Defining Precision in the Diagnosis and Classification of Adjacent Segment
Intervertebral Disc degeneration: A Systematic Review
WEB APPENDIX
Supplemental Table 1. Search Strategy for Key Question 1a
Database: PubMed
Search dates: 03/09/12 (Searches #1-3); 04/18/12 (Searches #4-8)
Search performed by: AR
Limit: English, only items with abstracts
Search terms
1
2
3
4
5
6
7
8
“Adjacent segment disease” OR “Adjacent segment diseases” OR
“Adjacent segment degeneration” OR “adjacent segment
degenerative*”
“Classification” OR “Classifications” OR “Diagnostic” OR
“Diagnosis” OR “System” OR “Systems” OR “Definition” OR
“Definitions” OR “evidence” OR “assessment” OR “assessments”
OR “evaluation” OR “grade” OR “grades” or “grading”
#1 AND #2 AND #3
Additional articles identified by hand-searching bibliographies,
PubMed’s “related citations” of relevant articles
Radiographic Grading of Degenerative Changes at Adjacent Levels
by Hilibrand (identified in Key Question 3)
“Adjacent segment” OR “Adjacent segments”
(“Radiography” OR “Radiographic” OR “Degenerative” OR
“Adjacent”) AND (“Hilibrand” OR “Hillibrand”)
#4 AND #5
Adjacent level ossification severity grading system by Park
(identified in Key Question 3)
“ossification” AND “Park”
#4 AND #7
Additional articles identified by hand-searching bibliographies,
PubMed’s “related citations” of relevant articles
Total
Number of articles retrieved from search: 189
Number of articles identified for full text evaluation: 12
Total number of articles included in KQ1a: 2
Number of
articles
280
4,705,527
177
n/a
975
77
9
121
1
2
189
Supplemental Table 2. Search Strategy for Key Question 1b
Database: PubMed
Search date: 03/09/12
Search performed by: RH
Limit: English, only items with abstracts
Search terms
1
2
3
4
5
6
7
8
9
10
11
14
15
16
17
18
19
20
21
22
23
24
25
26
“Adjacent segment” OR “Adjacent segments”
Degenerative Cascade of Spine Disease by Kirkaldy-Willis
“Degenerative Cascade of Spine Disease” OR “Kirkaldy”
#1 AND #2
Stages of Disc Degeneration by Adams
“Stages of Disc Degeneration” OR “Adams”
#1 AND #4
Modic Changes
“Modic”
#1 AND #6
UCLA Grading System for Intervertebral Space Degeneration
“UCLA”
#1 AND #8
Harborview Disc Disease Severity Score by Mirza
“Harborview” OR “Mirza”
#1 AND #10
Osteoarthritis Severity Grade by Lane
“Osteoarthritis Severity” OR “Lane”
#1 AND #14
Intervertebral Disc Severity Grading System by Thompson
“Intervertebral Disc Severity” OR “Thompson”
#1 AND #16
Magnetic Resonance Classification of Lumbar Intervertebral Disc
Degeneration by Pfirrmann
“Magnetic Resonance Classification of Lumbar Intervertebral Disc
Degeneration” OR “Pfirrmann”
#1 AND #18
Osteoarthritis Severity Grade by Kellgren and Lawrence
“Osteoarthritis Severity” OR “Kellgren” OR “Lawrence”
#1 AND #20
Facet Joint Disease Severity Grade by Pathria
(“Facet Joint” AND (“Grade” OR “Severity”)) OR “Pathria”
#1 AND #22
Lumbar Facet Joint Disease Severity Grade by Weishaupt
(“Lumbar Facet Joint Disease” AND (“Grade” OR “Severity”)) OR
“Weishaupt”
#1 AND #24
Lumbar Spine Radiographic Grading System by Wilke
(“Lumbar Spine Radiographic” AND (“Grade” OR “Grading” OR
“System”)) OR “Wilke”
Number of
articles
965
67
0
23,385
1
319
4
32,825
8
3589
0
20,467
1
40,278
20
256
0
21,518
5
173
0
326
0
1507
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
#1 AND #26
Cervical Spine Radiographic Grading System by Kettler
(“Cervical Spine Radiographic” AND (“Grade” OR “Grading” OR
“System”)) OR “Kettler”
#1 AND #28
Classification of Lumbar Degenerative Disc Disease by Thalgott
(“Lumbar Degenerative Disc Disease” AND “Classification”) OR
“Thalgott”
#1 AND #30
Carragee Lumbar Disc Herniation Classification
(“Lumbar Disc Herniation” AND “Classification”) OR “Carragee”
#1 AND #32
Radiographic Scoring System for Osteoarthritis of the Lumbar Spine
by Weiner
(“Radiographic Scoring System” AND “Osteoarthritis”) OR
“Weiner”
#1 AND #34
Myelopathy Disability Index (MDI) by Casey
“Myelopathy Disability Index” OR “MDI” OR “Casey”
#1 AND #37
Cooper Scale
“Cooper”
#1 AND #38
Harsh Scale
“Harsh”
#1 AND #40
European Myelopathy Score (EMS) by Herdman
“European Myelopathy Score” OR “EMS” OR “Herdman”
#1 AND #42
Japanese Orthopedic Association (JOA) Scale by Hukuda
“Japanese Orthopedic Association” OR “Japanese Orthopaedic
Association” OR “JOA” OR “Hukuda”
#1 AND #44
Cervical Spondylotic Myelopathy Classification System by Muhle
“Cervical Spondylotic Myelopathy Classification” OR “Muhle”
#1 AND #46
Nurick Scale
“Nurick”
#1 AND #48
Classification of Increased Signal Intensity by Yukawa
(“Classification” AND “Increased Signal”) OR “Yukawa”
#1 AND #50
Number of articles retrieved from search: 82
Number of articles retrieved from hand searching: 0
