MS - Bloch Flashcards
Where is there a greater geographic risk of MS?
the farther away from the equator; Reno and farthernorth
What two groups of people never get MS?
Inuits and Laplanders of Northern Scandinavia
Less sun exposure leads to a (higher/lower) risk of MS
higher
How many times more likely are women to get MS?
2-3x
when do women usually get their first MS attack/
after first pregnancy; espcially after nursing as the hormones affect the immune system
How long is a cancer Dx postponed in pts with MS?
10 years
What vitamin has a huge protective factor against MS?
vitamin D; >20 minutes of sun per day
what are the symptoms of MS?
severe pain under eye (has moved to eye) blurry vision memory problems FATIGUE leg numbness hip pain indicates spinal lesion
when is MS onset most common?
20s-30s
Describe the MOA of MS?
WBCs see myelin as foreign, cross the BBB and cause white matter lesions
Why is optic neuritis a common manifestation of MS?
high vascularization leads to larger WBC deposition
What percent of pts progress from optic neuritis to MS?
90%
T/F: DMARDS should be started at the time of the first MS attack
true
T/F: MS is more common with other autoimmune presentation
true
What are the side effects of betaseron (IFN)?
fatigue and flu like sx
By what percent does betaseron reduce the relapse rate of MS?
30%
What are the side effects of copaxone?
welts and liponecrosis
What is the MOA of copaxone?
co-polymer with unknown MOA; thought to maybe create a protective layer that makes it harder for WBCs to attack
What is the first oral DRMARD?
Fingolimide
What is the MOA of fingolimide?
sphingosoine receptor agonist
which cells have sphingosine receptors?
T cells
What happens with fingolimide attaches to T cells?
enter lymph nodes and never leave; no WBC circulation
What are the side effects of fingolimide?
heart
BP
eye
By what percent does fingolimide reduce relapse rates/
50%
What is the most effective drug in MS?
Tysabri
what is the MOA of tysabri?
prevents T cells from crossing the BBB
by what percent does tysabri reduce relapse rates?
70%
What are the issues that present after being on tysbri for 2 years or more?
increased risk of certain infections
increased reactivation of the John Cunningham virus (leads to PML progressive multifocoal leukoencephalopathy)
In which group of pts on tysabri will get PML from a JC virus reactivation/
HIV or chemo pts
T/F: you can develop allergies to tysabri and IFN treatment
true
T/F: life expectancy is now normal in pts with MS
true
MS is associated with which HLA protein?
HLA-DR2
what are some of the proinflammatory neurotoxic factors?
TH1 and TH17 cytokines TNF IL-1 osteopontin leukotrienes MMP plasminogen activators nitric oxide reactive oxygen species glutamate antibody + complement cell-mediated cytotoxicity neurotrophins via p75NTR?
what are the anti-inflammatory and neuroprotective factors?
TH2 cytokines TGF-beta soluble TNF receptor soluble IL-1 receptor IL-1 receptor antagonist some prostaglandins lipoxins TIMP antithrombin ***BDNF NGF NT3 neurotrophic NT4/5 factors GDNF LIF ***
In MS, (blank) type cytokines predominate
proinflammatory
Active inflammation has what two destructive effects on neurons?
demyelination
axonal transectoin
at what age do you normally get MS?
between 20 and 50; Dx in young kids and older adults; women:men 2-3:1
What ethnicity gets MS more often?
N. european; more common in caucasians than hispanics or African americanns; RARE IN ASIANS
MS is more common in which biome?
temperate climes
what percent of people with MS have a blood relative with MS?
20%
What are multiplex families?
there is a higher risk in families in which there are multiple family members with MS
Is MS a clinical or lab Dx?
clinical
What are the paraclinical tests that support an MS dx?
MRI
spinal fluid
evoked potentials
What are the Dx criteria for MS?
dissemination in time and space: evidence that damage has occurred in two separate areas of the CNS at diff. pts in time
What is the workup up order for Dx of MS?
