INVITED REVIEW

J Neurosurg Spine 38:372–381, 2023

Multilevel cervical disc arthroplasty: a review of optimal

surgical management and future directions
*Tsung-Hsi Tu, MD, PhD,1,3 Ching-Ying Wang, MD,1,3 Yu-Chun Chen, MD, PhD,2–4 and
Jau-Ching Wu, MD, PhD1,3
1
Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan; 2Department of Family
Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 3School of Medicine, National Yang Ming Chiao Tung University,
Taipei, Taiwan; and 4Big Data Center, Taipei Veterans General Hospital, Taipei, Taiwan

OBJECTIVE Cervical disc arthroplasty (CDA) has been recognized as a popular option for cervical radiculopathy or
myelopathy caused by disc problems that require surgery. There have been prospective randomized controlled trials
comparing CDA to anterior cervical discectomy and fusion (ACDF) for 1- and 2-level disc herniations. However, the
indications for CDA have been extended beyond the strict criteria of these clinical trials after widespread real-world
experiences in the past decade. This article provides a bibliometric analysis with a review of the literature to understand
the current trends of clinical practice and research on CDA.
METHODS The PubMed database was searched using the keywords pertaining to CDA in human studies that were
published before August 2022. Analyses of the bibliometrics, including the types of papers, levels of evidence, countries,
and the number of disc levels involved were conducted. Moreover, a systematic review of the contents with the emphasis
on the current practice of multilevel CDA and complex cervical disc problems was performed.
RESULTS A total of 957 articles published during the span of 22 years were analyzed. Nearly one-quarter of the
articles (232, 24.2%) were categorized as level I evidence, and 33.0% were categorized as levels I or II. These studies
clearly demonstrated the viability and effectiveness of CDA regarding clinical and radiological outcomes, including neu-
rological improvement, maintenance, and preservation of segmental mobility with relatively low risks for several years
postoperation. Also, there have been more papers published during the last decade focusing on multilevel CDA and
fewer involving the comparison of ACDF. Overall, there was a clustering of CDA papers published from the US and East
Asian countries. Based on substantial clinical data of CDA for 1- and 2-level disc diseases, the practice and research of
CDA show a trend toward multilevel and complex disease conditions.
CONCLUSIONS CDA is an established surgical management procedure for 1- and 2-level cervical disc herniation and
spondylosis. The success of motion preservation by CDA—with low rates of complications—has outscored ACDF in
patients without deformity. For more than 2-level disc diseases, the surgery shows a trend toward multiple CDA or hybrid
ACDF–CDA according to individual evaluation for each level of degeneration.
https://thejns.org/doi/abs/10.3171/2022.11.SPINE22880
KEYWORDS cervical disc arthroplasty; disc replacement; artificial disc; range of motion; adjacent-segment disease

C
ervical disc arthroplasty (CDA) has been recog-
nized for some 2 decades as an effective and safe
alternative to anterior cervical discectomy and fu-
sion (ACDF) for cervical disc diseases. Young patients
with 1- or 2-level radiculopathy or myelopathy caused by
disc herniations or spondylosis but minor facet arthropa-
thies are ideal candidates for CDA. The clinical perfor-
mances of CDA have been extensively studied since the
early 2000s by numerous prospective randomized clinical
trials under the US FDA Investigational Device Exemp-
tion (IDE) regulation.1–3 Neurological improvements and
all the patient-reported outcomes of CDA are at least equal
to those of ACDF. Moreover, these studies have demon-
strated that the effectiveness of CDA in the improvement
of neurological function and clinical outcomes is sustain-
able in longer-term (up to 10 years) follow-ups.4–12 In fact,

ABBREVIATIONS ACDF = anterior cervical discectomy and fusion; ASD = adjacent-segment disease; CDA = cervical disc arthroplasty; IDE = Investigational Device
Exemption; IISI = increased intramedullary signal intensity; mJOA = modified Japanese Orthopaedic Association; RCT = randomized controlled trial; ROM = range of
motion; UK = United Kingdom.
SUBMITTED September 28, 2022. ACCEPTED November 4, 2022.
INCLUDE WHEN CITING Published online December 16, 2022; DOI: 10.3171/2022.11.SPINE22880.
* Y.C.C. and J.C.W. contributed equally to this work.

