Studying missingness in spinal cord injury data: challenges and impact of data imputation.

BACKGROUND: In the last decades, medical research fields studying rare conditions such as spinal cord injury (SCI) have made extensive efforts to collect large-scale data. However, most analysis methods rely on complete data. This is particularly troublesome when studying clinical data as they are prone to missingness. Often, researchers mitigate this problem by removing patients with missing data from the analyses. Less commonly, imputation methods to infer likely values are applied. OBJECTIVE: Our objective was to study how handling missing data influences the results reported, taking the example of SCI registries. We aimed to raise awareness on the effects of missing data and provide guidelines to be applied for future research projects, in SCI research and beyond. METHODS: Using the Sygen clinical trial data (n = 797), we analyzed the impact of the type of variable in which data is missing, the pattern according to which data is missing, and the imputation strategy (e.g. mean imputation, last observation carried forward, multiple imputation). RESULTS: Our simulations show that mean imputation may lead to results strongly deviating from the underlying expected results. For repeated measures missing at late stages (> = 6 months after injury in this simulation study), carrying the last observation forward seems the preferable option for the imputation. This simulation study could show that a one-size-fit-all imputation strategy falls short in SCI data sets. CONCLUSIONS: Data-tailored imputation strategies are required (e.g., characterisation of the missingness pattern, last observation carried forward for repeated measures evolving to a plateau over time). Therefore, systematically reporting the extent, kind and decisions made regarding missing data will be essential to improve the interpretation, transparency, and reproducibility of the research presented.

Two-year clinical outcomes of a multicenter randomized controlled trial comparing two interspinous spacers for treatment of moderate lumbar spinal stenosis.

BACKGROUND: Interspinous spacers are a minimally invasive surgical alternative for patients with lumbar spinal stenosis (LSS) unresponsive to conservative care. The purpose of this prospective, multicenter, randomized, controlled trial was to compare 2-year clinical outcomes in patients with moderate LSS treated with the Superion(®) (Experimental) or the X-Stop(®), a FDA-approved interspinous spacer (Control). METHODS: A total of 250 patients with moderate LSS unresponsive to conservative care were randomly allocated to treatment with the Experimental (n = 123) or Control (n = 127) interspinous spacer and followed through 2 years post-treatment. Complication data were available for all patients and patient-reported outcomes were available for 192 patients (101 Experimental, 91 Control) at 2 years. RESULTS: Zurich Claudication Questionnaire (ZCQ) Symptom Severity and Physical Function scores improved 34% to 36% in both groups through 2 years (all p < 0.001). Patient Satisfaction scores at 2 years were 1.8 ± 0.9 with Experimental and 1.6 ± 0.8 with Control. Axial pain decreased from 59 ± 26 mm at baseline to 21 ± 26 mm at 2 years with Experimental and from 55 ± 26 mm to 21 ± 25 mm with Control (both p < 0.001). Extremity pain decreased from 67 ± 24 mm to 14 ± 22 mm at 2 years with Experimental and from 63 ± 24 mm to 18 ± 23 mm with Control (both p < 0.001). Back function assessed with the Oswestry Disability Index similarly improved with Experimental (37 ± 12% to 18 ± 16%) and Control (39 ± 12% to 20 ± 16%) (both p < 0.001). Freedom from reoperation at the index level was 84% for Experimental and 83% for Control (log-rank: p = 0.38) at 2 years. CONCLUSIONS: Both interspinous spacers effectively alleviated pain and improved back function to a similar degree through 2 years in patients with moderate LSS who were unresponsive to conservative care. TRIAL REGISTRATION: NCT00692276.

Methylprednisolone in acute traumatic spinal cord injury: case-matched outcomes from the NASCIS2 and Sygen historical spinal cord injury studies with contemporary statistical analysis.

