Allan D. Levi

A comprehensive review of the safety profile of bone morphogenetic protein in spine surgery.

WE REVIEW OUR current understanding of the development and potential clinical applications of bone morphogenetic protein (BMP) in spine surgery. We also review the evidence for adverse events associated with the use of BMP and suggest potential reasons for these events and means of complication avoidance. Bone morphogenetic protein 2 (rhBMP-2) is approved by the Food and Drug Administration for anterior lumbar interbody fusion; rhBMP-7, on the other hand, is approved for long bone defects and has received a humanitarian device exemption for revision posterolateral lumbar operations and recalcitrant long bone unions. Nevertheless, “off-label” use in various spinal procedures has been reported and is increasing in frequency. Specific guidelines for rhBMP-2 and rhBMP-7 use are lacking because of the limited availability of randomized controlled clinical trials and its diverse use in many spinal applications. Mechanisms of delivery, carrier type, graft position, surgical location, and variations in BMP concentration may differ from one surgery to the next. Adverse events linked to either rhBMP-2 or rhBMP-7 use include ectopic bone formation, bone resorption or remodeling at the graft site, hematoma, neck swelling, and painful seroma. Other potential theoretical concerns include carcinogenicity and teratogenic effects. In this review, we provide the reader with a historical perspective on BMP, current and past research to support its use in spinal procedures, and a critical analysis of the complications reported thus far.

An anatomical study of the lumbosacral plexus as related to the minimally invasive transpsoas approach to the lumbar spine.

OBJECT Minimally invasive anterolateral approaches to the lumbar spine are options for the treatment of a number of adult degenerative spinal disorders. Nerve injuries during these surgeries, although rare, can be devastating complications. With an increasing number of spine surgeons utilizing minimal access retroperitoneal surgery to treat lumbar problems, the frequency of complications associated with this approach will likely increase. The authors sought to better understand the location of the lumbar contribution of the lumbosacral plexus relative to the disc spaces encountered when performing the minimally invasive transpsoas approach, also known as extreme lateral interbody fusion or direct lateral interbody fusion. METHODS Three fresh cadavers were placed lateral, and a total of 3 dissections of the lumbar contribution of the lumbosacral plexus were performed. Radiopaque soldering wire was then laid along the anterior margin of the nerve fibers and the exiting femoral nerve. Markers were placed at the disc spaces and lateral fluoroscopy was used to measure the location of the lumbar plexus along each respective disc space in the lumbar spine (L1-2, L2-3, L3-4, and L4-5). RESULTS The lumbosacral plexus was found lying within the substance of the psoas muscle between the junction of the transverse process and vertebral body and exited along the medial edge of the psoas distally. The lumbosacral plexus was most dorsally positioned at the posterior endplate of L1-2. A general trend of progressive ventral migration of the plexus on the disc space was noted at L2-3, L3-4, and L4-5. Average ratios were calculated at each level (location of the plexus from the dorsal endplate to total disc length) and were 0 (L1-2), 0.11 (L2-3), 0.18 (L3-4), and 0.28 (L4-5). CONCLUSIONS This anatomical study suggests that positioning the dilator and/or retractor in a posterior position of the disc space may result in nerve injury to the lumbosacral plexus, especially at the L4-5 level. The risk of injuring inherent nerve branches directed to the psoas muscle as well as injury to the genitofemoral nerve do still exist.

