue with repeated activity)
What is defective in non-dystrophic inherited and acquired myotonias (specifically myotonia congenita and para-myotonia congenita)
mutation in voltage gated Na channels (delay in sodium inactivation)
Beckers myotonia congenita
(group of non-dystrophic inherited and acquired myotonias)
1. Inheritence
2. ___- and ____ myotonia but less severe than thompsons
3. age of onset _____
- AR
- percussion and action myotonia but less severe than thompsons
- 4-12 yoa
Para myotonia congenita
(group of non-dystrophic inherited and acquired myotonias)
1. opposite of _____
2. what is the paradoxical effect with exercise
3. EMG: ____ with decreasing temperatures
4. decreased ____ with cooling and exertion
5. Mutation is in
- Myotonia congenita
- paradoxical effect with exercise (do worse with activity) opposite of warm up phenom seen myotonia congenita.
- increased electrical myotonia with decreasing temperatures
- CMAP with cooling and exertion
- mutation is in voltage gated sodium channels (delay in sodium inactivation)
Name the most common congenital myopathies: 4
- central core
- nemaline rod
- centronuclear
- fiber type disproportion
Congenital myopathies present with ____ feet, ____ tone, and ___ spine deformities.
club feet, hyoptonia, kyphosis
T1 fibers affected > T2
Central core congenital myopathy:
1. inheritence
2. lower or upper extremity?
3. prone to ______.
4. delayed ____
5. Biopsy?
6. Walk at
- Autosomal dominant
- BLE > UE - symmetric
- malignant hyperthermia
- milestones
- “hollowed out”
- 3-7 yoa
also infantile onset, hypotonia, gowers sign
Nemaline Rode congenital myotaphty
1. inheritence
2. ____ at birth
3. ____ onset
4. biopsy?
5. ___ types
- AD
- hypotonic
- infantile onset
- abnormal rods in muscle fibers; in z-line
- four different types
Pathology?
high arch palates, weak sucking and weak cry. nuclei are centrally located in all muscle fibers, hypotonic at birth.
inheritence?
centronuclear congenital myopathy
AR
Pathology?
weak cry, weak suck, hypotonic baby, multiple joint contractures including club foot, high arched palate, congenital hip dislocation, kyphoscoliosis. Type 1 muscle fibers more numberous but smaller than T2 muscle fibers.
congenital fiber type disproportion congenital myopathy
Mitochondrial myopathies have what classic finding on muscle biopsy?
ragged red fibers
What is the mutation in congenital fiber type disproportion congenital myopathy?
herterozygous TPM3 mutation
Name the most common metabolic myopathies:
1. (a & b)
2. (a & b)
3. (a, b, & c)
- glycogen storage disorder
- mcardles disease (muscle phosphorylase deficiency)
- pompes disease - acid maltase deficiency - lipid metabolism disorder
- carnitine deficiency
- carnitine palmytyltransferase deficiency - Periodic paralysis
- hypo K
- normo K
- hyper K
Mcardles metabolic myopathies is type _____ glycogen metabolic storage disorder.
1. secondary to ____ deficiency
2. presents as (3)
3. biopsy?
V
- phophorylase enzyme deficiency
- muscle pain, stiffness, cramps with exercise intolerance
- large glycogen vacuoles on biopsy
Pompe’s disease is a glycogen storae disorder with ____ deficiency.
This deficiency causes _____ defect
Associated with _____
acid maltase enzyme deficiency
Type II glyconeogenesis deficiency
myotonia (only dystrophy with myotonia)
Name the two lipid metabolism deficiency disoriders (not on test)
- carnitine def
- carnitine palmityltransferase def
will see ______ for periodic focal paresis/paralysis.
1. inheritence?
2. failure of?
hypo, normo, or hyper-K levels.
1. AD
2. failure of action potential propogation along muscle membrane
____ presents as progressive weakness that affects the shoulder and hip girdles in an acute, subacute, or chronic presentation. Typically symmetric but can be asymmetric. Frequent complaints of muscle pain.
___ in urine
____ more common in (M vs F)
increased levels of ____ and ____
Polymyositis - acquired inflammatory myopathy
myoglobin
females > males (especially AAs)
CK and aldolase
what is on biopsy in polymyositis
inflammatory cells (lymphocytes and plasma cells) in connective tissue around the muscle fibers as well as necrosis
_____ will have classic heliotropic rash around the eyes
dermatomyositis. Presents just like polymyositis otherwise
progressive weakness that affects the shoulder and hip girdles in an acute, subacute, or chronic presentation. Typically symmetric but can be asymmetric. Frequent complaints of muscle pain.
Inclusion body myositis
1. Insidious onset of ____ and ____ over years
2. ______ extremities frequently affected
3. No complaints of _____
4. No _____ component in the pathology so no weakness/pain
5. Male ___: Female ____
6. age of onset:
7. Elevated ____
8. Does not respond to ____
9. Biopsy:
10. Electron microscopy:
- weakness and fatigue
- proximal lower extremities
- pain (as opposed to polymyositis)
- inflammatory
- 3:1
- mid 50s
- CK but not greater than 10 times normal
- steroids (as opposed to polymyositis)
- rimmed vacuoles with basophilic inclusion bodies
- intranuclear and intra-cytoplasmic filaments (pathognomonic)
What will be seen on electron microscopy and biopsy with inclusion body myositis
Bx: rimmed vacuoles with basophyilic inclusion bodies
EM: intranuclear and intra-cytoplasmic filaments
Name the 4 most common endocrine myopathies
- hypo/hyper thyroidism
- hyperparathyroidism
- adrenal- excess (cushings) too little (addsons)
- pituitary
Name the 3 most common toxic or drug induced myopathies
- alcohol - causes myopathic problemsn just like polyneuropathic processes
- any cholesterol lowering agent (statins and others)
- steroid myopathy
name the 3 most common etiologies for infectious myopathy
- HIV (syhpillus of the 20th century: any peripheral, central neuropathic problem, myopathic problems)
- Viral (influenza, coxsackie, echovirus, adenovirus, herpes simplex)
- Parasitic
- Protozoans (toxoplasmosis)
- Cestode (cystercercosis)
- Nematode (trichinosis)
Critical illness myopathy/neuropathy will have
1. ___ and ___ findings
2. extreme ____
3. ____ process
4. ____ pattern
- neuropathic and myopathic findings
- extreme weakness
- inflammatory process (can have some extensive steroid use as well but will see findings on EMG)
- asymmetric pattern
