Multiple Sclerosis Flashcards
what is MS?
- progressive autoimmune disease characterized by inflammation, selective demyelination, and gliosis
- demyelinating lesions (plaques) impair neural transmission, causing nerve fibres to fatigue rapidly
- characterized by replase, remission, progression
- unpredictable course
describe the pathophysiology of MS
is white matter or gray matter more affected?
- abnormal immuno-mediated response attacks myelin, oligodendrocytes, and the axons themselves throughout the CNS
- activation of immune cells that cross BBB, enter CNS, and initate damaging inflammatory cascade of events
- acute inflammatory attack, gradually subsides (REMISSION)
- remyelination often incomplete
- with time, anti-inflammatory response/remyelination cannot keep up
- demyelination areas undergo gliosis
- white matter > gray matter
epidemiology of MS
- Most common cause of disability in young and middle-aged adults
- >900,000 cases in US
- 362 per 100,000
- average age of onset between 15-50 years
describe the etiology/cause of MS
an autoimmune disorder without a clear origin
thought to be viral/infectious
several different triggers
Predisposing factors for MS
- Women > Men (3:1)
- Population genetics
- Caucasian of Nordic origin
- Higher income countries
- Temperature zones (genes and geography)
- western europe and north america
- inconsistent latitude effect
- low vitamin D exposure during childhood and teenage years
- exposure to Epstein-Barr virus
how is MS diagnosed?
- Clinical presentation
- MRI
- dissemination in space
- dissemination in time
- Additional lab tests
- visual evoked potentials
- lumbar puncture
- elevated IgG index, pressure of oligoclonal bands, or both
what is dissemination in space? Where are the most common areas this occurs in?
refers to plaque build up in different areas of the CNS, most common in MS:
- periventricular
- juxtacortical
- infratentorial
- spinal cord
T/F: early detection of MS doesn’t change much
FALSE
significant decline in number of attacks, lesion sites, and disability in pts that participate in early drug treatment protocols
what is a CIS?
- clinically isolated syndrome
- first clinical episode of a disease that shows characteristics of inflammatory demyelination that could be MS but has yet to fulfill criteria of dissemination in time
- can be monofocal or multifocal
common sites for CIS
- optic nerve
- brainstem
- spinal cord
initial treatment for CIS
- high-dose glucocorticoids for acute symptoms
risk factors for conversion of CIS to MS
- polysymptomatic presentation
- >/= T2 MRI lesions
- Oligoclonal bands present in CSF, not in serum
relationship between CIS and MRI findings
- CIS + MRI findings indicative of early event = confirmed MS diagnosis
- CIS + MRI findings = 60-80% chance of MS developing
- CIS without MRI findings = 20% chance of MS developing
S/S of optic neuritis resulting from CIS
- unilateral reduced visual acuity
- Orbital pain particularly with eye movement
- reduced color vision
- afferent pupillary defect
- retrobulbar or mild disc swelling
S/S of brainstem CIS (8)
- bilateral internuclear opthalmoplegia
- ataxia and gaze evoked nystagmus
- 6th nerve palsy
- multi-focal symptoms
- facial sensory loss
- vertigo
- ataxia
- dysarthria
S/S of spinal cord CIS
- incomplete transverse myelitis
- (+) Lhermitte’s sign
- sphincter symptoms
- asymmetric limb weakness
- symptom progression between 4 hours and 21 days
MS Clinical Signs and Symptoms
- Motor function deficits
- Sensory function deficits
- Visual deficits
- Cognitive function
- Poor tolerance for temperature increases
- Fatigue
- Pain
- sleep disorders
- speech and swallow impairments
- dizziness
- bowel and bladder dysfunction
- sexual dysfunction
motor function deficits MS (3)
- weakness
- spasticity
- coordination (cerebellar)
sensory function deficits MS
- complete loss of sensation rare
- numbness
- paresthesia
- proprioceptive/kinesthetic deficits
cognitive function deficts MS
- Hallmark → slowed information processing speed
- Attention deficits (divided, sustained)
types of pain present in MS (5)
- trigeminal neuralgia
- paroxysmal limb pain
- headache
- chronic neuropathic pain
MS and heat insensitivity
What does Uhthoff mean?
