Anterior Cervical Arthrodesis & Pseudarthrosis

Diagnosis and Treatment

Disclosures

 FDA Device Status: Off-label use of InFuse discussed (Medtronic)  Conflict of Interest: None  Paid Consultant: Zimmer  Hospital Agreement: Rose Spine Institute

OPTIONS

Background

  Fusion  (-) motion  (-) lucency  (+) bony ingrowth Pseudarthrosis  without detectable motion  with obvious motion  symptomatic vs. asymptomatic

AR – 3 - LEVEL

Is there a Problem?

 Fusion Rates  One Level ACDF 93-95%  Two Level ACDF 70-75% (100%)  Three Level ACDF 50-60% Two & Three Level Fusion Rates UNACCEPTABLE

Five FDA IDE Trial Data from Texas Back Institute of CDR v. ACF      127 patients (81 CDR, 46 ACF) 12-60 month follow-up (1) 1.2% reoperation in CDR (adj. segment) (2) 4.3% reoperation in ACF (pseudo) (1) 2.2% reoperation in ACF (adj. segment)  No difference between ACF v. CDR  Blood loss, op time, LOS, NDI Guyer, R.D. et al., CSRS paper 65, 2010

Anterior Cervical Pseudarthrosis

67% symptomatic (28% asymptomatic for 2 years) 33% asymptomatic Re-operation : fusion: 19 Excellent, 1 Good Phillips, FM et al: Spine, 1997

Bohlman, HH., et. al: JBJS, 1993

Pseudarthrosis of the Cervical Spine: A Comparison of Radiographic Diagnostic Measures    Solid Fusion (18), Pseudarthrosis (11) Flexion-extension radiographs Manual measurement technique  Cobb angle (IVM)  Distance between tips of spinous processes (SPD)  SPD BETTER in reliability, specificity & sensitivity  Pseudarthrosis: Greater than 2 mm difference in sp. process distance Cannada, LK, et al; SPINE, 28:46-51, 2003

Radiographic Motion Thresholds Cobb Angle

  Kimax QMA, medical metrics software  (accuracy: 0.5deg motion, 0.5mm translation) FDA guideline: 4 degrees of motion defines Pseudoarthrosis Hipp, JA, et al: SPINE, 2005

Failure Rate

Pseudoarthrosis Detection

Guidelines are needed to define how much IVM should be of clinical concern.

MMI FDA

Dependence of Pseudoarthrosis Rate on the Threshold Used to Define Fusion

Threshold Cervical Range-of-Motion Necessary to Detect Abnormal Intervertebral Motion in Cervical Spine Radiographs    Cadaver Study Need to Flex-Extend to a minimum range of 60 degrees before evaluation for instability in the sub-axial spine Center of rotation most sensitive in determining abnormal motion and potential injury Hwang, H., Hipp, J.A., et. al., SPINE, 33:E261-7, 2008

Short Term Comparison of Cervical Fusion with Static and Dynamic Plating Using Computerized Motion Analysis     Computerized evaluation of digital films can improve accuracy and reproducibility of analysis of AC Fusion.

Angular Threshold of 2 Degrees  Accuracy error of 0.5 degrees  Reproducibility error of 0.9 degrees 2 Degrees allows for some natural motion at fusion Dynamic plates = Static plates Goldberg, G., Albert, T., et al., SPINE 32:E371-375, 2007

Fusion Rate

    2 level ACDF (Thomas Jefferson/Rothman Institute) ACDF/Static Plate/autograft: 87.8% per level ACDF/Dynamic Plate/allograft: 89.8% per level All pseudarthrosis patients were asymptomatic (10-13 months) Goldberg, G., Albert, T., et al., SPINE 32:E371-375, 2007 Short Term Comparison of Cervical Fusion with Static and Dynamic Plating Using Computerized Motion Analysis

Patient TT – C7 Stabilized

C6-7 Rotation = 4.9º

Patient TT – C6 Stabilized

C6-7 Rotation = 4.9º; C5-6 Rotation = 1.1º

Patient TT – C5 Stabilized

C5-6 Rotation = 1.1º; C4-5 Rotation = 5.0º

Patient TT – C4 Stabilized

C4-5 Rotation = 5.0º

Study Demographics

 Symptomatic patients one year after ACDF who underwent PSF to address symptoms / pseudarthrosis  Pre-op CT scan, Radiographs with flexion/extension  Intra-operative findings to clarify pre-op data  Motion evaluated at the facet joints Ghiselli, Wharton, Hipp, Wong, Jatana., SPINE 2011

Study

 2003 – 2005  24 levels, ACDF, minimum 1 year after surgery, with recurrent symptoms  Neck Pain, Radiculopathy  Age 35-69  One 1 level, four 2 level, five 3 level  Diagnostic Imaging, X-rays, CT scan, posterior spinal fusion

Methods

 Inter-vertebral motion (IVM) at fusion level  Quantification by medical metrics (Kimax QMA software)  CT scan reviewed by neuro-radiologist  Intra-operative motion noted at facet joints  Correlation between findings, CT scan and motion analysis reviewed

Results

 13/24 levels pseudarthrosis (intraoperative)  7/13 less than 2 degrees of IVM (0-7.2 degrees)  11/24 levels with fusion, IVM range 0 – 0.9 degrees  CT scan 9/13 (+) pseudarthrosis

Statistical Analysis

Sensitivity Specificity PPV 4 Degree QMA threshold 1 Degree QMA threshold CT Scan CT Scan + 1 Degree QMA

