Multiple Sclerosis

Front 1

- 30-80 per 100,000 population;
- 250,000-500,000 individuals affected with the diseaes in the US

Back 1

Incidence of MS

Front 2

- One of the most common causes of neurologic disability in young adults

Back 2

MS

Front 3

Affects mainly young adults between ages of 20-40; mean age of onset is 31
- Twice as common in women than in men

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MS

Front 4

Lapps in Scandiavia; Native Americans and Alaskin Inuit in North America; Asians; African Blacks; white populations are at a greater risk than Asian or African

Back 4

Populations that rarely suffer from MS

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The farther one travels from the earth's equator, the more cases of ____ per capita. Great Britain, Scandinavia, and Canada have 3 of the highest rates in the world

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MS - Geographic distribution

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The location where a person spends the first ___ years of life determines a greater or lesser likelihood of developing MS as opposed to where they live at the time of diagnosis

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1st 15 years of life

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Faroe Islands (Denmark) after they were occupied by British troops in WW II; Shetland Orkney Island, Iceland, and Sardinia

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MS Epidemics

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Approximately ___% of patiens with MS have another family member with MS

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20% with another family member with MS

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Identical twin of someone with MS is __ - __% increasd risk;

Back 9

25-35% increased risk between identical twins

Front 10

First degree relative (child or sibling) is at a ___% increased risk of developing MS

Back 10

5% increased risk between first degree relatives.

Front 11

this compenent of chomosome 6 is implicated in MS; after 1 attack of optic neuritis if ____ is found, the likelihood of having a second attrack in 5 years increases 2 fold

Back 11

Human Leukocyte Antigen (HLA-DR2)

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- Dissemination in Time
- Dissemination in Space
- No other explanation for the attacks or the symptoms the person is experiencing

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(McDonald) Criteria for Clinical Diagnosis of MS (Polman et al, 2005)

Front 13

occurrence of two or more distinct attacks

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Dissemination in Time

Front 14

Objective clinical evidence of two or more lesions in separate locations within the myelinated regions of the CNS (ie. cerebral white matter, brain stem, cerebellar tracts, optic nerves, spinal cord)

Back 14

Dissemination in Space

Front 15

Indicate nerve conduction dysfunction due to MS demyelination

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Evoked Potentials

Front 16

The patient sits before a screen on which an alternating checkerboard pattern is displayed

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Visual Evoked Potentials (VEP)

Front 17

The patient hears a series of clicks in each ear

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Brainstem Auditory Evoked Potentials (BAEP)

Front 18

Short electrical impulses are administered to an arm or leg

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Sensory Evoked Potentials (SEP)

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- Mildly elevated WBC count
- Elevated immunoglobulin G (IgG) compared to blood. (IgG functions as antibody in the immune response)
- 2 or more unique oligoclonal bands (represent antibodies) by ___ protein electrophoresis

Back 19

CSF Analysis Abnormalities in MS

Front 20

- One of the most important diagnostic tests
- detect plaques throughout CNS caused by myelin destruction, as well as cerebral and spinal cord atrophy
- Demyelinating lesions can affect any structure in the CNS

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MRI Imaging for MS

Front 21

Exposure to a ____ in a genetically susceptible individual or within a critical time period in development (0-15 yrs) may cause MS, with acute attacks relating to a reactivation of a latent infection

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Possible Etiology of MS: Infectious Agent

Front 22

- Epstein-Barr Virus (EBV)
- Human Herpese Virus 6 (HHV-6)
- Chlamydia pneumoniae bacterium

Back 22

Infectious Agents possibly implicated in MS Etiology

Front 23

- A demylinating disease of the CNS that is induced in laboratory nimals by subcutaneous injection of myelin peoptide antigens (myelin basic protein (MBP))
- Serves as an animal model for MS
- Much of our current knowledge about the pathology and immunology of MS has been gained from studies of animals with ____

