Professional Documents
Culture Documents
and
Spinal Cord Injury
A. Curt, MD FRCPC
Spinal Cord Injury Center, University of Zuerich
University Hospital Balgrist
Neurotrauma
Neurotrauma
Brain
Spinal cord
CNS
PNS
The challenge
informed clinical trials in human SCI
appraisal of pre-clinical studies in SCI
proof of mechanisms in human SCI
2002
2003
2004
2005
2006
2007
2008
2009
Scientific output
International recognition
20
15
10
5
0
2004
2005
2006
2007
2008
2009
100
80
60
40
20
0
ASIA B
ASIA C
ASIA D
70
60
40
30
20
10
C07
C07
C06
C06
C06
C06
C05
C05
C05
C05
C05
C04
C04
C04
C04
C03
0
C01
50
Level of Injury
80
80
80
60
40
ASIA motor
100
60
40
20
20
60
40
20
0
0
30
60
90
120
150
180
210
240
270
300
330
360
30
60
90
120 150
180
210 240
270
300 330
360
100
100
SCIM in %
60
40
20
SCIM
80
SCIM
60
40
30
60
90
90
120
150
180
210
240
270
300
330
360
80
60
SCIM
40
0
0
60
20
20
30
100
SCIM in %
80
SCIM in %
conus/cauda
100
ASIA motor
ASIA motor
Complete tetra
100
30
60
90
30
60
90
120
150
180
210
240
270
300
330
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
360
90
80
77
SCIM score
70
69
68
60
56
55
50
40
30
26
20
20
14
10
0
0
30
60
90
120
150
180
210
240
270
300
330
360
Objectives of talk
Is there spinal cord repair in clinical recovery?
Sensitive assessment of longitudinal spinal and segmental
pathways?
Spinal cord plasticity and proof of mechanism / concept of
interventional trials?
lesion
Functional recovery in
incomplete spinal cord injury
Outcome measures:
high clinical value
!
!
s
m
s
i
10-m walk test
n
a
h
6-minute walk test
c
e
m
Timed up and go test
f
o
s
n
LEMS (manual muscle testing)
a
e
m
SCIM III (walking items)
o
n
t
WISCI
II
u
b
Modified Ashworth Test
e
Robotic SCI rehab devices
l
b
a
t
u
b
i
r s!!
t
t
a
m
s
s
e ni
g
n
a
a
h
c
h
c
e
d
m
e
e
c
l
u
p
i
t
d
l
n
u
I
m
to
Gait Trainer
Armeo
AutoAmbulator
ReoTM
Lokomat
InMotion
Erigo
ARMin
acute
acute
chronic
acute
acute
chronic
chronic
Clinical Neurophysiology of
Spinal Cord Function
Spinal pathway
Method
Acceptance
Clinical
correlate
cortico-spinal1
MEP
routine
central
paresis
dorsal column2
SSEP
dSSEP
routine
proprioception
sympa-thetic3
SSR
routine
cardiovascular
control
spino-thalamic4
EP
(CHEPs)
routine
pain/temp
perception
vestibulo-spinal5
GVS
investigational
postural
instability
peripheral system6
NCS / Reflex
EMG
routine
peripheral
paresis
1
3
4
6
1
5
Dietz V, Curt A. Neurological aspects of spinal cord repair: promises and challenges. Lancet Neurology 2006
Paresis in iSCI
MMV remains unchanged with frequency, ROM becomes reduced with frequency and
but is reduced in iSCI
is lower in iSCI
Dexterity in iSCI
Range of motion
ROM
Accuracy
iSCI patient
control
Time
Dexterity in iSCI
Accuracy
Dexterity in iSCI
Accuracy
Dexterity in iSCI
Dexterity in iSCI
accuracy in simple activation
Swing phase
timing of activation
releasing the antagonist
dorsiflexion in ambulation
Wirth B, van Hedel H, Curt A. Foot control in incomplete SCI: distinction between paresis and dexterity. Neurological Res 2007
TMS trigger
Cumulus sum
Diehl P, Kliesch U, Dietz V, Curt A. Impaired facilitation of motor evoked potentials in incomplete spinal cord injury. J Neurology 2006
Standardized
regression
coefficient
p-value
Standardized
regression
coefficient
p-value
R2adj.
Max Movement
Velocity 0.8 Hz
-0.435
0.046
0.542
0.016
Max Movement
Velocity 1.6 Hz
-0.571
0.013
0.367
0.091
0.350
Max Movement
Velocity 2.4 Hz
-0.606
0.002
0.589
0.002
0.616
Max Ankle
Torque
-0.505
0.039
excluded
0.205
excluded
0.000
Manual Muscle
Testing
excluded
0.371
Hedel vH, Murer C, Dietz V, Curt A. The amplitude of lower leg motor evoked potentials is a reliable measure when controlled for torque and motor task.
J Neurol 2007
SSEP recordings
normal
reduced
reduced
slowed
suspected
abolished
P = 44 ms
P = 53 ms
1. mth
3. mths
6. mths
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
Message I
No obvious spinal cord repair in respect of
remyelination of longitudinal spinal pathways!
Dermatomal SSEP
Electrical Perception Threshold (EPT)
Kramer J, et al.. D-SSEP and EPT for the assessment of posterior cord function in SCI.
J Neurotrauma 2008
Pre-surgical MRI
Dermatomal SSEP
C4
C5
C6/7
C6
C7
C8
Kramer J, et al.. D-SSEP and EPT for the assessment of posterior cord function in SCI. J Neurotrauma 2008
T4
T7
T 10
Spinothalamic pathways
a-Delta / C-fiber stimulation (CHEPs)
C4
C5
C8
C4
Non-affected
C5
Pathological
C6
Abolished
Segmental CHEPs
Ulnar SSEP
Tibial SSEP
Message II
Limited recovery of segmental pathways
close to the epicenter of lesion!
Strength
49/50
Sensibility
21/24
Prehension
42/42
98%
88%
100%
ADM
right
median
right
C6
right
C6
right
MNCS
MEP/TMS
SSEP
CHEP
dSSEP
T7
Cz
[V]
15
10
CHEPs
T7
-5
regular
-10
-15
100
200
300
400
500
600
700
800
900
[ms]
MEP
latency
Message III
There is a huge spinal cord plasticity dependent
on the pathophysiological background!
Do we underestimate potential approaches to
induce slowly evolving recovery?
neuronal
deficit
neuronal
structure
Neurotrauma
In human SCI:
CORTICOL CONTROL
SPINAL CONDUCTION
Brain control
Preservation - Reorganization
No effective remyelination
Propriospinal pathways ?
Adaptation of motoneurones
and muscle properties
SPINAL SEGMENTS
Dexterity
Weakness
MOTOR OUTPUTS