Number of articles identified for full text evaluation: 41
Total number of articles included in KQ1b: 12
8
241
2
32
1
139
0
6845
1
6919
0
28,024
1
3305
0
5918
0
904
23
249
0
167
5
1393
2
Supplemental Table 3. Search Strategy for Key Question 2
Database: PubMed
Search dates: 03/19/12 (searches #1-13); 04/18/12 (searches #14-17)
Search performed by: AR
Limit: English, only items with abstracts
Search terms
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
Reliab*[Ti] OR valid* OR intertest* OR interobserv* OR intratest*
OR intraobserv* OR interrat* OR intrarat* OR “Validation
Studies”[Publication Type] OR “Reproducibility of results”[MeSH]
Spine OR Spinal OR “Spine”[MeSH] OR vertebrae* OR vertebral
OR intervertebral OR lumbar OR cervical OR thoracic OR
lumbosacral OR “Cervical Vertebrae”[MeSH] OR “Lumbar
Vertebrae”[MeSH] OR “Thoracic Vertebrae”[MeSH] OR
“Intervertebral Disc”[MeSH] OR “Sacrum”[MeSH]
#1 AND #2
Modic Changes
“Modic”
#3 AND #4
UCLA Grading System for Intervertebral Space Degeneration
“UCLA”
#3 AND #6
Osteoarthritis Severity Grade by Kellgren and Lawrence
“Osteoarthritis Severity” OR “Kellgren” OR “Lawrence”
#3 AND #8
Radiographic Scoring System for Osteoarthritis of the Lumbar Spine
by Weiner
(“Radiographic Scoring System” AND “Osteoarthritis”) OR
“Weiner”
#3 AND #10
Japanese Orthopedic Association (JOA) Scale by Hukuda
“Japanese Orthopedic Association” OR “Japanese Orthopaedic
Association” OR “JOA” OR “Hukuda”
#3 AND #12
Radiographic Grading of Degenerative Changes at Adjacent Levels
by Hilibrand
(“Radiography” OR “Radiographic” OR “Degenerative” OR
“Adjacent”) AND (“Hilibrand” OR “Hillibrand”)
#3 AND #14
Adjacent level ossification severity grading system by Park
“ossification” AND “Park”
#3 AND #16
Number of articles retrieved from search: 170
Number of
articles
461,235
438,662
16,633
319
30
32,877
65
21,559
18
6,849
17
904
31
77
9
121
0
Number of articles on predictive validity and/or reliability of the above severity measures as
referenced in the AO Spine Severity chapters18: 19
Total number of articles included for ti/abs evaluation: 189
Number of articles identified for full text evaluation: 46
Total number of articles included in KQ2: 0
Supplemental Table 4. Articles excluded at full-text reviewKQ1a
Author
1. Bartolomei8
2. Cheh19
3. Hilibrand62
4. Lund97
5. Robertson139
6. Yi169
7. Hilibrand63
8. Throckmorton
Year
2005
2007
2004
2011
2005
2009
1997
2003
Reason for exclusion
Not a formal classification system
Not a formal classification system
Not a formal classification system
Not a formal classification system
Not a formal classification system
Not a formal classification system
Not a formal classification system
Not a formal classification system
2010
Not a formal classification system
154
9. Ryu141
KQ1b
Author
Year
Reason for exclusion
UCLA Grading System for Intervertebral Space Degeneration
1. Gamradt43
2005
UCLA grading system not used
2. Liao95
2011
UCLA system used to measure degeneration but not included in
criteria to measure ASD.
Intervertebral Disc Severity Grading System by Thompson
3. Cakir16
2005
Thompson grading system not used
4. Gillet47
2003
Thompson grading system not used
5. Huang65
2009
Thompson grading system not used
85
6. Koakutsu
2010
Thompson grading system not used
7. Koller86
2009
Used modified grading system of Kellgren but not Thompson
8. Sasso144
2008
Thompson grading system not used
9. Yang167
2008
Used UCLA grading system but not Thompson’s grading system
173
10. Yoshida
1998
Thompson grading system not used
Cooper Scale
11. Cooper24
2007
Cooper scale not used
JOA (Japanese Orthopedic Association) Scale
12. Chen20
2011
JOA scale not used to define ASD
13. Chiba22
2006
JOA scale not used to define ASD
14. Elsawaf33
2009
JOA scale not used to define ASD
57
15. Hayashi
2008
JOA scale not used to define ASD
16. Matsumoto100
2006
JOA scale not used to define ASD
17. Min104
2008
JOA scale not used to define ASD
105
18. Min
2007
JOA scale not used to define ASD
19. Ogawa115
2009
JOA scale not used to define ASD
20. Okuda116
2006
JOA scale not used to define ASD
21. Okuda117
2007
JOA scale not used to define ASD
118
22. Onda
2006
JOA scale not used to define ASD
23. Peng127
2011
JOA scale not used to define ASD
24. Sakai142
2009
JOA scale not used to define ASD
Nurick Scale
25. Gok50
2008
Nurick scale not used to define ASD
26. Wang158
2003
Nurick scale not used to define ASD
Author
Year
Reason for exclusion
Classification of Increased Signal Intensity by Yukawa
27. Nakashima112
2012
Yukawa scale not used
28. Yoshida172
2010
Yukawa scale not used
Hilibrand criteria*
29. Ishihara67
2004
Hilibrand scale used to grade outcome of ASD, not diagnosis
*Not described in AO Spine Severity Measures18.
