ARTICLE IN PRESS

TagedAPRFiur TagedAPREn TagedAPRFiur TagedAPREn

TagedAPREnThe Spine Journal 000 (2024) 1−12

Narrative Review
TagedAPRH1Evolution of lumbar degenerative spondylolisthesis with
key radiographic featuresTagedAPTREn
TagedAPRArvin Saremi, MD, MSa,b,*, Kush K. Goyal, MDa, Edward C. Benzel, MDa,
R. Douglas Orr, MDaTagedAPREn
TagedAPR Center for Spine Health, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
a
b
Case Western Reserve University School of Medicine, 9501 Euclid Ave, Cleveland, OH 44106, USATagedAPTREn
Received 30 April 2023; revised 4 December 2023; accepted 2 January 2024

TagedAPRAbstract Spondylolisthesis is a common finding in middle-aged and older adults with back pain. The patho-
physiology of degenerative spondylolisthesis is a subject of controversy regarding not only its etiol-
ogy but also the mechanisms of its progression. It is theorized that degeneration of the facets and
discs can lead to segmental instability, leading to displacement over time. Kirkaldy-Willis divided
degenerative spondylolisthesis into three phases: dysfunction, instability, and finally, restabiliza-
tion. There is a paucity of literature on the unification of the radiological hallmarks seen in spondy-
lolisthesis within these phases. The radiographic features include (1) facet morphology/
arthropathy, (2) facet effusion, (3) facet vacuum, (4) synovial cyst, (5) interspinous ligament bursi-
tis, and (6) vacuum disc as markers of dysfunction, instability, and/or restabilization. We discuss
these features, which can be seen on X-ray, CT, and MRI, with the intention of establishing a time-
line upon which they present clinically. Spondylolisthesis is initiated as either degeneration of the
intervertebral disc or facet joints. Early degeneration can be seen as facet vacuum without consider-
able arthropathy. As the vertebral segment becomes increasingly dynamic, fluid accumulates within
the facet joint space. Further degeneration will lead to the advancement of facet arthropathy, degen-
erative disc disease, and posterior ligamentous complex pathology. Facet effusion can eventually
be replaced with a vacuum in severe facet osteoarthritis. Intervertebral disc vacuum continues to
accumulate with further cleft formation and degeneration. Ultimately, autofusion of the vertebra at
the facets and endplates can be observed. With this review, we hope to increase awareness of these
radiographical markers and their timeline, thus placing them within the framework of the currently
accepted model of degenerative spondylolisthesis, to help guide future research and to help refine
management guidelines. © 2024 Elsevier Inc. All rights reserved.TagedAPTREn

TagedAPRKeywords: Facet arthropathy; Facet effusion; Facet morphology; Facet vacuum; Interspinous ligament bursitis; Lumbar
degenerative Spondylolisthesis; Lumbar instability; Spondylolisthesis timeline; Synovial cyst; Vacuum discTagedAPTREn

TagedAPRH1IntroductionTagedAPTREn degenerative spondylolisthesis into three phases: phase of

dysfunction, a stage of functional abnormalities with minimal
TagedAPRSpondylolisthesis is a common finding in middle-aged and
anatomic changes; phase of instability, involving further
older adults with back pain. There is a paucity of literature on
degeneration of the disc, facets, and ligaments; finally, phase
the unification of the radiological hallmarks of spondylolis-
of restabilization, through osteophytes and fibrosis formation
thesis. The pathophysiology of degenerative spondylolisthesis
of the facets and intervertebral disc [1].TagedAPTREn
is a subject of controversy. It is theorized that degeneration
TagedAPRWe plan to identify, display, and discuss the radiographi-
of the facets and discs can lead to segmental instability, lead-
cal features that can be seen on X-ray, CT, and MRI, with
ing to displacement over time. Kirkaldy-Willis divided

TagedAPREnFDA device/drug status: Not applicable.
TagedAPREnAuthor disclosures: AS: Nothing to disclose. KKG: Nothing to disclose.
ECB: Nothing to disclose. RDO: Stock Ownership: Agoda Medical
(none), Tyber Medical (none); Speaking and/or Teaching Arrangements
(B); Board of Directors: World Spinal Column Society (none).
TagedAPREn*Corresponding author. Case Western Reserve University School of
Medicine, Health Education Campus, 9501 Euclid Ave, Cleveland, OH
44106, USA.
E-mail address: arvin.saremi@case.edu (A. Saremi).

https://doi.org/10.1016/j.spinee.2024.01.001
1529-9430/© 2024 Elsevier Inc. All rights reserved.
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TagedAPRFiurTagedAPREn2 A. Saremi et al. / The Spine Journal 00 (2024) 1−12

