Allogeneic Disc Progenitor Cells Safely Increase Disc Volume and Improve Pain, Disability, and Quality of Life in Patients With Lumbar Disc Degeneration-Results of an FDA-Approved Biologic Therapy Randomized Clinical Trial.

BACKGROUND: Progenitor cells derived from intervertebral disc tissue demonstrated immunomodulatory and regenerative properties in preclinical studies. We report the safety and efficacy results of a US Food and Drug Administration-approved clinical trial of these cells for the treatment of symptomatic degenerative disc disease. METHODS: Sixty patients with symptomatic single-level lumbar degenerative disc disease (mean age 37.9 years, 60% men) were enrolled in a randomized, double-blinded, placebo-controlled Phase I/Phase II study at 13 clinical sites. They were randomized to receive single intradiscal injections of either low-dose cells (N = 20), high-dose cells (N = 20), vehicle alone (N = 10), or placebo (N = 10). The primary endpoint was mean visual analog scale (VAS) pain improvement >30% at 52 weeks. Disc volume was radiologically assessed. Adverse events (AEs), regardless of whether they were related to treatment, were reported. Patients were assessed at baseline and at 4, 12, 26, 52, 78, and 104 weeks posttreatment. RESULTS: At week 52, the high-dose group had a mean VAS percentage decrease from baseline (-62.8%, P = 0.0005), achieving the endpoint of back pain improvement >30%; the mean change was also significantly greater than the minimal clinically important difference of a 20-point decrease (-42.8, P = 0.001). This clinical improvement was maintained at week 104. The vehicle group had a smaller significant decrease in VAS (-52.8%, P = 0.044), while the low-dose and placebo groups showed nonsignificant improvements. Only the high-dose group had a significant change in disc volume, with mean increases of 249.0 mm3 (P = 0.028) at 52 weeks and 402.1 mm3 (P = 0.028) at 104 weeks. A minority of patients (18.3%) reported AEs that were severe. Overall, 6.7% of patients experienced serious AEs, all in the vehicle (n = 1) or placebo (n = 3) groups, none treatment related. CONCLUSIONS: High-dose allogeneic disc progenitor cells produced statistically significant, clinically meaningful improvements in back pain and disc volume at 1 year following a single intradiscal injection and were safe and well tolerated. These improvements were maintained at 2 years post-injection. CLINICAL TRIAL REGISTRATION: NCT03347708-Study to Evaluate the Safety and Preliminary Efficacy of Injectable Disc Cell Therapy, a Treatment for Symptomatic Lumbar Intervertebral Disc Degeneration.

Review of concentration yields in commercially available platelet-rich plasma (PRP) systems: a call for PRP standardization.

Platelet-rich plasma (PRP) has become increasingly popular in pain medicine with hopes of becoming a safe, effective alternative to routine treatments. However, given its autologous nature, PRP injectate may differ depending on the specific manufacturer and protocol. Currently, there is no standardization of reporting protocol. This systematic review compiles and standardizes values on PRP preparation and final product composition of platelets, white cell count, and growth factors for ease of comparison. On review of 876 studies, 13 studies were selected according to our inclusion criteria. Data from 33 PRP systems and protocols were extracted and standardized. Overall, PRP final product concentrations as well as PRP preparation protocols varied widely between systems. However, platelet concentration was directly correlated with both volume of blood collected and device centrifugal force. In conclusion, there is a large heterogeneity between PRP separation systems that must be resolved for proper study of this promising treatment.

Is the lateral jack-knife position responsible for cases of transient neurapraxia?

OBJECTIVE: The lateral jack-knife position is often used during transpsoas surgery to improve access to the spine. Postoperative neurological signs and symptoms are very common after such procedures, and the mechanism is not adequately understood. The objective of this study is to assess if the lateral jack-knife position alone can cause neurapraxia. This study compares neurological status at baseline and after positioning in the 25° right lateral jack-knife (RLJK) and the right lateral decubitus (RLD) position. METHODS: Fifty healthy volunteers, ages 21 to 35, were randomly assigned to one of 2 groups: Group A (RLD) and Group B (RLJK). Motor and sensory testing was performed prior to positioning. Subjects were placed in the RLD or RLJK position, according to group assignment, for 60 minutes. Motor testing was performed immediately after this 60-minute period and again 60 minutes thereafter. Sensory testing was performed immediately after the 60-minute period and every 15 minutes thereafter, for a total of 5 times. Motor testing was performed by a physical therapist who was blinded to group assignment. A follow-up call was made 7 days after the positioning sessions. RESULTS: Motor deficits were observed in the nondependent lower limb in 100% of the subjects in Group B, and no motor deficits were seen in Group A. Statistically significant differences (p < 0.05) were found between the 2 groups with respect to the performance on the 10-repetition maximum test immediately immediately and 60 minutes after positioning. Subjects in Group B had a 10%-70% (average 34.8%) decrease in knee extension strength and 20%-80% (average 43%) decrease in hip flexion strength in the nondependent limb. Sensory abnormalities were observed in the nondependent lower limb in 98% of the subjects in Group B. Thirty-six percent of the Group B subjects still exhibited sensory deficits after the 60-minute recovery period. No symptoms were reported by any subject during the follow-up calls 7 days after positioning. CONCLUSIONS: Twenty-five degrees of right lateral jack-knife positioning for 60 minutes results in neurapraxia of the nondependent lower extremity. Our results support the hypothesis that jack-knife positioning alone can cause postoperative neurological symptoms.