372 J Neurosurg Spine Volume 38 • March 2023 © 2023 The authors, CC BY-NC-ND 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

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CDA outscores ACDF in successful preservation of neck
mobility at the indexed levels by maintaining or restoring
physiological motion of the cervical spine. Furthermore,
the theoretical benefit of alleviating adjacent-segment dis-
ease (ASD) by CDA has also been demonstrated in the
reports with long follow-ups.13–19 These advantages were
reportedly applicable for 1- and 2-level CDA.
Symptomatic patients with multilevel (i.e., 2 or more)
cervical disc herniations and spondylosis are not rare, and
they frequently need surgery as degeneration progresses.
Although multilevel ACDF has been a widely accepted
surgical option for many decades, it has not been free of
long-term problems.20,21 Even with the most advanced in-
strumentation and biologics, multilevel ACDF is inevitably
plagued—at least for some patients—with pseudarthrosis,
loss of neck motion, and increased risk of ASD.22,23 These
issues are likely to be more prominent as the constructs
get longer. Thus, CDA has emerged as an ideal alternative
in these clinical scenarios, with the benefit of obviating
fusion and preserving motion to improve the postoperative
quality of life in patients with multilevel disc pathology.
Current spine practices worldwide include use of CDA in
multiple and skip levels, combined use of ACDF and CDA
either sequentially for ASD or simultaneously (e.g., hybrid
constructs) for the different levels in the management of 2
or more levels of disc herniations. However, these diversi-
fied indications have not been included in the FDA trials.
Despite excellent results having been demonstrated with
these surgical strategies, the reports have often come from
retrospective series, and therefore more investigations are
warranted.24–29
Application of CDA for multilevel cervical disc her-
niations and spondylosis is promising and will continu-
ally evolve. Future perspectives on CDA will focus on the
expanded indications that were not addressed by previous
trials. Therefore, this review focuses on reports of CDA
in the past 2 decades, primarily focused on patients with
multilevel disc disease with cervical spondylosis, with or
without myelopathy, and various other clinical scenarios.
This is a complete review of the literature, with an in-depth
bibliographic analysis aimed to depict the trends of CDA
in clinical practice, research, and future perspectives.
Methods
A literature search of the PubMed database limited to
English-language papers and using the keywords “disc
arthroplasty,” or “cervical arthroplasty,” or “disc replace-
ment,” or “artificial disc” in the text and “cervical” in
the abstract/title was conducted on August 20, 2022. The
analysis was exclusively confined to human studies. All
the downloaded abstracts and articles were reviewed by
C.Y.W. and T.H.T. independently for categorization.
The articles were categorized into 6 types of formats:
systematic review, prospective trial, prospective cohort,
retrospective study, case report, and others; and analyzed
by country of publication. The systematic review category
included meta-analyses and prospective trials that were
randomized controlled trials (RCTs). Both prospective
and retrospective cohort studies used statistical analysis
to make conclusions, whereas case reports were defined as
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Tu et al.
reports that had low case numbers and no statistics. Any
other types of articles, including editorial summaries,
technical notes, and letters were all categorized as others.
To evaluate the trends of research activity, the annual
cumulative publication was plotted. The affiliations and
countries of the authors of the articles on CDA were all
analyzed. The country of origin of each article was as-
signed using the first author’s first affiliation. The number
of participants in each study population was obtained from
the abstract of each of the case reports and case series. Ar-
ticles without an identifiable number for study population
in the abstract were excluded. The citation count of each
paper was obtained from the Web of Science (Clarivate
Analytics). To analyze the evolution of surgical practice
for CDA, all the articles regarding treatment were divided
into 3 categories: CDA, hybrid, and ACDF, which mainly
focused on patients with CDA, hybrid surgery, and using
ACDF for comparison or control, respectively. The num-
ber of disc levels treated surgically was also stratified into
1-, 2-, and 3-level only, and multilevel (2, 3, or more levels
of involvement). This information was determined first
from the abstract; if not available in the abstract, the full
text was reviewed. The level of evidence of each article
was assigned according to the Oxford Center of Evidence-
Based Medicine.
Results
There were 1237 articles focusing on CDA that were
published between 2000 and 2022; these were extracted
from PubMed for investigation on August 20, 2022. Af-
ter review, 280 articles were excluded due to the follow-
ing reasons: no abstract, retracted, not focusing on human
CDA, or biomechanical studies (e.g., laboratory tests, fi-
nite element models, cadaveric or animal studies). Thus,
a total of 957 papers were analyzed and categorized into
6 types. Retrospective cohort studies (n = 370) were the
most published type, followed by systematic reviews and
meta-analyses (n = 124), prospective trials (n = 108), case
reports (n = 95), prospective cohorts (n = 82), and others
(Fig. 1).
There has been an exponential growth of the annual
numbers of publication on CDA during the past 2 decades
(Fig. 2). Articles focusing on CDA alone were responsible
for most of the exponential growth, whereas the increase
of numbers of studies that included ACDF for comparison
had grown rapidly during 2014–2018 and then had decel-
erated since that period. Reports involving ACDF com-
prised one-third (n = 316, 33.0%) of the total manuscripts
published during the past 2 decades. During 2014–2018,
reports commonly provided head-to-head comparison of
CDA to ACDF, including numerous RCTs in the US and
Europe. Moreover, the articles on hybrid CDA–ACDF
surgery have always been a minority, but have steadily
increased in the past decade, and markedly after 2017.
Also, these articles on hybrid CDA–ACDF commonly in-
volved at least 2 disc levels and dealt with more complex
disease. These results indicated that CDA has become an
established treatment and that studies involving ACDF,
the prior gold standard for comparison, have become less
frequently needed over the years.
J Neurosurg Spine Volume 38 • March 2023 373
Tu et al.
FIG. 1. Data processing flowchart of CDA research published between 2000 and 2022. The total number of articles of the 6
publication types is 957.
Among the 957 articles on CDA, 232 were categorized
as level I evidence, including 124 systematic reviews and
108 prospective trials (Fig. 3). There were 82 and 370 pro-
spective and retrospective cohort studies, categorized as
level II and III evidence, respectively. There were 95 case
reports, categorized as level IV evidence, whereas the oth-
er 178 articles—including letters, editorials, and experts’
reviews and comments—were counted as level V and
“others.” Nearly two-fifths (38.9%) of the articles were ret-
rospective cohort studies, indicating that there was a great
need to seek data from real-world experiences. Also, the
category of systematic review and meta-analysis, summed
to 124 (13.0%), contributed to more than half of the level
I evidence, indicating the robust support for CDA in the
FIG. 2. Cumulative publication counts by publication year and surgical
modalities on CDA research published between 2000 and 2022 (n =
957). The “Hybrid” category includes studies involving CDA and fusion
constructs in the same patient.
374 J Neurosurg Spine Volume 38 • March 2023
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literature. The US published the most articles in every
level of evidence except in level Ia, in which China had the
largest number of publications. Interestingly, most CDA
publications (approximately 70%) from Taiwan, Korea,
and Italy were retrospective cohort studies, and there were
far more review articles published in the US by numbers
and ratios. Obviously, there has been an ongoing enthusi-
asm for research on CDA worldwide, with a considerable
amount originating from Asian countries during recent
years.
There was a remarkable country preference among the
957 articles reviewed; almost two-fifths (39.2%, n = 375)
of the publications came from the US (Table 1). Overall,
FIG. 3. Cumulative publication counts by publication year and level of
evidence on CDA research published between 2000 and 2022 (n = 957).
Level I includes prospective case-control studies, prospective RCTs,
meta-analyses, and systematic reviews; level II consists of prospec-
tive cohorts; level III consists of retrospective studies; level IV includes
letters, case reports, and practice guidelines; and level V consists of
literature reviews.
 Tu et al.

