Lecture 6: Degenerative CNS Disorders: Multiple Sclerosis and Amyotrophic Lateral Sclerosis Flashcards
Multiple Sclerosis: This is a CNS dysfunction of both white and gray matter (brain and spinal cord)
However, what are the three main pathophysiology compoents?
* In this condition the formation of what happens that leads to disability and eventually relapses/remissions
1) Immune response dysfunction - immune system is disregulated
2) Myelin Destruction (regernation slow or incomplete [in the CNS regeneration does happen, other areas take on functions]; eventually unable to regenerate)
3) Axonal damage/loss (intracellular components)
Formation of plaques –> disability –> relapses/remissions
NOTE: its not directly impacting PNS, however the connection to PNS will be affected eventaully. But its not directly impacting the PNS
is MS hereditary?
* However, what chance do idential twins have of developing it?
Not hereditary, however, is triggered in susceptible individuals. whenever they’re going through puberty they most susecptable if exposed to it
Identical twins have a 25% chance of developing MS. Somehow they’re more susecptable
What environmental risk factor is there for MS
What virus has been linked to MS?
Latitude: the further from the equator WHEN YOUNG the higher chance of development
* High risk areas = New Zealand, Southeastern Australia, Nothern US, Northern/Central Europe, Italy, Canda
Epstein-Barr virus has been linked to MS (herpes virus family)
* Almost all clients affected by MS test positive for this virus (but not all with this virus have MS)
Modifiable risk factors: Smoking (studies have shown that stopping smoking before or after MS diagnosis can slow progression) high salt diet, obesity, low vitamin D levels, gut
Who gets MS more men or women
* age its typically diagnosed
* When is it typically aquired
women 2-3 times more
Caucasians most affected, japenese least affected
typically daignosed between 20-50
Theory that MS is acquired early in adolsence
* Those older than 15 who migrate retain the risk of their birth place
* Migration before age 15 can lower their risk
* Exposed to something in prepubescent years may predispose those affected
So if you start in canda and move near the equator less than 15 = decreased risk
MS = dysregulated immune system
Makeup of the immune system is CD4 and CD8 cells (also called T cells, lab panels refer to these in counts) B cells, immunoglobulins (more specificlly IGC)
Immune system has adaptive and innate components. Adapative immunity = WBCS, which are T and B cells. T cells are produced in the thymus and produce antigens. B cells are produced in the bone marrow and produce antibodies.
With MS myelin (from oligodendrocytes in CNS) and axons are being destroyed. Myelin is key for transmission of information across nerves, the health of the NS and a cushion for the NS.
Abnormal immune response causes inflammation in the CNS –> damaged/destoryed myelin/oligodyndrocytes/underlying nerve fibers –> procudes damaged areas of nerves (scars) that show up on MRI –> slowed nerve conduction
* myelin and axon are destoryed in MS
MS is the “perfect storm”
Hypothesis = virus induced immune mediated response
Immune mediated NOT autoimmune
Due to overactive immune system
Genetric predisposition that is triggered by environmental factors
* You’re predisposed then your environment makes it worse
Four things that make an MS prognosis more favoriable
More variable
* Female (they’re more likely to get it but symptoms are less severe)
* Onset at early age
* Mono-regional attacks - one area attacks (starts in just 1 arm first or just 1 leg first, not bilateral or affecting trunk first)
* Complete recovery between exacerbations (episodes)
Poor prognosis things for MS (5)
Poor prognosis:
* Male (less likelt to get but when they do its much worse)
* Older age at oneset (greater than 40)
* Brainstem symptoms (nystagmus tremor, ataxia, dysarthria) - think more bilateral
* Poor recovery from exacerbation (get another one before the first one ends)
* Frequent rate of attacks
Diagnosis of MS
* Careful medical history
* Neuro exam
* MRI - sensitive (rule out)
* Evoked potentials - visual, brainstem, sensory, motor, cognitive. Study of nerve conduction in CNS looking for demyelination. - looks at the quickness of these impulses in that area
* Spinal fluid (CSF) analysis - specific (spin) - positive = rules in
Imaging: McDonald Criteria
* 2 or more attacks with dissemination in space and time (space = 2 separate areas of CNS time = at least 30 days apart)
Explain the McDonald Criteria for MS imaging
* how many seperate areas?
