neuroplastic responses to rehabilitation …neuroplastic responses to rehabilitation in children and...

NEUROPLASTIC RESPONSES TO REHABILITATION IN CHILDREN

AND INFANTS WITH CEREBRAL PALSY

Thubi H. A. Kolobe, PT, PhD, FAPTAUniversity of Oklahoma Health Sciences Center

Department of Rehabilitation [email protected]

Thubi Kolobe, PT, PhD; Andrew Gordon, PhD; Jill Hea thcock, MPT , PhD; Laura Prosser, PT , PhD

Acknowledgements

• National Institute of Child and Human Development

• National Institute of Neurological Disorders and Stroke

• APTA Section on Pediatrics

• Research Summit III Participants

Why Neuroplastic Responses?

• PT Interventions for children with an injured brain: – Persistent mixed results.– Small magnitude of change or gains– Sustainability

– Outcomes and outcome measures.– Structure-function relationship– Cost

– Huang et al, 2009; Mockford et al, 2008; Harris, 1997.

Why Neuroplastic Responses? • Relieving spasticity is not sufficient therapy to cause

long term change (Hoare et al, 2010).

• Repetition not be sufficient to attain meaningful changes in motor behavior if participants are not actively engaged in an intervention (Kleim and Jones, 2010).

• Pathophysiological evidence for decreased cortical inhibition and results of increasing inhibition (Benninger et al., 2011)

• Evidence that you gain what you train (Sakzewski et al, 2011)

• Development in brain imaging technology and capability.

Major Contributing Factors

• Heterogeneity of diagnoses and functional levels

• Differential responses to interventions (age maturation and family attributes)

• Limited understanding of the mechanism involved

• Lack of sensitive and responsive outcome measures.

• Intervention –related dosing

Structural and Behavioral changes: The disconnect

• What is motor learning without a good motor?

• Threshold for change

–Cortical reorganization and function

–Changes in muscle structure and gait

–Sustainability

–Mechanisms for adaptive learning

–Level of influence

Institute of Medicine, 2009

“By 2020 -- 90% of clinical decisions will be supported by accurate, timely, and up to date clinical information, and will reflect the best available evidence on what works for whom, under what circumstances”

Translation

• We can pick efficacious interventions

• We know their parameters: � How much for whom� How long

� Feasibility� Outcomes� Mediating effect� Cost

Translation

• The optimal dose for interventions and for clinically important change.

• The optimal dosage and interventions to improve to improve body structure and function, activity, and participation.

• How treatment outcomes are attained.

• How treatment outcomes are sustained

• The mechanism involved (structure-to-behavior change or vice versa)

Dosing

• Frequency (how often, number of sessions for a given intervention/day/week/month)

• Intensity (how hard, such as the number of repetitions per minute, day, week, or amount of wor k)

• Time (onset and duration)

• Type of an intervention (includes task practice, behavioral shaping, structured vs. unstructured training, and amount of feedback or reward).

American Council on Exercise, 2003

Research Summit III (RS III)

• Goals:o Platform for research development o Method to secure position for PT in rehabilitation,

prevention, health promotion, and health services research for children with or at risk for disabilities and their families

o Opportunity for creating networks among PT researchers and other disciplines

o Mechanism to develop multi-site research programs across multiple disciplines that is led by PT researchers

o Catalyst to move the PT research field forward

RS III (2011)Participants

FACULTY PhD PT Non-PT CLINICIANS

24** 22 26(56%)

20(44%)

6**

Key Questions� HOW MUCH of WHAT should be done for WHOM?

� BY WHOM? Does all need to be done in therapy?

� HOW LONG? Are we talking Antibiotics (short term) or Insulin (forever)?

� Is the optimal dose compatible with real life?

� Role of technology in providing or augmenting dose?

� HOW TO MEASURE how much is enough? Behavior vs. biomarkers.

� How to afford or fund what may be needed?

