Myopathies Flashcards
(124 cards)
1
Q
What is the Ddx for weakness?
A
- Metabolic disturbances due to endocrine/electrolyte abnormalities
- Systemic illness from infection, immunologic or neoplastic origin
- UMN disease
- Neuromuscular disease
2
Q
What is a myopathy?
A
A disease of muscles resulting in weakness and variable pain and wasting
3
Q
What are the three types of myopathies?
A
- Muscular dystrophy
- Inflammatory myopathies
- Metabolic myopathies
4
Q
What features are associated with dystrophic myopathies?
A
- Fiber splitting
2. Increased connective tissue
5
Q
What are the different types of muscular dystrophy?
A
- Duchenne
- Becker
- Fascio-scapulo-humeral (FSH)
- Myotonic
- Limb girdle
- Emery-Dreifuss
- Oculo-pharyngeal
6
Q
What are the main areas of weakness in Duchenne MD?
A
Proximal upper and lower limbs
7
Q
What are the main areas of weakness in Emery-Dreifuss MD?
A
Proximal upper limb and distal lower limb
8
Q
What are the main areas of weakness in Limb Girdle MD?
A
Proximal upper and lower limbs
9
Q
What are the main areas of weakness in Fascio-scapulo-humeral (FSH) MD?
A
Proximal upper limbs + calfs + face
10
Q
What are the main areas of weakness in Oculopharyngeal MD?
A
Proximal upper and lower limbs + eyes + throat
11
Q
Describe the genetics and onset of Duchenne’s MD
A
X-Linked recessive
Xp21 large deletion
Onset at age 5
12
Q
Describe the genetics and onset of Becker MD
A
X-Linked recessive
Xp21
Onset at age 10
13
Q
Describe the genetics and onset of FSH MD
A
Autosomal Dominant
Chromosome 4
Onset 10-20
14
Q
Describe the genetics and onset of Myotonic MD
A
Autosomal Dominant
Chromosome 19
Onset 15-30
15
Q
Describe the genetics and onset of Limb Girdle MD
A
AR/AD
Onset 10-30
16
Q
What is the initial weakness in Duchenne’s MD?
A
Pelvic- will have Gower’s Sign
17
Q
What is the initial weakness in Becker’s MD?
A
Pelvic
18
Q
What is the initial weakness in FSH MD?
A
Shoulder
19
Q
What is the initial weakness in Myotonic MD?
A
Distal Weakness
20
Q
What is the initial weakness in Limb Girdle MD?
A
Pelvic-Shoulder
21
Q
Which muscular dystrophies show early facial weakness?
A
FSH and Myotonic MD
22
Q
Which muscular dystrophies show late facial weakness?
A
Duchenne and Becker MD
23
Q
Which MD spares the face?
A
Limb Girdle MD
24
Q
Which muscular dystrophy has a rapid progression?
A
Duchenne’s MD
25
Which muscular dystrophies have elevated CK?
Duchenne + Becker + Limb Girdle
26
Which MD has a normal EKG?
FSH
27
Describe the muscle histology for Duchenne MD
Macrophage invasion + necrotic fibers
28
Patholophysiological difference between Duchenne and Beckers MD
```
Duchenne = Out of Frame mutation in Dystrophin
Beckers = In frame mutation in Dystrophin
```
29
What is the consequence of mutated Dystrophin?
It weakens the sarcolemma and leads to muscle necrosis
30
What are the clinical features of Duchenne's MD?
1. Difficulty running, waddling gait
2. Calf Pseudohypertrophy
3. Neck flexor weakness
4. Lumbar Lordosis
5. CI
6. Wheel chair by 13
7. Intestinal pseudo-obstruction
8. Cardiomyopathy --> HF
9. Respiratory failure
31
Typical age of death in patient with DMD?
20
32
What is the treatment for Duchenne's MD?
1. Prednisone
| 2. Deflazacort (best started by age 4-7)
33
How do steroids benefit patients with DMD?
1. Prolong ambulation
2. Delay respiratory failure
3. Stabilize the sarcolemma
4. Increase muscle mass
34
Why are 8% of female carriers of DMD symptomatic?
X-linked inactivation turns off the healthy dystrophin gene
35
What is the typical presentation in symptomatic female carriers of DMD?
1. Mild risk of heart disease, muscle weakness and CI
2. Myalgia
3. Elevated CK and aldolase
36
Compare the symptoms of Becker's MD to DMD
Beckers presents with calf pseudohypertrophy and early thigh weakness, but patients are less likely to have the GI obstruction, heart failure, CI and contractures seen in DMD patients
37
What will EMG show for DMD and Becker's MD?
