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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_6011_Библиотеки_им_академика_М_И_Перельмана.pdf
C H A P T E R 1 0 Kinematics of the Aging Spine
55
TA BL E 10 1 IVA Data sets Consult ed an d S creene d
in This Analysis , and the Reason for Exc lusi on
Lumbar IVA Datasets
Investigator Year Included? If not, why?
Knutsson 1944 No SD not published
Tanz 1953 No Method not Standard of Care
Kapandji 1974 No SD not published
White & Panjabi 1978 No SD not published
Twomey 1979 No SD not published
Pearcy 1984 Yes
Tibrewal 1984 No SD not published
Boden 1989 Yes
Russell 1993 No SD not published
Greene 1994 No SD not published
Frobin 1996 Yes
Van Herp 2000 No SD not published
Troke 2001 No SD not published
Wong 2004 No Method not Standard of Care
Wong 2006 No Method not Standard of Care
Cervical IVA Datasets
Investigator Year Included? If not, why?
Aho 1955 Yes
Bhalla 1969 No Outlier dataset
Penning 1986 No SD not published
Dvorak 1988 Yes
Lind 1989 Yes
Frobin 2002 Yes
Reitman 2004 No Method not Standard of Care
*
e Bhalla cervical dataset from 1969 had a published standard deviation that was four times
lower than the average reported for other datasets, and was therefore considered an outlier
and excluded from the meta-analysis. All other published standard deviations consistently
fell within a narrow band of within about ± 25% of the average across all studies.
*
*
if observed IVA is sufficiently high. For example, if IVA is confirmed to be
above the mean for any level, then it would be possible to rule out hypomobility (even the subtle hypomobilities described in the previous paragraph). It is similarly possible to rule out hypermobility if observed IVA
is sufficiently low. However, one must consider the effects of interobserver
variability in IVA measurements to be sure that a measurement is above
or below the mean in producing threshold values to rule out hypomobility
and hypermobility. In quantifying the interobserver variability at one investigational site, Lim et al.
3
reported that the 95% confidence interval for the
interobserver variability in lumbar IVA measurements is ±5.2°. However,
as this study took place at only one site, it almost certainly underestimates
the actual interobserver variability that exists across different clinical sites.
Nonetheless, if one uses the Lim estimate and assumes that an IVA measurement must be 5.2 ° above/below the mean to be 95% confident that the
observed IVA is actually above/below the mean, and if one further assumes
that any IVA measurement above/below the mean rules out hypo/hypermobility, then one can produce the “rule-out” thresholds for hypomobility
and hypermobility given in Table 10-4. However, there are some limitations
associated with the data used to create these threshold values (as described
in the caption for Table 10-4), so therefore they should be considered non-
definitive until these limitations are addressed and new thresholds can be
produced.
In conclusion, the diagnostic efficacy of using IVA to detect the follow-
ing conditions can be summarized as:
Immobility: Low specificity (high rate of false positives), so immobil-
ity should not be “ruled in” for IVA of 5° or less. May be definitively
“ruled out” for IVA greater than 5°.
Pseudarthrosis: May be definitively ruled in for IVA greater than 5°.
Low sensitivity (high rate of false negatives) so pseudarthrosis should
not be ruled out for IVA less than 5°.
Hypomobility: Effectively undetectable (thresholds below what is
considered fused). A nondefinitive rule-out diagnosis for hypomobility can be made if IVA is above the threshold values listed in Table
10-4.
Normal Motion: Rule in diagnosis of normal motion should be con-
sidered non-definitive, because both sensitivity and specificity are low.
May be ruled out with a high degree of confidence if IVA is above
hypermobility thresholds (i.e., if hypermobility is ruled in).
Hypermobility: May be definitively ruled in for IVA values above
the hypermobility thresholds given in Table 10-3. Low sensitivity (i.e.,
high rate of false negatives), so hypermobility should not be ruled out
if IVA is below the thresholds. May be nondefinitively ruled out if
IVA is less than the threshold values given in Table 10-4.
The root cause of this poor diagnostic efficacy in the use of IVA in the
detection of different functional presentations is the high degree of measurement variability associated with the current standard of care for measuring IVA. As a consequence, any reduction to IVA measurement variability
would serve to increase the diagnostic efficacy of using IVA in the detection
of the functional presentations given earlier.
negative in the detection of normal motion as well as a false positive in the
detection of immobility).
The second problem lies with the thresholds for detecting both intervertebral hypermobility and hypomobility. The thresholds for hypermobility are
so high because IVA measurement variability is so large. Having such a high
threshold for hypermobility (the average threshold for lumbar levels is 22°
and for cervical levels is 26°, from Table 10-3) ensures that only the grossest of
rotational hypermobilities will register as being definitively hypermobile; thus
subtle hypermobilities remain undetected and register as “normal.” Similarly,
with hypomobility, high IVA variability makes the hypomobility thresholds
so low that only the grossest of hypomobilities could register as being definitively hypomobile. As a consequence, the sensitivity of using IVA to detect
hyper/hypomobility as well as the specificity of using IVA to detect normal
motion are both reduced (those patients who register as normal but who have
a subtle hyper/hypomobility are a false positive in the detection of normal
motion as well as a false negative in the detection of hyper/hypomobility).
A third problem arises when one tries to use IVA to rule out hypomobility or hypermobility. It is theoretically possible to rule out hypomobility
Conclusions: Implications for the Practitioner Regarding the Clinical Application of RoM Measurements
The current standard of care for functional testing of the spine provides
IVA results that can be overinterpreted if measurement variability is not
properly accounted for. Based on a comprehensive analysis of the effects of
this variability, it is possible to put forward a set of clinical practice suggestions that are consistent with the published literature and that properly
account for the effects of all sources of measurement variability:
1. Definitive diagnoses that can be made using the current standard of
care for functional testing of the spine:
When an instability is suspected, any IVA measurement above the
hypermobility thresholds given in Table 10-3 should be considered
definitively hypermobile.
