A Controlled Single-Centre Pilot Study to Evaluate the Effect of Prophylactic Surgery in Asymptomatic Degenerative Cervical Cord Compression

Abstract

Study Design

Single-centre controlled pilot study.

Objectives

To evaluate the effect of prophylactic surgery and to review the biases of a therapeutic trial in asymptomatic degenerative cervical cord compression (ADCC) patients.

Methods

Patients with ADCC and at least 1 predictor of progression to symptomatic degenerative cervical cord myelopathy (DCM) were offered either prophylactic surgery or standard structured rehabilitation. Recruited patients were clinically followed to detect the development of symptomatic DCM.

Results

Forty-one patients treated surgically and 68 patients treated non-surgically completed the minimum 36 months’ follow-up; 3 recruited patients were lost from evaluation. The surgical group had a higher Neck Disability Index score and more severe MRI compression. A matched subgroup of 41 non-surgical patients was created to reduce potential bias. During the follow-up period we observed progression to symptomatic DCM in 1 surgical case (2.4%) compared to 9 patients in the non-surgical group (13.2%, P = 0.054) and 7 cases in the matched non-surgical group (17.1%, P = 0.029). We observed non-serious early postoperative complications in 4 patients, which resolved spontaneously or after surgical revision. In 9 patients with progression to DCM, the myelopathy was mild with mJOA scale 15-17. One patient in the non-surgical group and 1 patient in the surgical group who progressed to DCM underwent surgery with a good outcome.

Conclusions

Prophylactic surgery led to a significant decrease in proportion of ADCC patients with progression to DCM. The results justify the organisation of a large randomized multicentre trial that may demonstrate the benefit of prophylactic surgery in ADCC patients.

Keywords

asymptomatic degenerative cervical cord compression degenerative cervical myelopathy prophylactic surgery

Introduction

Mechanical stress, vulnerability and time are key components of a framework to explain the somewhat complex pathophysiology of degenerative cervical myelopathy (DCM).¹ Unlike compression, which can be visualised by MRI, the other mechanical forces are difficult to document or quantify. MRI evidence of spinal cord compression is therefore a key element in the diagnosis of DCM, along with clinical signs and symptoms of myelopathy.^2,3 The relative resilience of the cervical spinal cord to mechanical compression leads to a relatively high prevalence of clinical-radiological discordance, i.e., some individuals may have MRI findings of degenerative cervical cord compression without the clinical signs and symptoms of myelopathy. This condition, termed asymptomatic or non-myelopathic degenerative cervical cord compression (ADCC, NMDCC), may eventually progress to symptomatic DCM and should be considered a precursor to DCM.

In the early years of the MRI era, ADCC was considered an exceptional condition,⁴ but now the estimated prevalence of ADCC in a healthy population is much higher than in DCM. A meta-analysis and systematic review showed an estimated prevalence of 24.2%, with a significantly higher prevalence of ADCC in older populations and in North American/European populations compared to Asian populations. In Caucasian European/North American populations over the age of 60, the prevalence was as high as 40%.^5,6 A recent study of 267 young adult volunteers (mean age 28.7 ± 5.6 years) found the presence of mild spinal cord compression in 24% of participants.⁷ ADCC is therefore a very common condition and a possible precursor of DCM, increasing the importance of its clinical management and influencing attitudes towards possible prophylactic surgery.

The first comprehensive systematic review and survey of patients with ADCC⁸ made a number of recommendations regarding the frequency, timing and predictors of myelopathy development in asymptomatic patients with ADCC. The authors suggested that patients with ADCC who have clinical or electrophysiological evidence of cervical radicular dysfunction or central conduction deficits appear to be at higher risk of developing myelopathy and should be counselled to consider surgical treatment. In a survey of 774 spine surgeons, the majority considered the presence of clinically symptomatic radiculopathy to be predictive of progression to myelopathy in ADCC patients. In a case presented as part of this survey with combined clinical evidence of radiculopathy but no myelopathy, with MRI evidence of multi-level spinal cord compression and intramedullary T2 hyperintensity, respondents most frequently favoured operative management over conservative management (665/774; 85.9%), with the majority (425/665; 63.9%) stating that the primary goal of surgery was to prevent the development of myelopathy.⁸ Subsequent AO Spine guidelines⁹ have further elaborated and modified this recommendation. ADCC patients with clinical evidence of radiculopathy, with or without electrophysiological confirmation, were considered to be at higher risk of developing myelopathy. It was recommended that these patients should be advised of this risk and offered either surgical intervention or non-operative management consisting of close serial follow-up or a supervised trial of structured rehabilitation. An evidence-based commentary¹⁰ confirmed the lack of evidence to support surgery in asymptomatic individuals with ADCC who have no risk factors for progression. For these patients, the authors suggested non-operative management, including education about the symptoms of myelopathy, clinical follow-up in 6-12 months, and avoidance of high-risk activities.