OBJECTIVE: Methylprednisolone (MP) to treat acute traumatic spinal cord injury (ATSCI) remains controversial since the release of the second National Acute Spinal Cord Injury Study (NASCIS2) in 1990. As two historical studies, NASCIS2 and Sygen in ATSCI, used identical MP dosages, it was possible to construct a new case-level pooled ATSCI data set satisfying contemporary criteria and able to clarify the effect of MP. METHODS: The new pooled data set was first modernized by excluding patients with injury levels caudal to T10, lower-extremity American Spinal Injury Association (ASIA) motor scores (LEMSs) ≥ 46, Glasgow Coma Scale scores ≤ 11, and age < 15 or > 75 years, and then standardized to the ASIA grading and scoring format. A new updated NASCIS2 data set from this pooled data set contained 31.6% fewer patients than the 1990 NASCIS2 data set. RESULTS: In the new pooled data set, recovery of LEMSs from baseline to 26 weeks, the primary outcome variable, was separated statistically into five different injury severity cohorts (p < 0.0001). The severity cohorts contained groups with severe floor (62.9%) and ceiling (10.7%) effects, which do not contribute to drug effects. The new NASCIS2 data set duplicated the p value for MP versus placebo in the sub-subgroup analysis of MP initiated ≤ 8 hours (the subgroup) and recovery of motor function on only the right side of the body (a further subgroup within the ≤ 8-hour subgroup), presented as the positive MP effect in the original NASCIS2 reporting. However, current statistical interpretation considers results seen only in post hoc sub-subgroups, without multi-test corrections, to be random effects without clinical significance. The combined case-level pooled data set from the NASCIS2 and Sygen studies increased the MP group from 106 to 431 patients, creating a new MP combined group. This new data set served as a surrogate for a contemporary MP study and found that administration of MP did not enhance ASIA motor score improvement in the lower extremities at 26 weeks. Secondary analysis of descending ASIA motor and sensory cervical neurological levels in cervical ATSCI patients at 26 weeks also found no MP drug effect. CONCLUSIONS: Analysis of both the new updated NASCIS2 data set and the new case-matched pooled data set from two historical ATSCI studies revealed that administration of MP after spinal cord injury did not demonstrate any enhancement in neurological recovery at 26 weeks. The results of this analysis warrant review by clinical guideline groups.

Early vs Late Surgical Decompression for Central Cord Syndrome.

Importance: The optimal clinical management of central cord syndrome (CCS) remains unclear; yet this is becoming an increasingly relevant public health problem in the face of an aging population. Objective: To provide a head-to-head comparison of the neurologic and functional outcomes of early (<24 hours) vs late (≥24 hours) surgical decompression for CCS. Design, Setting, and Participants: Patients who underwent surgery for CCS (lower extremity motor score [LEMS] - upper extremity motor score [UEMS] ≥ 5) were included in this propensity score-matched cohort study. Data were collected from December 1991 to March 2017, and the analysis was performed from March 2020 to January 2021. This study identified patients with CCS from 3 international multicenter studies with data on the timing of surgical decompression in spinal cord injury. Participants were included if they had a documented baseline neurologic examination performed within 14 days of injury. Participants were eligible if they underwent surgical decompression for CCS. Exposures: Early surgery was compared with late surgery. Main Outcomes and Measures: Propensity scores were calculated as the probability of undergoing early compared with late surgery using the logit method and adjusting for relevant confounders. Propensity score matching was performed in a 1:1 ratio by an optimal-matching technique. The primary end point was motor recovery (UEMS, LEMS, American Spinal Injury Association [ASIA] motor score [AMS]) at 1 year. Secondary end points were Functional Independence Measure (FIM) motor score and complete independence in each FIM motor domain at 1 year. Results: The final study cohort consisted of 186 patients with CCS. The early-surgery group included 93 patients (mean [SD] age, 47.8 [16.8] years; 66 male [71.0%]), and the late-surgery group included 93 patients (mean [SD] age, 48.0 [15.5] years; 75 male [80.6%]). Early surgical decompression resulted in significantly improved recovery in upper limb (mean difference [MD], 2.3; 95% CI, 0-4.5; P = .047), but not lower limb (MD, 1.1; 95% CI, -0.8 to 3.0; P = .30), motor function. In an a priori-planned subgroup analysis, outcomes were comparable with early or late decompressive surgery in patients with ASIA Impairment Scale (AIS) grade D injury. However, in patients with AIS grade C injury, early surgery resulted in significantly greater recovery in overall motor score (MD, 9.5; 95% CI, 0.5-18.4; P = .04), owing to gains in both upper and lower limb motor function. Conclusions and Relevance: This cohort study found early surgical decompression to be associated with improved recovery in upper limb motor function at 1 year in patients with CCS. Treatment paradigms for CCS should be redefined to encompass early surgical decompression as a neuroprotective therapy.

A Novel Method to Classify Cervical Incomplete Spinal Cord Injury Based on Potential for Recovery: A Group-Based Trajectory Analysis.

The outcomes of cervical incomplete spinal cord injury (SCI) are heterogeneous. This study sought to dissociate subgroups of cervical incomplete SCI patients with distinct longitudinal temporal profiles of recovery in upper limb motor function. Patients with cervical incomplete SCI (American Spinal Injury Association Impairment Scale [AIS] B-D; C1-C8) were identified from four prospective, multi-center SCI datasets. A group-based trajectory model was fit to longitudinal upper extremity motor scores out to 1 year. Multi-variable multinomial logistic regression was performed to identify features that characterize each trajectory group. A classification system for predicting trajectory group at baseline was developed by recursive partitioning. In total, 801 patients were eligible. Four distinct trajectory groups were identified: 1) "Poor outcome": Severe injury, very minimal recovery; 2) "Moderate recovery": Moderate-to-severe injury, moderate recovery; most recovery occurs by 6 months, with mild, gradual recovery continuing thereafter; 3) "Good recovery": Moderate injury, good recovery; most recovery occurs by 3 months, with mild, gradual recovery continuing thereafter; and 4) "Excellent outcome": Mild injury, recovery to normal/near-normal by 3 months. On adjusted analyses, older age was associated with lower likelihood of "excellent outcome" (p = 0.020). AIS C and D injuries were associated with "moderate recovery," "good recovery," and "excellent outcome" (p < 0.001). Mid-cervical injuries occurred more frequently in "moderate recovery," "good recovery," and "excellent outcome" (p < 0.001) groups. Early surgical decompression (< 24 h) was associated with increased propensity for "good recovery" (p = 0.039) and "excellent outcome" (p = 0.048). A classification model based on recursive partitioning could predict trajectory group using age, AIS grade, and neurological level with an area under the curve of 0.81. Patients with cervical incomplete SCI demonstrate distinct temporal profiles of recovery in upper limb motor function. The trajectory a patient is likely to follow may be predicted at baseline with fair accuracy.

