Block 4 Path Exam -- Neuromuscular Pathology

Front 1

What is the difference between primary and secondary myopathies?

Back 1

Primary -- defect in muscle structure/function

Secondary -- acquired muscle dysfunction
(due to something outside of the muscle itself, ie toxins)


NOTE: same distinction applies between primary and secondary neuropathies

Front 2

What clues can be used to differentiate myopathies from neuropathies (3)?

Back 2

Myopathy -- motor, proximal, no autonomic involvement

Neuropathy -- motor & sensory, distal, often autonomic involvement

Front 3

What is pseudohypertrophy?

What is it a sign of?

Back 3

When muscle seems to be enlarged
Actually due to replacement of muscle by fat/connective tissue

Sign of myopathy

Front 4

What is myotonia?

Back 4

Delayed relaxation of muscles

Front 5

What are muscular dystrophies defined as?

Back 5

Primary, genetically transmitted diseases
Entail a progressive muscle wasting and weakness

Front 6

Duchenne's and Becker dystrophies are due to mutations in what?

Back 6

Dystrophin gene

Front 7

Different characteristics of Duchenne vs. Becker dystrophies

Back 7

--- Duchenne --
SEVERE, manifests by ~ 5 y.o., rapidly progressive
wheelchair dependence by 10-12 y.o., death in early 20s

--- Becker ---
MILD, onset in late childhood, slower progression
Many pts. have nearly normal lifespan

Front 8

How do people w/ Duchenne dystrophy present at birth?

Back 8

NORMAL

Front 9

How are Duchenne and Becker dystrophies transmitted?

Back 9

X-linked inheritance

NOTE: female carriers CAN have myopathic symptoms

Front 10

What other body parts can Duchenne and Becker dystrophies affect (2)?
(beyond skeletal muscle)

Back 10

Cardiac muscle and brain
SO, pts. can also have cardiomyopathy and mild mental retardation

NOTE: cardiac disease is much rarer in Becker MD

Front 11

Limb girdle dystrophies are due to defects in what?
(part of the dystrophin complex)

Back 11

Sarcoglycans

Front 12

Congenital muscular dystrophy is due to defects in what?
(part of the dystrophin complex)

Back 12

Merosin (laminin-2)

Front 13

What does the dystrophin complex do?

Back 13

Links the actin cytoskeleton to the extracellular matrix

Front 14

What is the most common adult-onset muscular dystrophy?

Back 14

Myotonic dystrophy

Front 15

What genetic abnormality is present in myotonic dystrophy?

Back 15

Trinucleotide repeat (CTG) expansion

n > 50 repeats equal disease

Front 16

What is Pompe disease?

Back 16

A congenital myopathy

Deficiency in acid maltase

Front 17

What are the big three INFLAMMATORY myopathies?

Back 17

Dermatomyositis
Polymyositis
Inclusion body myositis

Front 18

What is the pathophysiology of dermatomyositis?

Back 18

Immune complexes deposit in capillaries of muscle and skin
(entails perivascular B and T cells)

Damaged capillaries cause muscle ischemic damage
(happens particularly at the periphery)

NOTE: dermatomyositis affects BOTH kids and adults

Front 19

What is the pathophysiology of polymyositis?

How does it present histologically?

Back 19

Cytotoxic T cell attack on muscle cells

Endomysial infiltrates, plus scattered atrophy

Front 20

What is the treatment for polymyositis?

Back 20

Responds to steroid treatment

Front 21

What group of people does polymyositis affect most?

Back 21

Adults, F > M

Front 22

What group of people does inclusion body myositis affect most?

Back 22

Adults, M >> F (3x)

Front 23

How does inclusion body myositis differ from polymyositis?

Back 23

Affects males more
Has more distal involvement
Has a highly specific pattern of rimmed vacuoles and/or inclusions
Is NOT responsive to steroid treatment

Front 24

Inclusions in inclusion body myositis resemble those found in what disease?

Back 24

Alzheimer's

Front 25

What is the pathophysiology of Mcardle's disease?

Back 25

Deficiency in the phosphorylase that breaks down glycogen

Front 26

What is the main therapy for Mcardle's disease?

Back 26

Dietary management

Front 27

What type of exercise can people w/ Mcardle's not tolerate?

What does doing this type of exercise cause?

Back 27

Can't tolerate brief and intense exercise

Causes cramping, and muscle swelling

Front 28

How is Mcardle's disease inherited?

Back 28

RECESSIVE inheritance

Front 29

What group of people does Mcardle disease affect most?

Back 29

Males

Onset is @ < 15 y.o.

Front 30

How is Pompe's disease inherited?

Back 30

RECESSIVE inheritance

Front 31

What are the three types of Pompe's disease?

Which is the most serious?

Back 31

Infantile onset
Childhood onset
Adult onset

Infantile onset is the most serious
(usually, pts. die before 1 year of age)

Front 32

In infantile Pompe's, where does glycogen accumulation occur?

Back 32

In most tissues

There is pronounced heart and liver involvement

Front 33

How can infantile Pompe's present?

Back 33

Cardiomegaly & CHF
Liver involvement
Weakness & hypotonia

Front 34

In childhood onset Pompe's, where does glycogen accumulation occur?

