Peripheral Nerve Pathology - Alston

Question 1

What are the characteristics of autonomic nerve fibers as well as pain and temperature sensation? What are their conduction speeds?

Answer 1

Thin, unmyelinated fibers, slow

Question 2

What are the fiber characteristics of light touch and motor nerves? What is the conduction speed?

Answer 2

Large diameter, myelinated fibers, fast

Question 3

Wallerian degeneration is the term to describe what type of neuropathic pattern?

Answer 3

Axonal neuropathy

Question 4

What are the stages of neuronal regeneration after an axon is transected? (Characteristics of Wallerian degeneration)

Answer 4

1. Day 1: Sheath disintigrates into spherical structures called myelin ovoids and macrophages are recruited to clean up.
2. Outgrowth of new branches (Schwann cells guide the growth.)
3. Pruning of sprouting axons

Question 5

Traumatic neuromas (psuedotumor) can result when what part of the healing process fails as a result of Wallerian degeneration?

Answer 5

Failure of the outgrowing axons to find their target - whorled proliferation of axons and Schwann cells results in painful nodule

Question 6

Reduction of signal strength would be a characteristic of what neuropathic change?

Answer 6

Axonal neuropathy (axonal loss)

Question 7

Are axons sparing in demyelinating diseases?

Answer 7

Yes, typically myelin is the primary target.

Question 8

How might Schwann cells and their myelin sheaths appear in a demyelinating disease?

Answer 8

Thinner and shorter

Question 9

Slower nerve conduction would be a characteristic of what neuropathic change?

Answer 9

Demyelination

Question 10

What part of the neuron is most commonly affected in neuronopathies? (Examples?)

Answer 10

Damage is at the level of the neuron cell body (viruses -herpes and certain toxins- platinum)

Question 11

Mononeuropathies affect one or more nerves? What is the cause?

Answer 11

Single nerves are affected - often due to trauma, entrapment, infection

Question 12

Polyneuropathies affect one or more nerves? Progression? Symmetric/asymmetric?

Answer 12

Usually multiple nerves symmetrically. Often start in feet and ascend w/ progression (stocking glove - hands start to be affected when deficit reaches knees)

Question 13

Mononeuritis multiplex affects one or many nerves? Pattern? Often due to?

Answer 13

Damage is to several nerves, but in haphazard pattern - often due to vasculitis

Question 14

Polyradiculoneuropathies are unique in that damage presents where? Symmetric/Asymmetric? Location?

Answer 14

Affect nerve roots as well as peripheral nerves - Symmetric in proximal and distal body

Question 15

Pt has weakness in distal limbs that has advanced over the past few days since he, “got vaccinated.” Decreased sensation and +1 Reflexes in the lower extremities w/ slow nerve conduction velocity in the lower legs. CSF proteins are high. Papilledema present. What is the likely diagnosis? What kind of neuropathic process is occurring? Where? How is this process mediated? Outcome?

Answer 15

Guillain-Barré - Inflammatory (Peripheral) neuropathy resulting in prominant demyelination near the nerve root, but can be widespread peripherally. T- cell (immune) mediated. Can result in respiratory depression - most recover.

Question 16

Pt has been treated with steroids after 2 years of progressive weakness starting at the feet bilaterally and ascending to his knees, now presenting in the hands. He has some sensory dysfxn. He has areflexia at the achilles and knees. The symptoms have relapsed and remitted over the whole course of illness, and is in remission after steroid Rx. Biopsy of myelin reveal IgG and IgM deposition and high macrophage content. Onion-bulb neurons are present as well. What is the diagnosis? What is the prevalence? How is this differentiated from Guillain-Barre?

Answer 16

Chronic Inflammatory Demyelinationg Poly(radiculo)neuropathy (CIDP) - most common acquired inflammatory peripheral neuropathy - time and course differentiate this disease from Guillain-Barre -

Question 17

Autoimmune diseases like RA, Sjögren syndrome, and SLE often take the form of what kind of neuropathy? How do they differ from vasculitic neuropathy?

Answer 17

Sensory or sensorimotor polyneuropathies - differ in that vasculitis is often secondary to other diseases

Question 18

Pt is being evaluated for numbness and tingling in the right hand and left foot. He has an Hx. of HTN and a family Hx. of heart disease with atherosclerosis. What is the likely diagnosis if the pt. is found to have a neuropathy? What pattern of neuropathy does this commonly follow? Inflammatory or non-inflammatory? Where is the neuronal damage? Biopsy of vasculature may reveal what?

Answer 18

Vasculitis neuropathy - mononeuritis multiplex - inflammatory - peripheral nerves w/ patchy axonal degeneration and loss - inflammatory infiltrates (macrophages, neutrophils, etc.) and vascular damage are used in identification

Question 19

Transient Pt with multiple gangrenous peripheral lesions and several missing fingers/toes presents to the emergency department. He has loss of sensation and pain in the feet and hands bilaterally as well as the face. Biopsy reveals Schwann cell destruction w/ proliferation of obligate intracellular pathogens. What is the likely invading pathogen? What is the neuropathic pattern?

