Inhibition of Neurogenic Inflammatory Pathways Associated with the Reduction in Discogenic Back Pain

Canseco Jose A.,Levy Hannah A.,Karamian Brian Abedi,Blaber Olivia,Chang Michael,Patel Neil,Curran John,Hilibrand Alan S.,Schroeder Gregory D.,Vaccaro Alexander R.,Markova Dessislava Z.,Surrey David E. 대한척추외과학회 2023 Asian Spine Journal Vol.17 No.6

Study Design: Retrospective cohort study.Purpose: This study aimed to determine whether the initiation of anti-calcitonin gene-related peptide (CGRP inhibitor) medication therapy for migraines was also associated with improvements in back/neck pain, mobility, and function in a patient population with comorbid degenerative spinal disease and migraine.Overview of Literature: CGRP upregulates pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, brain-derived neurotrophic factor, and nerve growth factor in spinal spondylotic disease, which results in disc degeneration and sensitization of nociceptive neurons. Although CGRP inhibitors can quell neurogenic inflammation in migraines, their off-site efficacy as a therapeutic target for discogenic back/neck pain conditions remains unknown.Methods: All adult patients diagnosed with spinal spondylosis and migraine treated with CGRP inhibitors at a single academic institution between 2017 and 2020 were retrospectively identified. Patient demographic and medical data, follow-up duration, migraine severity and frequency, spinal pain, functional status, and mobility before and after the administration of CGRP inhibitors were collected. Paired univariate analysis was conducted to determine significant changes in spinal pain, headache severity, and headache frequency before and after the administration of CGRP inhibitors. The correlation between changes in the spinal pain score and functional or mobility improvement was assessed with Spearman’s rho.Results: In total, 56 patients were included. The mean follow-up time after the administration of CGRP inhibitors was 123 days for spinal pain visits and 129 days for migraine visits. Back/neck pain decreased significantly (<i>p</i> <0.001) from 6.30 to 4.36 after starting CGRP inhibitor therapy for migraine control. As recorded in the spine follow-up notes, 25% of patients experienced a functional improvement in the activities of daily living, and 17.5% experienced mobility improvement while taking CGRP inhibitors. Change in back/ neck pain moderately correlated (ρ=−0.430) with functional improvement but was not correlated with mobility improvement (ρ=−0.052).Conclusions: Patients taking CGRP inhibitors for chronic migraines with comorbid degenerative spinal conditions experienced significant off-target reduction of back/neck pain.

Correction of Spinal Sagittal Alignment after Posterior Lumbar Decompression: Does Severity of Central Canal Stenosis Matter?

Trenchfield Delano,Lee Yunsoo,Lambrechts Mark J.,D’Antonio Nicholas,Heard Jeremy,Paulik John,Somers Sydney,Rihn Jeffrey A.,Kurd Mark,Kaye David,Canseco Jose,Hilibrand Alan,Vaccaro Alexander Richard,Ke 대한척추외과학회 2023 Asian Spine Journal Vol.17 No.6

Study Design: This study adopted a retrospective study design.Purpose: Our study aimed to investigate the impact of central canal stenosis severity on surgical outcomes and lumbar sagittal correction after lumbar decompression.Overview of Literature: Studies have evaluated sagittal correction in patients with central canal stenosis after lumbar decompression and the association of stenosis severity with worse preoperative sagittal alignment. However, none have evaluated the impact of spinal stenosis severity on sagittal correction.Methods: Patients undergoing posterior lumbar decompression (PLD) of ≤4 levels were divided into severe and non-severe central canal stenosis groups based on the Lee magnetic resonance imaging (MRI) grading system. Patients without preoperative MRI or inadequate visualization on radiographs were excluded. Surgical characteristics, clinical outcomes, and sagittal measurements were compared. Multivariate logistic regression was performed to determine the predictors of pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), and pelvic incidence minus lumbar lordosis (PI–LL).Results: Of the 142 patients included, 39 had severe stenosis, and 103 had non-severe stenosis. The mean follow-up duration for the cohort was 4.72 months. Patients with severe stenosis were older, had higher comorbidity indices and levels decompressed, and longer lengths of stay and operative times (<i>p</i> <0.001). Although those with severe stenosis had lower lordosis, lower SS, and higher PI–LL mismatch preoperatively, no differences in Delta LL, SS, PT, or PI–LL were observed between the two groups (<i>p</i> >0.05). On multivariate regression, severe stenosis was a significant predictor of a lower preoperative LL (estimate=−5.243, <i>p</i> =0.045) and a higher preoperative PI–LL mismatch (estimate=6.192, <i>p</i> =0.039). No differences in surgical or clinical outcomes were observed (<i>p</i> >0.05).Conclusion: Severe central lumbar stenosis was associated with greater spinopelvic mismatch preoperatively. Sagittal balance improved in both patients with severe and non-severe stenosis after PLD to a similar degree, with differences in sagittal parameters remaining after surgery. We also found no differences in postoperative outcomes associated with stenosis severity.