In addition, some authors have suggested that individuals with ADCC are at increased risk of acute myelopathy following mild trauma.^11,12 This suspicion has led some surgeons to recommend decompression surgery to prevent this trauma-induced myelopathy in individuals thought to be susceptible.^10,13,14 This issue has been and remains controversial.¹⁵ Several studies addressing this issue have shown that the risk of developing spinal cord injury in ADCC patients after mild trauma is probably low.^16-19

To date, no trials have directly compared prophylactic surgery with non-operative management in patients with ADCC, either with or without radiculopathy. As a result, the AO Spine Guideline Development Group considered the available evidence to be of low overall quality and the strength of their recommendation to be weak.⁹

Due to some unresolved ethical and practical issues regarding a randomised trial in ADCC patients, which we discuss in the Discussion section, we decided to conduct a single-centre, non-randomised, controlled pilot study. The aim was to evaluate the effect of prophylactic surgery and to review the pitfalls and biases of a trial in ADCC patients.

Materials and Methods

Participants

The study was approved by The Ethics Committee and all participants signed an informed consent form.

The study sample was recruited from 2 populations. The first source of recruitment was a cohort of consecutive subjects referred to the Department of Neurology between January 2017 and December 2020, with clinical signs and symptoms of cervical radiculopathy and/or moderate-to-severe chronic or intermittent axial cervical pain. The second source of recruitment was subjects who had previously been found to have MRI evidence of degenerative cervical cord compression in an epidemiological study of the prevalence of degenerative cervical cord compression.⁶ Clinical follow-up ended in June 2024. Patient’s recruitment and follow-up were displayed in flow diagram (Figure 1).

Figure 1.

Flow diagram of study participant recruitment and follow-up. MRI, magnetic resonance imaging; DCM, degenerative cervical myelopathy.

All subjects in the study had to meet the following inclusion criteria:

• MR evidence of degenerative compression of the cervical spinal cord with or without concomitant cervical cord signal intensity changes on T2/T1 images (see “Imaging” below)

• Absence of any current myelopathic clinical signs and symptoms likely to be due to cervical cord involvement, from the following list.

Symptoms:

⁃ Gait disturbance

⁃ Numb and/or clumsy hands

⁃ Lhermitte’s phenomenon

⁃ Bilateral arm paresthesias

⁃ Lower or upper limb weakness

⁃ Urinary urgency, frequency, or incontinence.

Signs:

⁃ Corticospinal tract signs:

◦ Hyperreflexia/clonus

◦ Spasticity

◦ Pyramidal signs (Babinski’s or Hoffman’s signs)

◦ Spastic paresis of any limb (most commonly lower limb spastic paraparesis)

⁃ Flaccid paresis of 1 or 2 upper extremities in the plurisegmental distribution

⁃ Atrophy of hand muscles

⁃ Sensory involvement in different distributions in the upper or lower extremities

(always plurisegmental)

⁃ Gait ataxia with positive Romberg’s sign.

• Presence of at least 1 proven predictor of increased risk of developing symptomatic DCM, i.e.:

◦ clinical and/or electrophysiological signs of radiculopathy, or

◦ electrophysiological evidence of the cervical spinal cord dysfunction, or

◦ higher degree of cervical cord compression defined by both compression ratio (CR) < 0.4 and cross-sectional area (CSA) < 70.1 mm.²⁰

Thus, all subjects met the diagnosis of asymptomatic degenerative cervical cord compression and consented to the study design. The design included assignment to either the surgical or non-surgical arm of the study and subsequent follow-up.

Clinical Evaluation

A detailed clinical examination was performed at baseline and every 6 months thereafter. The aim was to detect possible clinical symptoms and signs of symptomatic DCM. In addition, surgical patients were followed 1 week and then 3 months after surgery to monitor early postoperative complications and changes in neurological status with a focus on myelopathic signs and symptoms. Furthermore, patients were educated about possible myelopathic symptoms and signs and were instructed to make an appointment for an immediate follow-up visit in the event of new neurological symptoms or signs.

A standardised, timed 10-m walk and run (as fast as possible) was evaluated, in terms of time taken and number of steps required.²¹

In addition to a detailed clinical assessment, the modified Japanese Orthopaedic Association (mJOA) score and the Neck Disability Index (NDI) were assessed at each visit. The mJOA scale at enrolment for all ADCC patients was equal to 18 points. Unlike the mJOA scale, which is based on an objective assessment of disability, the NDI reflects a subjective assessment of neck symptoms and their severity.

Clinical evaluation, focusing on the determination of development of symptomatic myelopathy (as the primary outcome), was performed by neurologists experienced in the diagnosis and practical management of myelopathic cases (ZKJ, MN).