Fig. 1. Evolution of lumbar degenerative spondylolisthesis features, broken down into the three phases proposed by Kirkaldy-Willis [1], with its associated
radiographically visible features. Instability is defined as >3 mm dynamic translation based on Boden et al. [2]. The Y-axis demonstrates the relative inci-
dence of each feature to each other. Dashed lines indicate possible obscurity on static (or supine) radiographs, requiring dynamic flexion-extension for better
visualization. ISL: Interspinous ligament.TagedAPTREn

the intention of establishing a timeline upon which they
present clinically. These features are routinely used in the
outpatient setting to assist with the diagnosis of spondylo-
listhesis and guide management. They consist of common
structural and degenerative changes within the facet joints,
posterior ligamentous complex, and the intervertebral disc.
These features include (1) facet morphology/arthropathy,
(2) facet effusion, (3) facet vacuum, (4) synovial cyst, (5)
interspinous ligament bursitis, and (6) vacuum disc as
markers of dysfunction, instability, and/or restabilization.
(Figs. 1 and 2).TagedAPTREn
TagedAPRIn this review, we hope to increase awareness of
these radiographical markers, thus placing them within
the framework of the currently accepted model of
degenerative spondylolisthesis, to help guide future
TagedAPRFiur
research and to help refine management guidelines. To
this aim, we will assemble a comprehensive review of
the current state of the literature on degenerative spon-
dylolisthesis within its radiographical context. We intend
to create a schematic timeline that explores the evidence
regarding each feature throughout the natural history of
spondylolisthesis.TagedAPTREn
TagedAPRH2SpondylolisthesisTagedAPTREn
TagedAPRSpondylolisthesis is defined as an acquired anterior or
posterior displacement of one vertebra over the subjacent
vertebra [3]. This anatomical disruption can be traumatic,
dysplastic, or pathologic in origin, compromising the struc-
ture of the vertebral body or arch. Spondylolisthesis is asso-
ciated with chronic degenerative processes within the

