Spinal Cord Injury: Impact of Functional Rehabilitation on Clinical Recovery

A. Curt, MD

Spinal Cord Injury Center, University of Zuerich

ICORD, University of British Columbia

Spinal Cord Injury:

Impact of Functional Rehabilitation on

Clinical Recovery

The Challenge in

Human SCI

• informed clinical trials in human SCI

• appraisal of pre-clinical studies in SCI

Informed clinical trials in human SCI

0

20

40

60

80

100

ASIA B

ASIA C

ASIA D

ASIA category 2 months post iSCI

P

e

d

e

s

tr

ia

n

s

6

m

o

n

th

s

p

o

s

t

iS

C

I

(%

)

Dobkin B et al (2006) Neurology

outcome measures and thresholds

Informed clinical trials in human SCI

outcome measures and thresholds

0 10 20 30 40 50 60 70 C 0 1 C 0 3 C 0 4 C 0 4 C 0 4 C 0 4 C 0 5 C 0 5 C 0 5 C 0 5 C 0 5 C 0 6 C 0 6 C 0 6 C 0 6 C 0 7 C 0 7 Level of Injury d e lt a m o to r s c o re

Species specific differences in:

• Rubro – reticulo – vestibulo spinal descending motor projections

• proprio – spinal pathways and influence of CPG on locomotor output

• requirements of body function to achieve ADL relevant outcomes

Appraisal of pre-clinical studies in SCI

from bench to bedside in SCI

neuro- plasticity / regeneration / repair / protection

Objectives of talk

• Is spinal cord repair related to clinical recovery?

• Assessment of longitudinal and segmental spinal pathways

• Value add of electrophysiological recordings for proof of

0 20 40 60 80 100 0 30 60 90 120 150 180 210 240 270 300 330 360 A S IA m o to r 0 20 40 60 80 100 0 30 60 90 120 150 180 210 240 270 300 330 360 A S IA m o to r 0 20 40 60 80 100 0 30 60 90 120 150 180 210 240 270 300 330 360 A S IA m o to r 0 20 40 60 80 100 0 30 60 90 120 150 180 210 240 270 300 330 360 S C IM in % SCIM 0 20 40 60 80 100 0 30 60 90 120 150 180 210 240 270 300 330 360 S C IM in % SCIM 0 20 40 60 80 100 0 30 60 90 120 150 180 210 240 270 300 330 360 S C IM in % SCIM

Functional recovery independent of

changes in motor deficit

Complete tetra

thoracic

conus/cauda

Curt A, Hedel vH et al.. Recovery from a spinal cord injury: Significance of compensation, neural plasticity and repair. J Neurotrauma 2008 Wirth B, et al.. Changes in activity after a complete spinal cord injury as measured by the Spinal Cord Independence Measure II (SCIM II). Neurorehabil Neural Repair 2007

Functional recovery in

incomplete

spinal cord injury

•

10-m walk test

•

6-minute walk test

•

Timed up and go test

•

LEMS (manual muscle testing)

•

SCIM III (walking items)

•

WISCI II

•

Modified Ashworth Test

Outcome measures:

high clinical value

bu

t n

o m

ea

ns

of

m

ec

ha

nis

ms

!!

Robotic SCI rehab devices

Gait Trainer AutoAmbulator

Lokomat

Erigo

Armeo ReoTM

InMotion

ARMin

Ind

uc

ed

ch

an

ge

s a

ttri

bu

tab

le

to

mu

ltip

le

me

ch

an

ism

s!!

Is there repair of damaged pathways?

peripheral

paresis

routine

NCS / Reflex

EMG

peripheral

system

postural

instability

investiga-tional

GVS

vestibulo-spinal

pain/temp

perception

investiga-tional

EP

(Laser-Heat)

spino-thalamic

cardio-vascular

control

routine

SSR

sympa-thetic

proprio-ception

routine

SSEP

dSSEP

dorsal

column

central

paresis

routine

MEP

cortico-spinal

Clinical

correlate

Acceptance

Method

Spinal

pathway

2

1

1

3

4

5

6

Clinical Neurophysiology of

Spinal Cord Function

Clinical Neurophysiology of

Spinal Cord Function

peripheral

paresis

routine

NCS / Reflex

EMG

peripheral

system

postural

instability

investiga-tional

GVS

vestibulo-spinal

pain/temp

perception

investiga-tional

EP

(Laser-Heat)