KQ2
Study
JOA
1. Bartels7
2. Fujiwara36
3. Fukui37 (Part 3
Validity study)
4. Fukui38 (Part 2
Endorsement )
5. Fukui39 (Part 2
Verification of its
reliability)
6. Fukui41 (Part 3
Determination of
reliability)
7. Fukui40 (Part 4
Establishment of
equations)
8. Singh151
9. Yonenobu171
10. Fukuoka42
11. Handa53
12. He58
13. Ikenaga66
14. Takayama152
Modic changes
15. Benneker9
16. Berg10
17. Carrino17
18. Fayad35
19. Hasegawa55
20. Kovacs89
21. Mann99
22. Misterska106
23. Mulconrey108
24. Peterson128
25. Thompson153
26. Wang159
27. Zook175
Reason for exclusion
2010
2003
2008
Study serves to validate JOA into the Dutch language
Not tested in ASD patients
Not tested in ASD patients
2007
Not tested in ASD patients
2007
Not tested in ASD patients
2007
Not tested in ASD patients
2008
Not tested in ASD patients
2001
2001
2004
2002
2005
2005
2005
Not tested in ASD patients
Not tested in ASD patients
Not ASD patients
Not ASD patients
Not ASD patients
Not ASD patients
Not ASD patients
2005
2011
2009
2009
2011
2009
2011
2011
2006
2007
2009
2011
2011
Not tested in ASD patients
Not tested in ASD patients
Not tested in ASD patients
Not tested in ASD patients
Not tested in ASD patients
Not tested in ASD patients
Not tested in ASD patients
Not tested in ASD patients
Not tested in ASD patients
Not tested in ASD patients
Not tested in ASD patients
Not tested in ASD patients
Not tested in ASD patients
Study
Reason for exclusion
28. Jones69
2005
Not tested in ASD patients
68
29. Jensen
2007
Not tested in ASD patients
Osteoarthritis Severity Grade (Kellgren/Lawrence)
30. Cote26
1997
Not tested in ASD patients
92
31. Lane
1995
Not tested in ASD patients
32. Rihn137
2008
Not tested in ASD patients
33. van Saase156
1989
Not tested in ASD patients
34. Kellgren78
1957
Not tested in ASD patients
136
35. Reijman
2004
Not tested in ASD patients
36. Kallman71
1989
Not tested in ASD patients
37. Scott148
1993
Not tested in ASD patients
79
38. Kessler
1998
Not tested in ASD patients
39. Bible13
2008
Patients had not undergone previous spinal surgery at
40. Simpson150
2008
Radiographic Scoring (Weiner)
41. Hicks60
2009
42. Kuhns90
2007
160
43. Weiner
1996
44. Weiner161
1994
45. Weiner162
2006
UCLA
46. Miyazaki107
2008
index level.
Patients had not undergone previous spinal surgery at
index level.
Not tested in ASD patients
Not tested in ASD patients
Not tested in ASD patients
Not tested in ASD patients
Not tested in ASD patients
Not tested in ASD patients
Supplemental Table 5. Definitions of ASD used by other studies included in the systematic reviews in this focus issue
1.
Author
Definition of ASD
Study type
1 Natural history of degenerative disc disease
NR
Aono (2010)4
Prospective populationbased study
Definition of symptomatic ASD
NR
2.
Author
Study type
Coric (2011)25
RCT
Definition of ASD
Definition of symptomatic ASD
Adjacent-level disc degeneration defined as
a progression of disc degeneration at
adjacent levels following treatment using the
radiographic grading scale below (appears to
be derived from UCLA grading system):
 At least a 2-grade increase in
degeneration, OR
 A 1-grade change in degeneration in cases
with pre-existing moderate ASD.
NR
Radiographic grading scale of disc
degeneration (derived from UCLA grading
system):
 None- negligible disc space narrowing, no
osteophyte formation, no endplate
sclerosis
 Mild: <33% disc space narrowing, mild
osteophyte formation, no endplate
sclerosis
 Moderate: 33-66% disc space narrowing,
moderate osteophyte formation, mild to
moderate endplate sclerosis
 Severe: >66% disc space narrowing,
severe osteophyte formation, moderate to
severe endplate sclerosis
3.
Author
Study type
Ekman (2009)32
RCT
4.
Hasset (2003)56
5.
Prospective populationbased study
Kanayama (2001)72
Retrospective cohort study
Definition of ASD
Definition of symptomatic ASD
ASD present when at least one of the
NR
following criteria met (the three radiographic
criteria based on A-P and lateral
radiographs):
 Disc height reduction > 2 SD over the
mean reduction in the Exercise group
(considered as natural history); OR
 Remaining mean disc height < 20% of
anterior vertebral height; OR
 Worsening of the UCLA score from pretreatment**; OR
 Totally reduced posterior disc height (0
mm) at long term follow-up.
NR
NR
One or all of the following criteria in
comparison with preoperative radiographic
findings‡:
 Disc-space narrowing (more than 2-mm
loss of posterior disc height);
 Spur formation;
 Spondylolisthesis (anterior or posterior
slip of the vertebra by more than 2 mm);
 Vacuum phenomenon.
Clinical evidence of adjacent segment
morbidity determined by:
Rate of salvage operation for adjacent segment
lesions.
6.
Author
Study type
Kauppila (1997/1998)76,77
7.
Prospective populationbased study
Kim (2009)81
Prospective cohort study
8.
Maldonado (2011)98
Prospective cohort study
Definition of ASD
Definition of symptomatic ASD
NR
NR
ASD present when at least one of the
following criteria met in comparison with
preoperative radiographic findings:
 Presence of new anterior or enlarging
osteophyte; OR
 Increase or new ≥30% narrowing of disc
space; OR
 Calcification of the anterior longitudinal
ligament (ALL) in adjacent segment(s)
One or all of the following criteria met in
comparison with preoperative radiographic
findings‡:
 Development of new anterior osteophyte
formation or enlargement of existing
osteophytes;
 Increased or new narrowing of a disc space
(> 30%);
 New or increased calcification of the
anterior longitudinal ligament;
 Formation of radial osteophytes.
