Nicholas C. Bambakidis, Eric M. Horn, Peter Nakaji, Nicholas Theodore, Elizabeth Bless, Tammy Dellovade, Chiyuan Ma, Xukui Wang, Mark C. Preul, Stephen W. Coons, Robert F. Spetzler and Volker K. H. Sonntag
Sonic hedgehog (Shh) is a glycoprotein molecule that upregulates the transcription factor Gli1. The Shh protein plays a critical role in the proliferation of endogenous neural precursor cells when directly injected into the spinal cord after a spinal cord injury in adult rodents. Small-molecule agonists of the hedgehog (Hh) pathway were used in an attempt to reproduce these findings through intravenous administration.
The expression of Gli1 was measured in rat spinal cord after the intravenous administration of an Hh agonist. Ten adult rats received a moderate contusion and were treated with either an Hh agonist (10 mg/kg, intravenously) or vehicle (5 rodents per group) 1 hour and 4 days after injury. The rats were killed 5 days postinjury. Tissue samples were immediately placed in fixative. Samples were immunohistochemically stained for neural precursor cells, and these cells were counted.
Systemic dosing with an Hh agonist significantly upregulated Gli1 expression in the spinal cord (p < 0.005). After spinal contusion, animals treated with the Hh agonist had significantly more nestin-positive neural precursor cells around the rim of the lesion cavity than in vehicle-treated controls (means ± SDs, 46.9 ± 12.9 vs 20.9 ± 8.3 cells/hpf, respectively, p < 0.005). There was no significant difference in the area of white matter injury between the groups.
An intravenous Hh agonist at doses that upregulate spinal cord Gli1 transcription also increases the population of neural precursor cells after spinal cord injury in adult rats. These data support previous findings based on injections of Shh protein directly into the spinal cord.
Eric M. Horn, Nicholas Theodore, Neil R. Crawford, Nicholas C. Bambakidis and Volker K. H. Sonntag
Lateral mass screws are traditionally used to fixate the subaxial cervical spine, while pedicle screws are used in the thoracic spine. Lateral mass fixation at C-7 is challenging due to thin facets, and placing pedicle screws is difficult due to the narrow pedicles. The authors describe their clinical experience with a novel technique for transfacet screw placement for fixation at C-7.
A retrospective chart review was undertaken in all patients who underwent transfacet screw placement at C-7. The technique of screw insertion was the same for each patient. Polyaxial screws between 8- and 10-mm-long were used in each case and placed through the facet from a perpendicular orientation. Postoperative radiography and clinical follow-up were analyzed for aberrant screw placement or construct failure.
Ten patients underwent C-7 transfacet screw placement between June 2006 and March 2007. In all but 1 patient screws were placed bilaterally, and the construct lengths ranged from C-3 to T-5. One patient with a unilateral screw had a prior facet fracture that precluded bilateral screw placement. There were no intraoperative complications or screw failures in these patients. After an average of 6 months of follow-up there were no hardware failures, and all patients showed excellent alignment.
The authors present the first clinical demonstration of a novel technique of posterior transfacet screw placement at C-7. These results provide evidence that this technique is safe to perform and adds stability to cervicothoracic fixation.
Nicholas C. Bambakidis, John Butler, Eric M. Horn, Xukui Wang, Mark C. Preul, Nicholas Theodore, Robert F. Spetzler and Volker K. H. Sonntag
✓ The development of an acute traumatic spinal cord injury (SCI) inevitably leads to a complex cascade of ischemia and inflammation that results in significant scar tissue formation. The development of such scar tissue provides a severe impediment to neural regeneration and healing with restoration of function. A multimodal approach to treatment is required because SCIs occur with differing levels of severity and over different lengths of time. To achieve significant breakthroughs in outcomes, such approaches must combine both neuroprotective and neuroregenerative treatments. Novel techniques modulating endogenous stem cells demonstrate great promise in promoting neuroregeneration and restoring function.
Mehmet Senoglu, Sam Safavi-Abbasi, Nicholas Theodore, Nicholas C. Bambakidis, Neil R. Crawford and Volker K. H. Sonntag
In this study the authors investigated the anatomical, clinical, and imaging features as well as incidence of congenital defects of the C-1 arch.
The records of 1104 patients who presented with various medical problems during the time between January 2006 and December 2006 were reviewed retrospectively. The craniocervical computed tomography (CT) scans obtained in these patients were evaluated to define the incidence of congenital defects of the posterior arch of C-1. In addition, 166 dried C-1 specimens and 84 fresh human cadaveric cervical spine segments were evaluated for anomalies of the C-1 arch.
