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 Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis (Lou Gehrig's 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.

Minimally invasive lateral mass screw fixation in the cervical spine: initial clinical experience with long-term follow-up.

OBJECTIVE: Lateral mass screw fixation of the subaxial cervical spine has been a major advancement for spinal surgeons. This technique provides excellent three-dimensional fixation from C3 to C7. However, exposure of the dorsal spinal musculature can produce significant postoperative neck pain. The incorporation of a minimal access approach using tubular dilator retractors can potentially overcome the drawbacks associated with the extensive muscle stripping needed for traditional surgical exposures. METHODS: A retrospective analysis was performed on the first 18 patients treated using lateral mass screws placed in a minimally invasive fashion. All patients, except 2 who were lost to follow-up, had a 2-year minimum clinical follow-up. All patients had a computed tomography (CT) scan in the immediate postoperative period to check the positioning of implanted hardware. Operative time, blood loss, and complications were ascertained. Fusion was assessed radiographically with dynamic radiographs and CT scans. RESULTS: Sixteen of the 18 patients underwent successful screw placement. Two patients had the minimal access procedure converted to an open surgery because radiographic visualization was not adequate in the lower cervical spine. Six cases involved unilateral instrumentation and 10 had bilateral screws. A total of 39 levels were instrumented. There were no intraoperative complications, and follow-up CT scans demonstrated no bony violations except in cases where bicortical purchase was achieved. All patients achieved bony fusion. CONCLUSION: A minimally invasive approach using tubular dilator retractors can be a safe and effective means for placing lateral mass screws in the subaxial cervical spine. Up to two levels can be treated in this manner. This approach preserves the integrity of the muscles and ligaments that maintain the posterior tension band of the cervical spine but requires adequate intraoperative imaging.

Pathological features including apoptosis in subacute posttraumatic ascending myelopathy. Case report and review of the literature.

Subacute posttraumatic ascending myelopathy (SPAM) is a rare disorder that may gradually emerge in the first 1 to 3 weeks after a spinal cord injury and is unrelated to syrinx formation or mechanical instability. In addition to several theories that have been put forth to explain the origin of this syndrome, the authors propose a possible role for apoptosis in the causation and the progression of SPAM. They discuss the various theories that have been proposed thus far, to place the role of apoptosis in perspective and use their case as an illustration.

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.

Adjacent segment disease: an uncommon complication after cervical expansile laminoplasty: case report.

OBJECTIVE AND IMPORTANCE: Adjacent segment disc disease is a well-described phenomenon that occurs after anterior cervical spinal fusion. One of the advantages of cervical laminoplasty over anterior approaches is that although the treated segments are stiffened, no formal fusion is performed. This is thought to reduce the biomechanical stresses placed on adjacent levels and thus decrease the likelihood of adjacent level degeneration. CLINICAL PRESENTATION: A 62-year-old man presented with myelopathy attributable to cervical spondylosis and underwent a C3-C7 laminoplasty. Improvements in gait were followed 2 years later by symptomatic disc degeneration and spinal cord compression at T1-T2, which rendered him wheelchair bound. INTERVENTION: The patient was treated with a laminectomy at the level of stenosis accompanied by posterior instrumentation and fusion from C5 to T3. This resulted in clinical improvement, and the patient was returned to his baseline ambulatory status. CONCLUSION: Adjacent segment disease is an uncommon complication that occurs after laminoplasty. Careful attention to preserving facet joint motion in the cervical spine may minimize the stresses placed on adjacent motion segments.

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.

Labeling Schwann cells with CFSE-an in vitro and in vivo study.

Schwann cell (SC) transplantation is a promising strategy for axonal regeneration in the nervous system. Identifying the grafted SCs is an important aspect of this approach. The current study sought to establish a simple, reliable, fluorescent labeling method for SCs with a lipophilic molecule, 5-(and-6)-carboxyfluorescein diacetate succinimidyl ester (CFSE). Human SCs were incubated with varying concentrations of CFSE for different time periods. Based on the viability of labeled SCs and its plating efficiency, 1 min incubation with 5 microM CFSE at 37 degrees C was selected as the optimal labeling condition. Flow cytometric analysis and fluorescence microscopy demonstrated that the fluorescence of labeled SCs would fade over 4 weeks. Immunostaining for the phenotypic expression of SC markers, including S100, GFAP, P75, and MHC-I/II at 1 and 4 weeks after incubation with CFSE showed no difference between labeled and non-labeled SCs. Mixed cultures of labeled human SCs and rat SCs for 48 h were performed in triplicate and demonstrated that no leakage of dye from labeled SCs in cell culture occurred across species. A total of 14 injections of 2x10(5) labeled SCs were performed within the spinal cord at T8 and/or L1 level in 9 nude rats. The animals were euthanized at 1 (6 injections) and 4 weeks (8 injections). Grafted labeled SCs survived for at least 4 weeks, and could be easily recognized in the nude rat spinal cord without leakage of dye to surrounding cells. The SCs migrated in white and gray matter 3-6 mm away from the injection and in the central canal for up to 12 mm. These results suggest that CFSE can be used as a fluorescent tracer of human SCs for both in vitro and in vivo studies, for a period of at least 4 weeks.