Back 34

Mainly in muscle

Front 35

How does childhood onset Pompe's present?

Back 35

Proximal, symmetric weakness (large muscles)

Front 36

In what age range do pts. w/ chilhood Pompe's die?

What do they die of?

Back 36

From age 3 - 24

Die of respiratory failure

Front 37

How does adult onset Pompe's present differently in young and old adults?

Back 37

Young adults -- fatigue

Old adults -- proximal weakness

Front 38

What group of muscles does adult onset Pompe's affect?

Back 38

Paraspinous muscles (causes atrophy)

Front 39

What is carnitine, and what does it do?

Back 39

Pseudo amino-acid

It shuttles fatty acids across the mitochondrial membrane
(plays an important role in FA metabolism)

Front 40

What set of muscles do mitochondrial myopathies often affect?

Back 40

Proximal muscles

Sometimes, w/ SEVERE involvement of extraocular muscles

Front 41

What is Kearns-Sayre syndrome?

Back 41

Ophthalmoplegia plus pigmentary degeneration of the retina

It is a mitochondrial myopathy

Front 42

What type of inheritance do mitochondrial myopathies show?

Back 42

Often, MATERNAL inheritance

Front 43

What is the pathophysiology of myasthenia gravis?

Back 43

Due to autoantibodies against ACh receptors

Front 44

What is the pathophysiology Eaton-Lambert Syndrome?

Back 44

Due to autoantibodies against presynaptic Ca channels

NOTE: this syndrome is usually paraneoplastic
(seems that Abs are triggered by a cancer Ag)

Front 45

What are differences between chronic vs. acute denervation changes?

Back 45

Acute cause scattered atrophy

Chronic first cause grouped atrophy
Ultimately, cause fiber-type grouping

Front 46

What is a dysesthesia?

Back 46

Condition in which a sense, particularly touch, is distorted

i.e. "pins and needles"

Front 47

What is Wallerian degeneration?

Back 47

Degeneration of an axon DISTAL to the site of injury

Front 48

What is a regenerating cluster?

What is it a sign of?

Back 48

Several adjacent sprouting axons myelinated by a single Schwann cell

Evidence of axonal damage

Front 49

What is onion bulb formation a response to?

Back 49

Schwann cell response to any chronic demyelinating process

Front 50

What group(s) of people does Guillan-Barre most affect?

Back 50

Young adults and > 55 y.o.

Male:Female is 1.25:1

Front 51

How is Guillan-Barre treated?

Back 51

Plasma exchange or IV IgG

Front 52

What type of infiltrate would be seen on a Guillan-Barre biopsy?

Back 52

Macrophagic infiltrate

Front 53

25% of cases of GBS are preceded by what?

Back 53

Campylobacter jejuni infection

Front 54

What pathological findings are seen in CIDP?
(chronic inflammatory demyelinating polyneuropathy)

Back 54

Early -- lymphocytic & macrophagic infiltrates

Late -- Onion bulbs

Front 55

How is CIDP treated?
(chronic inflammatory demyelinating polyneuropathy)

Back 55

Responds to steroids

Front 56

How does diabetic neuropathy often present?

Back 56

As a distal, sensory, polyneuropathy

Front 57

What happens to capillaries in diabetic polyneuropathy?

Back 57

Capillary walls get thickened and hyalinized

Front 58

What fibers are most affected in vasculitis neuropathy?

Back 58

Large, myelinated fibers are most severely affected

Front 59

How does Charcot-Marie-Tooth disease present?

Back 59

Loss of muscle tissue
Loss of touch sensation (predominantly extremities)

Front 60

What does connexin32 do?

What do mutations in it cause?

Back 60

Forms gap junctions

Point mutations in it cause X-linked CMT
(inheritance is X-linked dominant)

Front 61

What protein is assoc. w/ both HNPP and CMT1A?
(hereditary neuropathy w/ pressure palsies)
(charcot-marie-tooth 1a)

Too little of it causes what?
Too much of it causes what?

Back 61

PMP-22

Too little (1 copy (due to deletion)) of it causes HNPP
Too much (3 copies (due to duplication)) of it causes CMT-1a

Front 62

What is revealed on biopsy in HNPP?
(hereditary neuropathy w/ pressure palsies)

Back 62

Tomaculae -- focal thickening of the myelin sheath

Front 63

When is the usual onset of HNPP?
(hereditary neuropathy w/ pressure palsies)

Back 63

Young adulthood

Front 64

What does protein P0 do?

Back 64

Helps maintain the structural integrity of the myelin sheath

Front 65

What are the 3 important peripheral Schwann cell myelin proteins?

Back 65

P0
PMP22
Connexin32

Front 66

When is the usual onset for CMT1A?
(charcot-marie-tooth 1a)

Back 66

1st decade of life

Front 67

What is the most prominent initial sign of CMT1A?
(charcot-marie-tooth 1a)

Back 67

Foot drop

NOTE: leg areflexia is present in 100% of the cases

Front 68

What does biopsy early vs. late in CMT1A show?

Back 68

Early -- excess myelin

Late -- myelin loss and onion bulb formation

Front 69

How is the gene for PMP22 inherited?

Back 69

Autosomal dominant inheritance