How do early perioperative changes in AIS grade correlate with long-term neurological recovery? A retrospective cohort study

Abstract

Context/Objective: Providing accurate counseling on neurological recovery is crucial after traumatic spinal cord injury (TSCI). The early neurological changes that occur in the subacute phase of the injury (i.e. within 14 days of early decompressive surgery) have never been documented. The objective of this study was to assess peri-operative neurological improvements after acute TSCI and determine their relationship with long-term neurological outcomes, measured 6–12 months following the injury.

Methods: A retrospective cohort study of 142 adult TSCI patients was conducted. Early peri-operative improvement was defined as improvement of at least 1 AIS grade between the pre-operative and follow-up (6–12 months post-TSCI) assessment. neurological improvement of at least 1 AIS grade.

Results: Out of the 142 patients, 18 achieved a peri-operative improvement of at least 1 AIS grade. Presenting a pre-operative AIS grade B and having shorter surgical delays were the main factors associated with stronger odds of achieving this outcome. Out of the 140 patients who still had potential for improvement at the time of the post-operative assessment, 44 achieved late neurological recovery (improvement of at least 1 AIS grade between the post-operative assessment and follow-up). Patients who presented a perioperative improvement seemed more likely to achieve later neurological improvement as well, although this was not statistically significant.

Conclusion: Our results suggest that it is important to assess early perioperative neurological changes within 14 days of surgery because it can provide beneficial insight on long-term neurological outcomes for some patients. In addition, earlier surgery may promote early neurological recovery.

Introduction

A traumatic spinal cord injury (TSCI) can have devastating physical, social and financial consequences for patients and their families (1). After a TSCI, prompt management and proper counseling are crucial to optimize long-term quality of life and social reintegration (2). To this end, early prediction of neurological recovery is essential for both patients and caregivers as it can guide treatment (e.g. surgical indication and procedures, care level, etc.) and allow to plan for the rehabilitation phase (e.g. specialized vs. non-specialized rehabilitation, discharge destination, return to work and activities, etc.).

Long-term spontaneous neurological recovery has been well documented after TSCI (3, 4), with most reports suggesting that about 30% of patients with American Spinal Association Injury Impairment Scale (AIS) grade A injury, 60% with AIS grade B injury, 80% with AIS grade C injury, and 10% with AIS grade D injury improve their AIS grade 1 year after the injury. In addition, although neurological recovery tends to plateau only at 12–18 months after the injury, it is believed that improvement mainly occurs within the first 3–4 months after the injury for about 80% of patients who eventually improve (4). However, despite this current state of knowledge, it remains difficult for clinicians during the acute care to counsel patients and families about the prognosis for neurological recovery, and therefore establish realistic goals for rehabilitation and community reintegration.

One major limitation of previous studies characterizing recovery after TSCI is the timing of the baseline neurological assessments. Although this was not documented in their study, Dvorak et al. (5) suggested that early motor improvement can occur within the first hours or days after the injury, and that the baseline neurological assessment should hence be performed before surgical intervention within 72 h of the injury. Performing the neurological assessment prior to surgery seems even more important nowadays, considering that the current trend for early surgery within 24 h of the injury is associated with improved neurological recovery 1 year after the injury (6, 7). Indeed, since surgical decompression aims at limiting the secondary injury to the spinal cord that occurs during the acute (<48 h) and subacute (48 h to 14 days) phases after the TSCI (1), it is surprising that the extent of recovery during the first 2 weeks after surgery has never been documented, as it could help improve our understanding of the impact of surgery on the process of neurological recovery.

In this context, the primary objective of this study is to characterize early neurological recovery in patients with TSCI (based on AIS grade changes between the pre-operative and post-operative neurological examinations). By doing so, this paper will also identify clinical factors associated with early perioperative improvement, with special attention to surgical timing, which will fill an important gap in our understanding of the effects of early surgery on neurological recovery. In a second step, the relationship between early neurological recovery and subsequent neurological recovery that occurs within the first year following the TSCI will be examined.

