Compressive and Demyelinating Disorders

Question 1

Demyelination can occur in:
a. peripheral nervous system only
b. central nervous system only
c. both

Answer 1

both

Question 2

Demyelination in the central nervous system is…

Answer 2

damage to oligodendrocytes

Question 3

Demyelination in the peripheral nervous system is…

Answer 3

damage to Schwann cells

Question 4

what is the most common mechanism of injury for demyelination in the CNS?

Answer 4

damage to the processes, usually an autoimmune mechanism (multiple sclerosis)

Question 5

what is the most common mechanism of injury for demyelination in the PNS?

Answer 5

○ Genetic deficits that impair the ability of Schwann cells to compact or produce myelin sheaths
○ Autoimmune – self-reactive antibodies, antibody complexes, or cytotoxic T-cells damage Schwann cells

Question 6

what is multiple sclerosis?

Answer 6

immune-mediated disease directed against the CNS -> loss of myelin and eventual loss of axons

Question 7

is multiple sclerosis more common in men or women?

Answer 7

3x more frequent in women

Question 8

what is the peak incidence for multiple sclerosis?

Answer 8

between 20-40

Question 9

true or false? * MS progresses straight to a chronic inflammatory picture with no preceding acute inflammation

Answer 9

true, typical of most autoimmune diseases

Question 10

what are the 2 phases of MS

Answer 10

○ 1st phase (active plaques): presence of typical leukocytes found during chronic inflammation
▪ Destroy myelin and oligodendrocytes that form it, though new oligodendrocytes can still be generated
Major leukocytes:
* CD4+ Th (likely mostly Th1 and Th17) and B-cells
* Macrophages (recruited and derived from microglia) and cytotoxic T-cells
○ 2nd phase (inactive plaques): loss of axons (and eventually neurons) with limited to no leukocytic infiltration and prominent gliosis

Question 11

explain active plaques

Answer 11

leukocytes are recruited from the circulation, across the BBB
Helper T-cells initiate an immune response against myelin (MBP which helps to compact the many layers of the myelin sheath)
These helper T-cells recruit other leukocytes into white matter (cytotoxic T-cells, macrophages) and activate them
- Cytotoxic T-cells seem to attack oligodendrocytes
* MBP-specific B-lymphocytes are also recruited into the CNS and produce anti-MBP antibodies – these also seem to help destroy the myelin sheath

Question 12

what is a flare?

Answer 12

period of worsened neurological symptoms

Question 13

what causes flares in MS?

Answer 13

Buildup of helper T-cells and cytotoxic T-cells in the CNS that attack white matter components and B-cells that produce myelin-specific antibodies

Question 14

As flares continue, there seem to be areas where lymphocytes reside “permanently” these are called

Answer 14

lymphocytic follicles

Question 15

where are the lymphocytic follicles most prominent?

Answer 15

around the meninges and blood vessels

Question 16

what are inactive plaques

Answer 16

plaques without prominent inflammation

Question 17

With loss of myelin and oligodendrocytes, axons tend to

Answer 17

degenerate

Question 18

explain how the axons degenerate

Answer 18

• “destabilization” of action potentials
• Fewer action potentials -> reduced trophic support for neurons – leading to neuronal cell death
• Expression of NMDA receptors on “ naked” axons and calcium-mediated cytotoxicity – glutamate is also toxic to oligodendrocytes

Question 19

Following demyelination, what happens to allow for action potential conduction

Answer 19

additional sodium channels are redistributed along the axon

Question 20

what are the most common initial symptoms of MS

Answer 20

• paresthesia’s in one or more extremities, the trunk, or one side of the face
• Weakness or clumsiness of a leg or hand
• Visual disturbances

Question 21

what is the L’hermitte’s phenomenon

Answer 21

Sensation of an “electrical shock” running down the back and along the limbs

Question 22

what is Uhthoff sign which is very common in MS patients

Answer 22

a transient worsening of neurologic function (initially described as blurry vision after a hot bath), with heat exposure, physical exhaustion (exercise), infection, or dehydration

Question 23

what is the symptom and history checklist called for clinical diagnosis of MS

Answer 23

MacDonald’s criteria

Question 24

what is the treatment of MS

Answer 24

no cure, steroids can be used for acute flares, immunomodulators can be used for chronic treatment

Question 25

what is the most common progression for MS patients

Answer 25

relapsing-remitting

Question 26

many relapsing-remitting patients progress to ?

Answer 26

secondary progressive

Question 27

what does neuropathy mean?

Answer 27

functional disturbance and/or pathological change in the PNS

Question 28

what does neuralgia mean?

Answer 28

pain in the distribution of a particular nerve, usually in the absence of objective signs

Question 29

what does neuritis mean?

Answer 29

inflammation of a nerve

Question 30

what does radiculopathy mean?

Answer 30

pain along a dermatome, implying that the problem is at the level of the nerve root

Question 31

what does plexopathy mean

Answer 31

neuropathy of the entire plexus

Question 32

polyneuropathy often presents as:

Answer 32

• symmetrical distal weakness
  symmetrical distal sensory loss
• hyporeflexia

Question 33

what does multiple mononeuropathy mean?

Answer 33

involves >1 nerve, but not in a symmetrical fashion

Question 34

Charcot-Marie-tooth Disease is also known as

Answer 34

hereditary motor and sensory neuropathy (HMSN)

Question 35

Charcot-Marie-tooth Disease is autosomal dominant or recessive inheritance?

Answer 35

autosomal dominant inheritance

Question 36

what is the most common inherited neurologic disorder

Answer 36

Charcot-Marie-tooth Disease

Question 37

what is CMT1

Answer 37

demyelination of peripheral nerves due to abnormal myelin production, damage to nerves, and thickened, palpable myelin sheaths

Question 38

what is CMT2

Answer 38

axonal death and degeneration without a primary defect in myelin (less frequent)

Question 39

what is the treatment for Charcot-Marie-tooth Disease

Answer 39

• Massage – ROM to prevent contractures
• Anti-inflammatories, analgesics

Question 40

what is Guillain-Barre Syndrome (GBS)

Answer 40

Acute onset immune-mediated demyelinating neuropathy

Question 41

what is the most common cause of acute flaccid paralysis

Answer 41

Guillain-Barre Syndrome (GBS)

Question 42

Guillain-Barre Syndrome (GBS) typically occurs after what?

Answer 42

an infection

Question 43

how does Guillain-Barre Syndrome (GBS) develop?

Answer 43

develops rapidly and typically involves predominantly motor symptoms

Question 44

one of the clinical features of Guillain-Barre Syndrome (GBS) is ascending symptoms. Explain that

Answer 44

weakness starts in the lower limbs, progresses to higher regions of the body

Question 45

one of the treatments for GBS is plasmapheresis. what is that?

Answer 45

removal of antibodies from the blood

Question 46

In the peripheral nervous system, compression of a nerve often leads to:

Answer 46

• pain
• loss of motor function
• loss of sensory function

Question 47

what are the theories of compressive nerve damage?

Answer 47

• Direct mechanical damage to the nerve -> loss of axonal function
• Ischemia- Compression of the vessels in the perineurium -> decreased blood flow and reduced function in the nerve

Question 48

what is Bell’s Palsy

Answer 48

Idiopathic paralysis of the facial nerve

Question 49

what is the most common cause of unilateral facial paralysis

Answer 49

Bell’s Palsy

Question 50

Bell’s Palsy cause was thought to be ?

Answer 50

compression of the facial nerve caused by edema/inflammation caused by herpes virus

Question 51

T or F: Bell’s palsy tends to self resolve (> 80% of case) over time

Answer 51

true