NR
NR
Author
Study type
Park (2012)123
Definition of ASD
Definition of symptomatic ASD
NR
NR
11.
Wilder (2003)165
At least one of the following criteria met in
comparison with preoperative radiographic
findings:
 Development of new spondylotic changes
in the adjacent vertebral bodies; OR
 A decrease of more than 10% in the height
of adjacent discs.
At least one of the following criteria met in
comparison with preoperative radiographic
findings:
 Anterior slip > 3 mm OR
 Local kyphosis > 5° at maximal flexion on
lateral radiograph.
NR
12.
Prospective populationbased study
Wilder (2011)164
NR
9.
Prospective cohort study
10.
Satoh (2006)146
Retrospective cohort study
13.
14.
15.
16.
Prospective populationbased study
2 Adjacent Segment Biomechanical Consequences of Spinal Surgery
NR
Ahn (2009)2
3
NR
Anakwenze (2009)
NR
Auerbach (2011)5
81
See above (1- Natural history of
Kim (2009)
degenerative disc disease)
Prospective cohort study
NR
Nabhan (2011)110
NR
NR
NR
NR
NR
NR
NR
Definition of ASD
Definition of symptomatic ASD
17.
18.
19.
Author
Study type
Park (2008)122
Park (2011)119
Peng-Fei (2008)126
NR
NR
NR
NR
NR
NR
20.
21.
22.
23.
24.
Porchet (2004)132
Powell (2010)133
Rabin (2007)135
Sasso (2011)145
Yi (2009)170
NR
NR
NR
NR
NR
NR
NR
NR
NR
NR
25.
26.
Retrospective cohort study
4 Adjacent segment disease and indication for fusion
Coric (2011)25
 See above (1- Natural history of
degenerative disc disease)
RCT
Disk protrusion in Klippel-Feil patients
Guile (1995)51
classified by sagittal MRI of cervical spine
Case series
in neutral, flexion, and extension:
 Type A: disk protruded into the subdural
space and approached, but never touched,
the spinal cord; OR
 Type B: disk touched or indented the
spinal cord, causing a concave defect.
59
PJK defined as any increased postoperative
Helgeson (2010)
kyphosis of > 15° on radiographs††.
Case series
NR
NR
NR
27.
Author
Study type
Hollenbeck (2008)64
Case series
Kanayama (2001)72
Retrospective cohort study
Kim (2009)81
Definition of ASD
Definition of symptomatic ASD
PJK defined as an increase in proximal
junctional flexion on radiographs.††
NR
 See above (1- Natural history of
degenerative disc disease)
 See above (1- Natural history of degenerative
disc disease)
 See above (1- Natural history of
degenerative disc disease)
NR
Prospective cohort study
28.
Kim (2005)83
Case series
29.
Koller (2009)86
30.
Retrospective cohort study
Lee (1999)94
Case series
Maldonado (2011)98
Prospective cohort study
Park (2012)123
Prospective cohort study
PJK defined as both of the following
NR
criteria††:
 Proximal junction sagittal Cobb angle ≥10°
AND
 Proximal junction sagittal Cobb angle of at
least 10º greater than the corresponding
preoperative measurement.
Presence of ASD based on modified
NR
Kellgren and Lawrence severity grades on
radiograph evaluations*
PJK defined as ≥ 5° above the summed
NR
normal angular segments in kyphosis††.
 See above (1- Natural history of
degenerative disc disease)
NR
 See above (1- Natural history of
degenerative disc disease)
NR
31.
Author
Study type
Pizzutillo (1994)131
Case series
32.
Ritterbusch (1991)138
Case series
33.
Rouvreau (1998)140
Case series
Satoh (2006)146
34.
Ulmer (1993)155
Case series
Definition of ASD
Definition of symptomatic ASD
Range of motion in Klippel-Feil patients
NR
defined by radiograph as:
 Class I: normal range of motion in both
upper and lower cervical segments with no
translational stability
 Class II: intersegmental hypermobility of
the upper cervical segment, basilar
impression, or iniencephaly
 Class III: intersegmental hypermobility of
the lower cervical segment, or radiographic
evidence of degenerative changes
 Class IV: a combination of the factors in
Class II and Class III
Anomalies in Klippel-Feil patients defined
NR
by MRI as:
 Subluxation: >5 mm OR
 Stenosis ≤9 mm
Mobility of all levels in Klippel-Feil patients
classified by radiograph as:
 Hypermobility (not quantified)
 Instability (not quantified)
 See above (1- Natural history of
degenerative disc disease)
Abnormalities in Klippel-Feil patients
defined by radiograph, CT and MRI as:
 Stenosis (not quantified) or
 Spondylosis (not quantified)
NR
NR
NR
35.
36.
37.
Author
Study type
Wang (2010)157
Definition of ASD
PJK defined as both of the following
criteria††:
Retrospective prognostic
 The measured Cobb angle > 10º AND
study
 Proximal junction sagittal Cobb angle at
least 10° greater than the corresponding
preoperative measurement.
5 Factors that influence the incidence of cervical ASD
Presence of ASD based on Kellgren and
Faldini (2011)34
Lawrence severity grades on radiograph
Case series
evaluations*:
 ASD present: Kellgren and Lawrence
severity grades 2, 3, or 4 (minimal,
moderate, or severe degeneration,
respectively)
 ASD absent: Kellgren and Lawrence
severity grades 0 or 1 (absent or doubtful
degeneration, respectively)
61
Qualitative grading of ASD based on
Hilibrand (1999)
Hilibrand Radiographic Grading Scale,
Retrospective cohort study which compares postoperative and
preoperative radiographic findings†:
 ASD present: grades II – IV
 ASD absent: grade I
Definition of symptomatic ASD
NR
NR
Symptomatic ASD defined as:
 Development of new radiculopathy or
myelopathy referable to a motion segment
adjacent to the site of a previous cervical
anterior arthrodesis on two consecutive
visits.
