Myelin Disorders Flashcards
Demyelinating Disease is a category of neurologic disease in which destruction of what is the predominant pathologic process?
myelin
Where is myelin in the CNS?
white matter (tracts of myelinated axons)
Where is myelin in the PNS?
peripheral nerves and nerve roots
What is a main cause of demyelinating disease?
autoimmunity
There are two main types of demyelinating diseases that occur within the CNS/PNS. What are they?
Monophasic vs. Chronic
Acute disseminated encephalomyelitis (ADEM) is a rare kind of inflammation that affects the brain and spinal cord, usually in children. Is ADEM a part of the CNS or PNS? Is it Monophasic or Chronic?
CNS; Monophasic
Guillain-Barre syndrome is a rare disorder in which your body’s immune system attacks your nerves. Weakness and tingling in your extremities are usually the first symptoms. These sensations can quickly spread, eventually paralyzing your whole body. Is GB syndrome a part of the CNS or PNS? Is it Monophasic or Chronic?
PNS; Monophasic
In MS, resulting nerve damage disrupts communication between the brain and the body. Multiple sclerosis causes many different symptoms, including vision loss, pain, fatigue, and impaired coordination. Is MS a part of the CNS or PNS? Is it Monophasic or Chronic?
CNS; Chronic
Chronic inflammatory demyelinating polyneuropathy (CIDP) is a neurological disorder – a condition that targets your body’s nerves. Symptoms aren’t the same for everyone, but you may be tired and have areas of numbness and pain. It can slow your reflexes and make your arms and legs feel weak. Is CIDP a part of the CNS or PNS? Is it Monophasic or Chronic?
PNS; Chronic
Demyelination impedes what?
saltatory conduction
Demyelination slows or blocks what?
signal transmission
Conduction Speed depends on 2 constants which are?
- Length
2. Time
Length Constant is how far an electrical impulse can travel along an axon without requiring what?
active regeneration by ion channels
Length Constant is determined by membrane ____
resistance
Time Constant is how quickly the membrane potential changes in response to what?
electrical impulse
Time Constant is determined by membrane _______ > resistance
capacitance
Resistance is the _____ of the cell membrane to ions. Increased resistance = less _____.
Leakiness; leaky
Capacitance is the amount of _____ stored in the cell membrane, which is the cations/anions lined up along the cell membrane. The closer together they are, the more strongly attracted they are to each other = ____ capacitance
charge; higher
In autoimmunity, the immune system attacks against self-______
antigens
______ breakdown is a fundamental pathologic process in neurologic autoimmune diseases
barrier
The CNS’s barrier is the _____, while the PNS’s is the ______.
BBB: Blood Brain Barrier
BNB: Blood Nerve Barrier
The BBB is composed of what kind of junctions?
Tight
Besides tight junctions, the BBB also is composed of what?
- Astrocyte end-feel
2. Pericytes
The BNB is composed of what 3 layers?
- Endoneurium
- Perineurium
- Epineurium
To reach myelin, the immune system must gain access to which layer of the BNB?
The endoneurium
Endoneurial inflammatory infiltrate is a hallmark pathologic finding
The endoneurium surrounds what?
the myelinated nerve fiber
The perineurium surrounds what?
fascicles (bundle of fibers)
The epineurium surrounds what?
the nerve (bundle of fascicles)
The BNB is composed of tight junction-forming _____ within the endoneurium
microvessels
The PNS is a ____ environment for myelin regeneration
supportive
The CNS is a ____ environment for myelin regeneration
prohibitive
Schwann Cells are to the _____ as Oligodendrocytes are to the ____
PNS; CNS
Different cell types means that there are different ____
antigens
GB Syndrome’s main process of attacking the body is via molecular ____
mimicry
In GBS, first there is exposure to a pathogen with a component that resembles a _____ cell component.
Next, the immune system sees this as an _____ and creates a defense against it, including antibodies and activated ___cells.
Third, the antibodies later mistake the ____ cells as foreign, even though they are not, and attack them.