Myopathic Units
38
What are non-medical treatments appropriate for Becker's MD?
1. Genetic Counseling
2. Physical Therapy
3. Orthopedic Complication
39
What is the genetic association with fascioscapulohumeral MD?
Autosomal Dominant deletion of D4Z4 on 4q35
40
Describe the symptoms of FSH MD
Slow wasting of facial, scapular, humeral and perineal muscles, down sloping shoulders + winged scapular and prominent clavicles
41
Is life expectancy altered in FSH MD?
No
42
Which muscle groups are affected by Myotonic Dystrophy 1?
Distal Muscle Groups
43
Which muscle groups are affected by Myotonic Dystrophy 2?
Proximal Muscle Groups
44
Which type of Myotonic Dystrophy is more common?
Type 1
45
What is the genetic association with the different types of Myotonic Dystrophy?
Type 1: CTG repeats in DMPK gene
| Type 2: CCTG repeats in zinc finger protein 9
46
Which hereditary pattern is seen with Myotonic Dystrophy Type 1?
Anticipation
47
What are symptoms of Myotonic Dystrophy Type 1?
1. Myotonia
2. Cataracts
3. Avoidant Personality
4. Hypersomnia
5. Hypogonadism
6. Mental Retardation
7. Cardiac issues
48
What is the genetic pattern observed in Limb Girdle Muscular Dystrophy Types 1 and 2?
Type 1: AD
| Type 2: AR
49
Other than proximal muscles, which organ systems may be involved in LGMD?
Cardiac and Respiratory Systems
50
What is the genetic defect seen in EMMD Type 1?
Emerin Defect, AR mutation of Xq28
51
What is the genetic defect seen in EMMD Type 2?
Lamin A/C, AD or AR
52
Which sub-class of Emery Dreifuss MD is associated with contractures?
Type 1
53
Which MD is associated with cardiac conduction abnormalities?
Type 1 Emery Dreifuss MD
54
What is the inheritance pattern for Oculo-pharyngeal MD?
Autosomal Dominant
55
When is the typical onset of OPMD?
Middle age
56
What is the pathological cause of OPMD?
Defect in the polyadenylate-binding protein (PABN1 due to GCG expansion or PABN2 due to GCA expansion)
57
What chromosome is PABN on?
14
58
What are the symptoms of OPMD?
1. Ptosis
2. Mild EOM weakness
3. Dysphagia
4. Mild limb weakness
5. Reduced gag reflex
59
What is the treatment for OPMD?
Oculoplasty or PEG
60
What is the age of onset for Polymyositis?
45-65
61
Which gender is more commonly affected by Polymyositis?
Women
62
What is the clinical presentation of Polymyositis?
Weak onset proximal muscle weakness + falls + lung and cardio involvement
63
How are dermatomyositis and polymyositis diagnosed?
CK + EMG and Bx
64
What is the treatment for Dermatomyositis and Polymyositis?
Immunosuppression
65
What is seen on histology with Polymyositis?
Endomysial inflammation
66
What is the age presentation for Dermatomyositis?
Bimodal (5-14 and 45-65)
67
Which gender is more commonly affected with Dermatomyositis?
Women
68
What is the clinical presentation of Dermatomyositis?
Rapid onset proximal weakness + heliotrope rash + Gottron's Sign + lung and cardio involvement
69
What disease may be associated with breast and lung malignancy?
Dermatomyositis (25%)
70
What disease is associated with Gottron's Papules on the hands?
Dermatomyositis
71
What is seen on histology with Dermatomyositis?
Perifascicular Atrophy
72
What is the most common inflammatory myopathy in adults over 50?
Inclusion Body Myositis
73
Which gender is more commonly affected by inclusion body myositis?
Men
74
What is the clinical presentation of inclusion body myositis?
Slow onset proximal and distal weakness + dysphagia
75
Which muscles are involved in inclusion body myositis?
Fingers and wrist flexors + quads + hip flexors
76
How is inclusion body myositis diagnosed?
CK + EMG + Bx
77
What is seen on biopsy of inclusion body myositis?
Rimmed vacuoles with amyloid inclusions + endomysial inflammation
78
How does inclusion body myositis respond to immunosuppression?
Poorly
79
Which myopathies are associated with cancer?
Dermatomyositis and Polymyositis
80
Which myopathy involves distal and proximal muscles and is often asymmetric?
Inclusion body myositis
81
What is the EMG result for Inclusion Body Myositis?
Myopathic + Neuropathic
82
Which inflammatory myopathy has the best response to steroids?
Dermatomyositis
83
What are the general causes of metabolic myopathies?
