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
- 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 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?
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
- 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
- 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
- trigeminal neuralgia
- paroxysmal limb pain
- headache
- chronic neuropathic pain
MS and heat insensitivity
- 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
- 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
- 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
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
