Multiple Sclerosis Flashcards
TRUE or FALSE: MS affects an older population
FALSE: younger population
What percentage of MS is pediatric? What percentage of MS patients have an onset or less than or equal to age 18?
- 6% total
- 3-10% under 18
Does MS affect males or females more?
females
TRUE or FALSE: there is decreased axonal density in MS plaques
TRUE
What are the causes of MS?
- genes
- infections (mono)
- sun
- smoking
- salt???
Which gene is associated with MS?
HLA
How is EAE produced and transmitted in animals?
- mice injected with myelin basic protein (MBP) and complete Freund’s adjuvant develop demyelinating disease (EAE)
- disease is mediated by myelin basic protein-specific TH1 cells
- disease can be transmitted by transfer of T cells from affected animal
Explain the model of molecular mimicry
- inject virus with MBP
- antigen presentation of virus to naive T cells
- expansion of virus-specific T cells + expansion of cross-reactive MBP-specific T cells
- enter CNS, recognize MBP, initiate inflammatory damage
What cells do CD4 T cell differentiate into in the CNS. What are the associated cytokines?
- TH1–> IL-2, IK-12, IFN-gamma, TNF-alpha
- TH17 –> IL-17, IL-23
What cells do CD4 T cells differentiate into in the respiratory system? What are the associated cytokines?
- TH2 –> IL-4, IL-5, IL-10, IL-13, IL-25, TGF-beta
- Treg –> TGF-beta, IL-10, IL-35
There is _____________ inflammation in MS plaques
peri-vascular
What pathogenetic events occur in MS?
- inflammation
- ionic imbalance and increased sodium levels
- microglia activation
- energy failure
- glutamate excitotoxicity
- astrocyte activation
- neuro-axonal degeneration
TRUE or FALSE: axonal transection in acute MS lesions can be remyelinated
FALSE
What is MS triggered by?
inflammation
Describe neurodegeneration in MS pathogenesis.
- mitochondrial injury leads to energy deficiencies
- oxidative stress leads to demyelination
- ionic imbalance due to glutamate excitotoxicity
- atrophy and degeneration
TRUE or FALSE: myelin loss and axon loss increase with the clinical course of MS
TRUE (see slide 27 chart?)
How do ocular lesions in MS manifest?
- blurred vision
- diplopia
How do cerebellar lesions in MS manifest?
- ataxic walk
- vertigo
- nystagmus
How do autonomic lesions in MS manifest?
- urinary incontinence
- sexual disorders
How do motor lesions manifest in MS?
- reduced strength and activity
- muscle spasms
- muscle weakness and loss of strength
How do sensory lesions manifest in MS?
- sensory loss
- hypesthesia
Why is it important to localize the lesion in MS before prognosis?
neurological symptoms depend on where the lesion is
Which reflex is primarily affected in MS?
motor reflex arc –> leads to spasticity
What is the definition of fatigue?
a feeling of physical tiredness and lack of energy distinct from sadness or weakness
Fatigue is severe in up to ____% of patients.
74
What is the worst symptom of MS in 50-60% of patients?
fatigue
What percentage of MS patients are affected by bladder dysfunction? What are some forms of bladder dysfunction?
- 75% of patients
- bladder overactivity: urgency, frequency, urge incontinence
- bladder inefficiency: incomplete emptying, residual urine
- detrusor-sphincter dyssynergia: co-contraction of bladder and urethral sphincter
Which fibers innervate the bladder?
- sympathetic
- parasympathetic
- somatic
What percentage of MS patients are affected by pain? In what ways can it present in MS?
- 40-50%
- PERSISTENT NEUROGENIC PAIN: burning dysesthesia of the limbs and/or trunk attributed to disruption of the SPINOTHALAMIC pathway
- PAROXYSMAL NEUROGENIC PAIN (trigeminal neuralgia): excruciating facial pain
Which cranial nerve is compressed in trigeminal neuralgia?
cranial nerve V (all 3 regions)
What do existing treatments for MS primarily target?
inflammation
What are the 3 main aspects of MS that should be targeted?
inflammation, neurodegeneration/demyelination, failure of repair/gliosis
There is a need for novel agents that directly target ___________.
PROTECTION and REPAIR of the CNS as well as targeting INFLAMMATION
What are traditional injectables for MS?
- beta-interferons (IFN-beta)
- glatiramer acetate
What are some oral therapies for MS?
- dimethylfumarate (DMF)
- fingolimod
- teriflunomide
- cladribine
What are some monoclonal antibodies for treating MS?
- natalizumab
- alemtuzumab
- ocrelizumab
- ofatumumab
What are some chemotherapies for MS?
- mitoxantrone
- cyclophosphamide
What is an experimental MS therapy option as of 2023?
autologous stem cell transplant
What is the mechanism of action for IFN-beta in treating MS? How effective is it?
- IFN-beta inhibits antigen presentation and T cell activation via IFN-beta receptor
- decrease pro-inflammatory TH1 cytokines
- nonspecific but effective, also side effects