Methods

Study population

A retrospective cohort study based on a database cohort of 600 + individuals admitted to a single Level 1 trauma center in Montreal, Canada for an acute TSCI between May 2010 and June 2021 was completed. For the current study, patients were included if they were 18 years or older on the day of admission, sustained a traumatic TSCI (AIS grade A to D) with a neurological level of injury (NLI) between C0 and L1 upon admission, and were managed surgically at our institution for decompressive surgery within 72 h of the injury. To be included in the final study cohort, database participants were also required to have complete post-operative and follow-up neurological examinations. Patients were excluded if they had a neurological condition prior to the TSCI that could confound the neurological examinations (e.g. stroke, traumatic brain injury, cerebral palsy, pre-existing TSCI, etc.) or if their postoperative examination was conducted more than 14 days after surgery. All included patients provided informed written consent during acute care and the study was approved by the institutional review board.

Data collection

All data were collected by research assistants that were uninvolved in patient care or data analysis. All patients were recruited shortly after admission to our institution and data were collected prospectively thereafter.

Sociodemographic variables (age, sex, Charlson Comorbidity Index) were collected upon admission, along with the injury severity score (ISS), which is a widely used measure of overall trauma severity (8). The Charlson Comorbidity Index (CCI) was dichotomized as follows: presenting no pre-existing comorbidity vs. presenting at least 1 pre-existing comorbidity (9). The surgical delay was also collected and consisted in the number of hours between the initial trauma and the beginning of the surgical procedure (time of incision). There was no intra-operative neuro-monitoring.

Full neurological examinations are routinely performed in our institution prior to, and shortly after decompressive surgery. All neurological examinations were performed according to the International Standards for the Neurological Classification of Spinal Cord Injuries (ISNCSCI) (10). Preoperative examinations were performed by a trained member of the orthopedic spine surgery service whereas post-operative assessments were performed by one trained physiatrist (physical medicine and rehabilitation) specialized in the acute management of spinal cord injuries within 14 days after surgery, during the subacute stage of the injury, as it is defined by Ahuja et al. (1) Members from the spine surgery also examined patients daily to verify patients’ neurological status. If a discordance arose between the assessments of the physiatrist and the spine surgery team, they always reconvened and re-evaluated the patient together to ensure that the correct assessment was retained. In order to account for variability in examination timing, the delay between surgery and the post-operative neurological assessment was collected. An additional neurological assessment was performed in the early chronic phase to characterize the final neurological status, 6–12 months following the injury. Again, the timing of assessment was characterized using the delay between TSCI and follow-up.

All neurological assessments allowed to determine the AIS grade (A, B, C, D or E), the NLI (which corresponds to the most caudal neurological level with normal sensory and antigravity motor function, provided that there is normal (intact) sensory and motor function rostrally), and the AIS motor score (which corresponds to the total sum of motor function scores of the key-muscles tested in the ISNCSCI) (10). For all analyzes, the NLI was dichotomized as follows: C1-C8 (tetraplegia) vs. T1-L1 (paraplegia).

Outcome variable

The main outcome variable of this study consisted in the achievement of an early peri-operative neurological improvement, defined as achievement of an AIS grade improvement of at least one AIS grade between the pre-operative and post-operative period during the acute care hospitalization. Secondarily, the AIS conversion rate was also assessed in the subsequent period, defined as between the post-operative period (during the acute care hospitalization) and the follow-up assessment which occurred at the medical appointment in the chronic period (6–12 months post injury), which is when the final patients generally reach their maximal neurological recovery (3).

Statistical analyzes

Early peri-operative neurological changes were first displayed using crosstabs (e.g. pre-operative AIS grade vs. post-operative AIS grade). Then, the characteristics of patients who achieved early peri-operative improvement were compared to those of patients who did not reach this outcome using t-tests and chi-square tests for continuous and categorical variables respectively. If more than 20% of the cells in a crosstab presented expected values that were inferior to 5, a Maximum Likelihood Ratio Chi-square test was conducted (11).

Multiple logistic regression was then performed with variables that were significantly different at the bivariate level between the two groups (as well as with clinically relevant variables, as determined by a senior spine surgeon and an experienced physiatrist) in order to identify clinical factors associated with peri-operative AIS grade conversion and assess the impact of the timing of surgery.

Finally, univariate and multivariate analyzes (as described above) were also conducted to determine the relationship between the presence of early (peri-operative) AIS conversion and presence of late subsequent neurological recovery, while taking into account relevant confounding factors.

All statistics were performed using IBM SPSS Statistics v.27 (Chicago, IL) and the level of significance was set to 0.05 for all inferential analyzes. Any missing data were handled with pairwise deletion.

