Chapter 27: Diseases of Peripheral Nerves

Question 1

Which painful nodule composed of non-neoplastic haphazard whorled proliferation of axonal processes and assoc. Schwann cells results from failure of axons to find their distal target during regeneration ?

Answer 1

Traumatic neuroma aka “pseudotumor”

Question 2

In cases of toxic and metabolic insults, axons often degenerate in what type of fashion?

What does this result in?

Answer 2

in a length-dependent fashion with the longest axons being most susceptible

-Results in a “dying-back” type of pattern progression

Question 3

What is the electrophysiologic hallmark of axonal neuropathies vs. demyelinating neuropathies?

Answer 3

• Axonal neuropthay = a reduction in signal strength
• Demyelinating neuropathy = slowed nerve conduction velocity

Question 4

What are the primary targets of damage in demyelinating neuropathies?

Answer 4

Schwann cells w/ their myelin sheaths

Question 5

Why is the peripheral nerve dysfunction caused by neuronopathies equally likely to affect proximal and distal parts of the body?

Answer 5

Damage at the level of neuronal cell body

-leads to a secondary degeneration of axonal processes

Question 6

What are two examples of insults that can leads to neuronopathies?

Answer 6

Infections (herpes zoster) and toxins (platinum compounds)

Question 7

Mononeuritis multiplex describes a disease process that damages several nerves in a haphazard fashion and is commonly due to what?

Answer 7

Vasculitis i.e., polyarteritis nodosum

Question 8

Characteristic “stocking and glove” distribution of sensory deficits is seen with what anatomic pattern of peripheral neuropathies?

Answer 8

Polyneuropathies

Question 9

What are the 4 categories of inflammatory neuropathies?

Answer 9

• guillain-barre
• chronic inflammatory demyelinating poly(radiculo)neuropathy
• neuropathy associated with systemic autoimmune diseases
• neuropathy associated with vasculitis

Question 10

Histologic features of Guillain-Barre Syndrome are characterized by what?

Answer 10

Inflammation** and **demyelination of spinal nerve roots and peripheral nerves = radiculoneuropathy

-inflammation of peripheral nerve: perivenular and endoneurial infiltration by lymphs, macrophages, and few plasma cells

Question 11

2/3’s of Guillain-Barre Syndrome cases are preceded by what; which etiologies have been implicated?

Answer 11

• Acute, influenza-like illness
• Campylobacter, CMV, EBV, and Mycoplasma penumoniae, or prior vaccination

Question 12

Morphologically what is the most prominent lesion (primary lesion) seen in Guillain-Barre Syndrome?

Answer 12

Segmental demyelination affecting peripheral nerves

Question 13

Clinical presentation of Guillain-Barre Syndrome is dominated by what signs/sx’s; what characteristic CSF finding will there be?

Answer 13

• Ascending paralysis and areflexia
• DTR’s lost early in the process
• ↑ CSF protein levels w/ little or no CSF pleocytosis (inflammatory cells remain confined to the roots

Question 14

What antibodies are present in Guillain-Barre?

Answer 14

anti-myelin antibodies

Question 15

How is Guillain-Barre Syndrome managed clinically?

Answer 15

Plasmapheresis and IV Ig

Question 16

What is the most common acquired inflammatory peripheral neuropathy?

Answer 16

Chronic inflammatory Demyelinating Poly(radiculo)neuropathy

Question 17

Chronic inflammatory Demyelinating Poly(radiculo)neuropathy is characterized by what type of neuropathy?

Answer 17

Symmetrical mixed sensorimotor polyneuropathy that persists for 2 months or more

-relapses and remissions evolve over years

Question 18

Which 2 features of Chronic inflammatory Demyelinating Poly(radiculo)neuropathy distinguish it from Guillain-Barre?

Answer 18

Time course (presence at least 2 months) and response to steroids

Question 19

How is Chronic inflammatory Demyelinating Poly(radiculo)neuropathy treated?

Answer 19

Glucocorticoids + IVIg + plasmapheresis

Question 20

Upon sural nerve biopsy in patient with Chronic inflammatory Demyelinating Poly(radiculo)neuropathy what is a characteristic finding?

Answer 20

Onion-bulbs: excessive proliferation –> multiple layers of Schwann cells wrap around an axon like the layers of an onion

Question 21

What is implicated in the inflammatory process of chronic inflammatory demyelinating poly(radiculo)neuropathy?

