Muscle Disorders Flashcards
(96 cards)
1
Q
What are the 5 questions you should include in your history for a patient with a muscle disease?
A
- What are the symptoms?
- What is the temporal course?
- Is there a family history of muscle disease?
- Are there provocative factors?
- Is there a pattern for symptoms?
- Are other symptoms involved?
2
Q
Wha is the most common pattern of acquired muscle weakness?
A
Proximal
3
Q
What are the “negative” symptoms of muscle disease?
A
weakness
fatigue
atrophy
exercise intolerance
4
Q
What are the “positive” symptoms of muscle disease (7) ?
A
myalgia
cramps
hypertrophy
contractures
stiffness
myotonia
myoglobinuria
5
Q
What are the 3 components to a muscle examination? Describe the specific aspects of each.
A
- Look
- atrophy, pseudohypertrophy, fasciculation
- Touch
- palpate for tenderness, check muscle tone
- Engage
- test power (0-5)
- weakness due to pain, fatigue, decreased effort?
- test power (0-5)
6
Q
What special test is being performed in the provided image?
What are 2 other tests for the same pathology?
A
Percussion Myotonia
percuss thenar emminence & there is an abnormal contraction of abductor pollicis brevis
Can also test: have them grip hand (+ = delay in opening); close eyes (+ = delay in opening)
7
Q
Percussion myotonia is seen in what two types of diseases?
A
myotonic dystrophy & channelopathies
8
Q
What change in reflexes do you see in muscle disease?
A
reflexes are never increased
9
Q
The presence of what additional symptoms indicate that a primary myopathy is unlikely?
A
sensory, bowel, or bladder symptoms
10
Q
What is the most important diagnostic test to perform when muscle disease is suspected?
A
Creatinine phosphokinase
11
Q
Is CPK usually elevated or depressed in muscle disease?
A
elevated
12
Q
CPK is markedly elevated in what 4 muscle diseases?
A
duschenne/Becker dystrophy
inflammatory myopathies
hypothyroid myopathy
rhabdomyolysis
13
Q
CPK is low/normal in what 4 muscle diseases?
A
dermatomyositis
steroid-induced myopathy
thyrotoxic myopathy
hyperparathyroidism
14
Q
What are the 4 major causes of Rhabdomyolysis?
A
neuroleptic malignant syndrome - antipsychotics
malignant hyperthermia- anesthesia
crush or blast injuries; muscle ischemia
statins (rare)
15
Q
What thyroid conditions can lead to acquired muscle diseases & what is the general CK associated with each?
A
- Hypothyroidism- myxedema (CK 10-100x)
- Hyperthyroidism- thyrotoxic myopathy (CK low/normal)
16
Q
What muscle issues do you see in hypoparathyroidism? Hyperparathyroidism?
A
- Hypoparathyroidism: tetany
- Hyperparathyroidism: proximal myopathy
17
Q
How will corticosteroid induced myopathy show up on biopsy?
A
type 2 fiber atrophy
18
Q
What exogenous steroid dosing should you start to be concerned about induced myopathy?
A
>30mg/day x weeks/months
19
Q
What is the most common type of electrolyte imbalance that can lead to myopathy?
A
hypokalemia
20
Q
If a person is on a statin, what additional medications drastically increases the chances of developing rhabdomyolysis?
A
calcium channel blocker
cyclosporine
gemfibrozil
21
Q
Why do statins cause myopathy?
A
they decrease mevalonate - a terpene / steroid precursor
22
Q
10% of patients on statins experience what muscle-related side effects?
A
myalgia/cramps
rhabdomyolysis is RARE (0.1%)
23
Q
What genetic factors predispose individuals to statin-induced muscle disease?
A
- 2% pop is homozygous for SNP
- rare autoimmune HMG-CoA Reductase
24
Q
What are the 4 substance that most commonly cause toxic myopathies?
A
EtOH, cocaine, colchicine, penicillamine
25
Antipsychotics can induce what syndrome that includes muscle disease? What are the symptoms of this syndrome?