TABLE 1. Publication counts and distribution of CDA research by countries and types of studies
Overall Level Ia Level Ib Level II Level III Level IV Level V
Top 10 No. % Top 10 No. % Top 10 No. % Top 10 No. % Top 10 No. % Top 10 No. % Top 10 No. %
US 375 39.2 China 59 47.6 US 66 61.1 US 16 19.5 US 112 30.3 US 67 40.9 US 77 74.0
China 218 22.8 US 37 29.8 China 13 12.0 China 15 18.3 China 100 27.0 China 24 14.6 South 4 3.8
Korea
South 67 7.0 Cana- 7 5.6 Swe- 5 4.6 Ger- 8 9.8 South 48 13.0 UK 12 7.3 France 3 2.9
Korea da den many Korea
Taiwan 37 3.9 Austra- 6 4.8 Ger- 5 4.6 Cana- 7 8.5 Taiwan 25 6.8 Taiwan 10 6.1 China 3 2.9
lia many da
Ger- 34 3.6 Brazil 4 3.2 South 3 2.8 France 7 8.5 Italy 12 3.2 Aus- 9 5.5 Ger- 3 2.9
many Korea tralia many
Aus- 27 2.8 The 4 3.2 Singa- 2 1.9 UK 5 6.1 Ger- 10 2.7 South 8 4.9 UK 2 1.9
tralia Nether- pore many Korea
lands
UK 26 2.7 UK 2 1.6 India 2 1.9 South 4 4.9 Aus- 9 2.4 Ger- 8 4.9 Italy 2 1.9
Korea tralia many
Cana- 25 2.6 Spain 1 0.8 Spain 2 1.9 Czech 3 3.7 Swit- 7 1.9 France 5 3.0 Aus- 2 1.9
da Re- zer- tralia
public land
France 21 2.2 Taiwan 1 0.8 Nor- 2 1.9 Bel- 2 2.4 Cana- 6 1.6 Cana- 4 2.4 Brazil 1 1.0
way gium da da
Italy 17 1.8 Austria 1 0.8 France 1 0.9 Austria 2 2.4 France 5 1.4 Swit- 2 1.2 Taiwan 1 1.0
zer-
land
Level I includes prospective case-control studies, prospective RCTs, meta-analyses, and systematic reviews; level II consists of prospective cohorts; level III consists of
retrospective studies; level IV includes letters, case reports, and practice guidelines; and level V consists of literature reviews.