- 80% of pts with MS are sensitive to increases in core body temp
- Uhthoff symptom
- increase in presence of neurological symptoms in response to heating condition
- pseudo-exacerbation
describe the neuroblockade hypothesis
hypothesis for heat insensitivity in MS pts
- demyelinated neurons ability to conduct APs decrease as temp increases
- Internal vs External sources
- internal = vigorous exercise, high fevers
- external = environmental temp, bathing or swimming in hot water
MS and Fatigue
- Up to 80% experience some type of acute or chronic fatigue
- 75% of which report fatigue as severe
- 50-60% report fatigue as most troublesome symptom
- # 1 cause of unemployment
- tends to worsen as day progresses
- exacerbated by heat, exercise
- primary, secondary fatigue
- central, peripheral, psychological factors
- can often lead to fear of fatigue → decreased physical activity → disuse → worsening disability
symptom exacerbation in MS (what counts as a symptom exacerbation)
- MS exacerbation = new and recurrent MS symptoms lasting >24 hrs
- Idiopathic vs Exacerbating factors
- viral or bacterial infections
- disease
- major or minor stressors
- Pseudo-exacerbations
what are pseudo-exacerbations?
transient worsening of symptoms
occurs due to stress, infection, overheating, or overexertion
List the 3 main classifications of MS
- RRMS
- SPMS
- PPMS
describe RRMS
Relapsing-Remitting MS
unpredictable attacks, which may or may not have permanent deficits, followed by periods of remission
- clearly defined episodes of acute worsening of neuro function followed by partial/complete recovery with periods of time between that pts are clinical free of disease progression
- relapses with full recovery or some remainig neuro S/S and residual deficits on recovery
describe SPMS
Secondary Progressive MS
initial relapsing-remitting MS that suddenly begins to have decline without periods of remission
- initially presents as RR period followed by steady worsening of neuro function with or without relapses
- remissions are minor, or can have plateau
describe PPMS
Primary-Progressive MS
steady increase in disability without attacks
- continous worsening from inital onset without distinct relapses or remissions
- may have occasional plateaus and temporary minor improvements
there used to be a 4th classification of MS, what was it?
PRMS
progressive relapsing MS
- steady worsening AND relapses, remissions and plateaus
- thought to be more common in ppl diagnosed later in life
medical management of MS consists of what 3 things?
- acute exacerbation treatment
- disease modifying medications
- symptom management
describe acute exacerbation treatment
- immunosuppressant drugs treat acute flare ups and shorten duration of episode
- ACTH
- Methylprednisolone
- Prednisone
what is the purpose of disease modifying medications?
- reduce frequency and severity of clinical attacks
- reduce development of lesion sites
- slow down the progression of disability
generally describe what different types of disease modifying drugs do
- Interferon Drugs
- slow progression of disease, decrease symptoms
- have horrible side effects that make the pt feel like crap
- Copaxone
- daily subcutaneous injection
- synthetic protein designed to mimic effects of myelin protein; expand T-cell and suppressor cell populations, alters antifen-producing cells
- Tysabri, Novantrone
- last resort, these really make the pt feel bad
symptom management in MS
- Fatigue
- amantadine, provigil
- Spasticity
- baclofen, diazepam (valium), dantrolene, baclofen-pump, phenol block surgery
- Pain
- neurontin, lyrica, dilantin
- Urinary dysfunction
- anticholinergic drugs
what is the EDSS?
a quick way to classify pts with MS based on 8 functional systems
list the 8 functional systems used in the EDSS
- Pyramidal
- Cerebellar
- Brainstem
- Sensory
- Bowel and bladder
- Visual
- Cerebral
- Other
how many levels are there for the EDSS?
