Week 2: Demyelinating, Inflammatory, and Skeletal Muscle Pathology

Question 1

Autoimmune demyelinating disorder characterized by distinct episodes of neurologic deficits separated in time and are attributable to patchy white matter lesions separated by space

Answer 1

Multiple Sclerosis (MS)

Question 2

Who most commonly gets Multiple Sclerosis (MS)

Answer 2

Females 20s-40s

Question 3

What are 2 genetic factors for Multiple Sclerosis (MS)?

Answer 3

• DR Haplotype of MHC
• Higher incidence if 1st degree relative

Question 4

What is an environmental factor for Multiple Sclerosis (MS)?

Answer 4

Increase in cases further away from equator (possibly related to vitamin D)

Question 5

What is a frequent eye manifestation of Multiple Sclerosis (MS)?

Answer 5

Optic Neuritis

Question 6

What is seen on CSF analysis for Multiple Sclerosis (MS)?

Answer 6

Increase protein, moderate pleocytosis, increase IgG

Question 7

ID

Answer 7

Multiple Sclerosis (MS)

gray-brown plaque around occipital horn of the lateral ventricle (arrows)

Question 8

ID

Answer 8

Multiple Sclerosis (MS)

Regions of demyelination (MS plaques) around the fourth ventricle lack
the normal blue staining of myelin (Luxol fast blue periodic acid–Schiff
stain)

Question 9

ID

Answer 9

Multiple Sclerosis (MS)

(A) Active demyelinating plaques appear very cellular due to the presence of numerous lipid-laden macrophages.

Question 10

ID

Answer 10

Multiple Sclerosis (MS)

(B) The same lesion stained with the Luxol fast blue periodic acid–Schiff stain shows a complete lack of myelin.

Question 11

ID

Answer 11

Multiple Sclerosis

(C) Relative preservation of axons is seen on the neurofilament immunostain (brown).

Question 12

Loss of myelin in the base of the pons

Answer 12

Central Pontine Myelinolysis

Question 13

ID

Answer 13

Central Pontine Myelinolysis

Question 14

What causes Central Pontine Myelinolysis

Answer 14

2-6 days after rapid correction of hyponatremia

Question 15

What can Central Pontine Myelinolysis lead to

Answer 15

Locked-In Syndrome

Question 16

ID these factors for Type 1- slow twitch muscle

Answer 16

Think marathon runners

Question 17

ID these factors for Type 2- fast twitch muscle

Answer 17

Think sprinters like Usain Bolt

Question 18

ID

Answer 18

Skeletal Muscle Atrophy

Neurogenic atrophy- angulated fiber

Question 19

ID

Answer 19

Skeletal Muscle Atrophy - Type 2

Can be due to disuse or prolonged corticosteroid therapy

Normally is a “checkerboard-like” pattern and approximately equal

Question 20

ID the muscle change seen here

Answer 20

Neurogenic - disruption in muscle innervation

Question 21

ID the muscle change seen here

Answer 21

Myogenic - direct injury to myofibers

Black arrow - Regenerated fiber
White Arrow - Degenerated (necrotic) fiber

Question 22

Immunologic disease where damage to small blood vessels contribute to muscle injury

Answer 22

Dermatomyositis

Question 23

Biopsies demonstrate deposition of _____ in capillary beds

Answer 23

C5b-9

Question 24

In dermatomyositis the autoantibody Anti-M2 is associated with what clinical feature?

Answer 24

Gottron papules and heliotrope rash

Question 25

In dermatomyositis the autoantibody Anti-Jo1 is associated with what clinical feature?

Answer 25

intersitital lung disease, nonerosive arthritis, and rash aka “Mechanic’s hands”

Question 26

In dermatomyositis the autoantibody Anti-P155/P140 antibodies is associated with what clinical feature?

Answer 26

paraneoplastic and juvenile cases

Question 27

ID

Answer 27

Dermatomyositis

Question 28

What muscle layer and histology sign is dermatomyositis associated with?

Answer 28

Perimysium and Perifascicular atrophy

Question 29

On IHC, what immune cells are seen in dermatomyositis?

Answer 29

CD4+ lymphocytes

Question 30

Adult-onset inflammatory myopathy that shares myalgia and weakness with dermatomyositis but lacks its distinctive cutaneous features

Answer 30

Polymyositis

Question 31

What muscle layer is polymyositis associated with?

Answer 31

Endomysium

Question 32

On IHC, what immune cells are seen in polymyositis?

Answer 32

CD8+ lymphocytes

Question 33

Most common inflammatory myopathy in patients > 65 years. Slowly progressive; most severe in quadriceps and distal upper extremities.

Answer 33

Inclusion Body Myositis

Question 34

ID

Answer 34

Inclusion Body Myositis ## Footnote White arrows: rimmed vacuoles (Trichrome stain)

Question 35

Caused by loss-of-function mutation of dystrophin gene on X chromosome. Deletions or frameshift mutations result in total absence of dystrophin

Answer 35

Duchenne Muscular Dystrophy (DMD)

Question 36

links the intracellular cytoskeleton to extracellular basement membrane

Answer 36

dystrophin

Question 37

Caused by loss-of-function mutation of dystrophin gene on X chromosome. Mutations result in truncated but not absent dystrophin

Answer 37

Becker Muscular Dystrophy

Question 38

ID

Answer 38

Atrophy in skeletal muscle

Question 39

ID

Answer 39

Fibrofatty replacement ## Footnote Can't tell whether DMD or BMD based on histology alone. Need an IHC for dystrophin and/or clinical vignette

Question 40

ID

Answer 40

Becker Muscular Dystrophy ## Footnote dimished dystrophin on IHC

Question 41

ID

Answer 41

Duchenne Muscular Dystrophy (DMD) ## Footnote complete absence of dystrophin on IHC

Question 42

When does Duchenne and Becker Muscular Dystrophy present and what is their life expectancies?

Answer 42

DMD - presents in early childhood (6-7 years of age) and life expectance is 25-30 years. (absence of dystrophin) BMD - presents in later childhood, adolescence or adulthood; near normal life expectancy. (diminished dystrophin)

Question 43

ID

Answer 43

Spinal Muscle Atrophy ## Footnote include large zones of severely atrophic fibers mixed with normal-sized or hypertrophic myofibers

Question 44

Neuropathic disorder where loss of motor neurons leads to muscle weakness. Presents with generalized hypotonia (“floppy infant”)

Answer 44

Spinal Muscle Atrophy ## Footnote Anything that causes hypotonia in babies/infants can be called floppy baby syndrome. i.e. infantile botulism caused by honey or dust particles can also be caused "floppy baby/infant". Not a very accurate diagnosis, but good description.

Question 45

What is the genetics for Spinal Muscle Atrophy?

Answer 45

Autosomal Recessive (AR); loss of function SMN1 gene