Activity in Cerebral Palsy: How it helps muscles (& brains!) Diane L. Damiano, PhD PT National Institutes of Health Bethesda MD USA.

Activity in Cerebral Palsy:Activity in Cerebral Palsy:How it helps muscles (& brains!)How it helps muscles (& brains!)

Diane L. Damiano, PhD PTDiane L. Damiano, PhD PT

National Institutes of HealthNational Institutes of Health

Bethesda MD USABethesda MD USA

Activity,

Activity,

Activity…….

TAKE HOME MESSAGE

Activity and Cerebral Palsy

Those with CP have one of the most sedentary lifestyles among pediatric disabilities (Longmuir & Bar-Or 2000)

Van den Berg-Emons et al (1995) estimated that ‘average’ child with CP would need to exercise 2.5 hours/day to reach activity levels of peers

Step Counts in CP by GMFCS LEVEL vs. Peers (Bjornson et al 2007)

Outline

• Discuss generalized effects of activity on muscle structure & function and motor outcomes (optimizing physical rehabilitation)

• Neurobiology of activity: potential role of activity-based protocols for promoting neural recovery and restoration of function

Muscles now known to be one of the most ‘plastic’ tissues in the body

“Muscles respond in a fairly stereotypical manner to the amount and type of activity imposed upon them”

Lieber et al, 2004

Muscle Myths

Previously thought that fiber types and # of fibers determined genetically and could not change (marathon runners & sprinters born, not made)

Rehabilitation of those with CP and other CNS disorders failed to include muscle strengthening or other intense training paradigms because it would > spasticity.

How Do Muscles Adapt? (Harridge, Exp Physiol, Review 2007)

Two basic mechanisms at the level of the muscle fiber (cell): 1. Change in mm size

Primarily by increase/decrease in fiber diameter Mediated by satellite cells that repair or grow muscles (or replace

themselves) Change in size directly related to maximal force output (In extreme cases (elite bodybuilders) & perhaps normal development

(Sjostrom, 1992) the number of fibers may increase)

2. Change in protein isoform (MHC) composition affects maximal shortening velocity (faster if > Type II)

How can muscle adaptations be indiced?

1. Decrease mm size• Immobilization• Decrease activity level (contractile activity)• Weightlessness

Increase mm size:• Placing loads on muscles, e.g. progressive resistance exercise (PRE)

2. Change protein isoform (MHC) composition• High or low frequency electrical stimulation or high intensity (speed)

voluntary training• Denervation

Schiaffino et al. Physiology 22: 269-278 2007

Muscle plasticity in adult & developing skeletal mm : changes in MHC composition induced by inactivity & fast-type activity in Type I fibers

What happens to muscles in CP?

From infancy on (& perhaps before) children w/ CP do not move as much as those w/o CP & move differently Muscles cells are not mature at birth; therefore in CP, muscles may

fail to develop properly from outset

If muscles are not used, they become progressively weaker– then it becomes even harder to move

To what extent is this preventable or reversible?

What CP Care Environment Does to Muscles

• Many treatments in CP weaken muscles:• Muscle-tendon lengthenings: <force-generation capability

(Delp & Zajac, 1992)• Orthoses: can cause atrophy of calf mms• Botulinum toxin: paralyzes one mm at a joint to allow >

stretch & enhance opposite mm function• ITB: depresses involuntary & voluntary muscle activity• PT: casting, splinting, restrictive garments, prior emphasis

on movement quality vs. quantity, ban on strengthening can limit muscle development

Strength in CP vs. Non-CP: Dominant Side

0

1

2

3

4

5

6

7

8

HFL HFS HE ABD ADD KF KE KE30 APFE APFF ADFF ADFF

ComparisonHemiplegiaDiplegia

(Wiley & Damiano, DMCN 1998)

Non-Dominant Side

0

1

2

3

4

5

6

7

8

HFL HFS HE ABD ADD KF KE KE30 APFE APFF ADFF ADFF

ComparisonHemiplegiaDiplegia

Strength by GMFCS Level

00.5

11.5

22.5

33.5

44.5

5

LEVEL I LEVEL I I LEVEL I I I

HamstringsQuads 30

Muscle Strengthening

• Multiple reviews in CP & other conditions showing that strength is predictably increased (Dodd, Tayl0r & Damiano 2002; Taylor, Dodd & Damiano 2006)