Results

After applying all the inclusion criteria, 171 patients remained. Of these, 29 were excluded because: (1) they presented a pre-existing neurological condition (n = 3), and (2) their post-operative neurological examination was performed later than 14 days after the surgery (n = 26). Hence, a total of 142 individuals were available for final analysis. All of these 142 individuals were operated for surgical decompression within 72 h of the injury. The average surgical delay was 24.9 ± 14.6 h, the median was 21.0 h and the interquartile range was 19.7 h. In total, 81 patients underwent cervical surgery (34 anterior cervical discectomies and fusions (ACDF), 26 posterior fusions with instrumentation, 3 anterior corpectomies, 3 laminoplasties, 9 combined antero-posterior ACDF plus posterior fusions with instrumentation, 1 laminoplasty plus caudal posterior fusion with instrumentation, and 2 anterior corpectomies plus posterior fusions with instrumentation) and 61 underwent thoracic, thoracolumbar or lumbar surgery (44 posterior fusions with instrumentation, 16 corpectomies, and 1 single level laminectomy).

Table 1 presents the AIS conversion rates in the peri-operative period following acute traumatic TSCI. In total, there were 24 AIS grade changes between the pre-operative and the post-operative neurological assessments. AIS grade improvement between these timepoints occurred in 18 of the 142 study participants (12.7%) while AIS grade deterioration occurred in 6 individuals. Specifically, early perioperative neurological improvement occurred in 8 of the 58 patients (13.8%) with initial AIS grade A, 6 of the 16 patients (37.5%) with initial AIS grade B, 2 of the 11 patients (11.1%) with initial AIS grade C, and 2 of the 50 patients (4%) with initial AIS grade D (Table 1). Patients who achieved this outcome had significantly shorter surgical delays (p < 0.001) and were more likely to present pre-operative AIS grades A and B injuries (P = 0.012), as compared to patients who did not display early AIS grade improvement (Table 2). AIS grade deterioration occurred in 1 patient with pre-operative AIS grade B, 2 patients with pre-operative AIS grade C and 3 patients with AIS grade D injuries.

Table 1.

AIS grade conversion in the peri-operative period (from pre- to post-operative assessment) following an acute traumatic TSCI (N = 142).

Post-op Pre-op	AIS grade A	AIS grade B	AIS grade C	AIS grade D	AIS grade E	Total
AIS grade A	50	6	2	0	0	58
AIS grade B	1	9	5	1	0	16
AIS grade C	1	1	14	2	0	18
AIS grade D	0	0	3	45	2	50
Total	52	16	24	48	2	142

- AIS grade, American Spinal Injury Association Impairment grade; TSCI, Traumatic spinal cord injury.

- Example: AIS grade A → There were 58 patients with pre-operative AIS grade A injuries. At the time of their post-operative assessment, 50/58 remained with an AIS grade A injury, 6 progressed to B and 2 to C. None (0) reached an AIS grade D or E.

- Light gray: cells in light gray represent patients who presented a forward conversion (improvement) in AIS grade between their pre-operative and post-operative assessments.

Table 2.

Univariate analysis of factors associated with early peri-operative neurological improvement (pre-operative to post-operative AIS grade conversion).

	Group 1: Achieved AIS grade conversion with surgery (n = 18)	Group 2: Did not achieve AIS grade conversion with surgery (n = 124)	P-Value
Sex, n = 142 Male, n (%) Female, n (%)	13 (72.2%) 5 (27.8%)	96 (77.4%) 28 (22.6%)	0.632a
Age, n = 142 <65 years, n (%) ≥65 years, n (%)	17 (94.4%) 1 (5.6%)	97 (78.2%) 27 (21.8%)	0.069a
ISS (mean ± SD), n = 127	20.1 ± 5.9	23.4 ± 8.5	0.121
Mechanism of injury, n = 142 Sports, n (%) Assault (blunt), n (%) Fall, n (%) Transport, n (%) Other, n (%)	0 (0%) 1 (5.6%) 6 (33.3%) 10 (55.6%) 1 (5.6%)	21 (16.9%) 5 (4.0%) 56 (45.2%) 39 (31.5%) 3 (2.4%)	0.060a
CCIb, n = 142 0, n (%) ≥ 1, n (%)	11 (61.1%) 7 (38.9%)	59 (47.6%) 65 (52.4%)	0.283
Surgical delay (mean ± SD), n = 142	16.9 ± 7.3	26.1 ± 15.0	<0.001
Pre-operative NLIb, n = 142 C1-C8, n (%) T1-L2, n (%)	11 (61.1%) 7 (38.9%)	72 (58.1%) 52 (41.9%)	0.806
Pre-operative AIScgrade, n = 142 A, n (%) B, n (%) C, n (%) D, n (%)	8 (44.4%) 6 (33.3%) 2 (11.1%) 2 (11.1%)	50 (40.3%) 10 (8.1%) 16 (12.9%) 48 (38.7%)	0.012a
Pre-operative AIScmotor score (mean ± SD), n = 142	45.2 ± 26.1	47.8 ± 19.2	0.135
Delay between surgery and post-op examination, days, n = 142 (mean ± SD)	5.722 ± 3.159	5.145 ± 3.771	0.538