- MRI with gadolinium
- Potential MS mimetics rule out (blood testing)
- LP (OBs and/or elevated IgG index or synth)
- Evoked potentials
What is clinically isolated syndrome?
first neuro event suggestive of demyelination; at high risk for developing MS if multiple silent lesions on MRi
What are the two most common types of CIS?
optic neuritis
transverse myelitis
What are the Sx of optic neuritis?
Sudden, but transient loss of visual acuity
Unilateral or bilateral
Retro-orbital pain exacerbated by eye movement
Normal optic disc
Reduced color perception
Decreased vision following activities that elevate body temperature
what are the Sx of transverse myelitis?
Ascending numbness from the feet, up the torso, potentially from hands to arms
Ataxia, balance problems
Electric shock sensations while flexing neck
Partial or complete paralysis
Bladder dysfunction
Bowel dysfunction
Sexual dysfunction
On MRI, what is the strongest correlation with progression of disability?
T1 precontrast black holes; shows axonal loss
what do you see on T1 gadolinium post contrast MRI?
white spots that show active BBB breakdown
What do you see on FLAIR MRI?
MS lesions as white spots
What do you see on T2 MRI?
the spinal fluid and the lesions both show up as white so its harder to tell what the fuck is going on
Which DMARDS are approved for relapsing forms of MS?
IFNb-1b IFNb-1a IM and SC Fingolimod dimethyl fumarate Tysabri **as monotherapy**
Why are tysabri and mitonaxotrone second line therapy?
safety concerns even though they are better tolerated
which DMARD is a humanized Mab?
tysabri
what type of MS is copaxone approve for?
relapsing-remitting MS
What are the negative prognostic indicators for MS?
Frequent, multifocal attacks Heavy MRI burden on initial scans Pyramidal involvement Ataxia Cognitive difficulties 5 year accumulation of disability Spinal progression (primary progressive MS)
What is the immediate Tx for a relapse?
corticosteroids if it sig. interferes with ADLs
Rehab if necessary
how do you define a relapse?
new neuro symptom lasting 24 hours or worsening of old symptom
What is the most common MS symptom?
fatigue
What are the “visible” symptoms of MS?
Spasticity Gait, balance, and coordination problems Speech/swallowing problems Tremor Weakness
What drug is approved to increase walking speed in MS?
Dalfampridine; oral K channel blocker that speeds nerve conduction
T/F: sensitivity to heat or cold can happen in MS
true; but heat is more common
How does an infection worsen MS symptoms
through raising the body temp
What’s an easy way to tell if someone is having a true relapse or a pseudoexacerbation?
urine screen for a UTI
What druugs can you give to treat the “small bladder” in MS?
oxybutynin
Tolteridine
trospium chloride
what drugs can you give to treat the “large bladder” in MS?
stimulating meds
intermittent self-catheterization
What drugs can you give to treat the dysynergic bladder?
Alpha adrenergic agonists like dibenzyline, terazosin ,Cardura, and put in a catheter
What can you give to treat nocturia?
DDAVP- desmopressin
What drugs can you give to manage MS pain?
gabapentin lamotrigine carbamazepine amitriptyline pregabalin
what kind of pain is MS pain?
burning, irritating, neuropathic pain
What psych disorder is often confused with MS symptoms?
depresssion; it is UNDER Dx’d and treated
What is the Tx for MS and depression?
Psychotherapy, meds, and exercise
what percent of people with MS will experience an MDD?
greater than 50%
suicide is how many more times common in MS pts?
7.5x
T/F: cognitive impairment is common in MS
false!!; only occurs in late or severe stages
Because MS is a white matter disease it does not effect what three architectural properties of the brain?
- brain volume
- gray matter
- cerebral cortex
What are the causes for memory problems in MS?
stress
anxiety
depression
Cogntive function correlates with…
lesion load and brain atrophy
T/F: cognitive dysfunction can occur as a first symptom in MS
true; although it normally happens later on; most common PROGRESSIVE MS
T/F: depression can worsen cognition
true
