Pathology - Myopathies

Question 1

What is denervation atrophy?

Answer 1

• Any process that affects anterior horn cells or axon in the PNS

Question 2

What is the most common form of spinal

muscular atrophy?

Answer 2

• Werdnig-Hoffmann disease

Question 3

What is the characteristic onset of Werdnig-Hoffmann disease?

• How long till progression to death?
• What type of spinal muscular atrophy is it?

Answer 3

• birth to 4 months
• death within 3 years
• type 1 spinal muscular atrophy

Question 4

What is Werdnig-Hoffman’s mode of transmittance?

- Where does the degeneration occur?

Answer 4

• Autosomal recessive
• degeneration occurs in the cells in the anterior horn of the spinal cord and the motor nuclei in the brainstem. Considered a LMN

Question 5

What is the characteristic deficiency in muscle movement?
How can this be identified in babies?
How does death occur?

Answer 5

• Absence of stretch reflexes in the anterior horn , results in a flaccid paralysis, especially of the trunk and limbs (hypotonia) - “Floppy babies”
• Lack of sucking ability
• respiratory failure - no treatment

Question 6

What is characteristic about Werdnig-Hoffman upon histological examination?

Answer 6

• Dark nuceli around the periphery and muscle atrophy

Question 7

What are the two x-linked muscular dystrophies?

Which one is more severe?

Answer 7

• Duchenne and Becker
• 2 most common
• Duchenne is most severe/ common ( Xp21 gene defect–> dystrophin)

Question 8

What muscular dystrophy has a more common onset in childhood as opposed to adulthood.

Answer 8

• Duchenne- younger child onset

- Becker - adult onset

Question 9

What are the clinical manfestations of Duchennes?

Answer 9

• muscle fiber size varies, increased # of internalized nuclei, degeneration necrosis and phagocytosis of muscle, increase in connective tissue (blue stain would tell this), regeneration of muscle fibers but an overall decrease over time.

Question 10

What is characteristic of muscular dystrophies upon histologic examination?
- How can you tell the difference between DMD and BMD?

Answer 10

• variation in muscle fiber size, increased endomysial connective tissue (with blue dye), centralized nuclei, and fibrosis and inflammatory cells and hypertrophy of remaining muscle fibers.
• Western blot comparing presence of Dystrophin.

Question 11

What stain is used to identify dystrophin?

Answer 11

• Immunoperoxidase stain, which would be present in small amount in Becker type muscular dystrophy.

Question 12

What occurs for the muscle at the later stages of muscle dystophy?
- What is an important clinical finding that results from this?

Answer 12

• Muscle is replaced by fat

- Pseudohypertrophy of the calf muscle filled with fat and connective tissue

Question 13

Where is Duchenne’s normally seen first and where does it progress to?
What is one factor present in the blood that can help identify muscle breakdown?

Answer 13

• begins in the pelvic girdle (trouble walking), extends to shoulder girdle (can’t life arms very high)
• Initial (1st decade) increase in CK levels than a leveling off years later due to less muscles.

Question 14

What are the effects on the heart and brain for Duchenne’s?

Answer 14

• Cardiac failure

- Cognitive impairment - MR

Question 15

What is myotonic dystrophy?

Answer 15

• impaired muscle relaxation and most common form of adult muscular dystrophy

Question 16

What type of transmission is responsible for Myotonic dystrophy?
What is muscle fibers are effected?

Answer 16

• Autosomal dominant disorder

- Atrophy of Type I and hypertrophy of type II fibers

Question 17

What is the main distinguishing factor myotonic dystrophy vs. Duchennes?

Answer 17

• There is not prominent necrosis and regeneration in myotonic dystrophy.

Question 18

What are the clinical manifestation of myotonic dystrophy?

Answer 18

• Patients complian of stiffness and unable to relax grip from handshake
• Affect many systems (endo, cataracts in all patients, CNS, SM)
• Facial, jaw muscle affected
• Gynecomastia
• Frontal balding

Question 19

What is a physical test for myotonic dystrophy?

Answer 19

On percussion of thenar muscles, the thumb moves sharply into opposition and adduction and slowly returns to initial position in individuals exhibiting a myotonic response.

Question 20

What is characteristic of an infant with myotonic dystrophy?

Answer 20

• The upper lip has an inverted V shape

Question 21

What are the diagnostic histological clues for myotonic dystrophy?

Answer 21

• Presence of central nuclei, variation in fiber size , fibrosis and long strings of nuclei in longitudinal sectionals.

Question 22

In toxic myopathies what features might proceed other signs?

Answer 22

Exophthalmos may precede other signs,

Question 23

What is caused be a decrease in thryoid function?

Answer 23

• muscle cramps
• movement and reflexes slowed
• Males:females 4:1

Question 24

What are some myopathic effects of binge drinking?

Answer 24

i) acute myopathy - rhabdomyolysis –>myoglobinuria (piss out myoglobin - red urine)
2) may lead to renal failure

Question 25

What might steroids induce?

Answer 25

1) proximal muscle weakness (difficulty walking or sitting down)
2) Muscle atrophy (type 2 fibers)

Question 26

What is a main feature of MG?

Answer 26

Loss of AcH receptors, increase in AcH antibodies
65% due to thymic hyperplasia
15% due to thymoma

Question 27

What are the clinical features of MG?

Answer 27

1) extraovular muscles: ptosis, diplopia
2) generalized weakness: tx with anti cholinesterase, prednisone, and plasmapheresis.
3) respiratory compromise was a major cause of death (95%)
4) decrease nerve conduction with repetitive stimulation

Question 28

How does Lambert-Eaton syndrome develop?

Answer 28

• develops as paraneoplastic process, a small cell CA of lung in ~60%
• Proximal muscle weakness–> with autonomic dysfunction

Question 29

What is a distinguishing feature of MG vs. LES treatment?

What is the effect on nerve conduction?

Answer 29

• LES: no benefit with anti-cholinesterase unlike MG.

- Increase nerve conduction with repetitive stimulation

Question 30

What autoimmunity might be a problem for LES?

Answer 30

an autoimmunity to Ca2+