Answer 21

T cells, as well as antibodies

Question 22

what leads to the recruitment of macrophages that strip myelin from axons in Chronic Inflammatory Demyelinating Poly(radiculo)neuropathy?

Answer 22

complement-fixing immunoglobulin G (IgG) and IgM can be found on the myelin sheaths and the deposition of these opsonins leads to recruitment of macrophages that strip myelin from axons

Question 23

Which systemic autoimmune diseases are often associated with peripheral neuropathies?

Answer 23

RA, Sjogren syndrome, or SLE

Question 24

How does neuropathy associated with systemic autoimmune diseases present?

Answer 24

they often take the form of distal sensory or sensorimotor polyneuropathies

Question 25

how does vasculitis often present?

Answer 25

as mononeuritis multiplex

Question 26

what are some examples of vasulitides associated with neuropathy? (anca associated)

Answer 26

- MPO-ANCA associated vasculitides - polyarteritis nodosa - PR3-ANCA

Question 27

what is the most common form of vasculitis associated with peripheral neuropathy?

Answer 27

a localized form referred to as nonsystemic vasculitic neuropathy, which is not associated with ANCAs

Question 28

what are the histologic characteristics of neuropathy associated with vasculitis?

Answer 28

peripheral nerves typically show patchy axonal degeneration and loss, some fascicles more severely affected than others -(perivascular inflammatory infiltrates often present)

Question 29

In lepromatous leprosy (Hansen Disease) Schwann cells are invaded by *Mycobacterium leprae* and what pattern of peripheral nerve damage will be seen?

Answer 29

**_Segmental_** demyelination and **re**myelination + **loss of _both_ myelinated** and ****_un_**myelinated** axons

Question 30

What are the histologic features associated with Leprosy associated neuropathy?

Answer 30

**_endoneurial fibrosis**_ and _**multilayered thickening of perineural sheaths_**

Question 31

Which type of neuropathy is seen with lepromatous leprosy (Hansen Disease) and which sensory fibers will be lost?

Answer 31

- **Symmetric polyneuropathy** affected **_cool_** distal extremities and face - Involves **_pain_** fibers, _loss of sensation_ = injury; since pt's are rendered unaware of injurious stimuli --\> **large traumatic ulcers**

Question 32

More localized nerve involvement associated with granulomatous nodules in the dermis is characteristic of what form of leprosy?

Answer 32

**Tuberculoid leprosy** = **T_H1 (cell-mediated) response**

Question 33

What are the features of tuberculoid leprosy?

Answer 33

granulomatous nodules in dermis **localized** nerve involvement injures cutaneous nerves axons, schwann cells, & myelin lost

Question 34

What is the histology associated with Tuberculoid leprosy?

Answer 34

fibrosis of perineurium and endoneurium

Question 35

What stain should you use if you suspect leprosy?

Answer 35

acid fast bacilli (AFB)

Question 36

lyme disease causes what type of neuropathy?

Answer 36

polyradiculoneuropathy

Question 37

early stage HIV infection causes what type of neuropathy?

Answer 37

mononeuritis multiplex

Question 38

Peripheral nerve dysfunction as a result of Diptheria is due to what; what are the early sx's and later findings?

Answer 38

- Result of diptheria **exotoxin** **-begins with paresthesias and weakness** - **_Early**_ loss of _**proprioception**_ and _**vibratory sensation_** - **Acute peripheral neuropathy** assoc. w/ **prominent bulbar** and **respiratory m. dysf.**

Question 39

If VZV is reactivated it travels along sensory nerves and leads to what?

Answer 39

**Painful, vesicular** skin eruption (**shingles**) in a _sensory_ **dermatomal** distribution

Question 40

Which dermatomes are commonly affected by VZV reactivation; what kind of damage is seen?

Answer 40

- **Thoracic** or **trigeminal** nerve **dermatomes** - Neuronal destruction and **_loss of affected ganglia_** **_-_regional necrosis and hemorrhage may be found** - **_Axonal degeneration_** of **periphral nerves** after **death of sensory neurons**

Question 41

Focal destruction of which neuronal structures may be seen with reactivation of VZV?

Answer 41

**Large motor neurons** in **anterior horn** or **cranial nerve nuclei**

Question 42

What is the most common pattern of peripheral neuropathy seen with Diabetes?

Answer 42

**Ascending distal _symmetric_ sensorimotor polyneuropathy**

Question 43

how does diabetic neuropathy present?

