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Multilevel degenerative cervical disc surgery

The aim of this study was to compare clinical and radiological outcomes of patients operated on for multilevel DCDD either by single- or two-stage ‘hybrid surgery’ combining cervical arthroplasty and osteosynthesis

Sandu Nora MD
Orabi Mikael MD
Arasho Belachew MD
Bernhard J Schaller MD PhD DSC
Department of Neurosurgery, Lariboisière University Hospital, Paris, France
This is a retrospective outcome study of patients operated on during May 2005 to April 2011 at Lariboisiere University Hospital. Clinical and radiological examination was done preoperatively and at between three to at least 36 months postoperatively. 
Eight patients had two-stage hybrid surgery and eight patients had single-stage surgery. Mean follow-up time was 38.2 months without clinical or radiological differences between the two groups. For 94% of the patients the clinical outcome was excellent or good (Odom Grade 1 or 2). 
The overall mean Japanese Orthopaedic Association (JOA) Score improved from 11.5 preoperatively to 14.3 at last follow-up. Both the JOA Score and Odom Grade demonstrated no postoperative statistical difference between the groups. All but one of the prostheses remained mobile and good fusion was achieved at the fusion levels. 
The hybrid technique, either performed as single- or as two-staged surgery, showed good clinical and radiological outcome for degenerative cervical disc disease (DCDD). There was no significant difference in JOA or Odom outcomes whether arthroplasty and osteosynthesis (OS) were in single- or two-stage. Therefore, the hybrid technique has its place in the treatment of DCDD and allows the combining the advantages of OS and arthroplasty, respectively. 
The treatment of DCDD by discectomy and OS via an anterior approach is well established.1–9 More recently, total disc replacement (TDR) has been systematically studied. The theoretical background of this technology is prevention of accelerated degeneration at adjacent levels.2,4,6,10–19 Those studies have well defined inclusion criteria and are generally prospective and randomised allowing analysis of one or more prostheses over the time.2,4–6,11,18–19 However, most of those studies also have some limitations due to their methodology as patients with prior cervical disc surgery are generally excluded. Consequently, the behaviour of an implanted prosthesis in a patient with an OS has only seldom been reported.1,32
In the present preliminary small exploratory outcome study, we therefore retrospectively analysed patients operated by the so-called hybrid technique (OS plus arthroplasty) in a single-centre. What is original is that patients with a single-stage procedure were compared to those with a two-stage procedure performed by the same surgical team over a minimum of three years.
Fig. 1: Flow chart depicting study design.
Study design 
Between May 2005 and April 2010, 66 consecutive patients were operated on at Lariboisière Hospital for DCDD by anterior discectomy with total disc replacement and represent the population of this preliminary small exploratory retrospective report. Of these, 88% had radicular symptoms only. Out of these 66 patients, eight (12%) patients already received a cervical OS in the past (Figure 1) and failed. Total disc replacement was therefore done in a second stage (‘two-stage hybrid surgery’, subgroup 1). Eight other patients (12%) of these 66 patients had arthroplasty and OS during the same operation (‘single-stage hybrid surgery’, subgroup 2). These two subgroups of patients were retrospectively analysed in the present study (Table 1).
Pre- and postoperative work-up and interventions
Every patient had preoperative standard and dynamic X-rays, a computed tomography (CT) and a magnetic resonance imaging study (MRI). In some cases, electrophysiological exams were done on an ad-hoc basis, but not systematically. Patients were informed about the procedure’s rationale and agreed, signing an informed consent, that the final decision could have been changed intraoperatively according to surgical findings. Postoperatively, every patient had standard X-rays and CT before discharge. At three months, further CT and dynamic X-rays were performed. Dynamic X-rays were repeated at 6, 12, 24 and 36 months.