Opportunity

• Translational Research

• Knowledge Translation

Intervention-Related Dosing

• Key mediator

• Multifactorial Parameters:

Brain, Muscle, Bone, and Family functioning

Interactions:– Active ingredients– Biomechanical, neuromuscular, psychological,

cognitive

Research Recommendations

• A treatment must first demonstrate effectiveness before dose-related studies can be undertaken.– Multisite trials– Dosing thresholds – titration

– Sustainability – linking structure and behavior– Uptake of intervention – repeated measures– Child and family engagement – self-efficacy

Practice Recommendations and Implications

• Systematic implementation and documentation of current treatments and treatment parameters

• Ask a dosing question• Transfer from therapy sessions to life

situations• Staging OT/PT Interventions• Standardizing outcomes• Models of care• Collaboration and research

“Viable Interventions”

• CIMT, mCIMT, HABIT

• Treadmill training

• Botox and exercise

• Task oriented practice/training• Augmentative interventions (technology and

robotics)– Boyd et al, 2010; Gordon et al, 2011; Taub E, et al, 2007; Hoare et

al, 2010; Franki et al, 2012; Kleim & Jones, 2010.

Can we train the brain?

• Evidence of neuroplasticity

• Cortical Reorganization

Current and novel rehabilitation protocols

• Prone locomotion

• Upper extremity

• Infant reaching

• Walking

Self-Initiated Prone Progression

•The earliest type of functional mobility available to infants -- severely compromised in children with CP.

•Develops during a period of highly active synaptic formation in the brain.

• Development during infancy linked to other systems, such as vision, arousal, vestibular function, and perceptual-cognition

• Not responsive to traditional interventions


Robotics and Movement Learning:• Bypass early mobility constraints

• Early initiation of training before the age of expected emergence of or independence in skill

• Theories: Neuronal group selection, motor learning and development, and perception-action


Integration

• Brain imaging• Kinematics• Kinetics

• Performance behavior• Skill

THANK YOU!

References• Franki I, Desloovere K, De Cat J, et al. The evidence-base for basic physical

therapy techniques targeting lower limb function in children with cerebral palsy: a systematic review using the International Classification of Functioning, Disability and Health as a conceptual framework. J Rehabil Med. May 2012;44(5):385-395.

• Gordon, AM, Hung, YC, Brandao, M, Ferre, CL, Kuo, H-C, Friel, K, Petra, E, Chinnan, A,

• Charles, JR. Bimanual Training and Constraint-Induced Movement Therapy in Children with Hemiplegic Cerebral Palsy: A Randomized Trial. Neurorehabilitation and Neural Repair 2011; 25: 692-702.

• Huang HH, Fetters L, Hale J, McBride A. Bound for success: a systematic review of constraint-induced movement therapy in children with cerebral palsy supports improved arm and hand use. Phys Ther 2009;89(11):1126-41.

• Hoare BJ, Wallen MA, Imms C, Villanueva E, Rawicki HB, Carey L. Botulinum toxin A as an adjunct to treatment in the management of the upper limb in children with spastic cerebral palsy (UPDATE). Cochrane Database Syst Rev. 2010(1):CD003469.

• Institute of Medicine of the National Academies. Initial National Priorities for Comparative Effectiveness Research. Washington, DC: National Academies Press; 2009

References• Kleim, J. A., and Jones, T. A. (2010). Principles of experience-

dependent neural plasticity: implications for rehabilitation after brain damage. American Speech-Language-Hearing Association, 51, S225-239.2

• Sakzewski, L., Ziviani, J., Boyd, R. N., MacDonnell, R., Abbott, D., and Jackson, G. (2011). Randomized trial of constraint-induced movement therapy and bimanual training on activity outcomes for children with congenital hemiplegia. Developmental Medicine & Child Neurology 53, 313-320.

• Stephen Rose, Andrea Guzetta, Kerstin Pannek, Roslyn Boyd. MRI structural connectivity, disruption of primary sensorimotor pathways, and hand function in cerebral palsy. Brain Connectivity 2011; Volume 1, Number 4, DOI: 10.1089/brai

• . Taub E, Griffin A, Nick J, Gammons K, Uswatte G, Law CR. Pediatric CI therapy for stroke-induced hemiparesis in young children. Dev Neurorehabil. 2007;10:1-16.