When pseudarthrosis is suspected in a previously fused segment, any
measurement above 5° should be considered definitive pseudarthrosis.
56
P A R T I I Basic Science of the Aging Spine
TA BL E 10 2 Normat ive IVA Data That Account for the Effec ts of Inte rsite Variabi lity, There by A llow ing for a More
Representa tive Account of Mean IVA Values Than Has Ever Been Publ ishe d in Any Sing le- Site Study
Pearcy ‘84 (n = 11) Boden ‘89 (n = 40) Frobin ‘96 (n = 61) Aggregated Across Sites
Lumbar Level
Mean SD Mean SD Mean SD Mean SD
*
L1/L2 13.0° 5.4° 8.2° 3.6° 11.8° 2.7° 10.6° 3.8°
L2/L3 13.0° 2.8° 7.7° 3.9° 13.9° 3.0° 11.6° 4.4°
L3/L4 13.0° 2.2° 7.7° 5.0° 14.2° 3.7° 11.8° 5.1°
L4/L5 15.0° 4.1° 9.4° 6.5° 16.4° 4.1° 13.8° 6.0°
L5/S1 14.0° 7.2° 9.4° 6.1° 13.2° 6.1° 11.9° 6.4°
Avg.
4.3° 5.0° 3.9° Intersite variability (aggregated
5.2°
SD, averaged across levels)
Average of the three sites’ intersubject/intrasite variability (the average SD across all levels at each site, averaged
across all three sites): 4.4°
Aho ‘55 (n = 15) Dvorak ‘88 (n = 28) Lind ‘89 (n = 70) Frobin ‘02 (n = 128) Aggregated Across Sites
Cervical Level
Mean SD Mean SD Mean SD Mean SD Mean SD
C2/C3 12.0° 5.0° 10.0° 3.0° 10.0° 4.0° 8.2° 3.3° 9.3° 3.8°
C3/C4 15.0° 7.0° 15.0° 3.0° 14.0° 6.0° 14.2° 4.7° 14.3° 5.1°
C4/C5 22.0° 4.0° 19.0° 4.0° 16.0° 6.0° 16.3° 5.3° 16.9° 5.5°
C5/C6 28.0° 4.0° 20.0° 4.0° 15.0° 8.0° 16.6° 6.7° 17.3° 7.4°
C6/C7 15.0° 4.0° 19.0° 4.0° 11.0° 7.0° 10.9° 6.5° 12.9° 6.9°
Avg.
4.8° 3.6° 6.2° 5.3 ° Intersite variability (aggregated SD,
5.8°
averaged across levels)
Average of the four sites’ intersubject/intrasite variability (the average SD across all levels at each site, averaged
across all four sites): 5.0°
*
All values are degrees of intervertebral rotation in the sagittal plane. Note the average intersubject/intrasite variability (i.e., the average of all four individual sites’ variability averaged across all levels) is 4.4°
for lumbar levels and 5.0° for cervical levels, while the average intersite variability (i.e., the aggregated variability from the superset of all sites averaged across all levels) is significantly higher at 5.2° (an
18% increase as compared to the average single-site variability) for lumbar levels and 5.8° (a 16% increase) for cervical levels. is represents the effects of variability between different clinical sites.
TA BL E 10 3 IVA Thres hold s for Hypo mobi lity and Hyp ermo bility
Lumbar Level
Hypomobile Threshold
(Mean − 2*SD)
Hypermobile Threshold
(Mean + 2*SD)
*
Cervical
Level
Hypomobile Threshold
(Mean − 2*SD)
Hypermobile Threshold
(Mean + 2*SD)
L1/L2 3.0° 18.3° C2/C3 1.7° 17.0°
L2/L3 2.8° 20.4° C3/C4 4.1° 24.5°
L3/L4 1.6° 22.0° C4/C5 5.8° 28.0°
L4/L5 1.7° 25.8° C5/C6 2.4° 32.1°
L5/S1 -1.0° 24.8° C6/C7 -0.8° 26.7°
*
All values are degrees of intervertebral rotation in the sagittal plane.
Any measurement below −5° (i.e., 5° of motion in the direction oppo-
site the bend) should be considered definitively paradoxical.
2. Nondefinitive diagnostic results possible with IVA measurements
Due to the significant false negative rate when it comes to the detection
of hypermobility, any IVA measurement above 5° but below the hyper-
mobility thresholds given in Table 10-3 should be considered nonde-
finitive, but potentially normal. It is currently impossible to definitively
rule in normal motion using today’s clinical standard of care.
Any IVA measurement ranging from −5° to 5° should be considered
nondefinitive, but potentially hypomobile, immobile, paradoxical, or
normal. If pseudarthrosis is suspected and an IVA of less than 5° is
observed, a corroborative spine CT view can be used to assist in the
detection of pseudarthrosis.
Hypomobility and hypermobility may be nondefinitively ruled out
16 *
based on the threshold values given in Table 10-4.
*Standard axial CT scanning cannot adequately reveal the hairline defect which frequently
characterizes a pseudarthrosis after posterior fusion, especially in the frequent presence of metal
fixation, or when the graft is irregular in shape and thickness. However, there is evidence that
thin-section helical CT is currently the most successful method of proving fusion or pseudarthrosis in interbody fusions with carbon cages. (See: Hutter CG: Posterior intervertebral body
fusion: a 25-year study, Clin Orthop 179:86-96, 1983. Also see: Lang P, Genant HK, Chafetz N,
Steiger P, Morris JM: ree-dimensional computed tomography and multiplanar reformations
in the assessment of pseudarthrosis in posterior lumbar fusion patients, Spine 13:69-75, 1988.)