Fig. 2. Evolution of lumbar degenerative spondylolisthesis illustrated in the three phases proposed by Kirkaldy-Willis [1], with its associated radiographical
features. The displayed features follow the same progression projected in Figure 1.TagedAPTREn
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TagedAPREnA. Saremi et al. / The Spine Journal 00 (2024) 1−12
connective tissue safeguarding the integrity of the spinal
column. This review focuses on radiographic features more
routinely observed in degenerative spondylolisthesis of the
lumbar spine.TagedAPTREn
TagedAPRThe epidemiology of degenerative spondylolisthesis is
both age and gender specific [4]. The prevalence increases
with age, more commonly found in patients older than 50
[5−7]. It is also reported more frequently in female patients
compared with males, as high as 6-fold [5,7]. There have
been variable reports of the prevalence of degenerative
spondylolisthesis in the general population, ranging from
6% to >20% depending on the population studied [5−8],
suggesting that both environmental and genetic factors play
a role. The lower lumbar vertebrae are the most vulnerable
to the development of spondylolisthesis as they bear the
greatest load. This is followed by the cervical region, with
rare occurrences of thoracic spondylolisthesis due to
increased stability provided by the costal architecture. The
highest prevalence is reported at L4−L5 vertebrae (1.5%
male; 5.9% female), with only a single level affected [6,7].
This level is the most susceptible due to the combination of
high sheering forces placed on the lower vertebrae and the
sagittal orientation of its facet joints. L5−S1 has higher
sheer forces, but more coronally oriented facets compared
with L4−L5. Prevalence is followed by L5−S1 (0.7%
male; 1.2% female) and L3−L4 (0.5% male; 1.2% female)
anterior displacement, though they frequently co-occur
with L4−L5 (34%) [6,7].TagedAPTREn
TagedAPRThe extent of displacement is commonly reported, based
on the method first described by Meyerding [9], graded on
a scale of I-V based on the percent slippage of the vertebral
body over the subjacent vertebrae. The grade increases in
25% intervals, with grade 5 defined as the entire body slip-
ping beyond the rim of subjacent vertebrae (spondylopto-
sis). The anterior displacement in the majority of reported
cases tends to be mild, rarely beyond >30% displacement
[10,11]. Higher-grade slips are generally not seen in degen-
erative spondylolisthesis. The classification does not, how-
ever, correlate with the degree of pain and progression of
degeneration [12,13]. It also does not characterize spondy-
lolisthesis based on other associated radiographic features,
which will be addressed below. Nonetheless, it is a well-
validated method for communicating the degree of devia-
tion [14,15].TagedAPTREn
TagedAPRThe pathophysiology of degenerative spondylolisthesis
is a subject of controversy. Some scholars propose that
instability in the spine, arising from alterations in the inter-
vertebral discs, is a central factor in the development of
spondylolisthesis [16]. Conversely, an alternative perspec-
tive underscores the primary role of degeneration, particu-
larly age-related changes in the facet joints, as the initiating
events in the cascade leading to vertebral slippage [17]. The
implication of facet joints in degenerative spondylolisthesis
is widely acknowledged, with controversy surrounding the
extent to which facet joint degeneration contributes to insta-
bility and slippage. Some posit that arthritic changes in
3
facet joints induce instability [17], while others emphasize
factors such as ligament laxity, as seen during pregnancy
and postmenopausal phases due to hormonal variation [18].
Nonetheless, degeneration of the facets and intervertebral
discs can lead to segmental instability. There is mechanical
strain placed on the anterior/posterior vertebral ligaments
and ligamentum flavum of the associated spinal level, lead-
ing to displacement over time [19]. With increased ligament
and facet joint laxity, the displaced vertebra is held in ante-
rior or anterolateral suspension during weight bearing. This
laxity allows for dynamic reduction back to its original
physiologic position, potentially obscuring detection on
supine MRI. Dynamic translation of >3mm on flexion-
extension radiographs is considered a marker of lumbar
segmental instability, though sagittal rotation >10˚ is also
an indicator [2,20]. Comparison of a neutral standing radio-
graph to a supine MRI can be more sensitive in detecting
dynamic instability than a flexion-extension radiograph
[21]. There is a risk of progression as further dynamic
mechanical force is placed on the ligaments, facets, and IV
disc. Only about a third of patients progress further [13].
Even after minimally invasive decompression surgery of
grade I/II spondylolisthesis without fusion, progression of
lumbar slippage beyond 5% is limited to only »32% of the
patients within 2 years of intervention [22]. Disc degenera-
tion with decreased intervertebral disc space that limits
motion is protective against progression [13], facilitating
restabilization of the spinal segment. Severe degeneration
and reduction of disc and joint space will eventually lead to
the end stage of spondylolisthesis, which includes auto-
fusion of the vertebral bodies at the facets and endplates
(restabilization) [23].TagedAPTREn
TagedAPRH2Facet morphology/arthropathyTagedAPTREn
TagedAPRLumbar facet morphology and arthropathy can be best
evaluated on CT. MRI can be utilized for better assessment
of connective tissue components such as the fibrous capsule
and hyaline cartilage, though it is less reliable in grading
arthropathy [24]. The lumbar facets are more sagittally ori-
ented with a slight inclination compared with the rest of the
spine and become increasingly more coronal as they
approach the sacrum. The mean transverse facet angle −
defined as the angle from the midsagittal plane − ranges
from 25.89˚ to 33.87˚ for T12−L2 while increasing to
40.40˚ to 56.30˚ for L3−L5 [25]. Variable degrees of tro-
pism (asymmetry) can be observed between same-level fac-
ets. A mean angle difference from 4.93˚ to 10.6˚ has been
reported in normal vertebrae [26−29]. The orientation of
the facets has been shown to be independent of sex and eth-
nic group, though age is controversial due to osteoarthritic
remodeling [25,30]. Classic radiographical hallmarks of
facet osteoarthritis and degeneration include joint space
narrowing, subarticular bone erosions, subchondral cysts,
osteophyte formation, and hypertrophy (Figs. 3 and 5) [31].
Facet arthropathy shares the same risk factors of increased
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Fig. 3. Standing lateral XR (top row), and supine axial CT and T2w MRI of the L4−5 facet joints (bottom row) of a female patient developing lumbar degen-
erative spondylolisthesis. Images highlight the progression of spondylolisthesis with associated facet degeneration and arthropathy over a 10-year period.
Early facet dysfunction is denoted by the appearance of vacuum (yellow arrow) that was eventually replaced by effusion. This is an example of posterior-to-
anterior dysfunction. The integrity of the L4−5 vertebral disc (not shown) was relatively preserved compared with the same-level facet.TagedAPTREn