**Neuroleptic malignant syndrome**
fever, muscular rigidity, rhabdomyolysis, delirium, death (5-10%)
26
What is the cause of Malignant Hyperthermia?
autosomal dominant **ryanodine receptor** mutation (chromosome 19) - exposure to depolarizing **muscle relaxants** (succinylcholine) or **inhaled anesthetics** (halothane, sevoflurane, desflurane)
this causes increased calcium release from sarcoplasmic reticulum
27
What are the symptoms seen in Malignant Hyperthermia?
muscle rigidity, hyperthermia, cardiac arrhythmias, CK elevation, metabolic acidosis, myoglobinuria
28
What is the treatment for malignant hyperthermia?
dantrolene
prevents release of calcium
29
What demographics of people are affected by criticla illness myopathy?
patients ventilated in ICU who are exposed to prolonged disuse and neuromuscular blocking agents
30
What are the symptoms of critical illness myopathy? muscle biopsy?
proximal flaccid weakness (usually not severe)
CK elevation
biopsy: loss of reactivity for myosin ATPase activity in type 1 fibers more than type 2 fibers
31
How can you tell the difference between steroid-induced myopathy vs critical illness myopathy:
biopsy?
causative drug?
distribution?
* **Steroid-induced myopathy**
* _biopsy_: **type 2** fiber atrophy
* _causative drug:_ prednisone \> 30mg/day
* _distribution:_ spares bulbar/facial and distal muscles
* **Critical Illness Myopathy**
* _biopsy:_ **type 1** atrophy \> type 2 atrophy
* _causative drug:_ neuromuscular blocking agents + disuse
* _distribution:_ proximal
32
What viral infections can cause localized myositis?
influenza A & B, HIV
33
What bacterial infections can cause localized myositis?
streprococci, MRSA
34
What parasitic infections can cause localized myositis?
trichinosis
cysticercosis
toxoplasmosis
35
What is the classic clinical picture of a patient with dermatomyositis?
female with subacute, symmetric, proximal \> distal weakness
(dysphasia/dysphagia, polyarthritis, interstitial lung disease)
often associated with cancer or other autoimmune conditions
36
What elevated lab values would you expect to see in a patient with dermatomyositis? Antibodies?
CK
LDH
aminotransferase
30% (+) myositis antibodies
37
Dermatomyositis is what type of condition?
microangiopathy directed against intramuscular blood vessels
38
What type of findings are seen in a muscle biopsy of a patient with dermatomyositis?
**perifascicular atrophy**
vasculitic changes
39
What is the treatment for dermatomyositis?
immunosuppression with steroids → then progress to steroid sparing agents (ie methotrexate/azathioprine)
40
What skin signs are associated with dermatomyositis? Are these always present?
heliotrope rash, V-sign, shawl sign, Gottron's papules
no- may not manifest until years after weakness starts
41
Initially dermatomyositis can look very similar to what condition? How can you distinguish?
polymyositis
distinguish via muscle biopsy (poly: cellular infiltration within the fascicle; dermato: perifascicular)
42
What is the classic clinical picture of a patient with polymyositis?
female with subacute, symmetric, proximal \> distal weakness
(dysphasia/dysphagia, polyarthritis, interstitial lung disease)
often associated with cancer or other autoimmune conditions
43
What elevated lab values would you expect to see in a patient with polymyositis? Antibodies?
CK
LDH
aminotransferase
30% (+) myositis antibodies
44
What type of findings are seen in a muscle biopsy of a patient with polymyositis?
Cellular infiltration within the fascicle; CD8+ mononuclear
45
How does polymyositis differ from polymyalgia rheumatica?
polymyalgia rheumatica has pain but _no weakness_
46
What is the treatment for polymyositis?
Immunosuppression
47
What is the most common acquired muscle disorder over age 50?
Inclusion Body Myositis
48
What is the common clinical picture of a patient with inclusion body myositis?
Male over the age of 50 with asymmetric progressive weakness of the finger flexors, wrist flexors, knee extensors and ankle dorsiflexors
medial/lateral anterior thigh atrophy
dysphasia
associated with other autoimmune conditions
49
What CK & serum lab values are seen in Inclusion Body Myositis?
_CK:_ mild / no elevation
_Serum:_ cytosolic 5'-nucleotidase 1A abs in 60% (worse prognosis)
50
What type of findings are seen in a muscle biopsy of a patient with Inclusion body Myositis?
Rimmed vacoules
51
What is the treatment for Inclusion body myositis?
minimal response to immunotherapy
52
What is dystrophin & what gene is it encoded by?
cytoplasmic protein that connects muscle fiber cytoskeleton to surrounding extracellular matrix through the cell membrane
DMD gene
53
What is the most common dystrophinopathy?
Duchenne muscular dystrophy
54
Duchenne Muscular Dystrophy shows what type of inheritance pattern?
X-linked recessive
55
Describe the progression of a patient with Duchenne Muscular Dystrophy.
* **3-6yr**
* wide based, wadded gait
* toe walking
* trouble running/walking
* neck weakness
* CK 50-100x nl
* **10yr**
* cannot climb stairs
* Gowers' sign
* **12yr**
* confined to wheelchair
* **Death by approx 20yr**
56
If a patient is still ambulatory beyond 16th birthday, they have what type of muscular dystrophy?