C H A P T E R 1 0 Kinematics of the Aging Spine
TA BL E 10 4 IVA Thres hold s for Ruli ng In/O ut Hypomo bility and Hyperm obil ity*
57
Hypomobile Hypermobile
Lumbar
Level
L1/L2 N/A 15.8° 18.3° 5.4° C2/C3 N/A 14.5° 17.0° 4.1°
L2/L3 N/A 16.8° 20.4° 6.4° C3/C4 N/A 19.5° 24.5° 9.1°
L3/L4 N/A 17.0° 22.0° 6.6° C4/C5 N/A 22.1° 28.0° 11.7°
L4/L5 N/A 19.0° 25.8° 8.6° C5/C6 N/A 22.5° 32.1° 12.1°
L5/S1 N/A 17.1° 24.8° 6.7° C6/C7 N/A 18.1° 26.7° 7.7°
*
All values are degrees of intervertebral rotation in the sagittal plane. It should be noted that the Lim et al.3 estimate of interobserver variability that was used to create these thresholds was derived
specifically for the lumbar spine (although it was also applied to the cervical spine in the Table 10-4 dataset) and does not include any effects of intersite variability. erefore these threshold
estimates should be considered nondefinitive until better data are available.
Rule In
(IVA <)
Rule Out
(IVA >)
Rule In
(IVA >)
Rule Out
(IVA <)
TECHNOLOGICAL ADVANCES THAT IMPROVE THE DIAGNOSTIC EFFICACY OF SPINAL FUNCTIONAL TESTING
As stated throughout this text, the current standard of care for measuring
IVA includes a high degree of both observer-related and subject-related
variability. Technological developments in recent years have been effective at
reducing both of these types of variability, and are discussed in this section.
However, this section only includes those methods which could feasibly be
adopted by the clinical practitioner and thus it does not discuss techniques
which are purely investigational or are otherwise infeasible for immediate
adoption (such as Roentgen Stereophotogrammatric Analysis,
skin-marker−based motion measurement techniques,
20
of in vitro measurement methods).
19
external
as well as a variety
Cervical
Level
intersubject/intrasite variability) decreased over 50%, from 2.8° to 1.3°, as
a result of using automated software-driven image analysis versus manual
image analysis. Other groups have been able to demonstrate similar results
using commercially available image analysis software. Using an automated
image analysis software program operated as a core lab service (QMA software operated by Medical Medtrics, Inc., Houston, Texas) instead of a manual image analysis process, Reitman et al. published a cervical IVA dataset
of 155 asymptomatic subjects and Hipp & Wharton published a lumbar
IVA dataset
an average standard deviation across cervical levels of 4.0°, while the Hipp
& Wharton study published an average standard deviation across all lumbar levels of 3.6. While these are the lowest published standard deviation
among different cervical or lumbar IVA datasets, these do represent a 20%
(cervical) and 18% (lumbar) reduction relative to the average value for inter-
Hypomobile Hypermobile
Rule In
(IVA <)
26
of 67 asymptomatic subjects. The Reitman study reported
Rule Out
(IVA >)
Rule In
(IVA >)
Rule Out
(IVA <)
subject/intrasite variability (i.e., the average of all individual sites’ average
Reducing IVA Observer-Related Variability by Improving the Reliability of Image Analysis Techniques
With respect to observer-related variability, previous studies have confirmed widely variable IVA results from measurements of the same images
taken by different observers. Lim et al.
9.6 degrees must exist between the IVA measurements from two observations in order to be 95% confident that there really is a difference in IVA.
This high degree of interobserver variability is a major contributor to overall
observed measurement variability. However, recent advances have successfully reduced this interobserver variability through several novel techniques.
There have been improvements over the years with respect to the methods for landmarking the radiographic images and deriving IVA and IVT
measurements from these images. Variability in IVA and IVT measurements
can be introduced through distortion errors inherent to all radiographic
images. Further, if patients move out of plane or have any significant axial
rotation in their spines during imaging, the resulting IVA and IVT measurements can become more variable. A group led by W. Frobin found that
interobserver variability in IVA and IVT measurements could be reduced
simply by using a more sophisticated method of landmarking radiographic
21,22
images.
This technique was found to significantly reduce the variability
in IVA and IVT measurements associated with radiographic image distor-
demonstrated that a difference of
standard deviation) from the datasets listed in Table 10-2 (5.0° cervical and
4.4° lumbar). From the Wong , Hipp & Wharton, and Reitman data sets
it can be shown that using automated software image analysis methods as
opposed to manual methods for measuring IVA can reduce interobserver
variability and thus also reduce observed intersite variability.
Collecting Dynamic Images “During the Bend”
through the Diagnostic Use of Fluoroscopy for
3
Functional Testing of the Spine
With the current standard of care for conducting functional testing of the
spine, only static images are collected while subjects hold static posture in
their MVBAs; no dynamic images are collected, and no images are collected during the bend. There have been several research groups who have
addressed this potential shortcoming by collecting dynamic images at points
throughout spine bending by using fluoroscopy.
tage of using fluoroscopy instead of standard radiographs is that if a functional problem is only present dynamically, or if it is only visible at positions
other than MVBA, it would never be detectable using the current standard
of care. However, although arguably superior to the current standard of
care, this method of functional imaging has never become widely used in
the United States, because most major American payer organizations have
refused to reimburse practitioners for such a use of diagnostic fluoroscopy.
27–33
The principal advan-
tion and with out-of-plane positioning of the subject during imaging.
There have been multiple groups who have successfully developed
software-based image analysis tools that have been shown to reduce this
interobserver variability. For example, one of the authors of this chapter,
Kris Wong, recently developed a software algorithm for automatically deriving IVA measurements from bending images. Wong et al. published two
datasets of normative values, one dataset that was derived manually,
second dataset that was derived using automated software image processing
algorithms.