Radiological Evaluation

MRI Protocol for Radiological Evaluation of Cervical Spinal Cord Compression

Cervical spinal cord compression was evaluated on images acquired on Philips Ingenia 1.5 T MRI scanner (Philips, Best, The Netherlands). The MRI protocol included sagittal T2 TSE (TE 100 ms, TR 2.1s, flip angle 90°, acquisition voxel size 3.3 × 0.3 × 0.3 mm), sagittal T1 TSE (TE 8 ms, TR 0.6s, flip angle 90°, acquisition voxel size 3.3 × 0.4 × 0.4 mm), sagittal STIR (TE 55 ms, TR 2.7s, TI 155 ms, acquisition voxel size 3.3 × 0.4 × 0.4 mm) and transversal T2 FFE (TE 9 ms , TR 0.5s, flip angle 25°, acquisition voxel size 4.0 × 0.6 × 0.3 mm) covering C2-7 spinal segments continuously.

Evaluation of the Cervical Spinal Cord Compression

Qualitative criteria for cervical spinal cord compression were defined as a change in the contour or shape of the spinal cord at the level of an intervertebral disc on axial MRI scan compared with the midpoint level of adjacent vertebrae. Visual identification of spinal cord compression was performed by consensus of 2 experienced radiologists (MK and TR with 15 and 5 years of experience, respectively). IntelliSpace Portal Concerto v10.1 software (Philips, Best, The Netherlands) was used for quantitative assessment of compression. Manual segmentation of the spinal cord contour was performed using the Bezier mode on T₂ -FFE axial images to calculate the cross-sectional area of the spinal cord (CSA). In addition, anteroposterior and laterolateral spinal cord diameters were measured on T₂ -FFE images and the compression ratio (CR) was calculated. In patients with multilevel compression, the maximum compression level (MCL) corresponded to the level with the lowest compression ratio.

Electrophysiological Evaluation

At baseline, short-latency SEPs were elicited from the median and tibial nerves by electrical stimulation of mixed nerves at the wrist and the ankle. Similarly, MEPs were elicited by means of transcranial and root magnetic stimulation and recorded from the abductor digiti minimi and abductor hallucis muscles on both sides. Details of the methodology of electrophysiological testing and interpretation of results with definition of central conduction abnormalities attributable to a possible cervical spinal cord lesion were described in previous publications.^22-24

Motor and sensory conduction studies were performed on 6 motor nerves (median, ulnar, and tibial nerves bilaterally) and 6 sensory nerves (ulnar, radial and sural nerves bilaterally) using conventional techniques.

Needle EMG of 6 muscles (deltoid, biceps brachii, triceps brachii, extensor digitorum communis, abductor pollicis brevis and abductor digiti quinti) was performed bilaterally with assessment of spontaneous activity, motor unit potential parameters, and interference patterns. EMG signs of acute motor axonal neuropathy in 1 myotome (C5–Th1) corresponding to radicular signs and symptoms were classified as radiculopathy. EMG signs of acute, subacute, or chronic motor axonal neuropathy in 2 or more adjacent myotomes (C5–Th1), unilateral or bilateral, were classified as signs of anterior horn cell lesion resulting from degenerative cervical myelopathy.

Study Design and Assignment to Study Arms

All ADCC subjects who met the inclusion criteria were informed of the potential risks and benefits of both surgical and non-surgical treatment and the current recommendations. They were then offered a free choice of either a surgical or a non-surgical treatment. They were assured that if they chose non-surgical treatment, they would be followed and if they progressed to DCM, surgical treatment would be considered. We attempted to reduce selection bias by using post-hoc statistical methods, i.e., propensity score matching to create a matched non-surgical group. The primary endpoint of the study was the detection of the development of symptomatic DCM. The presence of DCM was based on the occurrence of at least 1 symptom and 1 sign (from the list used as exclusion criteria - see above), that were likely to be due to degenerative cervical cord compression, were not present at the baseline, and had no other topical or aetiological explanation. The secondary endpoint of the study was to identify variables that might influence the choice of treatment.

Surgical Treatment and Post-surgical Follow-Up

Spondylosurgeons who performed surgery adhered to the following rules for the choice of surgical procedure.

Anterior procedures were indicated in the presence of anterior spinal cord compression in 1-3 levels. After removal of the disc and posterior osteophytes (decompression) with routine use of a microscope, the disc was replaced by a cage with fixation to the adjacent vertebrae with screws (STACC cages) or blades (ROI cages). If the disc was replaced by autograft or allograft, it was necessary to bridge and fix the segments with plates and screws. Smaller kyphosis could be fixed in this way. Most cases were treated from an anterior approach.

Other types of procedures were indicated only in individual cases.