Becker's Muscular Dystrophy
57
What are the classic exam finding seen in patients with Duchenne Muscular Dystrophy?
calf pseudohypertrophy (fatty infiltration)
low reflexes
58
What sign is shown in the provided image? It is indicative of what pathology?
Gowers' Sign
Duchenne Muscular Dystrophy
59
What is the treatment plan for patients with Duchenne Muscular Dystrophy?
Multidisciplinary approach
**Corticosteroids should be offered to all boys with DMD (deflazacourt)**- prolongs walking, reduces falls, improves respiration, decreases scoliosis, improves cardiac & cognitive function
60
What is the recessive pattern of Becker Muscular Dystrophy?
X-linked recessive (Xp21)
61
What is the onset & presentation of Becker Muscular Dystrophy?
CK value?
Similar to DMD but milder phenotype (also have calf pseudohypertrophy)- presents later
_onset:_ 5-6 yr or 5th-6th decade (older onset = slower progression)
CK = 20-80x normal
62
What is the typical life-expectancy of a patient with Becker Muscular Dystrophy?
4th-5th decade
63
Becker Muscular Dystrophy is an important differential in what seemingly unrelated condition?
adult onset idiopathic dilated cardiomyopathy
64
What are the features seen in Emery-Dreifuss Muscular dystrophy?
* **early contractures**
* **no pseudohypertrophy**
* humeroperoneal weakness in childhood
* cardiac arrhythmia/conduction block
65
What is the cause of Facioscapulohumeral Muscular Dystrophy?
Inheritance Pattern?
Chromosome 4
when D4Z4 tandem repeat is truncated to 10 or less, this induces _DUX4_ gene transcript
Autosomal dominant (30% sporadic)
66
What is the typical presentation & progression of a patient with Facioscapulohumeral Muscular Dystrophy?
M=F
onset teens- symptoms usually fully manifested by age 20yr
(descending weakness)= facial (eye/lip) → scapular → proximal arm → leg
spares the deltoid
67
Limb-Girdle Muscular Dystrophy Group has what type of inheritance pattern?
autosomal recessive
68
What is the most common type of Limb-Girdle Muscular Dystrophy Group? Onset?
Calpainopathy - 75% onset before 20 yr
69
What are the symptoms seen in Limb-Girdle Muscular Dystrophy Group? Treatment?
* Symmetric proximal leg weakness \> shoulder-girdle
* very severe hip extensor, hip adductor, knee flexor weakness
* weakness of deltoid (late)
* Scapular winging, abdominal laxity
* generally spaces facial muscles
* normal life span
No disease modifying therapy
70
What is the most common muscular dystrophy in adults?
myotonic dystrophy (F=M)
71
What is the inheritance pattern of Type 1 & Type 2 Myotnic Dystrophy? Specific mutations?
* Type 1:
* autosomal dominant
* Chromosome 19
* unstable CTG repeat (anticipation- phenotype shows up earlier in successive generations)
* Type 2:
* autosomal dominant
* Chromosome 3
* CCTG (no anticipation)
72
Describe the difference in presentation between Type 1 & Type 2 Myotonic Dystrophy?
* Type 1:
* Distal weakness
* finger & wrist extensor → neck/jaw/facial
* “Hatchet face” w/ myotonia on exam (grip/percussion/eyelid)
* cardiorespiratory involvement
* insulin resistance
* Death by 50
* Type 2:
* proximal weakness:
* legs/mild neck flexor weakness
* mild / no myotonia
* lung spared
* les cardiac involvement
* normal lifespan
73
What condition is characteristic by the provided image?
Type 1 Myotonic Dystrophy
“Hatchet Face”
74
What is the cause of Pompe Disease (GSD Type II)? Inheritance pattern?
Autosomal Recessive
Chromosome 17 - mutation with acid maltase (acid-alpha glucosidase)
glycogen is not converted to glucose → abnormal glycogen accumulation in lysosomes / cytoplasm
75
What is the difference in Pompe Disease presentation in infants vs. adults?
* Infants (severe)
* hypotonia, enlarged tongue, cardiomegaly, hepatomegaly
* die age 1-2yr
* Adults (milder)
* pelvic \> shoulder weakness, abdominal/diaphragm weakness
76
What abnormal lab tests would you expect to see in a patient with Pompe Disease (GSD Type II)?
* CK: elevated
* EMG: irritable myopathy, myotonia
* Pulmonary testing: FVC supine
* Acid maltase activity: abnormal
77
Treatment of Pompe Disease (GSD Type II)?
alglucosidase alpha (myozyme)
78
Which GSD is static vs dynamic?