24
Both datasets were measured from active flexion- extension
23
and a
bending of the lumbar spine. The average standard deviation across the
lumbar levels measured in this study (a measurement of the observed
Reducing the Subject-Related IVA Variability Introduced through Uncontrolled Bending During Imaging
Subject-related variability is perhaps the largest contributor to overall IVA
measurement variability. A large amount of subject-related variability is introduced as a result of the way patients bend during imaging. According to the
current clinical standard of care, patients are instructed to bend their spines
to their MVBA in both flexion and extension, and then hold those postures
static while standard radiographs are captured. However, MVBA bending is
25
58
L4/L5 Intervertebral Motion Plot (Asymptomatic Subject)
L4/L5 Rotation (°)
P A R T I I Basic Science of the Aging Spine
highly variable, as subjects have different bending abilities and therefore bend
to highly variable MVBAs. Further, the willingness of the subject to bend
consistently to the same MVBA from test to test is also dependent upon
the patient’s perception of or fear of pain, which can be highly variable and
unpredictable. One study examined the intrasubject variability in MVBA
bending of the lumbar spine, and found that for the average patient, total
gross lumbar spine bending varies about 26% from morning to evening.
Because gross spinal motion can be devolved into the sum of the individual
motions at each intervertebral level, it stands to reason that any variability in
overall gross spine bending will be reflected in intervertebral motion.
In addition to the diurnal variation that any given patient exhibits in
spine bending MVBAs, there is also a high degree of variability in MVBA
from subject to subject. This variability can be expected to be considerable,
given the range of sensitivity or stoicism of subjects, their level of pain, and
their fear or resilience in the face of it. In the cervical spine, there is a wide
range of MVBA observed in normal asymptomatic subjects. The 95% confidence interval on observed sagittal plane cervical spine MVBA was measured to range from 34° to 82° of total gross motion — a very large range.
The authors of that study, which measured both total gross cervical spine
motion and cervical intervertebral motion (IVA), observed that “… this
variation in gross motion between individuals had a highly significant effect
on all measures of IVM [intervertebral motion].”
also been measured in the lumbar spine among sufferers of chronic back
34
pain.
The 95% confidence interval on observed sagittal plane lumbar
MVBA was reported to range from 25° to 93° of total gross motion, an even
larger range than was observed in the cervical spine among asymptomatics.
Clearly, this high degree of variability in MVBA plays a large role in
driving the high levels of overall variability in IVA measurements. As discussed previously in this chapter, it is the high degree of variability in IVA
that renders these measurements so clinically ineffective. Controlling the
variability associated with MVBA bending therefore should be expected to
reduce IVA measurement variability, and thus increase the diagnostic efficacy of functional testing of the spine.
One means of addressing for the variability in MVBA bending is to
normalize IVA measurements against the measurements of total range of
motion between an entire spinal region. For example, in the lumbar spine
the IVA from any given level can be divided by the total bending that occurs
between L1 and S1 to express IVA as a percentage of total lumbar range of
motion. By doing this, it is possible to reduce the effects of the variability
introduced by MVBA bending. In the case of the lumbar spine, this method
has been shown to be an effective means of addressing the variability inherent in MVBA bending.
ful in studies involving the cervical spine.
29,30
This method has also been shown to be success-
25
Another means of addressing IVA measurement variability caused by
MVBA bending is through the use of passive rather than active spine bending. Dvorak and Panjabi (one of the authors of this chapter) published a
study in 1991 in which they used a passive bending technique to decrease
the variability in MVBA.
8
In this study, an assistant applied a pulling force
to subjects as they bent into flexion. The assistants attempted to pull the
patients into passive flexion with as constant a force as possible, and in
so doing provided a level of standardization in the bending angles of the
patients. In this study of 41 patients, the authors reported an average standard deviation of 2.8° in the IVA measurements across the lumbar levels
from passive lumbar bending, which represents a 36% reduction to the
observed intersubject/intrasite variability as compared to the mean value
of 4.4° for the average standard deviation across lumbar levels from the
MVBA datasets listed in Table 10-2.
Another means of addressing the IVA variability caused by MVBA
bending is to take IVA measurements from standardized bending angles
(SBA). For the remainder of this text, IVA measurements taken from SBA
will be referred to as sIVA, while IVA measurements taken from MVBA
will be referred to as IVA. Wong (an author of this chapter) et al. developed
a novel method of measuring sIVA that involved the use of an electrogoniometer connected to a fluoroscope, such that the electrogoniometer could
trigger the capturing of images of the lumbar spine at every 10° of lumbar bending.
software was utilized to derive sIVA measurements from the fluoroscopic
23,24,31
Once images were collected, automated image analysis
images. In that study, the authors reported an average standard deviation of 1.3° in the measurements of sIVA across the lumbar levels, which
25
Variation in MVBA has
represents a 72% reduction to the observed intersubject/intrasite variability
as compared to the mean value of 4.4° for the average standard deviation
across lumbar levels from the IVA datasets listed in Table 10-2.
Motion Control Technology Used in Combination
with Digital Videofluoroscopy and Automated
34
Image Analysis Software
A group in Bournemouth, England led by Alan Breen, one of the authors
of this chapter, has developed a patient handling system intended to reduce
subject-related variability by controlling and standardizing the bending of the
subject during imaging. This system involves a powered articulating device
that is capable of rotating the subject’s spine through a controlled and standardized sweep of spine bending during imaging. These devices are capable of
providing controlled standardized spine bending in flexion/extension and lateral bending, cervical and lumbar spine motion, and standing active (weightbearing) as well as recumbent passive (nonweightbearing) spine bending.
Using this device, sIVA can be measured in recumbent passive spine bending
and both sIVA and IVA can be measured in standing active spine bending.
Breen et al. have integrated other recent technological developments —
namely the use of digital videofluoroscopy plus the development of automated image analysis software to track vertebral bodies in sequential fluoro
scopic images — together with these patient handling devices to produce a
new system for conducting functional testing of the spine. Breen et al. have
called this the OSMIA system, which stands for Objective Spinal Motion
Imaging Assessment. Various components of this system have been discussed in a string of publications starting in 1988.
validation testing of the passive recumbent integrated system was published
40
in 2006.