Retroperitoneal oblique corridor to the L2-S1 intervertebral discs: an MRI study.

OBJECT The purpose of this study was to analyze MR images of the lumbar spine and document: 1) the oblique corridor at each lumbar disc level between the psoas muscle and the great vessels, and 2) oblique access to the L5-S1 disc space. Access to the lumbar spine without disruption of the psoas muscle could translate into decreased frequency of postoperative neurological complications observed after a transpsoas approach. The authors investigated the retroperitoneal oblique corridor of L2-S1 as a means of surgical access to the intervertebral discs. This oblique approach avoids the psoas muscle and is a safe and potentially superior alternative to the lateral transpsoas approach used by many surgeons. METHODS One hundred thirty-three MRI studies performed between May 4, 2012, and February 27, 2013, were randomly selected from the authors' database. Thirty-three MR images were excluded due to technical issues or altered lumbar anatomy due to previous spine surgery. The oblique corridor was defined as the distance between the left lateral border of the aorta (or iliac artery) and the anterior medial border of the psoas. The L5-S1 oblique corridor was defined transversely from the midsagittal line of the inferior endplate of L-5 to the medial border of the left common iliac vessel (axial view) and vertically to the first vascular structure that crossed midline (sagittal view). RESULTS The oblique corridor measurements to the L2-5 discs have the following mean distances: L2-3 = 16.04 mm, L3-4 = 14.21 mm, and L4-5 = 10.28 mm. The L5-S1 corridor mean distance was 10 mm between midline and left common iliac vessel, and 10.13 mm from the first midline vessel to the inferior endplate of L-5. The bifurcation of the aorta and confluence of the vena cava were also analyzed in this study. The aortic bifurcation was found at the L-3 vertebral body in 2% of the MR images, at the L3-4 disc in 5%, at the L-4 vertebral body in 43%, at the L4-5 disc in 11%, and at the L-5 vertebral body in 9%. The confluence of the iliac veins was found at lower levels: 45% at the L-4 level, 19.39% at the L4-5 intervertebral disc, and 34% at the L-5 vertebral body. CONCLUSIONS An oblique corridor of access to the L2-5 discs was found in 90% of the MR images (99% access to L2-3, 100% access to L3-4, and 91% access to L4-5). Access to the L5-S1 disc was also established in 69% of the MR images analyzed. The lower the confluence of iliac veins, the less probable it was that access to the L5-S1 intervertebral disc space was observed. These findings support the use of lumbar MRI as a tool to predetermine the presence of an oblique corridor for access to the L2-S1 intervertebral disc spaces prior to lumbar spine surgery.

Femoral Neurogram Before Transpsoas Spinal Access at L4-5 Intervertebral Disk Space: A Proposed Screening Tool.

STUDY DESIGN: Observational study. OBJECTIVE: To illustrate the variability of the course of the femoral nerve across the L4-5 disk space, and to present a novel application of transforaminal epidural steroid injections (TFESI) in the visualization of femoral nerve roots. SUMMARY OF BACKGROUND DATA: A concern regarding the lateral retroperitoneal transpsoas approach is the proximity of the lumbar plexus. Current techniques of assessing the proximity of neural tissue to the L4-5 disk space have limited capabilities. METHODS: A total of 100 patients were selected for L4-5 TFESI (L4 selective nerve root blocks) because of lumbar radiculopathy. L4 neurograms were obtained while performing L4-5 TFESI under flouroscopic guidance, using a retroneural technique. The course of the L4 root/femoral nerve was then evaluated under fluoroscopy in the anteroposterior and lateral planes. Images were then reviewed by a radiologist, physiatrist, and 2 orthopedic spine surgeons. RESULTS: Fluoroscopic evaluation revealed that the pattern of location of the femoral nerve was highly variable. In males, it was located 4.7% in zone 2, 32.5% in zone 3, 53.5% in zone 4, and 9.3% in zone P. In female patients, it was located 7.0% in zone 2, 14% in zone 3, 54.4% in zone 4, and 24.6% in zone P. CONCLUSIONS: An L4 neurogram will provide an accurate trajectory of L4 root/femoral nerve as it crosses the L4-5 intervertebral disk space. An accurate assessment is essential to help minimize the increasing frequency of thigh pain, paresthesias, and weakness associated with the lateral access to the L4-5 intervertebral disk space. Femoral nerves that fall within zones 2 and 3 will require more manipulation during retraction and may be better suited with a different surgical approach.