For each patient an individual surgical treatment plan was established. For each pathological level either arthroplasty or OS were decided based on conventional indications. The surgical technique used for these procedures was described earlier in detail.20
During the up to nine-year observation period, four different prostheses were under evaluation in our institution: Bryan Cervical Disc® (Medtronic Inc., Memphis/ TN, USA), Mobi C® (LDR, Troyes, France), Physiodisc® (Kiskomedica, St. Priest, France) and ProDisc-C® (Synthes Inc., West Chester/PA, USA). OS were done either with titanium cages (C-Varlock® (Kiskomedica, St. Priest, France)) or with iliac bone graft combined together with plate (Reflex cervical plate® (Stryker Spine Inc., France). The decompression was performed in each case by a standard anterior approach.20
Inclusion and exclusion criteria
The inclusion criteria for this outcome study were:
1. One or more of the following symptoms and signs of cervical disc degeneration.
(a) Persistent severe myelo- and/or radiculopathy not responding to conservative management for at least two months.
(b) Cervical radiculopathy with progressive paresis.
(c) Selected cases with myelopathy secondary to cervical spinal canal stenosis that can be adequately decompressed with anterior cervical discectomy with fusion.
(d) Selected cases with predominantly neck pain and headache and lack of radicular pain.
(e) Cervical pathology in three consecutive levels or more.
2. Radiologically documented cervical disc degeneration with compression of cervical nerve roots and/or spinal cord, which most likely explain the clinical symptoms and signs.
The exclusion criteria for this outcome study were:
1. Cervical trauma within the past four weeks.
2. Cervical neoplasia.
3. Ongoing cervical infection.
4. Cervical congenital deformity.
Data management and outcome variables
For all patients, general clinical and radiological data were collected. Independent examiners examined patients preoperatively, at discharge and in the outpatient clinic at 3, 6, 12, 24 and 36 months. Perioperative complications were defined as complications until one month after the operation. The primary end points were the JOA Score and the Odom Grade.
JAO was done the day before operation and at every visit in the outpatient clinic. In Table 1, there is the postoperative score at three years after the operation. The Odom Grade was also collected at every outpatient clinic visit and in Table 1 included after three years postoperatively. Secondary outcomes were mobility of the prosthesis.
All the statistical analyses were performed using statistical software (JMP, SAS Institute Inc., USA) on a commercially available computer. Data were tested for normality using the D’Agostino & Person omnibus normality test. Data normally distributed are represented by mean (SE).
Analyses of continuous, independent variables were done with use of Wilcoxon rank-sum test because of the sparse data. Fisher’s test was used to compare categorical, independent variables also because of the sparse data. The level of significance was set for both at p<0.05. Bonferroni-corrected p values were determined. 
Individual logistic regression analysis was performed on possible confounding variables, such as the duration of symptoms, age, former surgery, and gender to determine the relationship of these variables with the outcome variables.
The population comprised of 16 patients, nine (56%) women and seven (44%) men. Their mean age was 44.2 years (SD 3.8 years). The studied population consisted of two subgroups:
– Group 1 (patients #1 to #8), with former cervical spine surgery, which was performed in a mean of 3.3 years before (SD 0.5 years) defined as ‘two-stage hybrid’.
– Group 2 (patients #9 to #16), without former surgery, in which osteosynthesis and prosthesis were realised simultaneously (so-called ‘one-stage hybrid’).
Patient’s characteristics in both subgroups demonstrated no statistical difference. Overall, the mean follow-up was 38.2 months; for subgroup 1 it was a mean of 38.8 months (SD four months) and for subgroup 2 it was a mean of 37.6 months (SD three months). Table 1 summarises the clinical and radiological data.
Overall, for 15 out of 16 patients (94%) operated on with the hybrid technique, the surgical outcome was excellent or good (Odom Grade 1 or 2). One patient remained unchanged (Odom Grade 3). 
Globally, the mean JOA Score improved from 11.5 (SD 2.875) preoperatively to 14.3 (SD 1.4) at the last postoperative follow-up (p<0.001); for group 1 there was an improvement to a mean JOA Score of 14.12 (SD 1.246) (p<0.002) and in group 2 to a mean JOA Score of 14.5 (SD 1.603) (p<0.03). There was no significant difference in improvement to a mean JOA Score between the two groups. 