The results from this performance and validation testing suggest
that the OSMIA system provides several important technical performance
advantages relative to the current clinical standard of care.
The OSMIA system is intended to integrate all of the key technical
performance benefits associated with other recent innovations in spinal
functional testing into a single, integrated system. First, by measuring sIVA,
the OSMIA system is intended to reduce subject-related variability similar
to that observed by Wong et al. Second, by using digital videofluoroscopy
imaging rather than standard radiographic imaging, the OSMIA system
collects data “during the bend” in a way similar to previous investigators.
Third, by using digital image-processing software to automatically track
and measure movements of vertebral bodies, the OSMIA system is also
intended to reduce observer-related variability.
See Figure 10-4 for an example of how the OSMIA system plots sIVA
against the gross lumbar bending angle (the angle between the thorax and
the pelvis). The OSMIA system has been tested on a normative cohort of
30 asymptomatic subjects, and among these subjects, motion patterns were
generally similar to that depicted in Figure 10-4.
15
10
5
0
5
Left Right
10
15
F IG UR E 1 0 -4 An example of a plot of sIVA vs. the gross lumbar bend-
ing angle from the OSMIA system. The graph depicts a typical sinusoidal curve
moving in the same direction as the trunk bend taken from sIVA collected at L4/
L5 from a patient tested with the OSMIA system in passive recumbent lateral
side bending to 40° in each direction.
32,35–39
Performance and
-
10
Paradoxical Immobility Hypomobility
-5
C H A P T E R 1 0 Kinematics of the Aging Spine
5
0
59
-10
F IG UR E 10 - 5 Case evidence of patients with lumbar degenerative disc disease presenting with apparent paradoxical motion, immobility, and apparent
hypomobility. These plots depict motion at the index level as measured directly presurgical to a fusion or dynamic stabilization procedure. These motion plots represent sIVA measurements from passive recumbent side bending. In contrast to the motion plot depicted in Figure 10-4, which includes both the left and right phases
of lateral lumbar spine bending, these motion plots represent intervertebral motion from only right lateral bending (to 40° of right lateral bending). The dashed
“Normal” line on each graph is representative of the motion plots that were observed among the asymptomatic cohort.
Apparently Normal Apparently Normal Apparently Normal
In addition to the asymptomatic subjects tested with the OSMIA
system, symptomatic patients have been tested prior to surgical fusion or
dynamic stabilization procedures. Among this patient cohort, there is case
evidence that many of the “theoretically detectable” functional presenta-
TA BL E 10 5 Mean sIVA, sIVA Stan dard Devi atio n ( SD),
and Hypo mobilit y and Hyp ermobil ity s IVA Thres hold s for
the Measurement System Descr ibed by Wong et al.
*
tions depicted in Figure 10-2 are detectable with the OSMIA system. See
Figure 10-5 for case evidence of patients presenting with paradoxical
motion, immobility, and intervertebral hypomobility.
NEW INSIGHTS INTO THE BIOMECHANICS OF THE AGING SPINE
Making use of these recent advances in functional testing technology, it is
now possible to begin to sharpen our understanding of the biomechanics
of the aging spine. Having these new capabilities opens up a new world of
insights into in vivo spine biomechanics that has been effectively off limits
due to the prohibitively high variability in IVA measurements associated
with the current clinical standard of care.
Physiologic Variation in sIVA among Normal Subjects Is Very Low
By producing such a dramatic reduction to the observed measurement variability, the Wong et al. data yield two profound discoveries. First, it is clear
Lumbar
Level
L1/L2 14.7 1.2 12.3 17.1
L2/L3 12.1 1.3 9.5 14.7
L3/L4 10.0 1.0 8.0 12.0
L4/L5 7.2 1.1 5.0 9.4
L5/S1 5.2 1.7 1.8
*
All values represent degrees of intervertebral rotation in the sagittal plane associated with SBA
bending from 10 degrees of extension to 40 degrees of flexion.
†
Note: Because the generally accepted threshold for fusion is 5°, it might not be advisable to
attempt to differentiate hypomobility from “functional fusion” at L5/S1. However, because
Wong et al.
with the current clinical standard of care, it is debatable whether or not the threshold for
“functional fusion” of 5° should apply.
Mean
sIVA SD
24
have demonstrated a much lower interobserver variability than is associated
Hypomobile
Threshold
(Mean − 2*SD)
†
Hypermobile
Threshold
(Mean + 2*SD)
8.6
that there is actually very little physiologic variation in the sIVA measurements among asymptomatic subjects. This fact has remained obscured by the
high variability inherent in today’s standard of care for functional testing of
the spine. In fact, there is such little physiologic variation that it becomes possible to define very tight ranges for the 95% confidence interval of observed
sIVA values. These ranges are narrow enough that it is possible to dramatically outperform the current clinical standard of care by: (1) being able to
of a pathological change, rather than a result of the normal aging process.
Because intervertebral hypomobility is often associated with older patients
with compromised disc height, it is important for practitioners to recognize intervertebral hypomobility observed with sIVA as being pathological,
and not assume that intervertebral hypomobility in older patients is to be
expected as part of the normal aging process.
differentiate hypomobility from immobility, (2) differentiating hypomobility
from normal motion, (3) detecting hypo/hypermobility with much tighter
thresholds, which improves both the sensitivity of hypomobility/hypermobility detection as well as the specificity of the detection of normal motion.
See Table 10-5 for the ranges for the detection of flexion-extension hypomo-
bility and hypermobility for the measurement system devised by Wong et al.
Age-Related Differences in the Functional
Presentations of Degenerative Spondylolisthesis
Patients
After conducting a study of sIVA in normal asymptomatic subjects, Wong
et al. used this new measurement system to examine sIVA in 91 degenera-
Rethinking the Conventional Wisdom Regarding Intervertebral Hypomobility and Age
A second profound finding of Wong et al. is that when sIVA is examined,
vertebral levels in normal subjects became less hypomobile as normal subjects experience healthy aging, not more hypomobile, as has been the conven-
tional wisdom. See Figure 10-6 for these results as reported by Wong et al.