Computer-assisted Fluoroscopic Targeting System for Pedicle Screw Insertion

OBJECTIVEBiplanar fluoroscopic imaging linked to a computer-driven mechanical end-effector is under development as a targeting system for spinal surgery. This technology has the potential to enhance standard intraoperative fluoroscopic information for localization of the pedicle entry point and trajectory, and it may be an effective alternative to the computed tomography-based image-guided system (IGS) in pedicle screw placement. A preclinical study to assess the accuracy and time efficiency of this system versus a conventional IGS was conducted. METHODSPedicle screw placement was performed in six cadavers from T1 to S1 levels using the ViewPoint IGS (Picker International, Inc., Cleveland, OH) on one side versus the Fluorotactic guidance system (Z-Kat, Inc., Miami, FL) on the other side. Of 216 possible pedicles, 208 were instrumented; 8 pedicle diameters were too small or were not adequately imaged. Postinsertion, each pedicle was assessed for the presence and location of cortical perforation using computed tomographic scanning and direct visualization. RESULTSThe number of successful screw placements was 89 (87.3%) of 102 for IGS and 87 (82.1%) of 106 for the Fluorotactic guidance system, respectively. The mean time to register and operate on one level using the Fluorotactic guidance system was 14:34 minutes (minutes:seconds), compared with 6:50 minutes using the IGS. The average fluoroscope time was 4.6 seconds per pedicle. CONCLUSIONOur data indicate that this first-generation fluoroscopy-based targeting system can significantly assist the surgeon in pedicle screw placement. The overall accuracy is comparable to an IGS, especially in the region of T9–L5. A second-generation system with a faster end-effector and user-friendly interface should significantly reduce the operating and fluoroscope time.

An analysis of postoperative thigh symptoms after minimally invasive transpsoas lumbar interbody fusion: Clinical article

OBJECTIVE The minimally invasive transpsoas interbody fusion technique requires dissection through the psoas muscle, which contains the nerves of the lumbosacral plexus posteriorly and genitofemoral nerve anteriorly. Retraction of the psoas is becoming recognized as a cause of transient postoperative thigh pain, numbness, paresthesias, and weakness. However, few reports have described the nature of thigh symptoms after this procedure. METHODS The authors performed a review of patients who underwent the transpsoas technique for lumbar spondylotic disease, disc degeneration, and spondylolisthesis treated at a single academic medical center. A review of patient charts, including the use of detailed patient-driven pain diagrams performed at equal preoperative and follow-up intervals, investigated the survival of postoperative thigh pain, numbness, paresthesias, and weakness of the iliopsoas and quadriceps muscles in the follow-up period on the ipsilateral side of the surgical approach. RESULTS Over a 3.2-year period, 59 patients underwent transpsoas interbody fusion surgery. Of these, 62.7% had thigh symptoms postoperatively. New thigh symptoms at first follow-up visit included the following: burning, aching, stabbing, or other pain (39.0%); numbness (42.4%); paresthesias (11.9%); and weakness (23.7%). At 3 months postoperatively, these percentages decreased to 15.5%, 24.1%, 5.6%, and 11.3%, respectively. Within the patient sample, 44% underwent a 1-level, 41% a 2-level, and 15% a 3-level transpsoas operation. While not statistically significant, thigh pain, numbness, and weakness were most prevalent after L4-5 transpsoas interbody fusion at the first postoperative follow-up. The number of lumbar levels that were surgically treated had no clear association with thigh symptoms but did correlate directly with surgical time, intraoperative blood loss, and length of hospital stay. CONCLUSIONS Transpsoas interbody fusion is associated with high rates of immediate postoperative thigh symptoms. While larger, prospective studies are necessary to validate these findings, the authors found that half of the patients had symptom resolution at approximately 3 months postoperatively and more than 90% by 1 year.

Clinical Outcomes Using Modest Intravascular Hypothermia After Acute Cervical Spinal Cord Injury

BACKGROUNDAlthough a number of neuroprotective strategies have been tested after spinal cord injury (SCI), no treatments have been established as a standard of care. OBJECTIVEWe report the clinical outcomes at 1-year median follow-up, using endovascular hypothermia after SCI and a detailed analysis of the complications. METHODSWe performed a retrospective analysis of American Spinal Injury Association and International Medical Society of Paraplegia Impairment Scale (AIS) scores and complications in 14 patients with SCI presenting with a complete cervical SCI (AIS A). All patients were treated with 48 hours of modest (33°C) intravascular hypothermia. The comparison group was composed of 14 age- and injury-matched subjects treated at the same institution. RESULTSSix of the 14 cooled patients (42.8%) were incomplete at final follow-up (50.2 [9.7] weeks). Three patients improved to AIS B, 2 patients improved to AIS C, and 1 patient improved to AIS D. Complications were predominantly respiratory and infectious in nature. However, in the control group, a similar number of complications was observed. Adverse events such as coagulopathy, deep venous thrombosis, and pulmonary embolism were not seen in the patients undergoing hypothermia. CONCLUSIONThis study is the first phase 1 clinical trial on the safety and outcome with the use of endovascular hypothermia in the treatment of acute cervical SCI. In this small cohort of patients with SCI, complication rates were similar to those of normothermic patients with an associated AIS A conversion rate of 42.8%.