Retroperitoneal oblique corridor to the L2-S1 intervertebral discs in the lateral position: an anatomic study.

OBJECT: Access to the intervertebral discs from L2-S1 in one surgical position can be challenging. The transpsoas minimally invasive surgical (MIS) approach is preferred by many surgeons, but this approach poses potential risk to neural structures of the lumbar plexus as they course through the psoas. The lumbar plexus and iliac crest often restrict the L4-5 disc access, and the L5-S1 level has not been a viable option from a direct lateral approach. The purpose of the present study was to investigate an MIS oblique corridor to the L2-S1 intervertebral disc space in cadaveric specimens while keeping the specimens in a lateral decubitus position with minimal disruption of the psoas and lumbar plexus. METHODS: Twenty fresh-frozen full-torso cadaveric specimens were dissected, and an oblique anatomical corridor to access the L2-S1 discs was examined. Measurements were taken in a static state and with mild retraction of the psoas. The access corridor was defined at L2-5 as the left lateral border of the aorta (or iliac artery) and the anterior medial border of the psoas. The L5-S1 corridor of access was defined transversely from the midsagittal line of the inferior endplate of L-5 to the medial border of the left common iliac vessel and vertically to the first vascular structure that crosses midline. RESULTS: The mean access corridor diameters in the static state and with mild psoas retraction, respectively, were as follows: at L2-3, 18.60 mm and 25.50 mm; at L3-4, 19.25 mm and 27.05 mm; and at L4-5, 15.00 mm and 24.45 mm. The L5-S1 corridor mean values were 14.75 mm transversely, from midline to the left common iliac vessel and 23.85 mm from the inferior endplate of L-5 cephalad to the first midline vessel. CONCLUSIONS: The oblique corridor allows access to the L2-S1 discs while keeping the patient in a lateral decubitus position without a break in the table. Minimal psoas retraction without significant tendon disruption allowed for a generous corridor to the disc space. The L5-S1 disc space can be accessed from an oblique angle consistently with gentle retraction of the iliac vessels. This study supports the potential of an MIS oblique retroperitoneal approach to the L2-S1 discs.

Can triggered electromyography be used to evaluate pedicle screw placement in hydroxyapatite-coated screws: an electrical examination.

OBJECTIVES: To assess if hydroxyapatite (HA)-coated titanium pedicle screws exhibit the same electroconductive characteristics as non-HA-coated screws. METHODS: Resistance measurements were obtained from a random sampling of 10 HA-coated pedicle screws and 10 non-HA-coated screws, and surgical conditions simulated. Surface resistivity measurements were taken for each screw to determine voltage drop over its entire length. RESULTS: The non-HA-coated screws tested showed low resistive properties and proved to be an ideal conductor of electrical current. The resistive properties associated with the HA-coated pedicle screws were found to be similar to those of commonly used insulators removing the effectiveness of triggered electromyographic responses. CONCLUSIONS: Based on test results, these data suggest that the resistance value of the HA-coated screw is large enough to prevent modern Intra-Operative Monitoring (IOM) equipment from delivering the necessary current through the shank of the screw to create a diagnostic electromyographic response. Any response that would be produced would be because of shunting of electric current from the non-coated head of the screw into adjacent tissue and not through the shank of the screw. These study results suggest that HA-coated screws cannot be stimulated to assist in determining the accuracy of pedicle screw placement.

Use of a newly developed delivery device for percutaneous introduction of multiple lead configurations for spinal cord stimulation.