Back 23

Experimental Allerigic Encephalomyelitis (EAE)

Front 24

Activated T-Helper cells enter the CNS and cause a cascade of events that initiate an immune response that stimulates
- Macrophages and microglia
- B cells

Back 24

Cell-Mediated Autoimmunity in MS

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- Stimulated by T Helper cells involved in cell-mediated autoimmunity in MS
- produce pro-inflammatory molecules that attack oligodendrocytes and myelin

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Macrophages and Microglia involved in Cell-Mediated Autoimmunity in MS

Front 26

- Activated by T Helper cells involved in cell-mediated autoimmunity in MS
- produce autoantibodies against myelin proteins

Back 26

B Cells involved in cell-mediated autoimmunity in MS

Front 27

Demyelination slows neural transmission and causes nerves to fatigue rapidly. With severe disruption, conduction block occurs. As the disease progresses, the axons themselves are damaged.
- Possible to regain some function via 1) axonal plasticity or 2) some remyelination by other oligodendrocytes, but will eventually lose it as axons degenerate

Back 27

MS Pathology

Front 28

Demylinated areas become filled with fibrous astrocytes that form glial scars called ____.
- Areas commonly affected include optic nerve, subcortical (especially periventricular white matter); corticospinal tracts, dorsal columns of the spinal cord, and cerebellar peduncles

Back 28

MS Plaques

Front 29

- Sensory Sx arms/legs = 33%
- Unilateral vision loss = 16%
- Polysymptoomatic onset = 14%
- Slowly progressing motor deficit = 9%
- Acute motor deficit = 5%
- Diplopia = 7%
- Other = 16%

Back 29

Symptoms at MS Onset

Front 30

- One of the most common initial symptoms of MS and presents unilaterally in 70% of cases
- Pt reports "cellphane in eye" or complete patchiness in vision, fading out of vision, or visual loss

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Optic Neuritis in MS

Front 31

UMN - Spasticity; Hypertonicity; Exaggerated Reflexes; Involuntary spasms

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MS Motor Impairments

Front 32

Paresthesias; Numbness
Impaired position sense; impaired vibratory sense
Pain – dysesthesias; Trigeminal neuralgia
Hypersensitivity; Lhermitte’s sign

Back 32

MS Sensory Impairments

Front 33

Dysphagia;
Dysarthria - scanning speech

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MS Impairments related to brainstem lesion

Front 34

Ataxia - dysmetria; dyssynergia; dysdiadochokinesia
Postural tremor; Intention tremor; Hypotonia
Truncal weakness; Dizziness; vertigo

Back 34

MS impairments related to cerebellar lesion

Front 35

Respiratory muscle weakness; respiratory muscle dyssynergia

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MS Respiratory Impairments

Front 36

Memory, attention, concentration, learning, reasoning, information processing, executive function
Depression; Euphoria; Emotional dysregulation

Back 36

MS Cogitive and Psychological Impairments

Front 37

Frequency, urgency, nocturia, incontinence

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MS Bowel and Bladder Impairments

Front 38

Thermal Regulation; Sexual Dysfunction
Autonomic Nervous System Dysfunction

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MS Misc. Impairments

Front 39

Muscle weakness; Fatigue; deconditioning; impaired mobility

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MS Secondary/Composite Impairments

Front 40

___% of MS patients are sensitive to changes in core body temperature, from both external (environment) and internal (vigorous exercise) sources
- Uhthoff symptoms/phenomenon
- Guthrie and Neslon's Neuroblockade Hypothesis

Back 40

Heat Intolerance

Front 41

Increase or presence of neurological symptoms in response to a heating condition. Change in bodyd temperatue that elicits signs range from 0.18-4.14 degrees F.

