Spinal Cord Injury - University of Calgary Spinal...Spinal Cord Injury (A presentation made at the...
Transcript of Spinal Cord Injury - University of Calgary Spinal...Spinal Cord Injury (A presentation made at the...
Spinal Cord InjurySpinal Cord Injury
(A presentation made at the Calgary Animal Referral and (A presentation made at the Calgary Animal Referral and Emergency Centre Rounds, Oct 11, 2007)Emergency Centre Rounds, Oct 11, 2007)
Aubrey A. Webb, DVM, PhDAubrey A. Webb, DVM, PhD
Hotchkiss Brain Institute and Faculty of Veterinary Hotchkiss Brain Institute and Faculty of Veterinary MedicineMedicine
University of CalgaryUniversity of Calgary
GoalsGoalsTo provide basic epidemiology of human and canine SCITo provide basic epidemiology of human and canine SCI
To get you to think about assessment techniques if one To get you to think about assessment techniques if one were to conduct a clinical trialwere to conduct a clinical trial
To get you to question the rigor in which you evaluate To get you to question the rigor in which you evaluate recovery after injury in SCI dogsrecovery after injury in SCI dogs
To provide current thoughts on the use of steroids for To provide current thoughts on the use of steroids for SCISCI
To update you on what is being done in clinical canine To update you on what is being done in clinical canine SCI trialsSCI trials
OutlineOutlineBasic epidemiology of spinal cord injury (SCI)Basic epidemiology of spinal cord injury (SCI)
Methods of evaluating recovery from SCIMethods of evaluating recovery from SCI
Mechanisms of SCI damageMechanisms of SCI damagePrimaryPrimarySecondarySecondary
Lines of SCI researchLines of SCI research
Corticosteroids?Corticosteroids?
Relatively recent, current, and forthcoming research in Relatively recent, current, and forthcoming research in canine SCIcanine SCI
May, 1995
Christopher ReeveSeptember 25, 1952 - October 10, 2004 Mcdonald et al, J Neurosurg, 2002
Rick Hansen – wheeled around world (40 000 km) from 1985-1987
Epidemiology Epidemiology -- HumansHumansTraumatic spinal cord injury (SCI)Traumatic spinal cord injury (SCI)
Approx. 16% of people with Approx. 16% of people with spinal cord injury die prior to spinal cord injury die prior to being admitted to a hospital being admitted to a hospital (Dryden et al, 2003)(Dryden et al, 2003)
Approx. Approx. 80%80% occur in malesoccur in males
Vast majority occurs in Vast majority occurs in individuals under 35 years of ageindividuals under 35 years of age
Motor vehicle accidents # 1 Motor vehicle accidents # 1 causecause
IncidenceIncidence: 35/million people : 35/million people affected annually = affected annually = 1100 1100 CanadiansCanadians affected affected annuallyannually
PrevalencePrevalence = approx. = approx. 36 000 36 000 peoplepeople living with SCI in Canada living with SCI in Canada todaytoday
0.0%
10.0%
20.0%
30.0%
40.0%
50.0%
60.0%
70.0%
Cervical Thoracic Lumbosacral
From Dryden et al, Can J Neurol Sci, 2003
From http://www.spinalcord.uab.edu/show.asp?durki=21446
Epidemiology Epidemiology -- HumansHumans
Epidemiology Epidemiology -- DogsDogs
Most common cause is Most common cause is prolapsedprolapsedintervertebralintervertebral discdisc
Observed in Observed in 0.02 0.02 -- 2%2% of all clinical cases of all clinical cases admitted to a veterinary hospital admitted to a veterinary hospital ((PriesterPriester, 1976; , 1976; Coates, 2000)Coates, 2000)
Type 1 disc extrusion is seen in Type 1 disc extrusion is seen in chondrodystrophicchondrodystrophic breeds at 3breeds at 3--6 years of 6 years of ageage
Type 2 disc Type 2 disc prolapseprolapse is seen in is seen in nonchondrodystrophicnonchondrodystrophic breeds and occurs breeds and occurs between 6 and 10 years of agebetween 6 and 10 years of age
60%60% of all dog and cat of all dog and cat SCIsSCIs, not resulting , not resulting from IVDD, are the result of from IVDD, are the result of motor vehicle motor vehicle accidentsaccidents (McKee, 1990) (McKee, 1990)
