Peripheral N & Skeletal M Path

Question 1

Segmental demyelination process

Answer 1

Schwann cell dysfunction leads to damage of the myelin sheath. Random internodes of myelin are injured (denuded axon) and remyelinated by multiple Schwann cells while the axon and myocytes remain intact. (Ex. Guillain-Barre Syn)

Question 2

How can you tell internodes are newly myelinated?

Answer 2

They are shorter than normal and take several to bridge the demyelinated region

Question 3

What is axon damage?

Answer 3

Axon damage affects whole neuron body or axon

Question 4

What is a focal lesion

Answer 4

traumatic transection of an axon, the distal portion undergoes Wallerian degeneration

Question 5

What are myelin ovoids?

Answer 5

Schwann cells that catabolize myelin & later engulf axon fragments producing small oval compartments

Question 6

If you see triangular ‘angulated’ muscle fibers what process has happened?

Answer 6

Denervation atropy

Axonal degeneration -> muscle fibers in motor unit lose neural input -> DA

Question 7

What determines muscle fiber type?

Answer 7

Motor neuron determines fiber type

Question 8

Type 1 v Type 2 neurons. (more for boards)

Answer 8

1 - Sustained force, weight bearing, red, slow-twitch. Lots of lipids with low glycogen

2 - sudden movements, purposeful motion, white, fast-twitch. Lots of glycogen with low lipids

Question 9

What would cause group atrophy of type 2 fibers?

Answer 9

Inactivity or disuse (limb fracture, pyramidal tract degeneration, neurodegenerative dz)

Glucocorticoid therapy -> steroid myopathy

Question 10

What are the pathologic reactions of myoctes? (4)

Answer 10

Segmental necrosis - loss of muscle fiber -> deposition of collagen and fat (Ex. Duchenne’s muscular dystrophy)

Hypertrophy - muscle fiber splitting; response to increase load

Regeneration - large internalized nuclei with prominent red RNA under trichrome stain

Vacuolization

Question 11

Describe the findings of peripheral neuropathy?

Answer 11

Tingling, stabbing, burning or “pins and needles”

Question 12

Difference between mononeuropathies and polyneuropathies?

Answer 12

Mono - involve a single nerve & deficits are restricted to region
Poly - multiple nerves are involved, usually symmetrically. Deficits ascend with dz progression (stocking & glove distribution)

Question 13

What is Mononeuritis multiplex and the associated dz’s?

Answer 13

Several nerves damaged in haphazard fashion.
Assoc. with vasculitis like polyarteritis nodosum (PAN)
Ex. HIV

Question 14

What is affected in polyradiculoneuropathies?

Answer 14

Nerve roots and peripheral nerves

Question 15

Bell’s Palsy

Answer 15

Mononeruopathy of CN VII

Asymmetrical facial drop assoc. with URI & DM. Usually resolves spontaneously

Question 16

What is Neurogenic bladder and the dz’s assoc. with it?

Answer 16

Lack of bladder control due to brain, spinal cord or nerve problem.

Assoc. with MS, Parkinson’s, DM, infections, or spina bifida.

Issue with nerves to bladder can cause overactive or underactive bladder

Question 17

Guillain-Barre

Answer 17

Acute inflammatory immune-mediated demyelinating polyneuropathy.
Anti-myelin abs are produced.
Segmental demyelination with perivenular and endoneurial infiltration.
Weakness begins in distal limbs with ascending paralysis. DTR’s disappear.
Incr. CSF production. Tx with plasmaphreresis or IVIg

Question 18

Chronic Inflammatory Demyelinating Poly(radiculo)neropathy

Answer 18

Most common aquired inflammatory peripheral neuropathy. Symmetrical and >2mo. Responds to steroids unlike GB! Sural nerve bx shows ONION BULBS

Question 19

Leprosy (Hansen dz)

Answer 19

Mycobacterium leprae cause segmental demyelination and loss of BOTH myelinated and unmyelinated axons. Endoneurial fibrosis and multilayered thickening of perineural sheaths occurs.
Symmetric polyneuropathy affects cool extremities. Pain fiber involvement & loss of sensation contribute to injuries. AFB (+)

Question 20

TB Leprosy

Answer 20

Granulomatous nodules in dermis. localized to nerve involvement. AFB (+)

Question 21

Diptheria

Answer 21

Exotoxin affects peripheral nerves beginning with paresthesias and weakness. Loss of proprioception and vibratory sensation early.

Question 22

VZV

Answer 22

Most common viral infection of PNS. Ascends to CNS via sensory ganglia. Reactivation of the virus = Shingles.
Loss of affected ganglia, necrosis & hemorrhage can be seen. Axonal degen. of PN after death of sensory neurons. Focal destruction of large motor neurons in anterior horns or CN motor nuclei.