Posterior procedures - open-door laminoplasty - were indicated for multilevel stenosis (over 3 segments) with preserved or balanced lordosis and combined anterior and posterior compression.

Combined procedures were indicated in the presence of multilevel (>3) severe stenosis (below 8 mm of the anteroposterior dimension of the spinal canal) and the presence of deformity - kyphosis, vertebral displacement and instability.

Open-door laminoplasty was usually followed by anterior discectomy, decompression and fusion with cages or plates and correction of any kyphosis. In cases of kyphosis and instability, posterior laminectomy with instrumented fusion was followed by anterior discectomy, decompression and fusion with cages or plates.

The extent of the surgery usually corresponded to the extent of the spinal canal narrowing. Usually, in case of kyphotic or more severe degeneration, the range of operated and instrumented segments was extended.

Non-surgical Treatment

Patients were offered the option of structured rehabilitation, which included a combination of physiotherapy, occupational therapy with modification of the work or home environment, pain management, activity modification with avoidance of activities that could aggravate symptoms and risky activities, and regular monitoring and evaluation. Rehabilitation was individualised, taking into account the patient’s specific symptoms, lifestyle and general health, and was monitored and adjusted.

Statistical Evaluation

Standard measures of summary statistics were applied to describe primary data; continuous parameters were summarised as median (5th–95th percentile range). Categorical parameters were expressed as absolute and relative frequencies. All continuous variables were tested for normality using the Kolmogorov-Smirnov test and visualization of N-P plots. Chi-squared test or Fisher’s exact test (when appropriate) for categorical variables and Mann-Whitney U test for continuous variables were used to examine differences between groups. Propensity score matching was used to create a non-surgical group matched to the surgical group. Power analysis for independent sample proportions was performed to calculate the required number of subjects in both groups (surgical and non-surgical) which enables to reject the null hypothesis that surgery is not associated with progression to DCM with a 80% probability. IBM SPSS Statistics 29 was used for statistical analyses.

Results

During the recruitment period, we recruited 112 patients who met the inclusion criteria of ADCC with higher risk of progression to DCM and who agreed to participate. Forty-two patients agreed to surgical treatment and underwent surgery, while 70 ADCC patients preferred non-surgical treatment and follow-up. One patient from the surgical group and 2 patients from the non-surgical group did not complete the minimum 3-year follow-up. Finally, 41 patients treated surgically (surgical group) and 68 patients with non-surgical treatment (non-surgical group) completed follow-up and their data were analysed. Ten of 41 patients treated surgically and 15 of 68 patients treated non-surgically were followed for 48 months. To minimise the bias between surgical and non-surgical groups, we created a matched non-surgical group (n = 41) controlled for age, sex and the presence of radiculopathy (as the most powerful predictor for DCM development) to the surgical group. The demographic, clinical, imaging and electrophysiological characteristics of the surgical and both no-surgical groups were summarised in Table 1.

Table 1.

Summary of Demographic, Clinical, Imaging and Electrophysiological Parameters of the Groups Studied. Continuous Variables are Summarised as Medians (5th-95th Percentile Range) and Categorical Variables are Expressed as Absolute and Relative Frequencies.

Parameter/Group		Surgical N = 41	Non-surgical N = 68	p1	Non-surgical (Matched) N = 41	p2
Age (years)		57.0 (41-77)	57.5 (28-77)	NS	57.0 (46-77)	NS
Females		22 (53.6%)	33 (48.5%)	NS	21 (51.2%)	NS
mJOA		18 (18-18)	18 (18-18)	NS	18 (18-18)	NS
NDI		10 (0-39)	7 (0-21)	0.020	8 (0-21)	0.053
Follow-up period (months)		36 (36-48)	36 (36-48)	NS	36 (36-48)	NS
Multilevel compression		30 (73.2%)	51 (75.0%)	NS	30 (73.2%)	NS
MCL	C3/4	3 (7.3%)	2 (2.9%)	NS	1 (2.4%)	NS
	C4/5	8 (19.5%)	21 (30.9%)	NS	10 (24.4%)	NS
	C5/6	21 (51.2%)	29 (42.7%)	NS	17 (41.5%)	NS
	C6/7	9 (22.0%)	16 (23.5%)	NS	13 (31.7%)	NS
Standardized gait	Number of steps	13 (7-20)	14 (9-18)	NS	14 (9-18)	NS
Standardized gait	Time (sec)	6.0 (4.6-14.4)	6.0 (4.2-9.8)	NS	6.0 (4.2-9.8)	NS
Standardised run	Number of steps	11 (8-14)	11 (7-17)	NS	11 (7-17)	NS
Standardised run	Time (sec)	4.0 (2.4-5.6)	4.0 (2.5-6.9)	NS	4.0 (2.5-6.9)	NS
Radiculopathy		15 (36.6%)	27 (39.7%)	NS	18 (43.9%)	NS
SEP abnormality		9 (22.0%)	17 (25.0%)	NS	10 (24.4%)	NS
MEP abnormality		5 (12.2%)	10 (14.7%)	NS	6 (14.6%)	NS
EMG abnormality		6 (14.6%)	9 (13.2%)	NS	6 (14.6%)	NS
Any electrophysiological abnormality		15 (36.6%)	22 (38.2%)	NS	17 (41.4%)	NS
Moderate to severe compression	CR ≤0.40	36 (87.8%)	43 (63.2%)	0.005	24 (58.5%)	0.003
	CSA ≤70 mm²	39 (95.1%)	62 (91.2%)	NS	35 (85.4%)	NS
	CR ≤0.40 and CSA ≤70 mm²	34 (82.9%)	41 (60.3%)	0.013	24 (58.5%)	0.015
CR		0.40 (0.19-0.57)	0.45 (0.21-0.60)	0.015	0.45 (0.21-0.60)	0.090
CSA (mm²)		52 (27-75)	58.5 (39-79)	0.016	60 (39-77)	0.006
Any positive predictive factor		41 (100%)	68 (100%)	NS	41 (100%)	NS
Progression to DCM		1 (2.4%)	9 (13.2%)	0.054	7 (17.1%)	0.029

