Todd J. Stewart

Repair of the Injured Spinal Cord and the Potential of Embryonic Stem Cell Transplantation

Traditionally, treatment of spinal cord injury seemed frustrating and hopeless because of the remarkable morbidity and mortality, and restricted therapeutic options. Recent advances in neural injury and repair, and the progress towards development of neuroprotective and regenerative interventions are basis for increased optimism. Neural stem cells have opened a new arena of discovery for the field of regenerative science and medicine. Embryonic stem (ES) cells can give rise to all neural progenitors and they represent an important scientific tool for approaching neural repair. The growing number of dedicated regeneration centers worldwide exemplifies the changing perception towards the do-ability of spinal cord repair and this review was born from a presentation at one such leading center, the Kentucky Spinal Cord Injury Research Center. Current concepts of the pathophysiology, repair, and restoration of function in the damaged spinal cord are presented with an overlay of how neural stem cells, particularly ES cells, fit into the picture as important scientific tools and therapeutic targets. We focus on the use of genetically tagged and selectable ES cell lines for neural induction and transplantation. Unique features of ES cells, including indefinite replication, pluripotency, and genetic flexibility, provide strong tools to address questions of neural repair. Selective marker expression in transplanted ES cell derived neural cells is providing new insights into transplantation and repair not possible previously. These features of ES cells will produce a predictable and explosive growth in scientific tools that will translate into discoveries and rapid progress in neural repair.

CERVICAL DEFORMITY CORRECTION

SUBAXIAL CERVICAL DEFORMITIES most often occur in the sagittal plane, primarily as kyphosis. Kyphosis may develop secondary to advanced degenerative disease, trauma, neoplastic disease, or after surgery. Whatever the cause, the development of cervical deformity should be avoided and corrected when appropriate because the greater the deformity, the greater the probability of an associated neurological deficit or chronic pain. Patients usually present with mechanical type cervical pain, with or without neurological deficit (i.e., myelopathy). They may also be relatively asymptomatic. Work-up includes appropriate imaging studies, such as radiographs, including dynamic images, and magnetic resonance imaging or computed tomography myelography. The deformity may be accurately assessed and an appropriate surgical strategy undertaken. Depending on flexibility of the deformity and the presence or absence of facet ankylosis, a dorsal, ventral, or combined approach may be used. All approaches are unique in their ability to correct a deformity and in their associated complications. A comprehensive discussion of each is undertaken.

MULTIPLE LEVEL DISCECTOMY AND FUSION

THE VENTROLATERAL APPROACH for surgical decompression of the cervical spine is widely used and well known to most spinal surgeons. Because compression of the spinal cord and nerve roots usually occurs ventral to the spinal cord, and the spinal cord does not tolerate traction, this approach allows safe and direct decompression of most compressive pathology. This article reviews the indications, diagnostic evaluation, and technique for multiple level discectomy and fusion. It further addresses the advantages and disadvantages of this technique compared with alternate surgical procedures.

The natural history and clinical presentation of cervical spondylotic myelopathy.

Cervical spondylotic myelopathy (CSM) refers to impaired function of the spinal cord caused by degenerative changes of the cervical spine resulting in spinal cord compression. It is the most common disorder in the United States causing dysfunction of the spinal cord. A literature review of the natural history of mild cervical myelopathy is undertaken. Clinical presentation and current concepts of pathophysiology are also discussed. While many patients with mild signs of CSM will stabilize or improve over time with conservative treatment, the clinical course of a specific individual patient cannot be predicted. Asymptomatic patients with cervical stenosis and abnormalities on electrophysiologic studies may be at higher risk for developing myelopathy.

NG2+ Progenitors Derived From Embryonic Stem Cells Penetrate Glial Scar and Promote Axonal Outgrowth Into White Matter After Spinal Cord Injury

The glial scar resulting from spinal cord injury is rich in chondroitin sulfate proteoglycan (CSPG), a formidable barrier to axonal regeneration. We explored the possibility of breaching that barrier by first examining the scar in a functional in vitro model. We found that embryonic stem cell‐derived neural lineage cells (ESNLCs) with prominent expression of nerve glial antigen 2 (NG2) survived, passed through an increasingly inhibitory gradient of CSPG, and expressed matrix metalloproteinase 9 (MMP‐9) at the appropriate stage of their development. Outgrowth of axons from ESNLCs followed because the migrating cells sculpted pathways in which CSPG was degraded. The degradative mechanism involved MMP‐9 but not MMP‐2. To confirm these results in vivo, we transplanted ESNLCs directly into the cavity of a contused spinal cord 9 days after injury. A week later, ESNLCs survived and were expressing both NG2 and MMP‐9. Their axons had grown through long distances (>10 mm), although they preferred to traverse white rather than gray matter. These data are consistent with the concept that expression of inhibitory CSPG within the injury scar is an important impediment to regeneration but that NG2+ progenitors derived from ESNLCs can modify the microenvironment to allow axons to grow through the barrier. This beneficial action may be partly due to developmental expression of MMP‐9. We conclude that it might eventually be possible to encourage axonal regeneration in the human spinal cord by transplanting ESNLCs or other cells that express NG2.