38.
Author
Study type
Ishihara (2004)67
Retrospective cohort study
39.
Katsuura (2001)75
Retrospective cohort study
40.
Komura (2012)87
Retrospective cohort study
41.
Nassr (2009)113
Retrospective cohort study
Definition of ASD
Definition of symptomatic ASD
ASD at the time of the procedure defined by
one or all of the following‡:
Plain radiographs
 Intervertebral disc narrowing of more than
2 mm compared with adjacent segments;
 Osteophyte formation of more than 2 mm;
 Anterior or posterior slip of more than 2
mm.
MRI
 Decreased signal intensity on T2-weighted
images and presence of disc protrusion.
At least one of the following criteria met in
comparison with preoperative radiographic
findings:
 Evident intervertebral disc space
narrowing; OR
 Newly developed instability (>3 mm) on
flexion-extension radiographs; OR
 Vertebral posterior spur formation
Presence of ASD based on Hilibrand
classification on plain/dynamic radiographs,
MRI, CT/CT myelographic evaluation†:
 ASD present: grades 3 and 4
 ASD absent: grades 1 and 2
Presence of ASD based on modified
Hilibrand Radiographic Grading Scale in
comparison with preoperative radiographic
findings†:
 Used Grades I – III only
Diagnosis of symptomatic ASD based on:
 Presence of new radiculopathy or
myelopathy symptoms referable to an
adjacent level; AND
 Presence of a compressive lesion at an
adjacent level by MRI or myelography
NR
Diagnosis of symptomatic ASD based on:
 Presence of new myelopathy and/or
radiculopathy after operation, and compatible
with radiographic changes.
NR
42.
43.
44.
Author
Study type
Wu (2011)166
Definition of ASD
Definition of symptomatic ASD
NR
Symptomatic ASD defined as:
Secondary ACDF surgery ≥ 3 months apart.
Retrospective cohort study
6 Effect of post-surgical coronal or sagittal malalignment on adjacent segment degeneration
NR
Faldini (2011)34
 See above (5- Factors that influence the
incidence of cervical ASD)
Ishihara (2004)67
 See above (5- Factors that influence the
 See above (5- Factors that influence the
incidence of cervical ASD)
incidence of cervical ASD)
NR
Katsuura (2001)75
 See above (5- Factors that influence the
incidence of cervical ASD)
91
Degenerative changes present when least
NR
Kulkarni (2004)
one of the following criteria met in
Retrospective cohort study comparison with preoperative or control
level MRI findings:
 Changes in indentation of anterior or
posterior subarachnoid spaces towards the
spinal cord; OR
 Canal changes; OR
 Disc height changes.
101
At least one of the following criteria met in
NR
Matsumoto (2010)
comparison with baseline MRI findings:
Retrospective cohort study  Decrease in signal intensity of
intervertebral disc (i.e., considerably
darker than CSF fluid); OR
 Marked increase in disc protrusion; OR
 Disc space narrowing increased by ≥25%;
OR
 Development of foraminal stenosis (i.e.,
that was not present in baseline images).
46.
Author
Definition of ASD
Definition of symptomatic ASD
Study type
7 Reducing the risk of adjacent segment disease in the cervical spine: Are motion sparing devices safer than fusion?
NR
Symptomatic ASD occurred when patient had
Burkus (2010)15
symptoms referable to adjacent level.
RCT
NR
Coric (2011)25
 See above (1- Natural history of
degenerative disc disease)
RCT
NR
Kim (2009)81
 See above (1- Natural history of
degenerative disc disease)
Prospective cohort study
NR
Maldonado (2011)98
 See above (1- Natural history of
degenerative disc disease)
Prospective cohort study
NR
NR
Murrey (2009)109
47.
RCT
Nabhan (2007)111
45.
RCT
NR
NR
48.
Author
Study type
Nunley (2011)114
Definition of ASD
Definition of symptomatic ASD
 Radiographic ASD diagnosed based on
Hilibrand grading system†.
Symptomatic ASD defined as the presence of
all the following diagnostic parameters:
 Patient exhibited clinical symptoms
(recurrent cervical
radiculopathy/myelopathy); AND
 Radiographic evidence of ASD; AND
 Absence of peripheral nerve pathologies;
AND
 Patient received active intervention
(subsequent medical management or
surgery) for ASD management.
See above (1- Natural history of
degenerative disc disease)
NR
ASD diagnosis was based on the following
criteria in comparison with preoperative
high-resolution CT scans or radiography:
 Degenerative changes, including
progression of facet arthritis, disc
degeneration, and uncinate process
degeneration; AND/OR
 Other radiographic changes, including disc
space collapse and spur formation.
NR
NR
Prospective cohort study
from 3 RCTs at 2
institutions
Park (2012)123
49.
Prospective cohort study
Ryu (2010)141
Prospective cohort study
50.
Sasso (2011)143
RCT
NR
51.
Author
Study type
Zhang (2011)174
Definition of ASD
Definition of symptomatic ASD
NR
NR
57.
