Multiple Sclerosis

MS

immune-mediated progressive neuroinflammatory disease affecting CNS, characterized by widespread inflammation and demyelination that outpaces recovery mechanisms such as neuroplasticity and remyelination

risk factors

• familial risk

• females > males

• temperate zones

• vitamin D deficiency

• viral exposure (espstein-barr virus)

• passive and active exposure to tobacco

• high BMI in early adolescence

disease cycle

1. genetic susceptibility + environmental (inflammatory) trigger

2. altered inflammatory process that crosses the BBB

3. inflammatory process attacks myelin sheaths in CNS

4. tissue repair/ remyelination phase (low level of attack)

Diagnosis requirements

• clinical exam (neurologic signs and symptoms, medical history)

• diagnostic tests (MRI)

• dissemination in space and time of lesions

CIS

• first clinical episode of a disease that shows characteristics of inflammatory demyelination that is suggestive of MS but has yet to fulfill full criteria of dissemination in time and space

• most transition to CDMS

• number of T2 lesions, lesion location, and presence of CSF and oligoclonal bands —> higher risk

RIS

• incidental brain or spinal cord lesion suggestive of MS without any symptoms

• 20-50% transition to CDMS w/in 5 years

• presence of enhanced or spinal cord lesions and age <37 at a higher risk of conversion

diagnostic criteria

• central vein sign

• paarmagnetic rim lesions

• kappa free light chains

• dissemination in time

relapsing remitting

• clearly defined episodes of acute worsening of neurologic function followed by complete or partial recovery with the between periods clinically fre of disease progression

secondary progressive

• phase 2 of RR MS

• initial RR period followed by a steady worsening of neurologic function and not related to acute relapses. acute relapse rate is reduced and remissions are minimal

primary progressive

• continuous worsening from initial onset without distinct relapses or remissions but may have periods of plateau

FSS

clinical ordinal rating ranging from 0-5 or 6, 7 functional systems (pyramidal, cerevellar, brainstem, sensory, bowel and bladder, visual, cerebral/mental)

EDSS-FF

scoring in conjunction with an ordinally rated observation scale from normal function to death (0-10). measures level of disability

medical short term management

• corticosteroids

• methylprednisone

• plasmaphersis exchange and OV immuniglobulins

Ampyra

• oral extended release potassium channel blocker

• used with EDSS 4-7, normal kidney function, and no seizure history

• improveds 25ft walk test, MSWS, TUG, 6MWT, 9 hole peg test, and BBS

factors for rapid disease progression

• age of onset <37

• primary or secondary smoking

• low vit D levels

• primary progressive phenotype

• high early relapse rate

• short interval between first and second relapse rate

• high EDSS score at onset

• polysmpytomitc at onset

• early cognitive decline

• high initial lesion volume

• + enhancing lesions at onset

• presences of infratetorial or spinal lesions

• presence of serium neurofilament

• presence of oligoclonal bands in csf

• retinal nerve fiber thinning

EDSS 0-3.5

• focus on prevention

• educate and maximize fitness levels

• no or subclinical mobility deficits

• standardized assessment importnat to detect emerging disability

• initial functional defects primarily impact gait speed, efficiency, and stability

EDSS 4-6

• focus on adaptation and prevention

• maximize fitness

• promote recovery of function

• prevent secondary co-morbidities

• may need to introduce compensatory strats such as bracing, ADs

• impairments ar emore readily apparant

• progressive impact on activity and particpation

• secondary impairments begin to develop

EDSS 6.5-9.5

• focus on compensation and prevention

• maximize fitness

• focus is largely preventative and improving/maintaining mobility through compensatory strategies that can be very meaningful

• significant mobility and functional limitations

• more pronounced co-morbidities

• longer “stable” periods

aerobic treadmill training

• 18 sessions (3/week for 6 weeks)

• 20 minutes at 70-80% HRM

• improved 6MWT, T25FW, BBS

corticospinal treadmill training

• 10 weeks (3x/week) in temperature controlled room (60°)

• 5 minute warmup/cool down + 30 minutes @40-65% HHR)

• <2 min rest breaks as needed

• increased corticospinal activation (short term) and exercise capacity (longer term)

• reductions in FSS and mFIS

endurance treadmill training

• 8 weeks (2x/week)

• 24 minutes (2 min warmup/cool down w/ 20 min walking including 3-5 minute break)

• on antigravity treadmill

• improved muscle oxidative capacity and endurance

cool room treadmill training

• for individuals with heat sensitivoty

• can extend particiation intensity and time to achieve enhanced CV and mobility ouctomes

VR treadmill training

enhances cognitive processing (attention, verbal fluency, depressive symptoms) and dual task postural control

High Intensity Fast Walking

• 20s fast walking with 1-3 minute rest between, 6-8 reps

• 2x/week for 6 weeks

• improves 25FWT, 6MWT, MiniBest

Intermittent walking

• 2 min walking with 2 min rest x3 reos

• 2/week for 4 weeks

• improved 6MWT

AFO

• improves gait speed and endurance

• improved MSIS and MSWS

• better improvements in stability

FES

• improves gait speed and endurance

• improved MSIS and MSWS

• better improvements in obstacle avoidance

• higher sub-score in competence, adaptability, and self esteem; lower levels of perceived exertion

• for foot drop: inc stride length, DF at initial contact and in swing, and improved walking speed (both while using and after)

RAS

• use with mid-moderate MS (EDSS 2-5)

• improved gait speed, stride length, cadence (medium effect)

• 20 min 3/week for 3 weeks

• significant reduction in movement-related brain activation for motor function, planning, attention