age and female sex with spondylolisthesis, and the same
high prevalence at the L4−L5 spinal level [32,33].TagedAPTREn
TagedAPRThe relationship between facet orientation and degenera-
tive spondylolisthesis has been a topic of investigation for
decades. Sato et al. [34] were the first to describe more sag-
ittally oriented facets, especially at the L4−L5 joint, as
more common in degenerative spondylolisthesis, followed
by multiple studies confirming the same observation [26,35
−39,40−47]. There is a three-fold increase in the likelihood
of L4−L5 spondylolisthesis when one facet reaches a criti-
cal threshold of >58˚ transverse angle. That risk doubles to
6-fold if both facets exceed that threshold [46]. Sagittal ori-
entation, but not tropism, has been shown to increase the
risk of facet arthropathy in patients with and without degen-
erative spondylolisthesis, though the angle remains more
sagittal in cases of spondylolisthesis [39,40]. Facet osteoar-
thritis is highly correlated with spondylolisthesis, with a
reported odds ratio of 19 [48]. Arthropathy can be a source
of restabilization, as demonstrated by the decreased motion
seen in the facet joints in patients with degenerative spon-
dylolisthesis [49].TagedAPTREn
TagedAPRH2Facet effusionTagedAPTREn
TagedAPRDetection of effusion within facets is a common finding
on routine MR imaging. They can be observed as curvilin-
ear hyperintensities within the joint capsule on axial and
sagittal T2-weighted images. Prevalence within the general
population is 34.3% with no association with age, gender,
or low back pain [50]. The presence of facet fluid, however,
can be a sign of degeneration. Segmental instability can
place high biomechanical stress on the facet joints. Over
time, this can lead to osteoarthritic changes, including accu-
mulation of synovial fluid within the joint capsule.TagedAPTREn
TagedAPRThere are several published works that examine whether
the segmental instability seen in degenerative spondylolis-
thesis is concomitant with facet fluid accumulation [50
−60]. It is widely accepted that facet effusion is a highly
reliable marker for segmental instability; instability which
might otherwise be missed on supine MRI. Mailleux et al.
[51] was one of the first to report cases of degeneration-
related spinal stenosis due to spondylolisthesis, only detect-
able on flexion-extension radiographs. These authors noted
that “the only hint of radiographic instability on MRI was a
high signal change on the T2-weighted axial image within
the facet joints.” Chaput et al. [52] conducted one of the
first retrospective comparative studies comprising 54
patients with and 139 patients without degenerative spondy-
lolisthesis. They showed that a >1.5 mm effusion is predic-
tive of degenerative spondylolisthesis. Cho et al. [53]
demonstrated a positive linear association between facet
fluid index (sum of effusion width over facet width) and
degree of L4−5 anterior slippage from flexion to extension.
In both studies, a noteworthy portion of their degenerative
spondylolisthesis patients did not have detectable vertebral
displacement on supine MRI (22% and 34.5%, respec-
tively). This shows a failure of supine MRI in detecting
spondylolisthesis in the absence of other radiographical
markers. Kuhns et al. [54] approximated the sensitivity of
supine MRI to detect L4−L5 degenerative spondylolisthe-
sis to be about 78% while lateral standing films are at 98%.
They also noted that the positive predictive value of mobile
lumbar degenerative spondylolisthesis goes from 52% to
100% when comparing >1 mm to >3.5 mm facet effusion.
Kinematic MRI can be an alternative option if instability is
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of concern. Wang et al. [55] demonstrated a positive predic-
tive value of 76% for instability when facet effusion is
>1 mm on kinematic MRI. Depending on the population
studied, however, there can a variability in the reported sen-
sitivity of the supine MRI in detecting lumbar DS.TagedAPTREn
TagedAPRThe most convincing evidence on the association of
facet effusion and segmental instability is presented by a
meta-analysis from Aggarwal et al. [56]. They quantitively
analyzed 10 papers with a total of 1,065 patients. They
determined that the odds ratio for unstable spondylolisthesis
in the presence of facet fluid was 7.55 (3.61−15.08;
p<.00001). The standard mean difference in fluid width
between stable and unstable degenerative spondylolisthesis
was 0.97 mm (0.38−1.57; p<.001). Per their recommenda-
tions, standing flexion-extension radiographs should be per-
formed for any patients with facet fluid >1 mm. It is
important to note that all patients enrolled in these studies
were symptomatic. In the absence of symptoms of back
pain, neurologic claudication, or stenosis, there have been
no reported associations between spondylolisthesis and
facet fluid [50].TagedAPTREn
TagedAPRFacet effusion is less frequently seen with higher grades
of spondylolisthesis. Chaput et al. [52] noted several cases
of degenerative spondylolisthesis in older patients over the
age of 70 where no significant effusion was seen despite
having severe degenerative changes and grade 3 spondylo-
listhesis. They indicated that these patients had reached a
“phase of relative stability“ in the degeneration cascade
since their anterolisthesis was also notable on supine MRI.
Cho et al. [53] reported that patients with negative supine
MRI but notable spondylolisthesis on flexion-extension
radiograph “had a lower mean age, but higher mean DMIs
[dynamic motion index] and FFIs [Facet Fluid Index]." A
facet fluid amount less than 0.5 mm has only a 10% proba-
bility of dynamic instability [61]. This suggests that facet
effusion is a transient marker of spondylolisthesis, specific
to the second phase of instability, which relatively fades as
the disorder progresses through its course.TagedAPTREn
TagedAPRH2Facet vacuumTagedAPTREn
TagedAPRJoint vacuum is a common benign phenomenon that is
routinely seen on CT. Joint expansion creates negative pres-
sure, leading to the accumulation of nitrogen gas within the
confined space of the capsule [62]. Within the facet joints,
vacuum is observed as a radiolucent, often lens-shaped strip
within a widened joint space. It frequently presents bilater-
ally at the level of the spondylolisthesis and is associated