Routine Blood Chemistry Predicts Functional Recovery After Traumatic Spinal Cord Injury: A Post Hoc Analysis.

BACKGROUND: Spinal cord injury (SCI) leads to various degrees of lifelong functional deficits. Most individuals with incomplete SCI experience a certain degree of functional recovery, especially within the first-year postinjury. However, this is difficult to predict, and surrogate biomarkers are urgently needed. OBJECTIVE: We aimed to (1) determine if routine blood chemistry parameters are related to neurological recovery after SCI, (2) evaluate if such parameters could predict functional recovery, and (3) establish cutoff values that could inform clinical decision-making. METHODS: We performed a post hoc analysis of routine blood chemistry parameters in patients with traumatic SCI (n = 676). Blood samples were collected between 24 and 72 hours as well as at 1, 2, 4, 8, and 52 weeks postinjury. Linear mixed models, regression analysis, and unbiased recursive partitioning (URP) of blood chemistry data were used to relate to and predict walking recovery 1 year postinjury. RESULTS: The temporal profile of platelet counts and serum levels of albumin, alkaline phosphatase, and creatinine differentiated patients who recovered walking from those who remained wheelchair bound. The 4 blood chemistry parameters from the sample collection 8 weeks postinjury predicted functional recovery observed 1 year after incomplete SCI. Finally, URP defined a cutoff for serum albumin at 3.7 g/dL, which in combination with baseline injury severity differentiates individuals who regain ambulation from those not able to walk. Specifically, about 80% of those with albumin >3.7 g/dL recovered walking. CONCLUSIONS: Routine blood chemistry data from the postacute phase, together with baseline injury severity, predict functional outcome after incomplete SCI.

The influence of timing of surgical decompression for acute spinal cord injury: a pooled analysis of individual patient data.

BACKGROUND: Although there is a strong biological rationale for early decompression of the injured spinal cord, the influence of the timing of surgical decompression for acute spinal cord injury (SCI) remains debated, with substantial variability in clinical practice. We aimed to objectively evaluate the effect of timing of decompressive surgery for acute SCI on long-term neurological outcomes. METHODS: We did a pooled analysis of individual patient data derived from four independent, prospective, multicentre data sources, including data from December, 1991, to March, 2017. Three of these studies had been published; of these, only one study previously specifically analysed the effect of the timing of surgical decompression. These four datasets were selected because they were among the highest quality acute SCI datasets available and contained highly granular data. Individual patient data were obtained by request from study authors. All patients who underwent decompressive surgery for acute SCI within these datasets were included. Patients were stratified into early (<24 h after spinal injury) and late (≥24 h after spinal injury) decompression groups. Neurological outcomes were assessed by American Spinal Injury Association (ASIA), or International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), examination. The primary endpoint was change in total motor score from baseline to 1 year after spinal injury. Secondary endpoints were ASIA Impairment Scale (AIS) grade and change in upper-extremity motor, lower-extremity motor, light touch, and pin prick scores after 1 year. One-stage meta-analyses were done by hierarchical mixed-effects regression adjusting for baseline score, age, mechanism of injury, AIS grade, level of injury, and administration of methylprednisolone. Effect sizes were summarised by mean difference (MD) for sensorimotor scores and common odds ratio (cOR) for AIS grade, with corresponding 95% CIs. As a secondary analysis, change in total motor score was regressed against time to surgical decompression (h) as a continuous variable, using a restricted cubic spline with adjustment for the same covariates as in the primary analysis. FINDINGS: We identified 1548 eligible patients from the four datasets. Outcome data at 1 year after spinal injury were available for 1031 patients (66·6%). Patients who underwent early surgical decompression (n=528) experienced greater recovery than patients who had late decompression surgery (n=1020) at 1 year after spinal injury; total motor scores improved by 23·7 points (95% CI 19·2-28·2) in the early surgery group versus 19·7 points (15·3-24·0) in the late surgery group (MD 4·0 points [1·7-6·3]; p=0·0006), light touch scores improved by 19·0 points (15·1-23·0) vs 14·8 points (11·2-18·4; MD 4·3 [1·6-7·0]; p=0·0021), and pin prick scores improved by 18·3 points (13·7-22·9) versus 14·2 points (9·8-18·6; MD 4·0 [1·5-6·6]; p=0·0020). Patients who had early decompression also had better AIS grades at 1 year after surgery, indicating less severe impairment, compared with patients who had late surgery (cOR 1·48 [95% CI 1·16-1·89]; p=0·0019). When time to surgical decompression was modelled as a continuous variable, there was a steep decline in change in total motor score with increasing time during the first 24-36 h after injury (p<0·0001); and after 36 h, change in total motor score plateaued. INTERPRETATION: Surgical decompression within 24 h of acute SCI is associated with improved sensorimotor recovery. The first 24-36 h after injury appears to represent a crucial time window to achieve optimal neurological recovery with decompressive surgery following acute SCI. FUNDING: None.