ranked from 0-10 in half increments
describe typical symptoms in EDSS 0-4.5
- symptoms
- ranging from no symptoms to mild-to-moderate fatigue, imbalance, sensory changes, mild walking impairment, and reduced visual acuity
- bowel-bladder symptoms
- altered mood state
- cog impairments
describe typical neurologic impairments in EDSS 0-4.5
- neuro impairments
- ranging from normal neuro exam to mild-to-mod impairments in:
- proprioception
- cerebellar function,
- vision muscle
- strength/tone/endurance,
- bladder function,
- cognition
- ranging from normal neuro exam to mild-to-mod impairments in:
describe typical functional limitations in EDSS 0-4.5 (3 listed)
- functional limitations
- ranging from no limitations to limited:
- endurance
- unsteadiness
- impaired information processing and memory
- ranging from no limitations to limited:
describe typical symptoms in EDSS 5-6.5
- symptoms
- progression of any or all symptoms present in 0-4.5
describe typical neurologic impairments in EDSS 5-6.5
- Neurologic impairments
- may include an increase in the impairments in previous levels
- worsening gait
- unilteral to bilateral spastic gait paresis
- foot drop with compensatory hip hike
- circumduction with progression from unilateral to bilateral assistance and/or use of MWC
- impairments to UE coordination
describe typical functional limitations in EDSS 5-6.5
- Functional limitations
- limited walking distance (20-200m)
- falls
- inability to safely dual motor/cognitive task
- work/home activities require adaptations
- compensatory strategies
- mobility aids (ranging from cane to wheelchair walker for daily use to a MWC for distance)
- transfers on/off floor and into/out of chairs increasingly challenging
- requries assistance from support partner for more complex daily activities
describe typical symptoms in EDSS 7-9
- continued worsening of all symptoms
describe typical neurologic impairments in EDSS 7-9
- sig impairment in many or all systems
describe typical functional limitations in EDSS 7-9
- functional limitations
- gait → from 10 ft with a walker to restricted to bed and WC
- transfers → from min A to total A
- bed mobility → from min A to total A
- seated balance → from independent to total A
- standing balance → from independent with bilateral support to unable to stand unaided
disability classification based on EDSS score
- 0-3.5 = normal to mild disability
- 4-5.5 = mild to moderate disability
- 6-7.5 = moderate to severe disability
- 8-9.5 = severe disability with restriction to bed or WC
describe the disease steps scale
- 0 = functionally normal with no limitations on activity or lifestyle
- 1 = mild disability, mild symptoms or signs
- 2 = moderate disability, visible abnormality of gait
- 3 = early cane, use of cane or other form of unilateral support for greater distances, but can walk at least 25 ft w/o it
- 4 = late cane, cane dependent, unable to walk 25 ft w/o cane or other form of unilateral support
- 5 = bilateral support, requires bilateral support to walk 25 ft
- 6 = confined to WC
- U = unclassified, used for pts who do not fit any above level
MS subjective outcome measures
- 12 item MS walking scale
- Fatigue scale for motor and cognitive function
- MSQOL - 54
- Modified fatigue impact scale
- Multiple Sclerosis Impact Scale (MSIS-29)
12-item MS walking scale
what EDSS scores does it correlate with? What is the cutoff score for fall risk?
EDSS 0-7.5
cutoff score for fall risk >/=75
Fatigue Scale for Motor and Cognitive Function
differentiate between motor and cognitive aspects of fatigue
MSQOL-54
SF-36 plus 18 MS-related items
Modified Fatigue Impact Scale
fatigue impact on physical, cognitive, psychosocial functioning
MSIS-29
Multiple Sclerosis Impact Scale
physical and pyschosocial difficulties related in MS in past 2 weeks
disease progression for MS
- varied and inconsistent response between pts
- inflammatory response
- patterns of demyelination
- extent of remyelination
- degree of axonal damage
- Patterns typically similar within patients
MS disease progression pertaining to AD use and life expectancy
- mean time before use of unilteral AD → 15-20 yrs
- life expectancy ~10 years less than age-matched peers
MS disease prognosis - Imaging
- white matter lesions on MRI at initial clinical presentation demonstrated an 88% chance of developing MS 7-10 years
- only 19% developed MS is no lesions were detected
- Appearance of a new lesion on T2 weighted MRI < 3 months after initial clinical episode = poor prognosis
- MIR findings
- favorable prognostic factors incldue:
- low total lesion burden
- low active lesion formation
- negligible myelin or axon loss
- favorable prognostic factors incldue:
MS Disease prognosis - Clinical
- Type of MS
- RRMS vs PPMS
- early SPMS onset
- level of recovery after intial insult
- time between relapses
- location of 2nd lesion site
- intiation of medical management
- type of symptoms at intial insult
- gender (males have faster progression)
- age at onset (older worse)
- Neuro findings at 5 years
Favorable prognostic factors
- female
- low rate of relapses per year
- complete recovery from first attack
- long interval between 1st and 2nd attack
- symptoms predominately from afferent systems
- younger age of onset
- low disability at 2 to 5 years from disease onset
- later cerebellar involvement
- involvement of only one CNS system at time of onset
unfavorable prognostic factors
- males
- high rate of relapse per year
- incomplete recovery from 1st attack
- short interval between 1st and 2nd attack
- symptoms predominately from efferent systems
- older age at onset
- sig disability at 2 to 5 yrs from the onset
- acute onset
- early cerebellar involvement
- involvement of more than one CNS system at the time of onset