What is the Right Dose of What is the Right Dose of Therapy?Therapy?

Andrew M. Gordon, Ph.D.Andrew M. Gordon, Ph.D.

Motor Learning

• Children with CP have impairments in motor planning and learning above and beyond impairments in motor execution (e.g., Gordon and Duff 1999; Duff & Gordon 2003; Shumway-Cook et al. 2003; Hung et al. 2013).

• However, they do improve with practice, but only with lots of practice (Neilson et al. 1990, Valvano & Newell 1998, Gordon et al. 1999; Hung et al. 2013).

• Thus, INTENSITY MATTERS!

• How can we provide opportunities for intensive practice?

• What is the “right dose of therapy”?

• What therapies should we dose?

Successful upper extremity training protocols

Novak et al. 2013 DMCNNovak et al. 2013 DMCN

How can we improve hand function?

Basic Science• Mott-Sherrington (1895)• Munk (1909)• Ogden and response in small increments (successive

approximations; Franz, 1917) • Tower, Berman, Taub• Merzenick, Nudo, Jones, Shallert, Kleim

Adult Stroke• First human studies of forced use: Ostendorf and Wolf (1981),

Wolf et al. (1989)• First human studies of CIMT: Taub et. al. (1993)• Extremity Constraint-Induced Therapy Evaluation (EXCITE)

multi-site randomized clinical trial (e.g., Wolf et al. 2006 JAMA; 2007; etc.)

• Reviews: Fritz SL, Butts RJ, Wolf SL. Expert Rev Neurother. 2012; 12(2):191-8.

Pediatr Phys Ther 2001;13:68–76

Reviews

• > 80 studies of peds CIMT, >30 RCT

Reviews:

• Sakzewski et al. (2009) Pediatrics. 123(6):e1111-22.

• Gordon (2011) Dev Med Child Neurol.• Gordon, AM Constraint-induced therapy and bimanual training in children with

unilateral cerebral palsy. In: R Shepherd (Ed.) Cerebral Palsy in Infancy and Early Childhood Optimizing Growth, Development and Motor Performance. Elsevier. (In Press).

• Andersen JC, Majnemer A, O'Grady K, Gordon AM. Semin Pediatr Neurol. 2013

CIMT studies CIMT studies in CPin CP

International consensus meeting on pediatric CIMT, January 2012, Stockholm, Sweden

Eliasson et al. (In Press)Eliasson et al. (In Press)

And the consensus on what we know was……

• It works!

• It works in young and older children

• It works when given 24/7 or just 2 hrs/day (in young children)

• It works with casts, slings, gloves, and no restraint whatsoever

• It works one-on-one, at home, in preschool, in day camps

• No evidence that any specific model of CIMT demonstrates greater improvement than another.


CIMT (day camp model)

• 26 CIMT/Bimanual training day camps at Columbia University since2002

• >180 children (age 3.5 to 17yrs), with many repeating

• 6hrs/day, 10-15 days

• BE AS CHILD-FRIENDLY AS POSSIBLE• Functional and play activities

• 1:1 interventionist/child ratio

• Repetitive (part) Practice

• Task (whole) Practice• Feedback: Positive Reinforcement

• Home practice• Logs


AH

A U

nit

AH

A U

nit

CaseCase--Smith et al. 2012Smith et al. 2012

Dosing

Gordon 2011 DMCNGordon 2011 DMCN

DosingDosing

Time

(s)

250

300

350

400

450

First pretest First TxPost-test

One yearPost-test

Second TxPost-test

First TxSecond Tx

So CIMT is not a one-time miracle.

Charles and Gordon (2007) DMCN

Intensity can be distributed over development

Rationale for bimanual control

• Even “less affected” hand is affected.

• Many bimanual movements may have never been practiced.

• Impaired ability to coordinate both hands together (Hung et al. 2004; 2010).

• Unlike unilateral impairments, these bimanual coordination problems may underlie some of the functional limitations these children experience.

• ~85% of parent goals found to be bimanual (Gordon et al. 2011, Brandao et al. 2012).