Nerve Root Sedimentation Sign: Can It Predict the Success for Surgical Intervention in Patients With Symptomatic Lumbar Spinal Stenosis?

INTRODUCTION:  The use of interspinous process devices are less invasive surgical methods designed to manage mild to moderate lumbar spinal stenosis symptoms. Symptomatic relief may not be seen in all patients undergoing this procedure. Magnetic resonance imaging (MRI) parameters have been used to predict the success of clinical outcomes in patients with symptomatic lumbar spinal stenosis for decompressive surgeries. The purpose of this study was to determine the feasibility of using nerve root sedimentation sign to predict mid- to long-term clinical outcomes of patients treated with interspinous spacers for lumbar spinal stenosis. METHODS: This was a retrospective study using prospective multicenter Food and Drug Administration Investigational Device Exemption (FDA IDE) trial (Superion™ and X-STOP®) data. Inclusion criteria were patients treated with interspinous spacers, aged 45 or older with lumbar spinal stenosis at one or more contiguous levels from L1 to L5 and symptoms of neurogenic claudication. Preoperative axial T2 weighted MRI images were used to determine nerve root sedimentation sign. Preoperative, six-week, one- and two-year postoperative clinical outcomes were measured using Oswestry Disability Index (ODI) scores. Clinical outcomes were compared between positive and negative nerve root sedimentation sign groups; p ≤0.05 was considered significant. RESULTS: This study included n=374 patients; 40 excluded; 334 included (113=positive nerve root sedimentation sign (NRSS) (34%) and 221=negative NRSS (66%)). At six weeks, significant postoperative ODI correction was noted in both groups (p<0.001). No significant differences in ODI scores were identified between groups. A subgroup analysis with MRI image quality grade 3 and certainty determination grade 5, six-week postoperative ODI correction was significant in both groups. Six-week, one- and two-year postoperative ODI scores were greater by 6 points in the positive nerve root sedimentation sign group compared to the negative nerve root sedimentation sign group. CONCLUSIONS:  Although satisfactory postoperative improvement occurred in both groups, there were statistically significant differences noted in certain sub-categories. The subgroup analysis indicated MRI image quality and nerve root sedimentation sign certainty of determination may be factors that may aid with planning the surgical management of lumbar spinal stenosis.

Gangliosides: Treatment Avenues in Neurodegenerative Disease.

Gangliosides are cell membrane components, most abundantly in the central nervous system (CNS) where they exert among others neuro-protective and -restorative functions. Clinical development of ganglioside replacement therapy for several neurodegenerative diseases was impeded by the BSE crisis in Europe during the 1990s. Nowadays, gangliosides are produced bovine-free and new pre-clinical and clinical data justify a reevaluation of their therapeutic potential in neurodegenerative diseases. Clinical experience is greatest with monosialo-tetrahexosyl-ganglioside (GM1) in the treatment of stroke. Fourteen randomized controlled trials (RCTs) in overall >2,000 patients revealed no difference in survival, but consistently superior neurological outcomes vs. placebo. GM1 was shown to attenuate ischemic neuronal injuries in diabetes patients by suppression of ERK1/2 phosphorylation and reduction of stress to the endoplasmic reticulum. There is level-I evidence from 5 RCTs of a significantly faster recovery with GM1 vs. placebo in patients with acute and chronic spinal cord injury (SCI), disturbance of consciousness after subarachnoid hemorrhage, or craniocerebral injuries due to closed head trauma. In Parkinson's disease (PD), two RCTs provided evidence of GM1 to be superior to placebo in improving motor symptoms and long-term to result in a slower than expected symptom progression, suggesting disease-modifying potential. In Alzheimer's disease (AD), the role of gangliosides has been controversial, with some studies suggesting a "seeding" role for GM1 in amyloid ß polymerization into toxic forms, and others more recently suggesting a rather protective role in vivo. In Huntington's disease (HD), no clinical trials have been conducted yet. However, low GM1 levels observed in HD cells were shown to increase cell susceptibility to apoptosis. Accordingly, treatment with GM1 increased survival of HD cells in vitro and consistently ameliorated pathological phenotypes in several murine HD models, with effects seen at molecular, cellular, and behavioral level. Given that in none of the clinical trials using GM1 any clinically relevant safety issues have occurred to date, current data supports expanding GM1 clinical research, particularly to conditions with high, unmet medical need.