* How many days apart?
When someone gets an MRI they need to get 2 ot mroe atatcks with dissemination (seperation of time and space)
* space = 2 seperate areas of CNS (think frontal and occipital lobe)
* CNS time = at least 30 days apart
KNOW: Differentitial diagnosis includes: HIV, lupus, progressive multifocal leukoencephalopathy
Which kind of MRI is dark, black holes, hypointensitities, gadolinum (shows inflamamtion), disability, new inflamamtion
* T1 or T2
T1
What kind of MRI is FLAIR - bright hyperintensisities, disease burden, total amount of scar, old and new (so shows everything combined not just the new - overall burden of disease)
* T1 or T2
T2
KNOW: Increased gray matter atrophy = increased brain atrophy and disability progression
Different MRI’s
T1 w/ contrast doesnt show the old lesions
T2 = shows old lesions, not just new inflammation
This is the same brain
knowledge check: How much time do we need between attacks for the mcdonalds scale?
at least 30 days between 2 different attacks
* NOTE: also they need to be in at least 2 separate areas of the brain
What is the most common form of MS?
* Makes up what % of cases?
Relapsing Remitting - 85% of cases
other types
Relapse = Exacerbation = Flare up = Attack
do Pt’s decide what phenotype of MS the pt has?
No, the neurologist does and perscribes medication accordingly
What phenotype of MS is definiend as relapses followed by periods of partial or complete recovery (remission)
* Disease stability evident between attacks
Relapsing Remitting (85% = most common)
NOTE: They will transfer to secondary progressive at some point, research shows approx 17 years after diagnosis is made
Goals for this pt: Quality of life, decrease occurrence of relapses (decrease relapse rate), slow disease progression, prevent disability and neuro symptom management
NOTE: Relapsing MS may now be the preferential term verses relapsing remitting
A relapse is defined as a new or old symptom that lasts _ hours and the absence of _
24 hours
Fever
What is a pseudorelapse/pseudoexacerbation?
A relapse that happens when a fever is present
* temporary worsening of symptoms brought on by concurrent illness, fever or infection
refer to MS neurologist for med managemnt - EX = steriods
NOTE: Relases can leave significant residual deficits
How often are relapses common?
Every 2-3 years, abrupt onset over a few days, stable (meaning it occurs for days/weeks, followed by partial or complete recovery over weeks/months
What kind of MS has no periods of stability, symptoms progress or get worse between relapses
Progressive Forms of MS
Primary progressive: considered a single attack
Secondary progressive: progression from RRMS
Progressive-relapsing: progressive accumulation of disability from onset, but clear acute clinical attacks, w/ or w/o full recovery
What kind of disease is a single dissemination in space, but no dissemination in time. Meaning theres one event but don’t go on to develop MS
Clinically isolated syndrome
* They’re having a symptom, but they don’t follow that mcdonald criteria. Nothing comes back and nothing becomes of it
* usually these pts don’t go on to develop MS
What is radiologically isolated syndrome?
Damage on scans but it does not relate to the symptoms
Advanced disease
* Can present challenges because disability and symptom set are at their highest
* Advanced MS needs: Pressure ucler, resp. complications, OT/ST, adaptations to physical and mental limitations
What percent of people have MS before 18?
* What is phenotype of MS called?
2-5%
Pediatric MS
Diagnosis chalening due to other childhood diagnoses that need to be ruled out with similar symptoms and characteristics
Knowledge check: Which phenotype would see stability between attacks?
relapsing-remitting
Typical feastures of MS
* Optical Neuritits - what is this?