with osteoarthritic changes of the facets. The first reported
observation of the vacuum phenomenon in association with
degenerative spondylolysis was published by Lefkowitz
and Quencher (1982) [63]. It was proposed that the traction
due to vertebral displacement leads to gas accumulation
within the zygapophyseal joint capsule. Traction implies
preservation of the neural arch and pars interarticularis,
making this feature unique to degenerative processes.TagedAPTREn
5
TagedAPRThe prevalence of facet vacuum has not been reported.
Within a cohort of 750 patients with clinically definitive
radiculopathy and low back pain, only 10 cases of spondy-
lolisthesis with facet vacuum were observed [64]. A study
by Sun et al. [65] reported 35 patients with vacuum facet on
CT in a total of 67 patients (52.24%) with L4-L5 degenera-
tive spondylolisthesis. In their study, the presence of a vac-
uum within the facet joints was associated with a higher
degree of segmental motion. A linear relationship was
observed between the width of the facet vacuum and the
degree of instability in these patients as well. Therefore,
facet joint vacuum can serve as a reliable marker for seg-
mental instability in degenerative spondylolisthesis. Taking
into consideration the full sequela of facet degeneration, we
predict facet vacuum, in the absence of severe arthropathy,
to be an earlier manifestation of segmental instability.
Higher intraarticular pressures during the early stages of
instability can lead to gas accumulation within the facets
(Figs. 3 and 5). With further joint degradation, facet effu-
sion can displace the gas, though it can reaccumulate in
later stages of osteoarthritis as the joint dries out. Further
studies are needed to investigate the prevalence and the
evolution of facet vacuum over time in spondylolisthesis as
a potential marker of progression toward higher degrees of
instability.TagedAPTREn
TagedAPRH2Synovial cystTagedAPTREn
TagedAPRJuxtafacet cysts, a term coined by Kao et al. [66] in
1974, are relatively rare findings within the lumbar spine,
with an incidence of 0.5-2.3%, depending on imaging
modality [67,68] They are found with the highest frequency
at L4−L5 (69%), followed by L5-S1 (17%) and L3−L4
(12%) levels [69]. Facet cysts can arise from either the lin-
ing of the facet joints or ligamentum flavum. They can pres-
ent anteriorly which can lead to neural compression and
symptoms, posteriorly away from neural components, or
present as both in a dumbbell shape. Anterior synovial cysts
are more commonly reported in the literature [67], though
the percentages of the two positions can vary depending on
the population studied [68,70]. Moreover, the propensity to
cause compression makes anterior cysts more prone to
detection. Cysts can be further subdivided into synovial
(with synovial lining) or ganglionic (without synovial lin-
ing) [71,66], though this differentiation is only histologi-
cally relevant. Contents of the cyst can consist of various
proteinaceous fluids, gas (vacuum), calcification, hemosid-
erin, hemorrhagic, or various osseous/cartilaginous compo-
nents [72]. MR imaging is the preferred modality for the
detection of cysts. They appear as well-circumscribed struc-
tures with a hyperintense core on T2-weighted images. CT
evaluation can provide additional information on the cyst
components as density can vary depending on the contents
within the cystic cavity.TagedAPTREn
TagedAPRThe pathogenesis of facet cysts has been a topic of debate,
though facet degeneration plays a vital role in cyst formation.
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As such, Gorey et al. [73] had them more appropriately rela-
beled as “spinal degenerative articular cysts”. Virtually all
patients with facet cysts have visible degenerative changes
on radiographs and MRI/CT imaging [67,74−76]. Degenera-
tion of the facet capsule can lead to protrusion of the synovial
lining when increased stress is placed on the joints, though
other pathological processes such as mucoid/myxoid denega-
tion and cellular metaplasia are also involved [67,77].TagedAPTREn
TagedAPRDegenerative spondylolisthesis, as a result of facet osteo-
arthritis, can precipitate the development of facet cysts but
not necessarily lead to their formation. Reust et al. [78] were
the first to propose an association between synovial cysts and
the facet degeneration seen in spondylolisthesis. Parlier-Cuau
et al. [79] were the first to quantitively report higher degener-
ative spondylolisthesis at the level of the facet joint synovial
cysts in 60% of their patients on plain radiographs. Other
rates of 33% [80], 54% [70], 40% [68,52], and 88% [67]
have since been described in the literature. Doyle et al. [68]
sample size of 303 and Chaput et al. [52] sample size of
193, both retrospective reviews, showed a higher frequency
of facet cysts in patients with degenerative spondylolisthesis
compared with those without. Synovial effusion, a previously
explained marker of segmental instability in spondylolisthe-
sis, is also appreciated at a higher rate with synovial cysts
[70]. However, synovial cysts seem to be independent of
TagedAPRFiur
instability. Chugh et al. [81] report a lack of correlation with
instability in lumbar degenerative spondylolisthesis. They
state that facet cysts may not indicate instability, though they
should not preclude performing dynamic films to evaluate
for instability. This finding might be explained by the obser-
vation that synovial cysts, unlike facet effusion, do not dissi-
pate (or at least, do so more slowly). We propose that
Juxtafacet cysts may form as a consequence of instability
and persist even after restabilization has been established
(Fig. 4). This statement is further supported by the fact that
cyst recurrence after postsurgical decompression without
fusion is <2% but no reoccurrence has been reported with
concomitant fusion [82,83].TagedAPTREn
TagedAPRH2Interspinous ligamentTagedAPTREn
TagedAPRPathological changes within the interspinous ligament
have traditionally been associated with Baastrup disease
[84]. It was originally explained as resulting from friction
between adjacent spinous processes during extension, with
associated spinous process eburnation, interspinous liga-
ment degeneration, and back pain [85]. The irritation
caused by this friction can induce the formation of an
adventitial bursa. Inflammation or fluid within the de novo