Effect of age on clinical and radiographic outcomes and adverse events following 1-level lumbar arthroplasty after a minimum 2-year follow-up.

OBJECT: Lumbar arthroplasty is approved in the US for the treatment of degenerative disc disease at 1 level in skeletally mature patients. However, a bias toward older patients (> 45 years of age) who are otherwise indicated for the procedure may exist. In this study, the clinical outcomes of patients from the Charité Investigational Device Exemption (IDE) study were analyzed on the basis of patient age. METHODS: There were 276 patients enrolled in the IDE study of the Charité Artificial Disc who underwent 1-level arthroplasty at either L4-5 or L5-S1, including 71 nonrandomized and 205 randomized individuals. Patient data were analyzed based on age (18-45 years [217 patients, Group 1] compared with 46-60 years [59 patients, Group 2]). Statistical analyses were performed based on 2-year postoperative improvements in Oswestry Disability Index (ODI), 36-item Short Form Health Survey (SF-36), and visual analog scale (VAS) scores (clinical outcome), as well as range of motion (radiographic outcome), and adverse events. RESULTS: There was no significant difference between the groups with respect to level implanted, operative time, blood loss, changes in ODI and VAS scores or any of the 8 component scores of the SF-36, compared with baseline, at all time points throughout the 24-month follow-up period (p > 0.10). Patient satisfaction was equivalent at 24 months, with 87% satisfaction in Group 1 and 85% satisfaction in Group 2 (no statistical difference). In addition, no significant differences were identified with respect to adverse events including approach related, neurological, technique related, or reoperation. CONCLUSIONS: Although patients > 45 years of age may have comorbidities or contraindications for arthroplasty for a number of reasons, particularly osteopenia, this analysis demonstrates that patients who are indicated for 1-level arthroplasty experience similar clinical outcome, satisfaction, or adverse events compared with their younger counterparts.

Effect of previous surgery on clinical outcome following 1-level lumbar arthroplasty.

OBJECT: A secondary lumbar surgery at a previously surgically treated level is believed to result in minimal clinical improvement. The clinical results of the CHARITE Investigational Device Exemption (IDE) study were analyzed to assess the effect of previous surgery on clinical outcomes following either total disc replacement with the CHARITE device or anterior lumbar interbody fusion with a BAK cage and iliac crest autograft. METHODS: Patients with prior microdiscectomy, laminectomy, or minimal medial facetectomy were not excluded from enrollment in the CHARITE IDE study. Thus, the following 3 groups were analyzed: all patients treated with the CHARITE Artificial Disc, whether randomized or nonrandomized; only patients treated with CHARITE devices randomized against patients with BAK devices; and control patients with BAK devices. Each group was further subdivided based on the patients' medical history, whether they had undergone prior surgery (prior surgery group) or had not (no prior surgery group). For all groups, baseline demographics were collected and compared for any potential recruitment bias. Postoperative improvements based on Oswestry Disability Index (ODI), visual analog scale (VAS), and patient satisfaction scores were further collected and statistically analyzed. RESULTS: For all 3 groups, there were no statistical differences in clinical improvement from 3 months to 2 years postoperatively as measured using ODI and VAS scores between the subgroups (those who had prior surgery and those who did not). CONCLUSIONS: Patients indicated for 1-level lumbar arthroplasty with previous lumbar decompressive surgery can be expected to have similar clinical outcomes to patients undergoing arthroplasty without prior lumbar decompressive surgery. Similarly, candidates for anterior lumbar fusion with prior decompressive surgery may experience similar benefits from the surgical procedure as those without.

Patient selection for lumbar arthroplasty and arthrodesis: the effect of revision surgery in a controlled, multicenter, randomized study.