the majority of published literature on CDA originated
from only 10 countries, with the top 5 (i.e., US, China, Ko-
rea, Taiwan, and Germany) contributing more than three-
quarters of the total. Of the 843 papers (88.1%) published
in 10 countries, 33.4% of the reports came from East Asia.
Furthermore, there was a tendency toward different types
of reports being published depending on the countries.
Most of the RCTs were conducted in the US and Ger-
many, whereas other countries published very few reports
of RCTs, and authors in China published the majority of
meta-analyses or systematic reviews (Fig. 4).
There was a clear trend toward publication of multi-
level CDA surgery. We calculated a total of 289 articles in
which the number of cervical disc levels involved could be
clearly identified. After analysis, these CDA articles were
categorized into 4 types according to the number of disc
levels treated: 1-level (107, 37.0%); 2-level (82, 28.4%);
3-level (10, 3.5%); and multilevel (i.e., 2 or more levels in-
volved) (90, 31.1%). The publication of CDA series has had
an exponential growth in recent decades, especially the 2-,
3-, and multilevel studies, which has increased remarkably
since 2013. Moreover, the volume of research on multilev-
el CDA surgeries has increased rapidly in the most recent
5 years, trending upward (Fig. 5).
Discussion
Trends of CDA Practice and Research
A clear trend of frequent publications of RCTs in the
CDA literature can be observed in the past 2 decades.
Especially in the US, the large number of FDA IDE tri-
als with mid- and long-term follow-up tremendously en-
hanced the overall quality of CDA literature, which is
unprecedented in the history of spine surgery literature.
Consequently, the abundance of level I evidence provides
momentum to generate high-quality meta-analyses and
systematic reviews. The consensus derived from evidence
has laid the foundation for reliable options for treatment of
cervical disc diseases by CDA, typically in 1- and 2-level
diseases, stemming from the IDE trial inclusion criteria.
Since 2007, CDA has reportedly been a safe and ef-
fective option for 1- and 2-level cervical radiculopathy,
myelopathy, or both, that were refractory to medical treat-
ment.5,30–33 Later reports with up to 10 years of follow-up of
prospective RCTs for level I evidence demonstrated trends
toward less revision surgery or ASD after CDA. However,
regional regulations and health insurance policies heavily
influenced the practice pattern of CDA. The US FDA gov-
erns rigid and strict regulatory requirements by requesting
that all CDA devices be challenged with multicenter, pro-
spective, controlled IDE clinical trials for approval in the
US market. On the other hand, the regulatory requirements
outside the US vary by region and are generally more flex-
ible. The differences in the stance of regulation not only
impacted the pattern of practice, but also were reflected in
the literature. The US IDE studies were specifically de-
signed around safety and effectiveness, whereas the stud-

