MS

Question 1

MS inbrief

Answer 1

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 2

etiology

Answer 2

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

Ongoing research in 3 fields: immunology, epidemiology, genetics

Immunologic Factors: Abnormal immune-mediated response that attacks myelin (T and B cells)
Environmental Factors: High risk in areas far from equator (role of Vitamin D), Smoking, Obesity
Infectious Factors: Under investigation - measles, canine distemper, human herpes virus-6, Epstein-Barr, Chlamydia pneumonia

Question 3

mechanisms of injury

Answer 3

non resolving inflammation –> neurodegeneration –> failure of compensatory strategies –> remyelination or neuroplasticity

Question 4

pathophysiology BBB

Answer 4

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 5

demyelination

Answer 5

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 6

demyelination - progression

Answer 6

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 7

diagnosis

Answer 7

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 8

transverse myelitis

Answer 8

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 9

diagnosis of MS - McDonald Criteria

Answer 9

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 10

MS clinical subtypes

Answer 10

Describes the behavior of the disease, not severity

Clinically Isolated Syndrome
Early MS sign, but may not develop MS

Relapsing-remitting (RRMS) (85%) (MOST COMMON)

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 11

RRMS

Answer 11

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

Question 12

clinical presentations for lesion located in cerebellum and cerebrum

Answer 12

balance problems, speech problems, co-coordination, tremors

Question 13

clinical presentation for lesion in motor nerve tracts

Answer 13

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

Question 14

clinical presentation for lesion in sensory nerve tract

Answer 14

altered sensation, numbness, prickling, burning

Question 15

primary signs and symptoms

Answer 15

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 16

MS Fatigue

Answer 16

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 17

Fatigue in MS - primary

Answer 17

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

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

Question 18

possible mechanisms of primary fatigue

Answer 18

acute inflammation in brain/spinal cord
cytokines release during inflammatory process
neuroendocrine processes due to hypothalamic dysfunction
autonomic impairment
excess metabolic work of brain dt activation of additional cortical areas to perform tasks
abnormalities in cortical subcortical networks mediated by thalamic lesions

Question 19

possible mechanism of secondary fatigue

Answer 19

sleep disturbances due to pain, spasticity
undiagnosed sleep disorders
depression
inactivity and deconditioning
side effects of disease modifying therapy
side effects of symptomatic therapy

Question 20

fatigue

Answer 20

a symptom

Question 21

fatiguability

Answer 21

how quickly a specific level of fatigue is achieved, a measure (sign) of physical/mental work capacity (objective performance)

Question 22

fatigability in MS

Answer 22

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 23

measuring fatigue and fatigability

Answer 23

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 24

temperature sensitivity and thermoregulation

Answer 24

pseudo-exacerbations/relapses
symptoms not associated with the disease’s active progression
symptoms subside upon restoration of core temperature
Why? diminished neural conduction of CNS nerve fibers

cold sensitivity less prevalence

Question 25

uhthoffs phenomenon

Answer 25

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

Question 26

how to improve exercise/activity tolerance

Answer 26

Hydrate with cold fluids Cool environment Regional cooling devices Cooling garments (e.g. vests) Lightweight, breathable clothing Incorporate cool down in HEP

Question 27

balance, gait and mobility

Answer 27

Ataxia, postural & intention tremors, hypotonia, truncal weakness ~ 50% of Relapsing Remitting MS (RRMS) require some assistance in walking Staggering, uneven steps, poor foot placement, uncoordinated limb movements, loss of balance, scissoring Increased FALL RISK

Question 28

autonomic dysregulation

Answer 28

Urinary Bladder Dysfunction 65% of MS patients suffer from at least one moderate-to-severe urinary symptom (frequency, urgency, nocturia, leakage increased risk of urinary tract infections d/t poor emptying probs physical interventions such as pelvic floor muscle training and behavioral treatment may be beneficial (PT!) Cardiovascular Dysfunction abnormal cardiovascular response (e.g. syncope, palpitation, dizziness, nausea, general weakness, hot flashes and sweating, tachy/bradycardia symptoms associated with orthostatic dysregulation occur in up to 63% of the patients GI Dysfunction constipation, incontinence, or combo dysphagia (swallowing issues), IBS, bloating, etc. Sexual Dysfunction (likely underdiagnosed) women (34% to 85%): vaginal dryness, lack of orgasm, decreased libido men (50% to 84%): erectile and ejaculatory dysfunction, dec. libido fertility issues

