Multiple sclerosis

Question 1

Quickly describe some of the etiology of MS?

Answer 1

Nearly 1 million people are living with MS in the US (2019 estimate)
Increasing?
Onset typically occurs between ages of 20 and 40
Immune response to EBV?
Women: 2-3x more common
Hormone-related?
Whites >African Americans >Hispanic >Asian/Native Americans
Genetic susceptibility? Immune system vulnerability?
Missing data?
Higher latitudes
Less sun exposure, Vitamin D?
45°−65°N

Question 2

Describe why the top half of the US tends to see more case of MS? or at least the theory for why!

Answer 2

the top half of the US has decreased Vitamin D intake leading to a vitamin D deficiency

Question 3

briefly describe MS?

Answer 3

Chronic inflammatory demyelinating disease of the CNS (anywhere!)
Immune-mediated disease (Autoimmune disease )
Cellular, molecular, and metabolic mechanisms of neuroaxonal damage
Slowing and blocking of saltatory conduction of action potentials
Significant symptom variability and unpredictability

Question 4

what is the current thought for the etiology of MS?

Answer 4

Primary etiology is unknown

Current Thought: interaction between genetic predisposition and an inciting environmental antigen produces an autoimmune demyelinating response in a susceptible host

MS is not hereditary but having a parent or sibling with MS significantly increases the risk of developing the disease
15% of pwMS have (+) family history
Increased risk if a family member has MS
If 1st degree relative: 1/100 risk
If twin: 1/4 risk

Question 5

what are three ongoing research field for MS?

Answer 5

immunology, epidemiology, genetics

Question 6

what is being studied in research for immunology factors of MS?

Answer 6

Abnormal immune-mediated response that attacks myelin (T and B cells)

Question 7

what are the environmental factors being researched for MS?

Answer 7

igh risk in areas far from equator (role of Vitamin D), Smoking, Obesity

Question 8

what are the infection factors being researched for MS?

Answer 8

Under investigation - measles, canine distemper, human herpes virus-6, Epstein-Barr, Chlamydia pneumonia

Question 9

what is the mechanism of injury for MS?

Answer 9

non resolving inflammation leads to neurodegeneration leading to failure of compensatory mechanisms leading to remylenation or neuroplasticity

Question 10

Diving deeper what is the pathophysiology of inflammation seen in MS?

Answer 10

Cytotoxic T-cells and macrophages attack and destroy the myelin

Leads to inflammation 

Mass effect of edema can lead to further damage
Controlling edema through steroids can limit the damage of MS attacks

Question 11

what is the pathophysiology of the blood brain barrier in MS?

Answer 11

BBB becomes more permeable
Antibodies and immune cells get easier access to CNS myelin
CNS myelin is wrongly identified as foreign substance and attacked
Resulting demyelination causes slowing of the neural transmission, rapid nerve fatigue, and conduction block

Question 12

what role do oligodendrocytes cause in the demyelination process of MS?

Answer 12

Destruction of oligodendrocytes
Provide support and insulation to axons in CNS
Oligodendrocytes count among the most vulnerable cells of the CNS, due to complex cell production process
Assemble myelin, enable fast saltatory impulse propagation
Axonal loss

Question 13

throughout the disease progression of MS what does demyelination look like? what measure is used to view the plaque formation?

Answer 13

Remyelination can occur in early stages
Restores nerve conduction integrity
Becomes less effective over time
Later Stages: myelin replaced by fibrous scarring called gliosis, which destroys the axons
Inhibits all transmission of impulses
Fibrous Astrocytes
Glial scars/plaques
MRI used to visualize plaque formation
Does not always correlate with clinical disability (similar to vertebral imaging related to clinical expression)

Question 14

How is MS diagnosed?

Answer 14

There is no single diagnostic test
Process of ruling out and confirming
Neurologist exam
Common neuroimaging and medical tests:
MRI scans of CNS – looking for lesions/plaques
Lumbar puncture – CSF analysis of characteristic proteins and inflammatory cells
Evoked potential tests – measure nerve conduction
Blood tests

Question 15

what does an MRI of the MS demylination show?

Answer 15

highly sensitive for detecting MS plaques in white matter

Question 16

what does a lumbar puncture for MS look at?

Answer 16

increased WBC’s: higher in MS but may also be higher if there are infections

Neurofilaments: components of myelin and may indicate myelin is under attack

Oligoclonal Bands: antibodies produced by the immune system that attack myelin. These antibodies bunch together and form visible bands. These bands may also be higher in other degenerative conditions so should not be used as a stand-alone measure.