• Changes in gait speed & other aspects of functioning noted often but not consistently

• Depends on ‘dose’ and ‘duration’. Must be done properly & for sufficient time to achieve benefits

• Must be maintained across lifespan

Muscle Fatigue in CP

• Fatigue is cited as main cause for decline or cessation in walking in CP (Bottos 2004)

• Cardio-respiratory endurance lower in CP • No reports on voluntary muscle fatigue in CP

• We hypothesized that those with CP would be more fatigable than age-matched peers, and that endurance would worsen with level of involvement

Methods

• Subjects: 18 w/ CP; 15 controls (ages 10-23y)• Fatigue Protocol:

• Biodex isokinetic dynamometer• Consecutive, maximal, (concentric)

reciprocal knee extension/flexion reps • 35 repetitions at 60 deg/s• Instructions: “Push all the way up as hard and fast as

possible; pull down….”• Verbal encouragement each repetition

Methods

Computed slope of the decline in torque (normalized to peak torque) in the quadriceps & hamstrings mms

0

0.2

0.4

0.6

0.8

1

0 5 10 15 20 25 30 35

REPETITIONS

NP

TK

E (

Nm

)

Results for the Quadriceps

0

0.2

0.4

0.6

0.8

1

0 5 10 15 20 25 30 35

CP

Repetitions

Nor

mal

ized

Pea

k T

orq

ue

0

0.2

0.4

0.6

0.8

1

0 5 10 15 20 25 30 35

CPControlsCP

Correlation of Slope & GMFCS

Spearman (r) = -0.50, p = .035

I II III

Slo

pe

KE

(N

-m)

·

N=10 n=5

n=10

0.0

0.2

0.4

0.6

0.8

1.0

I II III

n=5

n=3

n=10

RESULTS

Group w/ CP had greater endurance in their quadriceps than controls; hamstrings not different in CP

Stackhouse et al. 2005 evaluated fatigue with electrically elicited contractions: found quadriceps (but not triceps surae) to be less fatigable in CP

We further found that the less functional (and weaker) they were, the greater their endurance tended to be

HOW DO YOU EXPLAIN THIS?

FATIGUE PARADOX

• Stronger individuals may fatigue more rapidly (inconsistent)

• Muscles in CP have predominance of Type I fibers (Rose 2001)

• The subjective complaint of fatigue is likely due to weakness. Individuals with CP are working at higher % of maximum, so this makes them feel more tired during a similar task - same thing happens in elderly

• Loss of strength with age increases fatigue even more

• Suggests that the most effective long term strategy to avoid fatigue is to maintain/increase strength to lessen relative effort

In Vivo Evidence of Muscle Plasticity

THIGH CT SCANS IN TWO MATCHED PATIENTS WITH COMPLETE SCI (n=56)

TRADTIONAL PT CONTROL 6+ MOS. OF FESCYCLING

(Sadowsky, McDonald, Damiano et al)

Introduction to Muscle Architecture

Fascicle geometry 1. Fascicle Length (FL) 2. Fascicle Angle (FA)

FL = MT / sin (FA) (Shortland et al, 2002)

Muscle size1. (2D) Muscle thickness (MT)2. (3D) Cross-sectional area (CSA)3. (3D) Muscle volume4. (3D) Muscle length

RF

RF

RECTUS FEMORIS 3D US

Longitudinal

Axial

Relationship of muscle size to strength in CP

• Ohata et al (2004, 2006) suggested that muscle thickness could be used as a surrogate measure of strength in CP, especially for those who are too young, too cognitively impaired or lack sufficient motor control.

MUSCLE THICKNESS IN ADULTS WITH CP (Ohata et al, Phys Ther 2006)

BY GMFCS LEVEL

BY STANDING ABILITY

Muscle Ultrasound (US)

GE VOLUSON730 E: linear (2D) & volume (3D) probes PARTICIPANTS:18 w/CP (12 ambulators), 20 Controls; 11 measured

before & after intense summer sports campMETHODS:

Muscles• Rectus Femoris (RF)• Vastus lateralis (VL)

Position: Supine with hips & knees in extension Measurements

• RF: 50% of ASIS to Patella

• VL: 50% of GT to lateral femoral condyle

Control CP

r = 0.85**

0

10

20

30

40

0 50 100 150 200 250 300

ISOMETRIC PEAK TORQUE (N.m)

