MS - Kedar Flashcards
Epidemiology of MS:
- Onset age:
- Female:male -
- Life expectancy
- Total lifetime cose:
- 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
MS Age adjusted risk percentages:
- Siblings:
- Parents:
- Children:
- Monozygotic twins
5: family recurrence rate:
Age-adjusted risk siblings (3%) parents (2%) children (2%) monozygotic twins 35%. Familial recurrence rate of 15%
Some say MS is related to what 4 thing?
?Latitude related ?Temperate climates ?Race related ?Region related
US prevalence of MS is:
US: prevalence is
0.1%~ 350,000
There is a possible prevalence in what area of US?
Northern states
- What is the pathologic hallmark of MS?
- affects what areas?
- sequelae?
- PLAQUE- axonal demyelination with relative preservation of axons
- Perivenular, periventricular white matter, brainstem and SC
3. Cerebral atrophy with ventricular dilatation
5 stages of pathogenesis for MS
- BBB disruption
- Activated T-cells
- Activate microglia
- Proinflammatory loop
- Myelin destruction
MS: Autoreactive T cell and B cells to myelin are usually held in check by ______.
Regulatory T cells
Regulatory T cells can be activated in MS pathology by what pathways?
- Infectious agent - (even EBV and chlamydia)
- Genetic predisposition
- environmental factors
3 potential triggers of MS
- Infectious agent-HTLV-1, HHV-6, EBV
2. Molecular mimicry
3. Exposure to CNS antigens- previous insult by injury/infection/disease
Demyelination shows what three things on EMG
Slows conduction
Blocked conduction
Temporal dispersion
(refractory period can become prolonged)
what is mechanical stimulation in MS? Caused by (2)
movement of axons that have lost their covering can give shock like sensation:
De-novo AP
Lhermitte phenomenon
what are examples of spontaneous action potentials in MS?
- Paroxysmal positive trigeminal neuralgia
- myokymia
- paraspinal muscle spasms
- photopsia
What are the top six presenting symptoms of MS? (with percentages)
Visual/oculomotor - 49 Paresis - 42 Paresthesias - 41 Incoordination - 23 Genitourinary/bowel - 10 Cerebral - 4
What percent of patient’s will have these symptoms during MS
- Visual/oculomotor
- Paresis
- Paresthesias
- Incoordination
- Genitourinary/bowel
- Cerebral
- 100
- 88
- 87
- 82
- 63
- 39
Charcot was the first to recognize what defecit in MS? percentage?
What 4 defecits are most commonly seen
Cognitive impairment - 35-65%
Patients with MS lose the ability to multitask
- Abstract conceptualization,
- recent memory,
- attention
- speed of processing
____% of MS patients have affective disturbance?
In what 3 ways?
66%
Depression (34% lifetime risk)
?association with bipolar disease
Pseudobulbar affect
correlated with MRI metrics of activity and progression
What is RIS in MS?
Radiologically isolated syndrome (RIS) - lesions consistently on scans without clinical s/s.
What is the deficit with pseudobulbar affect?
decreased conduction b/w cortex and cerebellum – emotional incontinence.
More cognitive impairment in patients with frontoparietal lesions.
5 notes on the management of MS?
Treat underlying disease Treat co-morbid psychiatric condition L-amphetamine (Morrow 2009) Modafinil Cholinesterase Inhibitors do not work
What is the lesion to the optic nerve in optic neuritis in MS
path?
relative afferent pupillary defect - usually unilateral; retrobulbar
Usually 2 week nadir with resolution at 4-6 weeks – if not: “atypical optic neuritis”
Optic Neuritis in MS is a _____ diagnosis:
1. presents as _____
2. Eye exam shows _____ (5)
3.
Clinical diagnosis
Acute/subacute d/v; retroorbital pain on EOM
Decreased acuity, color, contrast, RAPD
central/cecocentral scotoma
ONTT was a study in MS regarding what:
Methods
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
The ONTT study for MS showed what at 6 months?
Quicker recovery with IV steroids
Visual recovery excellent for ALL groups
INCREASED # of new attacks with oral
prednisolone alone
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)
According to ONTT:
- Those with Optic nueritis who convert to MS were _____ %.
- What % had normal MRI at baseline?
- What percent had abnormal MRI at baseline?
- 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.
What are the other CNs/pathology associated with MS
Ocular dysmotility INO Nystagmus Trigeminal neuralgia Facial myokymia, hemifacial spasm
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
Motor pathways associated with MS: (2)
Corticospinal tract dysfunction: paraparesis> upper extremity more common UMN signs of spasticity; hyerrelexia; clonus; extensor plantar reflex
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
MS patient’s:
1. Bladder - most common complaint? what about later stages?
2, Bowel: ___ more common
3. Sexual: ___%s
- Bladder - Commonest complaint is urgency from uninhibited detrusor contraction
Later stages- atonic dilated UB - Bowel Constipation more common
- Sexual - 50% completely inactive. 20% less active Multifactorial
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”
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)
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
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
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
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
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
Name the 4 “poor” prognostic factors of MS
- Male
2 Older age at presentation - Progressive course at onset
- Presentation with brainstem/pyramidal or cerebellar signs
5 management principles of MS
- 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.
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
- relapses of MS managed by
- dose
- How does it work?
- 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
____ is best medication for rapidly progressive
2nd?
- Natalizumab - selectively locks to alpha interveron molecule preventing release into CNS. (associated with PML (JC virus) (“prevents adhesion and transmigratin”)
- Mitoxantrone
Treatment for primary progressive MS?
none
Three reasons to switch to mitoxantrone in MS therapy
drawback?
- RR - accumulating disability while on interferon/copaxone)
- rapidly progressing disability
- secondary progressive disease
bad on heart
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
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)
- Recombinant protein, slow accumulation of disability, IM, weekly, 30ug
- Recombinant protein, reduces frequency of relapses, SC, 3x/week, 22ug, 44ug
- Recombinant protein, reduces frequency of relapses, SC, every other day, 0.25mg (8MIU)
- Polypeptide mixture, reduce frequency of relapses, SC, daily, 20mg
Three major side effects of interferon-B with MS patient’s
- Flu-like symptoms
- Injection-site reactions (SC > IM)
- Changes in hepatic enzymes and/or
lymphocyte counts
2 side effects of glatiramer acetate in MS patients
1 Injection-site reactions
2 Systemic reactions
- What is the immunomodulating agent used in MS?
- What is it
- Risk of ____
- Binds to ____
- Humanized IgG4k
- Monoclonal antibody produced in murinemyeloma cells
- Risk of PML
- Binds to D4 integrin
Three approved oral medications for MS:
Mechanism?
- Fingolimod: Sphingosine 1 phosphate
analog
2. DMF/BG-12: apoptosis of activated T-cells - Laquinimod: mechanism unknown
5 types of symptom management in MS?
- Cerebellar tremor Isoniazid, Benzodiazepines, Clonazepam, Surgery
- Mood disorders: SSRI, Counseling,
- Fatigue, Amantadine, Provigil, Methylphenidate, Antidepressants
- Spasticity Baclofen (oral v pump), Tizanidine, Dantrolene, Botulinum toxin, Gabapentin, Diazepam, Physical therapy,
- Bladder dysfunction Oxybutinin, Tofranil. Tolterodine tartrate, Straight catheterization, Culture and treat UTIs