* * Lhermittes sign =
* Sensory changes; numbness/tingling = very common
* Neurogenic bladder
Optical Neuritits = inflammation of the optic nerve which can lead to vision changes and pain in the ye
* vision changes are very common w/ MS
Lhermittes sign - pt has meneingeal irrattion / in the head / spine = sharp shooting pain down the spine/back
Neurogenic bladder = lack bladder contorl due to a brain/SC problem
What are our 2 initial signs/symptoms of MS?
Visual impairement
Sensory changes
Stages of MS
Take away: as someone progresses mobility changes / dependent on wheel chair / short distance ambulators
compensatory = compensating when fucntion is lost / not anticipating being back
Preventitive is always relative
* Think preventing pressure ulcers
S/S breakdown of MS
Primary, secondary, tertiary - on quiz
* what are the two primary symptoms of MS?
* What are the 3 secondary
* What are the two tertiary
NOTE: maybe don’t memorize these exactly because its an exahustive list. More know priamry vs secondary vs tertiary
Primary: - think more front lien damage - optic enrve damage leads immediately to vision deficits
1) Fatigue - optic nerve is affected
2) Visual changes
Secondary: - isnt happening due to that front line damage - “I cant get up and move around (due to fatigue/decerased mobility) so I’m at risk for skin breakdown. “the effects of the primary”
1) UTI
2) Skin breakdown
3) Falls - I have foot drop (primary) because spinal cord is messed up, so i have falls (secondary)
Tertiary: - more participation in ICF model. Think losing a job due to falling all the time and you’re a liability. you’re not safe at work. Participation is lost because of some symptom of MS
1) Social isolation - can’t go out in community.
2) Loss of job
What are invisible symptoms of MS?
Something we cannot see in the person
“Fatigue, cognitive changes, dysesthesias / paresthesias, bladder/bowel dysfunction, depression or other mood disorders”
* Things other people cannot visually see in the person
S/S of MS
Most common:
* fatigue (95% pts)
Depression is common w/ MS w/ 50% of people experienceing at least 1 major depresive epsisode
we have tools we can use instead of asking them if they’re depressed
Note: Cognititve Dysfunction does not equal physical disability
Other imaprements w/ MS
Impacts of inactivity
shouldnt have new symptoms - symptoms should be relatively contorleld
For Amyotrophic Latearl Sclerosis (ALS)
Which decade of life does ALS pop up in typically?
5th decade or lateral
cause is unknown
w/ ALS
Degenreation and loss of motor nuerons, w/ astricytic gliosis and microglial proliferation
Lower motor nueron axons also affected
Active immune process
Glutamate excitotoxicity plays a role
Oxidative damage to cells
Death of the peripheral motor nueron in the brainstem and SC leds to denervation and atrophy of the corresponding muscle fibers
Selective neuronal cell death - motor neurons of brainstem and SC, spare soculomtor nuclei
Eventual spread into the prefrontal, parietal, and temporal areas, as well as into the subthalamic nuclei and reticular formation
vision stuff is spared
Clinical manigestations of ALS
Both upper and lower motor neurons impacted
speech /swallowing
extremity deformitites due to lack of tone (think thenar emeince)
common inital presentation for ALS is assymetrical distal motor weakness
* think weakness in hand or drop foot
patient rpesentation of ALS
common inital presentation for ALS is assymetrical distal motor weakness
* think weakness in hand or drop foot
Spared sensation, cognition, eye movement, autonomic, bowel, bladder and sexual function
early, middle, late stages of MS
note: in later stages the pt is usually dependent on the chair
* unfortunately they will get to thsi care relatively quick
Notice the pitting w/ ALS
* divit in thenar emince
For ALS
how long does medication extend life in ALS?
* which medication is this?
2-3 months
Riluzole - glutamate inhibitor
For ALS
