MS - Kedar Flashcards
1
Q
Epidemiology of MS:
- Onset age:
- Female:male -
- Life expectancy
- Total lifetime cose:
A
- Onset- 15- 45y; mean 30y
- Female>Male (~1.77:1)
- Life- expectancy decreased (58.1y vs 70.5y)
- Total lifetime cost/pt 1994: 2.5 million
2
Q
MS Age adjusted risk percentages:
- Siblings:
- Parents:
- Children:
- Monozygotic twins
5: family recurrence rate:
A
Age-adjusted risk siblings (3%) parents (2%) children (2%) monozygotic twins 35%. Familial recurrence rate of 15%
3
Q
Some say MS is related to what 4 thing?
A
?Latitude related ?Temperate climates ?Race related ?Region related
4
Q
US prevalence of MS is:
A
US: prevalence is
0.1%~ 350,000
5
Q
There is a possible prevalence in what area of US?
A
Northern states
6
Q
- What is the pathologic hallmark of MS?
- affects what areas?
- sequelae?
A
- PLAQUE- axonal demyelination with relative preservation of axons
- Perivenular, periventricular white matter, brainstem and SC
3. Cerebral atrophy with ventricular dilatation
7
Q
5 stages of pathogenesis for MS
A
- BBB disruption
- Activated T-cells
- Activate microglia
- Proinflammatory loop
- Myelin destruction
8
Q
MS: Autoreactive T cell and B cells to myelin are usually held in check by ______.
A
Regulatory T cells
9
Q
Regulatory T cells can be activated in MS pathology by what pathways?
A
- Infectious agent - (even EBV and chlamydia)
- Genetic predisposition
- environmental factors
10
Q
3 potential triggers of MS
A
- Infectious agent-HTLV-1, HHV-6, EBV
2. Molecular mimicry
3. Exposure to CNS antigens- previous insult by injury/infection/disease
11
Q
Demyelination shows what three things on EMG
A
Slows conduction
Blocked conduction
Temporal dispersion
(refractory period can become prolonged)
12
Q
what is mechanical stimulation in MS? Caused by (2)
A
movement of axons that have lost their covering can give shock like sensation:
De-novo AP
Lhermitte phenomenon
13
Q
what are examples of spontaneous action potentials in MS?
A
- Paroxysmal positive trigeminal neuralgia
- myokymia
- paraspinal muscle spasms
- photopsia
14
Q
What are the top six presenting symptoms of MS? (with percentages)
A
Visual/oculomotor - 49 Paresis - 42 Paresthesias - 41 Incoordination - 23 Genitourinary/bowel - 10 Cerebral - 4
15
Q
What percent of patient’s will have these symptoms during MS
- Visual/oculomotor
- Paresis
- Paresthesias
- Incoordination
- Genitourinary/bowel
- Cerebral
A
- 100
- 88
- 87
- 82
- 63
- 39
16
Q
Charcot was the first to recognize what defecit in MS? percentage?
What 4 defecits are most commonly seen
A
Cognitive impairment - 35-65%
Patients with MS lose the ability to multitask
- Abstract conceptualization,
- recent memory,
- attention
- speed of processing
17
Q
____% of MS patients have affective disturbance?
In what 3 ways?
A
66%
Depression (34% lifetime risk)
?association with bipolar disease
Pseudobulbar affect
correlated with MRI metrics of activity and progression
18
Q
What is RIS in MS?
A
Radiologically isolated syndrome (RIS) - lesions consistently on scans without clinical s/s.
19
Q
What is the deficit with pseudobulbar affect?
A
decreased conduction b/w cortex and cerebellum – emotional incontinence.
More cognitive impairment in patients with frontoparietal lesions.
20
Q
5 notes on the management of MS?
A
Treat underlying disease Treat co-morbid psychiatric condition L-amphetamine (Morrow 2009) Modafinil Cholinesterase Inhibitors do not work
21
Q
What is the lesion to the optic nerve in optic neuritis in MS
path?
A
relative afferent pupillary defect - usually unilateral; retrobulbar
Usually 2 week nadir with resolution at 4-6 weeks – if not: “atypical optic neuritis”
22
Q
Optic Neuritis in MS is a _____ diagnosis:
1. presents as _____
2. Eye exam shows _____ (5)
3.
