MS Flashcards
MS inbrief
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
etiology
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
mechanisms of injury
non resolving inflammation –> neurodegeneration –> failure of compensatory strategies –> remyelination or neuroplasticity
pathophysiology BBB
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
demyelination
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
demyelination - progression
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)
diagnosis
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
transverse myelitis
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
diagnosis of MS - McDonald Criteria
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
MS clinical subtypes
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
RRMS
Episodes of rapid, abrupt deterioration with variable degrees of recovery over time
Periods of deterioration are called relapses, flares, or exacerbations
clinical presentations for lesion located in cerebellum and cerebrum
balance problems, speech problems, co-coordination, tremors
clinical presentation for lesion in motor nerve tracts
muscle weakness, spasticity, paralysis, vision, bladder and bowel
clinical presentation for lesion in sensory nerve tract
altered sensation, numbness, prickling, burning
primary signs and symptoms
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
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
Fatigue in MS - primary
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’
possible mechanisms of primary fatigue
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
possible mechanism of secondary fatigue
sleep disturbances due to pain, spasticity
undiagnosed sleep disorders
depression
inactivity and deconditioning
side effects of disease modifying therapy
side effects of symptomatic therapy
fatigue
a symptom
fatiguability
how quickly a specific level of fatigue is achieved, a measure (sign) of physical/mental work capacity (objective performance)
fatigability in MS
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
measuring fatigue and fatigability
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
temperature sensitivity and thermoregulation
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
uhthoffs phenomenon
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
how to improve exercise/activity tolerance
Hydrate with cold fluids
Cool environment
Regional cooling devices
Cooling garments (e.g. vests)
Lightweight, breathable clothing
Incorporate cool down in HEP
balance, gait and mobility
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
autonomic dysregulation
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
sensory changes
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
MS pain
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
Lhermittes sign and test
passive or active neck flexion
pain/electrical sensation shooting down back or into legs
- myelopathy
- MS
Medical Management: DMT disease modifying therapy
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
Medical Management - steroids (exacerbation management)
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
to be considered a new MS relapse
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
Medical Management - spasticity
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
key points
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
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?
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