spino-thalamic

cardio-vascular

control

routine

SSR

sympa-thetic

proprio-ception

routine

SSEP

dSSEP

dorsal

column

central

paresis

routine

MEP

cortico-spinal

Clinical

correlate

Acceptance

Method

Spinal

pathway

2

1

1

3

4

5

6

EMG recordings

MEP – silent period

Torque performance

TMS trigger

Cumulus sum

Motor evoked potentials

Paresis in iSCI

MMV remains unchanged

with frequency,

but is reduced in iSCI

ROM becomes reduced

with frequency and

R

OM

Accuracy

R

a

n

g

e

o

f

m

o

ti

o

n

Wirth et al, J Neurol 2008

accuracy in simple activation

–

timing of activation

–

releasing the antagonist

dorsiflexion in ambulation

–

initiation of swing phase

visually controlled tracking task

–

accuracy of tonic and phasic

activation

Dexterity in iSCI

Swing phase

CST conductivity during recovery

P<0.001 p=0.002

P<0.001

Follow up study in acute iSCI

SSEP recordings

normal

abolished

suspected

reduced

reduced

slowed

P = 40.5 ms

P = 44 ms

P = 53 ms

1. mth

3. mths

6. mths

Follow-up SSEP in ASIA C/D

Iseli E, Cavigelli A, Dietz V, Curt A. Prognosis and recovery in ischemic and traumatic SCI: Clinical and electrophysiological evaluation. J Neurol Neurosurg Psychiatry 1999

absolute latency (p40)

-3.11

-1.1

-3.46

-1.01

-40

0

A

B

CD

A

B

CD

PARA (p=0.23)

TETRA (p=0.51)

no significant change (student t t est)

c

h

a

n

g

e

i

n

p

e

rc

e

n

t

interpeak latency

-2.78

-3.04

-40

0

A

B

CD

A

B

CD

PARA (p=0.28)

TETRA (p=0.8)

no significant change (student t test)

c

h

a

n

g

e

i

n

m

s

SSEP amplitude

0.02

0.43

0.04

0.09

0.58

0.78

0

0.5

1

1.5

2

A

B

CD*

A

B

CD**

PARA

TETRA

a

m

p

li

tu

d

e

(

m

V

)

latency, interpeak latency

amplitude

Kramer J, et al.. D-SSEP and EPT for the assessment of posterior cord function in SCI. J Neurotrauma 2008

Dermatomal – SSEP

Dermatomal SSEP

C4

C5

C8

C6

C7

Pre-surgical MRI

Male 41yrs, fall injury

C6 ASIA A

D SSEP@R

C6/7

C4

C5

C6

C7

C8

C4/5

Female 53 yrs, MVA

C6 ASIA A

C4

C5

C6

C8

Preliminary Findings:

CHEP

Preliminary Findings:

CHEP

C4

C5

C6

Non-affected

Pathological

Abolished

Electrical Perception & Pain Thresholds

C5/6

Male 58yrs, fall injury

C5 ASIA B

Dermatomal Sensory Assessment

dSSEP of the trunk

from schematic drawing to reality

Complete paraplegia ASIA A

male 37 years, T5/6 dislocation fracture

T 2

T 4

T 7

Take home messages

•

No simple relation of specific pathways to complex function

•

Strong impact of functional rehabilitation on clinical outcomes

•

Electrophysiological recordings can be used to assess changes in

damaged pathways for proof of mechanism

but

don’t serve as outcome

Balgrist Clinic

M Schubert

G Lindemann

M Wirz

C Ruhde

Balgrist Research

V Dietz

H Hedel

B Wirth

P Halder

S Wydenkeller

J Blum

MRI UniZH

S Kollias

S Hotz

Rehab Eng ETHZH

R Riener

S Micera

R Gasser

ICORD

J Steeves

W Tetzlaff

J Kramer

P Taylor

Brain Res

Center UniZH

M Schwab

A Buchli

B Zoerner

G Courtine

Hocoma

G Colombo