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Neuro Rehab II > MS - Kedar > Flashcards

MS - Kedar Flashcards

1
Q

Epidemiology of MS:

  1. Onset age:
  2. Female:male -
  3. Life expectancy
  4. Total lifetime cose:
A
  1. Onset- 15- 45y; mean 30y
  2. Female>Male (~1.77:1)
  3. Life- expectancy decreased (58.1y vs 70.5y)
  4. Total lifetime cost/pt 1994: 2.5 million
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2
Q

MS Age adjusted risk percentages:

  1. Siblings:
  2. Parents:
  3. Children:
  4. Monozygotic twins
    5: family recurrence rate:
A 
Age-adjusted risk
„ siblings (3%)
„ parents (2%)
„ children (2%) 
„ monozygotic twins 35%. 
„ Familial recurrence rate of 15%
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3
Q

Some say MS is related to what 4 thing?

A 
?Latitude related
„ ?Temperate climates
„ ?Race related
„ ?Region related
„
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4
Q

US prevalence of MS is:

A

US: prevalence is

0.1%~ 350,000

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5
Q

There is a possible prevalence in what area of US?

A

Northern states

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6
Q
  1. What is the pathologic hallmark of MS?
  2. affects what areas?
  3. sequelae?
A
  1. PLAQUE- axonal demyelination with relative preservation of axons
  2. Perivenular, periventricular white matter, brainstem and SC
    „3. Cerebral atrophy with ventricular dilatation
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7
Q

5 stages of pathogenesis for MS

A
  1. BBB disruption
  2. Activated T-cells
  3. Activate microglia
  4. Proinflammatory loop
  5. Myelin destruction
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8
Q

MS: Autoreactive T cell and B cells to myelin are usually held in check by ______.

A

Regulatory T cells

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9
Q

Regulatory T cells can be activated in MS pathology by what pathways?

A
  1. Infectious agent - (even EBV and chlamydia)
  2. Genetic predisposition
  3. environmental factors
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10
Q

3 potential triggers of MS

A
  1. Infectious agent-HTLV-1, HHV-6, EBV
    2.„ Molecular mimicry
    „3. Exposure to CNS antigens- previous insult by injury/infection/disease
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11
Q

Demyelination shows what three things on EMG

A

Slows conduction
„ Blocked conduction
„ Temporal dispersion

(refractory period can become prolonged)

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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

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13
Q

what are examples of spontaneous action potentials in MS?

A
  1. Paroxysmal positive trigeminal neuralgia
  2. myokymia
  3. paraspinal muscle spasms
  4. photopsia
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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
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15
Q

What percent of patient’s will have these symptoms during MS

  1. Visual/oculomotor
  2. Paresis
  3. Paresthesias
  4. Incoordination
  5. Genitourinary/bowel
  6. Cerebral
A
  1. 100
  2. 88
  3. 87
  4. 82
  5. 63
  6. 39
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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

  1. Abstract conceptualization,
  2. recent memory,
  3. attention
  4. speed of processing
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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

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18
Q

What is RIS in MS?

A

Radiologically isolated syndrome (RIS) - lesions consistently on scans without clinical s/s.

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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.

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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
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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
Q

ONTT results at 15 years in MS patients

A 
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
Q

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.
A 
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
Q

What are the other CNs/pathology associated with MS

A 
Ocular dysmotility
„          INO
„          Nystagmus
„ Trigeminal neuralgia
„ Facial myokymia, hemifacial spasm
28
Q

Sensory pathways associated with MS: (3)

A

ALS system- pain/temp/light touch
„ Dorsal column- jt. Position/vibratory
„ Dorsal root entry zone- band like
sensation in thoraco-abdominal area

29
Q

Motor pathways associated with MS: (2)

A 
Corticospinal tract dysfunction: 
paraparesis> upper extremity more 
common
„ UMN signs of spasticity; hyerrelexia; 
clonus; extensor plantar reflex
30
Q

Name the cerebellar abnormalities in MS (8)

A 
1. Gait imbalance
„2. Dysarthria- usually scanning speech
3. Dysmetria, 
4. dysdiadochokinesia, 
5. rebound phenomenon, 
6. truncal ataxia; 
7. EOM abnormalities; 
8. nystagmus
31
Q

MS patient’s:
1. Bladder - most common complaint? what about later stages?
2, Bowel: ___ more common
3. Sexual: ___%s

A
  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
Q

How is MS diagnosed?

A

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
Q

what is the reason for oral prednisolone contraindication in optic neuritis

A

only kills helper cells keeping memory cells alive which increases risk for increased # of attacks (LAs opposed to IV steroids)

34
Q

MRI features of MS:
Character (4)
Location (5)

A 
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
Q

MS relapse: Acute neurologic episodes
Lasts ____
What is pseudorelapse?

A

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
Q

Describe the 3 different patterns of MS

A 
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
Q 
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
A 
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
Q

Name 4 “good” prognostic factors of MS

A 
1. „ Female
2„ Early age of onset
„3.  Initial RRMS with sporadic relapse
„4.  Presentation with ON/ sensory symptoms/ 
cranial neuropathy
39
Q

Name the 4 “poor” prognostic factors of MS

A
  1. „ Male
    2 „ Older age at presentation
  2. „ Progressive course at onset
  3. „ Presentation with brainstem/pyramidal or cerebellar signs
40
Q

5 management principles of MS

A
  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
Q

Treating relapse with IV Methylpred x 3-5 days decreases what?

A

risk of another attack for next 3-5 months

(after progression of disease this wont matter

42
Q
  1. relapses of MS managed by
  2. dose
  3. How does it work?
  4. benefit?
A

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
Q

____ is best medication for rapidly progressive

2nd?

A
  1. Natalizumab - selectively locks to alpha interveron molecule preventing release into CNS. (associated with PML (JC virus) (“prevents adhesion and transmigratin”)
  2. Mitoxantrone
44
Q

Treatment for primary progressive MS?

A

none

45
Q

Three reasons to switch to mitoxantrone in MS therapy

drawback?

A
  1. RR - accumulating disability while on interferon/copaxone)
  2. rapidly progressing disability
  3. secondary progressive disease

bad on heart

46
Q

How does mitoxantrone work?

A

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
Q 
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)
A
  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
Q

Three major side effects of interferon-B with MS patient’s

A
  1. Flu-like symptoms
  2. Injection-site reactions (SC > IM)
  3. Changes in hepatic enzymes and/or
    lymphocyte counts
49
Q

2 side effects of glatiramer acetate in MS patients

A

1 Injection-site reactions

2 Systemic reactions

50
Q
  1. What is the immunomodulating agent used in MS?
  2. What is it
  3. Risk of ____
  4. Binds to ____
A
  1. Humanized IgG4k
  2. Monoclonal antibody produced in murinemyeloma cells
  3. „ Risk of PML
  4. „ Binds to D4 integrin
51
Q

Three approved oral medications for MS:

Mechanism?

A
  1. Fingolimod: Sphingosine 1 phosphate
    analog
    2.„ DMF/BG-12: apoptosis of activated T-cells
  2. „ Laquinimod: mechanism unknown
52
Q

5 types of symptom management in MS?

A
  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

Neuro Rehab II (6 decks)

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