^aMaximum likelihood ratio chi-square test conducted (>20% of crosstab cells had expected values that were inferior to 5).

^bCharlson comorbidity index.

^cAmerican spinal injury association impairment scale.

At the multivariate level, having a pre-operative AIS grade B (as opposed to AIS grade D) was associated with ten-fold odds of achieving peri-operative AIS grade conversion (OR = 9.676; P = 0.013). Longer surgical delays also remained negatively associated with the outcome (OR = 0.931; P = 0.040), with lower odds of perioperative improvement in patients with later surgery (Table 3). In addition to these variables, the delay between surgery and post-op examination was input as a potential confounder to minimize the risk of observation bias but it did not show significance in the final equation (P = 0.345).

Table 3.

Results from the multiple binary logistic regression analysis of factors associated with early peri-operative neurological improvement (AIS conversion from the pre- to post-operative assessment) N = 142.

Variables	Odds ratio	95% Confidence interval	P-value
Surgery delay (h)	0.931	0.870–0.997	0.040
Pre-operative AISagrade
A	2.133	0.401–11.341	0.374
B	9.676	1.628–57.401	0.013
C	2.662	0.325–21.836	0.362
D (reference)	–	–	–
Delay between surgery and post-op examination, days, n = 142 (mean ± SD)	1.069	0.931–1.228	0.345

^aAmerican spinal injury association impairment scale.

Out of the 124 patients who did not show improvement peri-operatively, 17 improved of at least 1 AIS grade between the post-operative assessment, and the follow-up visit, during the early chronic phase. More specifically, 9 of 52 (17.3%) patients with post-operative AIS grade A improved within the first year, as did 7 of 10 (70.0%) patients with post-operative AIS grade B, 14 of 17 (82.4%) patients with post-operative AIS grade C, and 6 of 45 (13.3%) patients with post-operative AIS grade D. On average, follow-up assessments were performed 329.8 ± 10.4 days following the initial trauma.

Out of the 140 patients who still had an opportunity for improvement at the time of their post-operative assessment (142 patients minus 2 individuals with AIS grade E upon post-operative examination), 44 achieved late neurological recovery (improvement between the post-operative and follow-up neurological assessments). These patients displayed significantly lower ISS on admission, as well as higher post-operative motor scores than individuals who did not manage late recovery. In addition, the former were significantly less likely to present a post-operative AIS grade A (as opposed to B or C) and seemed to present paraplegia in higher proportions, although this was not significant. Finally, there was a clear tendency toward a higher proportion of early recoverers in the group of late recoverers (i.e. individuals who achieved early peri-operative neurological recovery were more likely to also display neurological recovery in the chronic phase), but this was not significant either (P = 0.089) (Table 4).

Table 4.

Univariate analysis of factors associated with late neurological improvement (post-operative to early chronic phase AIS grade conversion).