Answer 19

Leprosy (Hansen Disease) aka mycobacterium leprae - specifically called “lepromatous leprosy” in this case - symmetric polyneuropathy - often affects pain fibers resulting in accidental traumatic injury, lesions, and gangrenous infection

Question 20

Tuberculoid leprosy differs from lepromatous leprosy in that it is characterized by what kind of reaction? What presents in the skin? What nerves are primarily affected?

Answer 20

Cell-mediated immune response to mycobacterium leprae - dermal nodules containing granulomatous inflammation in the skin - cutaneous nerves are infected resulting in fibrosis of peri/endoneurium

Question 21

Lyme disease can lead to what kind of neuropathy? Facial symptoms?

Answer 21

Polyradiculoneuropathy as well as unilateral/bilateral facial nerve palsies

Question 22

HIV can result in what type of neuropathy? What might its progression resemble initially?

Answer 22

Mononeuritis multiplex as well as demyelination resembling CIPD/guillian-Barre.

Question 23

What is the most common cause of peripheal neuropathy?

Answer 23

Diabetes

Question 24

Diabetes most commonly presents with what pattern of neuropathy? Ascending/Descending? Sensory or motor or both? Symmetric or not? What other neurological systems are affected? What is happening to the vasculature around the neurons? What occurs in the myelin?

Answer 24

Ascending distal symmetric sensorimotor polyneuropathy (numbness, loss of pain sensation, balance issues, paresthesia) - Autonomic dysfxn (sexual dysfxn, urinary issues, postural hypotension) (Asymmetric neuronal loss may be associated with vasculitis) - Endoneurial arterioles show thickening and periodic acid-Schiff positivity (aka PAS) - Myelin loss and stages of regeneration may be present

Question 25

Pt presents with muscle cramps, painful sensation when touched distally (distal dyesthesia), and areflexia w/ deep tendon reflexes. The pt experiences these symptoms symmetrically. What is the diagnosis? Demyelination or axonal?

Answer 25

Axonal loss due to uremic neuropathy

Question 26

Pt presents with carpal tunnel syndrome and sensory polyneuropathy distally. What hormone level may need to be evaluated?

Answer 26

Thyroid (hypothyroidism)

Question 27

B12 (cyanocobalamine) deficiency classically results in damage to what important neural structures?

Answer 27

Long tracts in the spinal cord as well as peripheral nerves

Question 28

Deficiency of thiamine (B1), Pyridoxine (B6), folate, vitamin E, copper and zinc are all associated w/ what pattern of neuropathy?

Answer 28

Peripheral neuropathy

Question 29

Pt presents with brachial and pelvic plexopathy and eventually develops drooping in the face before being evaluated by his physician. Scans reveal mononeuropathies from compression at the apex of the lung, the pelvis, and the base of the skill due to what?

Answer 29

Tumors

Question 30

Cisplatin and taxane can result in neuropathy. What are these treatments for?

Answer 30

Chemotherapeutic agents often result in neuropathy

Question 31

Man presents with a complex sensorimotor neuronopathy that began distally in an asymmetric and multifocal pattern. Blood tests reveal anti-Hu antibodies and elevated CD 8+ cells in the dorsal root ganglion. What is the likely cause of his symptoms?

Answer 31

Paraneoplastic disease process resulting in immunoglobulin attack of proteins similarly expressed on cancer cells and normal neurons.

Question 32

What types of cells might secrete monoclonal Ig or Ig fragments that damage nerves? What kinds of cancer may lead to this?

Answer 32

B-cells - lymphomas

Question 33

Genes encoding myelin, growth factors, proteins that regulate mitochondrial fxn, vesicle and axonal transport, heat shock proteins, and cell membrane structure and fxn may be associated with what group of neurological diseases?

Answer 33

(Hereditary) Inherited peripheral neuropathies

Question 34

Pt presents with distal muscle atrophy (peroneal muscle atrophy), sensory loss, and foot deformity (pes cavus). Biopsy reveals Schwann cell hyperplasia and onion bulb neurons. Some areas of nerve involvement are actually palpable. Genetic testing reveals CMT genes are involved. What is the likely diagnosis? What are the 3 CMT variations? What is the onset/pattern of inheritance? Associated genes for each?

Answer 34

Charcot-Marie-Tooth
(HMSN1) CMT1: Autosomal dom - most common - 20s age of onset - PMP22 (peripheral motor protein) on chromosome 17p11.2-p12
CMTX: X-linked - GJB1 gene (encoding connexin 32 - a gap jxn for Schwann cells)
(HMSN2) CMT2: (severest form) autosomal dom. - associated w/ axonal degeneration - early childhood onset - (MFN2 gene - required for normal mitochondrial fusion)

Question 35

What is the most common symptom of hereditary sensory neuropathy w/ or without autonomic neuropathy? What is the common result? Demyelination or axonal?

Answer 35

Loss of pain and temperature sensation - pain loss = frequent traumatic injury - typically axonal neuropathy

Question 36

Pt. presents with truncal and peroneal muscle atrophy and sensory loss with foot deformity. Tests and Hx reveal autosomal recessive pattern of inheritance in family. Enlarged nerves can be palpated in the skin. What si the diagnosis and the associated dysfxnal gene?

Answer 36

Dejerine-Sottas 
CMT 3 (HMSN3)