5% of dogs involved in motor vehicle 5% of dogs involved in motor vehicle accidents will have SCI accidents will have SCI ((KolataKolata, 1975), 1975)
From Neurology for the Small Animal Practioner, Chrisman, Mariani, Platt, Clemmons
IntervertebralIntervertebral disc disease disc disease -- dogsdogs
15% occur at cervical level15% occur at cervical level
85% 85% thoracolumbarthoracolumbar levellevelT12T12--T13 T13 –– 26%26%T13T13--L1 L1 –– 25%25%L1L1--L2 L2 –– 13%13%L2L2--L3 L3 –– 8%8%L3L3--L4 L4 –– 7%7%L4L4--L5 L5 –– 6%6%L5L5--L6 L6 –– 2%2%
From Neurology for the Small Animal Practioner, Chrisman, Mariani, Platt, Clemmons
Assessment of RecoveryAssessment of Recovery
Endpoint measuresEndpoint measures
KinematicsKinematics
KineticsKinetics
Physiological measuresPhysiological measures
Assessment of RecoveryAssessment of Recovery
Endpoint MeasuresEndpoint MeasuresQuantitativeQuantitativeSimple to performSimple to performRelatively inexpensiveRelatively inexpensiveRequires little training or experienceRequires little training or experienceIdentifies whether task is performedIdentifies whether task is performedDoes not identify how a task is performedDoes not identify how a task is performed
Endpoint measuresEndpoint measures
Endless listEndless list
Number of pellets of food grasped in XNumber of pellets of food grasped in X--amount of amount of timetimeNumber of footfalls while crossing a ladder, Number of footfalls while crossing a ladder, horizontal beamhorizontal beamTime to swim from one point to anotherTime to swim from one point to anotherLimb use while rearingLimb use while rearingWithdrawal thresholdWithdrawal thresholdEtc, etc, etc.Etc, etc, etc.
Tapered BeamTapered Beam
Withdrawal ThresholdWithdrawal Threshold
Webb et al, Behav Brain Res, 2003
Assessment of RecoveryAssessment of Recovery
KinematicsKinematicsQualitativeQualitativeSemiquantitativeSemiquantitative (ordinal rating scales)(ordinal rating scales)Quantitative Quantitative -- highly objectivehighly objectiveRequires variable amounts of trainingRequires variable amounts of trainingAnswers how a behaviour is performedAnswers how a behaviour is performed
KinematicsKinematics
Movement notation Movement notation
Rating scales (e.g. Canine Rating scales (e.g. Canine locomotorlocomotorrating scale)rating scale)
Quantitative kinematicsQuantitative kinematicsUse of motion analysis system (e.g. Peak Use of motion analysis system (e.g. Peak MotusMotus))
SemiquantitativeSemiquantitative kinematicskinematics
Metz and Whishaw, J Neurosci Methods, 2002
Quantitative KinematicsQuantitative Kinematics
Webb et al, Behav Brain Res, 2003
Assessment of RecoveryAssessment of Recovery
KineticsKineticsQuantitativeQuantitativeHighly objectiveHighly objectiveRequires substantial amount of trainingRequires substantial amount of trainingAnswers how a behaviour is performedAnswers how a behaviour is performed
KineticsKinetics
Use of force measuring devices to Use of force measuring devices to measure:measure:
Strength of graspingStrength of grasping
Ground reaction forcesGround reaction forces
Force to Break Force to Break a Piece of a Piece of
PastaPasta
Ballerman et al, Brain Res Bull, 2001
Ground Ground Reaction Reaction ForcesForces
Webb and Muir, Eur J Neurosci, 2003
Physiological MeasuresPhysiological Measures
Recommendations regarding Recommendations regarding behavioural analysis of SCI dogsbehavioural analysis of SCI dogs
Perform a series of neurological evaluationsPerform a series of neurological evaluations
Use a logical and complimentary battery of testsUse a logical and complimentary battery of testsEnsure tests are appropriate for speciesEnsure tests are appropriate for speciesEnsure tests are appropriate for level of SCIEnsure tests are appropriate for level of SCI