• During bimanual movements the non-involved hand could provide a template for the involved hand when movements are either performed sequentially (Gordon et al. 1999, 2006, Raghavan et al. 2006) or simultaneously (Utley et al. 2004, Steenbergen et al. 2008).

Hand-Arm Bimanual Intensive Therapy (HABIT)

HABITHABIT•• No restraintNo restraint•• Same duration as CIMT (2Same duration as CIMT (2--3 weeks)3 weeks)•• Bimanual activities (e.g., cards, Bimanual activities (e.g., cards,

wrapping presents, video games, ball wrapping presents, video games, ball throwing, zipping a jacket)throwing, zipping a jacket)

•• Day camp (1Day camp (1--1 interventionist1 interventionist--child)child)

Task DesignationTask Designation•• StabilizerStabilizer•• Passive/active assistPassive/active assist•• ManipulatorManipulator

•• Gordon et al. (2007, 2008, 2011Gordon et al. (2007, 2008, 2011))

Charles and Gordon, (2006) Dev Med Child Neurol Charles and Gordon, (2006) Dev Med Child Neurol Nov;48(11):931Nov;48(11):931--6. 6.

Randomized trial comparing CIMT and bimanual training (HABIT) that

maintains the intensity of practice associated with CIMT

n=42, 90hrs training

Hypothesis: participants in the CIMT group will have greater improvements in unimanual dexterity whereas participants in the bimanual training group will have greater improvements in bimanual hand use—i.e., specificity of training.

Gordon et al. (2011), Neurorehab & Neural RepairGordon et al. (2011), Neurorehab & Neural Repair

Gordon et al. (2011), Neurorehab & Neural RepairGordon et al. (2011), Neurorehab & Neural Repair

No specificity of training

HABITHABITCIMTCIMT

Specificity of training

Hung et al. (2011)Hung et al. (2011)

DrawerDrawer

SwitchSwitch

HandleHandle

Reflective markerReflective marker

Movement overlap of the two Movement overlap of the two hands increases after bimanual hands increases after bimanual

trainingtraining

Normalized Movement Overlap

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

pre post

involved HABIT

non-invovled HABIT

Involved CIT

non-invovled CITOve

rlap

(%)

Ove

rlap

(%)

00

1010

2020

4040

3030

6060

5050

Goals

Brandao et al. (2012)Brandao et al. (2012) Green et al. (2013)Green et al. (2013)

Magic HABITMagic HABIT

Dosing

Gordon 2011 DMCNGordon 2011 DMCN

• Single-pulse TMS mapping, Magstim 200 stimulator, figure-8 coil.

• Co-registered TMS stimulation sites to individual MRIs, Brainsight software.

• Recorded EMG in digit, wrist, and biceps muscles bilaterally during TMS.

• Mapped hand representation bilaterally, 1 cm intervals, centered around spot of greatest activation of digit muscle.

• Mapping intensity – 110% pre-training motor threshold.

• Same TMS intensity used before and after training.

Cortical representations

Friel et al. (In Preparation)Friel et al. (In Preparation)

TMS Map TMS Map –– Affected Hand, Affected Hand, Structured Skill TrainingStructured Skill Training


Skill training

• Newly learned movements are represented over large cortical areas (e.g., Kleim et al. 1998, Plautz et al. 2000)

• Active training vs. “forced use” in feline model of hemiplegia (Friel et al. 2012).

• "repetitive motor activity alone does not produce functional reorganization of cortical motor maps… Instead, motor skill acquisition, or motor learning, is a prerequisite factor in driving representational plasticity in motor cortex”(Nudo 2003).

Does structured practice matter?

• RCT of 24 children, age 6-14yrs

• Structured practice group: Environmental constraints manipulated, skill progression, part-practice (shaping), goal-directed.

• Unstructured practice group: Bimanual play

• Day-camp environment, 6 hrs/day, 15 days

• AHA, Jebsen-Taylor, Abilhand-Kids, COPM

• Testing immediately before and after tx, 6-months

• Evaluator and interventionistsblindedBrandao et al. (In Preparation)Brandao et al. (In Preparation)

Similar improvements regardless of practice type

Brandao et al. (In Preparation)Brandao et al. (In Preparation)

• Hand Map expands for structured practice group

• But not for unstructured practice group

• Motor Learning!!!