	Group 1: Achieved late AIS grade conversion (n = 44)	Group 2: Did not achieve late AIS grade conversion (n = 96)	P-Value
Early peri-operative neurological improvement, n = 140 Yes, n (%) No, n (%)	8 (18.2%) 36 (81.8%)	8 (8.3%) 88 (91.7%)	0.089
Surgical delay, h (mean ± SD), n = 140	25.1 ± 15.2	24.9 ± 14.4	0.968
Sex, n = 140 Male, n (%) Female, n (%)	31 (70.5%) 13 (29.5%)	76 (79.2%) 20 (20.8%)	0.260
Age, n = 140 <65 years, n (%) ≥65 years, n (%)	35 (79.5%) 9 (20.5%)	77 (82.3%) 19 (17.7%)	0.927
ISS (mean ± SD), n = 125	20.0 ± 4.8	24.3 ± 9.2	<0.001
Mechanism of injury, n = 140 Sports, n (%) Assault (blunt), n (%) Fall, n (%) Transport, n (%) Other, n (%)	7 (15.9%) 2 (4.5%) 20 (45.5%) 13 (29.5%) 2 (4.5%)	14 (14.6%) 4 (4.2%) 42 (43.8%) 34 (35.4%) 2 (2.1%)	0.913a
CCIb, n = 140 0, n (%) ≥ 1, n (%)	21 (47.7%) 23 (52.3%)	48 (50.0%) 48 (50.0%)	0.803
Post-operative NLIb, n = 140 C1-C8, n (%) T1-L2, n (%)	29 (65.9%) 15 (34.1%)	49 (51.0%) 47 (49.0%)	0.100
Post-operative AIScgrade, n = 140 A, n (%) B, n (%) C, n (%) D, n (%)	9 (20.5%) 10 (22.7%) 19 (43.2%) 9 (20.5%)	43 (44.8%) 6 (6.3%) 5 (5.2%) 42 (43.8%)	<0.001a
Post-operative AISc motor score (mean ± SD), n = 140	43.9 ± 29.0	59.4 ± 25.9	0.002
Delay between TSCI and follow-up examination, days, n = 140 (mean ± SD)	342.0 ± 107.5	324.9 ± 99.5	0.357

^aMaximum likelihood ratio chi-square test conducted (>20% of crosstab cells had expected values that were inferior to 5).

^bCharlson Comorbidity Index.

^cAmerican Spinal Injury Association Impairment Scale

At the multivariate level, individuals with post-operative AIS grades of B and C were highly more likely to achieve late neurological improvement when referenced to AIS grade D individuals (AIS grade B: OR = 39.633; P = 0.002; AIS grade C: OR = 26.515; p < 0.001). As for the achievement of early peri-operative neurological recovery, it remained unsignificant at the multivariate level (P = 0.106). The delay between the TSCI and the timing of the follow-up neurological assessment was also input as a potential confounder, once again to minimize the risk of observation bias. However, it was not a significant of neurological improvement (P = 0.969) (Table 5).

Table 5.

Results from the multiple binary logistic regression analysis of factors associated with late neurological improvement (post-operative to early chronic phase AIS grade conversion).

Variables	Odds ratio	95% Confidence interval	P-value
Perioperative neurological improvement (Yes)	0.275	0057– 1.317	0.106
Post-op AISagrade
A	3.000	0.473–19.015	0.244
B	39.633	4.034– 389.422	0.002
C	26.515	3.818– 184.152	<0.001
ISSb	0.893	0.823–1.018	0.031
Post-op AIS motor score	1.001	0.975–1.027	0.960
Delay between TSCI and follow-up examination	1.000	0.995–1.005	0.969

^aAmerican spinal injury association impairment scale.

^bInjury severity score.

Discussion

This study is the first to document early peri-operative neurological changes following TSCI. Current guidelines recommend that a clinical neurological assessment be performed within 72 h of the accident to determine the preliminary prognosis for neurological recovery (12). Adding to these recommendations, our study suggests that it is also important to document the early perioperative changes in neurological status – within the first 2 weeks after surgery – as it can help direct acute care clinicians in establishing early prognosis after traumatic TSCI. In doing so, the reported findings also highlight the need to obtain a proper baseline neurological assessment prior to performing surgery. Finally, by identifying a significant association between early surgery and perioperative neurological improvement, this study also supports recent research in favor of prompt surgical management following TSCI and raises questions pertaining to the mechanisms underlying surgical effectiveness.

Early perioperative neurological improvement (improvement of AIS grade) was observed predominantly for motor-complete TSCI. Overall, 8 of the 58 patients (13.8%) with AIS grade A, 6 of the 16 patients (37.5%) with AIS grade B, 2 of the 18 patients (11.1%) with AIS grade C, and 2 of the 50 patients (4%) with AIS grade D TSCI improved their AIS grade within the first 2 weeks following surgery. This somewhat contrasts with previous literature on spontaneous neurological recovery, which tends to describe more recovery in patients with AIS grade C injuries (3). This finding might suggest that early neurological improvements possibly depend on different mechanisms. More specifically, it can be hypothesized that early perioperative neurological improvements are linked to the initial amount of preoperative spinal cord compression that is eventually relieved by decompressive surgery. This would then explain why motor-complete patients seem to display more peri-operative improvements as they typically present greater compression of the spinal cord (as well as more intramedullary abnormalities), such that they are subjected to greater secondary injury prior to decompressive surgery and would thus benefit more from surgery than motor-incomplete individuals (13–16).

