Topic 20: Multiple Sclerosis Flashcards
What is the prevalence of multiple sclerosis around the world?
causes decrease toward the equator
due to: European background, lack of sun exposure
What is the most common age of onset of MS?
ages 15-25
What is the prevalence of pediatric MS?
6% of MS in total
3 to 10% of MS patients onset </= age 18
What is the prevalence of MS based on gender?
3:1, female:male
What is relapsing-remitting progression of MS?
symptoms then back to baseline
or symptoms that decrease but don’t go fully back to baseline
What is secondary progression of MS?
around 70% of the time
no fluctuations, just steady progression?
What is the Expanded Disability Status Scale (EDSS)?
evaluating the motor changes, not cognitive ones
What is the pathology of MS?
many lesions in the white and gray matter
lesions damage the nerve fibers and tracts
location of lesion causes symptoms
What is the relationship between MS and myelination?
demyelination, remyelination, axonal transection
decreased axonal density in MS plaques
What are the causes of MS?
genes
environment: infections (EBV, Mono, could bring things to the surface), smoking, sun exposure, sodium (activates the immune system)
What is the genetic contribution to multiple sclerosis risk?
no Mendelian relationship
genome wide association studies: HLA or MSC
How can EAE be produced in animals?
can be produced by myelin-specific T cells
mice injected with myelin basic protein and complete Frund’s adjuvant develop demyelinating disease (EAE)
the disease is mediated by myelin basic protein-specific T cells
disease can be transmitted by transfer of T cells from affected animal
What is the immunology of EAE?
- inject MBP
- in a pool of naïve T cells there will be a MBP-recognizing cell
- MBP-specific T cells cause antigen presentation
- there is an expansion of MBP-reactive T cells and they enter the CNS
- these cells are reactivated in the CNS, products produce CNS pathology
How is the process of EAE a model of molecular mimicry?
- virus with molecular similarity to myelin protein (e.g. MBP) interacts with a pool of naïve cells that contains virus-recognizing cells and MBP-recognizing cells
- there is antigen presentation of virus to naïve T cells
- this causes expansion of virus specific T cells trying to get rid of viruses, and expansion of cross-relative MBP-specific T cells which cause accidental activation which can cause alkaline reaction
- these cells enter the CNS, recognize MBP, and initiate inflammatory damage
What do naïve CD4 T cell differentiate into?
differentiate into Th1, Th2, Th17, and T regulatory cells
different path based on environment
What is MS pathogenesis based on B lymphocytes?
antigen presentation
Breg dysfunction
antibody production
ectopic germinal centers
cytokine activation of astrocytes/microglia
What kind of inflammation is seen in MS plaques?
peri-vascular inflammation
What is the pathogenesis of MS in neurons?
astrocyte activation
neuro-axonal degeneration
microglia activation
energy failure
glutamate excitotoxicity
inflammation
ionic imbalance and increased sodium levels
demyelination
activate microglia, axonal death, swelling of axons, demyelination
What is immune dependent neurodegeneration in MS?
immune dependent, immune system is causing damage, microglia, astrocyte, and B cell caused
What is immune independent neurodegeneration in MS?
microglia: mtDNA mutation, energy deficiencies, ROS/RNS, mitochondrial injury
astrocyte: demyelination, Fe3+, oxidative stress
B cell: influx of Ca++, glutamate excitotoxicity, ionic imbalance
immune independent due to the swelling, even if inflammation stopped these pathways will continue
What is the brain atrophy in MS?
enlarged ventricles
damage to white and grey matter
What are clinical manifestations of MS?
symptoms in almost any area
ocular: blurred vision, diplopia
cerebellar: ataxic walk, vertigo, nystagmus
autonomic: urinary incontinence, sexual disorders
motor: reduced strength and activity, muscle spasms, muscle weakness and loss of strength
sensory manifestations: tuning fork, sensory changes, hypesthesia, progressive sensory loss
What is fatigue?
a feeling of physical tiredness and lack of energy distinct from sadness or weakness
very difficult for patients or caregivers to describe
severe in up to 74% of patients, worst symptom of the disease in 50-60% of patients
What is bladder overactivity?
urgency, frequency, urge incontinence