Fig. 4. Standing lateral XR (1), and supine sagittal (2) and axial (3) T2w MRI of two patients with lumbar degenerative spondylolisthesis with associated
facet synovial cysts. Patient (A) exhibits a relative phase of instability with a larger facet effusion >1.5mm and dynamic translation >3 mm on XR versus
MRI. Disc desiccation, reduced disc height, and a thicker-walled cyst in patient (B) demonstrate that it is further along the degeneration cascade. Though the
markers of instability have dissipated (ie, facet effusion), the facet cyst has remained in patient (B). Yellow arrows demark facet cysts. Yellow bars indicate
the measured length.TagedAPTREn
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bursa can be detected on MR imaging as T2 enhancement
within the interspinous ligament [86].TagedAPTREn
TagedAPRWithin recent years, Yang et al. [87] have proposed that
anterolisthesis can be a trigger for adventitial bursa forma-
tion. The shearing forces caused by the dynamic anteropos-
terior displacement in the unstable vertebrae may be
enough to produce the necessary friction to irritate the inter-
spinous ligament. Anterolisthesis, among other vertebral
changes (disc bulging and central canal stenosis), has been
shown to significantly correlate with adventitial bursitis
[86]. There is a rise in the prevalence of Baastrup disease
with increasing age (>40% after the age of 50), most com-
monly occurring at the L4−L5 level [88], similar to the
prevalence of spondylolisthesis. Therefore, it is reasonable
to consider spondylolisthesis as one, but not the sole,
degenerative process leading to adventitial bursitis.TagedAPTREn
TagedAPRWe agree with the rationale that signal changes in the
interspinous ligament can be an early indicator of segmental
instability, though only if it presents in the absence of sub-
stantial spinous process eburnation. The presence of ebur-
nation might indicate other pathological etiologies.
Adventitial bursitis on MRI without spinous process
involvement should prompt further examination with stand-
ing X-ray with flexion/extension to assess the existence or
degree of anterolisthesis. Over time, inflammation within
the adventitial bursa can subside, obscuring its detection.
There is no longitudinal evidence to our knowledge that
demonstrates restabilization as a potential basis for adventi-
tial bursa reduction or disappearance. Other concurrent
degenerative or traumatic processes can lead to the recur-
rence of bursitis and the presentation of symptoms. Never-
theless, segmental instability can leave the patient more
susceptible to initial formation and recurrence of adventitial
bursitis.TagedAPTREn
TagedAPRH2Vacuum discTagedAPTREn
TagedAPRVacuum disc phenomenon refers to the accumulation of
gas within the intervertebral disc space. Cleft formation
within sections of the intervertebral disc, secondary to
pathologies of the disc or vertebra, is the basis for vacuum
formation. The vacant space attracts gas from the surround-
ing soft tissue. Gas contained within the disc mainly con-
sists of nitrogen, with traces of carbon dioxide and oxygen
[89]. It is routinely seen on spine radiographs as radiolucent
streaks within the intervertebral disc, more prominently
visualized on sagittal view in extension. It can become
obscured in the neutral or flexed position. For this reason,
CT is considered the gold standard for detection. Gradient
Echo MRI can be almost as sensitive as CT in detecting
vacuums [90], with the added benefit of better anatomical
assessment of the disc and vertebral components [91], On
MRI, it appears as an area of hypointensity or complete
absence of signal. The space can sometimes be filled with
fluid and appear as a hyperintense streak on T2 images
[92]. Gas within the clefts of the intervertebral cavity can
7
be a source of back pain, aggravated with a change in posi-
tion or atmospheric pressure [93]. Incidence in adults with
complaints of low back pain on full extension radiographs
can be up to 3%, with 70-75% located within the lumbosa-
cral discs [94]. In the elderly population of age >65, the
incidence increases to »20% irrespective of back pain [95].TagedAPTREn
TagedAPRThe vacuum phenomenon was first demonstrated by
Magnusson [96] in a case of a patient with spondylosis
deformans on lateral lumbar x-ray. Knutsson [97] further
explained the phenomenon in the context of disc degenera-
tion (intervertebral osteochondrosis). He proposed that the
location and appearance of the vacuum is specific to its eti-
ology, spondylosis deformans versus osteochondrosis. Cen-
tral or paracentral endplate-adjacent, linear, horizontally
oriented streaks predominate in degenerative disc disease
with cleft formations in the nucleus pulposus, whereas short
linear collections near the anterior vertebral rim are more in
association with spondylosis because of alterations in the
outer aspects of the annulus fibrosus [97,98]. It has been
hypothesized that endplate degeneration, leading to cyto-
kine activation and delayed nutrient transport, is the main
pathogenesis of cleft formation [99], though this hypothesis
has never been experimentally explored. Cartilaginous
nodes, vertebral collapse, osteonecrosis, osteomyelitis, dis-
citis, and trauma are other possible etiologies for vacuum
within the intervertebral discs with their distinct presenta-
tions [98,100]. In degenerative spondylolisthesis, the
degenerative pattern of vacuum is what is mainly seen in
routine assessment.TagedAPTREn
TagedAPRThe current consensus in the literature is that the vacuum
phenomenon is a predictor of vertebral instability. The
study that demonstrated this was by Liao et al [101]. They
reported a higher rate of pseudoarthrosis in patients receiv-
ing posterior lateral fusion without an interbody cage who
had an anterior vacuum disc at the same segment as their
degenerative spondylolisthesis. They concluded that the
anterior vacuum was a marker of instability, requiring inter-
body fusion with a cage for more anterior support. In Lin et
al. [102], another study on the same cohort, it was demon-
strated that vacuum disc was more predictive of anterior
instability in degenerative compared with isthmic spondylo-
listhesis, with higher pseudoarthrosis rates. They added that
the association with instability is not absolute and requires
flexion-extension radiographs to confirm instability.TagedAPTREn
TagedAPRHowever, evidence shows that the association of spon-
dylolisthesis with disc degeneration itself follows a differ-
ent pattern. Kalichman et al. [48] after examining facet
joint osteoarthritis and intervertebral disc narrowing in a
cohort of 188 individuals (ages 40−80 years) did not find
an association of spondylolisthesis with disc narrowing,
only with facet osteoarthritis. They concluded that segmen-
tal instability is caused primarily by facet dysfunction,
which in turn may accelerate disc degeneration. Similar
findings were reported by Fujiwara et al. [103]. In a sample
of 70 patients (average age of »46 years), they found that
anterior translatory instability (vertebral movement of
 ARTICLE IN PRESS
TagedAPRFiurTagedAPREn8 A. Saremi et al. / The Spine Journal 00 (2024) 1−12