RCT
8 Adjacent level ossification
Presence of adjacent level ossification based
Garrido (2011)44
on severity grades developed by Park
RCT
(2005)120 on radiograph evaluations§
120
Presence of adjacent level ossification based
Park (2005)
on severity grades on radiographic
Cohort study
evaluations§
121
Presence of adjacent level ossification based
Park (2007)
on severity grades developed by Park (2005)
Cohort study
on radiographic evaluations§
Presence of adjacent level ossification based
Park (2010)124
on severity grades developed by Park (2005)
Cohort study
on radiographic evaluations§
168
Presence of adjacent level ossification based
Yang (2009)
on severity grades developed by Park (2005)
Case series
on radiographic evaluations§
9 Treatment of ASD in the cervical spine
NR
Baba (1994)6
58.
Case series
Gause (2008)45
52.
53.
54.
55.
56.
Case series
NR
NR
NR
NR
NR
NR
NR
At least one of the following criteria met in
comparison with preoperative radiographic
findings and consistent with radiographic level
of segmental degeneration:
 Radicular symptoms OR
 Myelopathic symptoms
59.
Author
Study type
Hilibrand (1997)63
Definition of ASD
Definition of symptomatic ASD
NR
Symptomatic ASD defined as the presence of
all of the following in comparison with
preoperative clinical evaluation, plain
radiographs, intrathecal myelography,
postmyelography CT, or MRI findings:
 New radiculopathy in a distribution referable
to a segment adjacent to a prior anterior
cervical fusion AND
 Radiographic evidence of segmental
degeneration with compression of nerve
roots and/or spinal cord.
Symptomatic ASD defined as:
 Cervical myelopathy resulting from adjacent
segment disease.
NR
Retrospective cohort study
60.
Matsumoto (2006)100
NR
61.
Matched cohort study
Phillips (2009)129
NR
62.
RCT
10 Predicting the risk of ASD in lumbar population
NR
Ahn (2010)1
63.
Retrospective cohort study
Ghiselli (2004)46
Retrospective cohort study
Lumbar degeneration classified by UCLA
grading scale**:
Grade I (no disease), Grade II (mild disease),
Grade III (moderate disease), or Grade IV
(severe disease)
NR
Symptomatic ASD diagnosis based on
presence of any of the following that were
symptomatic enough for patient to elect
revision surgery:
 Instability;
 Radiculopathy; OR
 Spinal stenosis
Author
Study type
Kaito (2010)70
Definition of ASD
Definition of symptomatic ASD
67.
At least one of the following criteria met in
Clinical (symptomatic) deterioration of L3-4
comparison with baseline radiographs:
defined by presence of all of the following:
Retrospective cohort study  Development of L3 antero- or
 Decrease of 4 or more points on the JOA
retrolisthesis more than 3 mm; OR
scale AND
 Decrease in L3-4 disc height of more than  Neurological impairment in accordance with
3 mm; OR
L3-4 canal stenosis based on MRI
 Intervertebral angle at flexion smaller than
-5°.
NR
Symptomatic ASD was defined when all of the
Lee (2009)93
following conditions are present:
case-control study
 Patient showed the relief of symptoms for at
least 6 months after the index operation;
AND
 Development of symptoms compatible with
the lesions in adjacent segments
demonstrated in radiological images; AND
 Patient had revision surgery for that
problem.
149
ASD defined as:
NR
Sears (2011)
 Progressive degeneration of disease to
Retrospective cohort study
adjacent levels following fusion.
11 Reducing the risk of adjacent segment disease in the lumbar spine: Are motion sparing devices safer than fusion?
NR
NR
Berg (2009)11
68.
randomized controlled trial
NR
Guyer (2009)52
64.
65.
66.
randomized controlled trial
NR
Author
Study type
Kanayama (2001)72
69.
retrospective cohort study
Kanayama (2009)73
Definition of ASD
Definition of symptomatic ASD
 See above (1- Natural history of
degenerative disc disease)
 See above (1- Natural history of
degenerative disc disease)
NR
Adjacent segment disease based on clinical
presentation and radiographic findings:
 Radiculopathy associated with newlydeveloped pathologies at neighboring levels
(L1-L2, L2-L3, L3-L4, and L5-S1).
Asymptomatic adjacent segment pathologies
not included in study.
NR
retrospective cohort study
70.
Kaner (2010)74
71.
prospective cohort study
Korovessis (2004)88
NR
Adjacent segment degeneration defined as
the presence of one or all of the following in
randomized controlled trial comparison with preoperative radiographic.
MRI, or CT myelography findings‡:
 Olisthesis;
 Osteophytes;
 Disc degeneration.
NR
72.
73.
Author
Study type
Putzier (2005)134
Definition of ASD
Presence of one or all of the following in
comparison with preoperative radiographs
and MRI scans‡:
 Axis deviation;
 Osseous remodeling processes;
 Stenosis;
 Spondyloarthroses assessed by the degree
of hydration of the intervertebral discs on
T2 weighted sagittal MRIs;
 Height of intervertebral space.
146
Satoh (2006)
 See above (1- Natural history of
degenerative disc disease)
12 Treatment of ASD in the lumbar spine
NR
Bertagnoli (2006)12
Case-series
74.
Chen (2001)21
Case-series
Adjacent instability defined by at least one
of the following and demonstrated by plain
radiographs and dynamic stress views:
 Spondylolisthesis OR
 Dynamic instability with slippage of more
than 4 mm and/or angle change of more
than 10° on flexion and extension.
 AND
 Spinal stenosis confirmed by myelogram.
Definition of symptomatic ASD
NR
NR
The following criteria confirmed by MRI, CT,
or discographic evaluation:
 Disabling low-back pain with or without
radicular symptoms resulting from L1 – S1
DDD.
Radiographic abnormalities correlated with
clinical symptoms, including pain, activity,
analgesic use, and overall satisfaction.
75.
Author
Study type
Djurasovic (2011)28
76.