OBJECTIVE: The Epiducer lead delivery system is a novel lead delivery device that can be used to percutaneously implant S-Series paddle leads (St. Jude Medical, Plano, TX, USA) as well as multiple percutaneous leads obviating the need for laminectomy and/or multiple needle sticks, respectively. This study evaluates the safety and usage of the Epiducer lead delivery system. METHODS: An Institutional Review Board-approved observational data collection study was conducted to evaluate usage patterns of the Epiducer system. In addition to the number and frequency of different lead configurations, the following procedural aspects of the surgery were recorded during the evaluation: angle of entry, distance from entry to final lead placement, and physician feedback. Descriptive statistics on adverse events, procedural aspects, and patient outcomes were compiled. RESULTS: Data were collected from 163 patients across 25 investigational sites. Physicians successfully implanted patients using the Epiducer during 89% of the procedures. Seven possible lead configurations were implanted. There were 96% and 92% of physicians "satisfied" or "very satisfied" with accessing the epidural space and placing multiple leads with the Epiducer delivery system, respectfully. Eighty-nine percent of physicians were "satisfied" or "very satisfied" with implanting an S-Series paddle lead using the Epiducer delivery system. Ninety-five percent of physicians were "satisfied" or "very satisfied" with the Epiducer delivery system overall. Ten patients (6%) experienced adverse events. CONCLUSION: Results suggest that the Epiducer delivery system allows for the safe and successful percutaneous implantation of paddle leads and/or multiple lead configurations. Furthermore, physicians are satisfied with the Epiducer delivery system.

Lumbar plexus anatomy within the psoas muscle: implications for the transpsoas lateral approach to the L4-L5 disc.

BACKGROUND: The transpsoas lateral surgical approach has been advocated as an alternative to direct anterior approaches for less invasive or minimally invasive access to the spine. Postoperative thigh pain, paresthesia, and/or weakness have been described after the use of this surgical approach. The purpose of this cadaveric anatomic study is to provide a description of the lumbar plexus as it relates to the transpsoas lateral surgical approach. METHODS: Dissection of the lumbar plexus was performed in eighteen cadaveric specimens. Needle markers were placed in the L2-L3, L3-L4, and L4-L5 discs in the midcoronal plane. The anatomic structures were surveyed, and the proximity of the needle to the neural structures was observed. RESULTS: In thirteen of the eighteen specimens, the femoral nerve received its contributions from the L2 to L4 nerve roots and was formed at the L4-L5 disc space. In all specimens, the femoral nerve passed dorsal to or directly at the midpoint of the disc. In three specimens, the needle displaced or was immediately adjacent to the femoral nerve. The femoral nerve was found between the needle and the posterior aspect of the L4-L5 disc space in thirteen of the eighteen specimens. CONCLUSIONS: Because of the proximity of the neural elements, in particular the femoral nerve, to the center of the disc space, the transpsoas lateral surgical approach to the L4-L5 disc space will likely cause intraoperative displacement of neural structures from their anatomic course during retractor dilation. Careful attention should be paid to retractor placement and dilation time during transpsoas lateral access surgery, particularly at the L4-L5 disc.

The IDET procedure for chronic discogenic low back pain.

STUDY DESIGN: Retrospective study with independent evaluation of patient outcomes approximately 1 year post-intradiscal electrothermal therapy (IDET). OBJECTIVE.: To assess functional status, symptoms, and subsequent treatments of patients treated with IDET. SUMMARY OF BACKGROUND DATA: IDET was introduced as a procedure for discogenic pain. Several studies reported improvement in >70% of patients. METHODS: Seventeen physicians referred 60 patients. Each patient had a positive discogram and had been treated with IDET. Patients were contacted approximately 1 year post-IDET, answered a telephone interview, and completed a self-administered questionnaire. Overall patient satisfaction, pain, functional and work status, analgesic usage, and subsequent treatments were noted. Kaplan-Meier survival curve was generated to predict the percentage that would undergo lumbar surgery after IDET. RESULTS: Average age was 40 years (range 25-64 years) with 66% males and 34% females. Of the 44 patients who responded, 6 patients had a lumbar surgery within 1 year. Their outcomes were excluded from descriptive analysis; 97% continued to have back pain, 11 (29%) reported more pain post versus pre-IDET, 15 (39%) had less pain, and 11 (29%) reported no change; 11 (29%) reported using more pain medication post-IDET, 10 (26%) used the same, 12 (32%) used less, and 5 (13%) used none; 19 (50%) were dissatisfied with IDET, 14 (37%) were satisfied, and 5 (13%) were undecided; 20 (53%) would have the procedure again, 12 (31%) would not, and 6 (16%) were unsure. Most patients wore a brace >6 hours/day after surgery (duration 1-15 months). Sixteen (42%) were employed full-time pre-IDET and 11 (29%) were employed full-time post-IDET. CONCLUSION: At 1-year post-IDET, half of patients were dissatisfied with their outcome. The percentage of patients on disability remained constant. The estimated proportion of patients undergoing fusion was predicted to be 15% at 1 year and 30% at 2 years.

Lumbar intervertebral thermal therapies.

In hopes of improving outcomes for patients with discogenic pain, less invasive techniques that reduce trauma and shorten the recovery period have been developed. This article attempts to present a comprehensive description of minimally invasive techniques, specifically heat treatments, for lumbar disc disease. The goal is to inform and educate the reader on the various thermal therapies available for lumbar disc disease by evaluating the scientific data in an objective manner.