Question 29

sensory changes

Answer 29

Altered sensations: paresthesias (abnormal sensations in absence of stimuli), dysethesias (abnormal interpretations of appropriate stimuli) Allodynia: central sensitization pain response to stimuli that normally do not provoke pain; neuropathic; processing error Disturbances of proprioception Damage interferes with the normal transmission of messages to the brain

Question 30

MS pain

Answer 30

Acute paroxysmal pain Trigeminal neuralgia – eating, shaving, or touching the face may trigger painful episodes Limb Pain– most common, burning/aching, worse at night and after exercise Hyperpathia Exaggerated reaction to stimuli; locate/identify painful stimuli erroneously; lowers pain threshold Chronic Neuropathic Pain (burning) Demyelination, neuroinflammation, and/or axonal damage in the CNS Stimulus-independent persistent pain Nociceptive: Musculoskeletal Pain or combo w/ neuropathic Due to muscle/ligament stress, abnormal postures, immobility, spasticity

Question 31

Lhermittes sign and test

Answer 31

passive or active neck flexion pain/electrical sensation shooting down back or into legs - myelopathy - MS

Question 32

Medical Management: DMT disease modifying therapy

Answer 32

CRAB Drugs (Copaxone, Rebif, Avonex, Betaseron) Decreases frequency and severity of relapsing and remitting MS Not a cure but limits progression Less effective in progressive MS Limit's ability of immune cells to cross BBB

Question 33

Medical Management - steroids (exacerbation management)

Answer 33

High dose intravenous methylprednisolone Prednisone Limits inflammatory response Restoration of BBB Less effective with repeated use Complications: Short term- fluid retention, increased BP, hyperglycemia Long term- HTN, diabetes, anxiety, psychosis, osteoporosis Not as effective for progressive MS

Question 34

to be considered a new MS relapse

Answer 34

old MS symptoms must become worse or new symptoms appeared – when symptoms change (vs baseline), you may be having a relapse symptoms must last for at least 24 hours – however, relapse symptoms generally last for days, weeks, or even months symptoms must occur at least 30 days from the start of the last relapse – MS symptoms should have been stable for about one month no other explanation for the symptoms – heat, stress, infections and other factors can make symptoms worse and can be mistaken for the start of a true relapse. When these factors are resolved, your symptoms should improve age, sex, pregnancy, serum levels of Vitamin D, interactions between genetic and environmental factors, and infectious diseases all appear to affect relapses The exact mechanism that leads to a relapse is unknown, but it's thought to be related to an increased overall immune response...some evidence that systemic infection (viral or bacterial), postpartum period, stress, and assisted reproduction (infertility treatment) may be associated with a flare-up Pseudo-exacerbations are NOT linked to new damage

Question 35

Medical Management - spasticity

Answer 35

Managed with oral meds (e.g. Baclofen, Zanaflex): modestly effective, sig. side effects Intrathecal baclofen- when spasticity is resistant to or ineffectively managed w/ oral medication Botulinum Toxin (Botox): focal spasticity ~3 months relief PT: stretching for 4 wks after injection Surgery Tendon, nerve release; selective rhizotomy *Spasticity can be useful Complete eradication of spasticity may diminish underlying strength that pwMS rely on; it’s a balancing act

Question 36

key points

Answer 36

MS is a progressive neurological disease of the CNS myelin Any CNS structure can be affected = any CNS symptom is possible Slowing and blocking of saltatory conduction of action potentials RRMS is the most common type of MS dx Fatigue is the most prominent and activity-limiting symptom in MS Exercise/activity tolerance and response must be monitored Medical and rehab therapies/management promotes decreased disability, increased QoL

Question 37

A PT performs an initial exam for a patient with a recent diagnosis of multiple sclerosis. The patient reports increased fatigue throughout the day, especially when walking their dog. What initial outcome measures would be MOST appropriate to include based on the patient's chief complaints?

Answer 37

a. 6-minute walk test; Modified Fatigue Impact Scale b. 6-minute walk test; Functional Reach Test  c. Activities-specific Balance Confidence Scale; Berg Balance Scale d. Dynamic Gait Index; Modified Fatigue Impact Scale