Peripheral Pathology

Question 1

Compare and contrast axonal regeneration and segmental regeneration

Answer 1

Axon= slow recovery

Segment =rapid recovery

Both= new myelin internodes are shorter and thinner

Question 2

Compare and contrast axon injury involved in axonal and segmental degeneration

Answer 2

Axonal: involves distal axon and its associated myelin sheath with chromatolysis

Segmental: spares axons

Question 3

compare and contrast the myofibers and nerve conduction presentation in axonal and segmental degeneration

Answer 3

Axonal: denervated myofibers become atrophied and there is no nerve conduction

Segmental: Muscle fibers are not affected and nerve conduction is only slowed

Question 4

Define Neuropraxia and describe it with regards to its features and prognosis

Answer 4

Definition: compression injury causing temporary disruption of nerve conduction

Features: whole nerve remains structurally intact

Prognosis: Good chance of complete recovery of nerve function

Question 5

Define Axonotmesis and describe it with regards to its features and prognosis

Answer 5

Definition: axon is damaged, but the perineurium and epineurium remain intact

Features: Chromatolysis and Wallerian Degeneration

Prognosis: good chance of at least partial recovery in a few months

Question 6

what is chromatolysis?

Answer 6

reaction of a neuronal cell body in response to an axonal injury

It reflects an increase in protein synthesis in effort to restore the integrity of the damaged neurons

Question 7

what does chromatolysis look like

Answer 7

swelling of the neuronal cell body

dispersion of Nissl Bodies

Displacement of the nucleus to the periphery

Question 8

What is Wallerian Degeneration

Answer 8

active neuronal degeneration process in response to axonal injury to clear axonal debris and prevent scarring

Question 9

Describe Wallerian Degeneration

Answer 9

1. Initially retained electrical excitability of axonal membranes distal to the injury for up to 36 hours
2. progressive degeneration of the distal segment cytoskeleton with dissolution of axonal membrane
3. Degradation of residual myelin sheath by macrophages and Schwann cells
4. Proximal stump stays in place, ultimately sprouting regenerative nerve fibers that ideally reinnervate the distal tissues

Question 10

Define Neurotmesis and describe it with regards to its features and prognosis

Answer 10

Definition: complete nerve resection

Features: connective nerve sheath damage

Prognosis: Chance of recovery is poor without surgical repair

Question 11

What is a traumatic neuroma

Answer 11

a painful, but benign nodular thickening resulting from a failure of the regenerating axons to find their distal target

Question 12

Compare and contrast Wallerian degeneration in CNS and PNS with regards to its cell type, timing and likelihood of regeneration

Answer 12

Question 13

why doesn’t regeneration occur in CNS Wallerian degeneration

Answer 13

persistence of myelin debris

secretion of inhibitory factors

dense glial scarring

Question 14

Why does myelin debris last for so long in CNS Wallerian degeneration

Answer 14

macrophages and microglia are slowly recruited due to the BBB

Question 15

Compare and contrast neurofibromas and schwannomas with respect to:

• location
• nerve involvement
• capsule presence
• patterns
• cell types involved
• risk of malignancy
• Associations

Answer 15

Question 16

Describe Neurofibromas

Answer 16

small nodular tumors of the skin and subQ tissues, arising from small cutaneous nerves

• has no neurologic deficits
• can be isolated
• may cause local pain or bleeding

Question 17

Describe the different subtypes of neurofibromas

Answer 17

Diffuse: large plaque-like elevations of the skin

Plexiform: multiple nodular masses affecting nerve roots, plexuses or large nerves

Question 18

What causes neurofibromas

Answer 18

germline mutations of NF1 on chromosome 17 cause intracellular neurofibromin proteins.

These proteins increase the RAS signalling cascade

Question 19

Describe the morphology of a neurofibroma

Answer 19

heterogenous composition of Schwann cells, admixed with perineural-like cells, fibroblasts and CD34+ spindle cells

Question 20

Complications of neurofibromas

Answer 20

Malignant peripheral nerve sheath tumors

Question 21

What are Malignant peripheral nerve sheath tumors and where do you usually find them

Answer 21

poorly defined tumor masses that frequently infiltrate along the axis of the parent nerve and invade soft tissues

Usually found on the:

• chest
• abdomen
• pelvis
• neck
• limb girdle

Question 22

how are most Malignant peripheral nerve sheath tumors formed

Answer 22

from transformation of a plexiform neurofibroma

Question 23

Describe the morphology of Malignant peripheral nerve sheath tumors

Answer 23

fasciculated arrangements of spindle cells, commonly seen with mitoses, necrosis and nuclear aplasia

S-100 +

Question 24

Describe a schwannoma with regards to symptoms, location, and appearance

Answer 24

symptoms resemble local compression of involved nerves or adjacent structures

Cranial vault: occurs at the cerebellopontine angle, where they are attached to the vestibular branch of CN8

Dura: involves sensory nerves

Extradural: can arise in association with large nerve trunks or soft tissue lesions without an identifiable associated nerve