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Tu et al.
FIG. 4. Level of evidence for CDA publication in different countries. Level I includes prospective case-control studies, prospective
RCTs, meta-analyses, and systematic reviews; level II consists of prospective cohorts; level III consists of retrospective studies;
level IV includes letters, case reports, and practice guidelines; and level V consists of literature reviews.
ies performed outside the US laid emphases on avoidance
of complications, patient selection, and expanding indica-
tions.34,35 The US IDE studies and numerous randomized
trials significantly enhanced the proportion of high-qual-
ity level I evidence in the CDA literature (24.2% of the
current bibliometric analysis) in comparison with general
spine publications (4.7%–20%).36,37 The US published the
most CDA-related articles, followed by China, South Ko-
rea, and Taiwan. Germany topped the CDA-related publi-
cations in Europe, followed by the United Kingdom (UK)
and France. The US had the largest number of prospective
RCTs, case-control studies, and review articles (Table 1).
The US FDA IDE trials strictly enrolled only patients
with 1- or 2-level disease, and thus most American CDA
publications reported outcomes in patients with 1- or
2-level disease. Currently, there have not been IDE trials
on 3 or more levels of CDA. However, as the efficacy of
CDA earned widespread appreciation all over the world,
more real-world evidence was shared and published in
FIG. 5. Cumulative publication counts by publication year and number of
disc levels involved in CDA research published between 2000 and 2022
(n = 957). “One-level” denotes only 1-level CDA; “Two-level” denotes
only 2-level CDA; “Three-level” denotes only 3-level CDA; and “Multi-
level” denotes 2 or more levels of involvement.
376 J Neurosurg Spine Volume 38 • March 2023
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other countires.3,31,38 As a result, the patient selection and
surgical indication as well as the number of discs treated
tends to be less stringent outside than inside the US.
Indications for Multilevel CDA
Multilevel CDA has emerged as an attractive surgical
option in the past decade and shares similar indications
with 2-level CDA surgery. The effectiveness and safety of
1- and 2-level CDA have been demonstrated by many US
FDA IDE trials with mid- to long-term follow-up in the
past decade. Compared to ACDF, CDA spares the need
for fusion across endplate surfaces and thus decreases the
chances of pseudarthrosis, ASD, and consequent reopera-
tions.39 However, the performance of 3 or more levels of
CDA has modest support from the literature. Chang et al.40
reported 50 patients who underwent 3-level CDA with im-
proved segmental mobility and similar clinical outcomes,
including relief of neck and arm pain, compared with a
matched cohort of 50 patients who received ACDF. Pi-
menta et al.41 also reported improved clinical outcomes
after multilevel CDA compared with the patients who un-
derwent single-level CDA. Joaquim and Riew42 performed
a meta-analysis for multilevel CDA and concluded that
the literature supports this option. Gornet et al.43 reported
on a retrospective series of 139 patients who had 3- or
4-level CDA with 7 years of follow-up, and demonstrated
improved patient-reported outcomes and a low reopera-
tion rate. According to the aforementioned reports, 3- or
4-level CDA is feasible for multilevel radiculopathy or
myelopathy, with satisfactory outcomes. It is worth not-
ing that patients with a shorter duration (< 6 months) of
symptoms and milder preoperative modified Japanese Or-
thopaedic Association (mJOA) severity would gain a dra-
matic improvement after CDA, implying an advantage for
early surgical intervention.44
Patients with cervical spondylotic myelopathy caused
by multilevel disc herniations or spondylosis are can-