Case series
Glassman (2002)48
Definition of ASD
Definition of symptomatic ASD
NR
NR
NR
Symptomatic ASD diagnosis based on chart
review of patients receiving extension of prior
lumbar fusion for treatment of ASD:
 Discogenic pain
 Spinal stenosis/herniated nucleus pulposus
 Spondylolisthesis
 Post discectomy instability
 Instability on flexion/extension radiographs
 Mechanical collapse/DDD
Symptomatic ASD diagnosis based on:
 Presence of low back and leg pain localized
to the adjacent level after prior fusion; AND
MR imaging or dynamic radiographic
evidence of any pathology immediately
adjacent to the prior fusion segment
including spinal stenosis, listhesis, or
instability.
Symptomatic ASD defined as the following:
 Symptomatic spinal stenosis adjacent to a
previously asymptomatic lumbar fusion.
The diagnosis of adjacent segment stenosis
confirmed by myelogram and CT evaluation.
Case-series
77.
Parker (2012)125
NR
Case Series
78.
Phillips (2000)130
Case-series
NR
79.
Author
Study type
Schlegel (1996)147
Case-series
80.
81.
Whitecloud (1994)163
Definition of ASD
Definition of symptomatic ASD
At least one of the following criteria met in
comparison with preoperative radiographic,
MRI, or CT/myelographic findings at a
segment adjacent to a previously
asymptomatic fusion:
 Spinal stenosis; OR
 Disc herniation; OR
 Instability/listhesis
NR
Patients initially presented with severe back
and leg pain
Symptomatic ASD defined as one or all of the
following‡:
Case-series
 Initial presentation of progressive and
functionally-limiting back and leg pain after
a previous lumbosacral fusion.
 Diagnostic studies consistent with
degenerative spinal/lateral recess stenosis or
segmental instability based on radiographs,
CT myelogram or MRI.
13 Proximal junctional kyphosis (PJK) following kyphosis or scoliosis surgery
PJK defined as both of the following
NR
Denis (2009)27
criteria††:
Retrospective prognostic
 Proximal junctional angle greater than 10°
study
AND
 Proximal junctional angle at least 10°
greater than the corresponding
preoperative measurement.
82.
Author
Study type
Kim, Bridwell (2008)82
Retrospective prognostic
study
83.
Kim, Lenke (2007)84
Retrospective prognostic
study
84.
Kim, Yagi (2011)80
Retrospective prognostic
study
85.
Lonner (2007)96
Retrospective prognostic
study
Definition of ASD
Definition of symptomatic ASD
PJK defined as both of the following
criteria††:
 Proximal junction sagittal Cobb angle ≥10°
AND
 Proximal junction sagittal Cobb angle at
least 10° greater than the corresponding
preoperative measurement.
PJK defined as both of the following
criteria††:
 Proximal junction sagittal Cobb angles
≥10° AND
 Proximal junction sagittal Cobb angle at
least 10° greater than the preoperative
measurement at 2 years postoperative.
PJK defined as both of the following
criteria††:
 Proximal junction sagittal Cobb angle ≥10°
AND
 Proximal junction sagittal Cobb angle of at
least 10º greater than the corresponding
preoperative measurement.
PJK defined as ≥10° in kyphosis††.
NR
NR
NR
NR
86.
Author
Study type
McClendon (2011)102
Case series
87.
Mendoza-Lattes (2011)103
Retrospective prognostic
study
Wang (2010)157
88.
Definition of ASD
Definition of symptomatic ASD
PJK defined as both of the following
criteria††:
 Proximal junction sagittal Cobb angle
+ ≥10° AND
 Development of proximal junction sagittal
Cobb angle at least +10° greater than the
corresponding preoperative measurement.
PJK defined as both of the following
criteria††:
 Proximal junction sagittal Cobb angle
≥10º, AND
 Proximal junction sagittal Cobb angle at
least 10º greater than the corresponding
preoperative measurement.
 See above (4- Adjacent segment disease
and indication for fusion)
Symptomatic PJK definition NR
Symptoms present in patients included pain,
neurological deficit, ambulatory difficulty,
and/
or social isolation.
Retrospective prognostic
study
14 Long thoracolumbar fusion
Segmental degeneration based on at least
Brown (2004)14
one of the following in comparison with
Retrospective cohort study preoperative radiographs:
 Presence and progression of L5-S1
spondylolisthesis by >2 mm OR
 Progressive loss of L5-S1 disc height by
>2 mm based on radiographs.
NR
NR
Symptomatic segmental degeneration defined
by:
 Revision
89.
Author
Study type
Cho (2009)23
Retrospective cohort study
90.
Eck (2001)29
Retrospective cohort study
Definition of ASD
Definition of symptomatic ASD
Presence of ASD based on modified Weiner Symptomatic ASD defined by:
classification161 on radiographic
 Clinical symptoms of pain caused by a
evaluation‡‡:
herniated disc, spinal stenosis, or junctional
kyphosis
 ASD present: grade 2 or 3 (advanced
degeneration)
 ASD absent: Grade 0 or 1 (healthy)
ASD defined as presence of at least two of
NR
the following conditions in comparison with
immediate postoperative radiographs:
 More than 5˚ loss of lordosis across a disc
space; OR
 Progressive disc space narrowing more
than 2 mm; OR
 Sclerosis of endplates/ facets with
osteophyte formation; OR
 Subluxation more than 2 mm;
Moderate to severe degenerative disc disease
defined as the presence of at least one of the
following:
 Anterior disc height of 7 mm or less; OR
 Subluxation of 2 mm or more; OR
 Presence of osteophytes; OR
 Segmental lordosis of 10˚ or less
91.
Author
Study type
Edwards (2004)30
Retrospective cohort study
92.
Edwards (2003)31
Retrospective cohort study
93.
Harding (2008)54
Retrospective cohort study
94.