Fig. 5. Standing lateral XR (top row), and supine axial (left) and coronal (right) CT of the L4−5 facet joints and intervertebral disc of a female patient devel-
oping lumbar degenerative spondylolisthesis. Images highlight the development of spondylolisthesis with the onset of disc degeneration, marked by vacuum
disc (yellow arrow) and end-plate changes, over a 12-year period. Early facet dysfunction is denoted by the appearance of a vacuum (yellow arrow). This is
an example of anterior-to-posterior dysfunction, with disc degeneration preceding facet degeneration. The white dashed line on axial CT indicates level of
the corresponding coronal slice.TagedAPTREn

>3mm) was positively associated with disc degeneration
and facet joint osteoarthritis. However, the association was
more strongly significant with facet osteoarthritis (p<.001)
than with disc degeneration (p<.05). These findings suggest
a posterior-to-anterior (facet-to-disc) progression of degen-
eration is more common (Fig. 3), the reverse (disc-to-facet)
progression is also possible (Fig. 5).TagedAPTREn
TagedAPRConsidering that disc degeneration is a recognized pre-
requisite for gas accumulation, it seems contradictory that a
vacuum disc would be present during stages of instability
before significant disc narrowing and subsequent segmental
restabilization takes hold. In both studies by Liao et al. and
Lin et al., the average anterior and posterior disc heights
were >5 mm within normal ranges. Two explanations could
reconcile these findings. It can be that even early degenera-
tive changes within the disc are enough to provide space for
gas accumulation. It is more likely that increased shearing
forces within the disc caused by instability introduce tran-
sient clefts for the vacuum to form. This would explain why
there is such high interpatient variability in detecting vac-
uum phenomena on standing flexion-extension radiographs.
In the same cohort of Liao et al. [101], there is a dramatic
decrease in the incidence of vacuum on flexion, whereas all
patients demonstrated streaks of vacuum on extension pre-
operatively. They interpreted this as “gas squeezed into the
disc space when the spine was extended and was pushed
into the vertebra marrow sinus or posterior longitudinal lig-
ament [on flexion].”TagedAPTREn
TagedAPRBased on the evidence, we believe that the vacuum
phenomenon can serve as an indicator of progression
from instability toward restabilization. Vacuum forma-
tion requires either a high-pressure system or simply an
empty space. During the stage of instability, the high
pressure dominates. Vacuum forms when negative pres-
sure is applied to the intervertebral disc space on exten-
sion. The discrepancy between the presence of vacuum
on flexion versus extension radiograph can be suggestive
of early degeneration or simply an occult injury to the
disc components. Examples of intervertebral vacuum on
extension were first reported by Knuttson et al. [104] in
hypermobile segments. As we proceed toward restabili-
zation, further disc degeneration and cleft formation
take place. Vacuum becomes increasingly more promi-
nent on stationary images (Fig. 5). This idea is further
supported by Murata et al. [105] that determined bulkier
morphology and wider distribution of vacuum sign is
correlated with MRI-graded advanced disc degeneration
and disc height narrowing.TagedAPTREn
TagedAPRH1SummaryTagedAPTREn
TagedAPRThrough a review of the literature, we propose a radio-
graphic timeline of spondylolisthesis as the disease pro-
gresses through the stages of degeneration, instability, and
restabilization (Figs. 1 and 2). Increased age, biological
female sex, and more sagittally oriented facets are known
risk factors for lumbar degenerative spondylolisthesis. The
process is initiated as either degeneration of the interverte-
bral disc or, more frequently, the facet joints. This can pres-
ent itself as a facet vacuum in the absence of major
arthropathy. The presence of facet vacuum is contended in
this paper to be an initial marker of dysfunction. As the ver-
tebral segment becomes increasingly mobile (dynamic
translation), fluid accumulates within the facet joint space.