Notes: p1: significance of difference between surgical and non-surgical groups; p2: significance between surgical and non-surgical matched groups. Bold letters indicate significant differences.

Abbreviations: p, statistical significance; NS, non-significant (P > 0.05); mJOA, modified Japanese Orthopaedic Association scale; NDI, Neck Disability Index; MCL, maximum compression level; sec, seconds; SEP, somatosensory evoked potentials; MEP, motor evoked potentials; EMG, electromyography; CR, compression ratio; CSA, cross-sectional area; DCM, degenerative cervical myelopathy.

There was no significant difference between the surgical group and either of the non-surgical groups in terms of age, proportion of women, mJOA scale, proportion of levels with maximum spinal cord compression and with multilevel compression, parameters of the standardised 10-metre gait and run, proportion of radiculopathy, SEP, MEP, EMG or the presence of any electrophysiological abnormality. The surgical group had a higher NDI score, lower CR and CSA values, a higher proportion of subjects with CR <0.40 and those with both CR <0.40 and CSA <70 mm². Similar differences were found between the surgical and matched non-surgical groups for CSA value, proportion of subjects with CR <0.40 and those with both CR <0.40 and CSA <70 mm².

Surgery

A total of 34 patients underwent anterior surgery with discectomy, decompression and fusion at 1 or more levels. The posterior approach was primarily used in 2 patients. In 5 cases, a combined single-stage posterior and anterior approach was used (Table S1).

Early postoperative complications were observed in 4 patients: Transient dysphonia, transient mild monoparesis of the right upper extremity, dysphagia due to retropharyngeal haematoma which was surgically removed and the dysphagia resolved, and left C5 root impairment signs and symptoms including paresis which resolved after removal of the haematoma and re-decompression at C4-5 level 5 days after the first surgery (Table S1).

In 1 case operated via posterior approach, myelopathic signs and symptoms (clumsy hand, ataxic gait, mJOA of 15) appeared 1 month after surgery together with radicular pain and instability of the cervical spine. The patient was re-operated 1 year after the first surgery using anterior discectomy, decompression and fusion at C5-T1 levels with disappearance of instability, radicular pain and slight improvement of myelopathic signs and symptoms (mJOA of 16).

Progression to DCM

During the follow-up period (minimum 36 months, range 36-48 months) we observed progression to symptomatic degenerative cervical myelopathy in 1 surgical case (2.4%) mentioned in the previous paragraph compared with 9 patients in the non-surgical group (13.2%, P = 0.054) and 7 cases in the matched non-surgical group (17.1%, P = 0.029).

In 9 patients with progression to DCM including 1 patient from the surgical arm, the myelopathy was mild with mJOA scale 15-17; in 1 patient from the non-surgical group, we observed worsening to mJOA scale of 14 point and the patient underwent surgery with a good outcome (improvement to mJOA of 17). The detailed symptomatology of cases with progression to DCM is summarised in Table S2.

The power analysis showed an 80% chance of correctly rejecting the null hypothesis that surgery is not associated with the progression to DCM with the 101 being the required number of subjects in both (surgical and non-surgical) groups (Table S3).