Circumferential vertebrectomy with reconstruction for holocervical aneurysmal bone cyst at C4 in a 15-year-old girl.

Study Design. The authors describe the unique case of a 15-year-old girl with a holovertebral aneurysmal bone cyst at C4, causing anterolisthesis and kyphosis, who underwent circumferential vertebrectomy with reconstruction and rigid fusion. Objective. To report an unusual manifestation of aneurysmal bone cyst, requiring special considerations for surgery. The discussion highlights emerging principles for treatment of this lesion, and cervical spine fusion, in the pediatric population. Summary of Background Data. There is no previous report of a holovertebral aneurysmal bone cyst of the pediatric cervical spine. The potential for neurologic or vascular compromise from this lesion is substantial if left untreated, and the risk of recurrence or other morbidity is significantly higher unless completely resected. Methods. A 15-year-old white female presented with a 4-month history of neck pain after a mild injury, but was neurologically intact. Diagnostic imaging revealed a holovertebral, multicystic, and osteolytic lesion with multiple fluid–fluid levels in the fourth cervical vertebra. Total vertebrectomy and repair were performed with fibular strut grafts and placement of rigid anterior and posterior instrumentation. This was accomplished in a single anteroposterior operative pass. Results. Surgical treatment produced a stable bony fusion with no neurologic or vascular sequelae. This approach minimizes the risk of recurrence and the possibility of postoperative spinal instability. Conclusion. Spinal aneurysmal bone cyst in children presents diverse challenges. These lesions should be treated with complete resection to minimize the chance of recurrence. In pediatric cases, defects created by resection should be corrected by fusion to minimize the risk of postoperative instability and growth abnormality. One-year followup demonstrated a stable construct, and the patient remains neurologically at her baseline.

Biopsy of the Superficial Cortex: Predictors of Effectiveness and Outcomes

BACKGROUND Brain biopsies of superficial cortex are performed for diagnosis of neurological diseases, but preoperative predictors of successful diagnosis and risks are lacking. OBJECTIVE We evaluated effectiveness and outcomes of superficial cortical biopsies and determined preoperative predictors of diagnosis, outcomes, morbidities, and mortality. METHODS A single-institution retrospective analysis of 170 patients who underwent open brain biopsies of superficial cortex was performed. Clinical predictors of effectiveness and outcomes were determined using univariate/multivariate analyses and a system for risk-benefit stratification was created and tested. RESULTS Brain biopsies led to successful diagnosis in 122 of 170 (71.8%) and affected management in 97 of 170 (57.1%) cases. Factors increasing the odds of diagnostic pathology included age older than 45 years (odds ratio [OR]: 2.67, 95% confidence interval [CI]: 1.34-5.27, P < .01), previous cancer diagnosis (OR: 3.64, 95% CI: 1.69-7.85, P < .001), focal (OR: 3.90, 95% CI: 1.91-8.00, P < .001) and enhancing (OR: 5.03, 95% CI: 2.41-10.52, P < .001) lesions on magnetic resonance imaging, biopsy of specific lesions on magnetic resonance imaging (OR: 9.34, 95% CI: 4.29-20.33, P < .001), and use of intraoperative navigation (OR: 6.59, 95% CI: 3.04-14.28, P < .001). Brain biopsies led to symptomatic intracranial hemorrhage, seizures, other significant morbidities, and perioperative mortality in 12.4%, 16.2%, 37.1%, and 8% of cases, respectively. Risk of postoperative intracranial hemorrhage was increased by a history of aspirin use (OR: 2.51, 95% CI: 1.23-5.28, P < .05) and age older than 60 years (OR: 2.66, 95% CI: 1.36-5.18, P < .01). CONCLUSION Effectiveness and risk of morbidity/mortality can be estimated preoperatively for patients undergoing open brain biopsies of the superficial cortex. Older age and specific imaging characteristics increase the odds of diagnostic biopsy. Conversely, older age and aspirin use increases the risk of postoperative complications.

