Neuropathology Peripheral

Question 1

What connective tissue component is a multilayered concentric connective tissue sheath that groups subsets of axons into fascicles?

Answer 1

Perineurium

Question 2

The inflammation seen in GBS is located in what 2 microstructures?

Answer 2

Perivenular and Endoneurial

Question 3

Besides axonal neuropathy and demyelination what else can be seen in the histopathology of DM neuropathy?

Answer 3

Endoneurial arterioles show thickening, hyalinanization and intense PAS positivity of their walls and extensive reduplication of the basement membrane

Question 4

Anti CV2 antibodies lead to what type of peripheral nerve damage?

Answer 4

Mixed axonal and demyelinating sensorimotor neuropathy

Question 5

What are the components of the POEMS syndrome?

Answer 5

Polyneuropathy
Organomegaly
Endocrinopathy
Monoclonal gammopathy
Skin changes

Question 6

Identify which CMT/genetic neuropathy results with alteration to the function of the ff:

1. Myelin protein zero
2. Duplication of a region in chromosome 17 that includes myelin protein 22 (PMP 22)
3. GJB1 which encodes conenexin 32
4. MFN2 gene required for mitochondrial fusion
5. Deletion of the gene encoding PMP22
6. Transthyretin gene and protein
7. alpha galactosidase
8. beta galactosidase

Answer 6

1. Myelin protein zero CMT1B
2. Duplication of a region in chromosome 17 that includes myelin protein 22 (PMP 22) CMT1A
3. GJB1 which encodes conenexin 32 CMT1x
4. MFN2 gene required for mitochondrial fusion CMT2a
5. Deletion of the gene encoding PMP22 Hereditary neuropathy with pressure palsy
6. Transthyretin gene and protein Familial amyloid polyneuropathies
7. alpha galactosidase: Fabry disease
8. beta galactosidase: Krabbe disease

Question 7

Tomaculi, or bulbous myelin sheaths at the end of internodes are found in?

Answer 7

HNPP

Question 8

What percentage of MG patients will have a thymoma?

How about thymic hyperplasia?

Answer 8

10%

30%

Question 9

What structure is inhibited in Lambert Eaton Myasthenic syndrome?

Answer 9

Presynaptic calcium channel

Question 10

What is the difference in the MOA of botox and curare in inducing weakness?

Answer 10

Botox: Blocks release of Ach
Curare: Blocks the Ach receptor

Question 11

What pattern of muscle fiber damage is seen

1. Dermatomyositis
2. Corticosteroid use
3. Disuse

Answer 11

1. Dermatomyositis: Perifascicular atrophy
2. Corticosteroid use: Type 2 fiber atrophy with sparing of type 1
3. Disuse: Type 2 fiber atrophy with sparing of type 1

Question 12

Identify if type 1 or 2 muscle fiber:

1. Fast movement
2. Aerobic exercise
3. Lipid content
4. Glycogen content
5. High oxidative capacity
6. High mitochondrial density
7. Pale red/ tan color

Answer 12

1. Fast movement 2
2. Aerobic exercise 1
3. Lipid content 1
4. High Glycogen content 2
5. High oxidative capacity 1
6. High mitochondrial density 1
7. Pale red/ tan color 2

Question 13

Group atrophy is a typical finding in what etiology of muscle damage?
When type grouping is seen what process is likely occurring/occurred?

Answer 13

Disrupted innervation

Reinnervation

Question 14

What vasculopathic changes are prominent in Dermatomyositis?

Answer 14

1. The vasculopathic changes can be
   seen as telangiectasias (dilated capillary loops) in the nail folds, eyelids, and gums, and as dropout of capillary
   vessels in skeletal muscle.
2. Biopsies of muscle and skin may show deposition of the complement membrane attack complex (C5b-9) within capillary beds in both tissues.

Question 15

What clinical characteristics are associated with the ff autoantibodies in dermatomyositis?
• Anti-Mi2 antibodies
• Anti-Jo1 antibodies
• Anti-P155/P140

Answer 15

Anti-Mi2 antibodies (directed against a helicase implicated
in nucleosome remodeling) show a strong association
with prominent Gottron papules and heliotrope
rash (described later).

Anti-Jo1 antibodies (directed against the enzyme histidyl
t-RNA synthetase) are associated with interstitial lung
disease, nonerosive arthritis, and a skin rash described
as “mechanic’s hands.”

Anti-P155/P140 antibodies (directed against several transcriptional
regulators) are associated with paraneoplastic
and juvenile cases of dermatomyositis.

Question 16

What is the classic histopathologic finding in dermatomyositis will differentiate it from PM?

Answer 16

Perifascicular atrophy
Perimysial connective tissue contains mononuclear cells

In PM: Mononuclear inflammatory cell infiltrates in endomysial CT. Sometimes myofibers with otherwise normal morphology
appear to be invaded by mononuclear inflammatory cells. Degenerating necrotic, regenerating, and atrophic myofibers
are typically found in a random or patchy distribution.

Question 17

What proportion of patietns with dermatomyositis also have:

1. Interstitial lung disease
2. Dysphagia
3. Associated malignancy

Answer 17

1. Interstitial lung disease 10%
2. Dysphagia 1/3
3. 15-24% in adults

Question 18

Whereas CD4+ T helper cells and deposition of C59b in capillary vessels is involved in DM what cells are seen in PM and IBM?