Globally, the mean Odom Grade was 1.875 (SD 0.5); for group 1 the mean Odom Grade was 2 (SD 0.534) and for group 2 it was 1.75 (SD 0.463). There is no statistical difference in Odom Grade between both groups.
Fig. 2a: Left: dynamic lateral cervical radiography (in extension): fusion at the operated level C6–C7, degenerative discopathy at the two cranial levels; note the retrolisthesis C4 on C5 (black arrow head). Right: Cervical MRI, T2-weighted significant degenerative disc protrusions in contact with the spinal cord. 
Fig. 2b: Dynamic lateral cervical radiographs in extension (left) and flexion (right): the prostheses remained mobile; the range of movement at C4–C5 and C5–C6 level was 8°, respectively.
First representative case, two-stage hybrid
A 44-year-old female (patient #5, subgroup 1) with history of cervical spine surgery (disc herniation C6–C7, discectomy and osteosynthesis four years before) and initially good outcome presented with recurrent arm and neck pain. Clinically, the patient had bilateral paraesthesia, clumsiness of the left arm left and pyramidal tract signs. 
The radiographies showed a good fusion at C6–C7, but a hypermobility at the cranial levels, especially at C4–C5 with a retrolisthesis (Figure 2A, left). The MRI showed degenerative protrusive discopathy with radicular compression (Figure 2A, right). The patient was operated on by an anterior approach with double-level total disc replacement (Bryan). Clinically, the patient recovered well (Odom Grade 2). The dynamic control X-rays showed good mobility of the prostheses at long-term follow-up (six years) and no hypermobility at adjacent levels (Figure 2B).
Fig. 3a: Lateral cervical spine radiographs (after first spine surgery): neutral position (left), in flexion (middle) and ¾ from the right (right). Note: fusion at C6–C7 level and degenerative discopathies cranially, especially at C4–C5 and C5–C6. At the C5–C6 level, there is discarthrosis and a right-sided foraminal stenosis. At the C4–C5-level there is a hypermobility.
Fig. 3b: Left: Cervical MRI, T2-weighted after second surgery: difficult interpretation due to artefacts. Middle: Cervical dynamic radiography (flexion): the C5–C6 prosthesis appears mobile in flexion. Right: Radiography, ¾ from the right: heterotopic ossification behind the prosthesis (McAfee Class 3), responsible of reduced mobility in extension.
Second representative case, two-stage hybrid
A 52-year-old female patient (patient #4, subgroup 1) with history of partial corpectomy at C6–C7 level (strut graft, five years before) presented a recurrence of bilateral C5 radiculalgia over one year. Radiographs showed fusion at C6–C7 level and cranial degenerative discopathies. At C5–C6 there was a right-sided foraminal stenosis and at C4–C5 a hypermobility (Figure 3A). 
The patient was re-operated on for C5–C6 discectomy and nerve root decompression and was implanted a disc prosthesis (Bryan). At six months postoperatively, the radiculalgia had disappeared. However, at one year postoperatively arm pain had recurred again (Odom Grade 3). The postoperative MRI did not show any major problems. CT and dynamic X-rays showed free intervertebral foramina and reduction of the preoperative hypermobility at C4–C5 level. However, the prosthesis’ mobility at C5–C6 level was partially reduced in extension by posterior heterotopic ossifications (McAfee Class 3) (Figure 3B).
Fig. 4a: Left: Cervical radiography, ¾ from the left: loss of the physiological lordosis and arthrotic foraminal stenoses at C5–C6 and C6–C7. Right: MRI, T2-weighted images showing multiple degenerative protrusions at C4–C5, C5–C6 and C6–C7; note the hyper signal at C4–C5 level.
Fig. 4b: Left: MRI, T2-weighted images showing well decompressed spinal cord with some artefacts due to the prosthesis at C4–C5 and two iliac bone grafts with plate at C5–C6 and C6–C7. Note the recovery of the lordosis. Right: Lateral cervical radiography showing the hybrid.