Biopsy of the superficial cortex

BACKGROUND Brain biopsies of superficial cortex are performed for diagnosis of neurological diseases, but preoperative predictors of successful diagnosis and risks are lacking. OBJECTIVE We evaluated effectiveness and outcomes of superficial cortical biopsies and determined preoperative predictors of diagnosis, outcomes, morbidities, and mortality. METHODS A single-institution retrospective analysis of 170 patients who underwent open brain biopsies of superficial cortex was performed. Clinical predictors of effectiveness and outcomes were determined using univariate/multivariate analyses and a system for risk-benefit stratification was created and tested. RESULTS Brain biopsies led to successful diagnosis in 122 of 170 (71.8%) and affected management in 97 of 170 (57.1%) cases. Factors increasing the odds of diagnostic pathology included age older than 45 years (odds ratio [OR]: 2.67, 95% confidence interval [CI]: 1.34-5.27, P < .01), previous cancer diagnosis (OR: 3.64, 95% CI: 1.69-7.85, P < .001), focal (OR: 3.90, 95% CI: 1.91-8.00, P < .001) and enhancing (OR: 5.03, 95% CI: 2.41-10.52, P < .001) lesions on magnetic resonance imaging, biopsy of specific lesions on magnetic resonance imaging (OR: 9.34, 95% CI: 4.29-20.33, P < .001), and use of intraoperative navigation (OR: 6.59, 95% CI: 3.04-14.28, P < .001). Brain biopsies led to symptomatic intracranial hemorrhage, seizures, other significant morbidities, and perioperative mortality in 12.4%, 16.2%, 37.1%, and 8% of cases, respectively. Risk of postoperative intracranial hemorrhage was increased by a history of aspirin use (OR: 2.51, 95% CI: 1.23-5.28, P < .05) and age older than 60 years (OR: 2.66, 95% CI: 1.36-5.18, P < .01). CONCLUSION Effectiveness and risk of morbidity/mortality can be estimated preoperatively for patients undergoing open brain biopsies of the superficial cortex. Older age and specific imaging characteristics increase the odds of diagnostic biopsy. Conversely, older age and aspirin use increases the risk of postoperative complications.

Biopsy of the Superficial CortexPredictors of Effectiveness and Outcomes

BACKGROUND Brain biopsies of superficial cortex are performed for diagnosis of neurological diseases, but preoperative predictors of successful diagnosis and risks are lacking. OBJECTIVE We evaluated effectiveness and outcomes of superficial cortical biopsies and determined preoperative predictors of diagnosis, outcomes, morbidities, and mortality. METHODS A single-institution retrospective analysis of 170 patients who underwent open brain biopsies of superficial cortex was performed. Clinical predictors of effectiveness and outcomes were determined using univariate/multivariate analyses and a system for risk-benefit stratification was created and tested. RESULTS Brain biopsies led to successful diagnosis in 122 of 170 (71.8%) and affected management in 97 of 170 (57.1%) cases. Factors increasing the odds of diagnostic pathology included age older than 45 years (odds ratio [OR]: 2.67, 95% confidence interval [CI]: 1.34-5.27, P < .01), previous cancer diagnosis (OR: 3.64, 95% CI: 1.69-7.85, P < .001), focal (OR: 3.90, 95% CI: 1.91-8.00, P < .001) and enhancing (OR: 5.03, 95% CI: 2.41-10.52, P < .001) lesions on magnetic resonance imaging, biopsy of specific lesions on magnetic resonance imaging (OR: 9.34, 95% CI: 4.29-20.33, P < .001), and use of intraoperative navigation (OR: 6.59, 95% CI: 3.04-14.28, P < .001). Brain biopsies led to symptomatic intracranial hemorrhage, seizures, other significant morbidities, and perioperative mortality in 12.4%, 16.2%, 37.1%, and 8% of cases, respectively. Risk of postoperative intracranial hemorrhage was increased by a history of aspirin use (OR: 2.51, 95% CI: 1.23-5.28, P < .05) and age older than 60 years (OR: 2.66, 95% CI: 1.36-5.18, P < .01). CONCLUSION Effectiveness and risk of morbidity/mortality can be estimated preoperatively for patients undergoing open brain biopsies of the superficial cortex. Older age and specific imaging characteristics increase the odds of diagnostic biopsy. Conversely, older age and aspirin use increases the risk of postoperative complications.

Impact of lateral mass anatomic variation on ideal polyaxial screw head mobility: technical considerations

Objective. To assess optimal angulation characteristics of lateral mass screws for subaxial (C3 to C6) fixation of the cervical spine in the neutral position. Background. In the typical Magerl or Anderson placement technique, the screw trajectory is ideally parallel to the facet joint. For the rod and screw to align properly, the screw head must rotate enough to become perpendicular to the rod. If the optimal angle for the screw head is limited by the screw design, abnormal torsional forces will be generated at the rod/screw interface inducing kyphosis. In this paper, we examined the spinal anatomy in patients with normal CTs to determine the necessary range of motion between tulip head and screw to prevent forced persuasion and abnormal cervical spine alignment. Methods. We examined subaxial radiographs of 292 vertebrae from C3 to C6 in 73 normal subjects. Computed tomography (CT) scans of the cervical spine with multiplanar reconstructions were evaluated in the axial and sagittal planes. A planned screw entry angle of 30° based upon the midpoint of the lateral mass was used in the axial plane, and parallel to the facet joint in the sagittal plane. The screw head angle (SHA) was then calculated from this 3D measured angle. Results. The measured SHA ranged from 27 to 60°. The average SHA was 43.8°. The average SHA was not significantly different between the levels measured with consistent range and standard deviation. Seventy-six percent (223/292) of levels measured required a SHA >40°, and 12% (36/292) required a SHA >50°. Conclusion. The authors recommend using cervical instrumentation systems that allow for at least 55° of freedom of the polyaxial head to prevent abnormal segmental forces. In systems with lesser angulation, technique modifications must be applied to prevent translational forces.