Question 17

what is a evoked potential test look at in a patient with MS?

Answer 17

Record how quickly the nerve signals reach the brain

May indicate problems along the nerve pathways that are subtle and not visible on an MRI or during neurological examination

Question 18

what does a blood test look at for a patient with MS?

Answer 18

Rule out other diagnosis that can present like MS such as infections and vitamin deficiencies

Question 19

what is transverse myelitis? why is it important to MS? what stage of transverse myelitis is more indicative of MS? what are some potential causes?

Answer 19

Inflammation on both sides of spinal cord
Myelin destruction scar formation slowed conduction

May be first symptom of MS

Increases risk of developing MS
15-80% will convert

Less likely if TM is severe rather than mild

1400 new cases in US each year
Potential causes: viral, bacterial, cancers

Question 20

what are the differential diagnosis that mimic MS?

Question 21

According to the McDonalds Criteria how is someone diagnosed with MS?

Answer 21

Made by Neurologist
Use of:
Medical Hx
Neurological examination
Laboratory tests- MRI gold standard
Ruling out other diagnoses
Evidence of damage in two separate areas of the CNS and damage must have occurred at two separate times at least 1 month apart

Question 22

Based off the McDonalds Criteria a patient has had two attacks and has 2 or more lesion what additional criteria do you need for diagnosis

Answer 22

none. clinical evidence alone will suffice

Question 23

Based off the McDonalds Criteria a patient has had two attacks and has 1 lesion what additional criteria do you need for diagnosis

Answer 23

dissemination in space on MR or await another attack

Question 24

Based off the McDonalds Criteria a patient has had 1 attack and has 2 lesion what additional criteria do you need for diagnosis

Answer 24

Dissemination in time on MR or awaits clinical attack implicating a different CNS site

Question 25

Based off the McDonalds Criteria a patient has had 1 attack and has 1 lesion what additional criteria do you need for diagnosis

Answer 25

dissemination in space and time

Question 26

Based off the McDonalds Criteria a patient has had 0 attack and lesions what additional criteria do you need for diagnosis

Answer 26

one year of disease progression and at least two of three criteria 1) dissemination in space in the brain 2) dissemination in space in the spinal cord based on 2 or more t2 lesions 3) postive CSF

Question 27

what is the life expetancy for patients with MS? what are the common co mobidities?

Answer 27

Life Expectancy 77.2 years for women, 72.2 years for men 77.8 years for patients with RR and 71.4 years for patients with PP Death due to MS Pneumonia- commonly due to aspiration Infections- decubitus ulcers, UTIs, URIs Falls Suicide Heart disease

Question 28

what do the activity and participation restrictions for a patient with MS?

Answer 28

15 years post dx: 20% bed-ridden; 20% will require the use of an assistive device for ambulation; 60% fully ambulatory 1/3 of people with MS go through life without any persistent disability

Question 29

what is a factors that lead to a good prognosis of MS?

Answer 29

young female sex onset with optic neuritis or an isolated sensory symptom full recovery from attack long interval to second relapse no disability after 5 years normal MRI/ low lesion load no posterior fossa lessions

Question 30

what is a factors that lead to a good prognosis of MS?

Answer 30

older age of onset male sex multifocal onset efferent system affected high relapse rate in the first 2-5 years substantial disability after 5 years abnormal MRI with large sessions loss posterior fossa lessions posible genomic factors

Question 31

what are the subtypes of MS?

Answer 31

Clinically Isolated Syndrome Early MS sign, but may not develop MS Relapsing-remitting (RRMS) (85%) Secondary progressive (SPMS) Decreased relapse/remit ~10-20 years after RRMS dx Progression-Relapsing (5%) Primary/Chronic progressive (PPMS) (10-15%) Attacks not well-defined Benign – “Inactive MS” Fulminant – “malignant MS”, rapid

Question 32

Describe the sub type of Relapsing-Remitting?

Answer 32

Episodes of rapid, abrupt deterioration with variable degrees of recovery over time Periods of deterioration are called relapses, flares, or exacerbations

Question 33

Describe the sub type of Secondary Progressive?

Answer 33

Begins as relapsing-remitting, then transitions into 2° progressive

Question 34

Describe the sub type of Primary Progressive?