Back 41

Uhthoff Symptom/Phenomenon

Front 42

A rise in temperature decreases nerve conduction in demyelinated fibers; the greater the degree of demyelination, the greater the conduction loss. Action potential voltage not able to jump across demyelinated regions

Back 42

Guthrie and Nelson's Neuroblockade Hypothesis for Heat Intolerance in MS

Front 43

Fatigue is reported by ___ - ___% of patients with MS

Back 43

75-97%

Front 44

For MS patients, ____ is:
- their worst or one of their worst symptoms
- interferes with physical functioning, comes on easily, adn causes frequent problems
- Severity not correlated with level of neurological involvement and appears to be a distinct symptom from depression

Back 44

Fatigue

Front 45

___ in MS is related to:
- Physical health - comorbid conitions, iatrogenic causes;
- Sleep Disorders
- Normal ____
- Psychological Health - anxiety, stress, depression, other;
- Environmental Conditions - physical, social, institutional, cultural;
- MS - Primary, Secondary (disability, deconditioning), pain

Back 45

Causes of Fatigue in MS

Front 46

Increased Central Fatigue adn Decreased efficiency of motor unit activation

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Factors contributing to Primary Fatigue in patients with MS

Front 47

Intermittent failure of motor pathways in the brain and spinal cord during rapid activity due to the presence of demyelinated plaque

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Increased Central Fatigue in MS contibutes to Primary Fatigue

Front 48

- Decreased oxidative capacity
- Slowing of muscle contractile properties
- Lower tetanic and twitch tension in muscles
- Decrease in number of slow-twitch (Type 1) oxidative fibers

Back 48

Decreased Efficiency of Motor Unit Activation in MS contributes to Primary Fatigue

Front 49

Some people with MS may experience abnormal HR and BP responses to exercise, but the data is not conclusive.
- Abnormalities may be related to the disease progression (tend to be found in pts who are more impaired)
- Abnormal HR and BP in response to exercise probably represent evidence of lesions located on or near the neurons involved in autonomic cardiovascular function

Back 49

Autonomic Nervous System Dysfunction in MS

Front 50

- Benign
- Relapsing-Remitting Multiple Sclerosis (RRMS)
- Secondary-Progressive Multiple Sclerosis (SPMS)
- Progressive-Relapsing Multiple Sclerosis (PRMS)
- Primary-Progressive Multiple Sclerosis (PPMS)
- Malignant or Fulminant Multiple Sclerosis

Back 50

Types of MS

Front 51

Few attacks adn littler or no disability after 20 years
- rare form

Back 51

Benign MS

Front 52

Symptom flare-ups followed by recovery; stable between attacks
- most common

Back 52

Relasing-Remitting MS
(RRMS)

Front 53

Second phase of RRMS;
Progressive worsening of symptoms with or without superimposed relapses; treatments may delay or prevent this phase

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Secondary-Progressive MS (SPMS)

Front 54

Progressiv course from the onset, sometimes combined with occasional acute symptom flare-ups

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Progressive-Relapsing MS
(PRMS)

Front 55

Gradual but steady accumulation of neurological proglems from onset

Back 55

Primary-Progressive MS (PPMS)

Front 56

Rapidly progressive diseaes course

Back 56

Malignant or Fulminant MS

Front 57

- 80% of individuals with MS start as ____; women 3x more likely to be diagnosed than men
- Temporary symptom flare-ups or "exacerbations" typically last 1-3 months, followed by remssions (complete or partial recovery)
- Common initial symptoms: Sensory disturbances, optic neuritis, diplopia

Back 57

Relapsing-Remitting MS
(RRMS)

Front 58

- Sensory Disturbances (numbness or tingling)
- Optic Neuritis (inflammation fo the optic nerve with visual change or loss, usually in one eye
- Diplopia (double vision)

Back 58

Common Initial Symptoms of Relapsing-Remitting MS
(RRMS)

Front 59

If untreated, >90% of individuals with RRMS may enter a second phase called ____ within 6-10 years.
- Characterized by progressive worsening of symptoms with or without relapses

Back 59

Secondary-Progressive MS
(SPMS)