This has very significant implications for the management of the aging spine.
While it has been shown that a patient’s MVBA decreases with progressing
41–43
age,
Wong et al. have proved that this is not due to a decreased motion
response of lumbar FSUs to gross lumbar bending. Therefore, intervertebral
hypomobility as observed with sIVA should be considered to be the result
tive spondylolisthesis sufferers. Among these 91 patients, Wong et al. found
the following spinal segmental mobility patterns:
12/91: (13%): Immobility
27/91: (30%): Hypomobility
13/91: (14%): Normal
39/91: (43%): Hypermobility
44
A multiple regression analysis was then conducted to compare the predictive power of gender, age, grade of slippage, and disc height (as measured in
the anatomical starting position) in predicting the mobility patterns that were
observed among this population of degenerative spondylolisthesis sufferers.
This analysis revealed that grade of slippage, followed by age, was a significant
60
IVFE L1/2 IVFE L2/3
IVFE (degrees)
IVFE (degrees)
IVFE (degrees)
P A R T I I Basic Science of the Aging Spine
15
10
5
15
10
5
15
10
A
B
C
D
5
0
10
5
0
10
5
0
0 10 20 30 40
ROM (degrees)
IVFE L3/4
A
B
C
D
0 10 20 30 40
ROM (degrees)
IVFE L5/S1
A
B
C
D
15
10
5
0
IVFE (degrees)
5
15
10
IVFE (degrees)
5
A
C
10
A
C
5
0
10
B
D
0 10 20 30 40
ROM (degrees)
IVFE L4/5
B
D
0 10 20 30 40
ROM (degrees)
F IG UR E 1 0- 6 Plot of sIVA versus gross lumbar bending angle for four age-defined cohorts. Wong et al. took sIVA measurements from 100 asymptomatic
volunteers, subdividing this group into four 25-patient age-defined cohorts (Group A = 21 to 30; Group B = 31 to 40; Group C = 41 to 50; and Group D = 51 and
above). Note that in each graph, the oldest cohort appeared to have the greatest sIVA values.
predictor of the observed mobility patterns. Specifically, younger patients with
grade 1 L4/5 degenerative spondylolisthesis predicted hypermobility, whereas
elder patients with grade 2 or above predicted a hypomobility pattern. These
findings are consistent with the findings of Takayanagi et al,
IVT and IVA in bending radiographs are both reduced in degenerative spondylolisthesis patients as compared to asymptomatic controls, and that both
IVT and IVA decrease as the grade of slippage increases.
SUGGESTIONS FOR THE CLINICAL USE OF FUNCTIONAL TESTING METHODS
A review of past knowledge shows that the current standard of care for
assessing spinal function is poorly suited to the management of the aging
spine. Hypomobility appears to be a condition that is more often associated
with the diseased aging spine than with diseased younger patients; however,
this is the one mobility pattern that is completely undetectable with the
current standard of care. Further, while the current standard of care is arguably more effective in detecting hypermobility than any other mobility pattern, this condition is most commonly associated with younger patients as
opposed to older patients. With respect to the use of functional diagnostics
to assist in the management of the aging spine, there is a strong case to be
made for the adoption of improved methods.
Suggestions Regarding the Clinical Use of the Current Standard of Care
The current standard of care for conducting functional testing of the spine
using standard radiographs and MVBA spine bending is the only method
that is widely available to all practitioners, and will remain so until improved
5
10
0 10 20 30 40
ROM (degrees)
methods become commercially available. Therefore the authors put forward
the suggestions given in Table 10-6 regarding the use of the current clinical
33
who found that
standard of care for conducting functional diagnostics of the spine.
Suggestions Regarding the Clinical Use of Recently Developed Methods for Conducting Functional Testing of the Spine
There have been innovations in functional testing technology that offer the
promise of definitively detecting those functional presentations most relevant to the aging spine (immobility, hypomobility, and normal motion).
These innovations involve a set of three potential changes to the current
clinical standard of care:
e use of automated image analysis software to derive IVA measure-
ments from radiographic images (as opposed to manual landmarking
methods).
e use of fluoroscopy to capture dynamic data regarding interver-
tebral motion during spine bending (as opposed to taking standard
radiographs of patients holding static postures at the extremes of spine
bending).
e use of sIVA and IVA rather than IVA alone.
The authors have already put forward the improvements to diagnostic efficacy that are potentially attainable through the adoption of these
improved methods. However, if any of these newer methods is to be
adopted, it is critical that all issues affecting patient safety are fully explored.
The authors have put the key considerations regarding patient safety associated with the adoption of these new methods for functional testing in
Table 10-7.
C H A P T E R 1 0 Kinematics of the Aging Spine
TA BL E 10 6 Su mmar y of Suggestio ns for t he Cl inic al Use of the Curre nt St andard of Ca re for Spinal Func tiona l Testing
Functional Testing Results
Suspected
Condition
(using the current clinical standard of care)
Diagnosed Result (Definitive
diagnoses are in bold) CommentsIVA Greater Than IVA Less Than
61
Rotational
instability
Pseudarthrosis in
previously fused
patients
IVA hypermobility
thresholds in Table 10-3
∞ Rotational Hypermobility (or
more generally, an “instability”)
Very low false positive rate; can base treatment decision on this result alone. High rate of false negatives,
so IVA below the hypermobility threshold should
not be used to rule out a rotational hypermobility.
5° IVA hypermobility
thresholds in
Table 10-3
Negative 5° (i.e., motion
5° Inconclusive: “Potentially
in the direction opposite
the spine bend)
negative ∞ Negative 5°
(i.e. motion in the
Inconclusive: “Potentially normal” Suspect normal motion in these patients; however.
do NOT base treatment decision solely on this
result.
