Lecture 6: Degenerative CNS Disorders: Multiple Sclerosis and Amyotrophic Lateral Sclerosis

Question 1

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

Answer 1

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

Question 2

is MS hereditary?
* However, what chance do idential twins have of developing it?

Answer 2

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

Question 3

What environmental risk factor is there for MS

What virus has been linked to MS?

Answer 3

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

Question 4

Who gets MS more men or women
* age its typically diagnosed
* When is it typically aquired

Answer 4

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

Question 5

So if you start in canda and move near the equator less than 15 = decreased risk

Question 6

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

Question 7

Question 8

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

Question 9

Four things that make an MS prognosis more favoriable

Answer 9

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)

Question 10

Poor prognosis things for MS (5)

Answer 10

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

Question 11

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)

Question 12

Explain the McDonald Criteria for MS imaging
* how many seperate areas?
* How many days apart?

Answer 12

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

Question 13

Which kind of MRI is dark, black holes, hypointensitities, gadolinum (shows inflamamtion), disability, new inflamamtion
* T1 or T2

Answer 13

T1

Question 14

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

Answer 14

T2

Question 15

KNOW: Increased gray matter atrophy = increased brain atrophy and disability progression

Question 16

Different MRI’s

T1 w/ contrast doesnt show the old lesions

T2 = shows old lesions, not just new inflammation

This is the same brain

Question 17

knowledge check: How much time do we need between attacks for the mcdonalds scale?

Answer 17

at least 30 days between 2 different attacks
* NOTE: also they need to be in at least 2 separate areas of the brain

Question 18

What is the most common form of MS?
* Makes up what % of cases?

Answer 18

Relapsing Remitting - 85% of cases

other types

Question 19

Relapse = Exacerbation = Flare up = Attack

Question 20

do Pt’s decide what phenotype of MS the pt has?

Answer 20

No, the neurologist does and perscribes medication accordingly

Question 21

What phenotype of MS is definiend as relapses followed by periods of partial or complete recovery (remission)
* Disease stability evident between attacks

Answer 21

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

Question 22

A relapse is defined as a new or old symptom that lasts _ hours and the absence of _

Answer 22

24 hours
Fever

Question 23

What is a pseudorelapse/pseudoexacerbation?

Answer 23

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

Question 24

How often are relapses common?

Answer 24

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

Question 25

What kind of MS has no periods of stability, symptoms progress or get worse between relapses

Answer 25

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

Question 26

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

Answer 26

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

Question 27

What is radiologically isolated syndrome?

Answer 27

Damage on scans but it **does not relate to the symptoms**

Question 28

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

Question 29

What percent of people have MS before 18? * What is phenotype of MS called?

Answer 29

2-5% Pediatric MS Diagnosis chalening due to other childhood diagnoses that need to be ruled out with similar symptoms and characteristics

Question 30

Question 31

Knowledge check: Which phenotype would see stability between attacks?

Answer 31

relapsing-remitting

Question 32

Typical feastures of MS * Optical Neuritits - what is this? * * Lhermittes sign = * Sensory changes; numbness/tingling = very common * Neurogenic bladder

Answer 32

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

Question 33

What are our 2 initial signs/symptoms of MS?

Answer 33

Visual impairement Sensory changes

Question 34

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

Question 35

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

Answer 35

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

Question 36

What are invisible symptoms of MS?

Answer 36

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

Question 37

What is the 1 unique need of someone w/ MS?

Answer 37

Heat sensitivity * Elevated temperature further impairs the ability of demyelianted nerve to conduct electrical impulses. Heat generally produces worsening of symptoms temporalrily but does not change disease processes known as Uhthoff's sign. An increase in less than one half degree celsius can cause major transient wekaness pts can overheat because bodies don't have the best thermoregulation * this can be exterenal (think outside in FL) * Or internal - I get worked up

Question 38

What is Uhthoff's sign?

Answer 38

Heat making symptoms worse w/ MS NOTE: Anincrease in 1/2 of a degree can cause major transiet weakness

Question 39

How many degree change does it take for pt w/ Ms to have heat sensitivity issue? * are new symptoms perminant

Answer 39

1/2 degree celcius transient

Question 40

S/S of MS Most common: * fatigue (95% pts)

Question 41

Knowledge check: S/S characterised as secondary?

Answer 41

Skin breakdown due to poor sensation

Question 42

Is there pain w/ MS?

Answer 42

Yes * However, it was intially thought as a painless disease NOTE: pain from immobility, spasticity, pain from overuse, neuropathic pain, trigeminal neuralgia NOTE: * lots of people use cannabis PT/OT ( depends on type of pain; trigeminal neuralgia and lhermittes type pain are treated w/ anticonulsants; dysesthesias which are painful sensations like MS hug, "nerve pain" are treated by anticonulsants or antidepressensats

Question 43

What is a MS hug?