Serotonin Reuptake Inhibitor Increases Pseudarthrosis Rates in Anterior Cervical Discectomy and Fusions

Lambrechts Mark James,D'Antonio Nicholas,Toci Gregory,Karamian Brian,Pezzulo Josuhu,Farronato Dominic,Canseco Jose,Kaye Ian David,Woods Barrett,Rihn Jeffrey,Kurd Mark,Lee Joseph,Hilibrand Alan,Kepler 대한척추외과학회 2023 Asian Spine Journal Vol.17 No.2

Study Design: Retrospective cohort.Purpose: To determine (1) the effects of serotonin reuptake inhibitors in pseudarthrosis rates after anterior cervical decompression and fusion (ACDF) and (2) to identify patient-reported outcome measures in patients taking serotonin reuptake inhibitors. Overview of Literature: Recent literature suggests that selective serotonin reuptake inhibitors (SSRIs) may inhibit fracture healing via downregulation of osteoblast differentiation. Spinal fusion supplementation with osteoblast-rich substances enhances spinal fusion, thus SSRIs may be detrimental.Methods: Patients with 1-year postoperative dynamic cervical spine radiographs following ACDF were grouped into serotonin reuptake inhibitor prescriptions (SSRI, serotonin-norepinephrine reuptake inhibitor [SNRI], or tricyclic antidepressant [TCA]) and no prescription (atypical antidepressant or no antidepressant). Pseudarthrosis was defined as ≥1 mm interspinous process motion on dynamic radiographs. Logistic regression models were controlled for confounding to analyze pseudarthrosis rates. Alpha was set at p - values of <0.05.Results: Of the 523 patients who meet the inclusion criteria, 137 (26.2%) were prescribed an SSRI, SNRI, or TCA. Patients with these prescriptions were more likely to have pseudarthrosis (p =0.008) but not a revision surgery due to pseudarthrosis (p =0.219). Additionally, these patients had worse 1-year postoperative mental component summary (MCS)-12 (p =0.015) and Neck Disability Index (NDI) (p =0.006). The multivariate logistic regression analysis identified SSRI/SNRI/TCA use (odds ratio [OR], 1.82; 95% confidence interval [CI], 1.11–2.99; p =0.018) and construct length (OR, 1.91; 95% CI, 1.50–2.44; p <0.001) as pseudarthrosis predictors. A SSRI/SNRI/TCA prescription was a revision surgery predictor due to adjacent segment disease on univariate analysis (OR, 2.51; p =0.035) but not on multivariate logistic regression analysis (OR, 2.24; p =0.10).Conclusions: Patients taking serotonin reuptake-inhibiting antidepressants are at increased risk of worse postoperative outcome scores, including NDI and MCS-12, likely due to their underlying depression. This may contribute to their greater likelihood of having adjacent segment surgery. Additionally, preoperative use of serotonin reuptake inhibitors in patients undergoing an ACDF is a predictor of radiographic pseudarthrosis but not pseudarthrosis revision.

Significance of Facet Fluid Index in Anterior Cervical Degenerative Spondylolisthesis

Lee Yunsoo,Heard Jeremy C.,Lambrechts Mark J.,Kern Nathaniel,Wiafe Bright,Goodman Perry,Mangan John J.,Canseco Jose A.,Kurd Mark F.,Kaye Ian D.,Hilibrand Alan S.,Vaccaro Alexander R.,Kepler Christophe 대한척추외과학회 2024 Asian Spine Journal Vol.18 No.1