Discussion

In a single-centre controlled trial, we observed a significant reduction in the short-term rate of progression to symptomatic DCM in ADCC patients at higher risk of progression to DCM who underwent prophylactic surgery compared with non-surgically treated ADCC patients who underwent standard rehabilitation, treatment and follow-up. We found a low rate of progression to symptomatic DCM in ADCC patients who underwent prophylactic surgery (2.4%) during the 3-year period and transient early postoperative complications in 4 cases (9.7%) that resolved after surgical revision (2 cases) or spontaneously (2 cases). In contrast, the rate of progression in the nonsurgical group (13.2% and 17.1% in the non-matched and matched nonsurgical groups, respectively) was comparable to rates seen in our previous observational studies^20,22 The difference in the proportion of patients with progression to DCM was close to significance (P = 0.054) compared to our non-matched non-surgical group. The potential bias inherent in an open-label, non-randomised study was at least partially controlled by the use of a matched non-surgical group when the difference already reached statistical significance (P < 0.05). Given the relatively small number of participants in our pilot study, we believe that the prophylactic effect of surgery is clinically relevant, at least in the short term.

In our previous large prospective study of 199 patients enrolled in ADCC, 22.6% developed symptoms of myelopathy at a median follow-up of 44 months (range 2-12 years). This cohort included patients with either radiculopathy or cervical pain.²² In another study from our group in 2017, 13.4% of patients (15/112) developed DCM at a median follow-up of 36 months.²⁰ This cohort was comparable to our current study, as it included patients with either non-myelopathic symptoms (radiculopathy, cervical pain) or completely asymptomatic subjects (in whom cervical cord compression was found in volunteers during the epidemiological study or incidentally). The only difference was that subjects with only mild compression were not included in the current study. However, other authors have reported lower rates of progression into symptomatic myelopathy, but in different populations. Matsunaga and coworkers²⁵ reported approximately 1% of patients with asymptomatic cervical stenosis developing clinical signs of myelopathy per year. However, these patients had cervical stenosis due to ossification of the posterior longitudinal ligament and cervical cord compression was not documented by MRI.

After explaining the known risks and benefits of prophylactic surgery for ADCC, about two-fifths of patients opted for surgery. This proportion should be taken into account when designing future trials and when considering patient adherence to treatment.

Our study has several limitations that should be highlighted and taken into account when interpreting our results. We didn’t use randomisation because of some ethical and practical issues. In a preparatory phase of this project, we intended to organise a multicentre national randomised trial in ADCC patients with a higher risk of progression to DCM to evaluate the effect of prophylactic surgery compared with non-operative management. However, the preparatory phase revealed serious problems, namely the lack of acceptance of non-operative treatment by some spinal surgeons, especially in cases of severe degenerative cervical cord compression. On the patient side, we observed difficulties in the acceptance of participation in such a randomised trial, in particular the lack of adherence to the outcome of randomisation by those who agreed to be recruited and were assigned to the surgical group (unpublished data). Therefore, we used a controlled trial design with a risk of bias that could influence the results. Our surgical and non-surgical groups, based on the decision of well-informed patients, did not differ in most parameters that could potentially influence the results, including age, proportion of women, standardised gait parameters, proportion of levels with maximum spinal cord compression and patients with multilevel compression, presence of radiculopathy, and proportion of electrophysiological abnormalities. However, there were some significant differences between the groups. The non-surgical group had a lower NDI score than the surgical patients. This difference could be explained by the fact that patients with more severe subjective problems have a higher tendency to choose surgical treatment, but could hardly influence the results based on objective assessment of myelopathic symptoms and signs. The other difference found was in the parameters that reflect the severity of compression detected by MRI, namely CR and CSA. Patients who opted for surgery had a significantly lower median CR, a lower CSA, and a higher proportion of cases with both CR <0.40 and CSA <70 mm2. An explanation for this difference may be found in the design of our study. A large proportion of patients consulted surgeons before entering our study. It might be expected that surgeons would be more likely to express a positive attitude towards surgery in patients with more severe compression seen on MRI. During the recruitment phase, we also showed MRI findings to patients, explained and commented them.

Unfortunately, our single centre study was statistically underpowered and did not allow us to match the 2 groups on all important parameters, including severity of compression. However, the potential bias of this difference in severity of compression in relation to our hypothesis (i.e., a decrease in the rate of progression to DCM after prophylactic surgery) could actually be spuriously increasing the rate of progression due to more severe compression in the surgical group. Despite this bias, the rate of progression in the surgical group remained low. The effect of this bias may explain why the difference did not reach statistical significance when using the non-matched non-surgical group. The severity of compression should be controlled for in a possible future randomised trial, if one is organised, together with other known predictors of progression, such as radiculopathy and spinal cord electrophysiological impairment.