Minimally invasive cervical expansile laminoplasty: an initial cadaveric study.

OBJECTIVE: Expansile laminoplasty has been successfully used to treat cervical myelopathy attributable to canal stenosis. However, detachment of the posterior cervical muscles is thought to contribute to postoperative axial neck pain and kyphosis. Minimizing the amount of muscular dissection might reduce the likelihood of these sequelae. METHODS: Six human cadaveric spines were used to assess the feasibility of a minimally invasive laminoplasty technique. A 22-mm tubular dilator port was used to access the lamina-facet junctions from C2 to C7, through bilateral stab incisions at C4-C5 and C5-C6. Troughs at the lamina-facet junctions were drilled bilaterally, and the contiguous laminae were lifted en bloc from one side. Ten-millimeter rib allograft spacers were inserted to maintain a gap on the open side. RESULTS: Exposure of six cervical levels was easily accomplished with two small incisions on each side. Drilling was achieved without dural violations. The midsagittal spinal canal diameter was increased by a mean of 38% and the spinal canal area was increased by an average of 43% at the level of C5. CONCLUSION: A minimally invasive approach for cervical laminoplasty could be performed in human cadavers. The measured increases in spinal canal space approximated those demonstrated to be associated with stabilization or improvement of neurological status.

Minimally invasive lateral mass screws in the treatment of cervical facet dislocations: technical note.

OBJECTIVE: The technique of lateral mass screw and rod or plate fixation is a major advancement in the posterior instrumentation of the cervical spine. This technique provides rigid three-dimensional fixation, restores the dorsal tension band, and provides highly effective stabilization in patients with many types of traumatic injuries. METHODS: Patient 1 was a 32-year-old man who had been in a motor vehicle accident. He presented with right C5 radiculopathy. X-ray findings included 45% anterolisthesis of C4 on C5, bilateral facet disruption, and right unilateral C4-C5 facet fracture and dislocation. The patient was placed in Gardner-Wells tongs, and the fracture was reduced with 25 pounds of traction. Patient 2 was a 56-year-old woman who had been in a motor vehicle accident that resulted in complete quadriplegia. Her initial imaging studies revealed a C3-C4 right unilateral facet fracture with subluxation. She was placed in traction, and her neurological status was reassessed. The findings of her neurological examination revealed improvement: she was found to have Brown-Séquard syndrome. Patient 3 was a 33-year-old man who was involved in a diving accident that resulted in bilaterally jumped facets at C3-C4. The patient was neurologically intact, and attempts at closed reduction were not successful. RESULTS: Patients 1 and 2 underwent anterior cervical discectomy with iliac crest autograft fusion and plating. They were then placed in the prone position, and a dilator tubular retractor system was used to access the facet joint at the level of interest. The facet joints were then denuded and packed with autograft. Lateral mass screws were then placed by means of the Magerl technique, and a rod was used to connect the top-loading screws. Patient 3 underwent posterior surgery that included only removal of the superior facet, intraoperative reduction, and bilateral lateral mass screw and rod placement. CONCLUSION: This technical note describes the successful placement of lateral mass screw and rod constructs with the use of a minimally invasive approach by means of a tubular dilator retractor system. This approach preserves the integrity of the muscles and ligaments that maintain the posterior tension band of the cervical spine.

Complications associated with lumbar stenosis surgery in patients older than 75 years of age.

OBJECT: An aging population will require that surgeons increasingly consider operative intervention in elderly patients. To perform this surgery safely will require an understanding of the factors that predict successful outcomes as well as complications. METHODS: Records of patients older than the age of 75 years who underwent lumbar spinal stenosis surgery were retrospectively reviewed. Preexisting medical illnesses were analyzed using the Charlson Weighted Comorbidity Index. Ambulatory function was rated on a four-point scale. Statistical analysis was performed using a one-tailed t-test with unpaired variance. Eighty-eight patients treated between 1994 and 2001 were identified. Forty-five percent were women and 52 patients underwent spinal fusion. The follow-up period averaged 21 months. Back pain was present preoperatively in 89%; after surgery 43% experienced complete relief and 33% partial improvement. Leg pain was present preoperatively in 98%; after surgery 43% experienced complete relief and 42% partial improvement. Of the 33 patients with preoperative gait disturbances, 61% improved at least one point on the ambulatory scale. Wound complications and systemic complications were demonstrated in 24 and 16 patients, respectively. There were no deaths. Age (p = 0.322), number of fused levels (p = 0.371), and the number of laminectomy levels (p = 0.254) were not predictive of complications. Length of operative time (p = 0.003) and the Charlson Weighted Comorbidity Index score (p = 0.088) were associated with both systemic and wound complications. CONCLUSIONS: Surgery in patients older than age 75 years can be conducted safely and with similar outcome rates as in younger patients. The Charlson Weighted Comorbidity Index score and operative time were predictive of the risk of complications.