Question 23

Peripheral neuropathy in DM

Answer 23

Most common cause of peripheral neuropathy, ascending distal symmetric sensorimotor polyneuropathy.
Sx: Numbness, loss of pain sensation, difficulty balancing. Paresthesias & dysesthesias. Diffuse vascular injury
Endoneurial arterioles show thickening, hylinization & intense PAS (+)

Question 24

Thyroid dysfunction

Answer 24

hypothyroidism -> compression mononeuropathies.

Question 25

Neuropathies assoc with monocolonal gammopathies (B-cell neoplasms)

Answer 25

POEMS: polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes

Question 26

Traumatic neuroma

Answer 26

small bundles of axons randomly orient after break in axon. Surrounded by organized layers of Schwann cells fibroblasts & perineural cells

Question 27

Compression/entrapment neuropathy

Answer 27

Carpel tunnel syn - median N. affecting thumb and first two fingers
Saturday night palsy - Radial n. Ex. falling asleep awkwardly.
Ulnar N. at elbow or peroneal N at knee
Morton neuroma - metatarsalgia, histological lesion=perineural fibrosis

Question 28

(3) inherited peripheral neuropathies

Answer 28

Charcot-Marie-Tooth (CMT) - AD
Familial Amyloid Polyneuropathies (FAP) - amyloid dep in PNs
Metaboli DOs

Question 29

Myasthenia gravis

Answer 29

More common in women. Circulating autoAbs. to AchR. Assoc. thymoma & thymic hyperplasia. Diminished responses after repeated stim. (worsens with exertion).
Tx: plasmapheresis & immunosuppression. Thymectomy

Question 30

Lambert-Eaton Syn

Answer 30

Ab block of Ach release by inhibition of presynaptic Ca2+ channel. Assoc. as paraneoplastic syn. with small cell carcinoma of the lung. Repetitive stim. incr. muscle response!

Question 31

Dermatomyositis has atrophy of what part of the nerve? What are the clinical sx? Assoc. organs affected? Antibodies?

Answer 31

Perifasicicular atrophy.
Lilac or heliotrope eyelids with periorbital edema. Telangiectasias. Grotton lesions on elbows, knees and knuckles. Proximal m. first so pts have trouble rising from chair. Interstitial lung dz and cardiac involvement with incr. risk for visceral cancers.
Anti-Mi2, anti-Jo1, and anti=P155/P140

Question 32

Polymyositis

Answer 32

Myalgia & weakness. Symmetrical proxima muscle involvement. Lacks cutaneous involvement. Endomysial infiltrates and random distribution of atrophy

Question 33

Inclusion body myositis

Answer 33

> 50 yo. Slowly progressivemuscle weakness most severe in quadriceps and distal extremities. Dysphagia. Rimmed vacuoles DOES NOT RESPOND TO STEROIDS OR IMMUNOSUPPRESSION

Question 34

How do you tx dermatomyositis and polymyositis?

Answer 34

Corticosteroids & immunosuppression

Question 35

Drugs and tx’s that can cause toxic myopathies?

Answer 35

Statins, antimalarial drugs, ICU myopathy, Thyrotoxic myopathy, alcohol.

Question 36

Duchenne Muscular dystrophy

Answer 36

X-linked, Xp21 gene. No dystrophin. Pseudohypertrophy

Question 37

Becker Muscular dystrophy

Answer 37

X-linked, Cardiac dz, decr. amount of dystrophin. Pseudohypertrophy

Question 38

Myotonic dystrophy

Answer 38

Myotonia sometimes elicited by percussion on thenar eminence. Stiffness & difficulty releasing grip. AD. CTG trinucleotide repeat
Sx: skeletal m weakness, cataracts, endocrinopathy & cardiomyopathy. Hatchet face

Question 39

Mitochondrial myopathies

Answer 39

sx: weakness, incr. serum CK or rhabdomyolysis. Extraoccular m involvement. Chronic progressive external ophthalmoplegia. (Leber, Leigh, Barth, Kearns- Sayre)

Question 40

Spinal muscular atrophy

Answer 40

Generalized hypotonia of infant. AR SMN1 on Ch 5. Wernig-Hoffman is the most common. Destruction of the anterior horns. Death <3yo

Question 41

RYR1 mut

Answer 41

Malignant hyperthermia! Signs of tachycardia, tachypnea, muscle spasms & hyperpyrexia. Anesthetic triggers large efflux of Ca2+. Tx with dantrolene

Question 42

Neurofibromatosis Type 1

Answer 42

Neurofibromas of PN, optic N glioma, lisch nodules & cafe au lait spots. “Bag of worms” on histo. MPNST transformation possible

Question 43

Neurofibromatosis Type 2

Answer 43

Bilateral schawnnomas (S100+) in CN VIII at cerebellopontine angle. Incr meningiomas and ependymomas