When possible, When possible, examine a variety of neural systemsexamine a variety of neural systems ––sensory (incl. pain), motor, and autonomicsensory (incl. pain), motor, and autonomic
Ensure that behaviour examined will answer your Ensure that behaviour examined will answer your questionquestion
Webb et al, Vet Rec, 2004
Mechanisms of InjuryMechanisms of InjuryPrimary injury mechanismsPrimary injury mechanisms
Secondary injury mechanismsSecondary injury mechanismsIschemiaIschemiaFree radical formationFree radical formationExcitotoxicityExcitotoxicityLocal electrolyte imbalancesLocal electrolyte imbalancesInflammationInflammation
Cell deathCell deathApoptosis and necrosisApoptosis and necrosis
Primary InjuryPrimary Injury
Webb et al, 2006
Secondary InjurySecondary Injury
From Rabchevsky, Arch Neurol, 2001
From www.Wingsforlife.com
Species DifferencesSpecies Differences
Sroga et al, J Comp Neurol, 2003 42 d
RAT
MOUSE
Species DifferencesSpecies DifferencesMouse
Hamster
Rat
1 wk 3 wk 8 wk
Inman and Steward, J Neurotrauma, 2003
Species DifferencesSpecies DifferencesMouse
Hamster
Rat
GFAP around periphery in all species
Inman and Steward, J Neurotrauma, 2003
Lines of SCI researchLines of SCI researchNeuroprotectionNeuroprotection
RegenerationRegeneration
Replacing lost tissueReplacing lost tissue
Promoting neural plasticityPromoting neural plasticity
Combinatorial approachesCombinatorial approaches
Treatment strategiesTreatment strategiesNeuroprotectionNeuroprotection
Methylprednisolone (NASCIS trials)Methylprednisolone (NASCIS trials)MinocyclineMinocyclineAntiAnti--integrinsintegrinsUse of Use of neurotrophinsneurotrophins
RegenerationRegenerationProinhibitoryProinhibitory
MyelinMyelinChondroitinChondroitin, , heparanheparan, and , and keratankeratan sulfate sulfate proteoglycansproteoglycans
Overcoming inhibitionOvercoming inhibitionNOGO antibody (INNOGO antibody (IN--1)1)RolipramRolipramChondroitinaseChondroitinase
Treatment strategiesTreatment strategiesBridging the gap and replacing lost tissueBridging the gap and replacing lost tissue
Schwann cellsSchwann cellsOlfactory Olfactory ensheathingensheathing gliagliaStem/precursor cellsStem/precursor cellsFetal tissueFetal tissue
Promoting neural plasticityPromoting neural plasticityTraining/rehabilitationTraining/rehabilitation
Combinatorial approachesCombinatorial approaches
MethylprednisoloneMethylprednisolone??Human clinical trials under scrutinyHuman clinical trials under scrutiny
No longer a standard of care in many Canadian No longer a standard of care in many Canadian hospitals (e.g. Calgary) hospitals (e.g. Calgary) (Hurlbert and Moulton, Can J (Hurlbert and Moulton, Can J NeurolNeurol SciSci, 2002; Hurlbert, , 2002; Hurlbert, Spine, 2006)Spine, 2006)
No longer a standard of care in veterinary No longer a standard of care in veterinary medicine medicine (Vitale and Coates, Standards of Care Newsletter, 2007)(Vitale and Coates, Standards of Care Newsletter, 2007)
Standard of care recommendations for dogs and Standard of care recommendations for dogs and humans are to:humans are to:
Ensure tissue perfusion/oxygenation and prevent Ensure tissue perfusion/oxygenation and prevent further spinal cord ischemia further spinal cord ischemia (Hurlbert 2006; Vitale and Coates, (Hurlbert 2006; Vitale and Coates, Standards of Care Newsletter, 2007)Standards of Care Newsletter, 2007)
Relatively recent, current and Relatively recent, current and forthcoming research for clinical canine forthcoming research for clinical canine
SCI researchSCI research
44--aminopyridineaminopyridine
Oscillating electrical fieldsOscillating electrical fields
SurfactantsSurfactants
Olfactory Olfactory ensheathingensheathing gliaglia
Questions ?Questions ?
Future lab link:Future lab link:www.webblab.ucalgary.cawww.webblab.ucalgary.ca
AcknowledgementsAcknowledgements
Brendan Kerr; Hisham Assem, Tanya NevilleBrendan Kerr; Hisham Assem, Tanya NevilleNSERCNSERCHBIHBIUCVMUCVMUCUCCheryl Cullen and Brennan WebbCheryl Cullen and Brennan Webb