OBJECT: Patient selection is perhaps the most important factor in successful lumbar surgery. In this study, the authors analyzed the clinical outcomes of patients enrolled in the CHARITE investigational device exemption (IDE) trial who underwent revision surgery after primary total disc replacement with CHARITE or an anterior lumbar interbody fusion (ALIF) with placement of a BAK cage and iliac crest autograft. This revision surgery was either a supplemental posterior lumbar fixation or a 360 degrees fusion. Statistical analysis was conducted to compare clinical success in patients who underwent revision surgery with those who did not. METHODS: The patients enrolled in the CHARITE IDE study were divided into 6 groups according to treatment and repeated operation status, and their Oswestry Disability Index (ODI) and visual analog scale (VAS) scores at the 2-year follow-up and at baseline were compared. The patients had received the following treatments by group: A) ALIF without reoperation; B) ALIF with conversion to 360 degrees fusion; C) arthroplasty (randomized) without repeated operation; D) arthroplasty with supplemental posterior lumbar fixation; E) arthroplasty (nonrandomized) without repeated operation; and F) arthroplasty (nonrandomized) with supplemental posterior lumbar fixation. Outcome scores in the groups of patients who required revision surgeries (Groups B, D, and F; 23 patients) were compared with the groups that did not require revision surgery (Groups A, C, and E; 299 patients). RESULTS: Patients who required revision surgery had a significantly lower level of clinical improvement than those who did not. The mean change in ODI score was -53.0% in Groups A, C, and E, but just -12.7% in Groups B, D, and F (p < 0.0001). The mean change in VAS score was -59.1% in Groups A, C, and E, compared to -23.4% in Groups B, D, and F (p < 0.0001). No significant differences were identified in analyzing absolute change in scores and the percentage change. A comparison of outcomes in patients who had undergone arthroplasty without reoperation (Groups C and E) with all patients who had undergone revision surgery (Groups B, D, and F) demonstrated similar results (p < 0.0001). CONCLUSIONS: The 7.1% of patients who underwent a secondary stabilization procedure had poor clinical improvement. This finding may indicate that if the alternative treatment had been the initial treatment, these patients would not have benefited, and further implies a 7.1% rate of imprecision in preoperative evaluation.

Distribution of in vivo and in vitro range of motion following 1-level arthroplasty with the CHARITE artificial disc compared with fusion.

OBJECT: One of the goals of lumbar arthroplasty is to restore and maintain range of motion (ROM) and to protect adjacent levels from abnormal motion, which may be a factor in transition syndrome following arthrodesis. In this study, in vitro ROM results were compared with in vivo, 2-year postoperative radiographic ROM evaluations. METHODS: Radiographs of patients enrolled in the CHARITE investigational device exemption study were analyzed at baseline and at 2 years postoperatively. The ROM in flexion/extension at the implanted and adjacent levels was measured, normalized, and compared with ROM results obtained using cadaver (in vitro) evaluations. RESULTS: Preoperative ROM distributions in patients enrolled for arthroplasty or fusion at the L4-5 level was as follows: 28% motion was observed at L3-4, 35% at L4-5 and 37% at L5-S1. Following a one-level arthroplasty at L4-5, the in vivo ROM distribution from L-3 to S-1 at the 2-year time point was 36% at L3-4, 30% at L4-5 and 35% at L5-S1. Following a one-level fusion with BAK and pedicle screws at L4-5, the in vivo ROM distribution from L-3 to S-1 at the 2-year time point was 45% at L3-4, 9% at L4-5 and 46% at L5-S1. CONCLUSIONS: The baseline as well as the 2-year in vivo data confirmed previously published in vitro data. One-level arthroplasty was shown herein to replicate the normal distribution of motion of the intact spine.

Interspinous Process Decompression Improves Quality of Life in Patients with Lumbar Spinal Stenosis.

Lumbar spinal stenosis has been shown to negatively impact health-related quality of life. Interspinous process decompression (IPD) is a minimally invasive procedure that utilizes a stand-alone spacer to serve as a joint extension blocker to relieve neural compression in patients with spinal stenosis. Using the 5-year results from an FDA randomized controlled trial of IPD, the quality of life in 189 patients treated with the Superion® spacer was evaluated with the SF-12. Physical and mental component summary (PCS, MCS) scores were computed preoperatively and at annual intervals. For the PCS, mean scores improved from 29.4 ± 8.1 preoperatively to 41.2 ± 12.4 at 2 years (40%) and to 43.8 ± 11.6 at 5 years (49%) (p<0.001 for both comparisons). At 2 years, 81% (103 of 128) of subjects demonstrated maintenance or improvement in PCS scores. The mean MCS score improved from 50.0 ± 12.7 preoperatively to 54.4 ± 10.6 and 54.7 ± 8.6 at 2 and 5 years, respectively (p>0.10 for both comparisons). These results demonstrate that the significant impairment in physical well-being found in patients with lumbar spinal stenosis can be ameliorated, in large part, by IPD treatment.

Hemodynamic parameters and timing of surgical decompression in acute cervical spinal cord injury.