This causes ________
Schwann
antigen; T
Schwann
Demyelination
Acute diarrheal illness commonly linked to GBS is known as
Campylobacter jejuni
Access to the breakdown of the BNB in GB Syndrome can help to identify if there is what hallmark sign?
endoneurial inflammatory infiltrate
In GBS, there is _____ demyelination
segmental
GBS is often preceded by a _____ or ___ infection, which may be mild.
respiratory; GI
Common subacute (days-weeks) characteristics of these disease mechanisms include infectious or autoimmune ______
demyelinating
What could antecedent diarrheal illness indicate in a patient suspects of GBS?
exposure to Schwann cell-mimicking pathogen
An important indicator of GBS is _____ weakness, which may be sub-acutely worsening pain/tingling then weakness in the distal ____ extremities
ascending; lower
How does ascending weakness occur in GBS?
- Demyelination causes a conduction block
- BNB becomes deficient distally
- Subacute presentation due to segmental demyelination and immune-mediated process
A major indicator of GBS besides ascending weakness is _____, where muscles do not respond to stimuli. Hyporeflexia also can occur.
Areflexia
GBS classic clinical presentation can also include cranial nerve deficits, especially CN ___, autonomic _____ and respiratory _____ which can lead to weakness of the respiratory muscles known as restrictive lung disease.
VII (7)
dysregulation
failure
Supportive care is key for treating GBS, which includes blood pressure monitoring and _____, if necessary
intubation
MS is defined by the presence of multiple “____” (sclerosis) of the ____ nervous system
scars; central
MS scars develop during _____ attacks over time
episodic
In MS, there is disruption in the _____ and __cells are targeted against the CNS’s myelin component
BBB; T
____ form “glial scars” in damaged after acute attacks known as “MS plaques”
astrocytes
Chronic plaques are visible with MRI, frequently _____ or juxtacortical
periventricular
What MRI contrast agent does NOT cross the BBB?
Gadolinium
Ataxia and dysmetria are _____ deficits (uncoordinated movments)
cerebellar
What is opthlamoplegia?
paralysis or weakness in the eye muscles caused by damage to the medial longitudinal fasciculus; ptosis
Inflammation of the optic nerve is known as
optic neuritis
Why is optic neuritis common with a CNS disease such as MS?
because the autoimmune disorder causes the body to attack the myelin sheath surrounding the optic nerve, which leads to swelling and damage
The CNS normally _____ reflexes via inhibitory modulation. If the CNS is damaged however, _____ can occur
dampens; hyperreflexia
What is the main population of MS?
young women
What is the onset/progression of MS?
subacute onset and progression (days)
In MS, neurologic deficits localize to multiple parts of the CNS, such as the brain, ____ nerve, brainstem, ____ cord and the _____.
optic
spinal
cerebellum
MS classically presents with __reflexia
hyper
MS tends to follow a replapsing/remitting or “____” pattern
episodic
For acute attacks of MS, what is the immunotherapy treatment?
steroids
For chronic attacks of MS, what is the immunotherapy treatment?
disease modifying drugs
What is the prognosis of MS?
rarely fatal
chronic cumulative disability can occur, may be severe but most patients do NOT experience substantial disability
Which system is better at myelin regeneration, the PNS or the CNS?
PNS
___ deficits are more likely to recover than deficits from ___ attacks because of the myelin regeneration process in the PNS vs. CNS
GBS; MS
Decreased _____ and increased ____ leads to ____ length constant and ____ time constant, which leads to an overall drop in ____ speed (length/time)
resistance capacitance decreased increased conduction
How does myelin affect resistance & capacitance?
Increases resistance and decreases capacitance
Insulation by myelination ____ dissipation of ions across membranes, which is why myelin increases the resistance
decreases
Myelin ___ the amount of charge stored by membranes by increasing the separation b/w cations and anions, which is why myelin decreases the capacitance
decreases
Demyelination causes the length constant to ____ and the time constant to ____
decrease
increase
Demyelination decreases the length constant by ____ the charge dissipation across the membrane
increasing
Demyelination increases the time constant by changing the membrane potential, making it ____ to respond to sodium channel activation
slower
Demyelination causes a slower conduction velocity because the length constant ____ and the time constant ___ (length/time)
decreases, increases
If you see contrast enhancement within an MS lesion on an MRI, what does that tell you?
Contrast enhancement indicates BBB breakdown, which is evidence of an acute MS exacerbation