HandHand--Arm Bimanual Intensive Therapy Arm Bimanual Intensive Therapy Including Lower Extremity (HABITIncluding Lower Extremity (HABIT--ILE)ILE)

• LE abilities may decrease during development in CP

• Interactions between UE and LE are rarely trained despite importance in everyday life

• We aimed to modify HABIT to include a systematic lower extremity and / or postural component

• Compare intensive HABIT-ILE with usual and customary (NDT-based) PT of equal duration.

Bleyenheuft and Gordon (Submitted)Bleyenheuft and Gordon (Submitted)

HABITHABIT --ILE ILE 90 h of treatment90 h of treatment

1 interventionnist / 1 child1 interventionnist / 1 child

9 h a day in 9 h a day in overnight campovernight camp

Control groupControl group90 h PT/OT over 4 mos.90 h PT/OT over 4 mos.

CrossCross --over designover designBleyenheuft et al. (In preparation)Bleyenheuft et al. (In preparation)

Results

Assessement 1 Assessement 2 Assessement 3

AH

A (

AH

A u

nit)

40

50

60

70

80

90

100


Ab

ilha

nd-k

ids

(log

its)

-2

0

2

4

6


AB

ILO

CO

-Kid

s (lo

gits

)

0

2

4

6

8


6 M

WT

(m

)

300

400

500

600

A

C D

B

Bleyenheuft et al. (In preparation)Bleyenheuft et al. (In preparation)

Feasibility of a HomeFeasibility of a Home--based Handbased Hand--arm Bimanual Intensive arm Bimanual Intensive Training for Young Children with Hemiplegic Cerebral Palsy Training for Young Children with Hemiplegic Cerebral Palsy

Ferre et al. In PreparationFerre et al. In Preparation

Preliminary Results: Bimanual hand use

Ferre et al. In PreparationFerre et al. In Preparation

Summary• Intensive (active) training works!

• Just increasing the dose of usual and customary (NDT-based) care does not benefit the child—ingredients matter!

• Both CIMT and bimanual training improve unimanual and bimanual function similarly in children with unilateral CP with some nuances (see also recent studies by Sakzewski, Wallen, Facchin, Hoare, Deppe).

• Not mutually exclusive of each other, and can perhaps be combined over time as seen fit.

• Skill training may enhance plasticity in motor cortex

Summary (cont.)

•Lower extremity benefits from combined UE and LE targeted intensity

•Dosing—more is better, but not more of the same, and it does not have to be delivered all at once!

•How do you get to Carnegie Hall?

•PRACTICE!

•Practice a lot, but practice the instrument you want to play!

AcknowledgementsAcknowledgements

Clinical studies: Marina Brandao, OT, PhD, YaMarina Brandao, OT, PhD, Ya--Ching Hung, PT, EdD, Cherie Kuo, PT, Claudio Ferre, MS, Ashley Ching Hung, PT, EdD, Cherie Kuo, PT, Claudio Ferre, MS, Ashley Chinnan, PT, Jeanne Charles, PT, MSW, PhD, Bert Steenbergen, EugChinnan, PT, Jeanne Charles, PT, MSW, PhD, Bert Steenbergen, Eugene Rameckers, PT, PhD, Yannick Bleyenheuft, PT, ene Rameckers, PT, PhD, Yannick Bleyenheuft, PT,

PhDPhD

TMS/Imaging: Kathleen Friel, PhD, Kathleen Friel, PhD, Sarah Lisanby, M.D., Jason Carmel, M.D. Arielle Stanford, M.D., Stefan Rowny, M.D., Joshua Berman, M.D. Charles Schroeder, Ph.D., Bruce Bassi, David Murphy, Jaimie Gowatsky, Joy Hirsch, Ph.D.,

Stephen Dashnaw, Glenn Castillo

Volunteers Volunteers

ParticipantsParticipants Supported by:Supported by:

http://www.facebook.com/CenterCPResearchThrasher Research FundThrasher Research Fund

CVS CaremarkCVS CaremarkEE--mail: [email protected]: [email protected]