• may increase remyelination or facilitate cortical reorganization

Task-specific balance challenges

• steady state, anticipatory, reactive control

• 2-3x/week, minimum of 40 min/session over 4-12 weeks

• include dual task challenges and sensory integration

vestibular rehab

• need to be CDMS, able to walk 100m, >45 mFIS, limited standing balance defined on computerized SOT

• 2/week for 6 weeks

• SOT, mFIS, and DHI score improved

• vestib rehab and fatigue management

dual task treadmill training

• EDSS 3.5

• 3/week for 6 weeks over 13-18 sessions

• gait speed and endurance, dual task gait speed improved

• VR improved cognitive processes

aerobic TherEx

• 2/week

• 10-40 minutes or 10 min intervals

• mod intensity (60-80% HRM or 11-13 RPE)

• lower risk of relapse

• lower lesion volume (RRMS)

• improvements in memory/learning, information processing, and attention/concentration

• enhances corticospinal excitability

• slower disability progression

• increase plasma BDNF levels and reduce serum neurofilament light chain markers

• consider heat sensitivity and blunted HR/BP response

high intensity resistance for fatigue

• EDSS 1-3

• 70% iRM

• 1-2/week for 12 weeks, 5-10 min warmup/cooldown

• 4 upper body, 3 lower body, 1 whole body

• reduced fatigue

• vary reps per motor group

HIIT

• 3-5/week

• 80-90% HRM, RPE 13-16

• short interval ( <45s) or long interval (2-4 min of work)

• high volume (> 16 min) or low volume (< 4 min)

aerobics + resistance

• EDSS 1.5-5.5

• resistance at 50% 1RM 2×10-15 with 30s recovery

• aerobic: 10 min on cycle ergonometer at 65% HRmax

• improved 10MWT, 6MWT, MSQOL

• does NOT improve TUG

• consider impact of impairments, pseudo-exacerbation, and safety

flexibility

• daily

• hold for 20-60s (15-20 min total)

• apply stretch to tolerance

• self stretch, do yoga, wear splints

aquatic therapy

• EDSS 1.5-8 (majority 2-3.5)

• 60 min per session, 3x/week for 8-12 weeks

• pool temps 82-88°

• improves fatigue, balance, QOL, and activity tolerance

cooling recommendations

• body temp is lower in the morning

• exercise in AC

• resistance is easier to tolerate than endurance

• cooling vests must fit well and need 30 min to take affect, last for 60-90 min

• vests with a neck or cap are more effective

changing physical activity levels

• moderate effect following intervention

• implement focused behavior change interventions

• lasts at least 12 weeks

motor imagery

• EDSS 2-2.6

• verbal guidance more effective

• 17-30 min, 2-7 days/week, for 4-8 weeks

• improved DGI, ABC, 10MWT/25’ WT, mFIS, 6MWT, and QOL

barriers to exercise

• lack of accessibility and knowledge of health and fitness staff in the community

• enjoyment

• impairment based limitations (fatigue)

• self-efficacy

effective behavior change

• goal setting

• overcome barriers

• recruit social support

• use activity monitors/ feedback systems

• face to face, tele-health monitoring, or virtual coaching

managing fatigue

• high intensity resistance and aerobic/endurance exercise

• exercise for primary fatigue —> immune modulation, upregulation of neuro-endorcrine growth factor, enhanced motor excitation and drive

• exercise for secondary fatigue —> decrease deconditioning, improve aerobic capacity, muscle strength, movement efficiency, social interaction

• mindfulness based stress reduction

• CBT

• edu

patient edu for fatigue management

• sleep hygiene

• activity log

• fatigue log

• activity modification

gait dysfunction

• most common activity limitation

• paretic, cerebellar ataxic, sensory ataxia, or mixed

• decreased gait speed, impaired dynamic balance in gait and endurance

• associated with neurological disability (decreased step count —> increased disability)

predictors of emerging disability

• changes in motor performance and fatigue —> changes in walking perception and endurance

• fatigue = strongest predictor of changes in walking

• strength = strongest predictor of endurance

motor dysfunction

• decreased fiber size, slow-twitch myofilaments, central conduction, neuron firing accuracy, muscle activation

• increased fast-twitch myofilaments

central vestibular function

tasks requiring central sensory integration (e.g. static standing SOT) —> inc self-reported fatigue (mFIS, FSS), balance impairment (FGA, ABC), and walking capacity (6MWT)

fatigue

• self-percieved lack of physical or mental energy that interefres with usual or desired activity

• subjective sensation or objective change in performance

primary fatigue

related to disease progression (e.g. demyelination, inflammation)

secondary fatigue

related to a systemic process (e.g. deconditioning, motor fatigue, CV fatigue)

fear of falls

• fear avoidance behaviors

• walking impairment

• impaired motor function

• impaired self reported mobility

core outcome measures

• 10MWT

• 6MWT

• ABCS

• FGA

• BBS

• 5xSTS

phsyiologic recovery

• acute: resolution of inflammation

• chronic: repair through re-myelination, cortical reorganization

• early disease stage: increase ipsilateral cortical and cerebellar activation

• late phases/progressive phase: inc bilateral sensorimotor activation incl secondary motor and non-motor areas

neuroplasticity

• neurogenesis, synaptogenesis, neuronal morphology

• number of axons, axon diameter, packing density, axonal branching, remyelination

• angiogenesis, glial number, cell size and brain volume

adaptive myelination

• cortical stimulation of axons through complex tasks —> oligodendrocyte proliferation, differentiation, and remyelination

• combine with challenging task training and exercise with DMTS/ pro-myelinating drugs —> significant improvements

• may be maladaptive

remyelinated axon

thinner and less robust!

effect of early and active engagement in PT

• slows disease progression

• inc neurological reserve

• promotes recovery of MS degeneration

• prevents secondary impairments and fatigue cycles