Question 25

What causes schwannomas

Answer 25

germline mutations of NF2 on chromosome 22, causes **loss of function mutations to merlin protein**. In its absence, cells **hyperproliferate in response to uninhibited growth factors** like EGFR

Question 26

Describe spinal muscular atrophy with respect to clinical features, subtyping, and prognosis

Answer 26

**symptoms**: muscle weakness, hypotonia, bulbar symptoms, preserved sensations, **Preserved eye movement and continence** Type 1: non-sitters Type 2: sitters Type 3: Walkers **Prognosis improves with later onset**

Question 27

what causes spinal muscular atrophy

Answer 27

**Autosomal recessive** inherited **mutation of SMN1 gene on chromosome 5q** causes **apoptosis of LMN** in late stages of fetal development and postnatal period

Question 28

Diagnostics of spinal atrophy

Answer 28

normal or mildly elevated Creatine kinase spontaneous large-amplitude, low frequency electrical activity with rarified interface pattern

Question 29

Morphology of spinal muscular atrophy

Answer 29

atrophy to groups of motor units interspersed with normal or hypertrophies motors skills

Question 30

what causes carpal tunnel syndrome and what contributes to it

Answer 30

cause: compression of the median nerve causes impaired blood flow and altered vascular structuring, leading to edema, hypoxia and axonal degeneration **_Contributions:_** prior wrist trauma manual work pregnancy hypothyroidism DM Rheumatoid arthritis dialysis associated amyloidosis

Question 31

clinical presentation of carpal tunnel syndrome

Answer 31

sensory impairment and motor weakness in medial nerve distribution thenar atrophy and motor weakness during thumb abduction and opposition weakened pinch grip **wrist flexion and tapping over the flexor surface exacerbate symptoms**

Question 32

presentation of Guillain Barre

Answer 32

ascending flaccid paralysis about 1-4 weeks post infection

Question 33

Pathology of Guillan Barre

Answer 33

autoantibodies against gangliosides or other known antigens of Schwann cells cause immune-mediated segmental demyelination and axonal degeneration

Question 34

Describe diagnostics seen in Guillain Barre

Answer 34

elevated proteins, but normal cells in CSF reduced nerve conduction velocity due to demyelination eith increased F wave frequency

Question 35

common pathogens in association with Guillain Barre

Answer 35

C. jejuni EBV CMV HIV Influenza Mycoplasm

Question 36

How do you differentiate from Guillain Barre and Chronic Inflammatory Demyelinating Polyradiculopathy

Answer 36

Chronic Inflammatory Demyelinating Polyradiculopathy's symptoms last for at least 2 months with subacute or chronic course relapses and remissions Pertaining to morphology: Chronic Inflammatory Demyelinating Polyradiculopathy displays onion bulb changes on biopsy

Question 37

What does Charcot-Marie Tooth Disease Look like

Answer 37

calf muscle atrophy (stork legs) symmetric distal sensorimotor polyneuropathy claw foot intrinsic hand musculature may become involved after several years

Question 38

What causes Charcot-Marie Tooth Disease

Answer 38

mutations of peripheral myelin protein PMP22 causes unstable myelin, which causes decreased impulse conduction velocity

Question 39

Describe the morphology of Charcot-Marie Tooth Disease

Answer 39

segmental demyelination and remyelination with onion bulb formations

Question 40

Associations of Charcot-Marie Tooth Disease

Answer 40

sleep apnea

Question 41

features of Leprosy polyneuropathy

Answer 41

segmental demyelination, remyelination loss of myelinated and demyelinated axons

Question 42

Describe the pathogenesis of Diptheria polyneuropathy and discuss its features

Answer 42

**Pathogenesis**: Diptheria toxin i**nhibits protein synthesis by deactivation of EF-2** and ADP ribosylation, **leading to nerve demyelination** **Features:** prominent bulbar and respiratory dysfunction

Question 43

describe the pathogenesis of VZV polyneuropathy and discuss its features

Answer 43

**Pathogenesis**: reactivation of latent virus within neurons of the sensory ganglia **Features**: shingles

Question 44

What is the most common cause of peripheral neuropathy and how does it occur

Answer 44

Diabetes Mellitus 1. hyperglycemia causes glycalation of proteins, lipids and amino acids 2. Glycation causes activation of inflammatory signaling through AGE receptors 3. Inflammatory signaling causes Endoneural arteriole hyalinization 4. Arterial hyalinization causes polyneuropathy

Question 45

Metabolic factors that cause polyneuropathy

Answer 45

uremia Vitamin B1 deficiency Vitamin B6 deficiency Vitamin B12 deficiency Vitamin E deficiency Chronic liver disease Chronic respiratory disease

Question 46

Per powerpoint, the following malignancies are associated with which neuropathies? ## Footnote **Lung apex neoplasms** **Malignant pelvic neoplasms** **meningeal carcinomatosis** **small cell lung cancer**

Answer 46

Lung apex neoplasms**= brachial plexopathy** Malignant pelvic neoplasms**= obturator palsy** meningeal carcinomatosis **causes cauda equina syndrome, yielding lower extremity polyradiculopathy** small cell lung cancer= **sensorimotor neuropathy**