Neonatal Stroke, Hemiparesis, Clinical protocols

Jill C. Heathcock MPT, PhDAssistant Professor

Division of Physical Therapy

Overview

• Promising Therapies • Protocols and Novel Adaptations• At risk infant populations• Children with Hemiparesis• Toddlers with CP

Upper Extremity

Infantand ChildReaching

Lower Extremity

Feet Reaching

and Treadmill Training

High(er) Dosing Clinical

Protocols

Typically Developing Infants and Young Children

• Development of the Nervous System• Critical Periods

o Activity dependent myelination in first year of life

o Activity dependent tract development and refinement in first 3 years (Martin 2005)

Infants with Neonatal Stroke

• Injury• Risk factors• Hemiplegia• Reaching

Neonatal Stroke

• Brain Structure– Non sedation MRI

• Spontaneous Arm Movements– Kinematics

• Reaching deficits as children with hemiparesis

Motor learning and the development of reaching skill

• Typically developing infants– Independently explore environment

• Reaching with the hands– 3 - 6 months (Gesell 1947, Thelen 1993)

• Role of spontaneous movements• Midline behaviors

– precursor to reaching (Galloway, 2004)– march to midline

Neonatal Stroke

• Brain ischemia or hemorrhage during perinatal stage

• Focal interruption of blood supply, occurring between 20 weeks of fetal life through 28th

postnatal day (Lynch 2009)

• Incidence : 1 in 1600 to 5000 births (Perlman, 1994. Estan,1997. Schulzke,2005. Lee, 2005. Laugesaar, 2007)

68

Neonatal Stroke

• Clinical presentation:• Seizures

• Signs and symptoms of neonatal encephalopathy• Delayed milestones

• Outcomes

• Died from the stroke: 3%• Neurologically normal: 40%• Motor and/or cognitive deficits: 57%

--- Lynch, 2001

69

Neonatal stroke is an important contributor to the pathogenesis of

cerebral palsy

Cerebral Palsy

• The incidence of cerebral palsy in infants with perinatal stroke is around 30 to 58 %

• --- Sreenan, 2000. Mercuri, 2004. Lee, 2005

• Hemiplegic cerebral palsy is the most common type of CP in stroke infants

• Asymmetric motor performance between both sides – Upper limb involved more– Distal part is more severe

70

Reaching and grasping

Reaching

• Reaching is an important functional ability and may related to other motor performance.

--- Fallang, 2003

• Poorer reaching performance, which include qualitative and quantitative results, in preterm population--- Fallang, 2003. Toledo, 2007. Heathcock, 2008

• To compare reaching development in infants with and without neonatal stroke.

71

Reaching, Grasping and Motor Skill Development

72

Reaching ExperimentHealthy Control group (n=16)

• Main visit effect (p<0.001). Reaching number increased over time on both sides.• There is no significant difference between right and left side on reaching

number in the bilateral reaching condition (p=0.734).

Reaching experiment

74

Grasping Experiment

• Main visit effects for visit and group P < 0.001 p = 0.029

• Neonatal stroke demonstrated less bi-manual toy manipulation

BSID-III

• Fine Motor

• Raw Scores

• Gross Motor

• Raw Scores

Target Training and Dose

• Home Program

• Daily (5 days/week) for 10 minutes

• 20 weeks – 75% = journal

Training

• Specific Movements– Bilateral

– Rationale• Midline experience

may be necessary for reaching (van Hof 2002)

• Children with hemiparesis have poor bilateral reaching skills (Utley, 2006)

• Poor Midline behaviors in preliminary project

Training

• Specific Movements– Single joint (Bhat, 2006)

– Rationale• Infants with brain injury

infants show increased coupling as compared to full term infants (Heathcock

2005, Heriza 1996, Vaal 2000, Jeng 2004)

• Children with hemiparesis show poor dissociation (Ronnqvist, L, 2007)

Effects of Training-Pilot

• Reaching • Grasping

Children with Hemiparesis

• Transcranial Magnetic Stimulation (TMS)

• Task-- reaching to a target

(photo)