Answer 43

MS pt's feeling like a squeeze at the center

Question 44

What is paresis? * If its due to deconditioning is it sage to perform progressive resisted EX? * When is it problematic to progressive overlead?

Answer 44

Muscle weakness If due to lack of use of muscle deconditioning) due to decreased mobility and activity, safe to perform preogressive resisted exercises for the muscles **If caused by damage in nerve fibers due to demyeliantion that innervates muscle, weight training for this is not effective and may even cause weaknes, lead to fatigue and reduce muscule endurance to affected areas** * Strategy: maintain tone and activity of muscles affected by nerve demyelination and strengthen surrounding muscles to dilinate between deconditioning vs lack of innervation we can do nerve condcution studies. We can do estem to see if we can get contraction at all.

Question 45

What is a spastic bladder?

Answer 45

Overactive and does not allow for complete urine emptying causing * Frequency or urination (because they cant empty it all out), urgency, nocturia, incontinence, inability to empty bladder completely NOTE: Untreated bladder issues can result in * Worsening of other MS symptoms including weakness and spasticity * Repeated UTI * Urosepsis (infection in blood) and skin breakdown * Challenges with work, home and social activities * Loss of independence, self esteem

Question 46

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

Question 47

Dizziness w/ MS * Often due to which CN?

Answer 47

8th cranial nerve vesitublochlear issue Could also be due to secondary BPPV Westibulopspinal pathway issues (helps maintain upright posture) MS issue due to demyelination VOR issue (coordinates eye movements during head motion)

Question 48

Note: Cognititve Dysfunction does not equal physical disability | Other imaprements w/ MS

Question 49

Which kind of memory is least likely to be affected w/ MS?

Answer 49

Long term memory

Question 50

Impacts of inactivity

Question 51

Knowledge check: know congintive function is not a direct linear realationship to a pts physical disability

Question 53

Disease Modifiying Therapies are specific to MS * What is the goal of DMTs?

Answer 53

DMTs used to reduce the relapse frequency w/ MS (common every 2 years) * Should limit the lvl of disability (note, more relapses = more disability becuse shit is damaged everytime we relapse. However, if were having less relapses that means were having less disbaility) They will also limit MRI disease activity (meaning on MRI's their will be less evidence of disease activity) Over 20 DMTs DMT adheerence: 60-76% for 2-5 years; non-adherence 25-30 * this low adherence is due to side effects / cost * dont need to memorize these #'s

Question 54

Types of DMTs: * Injectable Agents * Infusible Agents * Oral Medications Don't need to know the individual names of these, just the side effects

Question 55

**Side effects of injectables DMTs** (4)

Answer 55

1) Injection site reactions 2) flu-like symptoms 3) Depression 4) Lab abnormalitties (**lipoatrophy** w/ GA) - causes dimpling of the skin

Question 56

**Single side effect of infusion** DMT (1)

Answer 56

UTI

Question 57

**Side effect of oral DMT's** (1)

Answer 57

GI

Question 58

Know: Progressive multifocal Leukoencephalopathy (PML) can occur as a side effect of somme DMT medications for MS * Pt's tested w/ this trait prior to medications

Question 59

Rare viral disease of the brain, potentially fatal opportunistic injection of cerebral oligodendrocytes caused by reactivity of latent JC virus. Labs include JCV testing to determine activity of the virus/presence of the virus. Presence DOES NOT mean you cannot be on certain medicaations, but risk/benefit is assessed and monitoring is required Clinical manigestations: cognitive and behabior disturbances, language dysfunction, hemiparesis, cortical visual deficits, seizures Immediate referral to ER/MD required

Answer 59

Progressive multifocal leukoencephalopthy (PML)

Question 60

What is Ampyra medacation used for? * Does this medication have side effects? * can you take breaks from this medication? * who is the medication contraindicated for?

Answer 60

Targets Effort of walking as well as speed w/ pts w/ MIS This is a "why not" medication because it has basically no side effects Needs strict adherence - needs to build up in system good for all types of MS but is contraindicated in pts w/ renal dysfunction and seizures

Question 61

shouldnt have new symptoms - symptoms should be relatively contorleld

Question 62

**What happens to exacerbations while prego?** * What about after?

Answer 62

70% decrease in risk of exacerbation during pregnancy 70% increase 3-6 months post partum Cessation of meds prior to conception during pregnancy and during breast feeding Consult w/ neurologist during planning or as soon as pregnancy is confumed Clinical trials ongoing for safety of meds during pregnancy

Question 63

Question 64

**Quiz question** Knwoledge check: flu like symptoms are a side effect of which DMT?

Answer 64

injectables

Question 65

For Amyotrophic Latearl Sclerosis (ALS)

Question 66

KNOW: Most people w/ MS has an adult onset 90% of cases occur sporadically Familial ALS is an inherited autosomal trait - occurs in 5% to 10% of all ALS cases

Question 67

Which decade of life does ALS pop up in typically?