Third representative case, one-stage hybrid
A 30-year-old female patient (patient #10, subgroup 2) who was overweight presenting a tetraparesis, sensory deficit in both arms and legs, respectively, a tetrapyramidal syndrome and gait problems evolving over several weeks (JOA Score 4). The somatosensory evoked potential (SSEP) of the arms were normal, but abnormal at the lower limbs. MEP showed abnormalities of the central motor pathways. Cervical radiographies showed loss of cervical lordosis and left-sided arthrotic foraminal stenoses, especially at C5–C6 and C6–C7 (Figure 4A, left). The MRI demonstrated that there were multiple disc protrusions at C4¬–C5, C5–C6 and C6–C7. 
In T2-weighted images there was an intramedullary hyper signal (Figure 4A, right). The patient was operated on for multiple discectomies and total disc replacement at C4–C5 (Bryan) and iliac bone grafts with a plate at C5–C6 and C6–C7. Neurological recovery was nearly complete (JOA Score 15). At 2.5 years postoperatively, there remained only slight hypaesthesia at the upper limbs, which were subjectively not disturbing (Odom Grade 2). The postoperative MRI showed a satisfactory decompression of the spinal cord and recovery of the cervical lordosis (Figure 4B, left). On the control radiographies the cervical lordosis also appears well restored (Figure 4B, right).
Fig. 5a: Left: Cervical radiography: loss of lordosis and discarthrosis at C5–C6; at C6–C7 there is a degenerative discopathy with preservation of discal height. Right: MRI, T2-weighted images: cervical disc herniations at C5–C6 and C6–C7 with preservation of the pre- and retro-medullary CSF signal; note the thickening of the yellow ligament at C6–C7.
Fig. 5b: Dynamic radiographies, flexion (left) and extension (right) at six months postoperatively: fusion through the cage at C5–C6 level (black arrowhead) and mobile prosthesis at C6–C7 level (range of movement is 160).
Fourth representative case, one-stage hybrid 
A 53-year-old female patient (patient #13, subgroup 2) with past medical history of severe head trauma 20 years before, suffered from chronic cervicalgia and bilateral arm pain predominating on the left side. At clinical presentation, she complained of deterioration of the pain six months before and installation of hypaesthesia and dysaesthesias. 
On clinical examination she had motor deficit in her left arm with amyotrophy of the intrinsic hand muscles and a left hemi-pyramidal syndrome (JOA Score 12). Cervical radiographs showed a loss of lordosis and arthrosis. At C5–C6 level there was an advanced degenerative discopathy with a discrete retrolisthesis. At C6–C7 there was a less important discopathy (Figure 5A, left). MRI showed cervical disc herniation at C5–C6 and C6–C7 (Figure 5A, right). 
The patient was operated on for two-level discectomies and total disc replacement at C6–C7 (Physiodisc) and a cage at C5–C6 (Varlock). Clinical evolution was good (JOA Score 14). At eight months postoperatively, only slight hypaesthesia persisted at the hand, which was subjectively well tolerated (Odom Grade 2). Postoperative MRI showed a good radiculo-medullary decompression. 
Postoperative dynamic radiographies show a good fusion at the osteosynthesis level and good mobility at the prosthesis level (Figure 5B).
Analyses of other variables (duration of symptoms, age, former surgery, gender) with individual regression analysis demonstrated no significant relationship between any of those variables and outcomes on the basis of the numbers available. 
Radiologically, the implanted prostheses remained mobile and no adjacent disc disease was observed. In one patient (#4), the mobility of the prosthesis was partially reduced (McAfee Class 3).
One patient (#9) presented a hemiparesis at postoperative day eight. This patient had a congenital cervical canal stenosis and was re-operated on with posterior decompression. This allowed for a good progression (Odom Grade 2) at the last the follow-up. Another patient was re-operated on for a cheloid wound for aesthetic reasons. 
During the follow-up period, no other patient needed revision surgery neither for persisting or recurring symptoms nor for device-related complications.
We could demonstrate in this outcome study that the hybrid technique either performed as single- or as two-staged surgery represents a valuable alternative to multilevel fusion in cervical surgery of the degenerative spine. An individual surgical treatment plan and appropriate patient selection represents the key to success in such a patient population.
