does fibronectin aggrecan complex predict response to epidural steroid injection?
DESCRIPTION
Does Fibronectin Aggrecan Complex Predict Response to Epidural Steroid Injection?. Lisa Huynh MD Matthew Smuck MD, Agnes Martinez-Ith, David J. Kennedy MD Department of Orthopaedic Surgery, PM&R Section, Stanford University, Redwood City, CA AAPM&R Annual Assembly November 16, 2014. - PowerPoint PPT PresentationTRANSCRIPT
Does Fibronectin Aggrecan Complex Predict Response to
Epidural Steroid Injection?Lisa Huynh MD
Matthew Smuck MD, Agnes Martinez-Ith,
David J. Kennedy MDDepartment of Orthopaedic Surgery, PM&R Section, Stanford
University, Redwood City, CA
AAPM&R Annual Assembly November 16, 2014
DISCLOSURES Lisa Huynh, MD
Nothing to disclose
Matthew Smuck, MD Cytonics Corporation (Research Support) North American Spine Society (Travel, Honoraria) The Spine Journal (Executive Editorial Board)
Agnes Martinez-Ith Cytonics Corporation (Research Support)
David J. Kennedy, MD Cytonics Corporation (Research Support) North American Spine Society (Travel, Honoraria) PM&R (Editorial Board)
BACKGROUND Extensive research on degenerative disc disease, yet
much remains to be learned Radicular pain secondary to mechanical compression
and inflammatory pathways ESI is an effective treatment for lumbar radicular pain,
but only in a proportion of patients1
Need a reliable approach to determine good candidates for ESIs
Not without riskCost containment
1. Ghahreman A, Ferch R, Bogduk N. The efficacy of transforaminal injection of steroids for the treatment of lumbar radicular pain. Pain Med 2010;11:1149-1168
BACKGROUND Inflammatory cytokines and protein biomarkers are
being studied as diagnostic indicators and potential therapeutic targets1
Elevated levels of metallomatrix proteases, nitric oxide, prostaglandin-E, (IL)-6, (TNF)-α , amongst others have been implicated in disk degeneration2,3
1. Golish SR, Hanna LS, Bowser RP, et al. Outcome of lumbar epidural steroid injection is predicted by assay of a complex of fibronectin and aggrecan from epidural lavage. Spine 2011;36:1464-9.
2. Kang JD, Georgescu HI, McIntyre-Larkin L, et al. Herniated lumbar intervertebral discs spontaneously produce matrix metalloproteinases, nitric oxide, interleukin-6, and prostaglandin E2. Spine 1996;21:271-2.
3. Kobayashi S, Baba H. Uchida K, et al. Effect of mechanical compression on the lumbar nerve root: localization and change of intraradicular inflammatory cytokines, nitric oxide, and cyclooxygenase. Spine 2005;30:1699-705
BACKGROUNDFibronectin
Large extracellular glycoproteinContains a number of domains to bind various
ligands including fibrin, collagen, glycosaminoglycans, and various cytokines1
Ability to cleave aggrecan2
AggrecanMajor proteoglycan in extra-cellular matrix
component of articular cartilage3
1. Potts JR, Campbell ID. Structure and function of fibronectin molecules. Matrix Biol 1996;15(5):313-20.2. Homandberg GA, Davis G, Maniglia C, et al. Cartilage chondrolysis by firbonectin fragments causes clevage of
aggrecan at the same site as found in osteoarthritic cartilage. Osteoarthr Cartil 1997;5(6):450-453.3. Abrams GD, Safran MR, Shapiro LM, et al. Fibronectin-aggrecan complex as a marker for cartilage degradation in
non-arthritic hips. Knee Surg Sports Traumatol Arthrosc 2014;22(4):768-73
BACKGROUND Fragmentation of fibronectin and aggrecan seen in
degenerative joint conditions and articular cartilage damage1
May facilitate signaling of inflammatory cascade Fibronectin-aggrecan complex (FAC) shown to be
associated with inflammation and pain in degenerative joint and spine conditions1,2
FAC predicts response to lumbar ESI for radiculopathy with HNP Single-center, prospective, consecutive case series of 27
patients underwent epidural lavage prior to ESI Primary outcome: PCS (of SF-36) >4.9 Presence of FAC predicted clinically significant improvement in
PCS after lumbar ESI
1. Scuderi GJ, Golish SR, Cook FF, et al. Identification of a novel fibronectin-aggrecan complex in the synovial fluid of knees with painful meniscal injury. J Bone Joint Surg Am 2011;93:336-40.