Study Design: Retrospective cohort study.Purpose: To correlate cervical facet fluid characteristics to radiographic spondylolisthesis, determine if facet fluid is associated with instability in cervical degenerative spondylolisthesis, and examine whether vertebral levels with certain facet fluid characteristics and spondylolisthesis are more likely to be operated on.Overview of Literature: The relationship between facet fluid and lumbar spondylolisthesis is well-documented; however, there is a paucity of literature investigating facet fluid in degenerative cervical spondylolisthesis.Methods: Patients diagnosed with cervical degenerative spondylolisthesis were identified from a hospital’s medical records. Demographic and surgical characteristics were collected through a structured query language search and manual chart review. Radiographic measurements were made on preoperative MRIs for all vertebral levels diagnosed with spondylolisthesis and adjacent undiagnosed levels between C3 and C6. The facet fluid index was calculated by dividing the facet fluid measurement by the width of the facet. Bivariate analysis was conducted to compare facet characteristics based on radiographic spondylolisthesis and spondylolisthesis stability.Results: We included 154 patients, for whom 149 levels were classified as having spondylolisthesis and 206 levels did not. The average facet fluid index was significantly higher in patients with spondylolisthesis (0.26±0.07 vs. 0.23±0.08, p <0.001). In addition, both fluid width and facet width were significantly larger in patients with spondylolisthesis (p <0.001 each). Cervical levels in the fusion construct demonstrated a greater facet fluid index and were more likely to have unstable spondylolisthesis than stable spondylolisthesis (p <0.001 each).Conclusions: Facet fluid index is associated with cervical spondylolisthesis and an increased facet size and fluid width are associated with unstable spondylolisthesis. While cervical spondylolisthesis continues to be an inconclusive finding, vertebral levels with spondylolisthesis, especially the unstable ones, were more likely to be included in the fusion procedure than those without spondylolisthesis.

Incidence, Risk Factors, and Outcomes of Incidental Durotomy during Lumbar Spine Decompression with or without Fusion

Toci Gregory,Lambrechts Mark James,Issa Tariq,Karamian Brian Abedi,Siegel Nicholas,Antonio Nicholas D’,Canseco Jose,Kurd Mark,Woods Barrett,Kaye Ian David,Hilibrand Alan,Kepler Christopher,Vaccaro Ale 대한척추외과학회 2023 Asian Spine Journal Vol.17 No.4

Study Design: Retrospective cohort study.Purpose: The primary objective of this study was to determine the incidence and risk factors for incidental durotomies during lumbar decompression surgeries. In addition, we aimed to determine the changes in patient-reported outcome measures (PROMs) based on incidental durotomy status.Overview of Literature: There is limited literature investigating the affect of incidental durotomy on patient reported outcome measures. While the majority of research does not suggest differences in complications, readmission, or revision rates, many studies rely on public databases, and their sensitivity and specificity for identifying incidental durotomies is unknown.Methods: Patients undergoing lumbar decompression with or without fusion at a single tertiary care center were grouped based on the presence of a durotomy. Multivariate analysis was performed for length of stay (LOS), hospital readmissions, and changes in PROMs. To identify surgical risk factors for durotomy, 3:1 propensity matching was performed using stepwise logistic regression. The sensitivity and specificity of the International Classification of Disease, 10th revision (ICD-10) codes (G96.11 and G97.41) were also assessed.Results: Of the 3,684 consecutive patients who underwent lumbar decompressions, 533 (14.5%) had durotomies, and a complete set of PROMs (preoperative and 1-year postoperative) were available for 737 patients (20.0%). Incidental durotomy was an independent predictor of increased LOS but not hospital readmission or worse PROMs. The durotomy repair method was not associated with hospital readmission or LOS. However, repair with collagen graft and suture predicted reduced improvement in Visual Analog Scale back (<i>β</i> =2.56, <i>p</i>=0.004). Independent risk factors for incidental durotomies included revisions (odds ratio [OR], 1.73; <i>p</i><0.001), levels decompressed (OR, 1.11; <i>p</i>=0.005), and preoperative diagnosis of spondylolisthesis or thoracolumbar kyphosis. The sensitivity and specificity of ICD-10 codes were 5.4% and 99.9%, respectively, for identifying durotomies.Conclusions: The durotomy rate for lumbar decompressions was 14.5%. No differences in outcomes were detected except for increased LOS. Database studies relying on ICD codes should be interpreted with caution due to the limited sensitivity in identifying incidental durotomies.

A Comparison of Radiographic Alignment between Bilateral and Unilateral Interbody Cages in Patients Undergoing Transforaminal Lumbar Interbody Fusion

Lambrechts Mark James,Heard Jeremy,D’Antonio Nicholas,Bodnar John,Schneider Gregory,Bloom Evan,Canseco Jose,Woods Barrett,Kaye Ian David,Kurd Mark Faisal,Rihn Jeffrey,Hilibrand Alan,Schroeder Gregory 대한척추외과학회 2023 Asian Spine Journal Vol.17 No.4