Intradural spinal arachnoid cysts in adults.

BACKGROUND Idiopathic arachnoid cysts are rare lesions not associated with trauma or other inflammatory insults. To date, there have been few large series describing the presentation and management of these lesions. METHODS Twenty-one cases of intradural spinal arachnoid cysts were identified (1994-2001). Pediatric patients and cases with antecedent trauma were excluded. There were eight women and 13 men with an average age of 52 years. Follow-up averaged 17 months. RESULTS Cysts were most commonly found in the thoracic spine (81%). Fifteen cysts were dorsal to the spinal cord and six were ventral to the spinal cord. All patients underwent laminectomy with cyst fenestration and radical cyst wall resection. Based upon intraoperative ultrasonography, four cysts were also shunted to the subarachnoid space, and seven patients had an expansile duraplasty with freeze-dried dural allograft. Of the seven patients with syringomyelia, three resolved with extramedullary cyst resection alone. Four required syrinx to subarachnoid shunting. Follow-up MRI demonstrated cyst resolution in all cases. All seven intramedullary syrinxes were decreased in size and four resolved completely. Weakness (100%), hyperreflexia (91%), and incontinence (80%) were more likely to improve than neuropathic pain (44%) and numbness (33%). One patient had increased numbness postoperatively. CONCLUSIONS Ventral cysts are more likely to cause weakness and myelopathic signs. Preoperative symptoms of neuropathic pain and numbness are less likely to improve than weakness and myelopathy. Utilizing intraoperative ultrasound to guide aggressive surgical treatment with the adjuncts of shunting and duraplasty results in a high rate of cyst and syrinx obliteration.

Bone marrow stromal cells for repair of the spinal cord: towards clinical application.

Stem cells have been recognized and intensively studied for their potential use in restorative approaches for degenerative diseases and traumatic injuries. In the central nervous system (CNS), stem cell-based strategies have been proposed to replace lost neurons in degenerative diseases such as Parkinsons disease, Huntingtons disease, and amyotrophic lateral sclerosis (Lou Gehrigs disease), or to replace lost oligodendrocytes in demyelinating diseases such as multiple sclerosis. Stem cells have also been implicated in repair of the adult spinal cord. An impact to the spinal cord results in immediate damage to tissue including blood vessels, causing loss of neurons, astrocytes, and oligodendrocytes. In time, more tissue nearby or away from the injury site is lost due to secondary injury. In case of relatively minor damage to the cord some return of function can be observed, but in most cases the neurological loss is permanent. This review will focus on in vitro and in vivo studies on the use of bone marrow stromal cells (BMSCs), a heterogeneous cell population that includes mesenchymal stem cells, for repair of the spinal cord in experimental injury models and their potential for human application. To optimally benefit from BMSCs for repair of the spinal cord it is imperative to develop in vitro techniques that will generate the desired cell type and/or a large enough number for in vivo transplantation approaches. We will also assess the potential and possible pitfalls for use of BMSCs in humans and ongoing clinical trials.

Clinical application of modest hypothermia after spinal cord injury.

There is widespread interest in the use of hypothermia in the treatment of CNS injury. While there is considerable experience in the use of cooling for a variety of brain pathologies, limited data exist after spinal cord injury. In the past few years, technological advances in the induction and maintenance of cooling have been achieved and can potentially allow for a more accurate evaluation of this form of treatment. We report a series of 14 patients with an average age of 39.4 years (range, 16-62 years) with acute, complete (AIS A) cervical spinal cord injuries who underwent a protocol using an intravascular cooling catheter to achieve modest (33 degrees C) systemic hypothermia. There was an excellent correlation between intravascular and intrathecal cerebrospinal fluid temperature. The average time between injury and induction of hypothermia was 9.17 +/- 2.24 h (mean +/- SEM); the time to target temperature was 2.72 +/- 0.42 h; the duration of cooling at target temperature was 47.6 +/- 3.1 h; the average total length of time of cooling was 93.6 +/- 4 h. There was a positive correlation between temperature and heart rate. Most documented adverse events were respiratory in nature. We were able to effectively deliver systemic cooling using the cooling catheters with minimal variation in body temperature. The study represents the largest, modern series of hypothermia treatment of acute spinal cord injury with intravascular cooling techniques and provides needed baseline data for outcome studies to include larger multi-center, randomized trials.

