Multiple sclerosis Flashcards
Quickly describe some of the etiology of MS?
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
Describe why the top half of the US tends to see more case of MS? or at least the theory for why!
the top half of the US has decreased Vitamin D intake leading to a vitamin D deficiency
briefly describe MS?
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
what is the current thought for the etiology of MS?
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
what are three ongoing research field for MS?
immunology, epidemiology, genetics
what is being studied in research for immunology factors of MS?
Abnormal immune-mediated response that attacks myelin (T and B cells)
what are the environmental factors being researched for MS?
igh risk in areas far from equator (role of Vitamin D), Smoking, Obesity
what are the infection factors being researched for MS?
Under investigation - measles, canine distemper, human herpes virus-6, Epstein-Barr, Chlamydia pneumonia
what is the mechanism of injury for MS?
non resolving inflammation leads to neurodegeneration leading to failure of compensatory mechanisms leading to remylenation or neuroplasticity
Diving deeper what is the pathophysiology of inflammation seen in MS?
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
what is the pathophysiology of the blood brain barrier in MS?
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
what role do oligodendrocytes cause in the demyelination process of MS?
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
throughout the disease progression of MS what does demyelination look like? what measure is used to view the plaque formation?
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)
How is MS diagnosed?
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
what does an MRI of the MS demylination show?
highly sensitive for detecting MS plaques in white matter
what does a lumbar puncture for MS look at?
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.
what is a evoked potential test look at in a patient with MS?
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
what does a blood test look at for a patient with MS?
Rule out other diagnosis that can present like MS such as infections and vitamin deficiencies
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?
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
what are the differential diagnosis that mimic MS?
According to the McDonalds Criteria how is someone diagnosed with MS?
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
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
none. clinical evidence alone will suffice
Based off the McDonalds Criteria a patient has had two attacks and has 1 lesion what additional criteria do you need for diagnosis
dissemination in space on MR or await another attack
Based off the McDonalds Criteria a patient has had 1 attack and has 2 lesion what additional criteria do you need for diagnosis
Dissemination in time on MR or awaits clinical attack implicating a different CNS site
Based off the McDonalds Criteria a patient has had 1 attack and has 1 lesion what additional criteria do you need for diagnosis
dissemination in space and time
Based off the McDonalds Criteria a patient has had 0 attack and lesions what additional criteria do you need for diagnosis
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
what is the life expetancy for patients with MS? what are the common co mobidities?
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
what do the activity and participation restrictions for a patient with MS?
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
what is a factors that lead to a good prognosis of MS?
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
what is a factors that lead to a good prognosis of MS?
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
what are the subtypes of MS?
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
Describe the sub type of Relapsing-Remitting?
Episodes of rapid, abrupt deterioration with variable degrees of recovery over time
Periods of deterioration are called relapses, flares, or exacerbations
Describe the sub type of Secondary Progressive?
Begins as relapsing-remitting, then transitions into 2° progressive
Describe the sub type of Primary Progressive?
Steady progressive deterioration
Pace of deterioration can vary
Describe the sub type of Progression-Relapsing
Relapses with a large degree of residual impairment
Relapses of greater or lesser severity with no plateaus
Also known as exacerbating-progressive
Describe the sub type of benign
Occasional symptoms without significant functional impairment
Describe the sub type of Fulminant (Marburg)?
Rapidly progressive, death may occur in a few weeks
Leading to early, severe disability, and death
what are the signs and symptoms of a lesion that occurs in the cerebrum and cerebellum?
balance problems, speech problems, co-ordination, tremors
what are the signs and symptoms of a lesion that occurs in the motor nerve tracts?
muscle weakness, spasticity, paralysis, vision problems, bladder, bowel problems
what are the signs and symptoms of a lesion that occurs in the sensory nerve tract?
altered sensation, numbness, pricklin, burning sensation
what are the primary signs and symptoms commonly seen?
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
what is the definition of MS fatigue?
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
what is the primary and secondary cause of MS?
Primary cause- due to disease
Secondary cause- due to deconditioning
what are the primary disease mechanisms of fatigue in ms?
Primary Disease mechanisms:
1. structural damage of white matter/grey matter (e.g. axonal loss)
- inflammatory processes
3.maladaptive network recruitment during task performance
- metacognitive interpretations of brain states that suggest ‘helplessness’
what are the primary symptoms of fatigue?
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
what are possible secondary symptoms of fatigue in MS?
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
what is the difference of fatigue and fatiguability?
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)
when specifically talking about Multiple sclerosis what does fatiguability mean in this population?
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
what are the two scales that can be used for fatiguability and MS?
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
what is the Uhthoff’s phenomenon noticed in patients with MS?
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