Study Design: Retrospective cohort study.Purpose: To compare radiographic outcomes between unilateral and bilateral cage placement in transforaminal lumbar interbody fusions (TLIF) and to determine if the rate of fusion at the 1-year postoperative point was different in patients who received bilateral versus unilateral cages.Overview of Literature: There is no clear evidence to dictate whether bilateral or unilateral cages promote superior radiographic or surgical outcomes in TLIF.Methods: Patients >18 years old who underwent primary one- or two-level TLIFs at our institution were identified and propensitymatched in a 3:1 fashion (unilateral:bilateral). Patient demographics, surgical characteristics, and radiographic outcomes, including vertebral endplate obliquity, segmental lordosis, subsidence, and fusion status, were compared between groups.Results: Of the 184 patients included, 46 received bilateral cages. Bilateral cage placement was associated with greater subsidence (1.06±1.25 mm vs. 0.59±1.16 mm, <i>p</i>=0.028) and enhanced restoration of segmental lordosis (5.74°±14.1° vs. −1.57°±10.9°, <i>p</i>=0.002) at the 1-year postoperative point, while unilateral cage placement was associated with an increased correction of endplate obliquity (−2.02°±4.42° vs. 0.24°±2.81°, <i>p</i><0.001). Bilateral cage placement was significantly associated with radiographic fusion on bivariate analysis (89.1% vs. 70.3%, <i>p</i>=0.018) and significantly predicted radiographic fusion on multivariable regression analysis (estimate, 1.35; odds ratio, 3.87; 95% confidence interval, 1.51–12.05; <i>p</i>=0.010).Conclusions: Bilateral interbody cage placement in TLIF procedures was associated with restoration of lumbar lordosis and increased fusion rates. However, endplate obliquity correction was significantly greater for patients who received a unilateral cage.

Effect of Interbody Composition on the Development of Pseudarthrosis Following Anterior Cervical Discectomy and Fusion

D’Antonio Nicholas,Lambrechts Mark James,Heard Jeremy,Bertiaume Emily,Toci Gregory,Karamian Brian Abedi,Breyer Garrett,Bodnar John,Canseco Jose,Hilibrand Alan,Schroeder Gregory,Vaccaro Alexander Richa 대한척추외과학회 2023 Asian Spine Journal Vol.17 No.3

Study Design: Retrospective cohort study.Purpose: To determine if polyetheretherketone (PEEK) or titanium alloy cages increase the rate of pseudarthrosis development or revision surgery rate compared with structural allograft following anterior cervical discectomy and fusion (ACDF) and identify if the cage type results in differences in patient-reported outcome measures (PROMs) versus structural allograft.Overview of Literature: PEEK and titanium alloy cages have become popular options for ACDF intervertebral spacers. However, while data is beginning to emerge on how cage types affect arthrodesis rates, the effect of their composition on PROMs is less clear.Methods: All patients aged >18 years who underwent primary one- to four-level ACDF at a single institution were retrospectively identified. Propensity matching was performed to compare patients’ PEEK or titanium alloy cages with structural allograft. Multivariate logistic regression analysis was performed to measure the effect of interbody spacer composition on the likelihood of pseudarthrosis development.Results: Of the 502 patients who received structural allograft and had 1-year postoperative dynamic radiographs, 96 patients were propensity matched to 32 patients who received a PEEK cage, and 162 patients were propensity matched to 54 patients who received a titanium alloy cage. Multivariate logistic regression analysis identified that PEEK cage implants (odds ratio [OR], 3.34; p =0.007) predicted pseudarthrosis development compared with structural allograft implantation. Titanium alloy cage (OR, 1.64; p =0.156) implantation was not predictive of pseudarthrosis. One-year postoperative PROMs were not significantly different between patients who received PEEK or titanium alloy cages and those who received structural allograft (all p >0.05).Conclusions: Compared with structural allograft, receiving a PEEK cage increased the risk of pseudarthrosis development following ACDF, whereas receiving a titanium alloy cage had no significant effect on pseudarthrosis development. One-year postoperative patient-reported outcomes were similar between patients who received structural allograft, PEEK, and titanium alloy interbody spacers.

Modified Frailty Index as a Predictor of Postoperative Complications and Patient-Reported Outcomes after Posterior Cervical Decompression and Fusion

Lambrechts Mark James,Tran Khoa,Conaway William,Karamian Brian Abedi,Goswami Karan,Li Sandi,O'Connor Patrick,Brush Parker,Canseco Jose,Kaye Ian David,Woods Barrett,Hilibrand Alan,Schroeder Gregory,Vac 대한척추외과학회 2023 Asian Spine Journal Vol.17 No.2