Peripheral nerve grafts promoting central nervous system regeneration after spinal cord injury in the primate.

OBJECT: Partial restoration of hindlimb function in adult rats following spinal cord injury (SCI) has been demonstrated using a variety of transplantation techniques. The purpose of the present study was twofold: 1) to determine whether strategies designed to promote regeneration in the rat can yield similar results in the primate; and 2) to establish whether central nervous system (CNS) regeneration will influence voluntary grasping and locomotor function in the nonhuman primate. METHODS: Ten cynomologus monkeys underwent T-11 laminectomy and resection of a 1-cm length of hemispinal cord. Five monkeys received six intercostal nerve autografts and fibrin glue containing acidic fibroblast growth factor (2.1 microg/ml) whereas controls underwent the identical laminectomy procedure but did not receive the nerve grafts. At 4 months postgrafting, the spinal cord-graft site was sectioned and immunostained for peripheral myelin proteins, biotinylated dextran amine, and tyrosine hydroxylase, whereas the midpoint of the graft was analyzed histologically for the total number of myelinated axons within and around the grafts. The animals underwent pre- and postoperative testing for changes in voluntary hindlimb grasping and gait. CONCLUSIONS: 1) A reproducible model of SCI in the primate was developed. 2) Spontaneous recovery of the ipsilateral hindlimb function occurred in both graft- and nongraft-treated monkeys over time without evidence of recovering the ability for voluntary tasks. 3) Regeneration of the CNS from proximal spinal axons into the peripheral nerve grafts was observed; however, the grafts did not promote regeneration beyond the lesion site. 4) The grafts significantly enhanced (p < 0.0001) the regeneration of myelinated axons into the region of the hemisected spinal cord compared with the nongrafted animals.

Polylactic acid mesh reconstruction of the anterior iliac crest after bone harvesting reduces early postoperative pain after anterior cervical fusion surgery.

OBJECTIVE: Autologous iliac crest bone enhances the rate of spinal arthrodesis. However, graft site complications are common, with donor site pain being particularly troublesome. Reconstruction of the hip defect with an absorbable polylactic acid mesh to restore the bony cortical contour has been proposed to reduce hip pain. METHODS: Thirty-nine consecutive patients treated by a single senior surgeon (BAG) during a 14-month period were studied. All patients had cervical spondylosis treated through an anterior approach supplemented with an autologous hip graft. Patients with preexisting hip pain were excluded. Pain was rated on a scale of 1 to 10 at 1 week and 3 months after surgery via a questionnaire. Postoperative pain medication regimens were standardized. RESULTS: Thirty patients were available for follow-up, 15 with mesh implantation and 15 without. Hip pain in the mesh-treated group averaged 4.7 and 1.6 at 1 week and 3 months, respectively. Hip pain in the standard-treatment group averaged 6.9 and 2.5 at 1 week and 3 months, respectively. These differences were statistically significant (P = 0.004 at 1 wk and 0.055 at 3 mo). Hospital length of stay was shorter in the mesh-treated group (2.1 versus 3.2 d, respectively), but this difference was not statistically significant. Two patients without mesh treatment complained of the cosmetic defect resulting from absent bone, and three had temporary difficulty with hip eversion or flexion. Two patients in the mesh-treated group developed seromas, which were treated conservatively. CONCLUSION: Reconstruction of the iliac crest reduces early postoperative pain. Other potential benefits may include shorter hospitalizations and a reduced incidence of hip weakness; however, careful attention to wound closure is necessary to prevent seroma formation.

Ganglionectomy of C-2 for the treatment of medically refractory occipital neuralgia.

Occipital neuralgia is a result of neuropathic pain transmission in the distribution of the greater occipital nerve. Because it is well anatomically localized, occipital neuralgia has been the focus of various surgical treatments. Ablation, decompression, and modulation of the C-2 nerve have all been described as effective treatments. The C-2 dorsal root ganglionectomy provides effective treatment for this disorder with a low incidence of unpleasant side effects. In this review the authors summarize the current treatment of occipital neuralgia.

The Effect of Methylprednisolone on Caspase-3 Activation after Rat Spinal Cord Transection.

Purpose: Caspase-3 is known as a crucial effector for apoptotic cell death. Apoptosis has recently been recognized as an important cell death mechanism after spinal cord injury (SCI). This study attempts to define the effect of methylprednisolone (MP) on the activation of caspase-3 in the lesioned area following SCI. Methods: Forty-eight rats with a complete transection of the thoracic spinal cord received a placebo or MP (30 mg/kg, iv.) at 5 min, 2 and 4 h post-injury and were then sacrificed at 12, 24 h, 3 or 7 days thereafter. Results: Caspase-3 positive cells in the lesioned area were immunocytochemically observed in both cord stumps and decreased in number with increasing distance from the lesion site. More caspase-3 positive cells were present in the MP-treated group than the control group at all time points, but the differences were not statistically significant. Conclusion: These results suggest that the MP-induced decrease of tissue loss following SCI may not involve a reduction of apoptotic cell death.