Neurologic deterioration secondary to unrecognized spinal instability following trauma - A multicenter study

Study Design. A retrospective study was undertaken that evaluated the medical records and imaging studies of a subset of patients with spinal injury from large level I trauma centers. Objective. To characterize patients with spinal injuries who had neurologic deterioration due to unrecognized instability. Summary of Background Data. Controversy exists regarding the most appropriate imaging studies required to “clear” the spine in patients suspected of having a spinal column injury. Although most bony and/or ligamentous spine injuries are detected early, an occasional patient has an occult injury, which is not detected, and a potentially straightforward problem becomes a neurologic catastrophe. Methods. The study was designed as a retrospective review of patients who had neurologic deterioration as a direct result of an unrecognized fracture, subluxation, or soft tissue injury of the cervical, thoracic, or lumbar spine from 8 level I trauma centers. Demographics, injury information, and neurologic outcome were collected. The etiology and incidence of the missed injury were determined. Results. A total of 24 patients were identified who were treated or referred to 1 of the participating trauma centers and had an adverse neurologic outcome as a result of the missed injury. The average age of the patientswas 50 years (range 18–92), and average delay in diagnosis was 19.8 days. Radiculopathy developed in 5 patients, 16 had spinal cord injuries, and 3 patients died as a result oftheir neurologic injury. The most common reason for the missed injury was insufficient imaging studies (58.3%), while only 33.3% were a result of misread radiographs or 8.3% poor quality radiographs. The incidence of missed injuries resulting in neurologic injury in patients with spine fractures or strains was 0.21%, and the incidence as a percentage of all trauma patients evaluated was 0.025%. Conclusions. This multicenter study establishes that missed spinal injuries resulting in a neurologic deficit continue to occur in major trauma centers despite the presence of experienced personnel and sophisticated imaging techniques. Older age, high impact accidents, and patients with insufficient imaging are at highest risk.

Delayed postoperative spinal epidural hematomas

BACKGROUND CONTEXT Symptomatic epidural hematomas after spinal surgery are uncommon and are usually diagnosed within 24 hours after surgery. PURPOSE We report a series of delayed epidural hematomas in a subset of patients who awoke from surgery neurologically unchanged and then deteriorated more than 3 days after their index procedure. The goals of this report are to outline the clinical presentation, radiological characteristics and outcome of this uncommon entity. STUDY DESIGN/SETTING We retrospectively reviewed the database of six spine surgeons over a 4-year period, looking for presence of epidural hematomas as a cause of clinical deterioration after an asymptomatic postoperative period of at least 3 days. PATIENT SAMPLE We identified a subset of patients who awoke from surgery neurologically unchanged and then deteriorated more than 3 days after spinal surgery. A total of 4,018 patients were identified over the 4-year period of review. OUTCOME MEASURES Presence of spinal epidural hematoma as a cause of clinical deterioration after an asymptomatic period of at least 3 days. The medical records, including the history, physical, preoperative and postoperative neurological examinations, as well as plain radiographs and magnetic resonance images, were reviewed. METHODS We retrospectively reviewed the database of six spine surgeons over a 4-year period. We looked for delayed spinal epidural hematomas as a cause of clinical deterioration after an asymptomatic postoperative period of at least 3 days. We examined potential risk factors for spinal extradural hematomas. RESULTS Of 4,018 patients, we identified seven with spinal epidural hematoma who presented more than 3 days after their index procedure. The initial presenting symptom, which heralded the subsequent onset of neurological deterioration, consisted of severe sharp pain with radiation to the extremities. The average time to neurological deterioration was 5.3 days. Fifty-seven percent of the patients had multiple previous spinal surgeries at the site of the epidural hematoma. Surgical evacuation of the epidural hematomas resulted in neurological improvement in five patients. Persistent neurological deficits were observed in two patients. CONCLUSION Delayed spinal epidural hematomas are an uncommon cause of delayed deterioration after spinal surgery. Previous surgery with attendant scarring that results in impairment of clot resorption may be a contributing factor in the development of the condition.