Suspect lower-than-normal motion in these patients;
hypomobile, Immobile,
Paradoxical, or Normal”
Paradoxical Motion (or more
however, do NOT base treatment decision solely on
this result.
Can base treatment decision on this result alone.
generally, an “instability”)
direction opposite
the spine bend)
5° ∞ Pseudarthrosis Can base treatment decision on this result alone.
Negative 5° (i.e., motion
5° Inconclusive: “Potential
in the direction opposite
the spine bend)
negative ∞ Negative 5° (i.e.,
pseudarthrosis”
Pseudarthrosis Can base treatment decision on this result alone.
Corroborative CT scan is suggested before considering a revision surgery although CT scans can have
low sensitivity.
motion in the
direction opposite
the spine bend)
TA BL E 10 7 The Auth ors’ Suggestio ns Re gardin g the Key Patient -Safety–Rela ted Issue s Relat ed to the Adopti on of Any of the
Newer Method s for Conduc ting Functiona l Testing of t he Spin e
Change to Functional Testing Method Key Patient-Safety Issues and Authors’ Suggestions
e use of automated image analysis software
instead of manual landmarking techniques
e use of fluoroscopy to capture dynamic images
of intervertebral motion during spine bending
instead of standard radiographs to capture images
of statically held spine bending postures
e use of sIVA and IVA rather than IVA alone
e software’s observer-related variability in IVA measurements must be validated to be lower than what has
been reported for manual landmarking techniques.
e accuracy and precision of the software in measuring IVA must be known.
If the observer-related variability is low enough, and if the accuracy and precision are good enough, it may be
feasible to institute different thresholds for the detection of pseudarthrosis, immobility, and paradoxical motion
than are currently used.
Fluoroscopy imaging may be substituted for standard radiographic imaging for the purpose of conducting
functional testing.
However, as image contrast for fluoroscopy can be poorer than that of standard radiographs, fluoroscopic
images may fail to detect certain conditions that require the high contrast provided by standard radiographs
(such as infection, skeletal neoplasia, etc.).
erefore, for any patient for whom fluoroscopy is substituted for standard radiographs for conducting
functional testing of the spine, a recently taken standard radiograph of the spine should also be available.
e total dose of radiation to the patient associated with any fluoroscopy-based protocol for conducting func-
tional testing should be measured and compared to that which would be received by the patient with standard
radiographic imaging. Any increase in effective dose to the patient needs to be carefully evaluated.
Using SBA instead of MVBA from which to take IVA measurements has been shown to reduce the
subject-related variability in these measurements (i.e., sIVA has less measurement variability than IVA).
e total observed intersite variability associated with sIVA would need to be validated before new thresholds
for detecting hypomobility, normal motion, and rotational hypermobility are adopted.
Testing protocols would likely need to include assessments of sIVA as well as IVA, as there are potentially
valuable diagnostic insights to be gained from observing IVA at the physiologic operating ranges of gross trunk
motion.
62
P A R T I I Basic Science of the Aging Spine
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Causes of Premature Aging of the Spine
Florence P. S. Mok, Dino Samartzis, Kenneth M. C. Cheung, and Jaro Karppinen
11
k e y p o i n t s
Various age-related factors are involved in the degenerative process of the
spine.
Premature aging of the spine can be affected by biochemical, biomechanical,
cardiovascular, lifestyle, and genetic factors.
Interactions between various etiological factors contributing to the premature
aging of the spine may be present.
Although premature aging of the spine may occur, such changes may not be
synonymous with clinical symptoms.
INTRODUCTION
The spine is the grand architect of the human body. Working in close symbiotic interplay between soft and bony tissues, the spine is responsible for
structure and function, as well as protection of the spinal cord and associated neural elements. Aging is an inevitable process that affects almost every
structure of the human body, including the spine. Age-related changes of the
spine are an expected facet of life with the progression of age. However, it is
not uncommon for physicians to encounter young patients presenting with
characteristics of advanced aging of the spine, the so-called premature aging
or degenerative changes.
Premature aging of the spine is a salient concern, in that if it achieves
clinical relevance associated with symptoms and impaired function, it has
the potential to incur severe socioeconomic consequences. To identify such
degenerative changes, advanced imaging, such as magnetic resonance imaging (MRI), has been a popular mainstay in the armamentarium of the physician for diagnostic and therapeutic interventions. However, numerous
studies have also documented that the severity of radiological changes is
not always associated with clinical symptoms (Figure 11-1).
it is essential to determine whether degenerative changes of the spine are
a part of the natural evolution of the spine because of age, or if they result
from a disease process (Figure 11-2) heralded by risk factors, possibly preventable, that prematurely change the spine. In this chapter, the authors
will discuss the numerous factors that may contribute to premature aging
of the spine.
1
Nonetheless,
PREMATURE AGING FACTORS
Biochemical
In humans, the notochordal cells in the nucleus pulposus (NP) dramatically decrease after birth, and they eventually disappear, probably
through apoptosis, and are replaced by chondrocyte-like cells by the
first decade. The reduction in notochordal cell population with maturity
could decrease proteoglycan production and contribute to the degenerative process. Furthermore, the naturally occurring cellular senescence, via
telomere shortening, plays a role in disc aging as well as degeneration.
However, degenerated discs are prone to increased cell senescence as the
exposure to various factors, such as interleukin-1 (IL-1), reactive oxygen
species, and mechanical load, further accelerate disc degeneration. Therefore exposure to such factors could induce premature senescence of the
2
disc.
In addition, degenerated discs have been shown to have higher concentrations and activities of degradative enzymes than normal discs,
which could be due to the phenotypic changes of disc cells in response
to various stimuli such as chemical mediators and mechanical loading.