Static: Pompe Disease (GSD Type II) - weak all the time
Dynamic: McArdle Disease (GSD Type V)
79
What is the cause of McArdle Disease (GSD Type V)? Inheritance pattern?
autosomal recessive
mutation in PYGM gene - cannot break down glycogen into glucose-1-phosphate
80
What is the typical onset of McArdle Disease (GSD V)? Symptoms? Lab values?
* _onset:_ 1st decade / maybe not until 20s/30s
* _symptoms:_
* exercise induced cramps/myalgias with **second wind** phenomenon
* myoglobinuri & muscle contracture with sustained exercise
* **CK elevation ~1000, sustained 1-2 months**
81
What is the treatment for McArdle Disease (GSD V)?
creatine, carbohydrate rich diet, vitamin B6
avoid excessive or intense exercise; have a candy bar on hand
avoid general anesthesia
82
What is the causes of Carnitine Palmitoyltransferase II Deficiency? Inheritance pattern?
autosomal recessive
CPT II is an inner mitochondrial membrane protein; defect causes impaired beta oxidation - disorder of lipid metabolism
83
What is the typical age of onset for Carnitine Palmitoyltransferase II Deficiency? Symptoms?
* _Onset_: 20-30s
* _Symptoms_: Recurrent myoglobinuria
* myalgias/cramps after exercise
* **do NOT** see second wind phenomenon
* **normal CK between exercise periods**
84
Carnitine Palmitoyltransferase II Deficiency is seen most commonly in what situations? Treatment?
gradual onset / resolutions of cramps; with prolonged exercise
seen more with fasting, infection, low carb or high fat diet
avoid valproic acid
85
What is the most common cause of recurrent myoglobinuria in adults?
Carnitine Palmitoyltransferase II Deficiency
86
Inheritance pattern of hypokalemic periodic paralysis? Cause?
autosomal dominant
voltage-gated calcium or ligand-gated sodium channel
(66% have CACNA1S mutation; SCN4A mutation less common)
87
Typical age of onset for hypokalemic periodic paralysis? Symptoms? Lab findings?
* _Onset_
* 10-20yrs - remits after 35 yrs of age (may have limb girdle weakness later in life)
* _Symptoms:_
* _long episodes_ of paralysis (hours to days)- 7/9 times per month
* paralysis usually spares the ocular, bulbar & respiratory muscles
* _Lab findings_:
* serum K \< 3 mEq/L; transient CK elevation
* Exercise EMG: increased cAMP amplitude without electrical myotonia
88
What are the triggers for Hypokalemic periodic paralysis?
intake high carb meal, EtOh, cold, resting after exercise, stress
89
What is the treatment for Hypokalemic periodic paralysis?
KCl
carbonic anhydrase inhibitors (acetazolamide) for prevention
avoid carbohydrate meals & strenuous exercise
mild exercise may abort an attack
90
What is the cause of hyperkalemic periodic paralysis? Inheritance pattern?
autosomal dominant channelopathy
voltage-gated sodium channel mutation (SCN4A)
91
Typical age of onset for hyperkalemic periodic paralysis? Symptoms? Lab findings?
* _onset:_
* 5-15 yr; remits after 20 yr of age
* _Symptoms_:
* Brief episodes of weakness (minutes to hours) involving proximal muscles - ~15 x / month
* _Lab_:
* serum K \> 5.0 mEq/L, not always
* Exercise EMG: increased cAMP amplitude with electrical myotonia
92
What are the triggers for Hyperkalemic periodic paralysis?
potassium rich foods, fasting, cold, rest after exercise
93
What is the treatment for Hyperkalemic periodic paralysis?
low K+ die, avoid fasting & strenuous exercise
ingestion of carbohydrates and slight exercise at onset of weakness may prevent the attack
thiazide diuretics or acetazolamide for prevention
94
What is the cause of autosomal dominant myotonia congenita (Thomsen's Disease)? Most commonly affected demographics?
Chloride channel mutation
M=F (more severe in M); infants
95
Typical age of onset for autosomal dominant myotonia congenita (Thomsen's Disease)? Symptoms?
* infants - myotonia at birth
* peculiar cry
* difficulty feeding
* inability to re-open eyes while having face washed
* myotonia worse in the cold
* athletic ability poor b/c slow & stiff movement
* unable to play winter sport
* complete long-distance events
96
Diagnosis & treatment of Autosomal dominant myotonia congenita (Thomsen's Disease)?
* _diagnosis_: EMG
* _Treatment:_ mexiletine, phenytoin, procainamide