VL M

T (

mm

)

r = 0.70**

0

10

20

30

40

0 20 40 60 80 100

*p < 0.05 **p < 0.01

Relationship of Muscle Thickness to Peak Torque

Rectus Femoris Cross-Sectional Areain CP by GMFCS Level and vs. Control

0

0.05

0.1

0.15

0.2

0.25

NON CP GMFCSI GMFCSII GMFCSIII GMFCSIV

NON CPGMFCSIGMFCSIIGMFCSIIIGMFCSIV

GMFCS X Normalized Cross-Sectional Area : r = 0.50, p =.05

CONTROL (23kg)

RFT=20.0 mm

RECTUS FEMORIS THICKNESS

GMFCS II(21kg)

RFT=13.3 mm

GMFCS III(25.6kg)

RFT=105 mm

GMFCS IV (28.4kg)

RFT=10.4 mm

CHANGE IN RECTUS CROSS SECTIONAL AREA (CSA) BY WEEKS IN SPORTS CAMP

R2 = 0.5534

-10

10

30

50

70

90

0 1 2 3 4 5 6

Weeks at Camp

CS

A (

% c

ha

ng

e)

r = 0.74

Does intense and prolonged physical activity > mm size in CP? (new evidence suggesting this is possible in as few as 3 weeks)

NEUROBIOLOGY OF ACTIVITYNEUROBIOLOGY OF ACTIVITY

Over the past 40 years, considerable data have been Over the past 40 years, considerable data have been accumulated on the beneficial physiological effects from accumulated on the beneficial physiological effects from physical activityphysical activity

We are now becoming aware what activity does for the brain We are now becoming aware what activity does for the brain (e.g. it decreases depression & slows cognitive decline in (e.g. it decreases depression & slows cognitive decline in Alzheimer's)Alzheimer's)

PROMOTING ACTIVITYPROMOTING ACTIVITY

• Activity should be done ‘early and often’; parents can have the Activity should be done ‘early and often’; parents can have the largest effect on this in infancylargest effect on this in infancy

• In addition to physical changes, personality, cognitive & social In addition to physical changes, personality, cognitive & social development may also be affected by early activity (or lack development may also be affected by early activity (or lack thereof)thereof)

Activty-Based Exercise Programs

• Catch-22: Those with CP need intense exercise to improve motor function, but they lack the motor function to exercise intensely.

• Therapeutic approach: Use of devices that force or enable person

to exercise beyond their voluntary capabilities Body-weight supported treadmill training Lokomat and other motor driven gait devices

FES and motor-assisted cycles

RANDOMIZED TRIAL OF TREADMILL TRAINING IN INFANTS WITH DOWN SYNDROME

(Ulrich DA, Ulrich BD, Angulo-Kinzler RM, Yun J 2001)

Description: 30 infants with DS assigned to control or home treadmill training beginning at independent sitting. Followed until onset of independent walking.

RESULTS

Review of BWSTT in Pediatric Rehabilitation (Damiano & DeJong, 2008 in press)

• Shown to be efficacious (RCT) in Down Syndrome to accelerate motor milestone acquisition; more intense training seems to increase activity levels at 2 years

• Pediatric SCI – prolonged training in a few individual cases with impressive anecdotal results in most (children can be taught to step even if they cannot move voluntarily)

• CNS impairments: 17 studies (no RCT) suggesting that this improves gait speed and GMFM D&E. No comparison to alternatives (e.g. over ground training)

RESULTS BWSTT: ICF ACTIVITYTable 6a. Cerebral palsy and other central motor impairments Outcome by ICF Category + Results

BWSTT only + Results BWSTT & other

+ Anecdotal results BWSTT

Results indicating no change or inconclusive

Activity & Participation 10 m Walk Test Free velocity Fast velocity GMFM A GMFM B GMFM C GMFM D GMFM E GMFM Total PEDI – mobility PEDI – self care Gait progression AIMS GMFCS Level Gillette FAQ WeeFIM transfers WeeFIM mobility Fugl-Meyer FAC Category SWAPS Therapist/ patient reported increase in participation