The alteration in disc cell phenotype leads to a cascade of biochemical
changes that include the following: (1) decrease in matrix synthesis (e.g.,
aggrecan, decorin, type II and type IX collagens); (2) downregulation in
the expression of growth factors and their receptors, which impairs the
regenerative processes; and (3) upregulation of the catabolic metabolism
through the increase in concentration and activity of matrix metalloproteinases (MMPs), reduction in tissue inhibitors of metalloproteinases
(TIMP) levels, as well as the increase in proinflammatory cytokines and
their receptor levels. Among all the cytokines, interleukin-1β in particular
seems to play a central role, because it suppresses matrix synthesis and
also stimulates the production of other inflammatory mediators, which
further enhances matrix catabolism.
2,3
Biomechanical
Clinically, disc degeneration is generally more prevalent and severe in the
lower lumbar discs, suggesting that higher mechanical loading in this region
may be a strong causative factor. Mechanical insults to the disc could induce
fatigue failures in the endplates or annulus, which accelerate the catabolic
cascade. However, mechanical loading is not a deleterious factor in itself
as loading within physiological range stimulates disc matrix turnover and
enhances anabolic factors, such as proteoglycan synthesis and TIMP production, whereas loading outside this range (less or more than optimal) is
detrimental to disc metabolism. In vivo animal studies showed that high
magnitudes or frequencies of dynamic and static compression induced cell
apoptosis, structural failure and increased catabolism, whereas downregulation of anabolic gene expressions has been shown in the discs exposed to
immobilization.
A cadaveric investigation by Videman et al8 reported that history of
occupational physical loading was related to disc degeneration and pathological changes of the lumbar spine, but a clear linear dose-dependent relationship was not established. In former elite athletes, more spinal degenerative
findings were presented in those who engaged in heavier loading exercises
versus light exercises, yet it only accounted for less than 10% of variability of
MRI findings, despite the extreme difference in loading conditions.
heavier lifetime physical loading, involving both occupational and leisure
time activities, accounted only for small amounts of variance in disc degeneration in MRI, being 7% over T12-L4 and 2% over L4-S1.
when accounting for individual anthropometric parameters, such as body
weight, lifting strength, and axial disc area in relation to disc degeneration,
although all with modest effect, the lifelong continuous loading associated
with these parameters was more influential than extrinsic physical loading
related to occupation and leisure activities.
4-7
9
In fact,
10
Moreover,
11
63
64
P A R T I I Basic Science of the Aging Spine
A
F IG UR E 11 -1 A, An 18-year-old nonsmoking female presented with
chronic low back pain for more than 2 years without history of lumbar injury.
Sagittal T2-weighted MRI shows no evidence of disc degeneration or other
radiological abnormalities. B, A 37-year-old female, who has never experienced
low back pain. Sagittal T2-weighted MRI of the lumbar spine shows severe disc
degeneration at L4-L5 and L5-S1, radial tear at L4-L5, and Grade I spondylolisthesis at L5-S1.
B
Atherosclerosis
The blood supply to the lumbar spine is derived from the abdominal aorta,
which gives off branches to supply regional vertebral segments (Figure 11-3).
The nutritional supply to the intervertebral disc (IVD) depends on the diffusion potential through the endplates of the vertebral bodies. Therefore
disc nutrition could be impeded by factors that diminish blood flow to the
vertebrae, by defects or calcification of the endplates, or a combination of the
three. An autopsy study by Kauppila et al.
13
determined that the severity of
disc degeneration was significantly associated with the grade of stenosis of
the segmental arteries supplying the disc, and this association was stronger
in the upper three lumbar levels than the lower two levels. Moreover, the
degree of disc degeneration also increased in line with the complexity of the
atherosclerotic lesions in the abdominal aorta. In accordance to the cadaveric studies by Kauppila et al.
association between impaired lumbar artery blood flow and diminished disc
diffusion in both healthy subjects
13
in vivo MRI studies have confirmed the
14
and patients with low back symptoms.15
It is generally thought that the reduced disc diffusion could in turn cause
disc degeneration, but no definite answer to this hypothesis is available. Furthermore, clinical low back symptoms were also found to be associated with
the presence of lumbar arterial stenosis.
tion to back symptoms is further substantiated in a long-term prospective
study by Leino-Arjas et al.
19
in which high baseline serum total cholesterol
16-18
An atherosclerotic contribu-
and triglyceride levels were associated with incident radiating low back pain
among Finnish industrial employees. The increased risk of abnormal levels
of cholesterol and triglycerides on radiating pain was independent of other
potential risk factors, such as age, gender, occupational class, work history,
exercise habits, smoking, and body mass index (BMI). The mechanism
through which atherosclerosis and occlusion of arteries affect disc degeneration may be directly related to diminished blood flow, and hence decreased
nutritional supply to the IVD, and also by the systemic inflammatory effect
associated with atherosclerosis.
12
A
F IG UR E 1 1- 2 A, A 16-year-old nonsmoking male presented with low
back pain but had no history of lumbar injury. T2-weighted MRI of the lower
thoracic and lumbar spine shows severe disc degeneration at L3-S1 and endplate irregularities over thoracic and lumbar spine. B, A 53-year-old asymptomatic female. Sagittal T2-weighted MRI shows no signs of disc degeneration or
other radiological abnormalities.
Aorta
Capillaries in
vertebral endplate
B
Segmental
artery
Intervertebral
disc
F IG UR E 1 1 -3 The segmental artery provides blood supply to the
vertebral body. (Adapted from Raj PP. Intervertebral disc: anatomy-physiology-
pathophysiology-treatment. Pain Pract 2008;8:18-44.)
Interosseous arteries
in vertebral body
In a long-term follow-up study of 98,407 female nurses, cardiovascular
risk factors, such as smoking, diabetes, hypertension, high cholesterol, obesity, and family history of myocardial infarction before the age of 60 years,
were significantly associated with an increased risk of lumbar disc herniation. Moreover, after adjustment for other cardiovascular risk factors, the
increased risk of symptomatic disc herniation exhibited a dose-dependent
relationship with smoking (p = .003) and overweight (p = .01).
20
an observational study of 270 Japanese elderly with a mean age of 68.4years,
However, in