BACKGROUND/OBJECTIVES: To evaluate the relationship between the severity of cervical spinal cord injury (SCI) (American Spinal Injury Association [ASIA] grade), presence of neurogenic shock, and timing of surgical intervention. This is a post-hoc analysis from the Sygen multicenter randomized controlled trial. METHODS: Blood pressure (BP) and heart rate (HR) data were collected when patients were first assessed in the emergency room (Time A) and at the time of randomization (Time B). Individuals were subdivided by ASIA grade and by the level of the systolic BP (SBP). RESULTS: Only individuals with cervical SCI from the Sygen trial (n = 577) were evaluated. Severe complete SCI (ASIA grade = A) was established in 57% of these patients. A total of 74 (13%) patients with neurogenic shock (SBP < 90 mmHg) at Time A were identified. The SBP increased significantly from Time A to Time B (P < 0.0001). The median time from SCI to surgical intervention, for ASIA A, was 80.9 hours for patients with initial SBP < 90 mmHg and 58 hours for patients with initial SBP > or = 90 mmHg (P = 0.025). Multivariable analysis after adjusting for confounders revealed a statistically significant difference in the time to surgical intervention based on SBP for ASIA A (P = 0.026), yet not for ASIA B or C/D. CONCLUSIONS: The presence of neurogenic shock was associated with a delay in the timing of surgical intervention in patients with cervical SCI. Detailed evaluation of autonomic dysfunctions following SCI including cardiovascular instability could improve our understanding of the complexities of clinical presentations and possible neurological outcomes.

Superion Interspinous Spacer Treatment of Moderate Spinal Stenosis: 4-Year Results.

OBJECTIVE: To determine 4-year clinical outcomes in patients with moderate lumbar spinal stenosis treated with minimally invasive stand-alone interspinous process decompression using the Superion device. METHODS: The 4-year Superion data were extracted from a randomized, controlled Food and Drug Administration investigational device exemption trial. Patients with intermittent neurogenic claudication relieved with back flexion who failed at least 6 months of nonsurgical management were enrolled. Outcomes included Zurich Claudication Questionnaire (ZCQ) symptom severity (ss), physical function (pf) and patient satisfaction (ps) subdomains, leg and back pain visual analog scale (VAS), and Oswestry Disability Index (ODI). At 4-year follow-up, 89 of the 122 patients (73%) provided complete clinical outcome evaluations. RESULTS: At 4 years after index procedure, 75 of 89 patients with Superion (84.3%) demonstrated clinical success on at least 2 of 3 ZCQ domains. Individual component responder rates were 83% (74/89), 79% (70/89), and 87% (77/89) for ZCQss, ZCQpf, and ZCQps; 78% (67/86) and 66% (57/86) for leg and back pain VAS; and 62% (55/89) for ODI. Patients with Superion also demonstrated percentage improvements over baseline of 41%, 40%, 73%, 69%, and 61% for ZCQss, ZCQpf, leg pain VAS, back pain VAS, and ODI. Within-group effect sizes all were classified as very large (>1.0): 1.49, 1.65, 1.42, 1.12, and 1.46 for ZCQss, ZCQpf, leg pain VAS, back pain VAS, and ODI. CONCLUSIONS: Minimally invasive implantation of the Superion device provides long-term, durable relief of symptoms of intermittent neurogenic claudication for patients with moderate lumbar spinal stenosis.

Five-year durability of stand-alone interspinous process decompression for lumbar spinal stenosis.

BACKGROUND: Lumbar spinal stenosis is the most common indication for spine surgery in older adults. Interspinous process decompression (IPD) using a stand-alone spacer that functions as an extension blocker offers a minimally invasive treatment option for intermittent neurogenic claudication associated with spinal stenosis. METHODS: This study evaluated the 5-year clinical outcomes for IPD (Superion®) from a randomized controlled US Food and Drug Administration (FDA) noninferiority trial. Outcomes included Zurich Claudication Questionnaire (ZCQ) symptom severity (ss), physical function (pf), and patient satisfaction (ps) subdomains, leg and back pain visual analog scale (VAS), and Oswestry Disability Index (ODI). RESULTS: At 5 years, 84% of patients (74 of 88) demonstrated clinical success on at least two of three ZCQ domains. Individual ZCQ domain success rates were 75% (66 of 88), 81% (71 of 88), and 90% (79 of 88) for ZCQss, ZCQpf, and ZCQps, respectively. Leg and back pain success rates were 80% (68 of 85) and 65% (55 of 85), respectively, and the success rate for ODI was 65% (57 of 88). Percentage improvements over baseline were 42%, 39%, 75%, 66%, and 58% for ZCQss, ZCQpf, leg and back pain VAS, and ODI, respectively (all P<0.001). Within-group effect sizes were classified as very large for four of five clinical outcomes (ie, >1.0; all P<0.0001). Seventy-five percent of IPD patients were free from reoperation, revision, or supplemental fixation at their index level at 5 years. CONCLUSION: After 5 years of follow-up, IPD with a stand-alone spacer provides sustained clinical benefit.

Interspinous Process Decompression: Expanding Treatment Options for Lumbar Spinal Stenosis.