didates for CDA.45–47 Due to arthrodesis-related conse-
quences,22,39,48–51 multilevel CDA is particularly appealing
for young patients with multilevel cervical spondylotic
myelopathy caused by disc-related problems or congenital
stenosis. Chang et al.1 reported a retrospective series of 37
patients younger than 50 years with cervical myelopathy
who were treated with either hybrid CDA–ACDF (2-level
CDA plus 1-level ACDF, 20 patients) or 3-level ACDF (17
patients). The mean (± SD) follow-up duration was 2.37
± 1.60 years. Both groups demonstrated similar clinical
improvement in visual analog scale neck pain and arm
pain scores as well as mJOA scores, whereas the hybrid
CDA–ACDF group significantly preserved the motion in
the index segments. Even for myelopathic patients who
have radiological evidence, CDA could be an effective op-
tion if the disease was limited to the disc. Chang et al.46
investigated the change in increased intramedullary sig-
nal intensity (IISI) in a retrospective series of 91 patients
with cervical disc disease who were treated with single-
level CDA. The mean follow-up duration was 30 months.
Twenty-two patients who had preoperative IISI were found
to have significantly regressed IISI postoperatively, com-
patible with clinical outcome improvements. The improve-
ment of patient-reported outcomes was similarly satisfac-
tory in patients with or without IISI. The study indicates
that CDA is an effective and safe alternative for patients
with myelopathy, even in those with IISI on preoperative
T2-weighted MRI.
Hybrid CDA–ACDF Surgery
For symptomatic patients with multilevel disc disease at
an unsynchronized stage of degeneration, hybrid constructs
combining CDA and ACDF or anterior cervical corpec-
tomy and fusion represent a reasonable solution.52 Fusion
not only takes care of disc herniation but also augments
alignment and facilitates treatment of facet joint arthropa-
thies. In contrast, CDA merely replaces the herniated disc
and aims to restore functional mobility. Therefore, from
a biomechanical aspect and design rationale of CDA, in-
dexed levels that are less spondylotic and expected to have
a larger range of motion (ROM) postoperation (typically
C4–5 or C5–6) are better targets for CDA. In contrast, fu-
sion can be applied to the indexed disc levels that are more
spondylotic, more kyphotic, less mobile, unstable, with
calcification, or focally ossified. When CDA is performed
adjacent to a fusion level, the mechanical environment that
it withstands is more challenging than that in a stand-alone
environment, with theoretical risks of prosthesis disloca-
tion.53,54 However, complications related to biomechanical
failures of hybrid CDA–ACDF constructs were rarely re-
ported. Most studies reported hybrid constructs to be simi-
larly effective in terms of clinical improvement compared
to ACDF, with the advantages of better preservation of
segmental as well as global ROM.1,29,46,47,52,55,56 When com-
pared with multilevel CDA, the hybrid construct might
be superior in restoring cervical lordosis because of the
ACDF being included.
Reoperations in patients with ASD related to previous
ACDF is another practical application for CDA. It is not
uncommon to see patients present with disc herniations
neighboring previous fusion constructs. In cohorts with
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Tu et al.
more than a decade of follow-up, a considerable portion of
patients (2.9%–5.6%) reportedly received a second opera-
tion after ACDF.21,57 The incidences of ASD requiring re-
operation were typically higher. For these young patients,
a hybrid construct in which the CDA performed for ASD
that occurred next to a previous fusion was better than an-
other ACDF, because it could avoid further motion limita-
tion and ameliorate future development of ASD. Several
reports unanimously demonstrated the clinical efficacy
and safety of such a strategy.41,58,59 However, studies with
larger patient numbers and longer follow-up are manda-
tory to compare the efficacy of treating ASD with CDA
and ACDF. Also, more studies are needed to elucidate the
best combination strategy for different designs of the hy-
brid construct when it comes to different spondylotic con-
ditions among various levels.
Contraindications for Multilevel CDA
Contraindications for multi- and single-level CDA
are similar, including kyphotic deformity, the presence
of ossification of the posterior longitudinal ligament, in-
competent facet joints, unstable ligamentous injury, and
ankylosis. Surgeons should consider each level of disc in-
dividually in patients with multilevel disc diseases. Those
levels of indexed discs that feature any of the aforemen-
tioned conditions would be better managed with ACDF.
Hybrid constructs might be a practical option for multi-
level discs with various severity of spondylosis. In patients
with multilevel moderate disc degeneration causing a slight
loss of lordotic curve or a mild kyphotic curve, multilevel
CDA has reportedly been beneficial to release the global
cervical stiffness from the limitation of spondylosis and
to allow the spine curvature to be compensated to a more
physiological configuration.60 The potential of such com-
pensation requires proper postoperative postural modifi-
cation and competent core muscle strength that could be
achieved through physical therapy.
Osteoporosis has long been considered a relative con-
traindication for CDA. However, for patients who need
cervical discectomy for decompression, the benefits of
ACDF over CDA in the osteoporotic scenario have not
been adequately investigated. The routine dual-energy
x-ray absorptiometry (DEXA) study before CDA is not
strictly enforced, and the complication profiles related to
bone quality (subsidence, dislodgment, etc.) among the
patients who did not undergo preoperative DEXA seem
no different, because many of the reports apparently over-
looked the issue. Scant data existed between osteoporosis
and CDA complications, and further investigation is there-
fore required for clarification.
Surgical Techniques for Multilevel CDA
The success of multilevel CDA relies on two funda-
mentals: neurological improvement and motion preserva-
tion. The key to ensuring patient satisfaction is adequate
decompression of neural elements and proper installation
of the artificial discs.52,61,62 Surgery with carefully executed
techniques may attain these two aims simultaneously.
Very similar techniques for CDA have been described
in publications from various institutions. For multilevel
CDA, the surgical technique is even more demanding
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Tu et al.