Answer 43

numbness, loss of pain sensation, difficulty with balance -paresthesias or dysesthesias

Question 44

Prevalence of peripheral neuropathy associated with diabetes is dependent on what?

Answer 44

**_Duration_** of the disease

Question 45

Biopsies of the affected peripheral nerves/arterioles in diabetes will show what finding and with what stain?

Answer 45

**Endoneurial arterioles** show _thickening_, hyalinization, and intense **PAS-(+)** of their walls + extensive _reduplication_ of basement membranes

Question 46

Diabetic peripheral neuropathy is characterized by a relative loss of which size and type of nerve fibers?

Answer 46

**_Small_** myelinated _and_ unmyelinated fibers

Question 47

What are "positive sx's" associated with diabetic peripheral neuropathy?

Answer 47

**_Paresthesias_** and **_dyesthesias_** = **painful sensations**

Question 48

what is believed to contribute to the damage of axons and Schwann cells in cases of DM neuropathy?

Answer 48

both metabolic and secondary vascular changes

Question 49

Other than peripheral neuropathy, what is another manifestation of diabetic nervous system dysfunction that is often seen?

Answer 49

**Autonomic dysfunction**: postural hypotension, incomplete bladder emptying (↑ infections) and sexual dysfunction

Question 50

Uremic neuropathy seen in setting of renal failure is a distal, symmetric neuropathy often associated w/ what signs and sx's?

Answer 50

**Muscle cramps** + **distal dysesthesias** + ↓ **DTRs**

Question 51

what is the primary event occurring in uremic neuropathy?

Answer 51

axonal degeneration is usually the primary event -regeneration and recovery common after dialysis

Question 52

what type of neuropathy is associated with hypothyroidism?

Answer 52

compression mononeuropathies (carpel tunnel) or distal symmetric predominantly sensory polyneuropathy

Question 53

what type of neuropathy is associated with hyperthyroidism?

Answer 53

-rare, associated with syndrome resembling Guillain-Barre

Question 54

What type of neuropathy is associated with vitamin b12 (cyanocobalamin) deficiency?

Answer 54

subacute combined degeneration with damage to long tracts in the spinal cord and peripheral nerves

Question 55

Besides vitamin B12, what other vitamin deficiencies are associated with peripheral neuropathy?

Answer 55

vitamin B1 (thiamine), vitamin B6 (pyridoxine), folate, copper, and zinc

Question 56

Which type of neuropathy is the most common paraneoplastic form and which malignancy is it most commonly associated with?

Answer 56

**Sensorimotor neuronopathy** in setting of **Small cell lung cancer** = **_most common_**

Question 57

What is a a distinctive presentation of neuropathy associated with monoclonal gammopathies?

Answer 57

**POEMS:** **P**olyneuropathy, **O**rganomegaly, **E**ndocrinopathy, **M**onoclonal gammopathy, and **S**kin changes

Question 58

"Saturday night palsy" is due to compression of which nerve?

Answer 58

**Radial nerve** in the **upper arm**

Question 59

Which nerve is affected in Morton neuroma and what histologic finding is seen?

Answer 59

- **Interdigital nerve** at **intermetatarsal sites** --\> **foot pain**; "walking on a marble" - **Histologically** = perineural fibrosis

Question 60

Demyelinating forms of Charcot-Marie-Tooth (CMT) disease are associated with what morphological features?

Answer 60

- **Demyelination** and **remyelination** including **Schwann cell hyperplasia** ---\> **Onion-bulb formation** - Hyperplasia may be so _severe_ that involved nerve is **palpably enlarged**

Question 61

What is the most common subtype of hereditary motor and sensory neuropathy (CMT) disease, what is the inheritance pattern, when and how does it present?

Answer 61

- **CMT1** = group of **autosomal _dominant_** disorders - Presents in **_2nd decade_** w/ _slowly_ progressive **distal demyelinating motor** and **sensory** neuropathy

Question 62

Which structures are injured in the CMT2 variant of CMT disease and when does it present?

Answer 62

**Axonal injury**; typically **_severe_** w/ **early childhood onset**

Question 63

Familial amyloid polyneuropathies are mainly due to germline mutations in which gene?

Answer 63

**Transthyretin** gene

Question 64

how does diabetic neuropathy present?

Answer 64

numbness, loss of pain sensation, difficulty with balance -paresthesias or dysesthesias