For individuals with motor-complete injuries who do not improve their AIS grade within 2 weeks of the surgery, results of this study are also in line with the TSCI literature and suggest that the potential for recovery varies significantly between AIS grade A (complete TSCI) and grade B (sensory-incomplete) injuries, with a higher potential for recovery within the first year in AIS grade B individuals (4). However, to our knowledge, this is the first study to suggest that while individuals with an initial (pre-operative) AIS grade A injury may display relatively higher potential for neurological recovery in the peri-operative period, those who remain with a complete TSCI two weeks after the injury will show a relatively poor rate of neurological recovery in the subsequent phase (with only 17% (9 of 52) of AIS conversion 1 year after the TSCI). On the opposite, failing to improve within 2 weeks of surgery when sustaining an AIS grade B injury is not associated with poorer prognosis for subset1 year, as 70% of patients with pre-operative AIS grade B injury who remained with AIS grade B injuries post-operatively eventually improved. In other words, these results suggest that absence of perioperative neurological improvement needs to be considered with care and in relation to pre-operative baseline neurological status. Hence, while absence of perioperative improvement in pre-operative AIS grade B individuals is not necessarily suggestive of poor long-term prognosis – as 70% of these will improve – the same scenario in pre-operative AIS grade A patients is not associated with the same positive long-term outcomes. Thus, these results highlight the importance of performing the neurological assessment at these two timepoints (pre- and post-operative (2 weeks) after a complete TSCI), in order to refine the early estimation of the neurological prognosis following a complete (AIS grade A) TSCI.

As for motor-incomplete individuals, this study is in line with the TSCI literature, suggesting that their potential for neurological recovery can be substantial (and highly variable) within the first year after the injury (4). However, as mentioned above, the presented results also show that the neurological improvement in the peri-operative period in this group is fairly limited as compared to patients with motor-complete TSCI. However, it is important to stress the fact that this result does not suggest that early surgical management is not warranted in motor-incomplete TSCI, but, rather supports the idea that processes underlying recovery after TSCI may be influenced differently following a motor-complete as opposed to a motor-incomplete injury. Indeed, as previously discussed, it is well known that motor-incomplete TSCI generally involve lesser compression of the spinal cord (and thus lesser degree of secondary injury to the spinal cord and greater preservation of neurological structures), which then may explain why early surgical decompression may have a lower impact on the perioperative improvement as compared to motor-complete injuries. However, since surgery is still known to impact long-term neurological recovery in motor-incomplete patients, this finding may suggest different mechanisms for the effectiveness of early surgery in motor-complete vs. motor-incomplete patients, possibly through allowing quicker rehabilitation management, which may further maximize patients’ outcomes, in terms of functional recovery and quality of life.

Results from the multivariate analyzes further support these results, as the pre-operative AIS grade and the shorter surgical delay being the only assessed clinical factors associated with the presence of AIS conversion during the peri-operative period. Moreover, an increased likelihood of neurological improvement within two weeks of surgery was identified for individuals with an initial AIS grade B injury, and in the subsequent phases for AIS grade B and C injuries. Earlier surgery was associated with an increased likelihood of conversion of the AIS grade within the first 2 weeks after surgery, which supports our overarching hypothesis, especially since the timing of surgery was not associated with later improvement. We therefore strongly recommend that the impact of surgery on recovery in research studies be assessed early within two weeks of the surgery, in addition to the recovery occurring later during the chronic phase. The beneficial role of early surgery on neurological recovery is already supported by previous studies (6, 7). However, our study is the first to investigate the association between early surgery and early vs. late recovery, thereby providing more insight on the benefits and mechanisms of early surgery after TSCI. It is possible that decompressive surgery may have its predominant role in limiting the secondary injury to the spinal cord during the acute and subacute phases, before later phases through which rehabilitation measures and neural plasticity are mostly in effect. Because of these findings, additional analyzes shown in Supplementary data (Supplementary Table 1) were performed to evaluate the potential impact of key surgical variables on perioperative neurological improvements. Overall, surgical variables (type of approach, number of levels instrumented) did not influence perioperative outcomes except for the number of levels fuzed in cervical surgeries. However, due to the large heterogeneity of underlying spinal cord lesions and due to the numerous confounding factors in play, this result is difficult to interpret and must be regarded with caution.