A
Clinical diagnosis
Acute/subacute d/v; retroorbital pain on EOM
Decreased acuity, color, contrast, RAPD
central/cecocentral scotoma
23
Q
ONTT was a study in MS regarding what:
Methods
A
Optic neuritis in MS patients
18-45 y/o with acute (<8 days) Optic Neuritis randomized to: Oral Prednisone (1mg/kg/day) X 14 days IV MP (1000 mg/day) X 3 days followed by oral prednisone (1mg/kg/day) X 14 days Oral Placebo X 14 days
24
Q
The ONTT study for MS showed what at 6 months?
A
Quicker recovery with IV steroids
Visual recovery excellent for ALL groups
INCREASED # of new attacks with oral
prednisolone alone
25
ONTT results at 15 years in MS patients
```
Visual function:
92% affected eyes 20/40 or better
1% < 20/200 (each eye)
Poor VA associated with higher
conversion to MS
Majority of subjects reported residual
visual dysfunction (Decrease in color and
contrast)
```
26
According to ONTT:
1. Those with Optic nueritis who convert to MS were _____ %.
2. What % had normal MRI at baseline?
3. What percent had abnormal MRI at baseline?
4. If no MS at 10 years, on ____ % chance of conversion to MS at 15 years.
```
Conversion to MS:
Overall: 50%
Normal MRI at baseline: 25%
Abnormal MRI (>/=1) at baseline = 75%
If no MS at 10 years, only 2% chance of
conversion to MS at 15 years.
```
27
What are the other CNs/pathology associated with MS
```
Ocular dysmotility
INO
Nystagmus
Trigeminal neuralgia
Facial myokymia, hemifacial spasm
```
28
Sensory pathways associated with MS: (3)
ALS system- pain/temp/light touch
Dorsal column- jt. Position/vibratory
Dorsal root entry zone- band like
sensation in thoraco-abdominal area
29
Motor pathways associated with MS: (2)
```
Corticospinal tract dysfunction:
paraparesis> upper extremity more
common
UMN signs of spasticity; hyerrelexia;
clonus; extensor plantar reflex
```
30
Name the cerebellar abnormalities in MS (8)
```
1. Gait imbalance
2. Dysarthria- usually scanning speech
3. Dysmetria,
4. dysdiadochokinesia,
5. rebound phenomenon,
6. truncal ataxia;
7. EOM abnormalities;
8. nystagmus
```
31
MS patient's:
1. Bladder - most common complaint? what about later stages?
2, Bowel: ___ more common
3. Sexual: ___%s
1. Bladder - Commonest complaint is urgency from uninhibited detrusor contraction
Later stages- atonic dilated UB
2. Bowel Constipation more common
3. Sexual - 50% completely inactive. 20% less active Multifactorial
32
How is MS diagnosed?
Must have 2 isolated clinical neurological insults separated by time and space>
"Clinical or diagnostic evidence of lesion
Dissemination in time
Dissemination in space"
33
what is the reason for oral prednisolone contraindication in optic neuritis
only kills helper cells keeping memory cells alive which increases risk for increased # of attacks (LAs opposed to IV steroids)
34
MRI features of MS:
Character (4)
Location (5)
```
Character
- > 3 mm, Ovoid
- periventricular
- Perpendicular to ventricles
- Enhancing/ring enhancement -- Means ACTIVE
Location
- Multiple white matter
- Brainstem, infratentorial
- Juxtacortical
- Corpus callosum
- Moth eaten, Callosal atrophy
```
35
MS relapse: Acute neurologic episodes
Lasts ____
What is pseudorelapse?