FIG. 6. Illustrative case of multilevel CDA surgery. A 57-year-old woman presented with arm pain, bilateral hand numbness, and
leg weakness that had lasted for 5 months. The MR images demonstrated C3–7 multilevel disc herniations with spondylotic my-
elopathy, as evident by increased intramedullary signal intensity on T2-weighted MRI, and a slightly lordotic neck (A). The patient
had tried physical therapy and other nonoperative management, which yielded little improvement. Therefore, she underwent CDA
at C3–7. There was significant improvement in clinical outcome, and the lateral dynamic cervical radiographs (B, flexion; C, exten-
sion; and D, anterior-posterior images) demonstrated preservation of segmental mobility.

because there are more variables during the surgery that
would substantially affect postoperative motion.26,63 Usu-
ally, the patient is positioned supine with gentle mandibu-
lar extension so that the cervical curve is neutral to slightly
lordotic. The disc space should not be overdistracted, to
prevent facet joint injury during the process of discecto-
my. Depending on the configuration of the prosthesis shell,
cautious endplate preparation is required. For the inferior
endplate, surgeons should aim to preserve as much of the
natural dome shape as possible. Also, the superior endplate
should be flattened sufficiently to maximize the contact
surface of the artificial disc. The posterior longitudinal lig-
ament is typically resected in our practice, along with the
resection of bilateral uncovertebral joints.61 This maneuver
achieves optimal direct cord and root decompression and
better reinstitutes the segmental motion in the partially
spondylotic levels, while the stability is maintained. To
maintain the long-term neural decompression and motion
preservation, the decompression stage of CDA should be
performed meticulously to the optimal extent—as com-
pared to ACDF, in which the indirect decompression by
interbody grafting tends to maintain the relaxation of neu-
ral elements. The optimal size and position of the implant
may be confirmed by intraoperative fluoroscopy. Avoid-
ance of oversizing the prosthesis in height is recommend-
ed because it may cause loss of motion, kyphotic configu-
ration, increased subsidence, and splaying of facet joints.
The endplate should be covered by the prosthesis as much
as possible to mitigate heterotopic ossification formation
and sinking of the prosthesis.64 The optimal position of
the implant should be confirmed in the sagittal plane by
using intraoperative fluoroscopy and in the coronal plane
with the aid of uncus location for midline determination.
The optimal placement of the prosthesis for restoration
of proper alignment is crucial for patients’ outcomes and
378 J Neurosurg Spine Volume 38 • March 2023
avoidance of complications such as heterotopic ossifica-
tion and neck pain (Fig. 6).
Radiographic Outcomes of Multilevel CDA
The merit of preservation of segmental motion by CDA
increases as more indexed levels are involved. Restoration
of segmental mobility is considered the most important
radiographic outcome of CDA, and in selected cases, the
indexed segmental mobility has reportedly been increased
after CDA surgery.2 For multilevel CDA, preservation of
segmental mobility in each indexed level is expected to be
like that in single-level CDA. Within the limited number
of reports on 3- or 4-level CDA, a slight gain in segmen-
tal mobility has been reported postoperation. Chang et al.
reported an average increase of 3.4° in ROM following
3-level CDA in a series of 50 patients. Reinas et al. re-
ported a gain in mobility of 1.3° ± 8.1° per level in 3- and
4-level groups versus 1.1° ± 4.7° in 2-level CDA.65 Interest-
ingly, the more levels of CDA performed, the more gain of
motion in each operated level is observed. Compared with
baseline global ROM, a statistically significant increase
of 7.2° ± 11.7° in 3- or 4-level procedures was observed,
whereas for patients with 2-level CDA, an increment was
shown but was not significant (1.6° ± 9.4°; p = 0.44). These
studies demonstrated the superiority of CDA in patients
who required multilevel surgeries. Other than segmental
and global motion, cervical spine alignment is also an im-
portant factor for postoperative neck pain, quality of life,
and progression of myelopathy or even deformity. It must
be cautioned, however, that multilevel CDA is not suitable
for patients with kyphotic deformity.
ASD After CDA
The theoretical benefit of mitigating ASD with CDA