The small number of cases in our study arms and the large number of variables/predictors with a possible impact on progression to DCM did not allow us to use multivariate analysis to confirm the independent influence of prophylactic surgery. Power analysis, based on the observed proportion of cases progressing to DCM in both arms of the study and using a power of 0.8, showed that the number of subjects studied should reach at least 101 individuals in both arms of the study to confirm a statistically significant influence of prophylactic surgery. There are certainly other aspects of cervical cord involvement in addition to the severity of compression, such as the type of compression, the number of levels with compression, or disturbed alignment of the cervical cord, which may inevitably influence the decision about the type of surgery and its outcome. These factors are difficult to standardise, but should also be taken into account when planning a future trial.

Finally, in addition to sample size and selection bias, single-centre studies have several other disadvantages, including limited generalisability, investigator bias, institutional politics and local regulations, and limited external validity of the study.

In conclusion, the results of our study are promising, but they should be interpreted with caution due to methodological limitations. The results of our study need to be confirmed in a large multicentre randomised trial that may demonstrate the benefit of prophylactic surgery in ADCC patients. The present study provides valuable information for the design of such a trial. In addition to a sufficiently large study population and duration of follow-up, the most important issue will be a study design that meets ethical standards and is acceptable to both patients and investigators, and that it maximally controls for all documented biases influencing the outcome, i.e., progression to symptomatic DCM.

Supplemental Material

Supplemental Material - A Controlled Single-Centre Pilot Study to Evaluate the Effect of Prophylactic Surgery in Asymptomatic Degenerative Cervical Cord Compression

Supplemental Material for A Controlled Single-Centre Pilot Study to Evaluate the Effect of Prophylactic Surgery in Asymptomatic Degenerative Cervical Cord Compression by Zdenek Kadanka, Martin Nemec, Richard Chaloupka, Ludek Ryba, Karel Maca, Dusan Matejicka, Tomas Rohan, Milos Kerkovsky, Tomas Horak, Magda Horakova, Eva Vlckova, and Josef Bednarik in Global Spine Journal

Footnotes

Acknowledgments

The authors thank to J. Cienciala and V. Tichy, who participated on the surgical part of the project.

Author contributions

Z. Kadanka organised recruitment and clinical follow-up and collected clinical data. M. Nemec participated in clinical follow-up and clinical data collection. R. Chaloupka, L. Ryba, K. Maca, and D. Matejicka participated in the planning and standardisation of the surgical part of the project and performed the surgical treatment and postoperative follow-up. T. Rohan and M. Kerkovsky performed all imaging assessments and calculations. T. Horak and M. Horakova participated in the literature review, performed statistical analysis and contributed to the drafting of the article. E. Vlckova performed and interpreted all electrophysiological assessments. J. Bednarik designed the study, interpreted the data and drafted the original manuscript. As guarantor of this work, he had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors contributed substantially to study design and data collection or data analysis and interpretation, participated in drafting or revising the article, discussed the results, and approved the final version of the manuscript. (except Z. Kadanka, who was unable to approve the original manuscript due to sudden death).

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Czech Health Research Council grants NV18-04-00159 and NU 22-04-00024 and by the Ministry of Health, Czech Republic – conceptual development of research organizations (FNBr, 65269705).

Ethical Statement

ORCID iD

Josef Bednarik

Supplemental Material

Supplemental material for this article is available online.

References

Davies

Mowforth

Gharooni

, et al. A new framework for investigating the biological basis of degenerative cervical myelopathy [AO spine RECODE-DCM research priority number 5]: mechanical stress, vulnerability and time. Glob Spine J. 2022;12(1_suppl):78S-96S. doi:10.1177/21925682211057546

Kalsi-Ryan

Karadimas

Fehlings

. Cervical spondylotic myelopathy: The clinical phenomenon and the current pathobiology of an increasingly prevalent and devastating disorder. Neuroscientist. 2013;19(4):409-421. doi:10.1177/1073858412467377

Badhiwala

Ahuja

Akbar

, et al. Degenerative cervical myelopathy - Update and future directions. Nat Rev Neurol. 2020;16(2):108-124. doi:10.1038/s41582-019-0303-0

Teresi

Lufkin

Reicher

, et al. Asymptomatic degenerative disk disease and spondylosis of the cervical spine: MR imaging. Radiology. 1987;164(1):83-88. doi:10.1148/radiology.164.1.3588931

Smith

Stewart

Davies

Kotter

MRN

. The prevalence of asymptomatic and symptomatic spinal cord compression on magnetic resonance imaging: a systematic review and meta-analysis. Glob Spine J. 2021;11(4):597-607. doi:10.1177/2192568220934496

Kovalova

Kerkovsky

Kadanka

, et al. Prevalence and imaging characteristics of nonmyelopathic and myelopathic spondylotic cervical cord compression. Spine. 2016;41(24):1908-1916. doi:10.1097/BRS.0000000000001842