Relapse- characteristic of MS
1. Lasting at least 24 hours in Absence of fever or metabolic derangement
2. Pseudorelapse is worsened symptoms in presence of fever/infection (if you increase temp of axons that's been denuded, conduction decreases)
3. All events within 30 days are unitary
36
Describe the 3 different patterns of MS
```
1. Relapsing - remitting
- Attacks with complete/incomplete recovery
- Stable between attacks
2. Primary progressive
- Gradual decline
- No attacks
3. Secondary - progressive
- Initially relapsing-remitting
- Then progression +/- attacks
```
37
```
Natural history of MS:
1. ____ % are RRMS; ____% are PPMS
2. ___% of RRMS develop SPMS within 10 yrs
____% RRMS develop SPMS eventually
____% never have a second relapse
____% lose ability to perform ADLs
```
```
Presentation
85% RRMS
15% PPMS
50% RRMS develop SPMS within 10y;
90% RRMS develop SPMS eventually
15% never have a second relapse
75% lose ADL
```
38
Name 4 "good" prognostic factors of MS
```
1. Female
2 Early age of onset
3. Initial RRMS with sporadic relapse
4. Presentation with ON/ sensory symptoms/
cranial neuropathy
```
39
Name the 4 "poor" prognostic factors of MS
1. Male
2 Older age at presentation
3. Progressive course at onset
4. Presentation with brainstem/pyramidal or cerebellar signs
40
5 management principles of MS
1. Treat acute relapses
2. Reduce relapse rates
3. Provide symptomatic management of fixed
neurological deficits
4. Prevent disability acquired through progression
5. Treat established progression.
41
Treating relapse with IV Methylpred x 3-5 days decreases what?
risk of another attack for next 3-5 months
(after progression of disease this wont matter
42
1. relapses of MS managed by
2. dose
3. How does it work?
4. benefit?
High dose steroids are mainstay
MP 1g/d x 3-5
Anti-inflammatory: inhibit transcription
proinflammatory cytokines (IL-1, IL- 2, TNF)
and proinflammatory enzymes
Reduce duration of relapses; do not affect
overall outcome or disease progression
43
____ is best medication for rapidly progressive
| 2nd?
1. Natalizumab - selectively locks to alpha interveron molecule preventing release into CNS. (associated with PML (JC virus) ("prevents adhesion and transmigratin")
2. Mitoxantrone
44
Treatment for primary progressive MS?
none
45
Three reasons to switch to mitoxantrone in MS therapy
drawback?
1. RR - accumulating disability while on interferon/copaxone)
2. rapidly progressing disability
3. secondary progressive disease
bad on heart
46
How does mitoxantrone work?
Type II topoisomerase inhibitor; it disrupts DNA synthesis and DNA repair in both healthy cells and cancer cells, by intercalation.
indicated for reducing neurologic disability and/or frequency of relapses. (also been seen to be used in prostate cancer and acute non-lymphocytic leukemia ANLL)
Cardiomyopathy is the bad effect due to being irreversible. Must monitor with regular echocardiograms or MUGA scans
47
```
Platform treatment for MS:
(Type, use, Injection, Administration, dose)
1. Avonex (Interferon B-1a)
2. Rebif (Interferon B-1a)
3. Betaseron (Interferon B-1b)
4. Copaxone (glatiramer acetate)
```
1. Recombinant protein, slow accumulation of disability, IM, weekly, 30ug
2. Recombinant protein, reduces frequency of relapses, SC, 3x/week, 22ug, 44ug
3. Recombinant protein, reduces frequency of relapses, SC, every other day, 0.25mg (8MIU)
4. Polypeptide mixture, reduce frequency of relapses, SC, daily, 20mg
48
Three major side effects of interferon-B with MS patient's
1. Flu-like symptoms
2. Injection-site reactions (SC > IM)
3. Changes in hepatic enzymes and/or
lymphocyte counts
49
2 side effects of glatiramer acetate in MS patients
1 Injection-site reactions
| 2 Systemic reactions
50
1. What is the immunomodulating agent used in MS?
2. What is it
3. Risk of ____
4. Binds to ____
1. Humanized IgG4k
2. Monoclonal antibody produced in murinemyeloma cells
3. Risk of PML
4. Binds to D4 integrin
51
Three approved oral medications for MS:
| Mechanism?
1. Fingolimod: Sphingosine 1 phosphate
analog
2. DMF/BG-12: apoptosis of activated T-cells
3. Laquinimod: mechanism unknown
52
5 types of symptom management in MS?
1. Cerebellar tremor Isoniazid, Benzodiazepines, Clonazepam, Surgery
2. Mood disorders: SSRI, Counseling,
3. Fatigue, Amantadine, Provigil, Methylphenidate, Antidepressants
4. Spasticity Baclofen (oral v pump), Tizanidine, Dantrolene, Botulinum toxin, Gabapentin, Diazepam, Physical therapy,
5. Bladder dysfunction Oxybutinin, Tofranil. Tolterodine tartrate, Straight catheterization, Culture and treat UTIs
