Spinal Cord Injury: Impact of Functional Rehabilitation on Clinical Recovery

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1 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

2 The Challenge in Human SCI informed clinical trials in human SCI appraisal of pre-clinical studies in SCI proof of mechanisms in human SCI

3 Informed clinical trials in human SCI outcome measures and thresholds Pedestrians 6 months post isci (%) ASIA B ASIA C ASIA D ASIA category 2 months post isci Fawcett J et al (2007) Spinal Cord Dobkin B et al (2006) Neurology

4 Informed clinical trials in human SCI outcome measures and thresholds delta motor score C01 C03 C04 C04 C04 C04 C05 C05 C05 C05 C05 C06 C06 C06 C06 C07 C07 Level of Injury Sygen control data (n=195 tetraplegic patients)

5 Appraisal of pre-clinical studies in SCI effectiveness and clinical relevance in humans 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

6 Proof of mechanism in human SCI from bench to bedside in SCI neuro- plasticity / regeneration / repair / protection

7 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 mechanism / concept of interventional trials

8 Functional recovery independent of changes in motor deficit 100 Complete tetra thoracic conus/cauda ASIA motor ASIA motor ASIA motor SCIM 80 SCIM 80 SCIM in % SCIM in % SCIM in % SCIM 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

9 Functional recovery in incomplete spinal cord injury 3 weeks after injury 12 weeks after injury

10 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 but no means of mechanisms!!

11 Robotic SCI rehab devices Gait Trainer AutoAmbulator Lokomat Erigo Induced changes attributable to multiple mechanisms!! Armeo ReoTM InMotion ARMin

12 lesion Is there repair of damaged pathways?

13 Clinical Neurophysiology of Spinal Cord Function Spinal pathway Method Acceptance Clinical correlate proprioception corticospinal 1 dorsal column 2 sympathetic 3 investigational spinothalamic 4 investigational vestibulospinal 5 MEP SSEP dssep SSR EP (Laser-Heat) GVS routine routine routine central paresis cardiovascular control pain/temp perception postural instability peripheral system 6 NCS / Reflex EMG routine peripheral paresis Dietz V, Curt A. Neurological aspects of spinal cord repair: promises and challenges. Lancet Neurology 2006

14 Clinical Neurophysiology of Spinal Cord Function Spinal pathway Method Acceptance Clinical correlate proprioception corticospinal 1 dorsal column 2 sympathetic 3 investigational spinothalamic 4 investigational vestibulospinal 5 MEP SSEP dssep SSR EP (Laser-Heat) GVS routine routine routine central paresis cardiovascular control pain/temp perception postural instability peripheral system 6 NCS / Reflex EMG routine peripheral paresis Dietz V, Curt A. Neurological aspects of spinal cord repair: promises and challenges. Lancet Neurology 2006

15 Motor evoked potentials EMG recordings MEP silent period Torque performance 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

16 Paresis in isci MMV remains unchanged with frequency, but is reduced in isci ROM becomes reduced with frequency and is lower in isci

17 Dexterity in isci Accuracy ROM Range of motion isci patient control Time Wirth et al, J Neurol 2008

18 Dexterity in isci Swing phase 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 Wirth B, van Hedel H, Curt A. Foot control in incomplete SCI: distinction between paresis and dexterity. Neurological Res 2007

19 CST conductivity during recovery P<0.001 p=0.002 P<0.001 Follow up study in acute isci Wirth B, Hedel vh, Curt A. Changes in corticospinal function and ankle motor control during recovery from incomplete SCI. J Neurotrauma 2008

20 SSEP recordings normal reduced reduced slowed suspected abolished

21 Follow-up SSEP in ASIA C/D P = 40.5 ms P = 44 ms P = 53 ms 1. mth 3. 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 mths

22 Follow-up: tibial nerve SSEP latency, interpeak latency amplitude absolute interpeak latency latency (p40) SSEP amplitude PARA (p=0.23) (p=0.28) TETRA (p=0.51) (p=0.8) 2 change in in percent ms 0-40 A B CD A B CD amplitude (mv) A B CD* A B CD** no significant change (student t t test) PARA TETRA

23 Segmental Sensory Recovery

24 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

25 Pre-surgical MRI Dermatomal SSEP C4 C5 C6/7 C6 C7 Male 41yrs, fall injury C6 ASIA A C8

26 D C4 C5 C4/5 C6/7 C6 C7 C8 Female 53 yrs, MVA C6 ASIA A

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

28 C4 Preliminary Findings: CHEP C5 Characteristic, reliable late evoked potentials C6 C8

29 Non-affected C4 Preliminary Findings: CHEP Pathological C5 Abolished C6

30 Dermatomal Sensory Assessment Electrical Perception & Pain Thresholds C5/6 Electrical Perception & Pain Thresholds ma R perception R pain Male 58yrs, fall injury C5 ASIA B C4 C5 C6 C7 C8

31 dssep of the trunk from schematic drawing to reality the T2-4 7 (50% equidistance) 10 schema

32 Complete paraplegia ASIA A male 37 years, T5/6 dislocation fracture T 2 T 4 T 7 T 10

33 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 measures

34 Thanks to the interdisciplinary research teams Balgrist Research V Dietz H Hedel B Wirth P Halder S Wydenkeller J Blum Balgrist Clinic M Schubert G Lindemann M Wirz C Ruhde Rehab Eng ETHZH R Riener S Micera R Gasser MRI UniZH S Kollias S Hotz Hocoma G Colombo Brain Res Center UniZH M Schwab A Buchli B Zoerner G Courtine ICORD J Steeves W Tetzlaff J Kramer P Taylor

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