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has been demonstrated in longer-term follow-up reports
of the FDA trials. The annual incidence of ASD varied
widely in the literature, ranging from 1% to 5%.57,66,67
Given the inherently low incidences of reoperation after
anterior discectomy, early CDA studies of insufficient
sample size or limited follow-up often failed to recognize
the differences.4 However, these same cohorts could eluci-
date significant differences in rates of ASD or reoperations
when the follow-up duration extended to more than 5–7
years.7,8,68–71
Reports of RCTs with longer follow-ups have demon-
strated the advantageous decrease in ASD requiring re-
operations after CDA. For 1-level CDA, the differences
reached significance at the 7-year follow-up (CDA 3.8% vs
ACDF 13.2%).72 Chang et al.73 conducted a systematic re-
view to evaluate the rates of reoperation due to ASD after
single-level CDA with a 2- to 7-year follow-up, and con-
cluded that the mean reoperation rate for ASD was 3.1%
for CDA, lower than the rate of 6.0% for ACDF. Long-
term results after 2-level CDA also demonstrated protec-
tion against ASD. Radcliff et al. reported 5-year results of
330 patients undergoing 2-level CDA versus ACDF, and
demonstrated lower rates of reoperation in patients who
underwent CDA than in those treated with ACDF (3.1%
vs 11.4%).74 Lanman et al.75 reported fewer ASD reopera-
tions in CDA than ACDF groups in a 2-level IDE trial with
a 7-year follow-up. There were few reports on ASD in 3
or more levels of CDA. However, longer fusion constructs
theoretically yield more biomechanical alterations and
thus are more prone to development of ASD. Therefore,
the superiority of CDA over ACDF in mitigation of ASD
might be more prominent in multilevel conditions.
Future Directions of CDA
Based on repeat scrutiny of the efficacy and safety of
1- and 2-level CDA with RCTs, there has been robust level
I and level II evidence. Moreover, there have been many
reports of retrospective cohorts, with anecdotal evidence,
for indications vaguely described in the FDA trials. Ex-
panding the indications of CDA to the gray zone is not un-
common in practices primarily outside the US. Research
on and practice of CDA in Asia and Europe have trended
toward multilevel application and level-specific determi-
nation of CDA or fusion. The current evidence supported
multilevel CDA in selected candidates as a safe and effec-
tive option, with low rates of revision surgery. Although
these studies are promising and demonstrate favorable
clinical and radiographic outcomes, RCTs and investiga-
tions with higher levels of evidence are warranted for 3 or
more levels of CDA surgery.
The success of multilevel CDA depends on selection of
the patients, an approach with tailor-made design of the
construct, and devices that can fit endplates of each disc—
which could vary from person to person in height, shape,
and concavity. The evolution of materials science and the
biomechanical properties of the successive generations of
cervical artificial discs will certainly enable the surgeon
to expand the indications of CDA and to push the enve-
lope.
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Tu et al.
Conclusions
CDA is an established surgical management procedure
for 1- and 2-level cervical disc herniation and spondylo-
sis. The success of motion preservation by CDA with low
rates of complications has outscored ACDF in spondylotic
patients without deformity. For more than 2-level disc dis-
eases, the surgery chosen trends toward multiple CDA or
hybrid CDA–ACDF according to individual consideration
for each level of degeneration.
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Disclosures
The authors report no conflict of interest concerning the materi-
als or methods used in this study or the findings specified in this
paper.
Author Contributions
Reviewed submitted version of manuscript: all authors. Approved
the final version of the manuscript on behalf of all authors: Wu.
Study supervision: Wu.
Correspondence
Jau-Ching Wu: Neurological Institute, Taipei Veterans General
Hospital, Taipei, Taiwan. jauching@gmail.com.
J Neurosurg Spine Volume 38 • March 2023 381