Kuhns (2007)90
Retrospective cohort study
Definition of ASD
Definition of symptomatic ASD
Presence of ASD based on modified Weiner Symptomatic ASD defined by:
classification161 on radiographic evaluation
Significant lumbosacral discomfort.
(severity defined by the most severe
radiographic component at a particular
level)‡‡:
 ASD present: grade 2 or 3 (advanced
degeneration)
 ASD absent: Grade 0 or 1 (healthy)
Presence of ASD based on modified Weiner Symptomatic ASD defined by:
classification161 on radiographic evaluation
 Significant lumbosacral discomfort.
(severity defined by the most severe
radiographic component at a particular level)
‡‡:
 ASD present: grade 2 or 3 (advanced
degeneration)
 ASD absent: Grade 0 or 1 (healthy)
ASD classified by UCLA grading scale (if
Symptomatic ASD defined by:
degeneration was asymmetric, the worse
 Presence of low back pain
score was used)**:
Grades I – IV
Presence of ASD based on modified Weiner NR
classification161 on radiographic evaluation
(severity defined by the most severe
radiographic component at a particular level)
‡‡:
 ASD present: grade 2 or 3 (advanced
degeneration)
 ASD absent: Grade 0 or 1 (healthy)
ACDF: anterior cervical diskectomy and fusion; ASD: adjacent segment degeneration; CSF: cerebrospinal fluid: CT: computerized tomography; DDD: degenerative disk disease;
MRI: magnetic resonance imaging; NR: not reported; SD: standard deviation
*Kellgren and Lawrence (1957)78 scale:
Grade Kellgren and Lawrence scale (Faldini 2011)34
0
Definite absence of radiographic degenerative
changes
Doubtful presence of degeneration
1
2
Degeneration is definitely present though of
minimal severity
Moderate degeneration
3
4
Severe degeneration. Formation of osteophytes,
periarticular ossicles, cartilage narrowing with
subchondral bone sclerosis, pseudocystic areas,
and altered bone shape are considered as evidence
of degeneration.
†Hilibrand Radiographic Grading Scale61,87,113,114:
Grade
Disease
Plain Radiography
Modified Kellgren and Lawrence scale (Koller
2009)86
Absence of degeneration in the disc (no ossification of
the ALL, anterior longitudinal ligament)
Minimal anterior osteophytosis (or ossification of the
ALL)
Definite anterior osteophytosis, possible narrowing of
the disc space, some sclerosis of the vertebral plates
Moderate narrowing of the disc space, definite sclerosis
of the vertebral plates, osteophytosis
Severe narrowing of the disc space, sclerosis of the
vertebral plates, multiple large osteophytes
I
II
None
Mild
Normal
Narrowing of disc space, no
posterior osteophytes
Magnetic Resonance
Imaging
Normal
Signal change in
intervertebral disc
III
Moderate
<50% of normal disc height,
posterior osteophytes
Herniated nucleus pulposus
without neural compression
IV
Severe
Same as for grade III
Spinal cord compression with
or without nerve-root
compression
Computed Tomography or
Myelography, or Both
Normal
Normal
Herniated nucleus pulposus; no
nerve-root cutoff or spinal cord
compression
Nerve-root cutoff with or without
spinal cord compression
Nassr (2009)113 used Grades I – III only.
‡It is not clear from the study whether any or all of the criteria must be present for an ASD diagnosis67,72,88,98,134,163.
§Adjacent Level Ossification grading44,120,121,124,168:
Grade 0 (none) - no ossification
Grade 1 (mild) - ossification extending across <50% of adjacent disc space
Grade 2 (moderate) - ossification extending across >50% of adjacent disc space
Grade 3 (severe) - ossification completely bridging adjacent disc space
**UCLA Grading Scale for Intervetebral Space Degeneration32,46,54:
Grade
Disc Space
Osteophytes
End Plate
Narrowing
Sclerosis
I
II
+
III
±
+
IV
±
±
+
Assigned grade based on the most severe radiographic finding evident on plain radiographs; categories are mutually exclusive when used for grading. Patients were rated on the
basis of the worst category satisfied. (+) present, (−) absent, and (±) either present or absent. An equivalent point scale was assigned to each segment based on the severity of the
grade (i.e., Grade I was assigned 1 point).
††The proximal junctional angle is defined as: 1) the Cobb measurement between the lower endplate of the uppermost instrumented vertebra and the upper endplate of 2
supradjacent vertebrae per Glattes (2005)49,80,82-84,102,103,157; 2) the Cobb measurement between the cranial endplate of the upper instrumented vertebra to the cranial endplate 2
vertebrae above27; 3) Kyphosis measured from 1 segment cephalad to the upper end instrumented vertebrae (EIV) to the proximal instrumented vertebrae96; 4) the measurement
from the caudal endplate of the upper instrumented vertebra to the cephalad endplate of the vertebra adjacent to the upper instrumented vertebra59; 5) the angle formed by lines
extended from the posterior wall of the upper instrumented vertebral body and the vertebra 2 levels proximal 64; or 6) Kyphosis measured from T2 to the proximal level of the
instrumented fusion94.
‡‡Modified grading system of Weiner23,30,31,90,161:
Grade 0- no degeneration (normal disc height, no spur formation, no eburnation, no listhesis, no gas present)
Grade 1- mild degeneation (<25% disc space narrowing, small spur formation, minimal eburnation, no listhesis, and no gas present)
Grade 2- moderate degeneration (25 - 75% disc space narrowing, moderate spur formation, moderate eburnation, listhesis >3 mm, and no gas present)
Grade 3- advanced degeneration (>75% disc space narrowing, large spur formation, marked eburnation, listhesis >5 mm, and the presence of gas)
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