Study Design: A retrospective cohort study.Purpose: To determine whether the 11-item modified frailty index (mFI) is associated with readmission rates, complication rates, revision rates, or differences in patient-reported outcome measures (PROMs) for patients undergoing posterior cervical decompression and fusion (PCDF).Overview of Literature: mFI incorporates preexisting medical comorbidities and dependency status to determine physiological reserve. Based on previous literature, it may be used as a predictive tool for identifying postoperative clinical and surgical outcomes.Methods: Patients undergoing elective PCDF at our urban academic medical center from 2014 to 2020 were included. Patients were categorized by mFI scores (0–0.08, 0.09–0.17, 0.18–0.26, and ≥0.27). Univariate statistics compared demographics, comorbidities, and clinical/surgical outcomes. Multiple linear regression analysis evaluated the magnitude of improvement in PROMs at 1 year.Results: A total of 165 patients were included and grouped by mFI scores: 0 (n=36), 0.09 (n=62), 0.18 (n=42), and ≥0.27 (n=30). The severe frailty group (mFI ≥0.27) was significantly more likely to be diabetic (<i>p</i> <0.001) and have a greater Elixhauser comorbidity index (<i>p</i> =0.001). They also had worse baseline Physical Component Score-12 (PCS-12) (<i>p</i> =0.011) and modified Japanese Orthopaedic Association (mJOA) (<i>p</i> =0.012) scores and worse 1-year postoperative PCS-12 (<i>p</i> =0.008) and mJOA (<i>p</i> =0.001) scores. On regression analysis, an mFI score of 0.18 was an independent predictor of greater improvement in ΔVisual Analog Scale neck (<i>β</i> =−2.26, <i>p</i> =0.022) and ΔVAS arm (<i>β</i> =−1.76, <i>p</i> =0.042). Regardless of frailty status, patients had similar 90-day readmission rates (<i>p</i> =0.752), complication rates (<i>p</i> =0.223), and revision rates (<i>p</i> =0.814), but patients with severe frailty were more likely to have longer hospital length of stay (<i>p</i> =0.006) and require non-home discharge (<i>p</i> <0.001).Conclusions: Similar improvements across most PROMs can be expected irrespective of the frailty status of patients undergoing PCDF. Complication rates, 90-day readmission rates, and revision rates are not significantly different when stratified by frailty status. However, patients with severe frailty are more likely to have longer hospital stays and require non-home discharge.

How Does the Severity of Neuroforaminal Compression in Cervical Radiculopathy Affect Outcomes of Anterior Cervical Discectomy and Fusion

Lambrechts Mark J.,Issa Tariq Z.,Lee Yunsoo,Tran Khoa S.,Heard Jeremy,Purtill Caroline,Fried Tristan B.,Oh Samuel,Kim Erin,Mangan John J.,Canseco Jose A.,Kaye I. David,Rihn Jeffrey A.,Hilibrand Alan S 대한척추외과학회 2023 Asian Spine Journal Vol.17 No.6

Study Design: This study is a retrospective cohort study.Purpose: This study aims to determine whether preoperative neuroforaminal stenosis (FS) severity is associated with motor function patient-reported outcome measures (PROMs) following anterior cervical discectomy and fusion (ACDF).Overview of Literature: Cervical FS can significantly contribute to patient symptoms. While magnetic resonance imaging (MRI) has been used to classify FS, there has been limited research into the impact of FS severity on patient outcomes.Methods: Patients undergoing primary, elective 1–3 level ACDF for radiculopathy at a single academic center between 2015 and 2021 were identified retrospectively. Cervical FS was evaluated using axial T2-weighted MRI images via a validated grading scale. The maximum degree of stenosis was used for multilevel disease. Motor symptoms were classified using encounters at their final preoperative and first postoperative visits, with examinations ≤3/5 indicating weakness. PROMs were obtained preoperatively and at 1-year follow-up. Bivariate analysis was used to compare outcomes based on stenosis severity, followed by multivariable analysis.Results: This study included 354 patients, 157 with moderate stenosis and 197 with severe stenosis. Overall, 58 patients (16.4%) presented with upper extremity weakness ≤3/5. A similar number of patients in both groups presented with baseline motor weakness (13.5% vs. 16.55, <i>p</i> =0.431). Postoperatively, 97.1% and 87.0% of patients with severe and moderate FS, respectively, experienced full motor recovery (<i>p</i> =0.134). At 1-year, patients with severe neuroforaminal stenosis presented with significantly worse 12-item Short Form Survey Physical Component Score (PCS-12) (33.3 vs. 37.3, <i>p</i> =0.049) but demonstrated a greater magnitude of improvement (Δ PCS-12: 5.43 vs. 0.87, <i>p</i> =0.048). Worse stenosis was independently associated with greater ΔPCS-12 at 1-year (β =5.59, <i>p</i> =0.022).Conclusions: Patients with severe FS presented with worse preoperative physical health. While ACDF improved outcomes and conferred similar motor recovery in all patients, those with severe FS reported much better improvement in physical function.