Limitations

Regarding the primary objective, the authors acknowledge that the conclusions are limited by the small number of patients after stratifying by AIS grade and by the number of patients achieving – or not achieving – neurological improvement, although we were still able to identify predictors of early recovery from our analyses. Unfortunately, the small number of patients means we could not examine all variables optimally, such as the NLI which we could only dichotomize in two categories (tetraplegia vs paraplegia) and not four (high tetraplegia, low tetraplegia, high thoracic and thoracolumbar) as is customary. In addition, a larger study is required to further improve our understanding of the mechanisms and benefits of early surgery. While the benefits of earlier surgery on AIS grade conversion was only observed for the 2-week timeframe after surgery, it is also possible that our inclusion criteria with regard to timing of surgery (only patients undergoing surgery within 72 h of the injury) have influenced our results. Also, it remains possible that recovery past the 2-week timeframe may have been associated with surgery if we had included patients with surgery performed later than 72 h after the injury. However, our actual practice is strongly focused around early surgery, and inclusion of those patients (e.g. patients transferred from other countries, associated injuries impacting on the safety for early surgery) would have introduced potential outliers or biases.

We also acknowledge that the results can be influenced by the 2-week timeframe that was set for defining early improvement. We believe that this timeframe is optimal for two reasons. First on a clinical viewpoint, patients with TSCI typically remain in the acute center for 3 weeks or more in Canada (17), such that re-assessing the neurological status 2 weeks after surgery will help defining an early prognosis during acute care based on our findings. Second, this timeframe also coincides with acute and subacute phases after the TSCI (1), which are thought to be impacted by early spine surgery.

Also, the authors recognize that further studies will be required to better understand the factors promoting early peri-operative improvement. In particular, the authors recommend that the relationship between spinal cord perfusion pressure and early neurological changes be examined in future research (18).

Finally, it is important to highlight that this study only considered the AIS grade as an indicator of neurological status and that although it is often regarded as the most important neurological outcome in outcome studies (7, 19), future research should be conducted on other important aspects of perioperative neurological recovery, including changes in motor and sensory scores.

Conclusion

In conclusion, this study provides important insight on the course of neurological recovery after TSCI and supports the hypothesis that early neurological improvements can occur as early as within two weeks of decompressive surgery, especially in patients with pre-operative AIS grade B injuries. Furthermore, the importance of early surgery for achieving early neurological improvement provides important new insights on the potential therapeutic mechanisms in play. In turn, the findings of this study may serve as an additional data point on which acute care clinicians could rely to provide improved counseling in the early stages after the injury, while taking into account all other relevant variables. In this sense, we recommend that full neurological assessments be performed prior to and shortly after surgery (during the subacute phase of the injury) to improve accuracy of prognosis and facilitate planning for rehabilitation and community reintegration.

Acknowledegements

We thank all the research staff at the Laboratoire d’Orthopédie-Colonne de l’Hôpital du Sacré-Coeur de Montréal. We also thank our patients for their essential participation in all our research initiatives.

Disclaimer statements

Contributors Dr. Mac-Thiong is chairholder of the Medtronic research chair in spinal trauma at Université de Montréal, owns stocks and is a board member in Spinologics, and has received a scholarship and research grants from the Fonds de recherche du Québec – Santé, an investigator-initiated research grant from Medline Industries, educational grants from Medtronic and Depuy-Synthes, as well as research grants from the U.S. Department of Defense – Congressionally directed medical research programs, Craig H. Neilsen Foundation, from Social TSCIences and Humanities Research Council, Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council, Praxis Spinal Cord Institute, Abbvie, Asahi Kasei Pharma and Vertex Pharmaceutical.

Dr. Richard-Denis has received a scholarship and research grants from the Fonds de recherche du Québec – Santé, an investigator-initiated research grant from Medline Industries, and a research grant from Praxis Spinal Cord Institute.

Dr. Briand, Mr. Dionne and Mr. Fournier have nothing to disclose.

We certify that all persons who met the authorship criteria were listed as authors on this paper. All the authors also confirm that they participated in the intellectual aspects of this work and take responsibility for its contents.

Funding This research was supported (in whole or in part) by HCA and/or an HCA affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA healthcare or any of its affiliated entities.

Conflicts of interest Authors have no conflict of interests to declare.