Valošek

Bédard

Keřkovský

Rohan

Cohen-Adad

. A database of the healthy human spinal cord morphometry in the PAM50 template space. Imaging Neuroscience. 2024;2:1-15. doi:10.1162/imag_a_00075

Wilson

Barry

Fischer

, et al. Frequency, timing, and predictors of neurological dysfunction in the nonmyelopathic patient with cervical spinal cord compression, canal stenosis, and/or ossification of the posterior longitudinal ligament. Spine. 2013;38(22 Suppl 1):S37-54. doi:10.1097/BRS.0b013e3182a7f2e7

Fehlings

Tetreault

Riew

, et al. A clinical practice guideline for the management of patients with degenerative cervical myelopathy: Recommendations for patients with mild, moderate, and severe disease and nonmyelopathic patients with evidence of cord compression. Glob Spine J. 2017;7(3 Suppl):70S-83S. doi:10.1177/2192568217701914

10.

Witiw

Mathieu

Nouri

Fehlings

. Clinico-radiographic discordance: An evidence-based commentary on the management of degenerative cervical spinal cord compression in the absence of symptoms or with only mild symptoms of myelopathy. Glob Spine J. 2018;8(5):527-534. doi:10.1177/2192568217745519

11.

Emery

. Cervical spondylotic myelopathy: Diagnosis and treatment. J Am Acad Orthop Surg. 2001;9(6):376-388. doi:10.5435/00124635-200111000-00003

12.

Shedid

Benzel

. Cervical spondylosis anatomy: Pathophysiology and biomechanics. Neurosurgery. 2007;60(1 Supp1 1):S7-13. doi:10.1227/01.NEU.0000215430.86569.C4

13.

Epstein

. Laminectomy for cervical myelopathy. Spinal Cord. 2003;41(6):317-327. doi:10.1038/sj.sc.3101477

14.

Lauryssen

Riew

Wang

. Severe cervical stenosis: operative treatment of continued conservative care? Spine Line. 2006;8(1):21-25.

15.

Murphy

Coulis

Gerrard

. Cervical spondylosis with spinal cord encroachment: should preventive surgery be recommended? Chiropr Osteopathy. 2009;17:8. doi:10.1186/1746-1340-17-8

16.

Chang

Ellingson

Salamon

Holly

. The risk of acute spinal cord injury after minor trauma in patients with preexisting cervical stenosis. Neurosurgery. 2015;77(4):561-565. doi:10.1227/NEU.0000000000000888

17.

Horak

Horakova

Kerkovsky

, et al. Evidence-based commentary on the diagnosis, management, and further research of degenerative cervical spinal cord compression in the absence of clinical symptoms of myelopathy. Front Neurol. 2024;15:1341371. doi:10.3389/fneur.2024.1341371

18.

Bednařík

Sládková

Kadaňka

, et al.

Are subjects with spondylotic cervical cord encroachment at increased risk of cervical spinal cord injury after minor trauma?

J Neurol Neurosurg Psychiatry. 2011;82(7):779-781. doi:10.1136/jnnp.2009.198945

19.

Rüegg

Wicki

Aebli

Wisianowsky

Krebs

. The diagnostic value of magnetic resonance imaging measurements for assessing cervical spinal canal stenosis. J Neurosurg Spine. 2015;22(3):230-236. doi:10.3171/2014.10.SPINE14346

20.

Kadanka

Adamova

Kerkovsky

, et al. Predictors of symptomatic myelopathy in degenerative cervical spinal cord compression. Brain Behav. 2017;7(9):e00797. doi:10.1002/brb3.797

21.

Kadanka

Skutil

Vlckova

Bednarik

. Walk and run test in patients with degenerative compression of the cervical spinal cord. J Clin Med. 2021;10(5):927. doi:10.3390/jcm10050927

22.

Bednarik

Kadanka

Dusek

, et al. Presymptomatic spondylotic cervical myelopathy: An updated predictive model. Eur Spine J. 2008;17(3):421-431. doi:10.1007/s00586-008-0585-1

23.

Bednarik

Kadanka

Dusek

, et al. Presymptomatic spondylotic cervical cord compression. Spine. 2004;29(20):2260-2269. doi:10.1097/01.brs.0000142434.02579.84

24.

Bednarík

Kadanka

Vohánka

Stejskal

Vlach

Schröder

. The value of somatosensory- and motor-evoked potentials in predicting and monitoring the effect of therapy in spondylotic cervical myelopathy. Prospective randomized study. Spine. 1999;24(15):1593-1598. doi:10.1097/00007632-199908010-00014

25.

Matsunaga

Sakou

Taketomi

, et al. Clinical course of patients with ossification of the posterior longitudinal ligament: A minimum 10-year cohort study. J Neurosurg Spine. 2004;100(Suppl 3):245-248.

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