Interspinous process decompression is a minimally invasive implantation procedure employing a stand-alone interspinous spacer that functions as an extension blocker to prevent compression of neural elements without direct surgical removal of tissue adjacent to the nerves. The Superion® spacer is the only FDA approved stand-alone device available in the US. It is also the only spacer approved by the CMS to be implanted in an ambulatory surgery center. We computed the within-group effect sizes from the Superion IDE trial and compared them to results extrapolated from two randomized trials of decompressive laminectomy. For the ODI, effect sizes were all very large (>1.0) for Superion and laminectomy at 2, 3, and 4 years. For ZCQ, the 2-year Superion symptom severity (1.26) and physical function (1.29) domains were very large; laminectomy effect sizes were very large (1.07) for symptom severity and large for physical function (0.80). Current projections indicate a marked increase in the number of patients with spinal stenosis. Consequently, there remains a keen interest in minimally invasive treatment options that delay or obviate the need for invasive surgical procedures, such as decompressive laminectomy or fusion. Stand-alone interspinous spacers may fill a currently unmet treatment gap in the continuum of care and help to reduce the burden of this chronic degenerative condition on the health care system.

Superion(®) InterSpinous Spacer for treatment of moderate degenerative lumbar spinal stenosis: durable three-year results of a randomized controlled trial.

PURPOSE: This report provides the 3-year clinical outcomes from the randomized, controlled US Food and Drug Administration Investigational Device Exemption trial of the Superion(®) for the treatment of moderate degenerative lumbar spinal stenosis. PATIENTS AND METHODS: The Superion(®) was evaluated in the treatment of subjects aged 45 years or older suffering from symptoms of intermittent neurogenic claudication, secondary to a confirmed diagnosis of moderate degenerative lumbar spinal stenosis at one or two contiguous levels from L1 to L5. Patients were treated between June 2008 and December 2011 at 31 investigational sites. Three hundred ninety-one subjects were included in the randomized study group consisting of 190 Superion(®) and 201 X-STOP(®) control subjects. The primary composite endpoint was individual patient success based on four components: improvement in two of three domains of the Zurich Claudication Questionnaire, no reoperations at the index level, no major implant/procedure-related complications, and no clinically significant confounding treatments. RESULTS: At 3 years, the proportion of subjects achieving the primary composite endpoint was greater for Superion(®) (63/120, 52.5%) than for X-STOP(®) (49/129, 38.0%) (P=0.023) and the corresponding success rates exceeded 80% for each of the individual components of the primary endpoint in the Superion(®) group (range: 81%-91%). Improvements in back and leg pain severity as well as back- and disease-specific functional outcomes were also maintained through 36 months. CONCLUSION: The 3-year outcomes from this randomized controlled trial demonstrate durable clinical improvement consistently across all clinical outcomes for the Superion(®) in the treatment of patients with moderate degenerative lumbar spinal stenosis.

Long-term Outcomes of the US FDA IDE Prospective, Randomized Controlled Clinical Trial Comparing PCM Cervical Disc Arthroplasty With Anterior Cervical Discectomy and Fusion.

STUDY DESIGN: Prospective, multicenter, randomized clinical trial. OBJECTIVE: To evaluate the long-term safety and effectiveness of the PCM Cervical Disc compared with anterior cervical discectomy and fusion (ACDF) in treatment of patients with symptomatic single-level degenerative spondylosis between C3-C4 and C7-T1 with or without prior cervical fusion. SUMMARY OF BACKGROUND DATA: The 2-year results of the PCM Cervical Disc trial have been reported previously. The current study reports the long-term results of the same trial. METHODS: Patients with single-level cervical spondylosis and radiculopathy with or without myelopathy unresponsive to nonoperative treatment were enrolled. The per protocol patient sample at 5 years included 293 patients (163 PCM, 130 ACDF). Adverse events and secondary surgical procedures are reported on the cohorts through current follow-up, which include 110 patients (68 PCM, 42 ACDF) at 7 years. RESULTS: At 5 years postoperative, all patient-reported outcomes-neck and arm pain visual analogue scale score, neck disability index, and general health (36-Item Short Form Health Survey physical and mental component scores: physical component summary, mental component summary)-were significantly improved from baselines in both groups, and mean scores were significantly better in the PCM group for neck disability index (P=0.001), neck pain (P=0.002), general health (Pphysical component summary=0.014; Pmental component summary=0.004), and patient satisfaction (P=0.005). PCM patients trended toward fewer 2- to 7-year device-related serious adverse events (1/214, 0.5% PCM; 2/190, 1.1% ACDF) and secondary surgical procedures (7/211, 3.3% PCM; 14/290, 7.6% ACDF). Adjacent-level degeneration was radiographically more frequent after ACDF (33.1% PCM, 50.9% ACDF; P=0.006) and was the primary indication for the increase in late-term secondary surgical procedures after ACDF. CONCLUSION: The long-term results show good clinical outcomes after ACDF and PCM arthroplasty. PCM patients showed greater improvement in neck disability index and neck pain scores with a lower rate of radiographical adjacent-level degeneration and a trend toward fewer secondary surgical procedures. These data support PCM arthroplasty to be a viable and sustainable alternative to ACDF. LEVEL OF EVIDENCE: 1.