Kinematics of reaching

• Case series

Combination Therapies

TMS CIMT

Feet Reaching

Lower Extremity

• ARMS– Full-term infants reach with their hands when they

are three to six months of age • preterm infants show delays in reaching even when age-

corrected for preterm birth – improved ability after several weeks of training

• LEGS– Full-term infants display adequate control of their

legs to repeatedly reach out and contact a stationary toy with their feet

• several weeks before they do so with their hands • improve this ability after several weeks of training

Galloway et al, 2004 and Lobo et al, 2005

Purposeful Control of the Legs

• Full-term infants begin to gain purposeful control of their legs within the first months of postnatal life – Two most commonly studies leg behaviors

• spontaneous kicking– no external feedback

– developmental progression

• “instrumented kicking”– significant external feedback

• 27 subject 8 weeks of age

• Hand and Feet– 6 trials– 30 seconds

• Results– Hands = 23 contacts (.88)

– Feet = 191 contacts (7)

Type

• Social Group

Feet Reaching Results

Both groups contacted the toy multiple time in the first session. There was an increase the number of contacts over time; Infants in the Movement group contacted the toy more frequently than the Social group

Average Foot-Toy Contacts per Session

0

5

10

15

20

25

30

35

40

45

1 2 3 4 5Session

Foo

t-T

oy C

onta

cts

Movement Group

Social Group*

Treadmill Training

• Infants– Novel Therapies

• Case studies

– Real time• Spina bifida• Full-term (healthy)

– Sensory Input

What is the optimal dosage to improve to improve functional ambulation?

• ManuscriptsoProtocol Ranges

� 4 – 30 minutes� 2 – 5 days per week

� 12 weeks – 30 weeks

� Gait speed� Target: normal speed for age� Adjusted each session

� Home vs. Clinical setting� Weights

Improvements

o Independent StepsoDistanceoGait Impairments

� Velocity, stride length, � Muscle activation� Coordination

� joint kinematics

oLevel of activityoLevel of participationoNeuroplasticity with MRI

• Outcomes• Varying Protocol• Limited description of Intervention• Locomotor Training vs. or in addition to

BWSTT• Span ICF

o but inconsistently

o Limited, if any, neuroplastic changes

High(er) Dosing Clinical Protocols

• STRIVESkilled Therapy focused on Repetition, Intensity, Variable practice, and Education

• Existing intensive therapy programs– Treadmill training for older, ambulatory children

– CIMT for children with hemiplegia

• Lack of an intensive therapy program for younger children and those who are non-ambulatory – Inspiration

– Motor learning

– Treatment individualized by participant• Focus on 1-2 specific goals

• Example goals– Prop sitting– Independent sitting– Commando crawling

– Walking with a device

– Outcome Measures• GMFM-66/GMFM-88

• Bayley-III

• Dose – 2 hours per day * 5 days per week * 4 weeks– 40 hours total

• Patients (n=18)– Age

• Mean = 26.39 months (SD = 11.75 months)

• Range = 11.2 to 50.1 months

– Diagnoses• Cerebral Palsy (n = 15)

• Developmental Delay (n = 2)• Myelomeningocele (n = 1)

Results Results

Conclusions

• STRIVE protocol appears to improve gross motor function in young children with cerebral palsy– 10 of 14 had a clinically meaningful change in

GMFM-66

• Younger age associated with greater changes

• May impact multiple domains of development

Acknowledgements

– Warren Lo, MD

– Nasser Kashou, PhD

– Chao-Ying Chen, MS– Ann Cahalan

– Hanna Sorg

– Sara Mrowzinski, SPT– Sarah Hendershot, DPT

– Rachel Ferrante, DPT

– Kathleen Stuart, DPT

– Helen Carey, PT, MS, PCS

100

Laura Prosser, PT, PhD

How do we facilitate neuroplasticity

& optimize motor learning?

Prosser et al. Dev Neurorehabil 2012.