Front 60

- 20% of all individuals with MS have this type; equally distributed between genders
- Steady accumulation of neurological problems from onset, without relapses or remissions

Back 60

Primary-Progressive MS
(PPMS)

Front 61

Life expectancy for people with MS is usually at least ____ years from disease onset

Back 61

25 years

Front 62

- Onset with only one symptom
- Benign and RRMS (drugs can help in this phase)

Back 62

Better Prognosis

Front 63

- Progressive (chronic) MS
- Onset after 40, especially males
- Significant pyramidal adn cerebellar signs with involvement at multiple sites at 5 years after diagnosis
- African Americans

Back 63

Worse Prognosis

Front 64

-Kurtzke Functional Systems Scores (FSS)
- Kurtzke Expanded Disability Status Scale (EDSS)

Back 64

Common Outcome Measures for MS

Front 65

Acute physical symptoms and neurological signs present for at least 24 hours, without any signs of infection

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Relapse

Front 66

Temporary worsening of symptoms (no myelin inflammation or damage) due to external influences (ie. infection, exhaustion, heat, depression, stress)

Back 66

Pseudoexacerbation

Front 67

Exacerbations treated with a high-dose, short-term course of ____

Back 67

Tx for Exacerbations:
Corticosteroids (IV Methylprednisolone then oral prednisone)

Front 68

- Rx for RRMS
- interferon beta-1b (immune system modulator with antiviral properties)
- Side Effects - flu-like symptoms, skin reaction
- Subcutaneous injections every other day

Back 68

Betaseron

Front 69

- Rx for RRMS
- Interferon beta-1a (immune system modulator with antiviral properties)
- Side Effects - Flu-like symptoms, HA
- Intramuscular injections weekly

Back 69

Avonex

Front 70

- Interferon beta-1a; (immune system modulator with antiviral properties) (Same drug as Avonex, but injected differently and in more frequent and higher doses)
- Side Effects - Flu-like symptoms, skin reaction
- Subcutaneous injections 3x/week
- Flu-like

Back 70

Rebif

Front 71

- Rx for RRMS
- Glatiramer Acetate - synthetic chain of 4 amino acids found in myelin (immune system modulator that blocks attacks on myelin)
- Side Effects - injection-site reaction as well as occasional systemic reaction
- Subcutaneous injections daily

Back 71

Copaxone

Front 72

- Rx for RRMS and SPMS
- can cause heart damage
- Antineoplastic agenet (immune system modulator and suppressor)
- Side Effects - Nausea, thinning hair, cardiotoxicity beyond 3 yrs. use
- IV infusion once every 3 months (2-3 years max.)

Back 72

Novantrone (Mitoxantrone)

Front 73

Large trials of long-term ___ use have shown that they:
- Reduce the number and severity of relapses
- Reduce the develoopment of new areas of inflammation as seen on MRI
- Delay progression of disability

Back 73

Drug Effects on MS

Front 74

- Amantadine (Symmetrel) - DA agonist
- Methylphenidate (Ritalin)
- Dextroamphetamine (Dexedrine)
- Provigil (modafinil) - norepinephrine agnonist - study showed that 9-wk tx significantly improved scores on each of the the 3 ___ assessment scales in 72 pts aged 18-65 with a dx of MS

Back 74

Treatment of Fatigue

Front 75

Research studies on the effect of ______ on pts with MS have shown:
- Increased ability to perform repetative activities
- Improvements in cognitive processing
- Improved motor function in 10 out of 14 ambulatory patients and six patients in wheelchairs

Back 75

Clinical studies on Liquid Cooling

Front 76

High level evidence that ____ is effective in improving strength and endurance, self-efficacy, and quality of life in pts with MS

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Exercise

Front 77

- Dr. Caroline Whitacre (OSU) recently found that blocking _____ might prevent progrsssion of MS
(women who are pregnant don't experience exacerbations)

Back 77

Macrophage Migration Inhibitory Factor (MIF)