MS Flashcards
What are potential triggers for MS?
Must involve genetics and environmental factors. Infection and viruses may also play a role
Of the hundreds of MS susceptibility genes identified; name 2 important ones
Strongest association with HLA-DRB1*1501 allele which is present in 30% high risk regions (3x risk for heterozygotes; 6x risk for homozygotes) and rare variants of CYP27B1
What likely drives the contribution of genes in MS? What effect does HLA have?
HLA Likely driven by gene-gene interactions and likely has an effect on immune-responses
Which race has the highest risk of MS?
White caucasians and northern Europeans
What is the hygiene hypothesis?
States that lack of exposure to infectious agents as a young child may lead to more diseases later in life. May fail to properly develop autoimmunity and contribute to MS
What effect does migration play in MS?
Migrating from higher to lower latitudes before the age of 15 can reduce your risk of MS
What is EBV infection?
Leads to infectious mononucleosis (IM)
How does EBV/IM infection affect MS?
Early EBV infection early in life seems to reduce MS risk; later in life seems to increase it. Thought is that the EBV nuclear antigen (EBNA) is similar in form/structure to myelin and the immune system might start to recognize myelin as an infection
Describe the the relapsing-remitting phase of MS
Characterized by frequent inflammation; demyelination; axonal transection; and remyelination. Relapses are more frequent and complete recovery from disability generally occurs
Describe the the secondary-progressive phase of MS
Inflammation and relapses occur infrequently; axonal loss is increased and disability progresses
What is thought to result in the loss of compensatory mechanisms that triggers the conversion from RRMS (relapsing-remitting) to SPMS (secondary progressive)?
The loss of axons beyond a critical threshold
What do immune cells inside the brain cause in MS? (2 things)
Demylination and axonal loss
Why do patients progress in MS?
Toxins (nitrous oxide; glutamate); Mitochondrial exhaustion; Neural-glial uncoupling; Ion channel dysfunction; Accelerated aging; Loss of compensation/Brain Reserve
What does CIS stand for?
Clinically isolated syndrome - the Pts 1st neurological episode
What does contrast enhancement at the site of a lesion on an MRI mean?
An active demylinating lesion. Site of active BBB disruption
Does MS affect white matter or gray matter?
BOTH
What forms the myelin sheath in the CNS? In the PNS?
Oligodendrocytes in CNS. Schwann cells in PNS
In a myelinated axon; where does electrical activity occur?
nodes of Ranvier (gaps in the myelin)
Why does demyelination lead to slowing of conduction velocity?
loss of saltatory conduction
Name 8 common MS Symptoms
Fatigue. Walking impairment. Spasticity. Cognitive impairment. Bladder dysfunction. Pain. Mood instability. Sexual dysfunction
Gait description in MS
Ataxic. Spastic. Paretic. Foot drop
What factors are involved in MS walking impairment?
Muscle weakness (Results in toe drag; foot drop; vaulting). Spasticity. Loss of balance/Sensory deficit (Affects ability to feel the floor/know where the foot is). Fatigue.
What affect does demyelination have on sodium channels?
Produces proliferation of sodium channels along the axon
How does proliferation of sodium channels affect nerve conduction?
With increased sodium entry into the cell there is slowing of nerve conduction. Ultimately there may be reversal of sodium-calcium exchanger > Calcium Influx (produces calcium-mediated nerve injury)
How can axons be preserved in EAE?
Sodium channel blockers (phenytoin and flecainide)
What medicine is used to improve walking speed in MS patients?
Dalfampridine
What is the mechanism of action of dalfampridine? How does this work?
K+ channel blocker. It enhances conduction of action potentials in demyelinated axons through inhibition of K+ channels. (doesn’t stop the immune response; but helps people walk better; think faster; decrease fatigue)
Other ways to treat MS?
Block action of B cells in the brain; block the blood-brain barrier; etc.
