MS vignette Flashcards
MS stats
> 400,000 americans
80% of MS patients between 16-46
female to male risk: 2.4:1
MS outcomes if untreated:
50% require cane or more support within 10 yrs
30% wheelchair or bed bound
avg. lifespan decreased by 5 yrs
___ is the leading cause of disability in young women and 2nd of young men
MS
potential triggers for MS
- infectious agent
- genetic predisposition
- environmental factors
all lead to an abnormal immunologic response, leading to MS
inflammatory processes occurring early in MS leads to
demyelination and axonal loss
immuniopathogenesis
- CNS damage (demyelination, transection, neuronal loss)
2. CNS repair (remyelination)
immune respinse in MS invloves
many cells , like B cell, macrophage, neurtophil, T cells,
brain lesions form an
oval chap around veins coming off the ventricles because demyelination occurs around the veins
dawson’s fingers
the lesion orientation in an outward array around the veins of the brain
The open ring sign
Active BBB disruption
Passage of inflammatory cells in to the CNS 5–10x more frequent than relapses Predictive of relapses, but lessens in SPMS Window 2-8 wk; mean 3 wk
Common MS symptoms
- fatigue
- walking impairment
- spacity
- cognitive impairment
- bladder dysfunction
- pain
- mood instability
- sexual dysfunction
MS walking impairment: Gait description:
- ataxic
- spastic
- paretic
- foot drop
MS walking impairment: disabling impact:
- negatively impacts work productivity, employability and income
- impairs activities of daily living, like deriving
- significantly affects quality of life
Factors involved in walking impairment
- muscle weakness
- spasticity
- loss of balance
- sensory deficit
- fatigue
Assessing walking impairment:
- timed 35- foot walk
- 500 meter walk
- 6 minute walk
- assess posture
- assess use of a device
- asses overuse of joint compensating
MS : Evoked potentials
- Prolonged Conduction Velocity = Demyelination
- Can measure conduction multiple ways
a. Visual stimulation
b. Brainstem stimulation, auditory pathways
c. Somatosensory system stimulation - Main use is to define a lesion as “demyelinating”, or identify a “second lesion” if MRI is negative
Prolonged Conduction Velocity =
Demyelination
affect of lesions in the brain on:
amplitude:
duration:
May see slowing, decreased amplitude, prolonged duration, or even total conduction block of potential
demyelination produces proliferation of
sodium channels along the axon
sodium channel blockade causes
- with increased sodium entry into cell, the slowing of nerve conduction
- ultimately there may be a reversal of sodium calcium exchanger –> calcium influx
- – this produces calcium mediated nerve injury - sodium channel blockers phenytoin and flecainide preserves the axons in EAE
Drugs to help manage walking impairment
dalfampridine
dalfalmpridine indication
to improve walking speed in patients with MS”
This is not a disease-modifying therapy”
dalfalmpridine mechanism
K+ channel blockade
enhances conduction of AP in demyelinated axons through inhibition of K+ channels
dalfalmpridine appropriate candidates:
- Contraindicated in patients with history of seizures or moderate to
severe renal impairment” - Monitor patients with history of multiple urinary tract infections”
MS is a
inflammatory demyelination disease
MS is a common CNS disease causing
disability and multiple neurological problems in patients
MS causes a decrease in
speed of conduction in nerves
MS results in
many lesion in the CNS (brain and spine)
Some MS treatments can also
increase the speed of conduction on the nerves
Conduction of an action potential is initiated with a
stimulus that depolarizes the membrane of a nerve cell.
This depolarization causes voltage-gated Na+ channels to _____.
open
A threshold voltage is reached when
enough voltage-gated Na+ channels have opened, so that sodium and potassium currents across the cell membrane are exactly equal and opposite (Na+ is entering the cell at the same rate that K+ is leaving the cell.)
As the depolarized membrane opens more voltage-gated Na+ channels, the balance between the sodium and potassium currents is tipped in the direction of
ENa and an action potential is fired.
The maximum voltage of the action potential is reached when the, ______.
The cell then begins to repolarize as the voltage-gated _______.
voltage-gated Na+ channels close
K+ channels open and K+ leaves the cell
The action potential is conducted along
a nerve as current (Na+ inside the cell) moves down the length of an axon from the initial action potential.
This propagated positive charge causes
depolarization in a neighboring region of the membrane and an action potential is again fired.
This process repeats, propagating the action potential down the length of an axon in either direction.
Myelin is an important component in______.
propagating action potentials
Myelin increases the _______, thereby increasing ______.
resistance and capacitance of cell membranes
conduction speed
Myelin wraps nerve axons, leaving only intermittent uncovered axonal regions: _____.
the nodes of Ranvier
The action potential is propagated from _______, due to the ability of myelin to ______
node to node very quickly and without loss of current
insulate the internodal regions of the axon.
Multiple sclerosis occurs when _______.
T-cells cross the blood-brain barrier and become trapped in the brain
The T-cells recognize myelin as an _____.
antigen
This recognition initiates a series of events in which
T-cells, B-cells, microglia and macrophages proliferate and are directed to the CNS.
The immune response leads to
inflammation, demyelination and axonal degradation.
Demyelination of axons causes inefficiency in an axon’s ability to
propagate signals to the rest of the body.
Electrode studies of the effects of MS on conduction have shown that demyelination causes
longer conduction periods, decreased amplitudes of action potentials and/or total conduction block.
Drugs aimed at alleviating the symptoms of MS include
sodium channel blockades and dalfampridine.
Sodium channel blockades work by
blocking some of the sodium channels that are exposed as a result of demyelination.
As sodium builds up, the cell’s Ca2+/Na+ exchanger ______, and____ enters the cell.
reverses direction
Ca2+
Calcium buildup in the axon leads to
degeneration.
Sodium channel blockades, such as Phenytoin and Flecainide have been shown to limit
calcium-mediated axonal degeneration.
Normally, myelin insulates these sodium to prevent
excess sodium from entering the axon.
An increase in sodium channels causes
sodium to buildup in the cell, as the Na+/K+ pump is not able to efficiently remove the excess sodium.
Dalfampridine has been shown to improve the:
walking speed of MS patients
Dalfampridine blocks______ in neurons, which leads to a _______.
K+ channels
prolonged action potential and increased conduction
In Phase III clinical trials, Dalfampridine was shown to improve walking speed by
25% (compared to a 5% improvement in the placebo group).
MS incidence pattern
related to migration patters
___ is a risk for MS
smoking
early on, MS is
asymptomatic
if you have demyelation, speed of transmission is
decreased
when speed of transmission is decreased, latency is
increased
A typical action potential begins at the ______
axon hillock
During the relapsing-remitting phase, the disease is characterized by
frequent inflammation, demyelination, axonal transection, and remyelination.
Immunopathogenesis of MS is the result of 3 components of the disease.
- Inflammatory activity
- Possible remyelination or regeneration
- Axonal destruction
In MS, blood brain barrier is _____.
leaky