Answer 18

Cytotoxic T cells– endomysial location

Question 19

What is the most common inflammatory myopathy in patients older than 50 years old?

Answer 19

Inclusion body myositis

Question 20

Rimmed vacuoles are found in what inflammatory myopathy? What do they contain?

Answer 20

IBM

beta amyloid, TDP 43, ubiquitin

Question 21

What are the main cellular elements that dystrophin links?

Answer 21

Cytoskeletal proteins linked to:
++ Transmembrane proteins: dystroglycan, sarcoglycan that are linked to ECM laminin
++ Dystrobrevin and syntrophins that are linked to caveolin

Question 22

What diseases result with mutations in the following proteins:

1. Caveolin and sarcoglycan proteins
2. Alpha 2 laminin (merosin)
3. Dystrophin

Answer 22

1. Caveolin and sarcoglycan proteins: LGMD
2. Alpha 2 laminin (merosin): Autosomal recessive congenital muscular atrophy
3. Dystrophin: Duchenne and Becker

Question 23

Which congenital myopathy presenting as floppy infant is consistent with the ff findings:
1. Cytoplasmic cores represent
demarcated central zones in
which the normal arrangement of sarcomeres is disrupted and mitochondria are decreased in number– Gene and locus involved is the Ryanodine Receptor-1 RYR1
2. Aggregates of spindle-shaped particles (nemaline rods); occur predominantly in type 1 fibers; derived from Z-band material (α-actinin) and best seen on modified Gomori stain or by electron microscopy AD NEM1—α-tropomyosin 3 (TPM3) gene;
1q22–q23

Answer 23

1. Central core disease

2. Nemaline myopathy

Question 24

What are the 2 histopathologic findings in Duchenne muscular dystrophy?

Answer 24

1. Segmental myofiber degeneration and regeneration associated with an admixture of atrophic myofibers. As the disease progresses fatty replacement, extensive variation in fiber size and endomysial fibrosis.
2. Complete absence of membrane associated dystrophin upon staining

Question 25

What are the 5 key features of myotonic dystrophy?

Answer 25

1. Myotonia 2. Weakness 3. Cataracts 4. Endocrinopathy 5. Cardiomyopathy

Question 26

What is the triad of emery dreifuss muscular dystrophy?

Answer 26

Humeroperoneal weakness Early contracures of the Achilles, spine and elbows Cardiomyopathy with conduction defects

Question 27

DUX4 gene overexpression results in what muscular dystrophy?

Answer 27

Fascioscapulohumeral dystrophy

Question 28

What enzyme is missing in Pompe disease? How about McArdle?

Answer 28

Acid maltase: deficiency results in impaired lysosomal conversion of glycogen to glucose Myophosphorylase deficiency: One of the more common glycogen storage diseases affecting skeletal muscle; it also results in episodic muscle damage with exercise

Question 29

Involvement of what muscle group sets mitochondrial myopathies apart?

Answer 29

EOMs-- have the MOST mitochondria per mass of any of the body's muscles Remember chronic progressive external ophthalmoplegia

Question 30

All mitochondrial DNA with inherited from?

Answer 30

Mom

Question 31

What are the 3 components of the Kearns Sayre syndrome?

Answer 31

1. Ophthalmoplegia 2. Pigementary degeneration of the retina 3. Complete heart block

Question 32

Mutations in the ff genes lead to which disease: 1. RYR1 2. SCN4A 4. CACNA1S or DHP receptor 5. CLCN1

Answer 32

1. RYR1: Central core myopathy and malignant hyperthermia (calcium channel) 2. SCN4A: Paramyotonia congenita and hyperkalemic periodic paralysis-- Sodium channel 4. CACNA1S or DHP receptor: Hypokalemic paralysis-- calcium channel 5. CLCN1: Myotonia congenita/ generalized myotonia (Becker)-- Chloride channel

Question 33

``` Antoni A (Dense) Antoni B (Loose) are findings in which tumor? ```

Answer 33

Schwannoma

Question 34

Which type of neurofibroma is associated with nerve roots or larege nerves and are UNIFORMLY NF1 ASSOCIATED?

Answer 34

* Superficial cutaneous neurofibromas often present as pedunculated nodules that can be seen isolated (if sporadic) or multiple (if NF1-associated). * Diffuse neurofibromas often present as a large plaquelike elevation of skin and are typically NF1-associated. * PLEXIFORM NEUROFIBROMA can be found in deep or superficial locations in association with nerve roots or large nerves and are uniformly NF1-associated.

Question 35

What tumor suppressor is missing in schwann cells of NF1 neurofibroma?

Answer 35

Neurfibromin

Question 36

What perecentage of NF1 patients will have Malignant peripheral nerve sheath tumor converting from plexiform neurofibroma?

Answer 36

5-10%

Question 37

A MPNST with a rhabdomyoblastic differentiation is called a?

Answer 37

Triton tumor

Question 38

What genes are the NF syndromes seen?

Answer 38

1: 17q11.2 2: 22q12