23%

77% 69% 85% 100% 100% 100% 100% 100% 100% 100% 100% NPV 52%

79% 73%

85%

4 Degree Threshold

 Study suggests a high PPV  Low sensitivity (23%)  ie: miss pseudarthrosis with < 4 degrees of motion  At 1 degree  Sensitivity higher (77%)

CT scan

 NPV is 73%  Subject to Type I, II errors

Anterior Cervical Fusion Assessment

 14 patients  CT, MRI, X-rays & Intra-operative findings  Kappa values  0.67 X-rays  0.81 CT Scan  0.48 MRI  CT scan agrees the best with intra-operative findings but not 100% Buchwowski, J.M., et al., SPINE 33:11, 1185-91, 2008

Conclusion 2008

 Symptomatic pseudarthrosis in the cervical spine can exhibit less than 2 degrees of IVM  No agreement - Current radiographic methods to diagnose pseudoarthrosis.

 The 4 degree angular motion threshold accepted by the FDA maybe too high.

 Threshold at less then 2 degrees yields the higher sensitivity, specificity, PPV and NPV Ghiselli, Jatana, Wharton, CSRS, 2007

Key Points

 Quantitative Motion Analysis (QMA) is an effective tool to diagnose cervical pseudarthrosis.

 Combining QMA with CT increases the NPV in diagnosing pseudarthrosis.

 Current thresholds for pseudarthrosis need to be redefined as they lack specificity.

Ghiselli, Wharton, Hipp, Wong, Jatana., SPINE 2011

ACDF : The Landscape

     Fusion rates decrease as levels fused increase Multi-level disease forces ant/post surgery  Same day, staged, later date Cervical deformity forces ant/post surgery Arthroplasty for multilevel disease not approved  Who knows if it ever will Stand alone laminectomy / laminoplasty / foraminotomy  limitations

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Improve the Environment

”  Don ’ t Fuse  Laminectomy  Laminoplasty  Multilevel arthroplasty  Anterior Corpectomy/Discectomy  Accept pseudoarthrsis rate and address as needed  Mechanical – Plate, Screw designs  Biological – Bone, Cells, BMP ’ s

RhBMP-2 REFERENCES                 Williams, B.J., CSRS paper #20, 2010 Pradan, B. et al., CSRS 2006, poster 26 (Delamarter) Alexander, G.A., et al., CSRS 2007, paper 7 Shen, H.X., et al., CSRS 2007, poster 14 Bae, H., et al., CSRS 2007, poster 21 Miller, C. et al., CSRS 2007, paper 17 (Delamarter) Singh, K. et al., CSRS 2007, paper 52 rhBMP-2 and repeat surgery Allen, T.R. et al., SPINE 2007, 32:26, 2996-3006 rhBMP-2, osteomyelitis Pradhan, B.et al., CSRS 2004, paper 31 (Delamarter) Patel,V., et al., CSRS 2004, paper41 (Delamarter) Smucker, J.D. et al., CSRS 2005, paper 50 Smucker, J.D. et al., SPINE 31, 2006 Longley, C.L. et al. CSRS 2005, paper 7 Bae, H.W. et al., CSRS 2005, poster 23 (Delamarter) Burd, T.A. et al., CSRS 2006, paper 37 Sheilds et al. SPINE 31: 2006

Comparison of the Incidence of Complications of Anterior Cervical Fusion with and without BMP: A Report of the Scoliosis Research Society Morbidity and Mortality Committee     2004-7, 5184 Cases, BMP used in 622 (12%) Superficial & deep infection, dysphagia, mortality 373 revisions (7.2%), BMP used in 107 (29%) Stat signif. Results  Overall complication rate 5.8% v. 2.4%  Overall infection rate 2.1% v. 0.4%  Deep infection rate 1.2% v. 0.2% Williams, B.J., CSRS paper #20, 2010

POSITIVE

 RhBMP-2 use in the neck works  Increase fusion rates  Decrease pseudoarthrosis rates  Decrease rate repeat surgery ?

 Cost is high

Shen, H.X. et al., CSRS 2007 (Riew,D)

          

Pseudoarthrosis in rhBMP-2 augmented multilevel ACF 127 cases, minimum 2 year follow up Fibular allograft and plate fixation 3 level - 77pts 4% 4 level - 32pts 16% 5 level - 8pts 17% Lowest level C6-7 - 14pts, C7-T1 - 2pts @6 mo. 10/16pts asymptomatic, @12 mo. 6/10pts fused Nonunion rate = 13.4% @ 6 mo. 8.7% @ 1 year Factors: revision surgery, age>50 (smoking, DM not signif. stat)

“

Long lever arm overwhelms the biologic advantage of BMP

”

EJ – 6mo, 1year

BMP Issues

 Heterotopic Bone Formation  Neural Irritation  Soft Tissue Swelling  Seroma/Hematoma  Immunologic footprint

2-LEVEL Fusion

AR – 3 - LEVEL PSF

PB – Myelopathy

PB - MRI

PB – Lami/Laminoplasty/PSF

Anterior Cervical Fusion

      Pseudarthrosis rates vary Patients may be asymptomatic for a long time No agreed upon radiographic criteria Probably underestimated Need to follow patients that have possible pseudarthrosis longer than one year Treatment Options not perfect  Revision anterior fusion  Posterior spinal fusion  BMP use in the neck is OFF-LABEL  Not 100% successful  Higher complications

Sanjay Jatana, MD Gary Ghiselli, MD David A. Wong, MD Scott A. Bainbridge, MD C. Deno Pappas, MD