2. Gajendran VK, Reuter M, Golish SR, et al. The fibronectin-aggrecan complex: Is it present in cervical disc disease? Phys Med Rehab 2011;3:1030-4.
3. Golish SR, Hanna LS, Bowser RP, Montesano PX, Carragee EJ, Scuderi GJ. Outcome of lumbar epidural steroid injection is predicted by assay of a complex of fibronectin and aggrecan from epidural lavage. Spine (Phila Pa 1976). 2011 Aug 15;36(18):1464-9.
PURPOSE
To investigate the fibronectin-aggrecan G3 domain complex (FAC) as a biomarker to predict response to epidural steroid injections in patients with lumbar disc herniations
METHODSStudy Design
Prospective, consecutive cohort study at a university spine center
Patient SampleTarget: 100 patientsScreened consecutive patients scheduled for ESIInclusion:
lumbar radicular pain positive physical exam findings
positive straight leg raise and/or diminished patellar or Achilles tendon reflex
MRI confirmed disc herniationExclusion:
negative lumbar MRI ESI in previous 3 months presence of any red flags minors, pregnant, prisoners, not competent to make decisions
METHODSUsing fluoroscopic guidance, performed
physiologic saline epidural lavageLavage sample collected prior to steroid
administrationELISA analysis to detect FACFAC positive if optical density was >0.06 at
450nm
1. Scuderi GJ, Cuellar JM, Cuellar VG, Yeomans DC, Carragee EJ, Angst MS. Epidural interferon gamma-immunoreactivity: a biomarker for lumbar nerve root irritation. Spine (Phila Pa 1976). 2009 Oct 1;34(21):2311-7.
2. Golish SR, Hanna LS, Bowser RP, Montesano PX, Carragee EJ, Scuderi GJ. Outcome of lumbar epidural steroid injection is predicted by assay of a complex of fibronectin and aggrecan from epidural lavage. Spine (Phila Pa 1976). 2011 Aug 15;36(18):1464-9.
METHODS
Outcomes Measures
Oswestry Disability Index (ODI) and Numeric Pain Rating Scale (NPRS) assessed at baseline and 6 weeks post-ESI
Criteria for success:”Responders”:
ODI improvement of 15 points, ANDNPRS reduction of 30%
“Nonresponders”All remaining participants
METHODS
Analysis Differences between group means evaluated using independent samples t-tests and two-by-two contingency table analysis.
ResultsTarget
N = 100
Screened N = 387
EnrolledN = 63
2 insufficient lavage samples
1 discontinued from hypotension
Age: 20-70 (mean 42.57 years)Sex: 55.6% males, 44.4% females
RESULTS
FAC Positive FAC Negative0
5
10
15
20
25
21
8
Oswestry Disability Index (ODI)
Mean O
DI
Score
Im
pro
vem
ent
FAC Positive FAC Negative05
1015202530354045
40
15
Numeric Pain Rating Scale (NPRS)
Mean %
NP
RS I
mpro
vem
ent
RESULTS
Sensitivity 26.7% (95% CI: 8-55.1%)Specificity 91.1% (95%CI: 78.8%-97.5%)p < 0.0982
Presence of FAC in Responders and Nonresponder Groups to ESI
Oswestry Disability Index and Numeric Pain Rating Scale at 6 weeks
Responders to ESI Nonresponders to ESI
FAC Positive 4 4
FAC Negative 11 41
Primary Outcome
RESULTS
Oswestry Disability Index Only at 6 weeksPresence of FAC in those with >15 point ODI
improvement versus those without
Responders to ESI Nonresponders to ESI
FAC Positive 8 0
FAC Negative 13 39
Sensitivity 38.1% (95% CI: 18.2-61.6%)Specificity 100% (95% CI: 90.9-100%)p <0.0001
DISCUSSIONGreater improvement in NPRS and ODI at 6
weeks in the FAC (+) group compared to FAC (-) group
Presence of FAC in disc samples from patients with radiculopathy is associated with improvement in disability following ESI
FAC has a role in predicting response to ESIs
DISCUSSIONLimitations
Amount of lavage fluid sample was variableStudy was underpowered Invasive sampling method with inherent risks
which may limit diagnostic potentialFurther studies needed to elucidate roles of
inflammatory markers
CONCLUSIONFAC status predicts disability, but not pain
outcomes 6-weeks after ESI in patients with lumbar disc herniations.
Thank You!Lisa Huynh, MDInterventional Spine Fellow
Department of Orthopaedic Surgery, PM&R DivisionStanford University
Stanford University Spine Center