Hybrid series of Lariboisiere Hospital
Patients in subgroup 1 had an osteosynthesis (OS) in a mean of 3.3 years before implantation of a prosthesis, which we call a “two-stage hybrid”. Of this group 88% had a good clinical outcome (Odom Grade 2) at distant follow-up after the second surgery. The results of those two-stage hybrids were comparable to those reported for patients with either a simple osteosynthesis or a simple arthroplasty.6,17,19,21–23 Because of these encouraging results we then performed a simultaneous OS and total disc replacement (TDR), so-called ‘one-stage hybrid’ (subgroup 2) in carefully selected patients. 
In those patients there was an indication for an osteosynthesis at one level and an arthroplasty at another based on classic criteria. There were constructs with prosthesis above a cage (‘prosthesis-on-cage’, see third representative case) or vice-versa (“cage-on-prosthesis”, see fourth representative case). As the outcome was excellent or good in 83%, which favourably compares with other techniques,4,6,12,14,17,23–25 we think that the association of an osteosynthesis and a disc prosthesis in the same patient is not contradictory. 
General experience with cervical disc prostheses and the ‘hybrid technique’
The surgical experience with cervical disc prostheses is constantly growing.4–6,12,14,16,22,26–30 However, many studies excluded patients with former cervical spine surgery, especially osteosynthesis. There are only very few papers who studied patients with an osteosynthesis (OS) and a prosthesis, so-called ‘hybrid technique’. The hybrid technique may be realised in two stages (patient with OS receiving later a prosthesis) or in a single stage operation (simultaneous OS and prosthesis).31–32
Discussing the two-stage hybrid technique, the concern may arise whether a patient with former fusion is at all suited for a prosthesis surgery. In fact, it may be argued that they are already in an advanced stage of spondylarthrotic pathology33–34 and thus predisposed for prosthesis’ fusion. In our study, we did not find any argument supporting this hypothesis. We therefore think that former cervical spine fusion is not a contraindication for prosthesis. 
These findings are consistent with the results published by Sekhon et al. whose cervical arthroplasty series comprised nine patients with former anterior interbody fusion.4 However, further reports are necessary to consolidate these data, because even when pooling our results with those of the already reported cases, the total number remains small.
Another consideration for the single-stage hybrid technique is that simultaneous implantation of prosthesis and osteosynthesis may have adverse biomechanic effects on each other. In fact, it may be hypothesised that in that setting that the adjacent osteosynthesis increases mechanical stress at the prosthesis level and may therefore lead to early dysfunction (dislocation, subsidence, accelerated wear, etc.).34–35
On the other hand, the adjacent prosthesis may favour pseudarthrosis at the fusion level by its motion-preserving effect. In this study, we did not find arguments to support this hypothesis of adverse effects and confirm the results that were recently published by Barbagallo.31
Limitations of this study
The goal of the study is only on outcome research followed by a standardised operation procedure performed either in one or two stages and assessed by semi-quantitative outcome scales (Odom, JOA). In such a study design, the small study size does not play a major role. However, the presenting signs and symptoms in this study are broad including radiculopathy and/or myelopathy, so that the series is too small to compare with a sufficient statistical power the different indications related to outcome or to make a subgroup analysis. 
A semi-quantitative scale, as Odom or JAO, has a tendency to overestimate the differences in functional outcome between two groups; especially in small sized study designs. But we have overcome this problem by independent examinations. Additionally, the potential variance of outcome, again important in small sample size, could be narrowed by the same operation team in a single centre study design. 
A comparison such as ours may be, for all these reasons, the most representative and valuable data realistically achievable in a preliminary retrospective study design. A larger prospective controlled study should nevertheless be performed to gain further and more detailed insights.
The hybrid technique either performed as single- or as two-staged surgery, showed good clinical and radiological outcomes for DCDD. There was no significant difference whether total disc replacement and OS were performed simultaneously (single-stage) or consecutively (two-stage). 
Therefore, the hybrid technique has its place in the treatment of DCDD and that it may combine the advantages of OS and arthroplasty in well selected patients. As the number of reported patients is limited, further prospective clinical evaluation of this technique is warranted.
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