Answer 67

5th decade or lateral cause is unknown

Question 68

Who gets ALS more male or female?

Answer 68

Male

Question 69

KNOW: Exposure to some toxin (think agent orange) can lead to ALS

Question 70

ALS * Amyotrophy = (muscle wasting) * Sclerosis = hardening / plaque formation Affects motor tracts (upper motor neurons) and/or motor neurons (lower motor neurons) - brain, brainstem, SC, cranial nerves are also affected

Question 71

What are the two possible onsets of ALS * Does it more fast or slow?

Answer 71

Onset: * Limbs - meaning arms/legs, typically distal to proximal * bulbar = more speech and swallowing Rapid and progressive

Question 72

Who tracts degenarate in ALS? * Neurons in what 2 places also degenerate * Which kind of horn cells also degenerate in the SC?

Answer 72

Corticospinal tracts degenerate in ALS Neurons in motor cortex and brainstem Anterior horn cells in the spinal cord remember this is a UMN diagnosis and the LMN are often involved as well

Question 73

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

Question 74

Disease course ALS * How long does ALS last?

Answer 74

27-43 months - its quick In most pts death occurs within 2-5 years after symptom onset usually results from respiratory failure, PNA about 10% of patients hhvae a much slower disease progression, living 10 years or longer

Question 75

Knowledge check: which of the following structures are typically spared w/ ALS

Answer 75

Oculomotor nucli

Question 76

Diagnosis of ALS * No specific test * Patient hx, physical exam, neuro exam requirements to be diagnosised w/ ALS * LMN signs by clinical, electropphysiological, or neuropathological exam - NEED LMN pathology * UMN signs by clinical observation (think babkinski) * Progression of the disease within a body region or to another nody region * Absence of electrophysiological and pathological evidence of other disease affecting UMN and LMN

Question 77

Psuedobulbar palsy happens in ALS. What is it?

Answer 77

Damange in the corticobulbar tract

Question 78

Progressive Bulbar palsy happens w/ ALS. What is it?

Answer 78

Result of crainial nerve nuclei involvement; weakness of the muscles involved in swallowing, chewing, and facial gestures; gasiculations of the tongue are typical; diffuclty with repsiration before weakness of the lumbs; dysarthria and exaggeration of the expression of emotion, or pseduobulbar affect * more speech swallowing speaking - its cranial nerve functions

Question 79

Primary lateral sclerosis is rare but occurs in ALS. What is it?

Answer 79

Results in neuronal loss in the cortex. Signs of corticospinal tract involvement include hyperactivity of tendon reflexes with spasticity, causing difficulty with active movement; weakness and spasticity of specific musclles represent the level and progression of the disease along the corticospinal tracts; no muscle atrophy, and fasiculations are not present * happens in the cerebral crotex * wont see attrophy of fasiculations

Question 80

Progressive spinal msucular atrophy happens in ALS. What is it?

Answer 80

**There is progressive loss of motor nuerons in the anterior horns of the spina cord, often beginning in the cervical area. There is progressive weakness, wasting, and fasiculations involving the small mucles of the hands. Other levels of the spinal cord can be the site of the intital disease process, with symptoms reflecting the level nivolved. These areas of weakness can be present w/o evidence of higher level corticospinal invovlement, such as spasticity. ** * closely related to ALS but tehcnially different * Anteiror horn cells lost * involves small msucles of hands

Question 81

Favorable prognosis of ALS (still fatal) * 5 of them

Answer 81

Age less than 35 Psychological health Limb onset - not bulbar Rating of function scale SNIP - respiratory test

Question 82

Knowledge check: who would have the most favorable diagnosis

Answer 82

limb onset/< 35

Question 83

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

Question 84

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**

Question 85

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

Question 86

Notice the pitting w/ ALS * divit in thenar emince

Question 87

For ALS

Question 88

how long does medication extend life in ALS? * which medication is this?

Answer 88

2-3 months Riluzole - glutamate inhibitor

Question 89

For ALS

Question 90

Question 91

Knowledge check: intital presentation for limb ALS

Answer 91

Asymmetrical distal motor weakness