1. Glycogen metabolism
2. Lipid metabolism
3. Electrolyte imbalance
4. Mitochondria
84
What are the symptoms of disorders of glycogen and lipid metabolism?
1. Exercise intolerance
| 2. Myoglobinuria and elevated CK following exercise
85
What are the genetics of most glycogen and lipid metabolic disorders?
Autosomal Recessive enzyme deficiencies
86
EMG findings for glycogen and lipid metabolic disorders are
Myopathic
87
How is the diagnosis of glycogen or lipid metabolic disorders made?
Biochemical analysis of muscle Bx
88
What is the deficiency in Pompe Disease?
Type II Acid Maltase
89
What are the symptoms of Pompe Disease?
Proximal muscle weakness + early respiratory insufficiency
90
What is the deficiency in Cori-Forbes Disease?
Type II Debrancher Deficiency
91
What are the symptoms of Cori-Forbes Disease?
Distal weakness + cardiomyopathy + PN
92
What is the deficiency in McArdle's Disease?
Type V Myophosphorylase Deficiency
93
What are the symptoms of McArdle's Disease?
Camps + Myoglobinuria + Second Wind Phenomenon
94
What is the deficiency seen in Tarui Disease?
Type VII Phosphofructokinase Deficiency
95
What are the symptoms of Tarui Disease?
Exercise intolerance + myoglobinuria
96
Explain the consequences of a Carnitine Palmitoyl Transferase II Deficiency
Carnitine is required for the transport of FA into the mitochondria; symptoms flare up during fasting
97
What are the symptoms of CPTII Deficiency?
Progressive proximal muscle weakness + tenderness and swelling of muscles with exercise + increased CK + myoglobinuria
98
What is seen on Bx of CPTII Deficiency?
Lipid Storage Vacuoles
99
Describe the clinical presentation of Hypokalemic Periodic Paralysis
Pt wakes up w/ weakness that lasts hours-days after having a large carb load of after exercise
100
What is the underlying cause of hypokalemic periodic paralysis?
L-Type Ca Channelopathy
101
Describe the clinical presentation of hyperkalemic periodic paralysis
Paralysis caused by a period of rest after fasting or exercise
102
What is the underlying cause of hyperkalemic periodic paralysis?
SCN4A Na Channelopathy
103
What is the Tx for Hyperkalemic Periodic Paralysis?
Eating or exercise
104
Myotonia congenita is caused by
CLCM1 (Cl) Channelopathy
105
Paramyotonia Congenia is caused by
CLCN1 or SCN4A Chennels
106
Inheritance pattern for mitochondrial myopathies
Maternal
107
Which type of myopathy is associated with neurologic symptoms?
Mitochondrial Myopathies
108
How is the diagnosis of mitochondrial myopathies made?
By finding ragged reg fibers on muscle biopsy and biochemical analysis of muscle for specific oxidative enzymes
109
What are the symptoms of Kearns-Sayre Syndrome?
1. CPEO
2. Retinitis Pigmentosa
3. Heart Block
110
What are the causes of provoked necrotizing polymyopathy?
Crush Injury, EtOH or extreme exertion
111
Which patients are more susceptible to provoked necrotizing polymyopathy?
Pts with Glycogen disorders
112
What is the clinical presentation of provoked necrotizing polymyopathy?
Pigmenturia + Tender Muscles
113
What is the Tx for provoked necrotizing polymyopathy?
IV Fluids + monitor CK + rarely dialysis
114
Which patients are more susceptible to malignant hyperthermia?
Pts with defects of Phosphodiesterase or RYR1 mutation
115
What is the clinical presentation of malignant hyperthermia?
Fasciculations + increased tone + temperature increase + rigidity following anesthetics (Halothane and Succinylcholine)
116
Tx for malignant hyperthermia?
Dantrolene + cooling blankets
117
What are the symptoms seen with Hypothyroid Myopathy?
1. Muscle cramps and proximal weakness
2. Delayed reflexes
3. Myoedema
4. Myokymia
5. Elevated CK
118
Which patients are more likely to develop critical illness myopathy?
ICU patients on high dose steroids or paralytics + ventilator patients
119
Describe the myopathy seen with acromegaly
Mild proximal muscle weakness
120
Describe the myopathy seen with Cushing's
Proximal weakness of the lower extremities
121
Describe the EMG findings for a myopathy
Low amplitude + short duration + polyphasic with rapid recruitment
122
Steroids result in what type of myopathy
Proximal Muscle Myopathy
123
Common medication that causes myopathy
Statins
124
Medication causing mitochondrial myopathy
AZT