Answer 34

Steady progressive deterioration Pace of deterioration can vary

Question 35

Describe the sub type of Progression-Relapsing

Answer 35

Relapses with a large degree of residual impairment Relapses of greater or lesser severity with no plateaus Also known as exacerbating-progressive

Question 36

Describe the sub type of benign

Answer 36

Occasional symptoms without significant functional impairment

Question 37

Describe the sub type of Fulminant (Marburg)?

Answer 37

Rapidly progressive, death may occur in a few weeks Leading to early, severe disability, and death

Question 38

what are the signs and symptoms of a lesion that occurs in the cerebrum and cerebellum?

Answer 38

balance problems, speech problems, co-ordination, tremors

Question 39

what are the signs and symptoms of a lesion that occurs in the motor nerve tracts?

Answer 39

muscle weakness, spasticity, paralysis, vision problems, bladder, bowel problems

Question 40

what are the signs and symptoms of a lesion that occurs in the sensory nerve tract?

Answer 40

altered sensation, numbness, pricklin, burning sensation

Question 41

what are the primary signs and symptoms commonly seen?

Answer 41

Fatigue 83.1% Heat sensitivity 80 Difficulty with walking/balance 67.2 Stiffness/spasms 63.1 Bladder problems 59.8 Memory and other cognitive problems 55.8 Pain and sensory problems 54.3 Emotional and mood problems 37.5 Vision problems 37.4

Question 42

what is the definition of MS fatigue?

Answer 42

MS fatigue: “...significant lack of physical and/or mental energy that is perceived by the individual or caretaker to interfere with usual or desired activity...” Studies show up to 97% prevalence Burdens: QoL and economic impact Major impact on ADLs, exercise, activity, employment, social participation

Question 43

what is the primary and secondary cause of MS?

Answer 43

Primary cause- due to disease Secondary cause- due to deconditioning

Question 44

what are the primary disease mechanisms of fatigue in ms?

Answer 44

Primary Disease mechanisms: 1. structural damage of white matter/grey matter (e.g. axonal loss) 2. inflammatory processes 3.maladaptive network recruitment during task performance 4. metacognitive interpretations of brain states that suggest ‘helplessness’

Question 45

what are the primary symptoms of fatigue?

Answer 45

active inflammation in brain/spinal cords cytokines released during inflammatory processes neuroendocrine processes due to hypothalamic dysfunction autonomic impairments excess metabolic work of brain due to activation of additional cortical areas to performs tasks abnormalities in cortical-subcortical networks mediated by thalamic lesions

Question 46

what are possible secondary symptoms of fatigue in MS?

Answer 46

sleep disturbances due to pain and spasticity undiagnosed sleep disorders depression inactivity and reconditioning side effects of disease-modifying therapies side effects of symptomatic therapy

Question 47

what is the difference of fatigue and fatiguability?

Answer 47

In neurological patients: fatigue is characterized as a symptom (subjective sensations) fatigability indicates how quickly a specific level of fatigue is achieved, a measure (sign) of physical/mental work capacity (objective performance)

Question 48

when specifically talking about Multiple sclerosis what does fatiguability mean in this population?

Answer 48

Fatigability: a (“vital”) sign Measurable change in physical performance after sustained or repeated use Specific motion, task, or body part that objectively worsens in performance over time PT role (assessment, education, OM, etc.) Associated signs: reduced gait speed, progressive weakness, worsening sensation/vision/speech, decreased quality with repetition

Question 49

what are the two scales that can be used for fatiguability and MS?

Answer 49

Modified-Fatigue Impact Scale (MFIS): comprehensive measurement for research and clinical practice 21-item questionnaire https://www.sralab.org/sites/default/files/2017-06/mfis.pdf subscales: physical, cognitive, psychosocial Fatigue Severity Scale (FSS): screening tool for fatigue (subjective) 9-item questionnaire https://www.sralab.org/rehabilitation-measures/fatigue-severity-scale 5-minute admin Excellent psychometric properties (e.g. reliability, responsiveness) No significant ceiling or floor effects High clinical utility

Question 51

what is the Uhthoff’s phenomenon noticed in patients with MS?

Answer 51

occurs in 60–80% of MS patients increases in core body temperature as little as ~ 0.5°C (~1℉) can trigger temporary symptoms worsening generally triggered by exposure to warm environment, hot baths/tubs, saunas, fever, or exercise lasts until core temperature returns to baseline values (~97.7 – 98.6℉)...less than 24 hours