Facet effusion is commonly considered a reliable marker of
instability. Further degeneration will lead to the advance-
ment of facet arthropathy, degenerative disc disease, and
posterior ligamentous complex pathology (eg, facet syno-
vial cyst and interspinous ligament bursitis). Facet effusion
can eventually be replaced with a vacuum in severe facet
osteoarthritis. Intervertebral disc vacuum continues to accu-
mulate with further cleft formation and degeneration. Ulti-
mately, as a mechanism for the spine to restabilize itself,
autofusion of the vertebra at the facets and endplates can be
observed. Further research is needed to demonstrate the pre-
cise incidence and relationship of these radiographic fea-
tures to one another within the spondylolisthesis cascade.TagedAPTREn
TagedAPRIt is important to note that while our findings and obser-
vations contribute insight into the condition, our work
should not be considered as definitive evidence for the natu-
ral history of degenerative spondylolisthesis that applies
universally to all patients. The nature of this condition is
complex and individual patients may exhibit significant var-
iations in their symptoms, progression, and treatment out-
comes. As such, personalized approaches to diagnosis and
management are crucial to effectively address the diverse
characteristics of spondylolisthesis in different patients.TagedAPTREn
TagedAPRH1Declaration of competing interestTagedAPTREn
agedAPTROne or more of the authors declare financial or profes-
sional relationships on ICMJE-TSJ disclosure forms.TagedAPTREn
TagedAPRH1AcknowledgmentsTagedAPTREn
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