Neuroplasticity & Infant learning

Motor learning during the development of

walking skill

Error and

Variability

Current strategies for gait training

Little Error or

Variability

• “Perfect” practice

• Regimented locomotor training programs

• Devices that compensate for poor postural control

Early mobility training for toddlers with

cerebral palsy – a pilot study

Prosser LA, Ohlrich L, Curatalo LA, Alter KA, Damiano DL

Rehabilitation Medicine Department, NIH Clinical Center, Bethesda, MD

Early Mobility Training

• 3x/week for 6 weeks

• 30 min of varied mobility training with dynamic weight support

• Mimic typical toddler motor play/exploration

• All sessions videotaped for later coding by activity

Why Dynamic Weight Support?

DynamicStatic

• Unconstrained movement

• Allows postural error and falls*

• Can closely mimic typical motor development*

• Movement constrained strap length

• No postural error allowed

• Not able to mimic typical toddler walking

Study Design

Single-subject design with repeated measures during

baseline and treatment phases

Assess

ment 1

Assess

ment 3

Assess

ment 5

Assess

ment 7

Assess

ment 2

Assess

ment 4

Assess

ment 6

Assess

ment 8

Baseline Mobility Training Withdraw

Participants

ID Age (yrs) Cause of CP GMFCS

1 1.5 Preterm (30 wks) III

2 2.3 Preterm (30 wks) III

3 1.4 Cerebral infection at birth II

4 1.0 Hypoxia at birth III

5 1.2 CVA near birth I

Introducing error and movement variability

21 month old, GMFCS II

Wk 6

(Pre-tx)

Wk 8

(After 2

wks of tx)

Therapy 6

Therapy 1

14 month old, GMFCS III

27 month old, GMFCS III15 month old, GMFCS I

m=0.295

Gross motor function

Changes attributable to treatment in 4/5


ID Baseline Treatment WithdrawRate during Tx

relative to Baseline

Rate during

Withdraw relative

to Baseline

MT01 0.05 0.55 0.04 10.8 0.7

MT02 0.16 0.61 0.08 3.8 0.5

MT03 0.30 2.05 0.20 7.0 0.7

MT04 0.05 0.77 0.24 15.1 4.6

MT05 1.56 0.46 -0.06 0.3 -0.04

Motor development rates


Are the changes related to treatment

activities?

GMFM C (Crawling

& Kneeling)

GMFM D

(Standing)

GMFM E (Walking,

Running, Jumping)

Not participating or breaks

(fussy, being held, etc)

Not

recordedTotal Falls

11:56 10:58 03:32 02:14 01:20 30:00 10

Video coding - exampleVideo coding - example

Outcomes by GMFM sub-scaleOutcomes by GMFM sub-scale

ID

Dimension change

explained by therapy

time (r2)

1 0.80

2 0.74

3 0.98

4 1.00

5 -

GMFM change vs. FallsGMFM change vs. Falls

1. Net change scores exceeded clinically

important differences for large treatment

effect

2. Net change scores were roughly half the

amount needed to increase 1 level on

GMFCS

1. Net change scores exceeded clinically

important differences for large treatment

effect

2. Net change scores were roughly half the

amount needed to increase 1 level on

GMFCS

Were the changes meaningful?

Participants, their families, their PTs

Diane Damiano, PT, PhD

Katharine Alter, MD

Laurie Ohlrich, PT

Lindsey Curatalo, MS

Joe Hidler, PhD

Sara Sadeghi

Cris Zampieri-Gallagher, PT, PhD

Hyung Park, PhD

Chris Stanley, MS

Acknowledgements

How do we best deliver and dose

rehabilitation interventions?

IT’S NOT EASY …Different dosing protocols for multiple impaired systems

IT’S NOT EASY …Are our interventions even effective?

IT’S NOT EASY …Is more or less actually better?

Dosing Parameters

Frequency 100s to 1000s+ repetitions

More than competing movement pattern?

(Some intermittent rest needed for consolidation)

Need to be creative to achieve high dose

Intensity Physical challenge with mental engagement

Time Duration: Months

TIMING: Earlier vs. later?

Type Functional context

Allows repeated practice

Encourages active engagement

126

Thank YouThank You

QuestionsQuestions

neuroplastic responses to rehabilitation …neuroplastic responses to rehabilitation in children and...

Documents