IV21&22 IV19 II14* II14*

IV10,20,, III18 II14*, IV15,20(IP), IV24 II14*, IV15,20, IV24 IV15 IV20(IP), IV24

IV9, V12 V16,23 V16,23 V16,23 V12,16,23 IV9,, V12,16,23 IV9, V16,23 V16 V16 V11,15,25

V13 V12 V12 V23

V16,25

IV9 IV10,15,17, V23 IV17, III18 IV15

IV15

IV15 IV9,20(OP) IV9, 21&22 IV9

IV9 V11

V12

IV17 IV20(OP)

* both groups did treadmill training

Potential Benefits of Treadmill Training in CPPotential Benefits of Treadmill Training in CP

• Strengthen anti-gravity muscles (by adjusting BWS or adding Strengthen anti-gravity muscles (by adjusting BWS or adding weights)weights)

• Increase gait speed (> belt speed)Increase gait speed (> belt speed)

• Improve gait symmetry (e.g. elongating shorter strides)Improve gait symmetry (e.g. elongating shorter strides)

• Improve interlimb coordination (through appropriate sensory Improve interlimb coordination (through appropriate sensory inputs + practice)inputs + practice)

• Increase endurance aerobic training)Increase endurance aerobic training)

• Combinations of aboveCombinations of above

Motor-Assisted Cycling• BWS treadmill training labor & cost intensive, difficult for therapist/ family

• External assistance needed for those who cannot cycle on their own due to paresis or lack of motor control (FES-cycles or new motor assist devices)

• Cycling can be performed in home with little or no assistance, trunk balance or WS

• Form of locomotion similar in phasing & frequency to walking (Ting, 2002)

• Evidence of shared neural circuitry & similar reflex modulation in walking & cycling (Brooke 1997)

Current Cycling Trial

PARTICIPANTS: 10 children w/ CP, ages 5-17, GMFCS III/IV

PROTOCOL: All perform 50RPM passive or active-assisted cycling 30 min/day for 5 days/week X 3 mos

GOAL: improve lower extremity coordination PRIMARY OUTCOMES: Changes in ‘comfortable’ &

‘as fast as possible’ cadence, variability in cadence, EMG reciprocation vs. synchronization

SECONDARY OUTCOMES: 1) changes in spasticity; 2) Changes in cortical activation in response to a sensory stimulation using fMRI – none able to be still enough

Case study from motor-assisted cycling studyCase study from motor-assisted cycling study

• 5 ½ yo boy with spastic diplegia5 ½ yo boy with spastic diplegia

• GMFCS III – ambulates w/ post walkerGMFCS III – ambulates w/ post walker

• Ashworth 3 (0-4) in quadriceps & hamstrings (strong catch in first Ashworth 3 (0-4) in quadriceps & hamstrings (strong catch in first half of motion)half of motion)

• Had adapted cycle, but needed assist from parents to ride Had adapted cycle, but needed assist from parents to ride

• He was able to cycle with the device part of the time (no resistance)He was able to cycle with the device part of the time (no resistance)

Cortical PlasticityCortical Plasticity

The brain is also use-dependent The brain is also use-dependent

• Dramatic changes in the PNS produce dramatic changes in brain (e.g. Dramatic changes in the PNS produce dramatic changes in brain (e.g. SCI; amputation)SCI; amputation)

• Spinal circuits can be accessed and trained – effects may be specific Spinal circuits can be accessed and trained – effects may be specific and localizedand localized

• Spinal circuits may be used to drive cortical changes that may be more Spinal circuits may be used to drive cortical changes that may be more generalizedgeneralized

• How do we help the brain recover?How do we help the brain recover?

What type of activity does brain like?What type of activity does brain like?

• Intense (amount, speed, mm activation)Intense (amount, speed, mm activation)

• Some imposed rhythm but variable (more neural control) Some imposed rhythm but variable (more neural control)

• Complex or interesting; solving problemsComplex or interesting; solving problems

• Electrical stimulation (other sensory stimulation)Electrical stimulation (other sensory stimulation)

• Locomotor training (loading/ proprioceptive input)Locomotor training (loading/ proprioceptive input)

Conclusions

Those with motor disorders need to be active their whole life to minimize negative plasticity in mm (e.g. atrophy) & optimize positive plasticity (e.g. >fiber size)

Increasingly obvious that we have been under-rehabilitating people with CP & other motor disorders

Potential for exercise and activity to restore neural function and connectivity just beginning to be realized, Muscle activation (electrical activity) appears necessary to drive cortical plasticity

THANK YOU

NIH CLINICAL CENTER