Altogether, 40 anomalies (2.95%) were found in 1354 evaluated cases. Of the 1104 patients in whom CT scans were acquired, 37 (3.35%) had congenital defects of the posterior arch of the atlas. The incidence of each anomaly was as follows: Type A, 29 (2.6%); Type B, six (0.54%); and Type E, two (0.18%). There were no Type C or D defects. One patient (0.09%) had an anterior arch cleft. None of the reviewed patients had neurological deficits or required surgical intervention for their anomalies. Three cases of Type A posterior arch anomalies were present in the cadaveric specimens.
Most congenital anomalies of the atlantal arch are found incidentally in asymptomatic patients. Congenital defects of the posterior arch are more common than defects of the anterior arch.
Sam Safavi-Abbasi, Joseph M. Zabramski, Pushpa Deshmukh, Cassius V. Reis, Nicholas C. Bambakidis, Nicholas Theodore, Neil R. Crawford, Robert F. Spetzler and Mark C. Preul
The authors quantitatively assessed the effects of balloon inflation as a model of tumor compression on the brainstem, cranial nerves, and clivus by measuring the working area, angle of attack, and brain shift associated with the retrosigmoid approach.
Six silicone-injected cadaveric heads were dissected bilaterally via the retrosigmoid approach. Quantitative data were generated, including key anatomical points on the skull base and brainstem. All parameters were measured before and after inflation of a balloon catheter (inflation volume 4.8 ml, diameter 20 mm) intended to mimic tumor compression.
Balloon inflation significantly shifted (p < 0.001) the brainstem and cranial nerve foramina (mean [± standard deviation] displacement of upper brainstem, 10.2 ± 3.7 mm; trigeminal nerve exit, 6.99 ± 2.38 mm; facial nerve exit, 9.52 ± 4.13 mm; and lower brainstem, 13.63 ± 8.45 mm). The area of exposure at the petroclivus was significantly greater with balloon inflation than without (change, 316.26 ± 166.75 mm2; p < 0.0001). Before and after balloon inflation, there was no significant difference in the angles of attack at the origin of the trigeminal nerve (p > 0.5).
This study adds an experimental component to the emerging field of quantitative neurosurgical anatomy. Balloon inflation can be used to model the effects of a mass lesion. The tumor simulation created “natural” retraction and an opening toward the upper clivus. The findings may be helpful in selecting a surgical approach to increase the working space for resection of certain extraaxial tumors.
Report of three cases
Eric M. Horn, Ruth E. Bristol, Iman Feiz-Erfan, Elisa J. Beres, Nicholas C. Bambakidis and Nicholas Theodore
✓Pseudomeningoceles rarely develop after cervical trauma; in all reported cases the lesions have extended outside the spinal canal.
The authors report the first known cases of anterior cervical pseudomeningoceles contained entirely within the spinal canal and causing cord compression and neurological injury. The authors retrospectively reviewed the cases of three patients with traumatic cervical spine injuries and concomitant compressive anterior pseudomeningoceles. The lesion was recognized in the first case when the patient’s neurological status declined after he sustained a severe atlantoaxial injury; the pseudomeningocele was identified intraoperatively and decompressed. After the decompressive surgery, the patient’s severe tetraparesis partially resolved. In the other two patients diagnoses of similar pseudomeningoceles were established by magnetic resonance imaging. Both patients were treated conservatively, and their mild to moderate hemiparesis due to the pseudomeningocele-induced compression abated.
The high incidence of anterior cervical pseudomeningoceles seen at the authors’ institution within a relatively brief period suggests that this lesion is not rare. The authors believe that it is important to recognize the compressive nature of these lesions and their potential to cause devastating neurological injury.
Nicholas C. Bambakidis, Nicholas Theodore, Peter Nakaji, Adrian Harvey, Volker K. H. Sonntag, Mark C. Preul and Robert H. Miller
The continuous regeneration of glial cells arising from endogenous stem cell populations in the central nervous system (CNS) occurs throughout life in mammals. In the ongoing research to apply stem cell therapy to neurological diseases, the capacity to harness the multipotential ability of endogenous stem cell populations has become apparent. Such cell populations proliferate in response to a variety of injury states in the CNS, but in the absence of a supportive microenvironment they contribute little to any significant behavioral recovery. In the authors' laboratory and elsewhere, recent research on the regenerative potential of these stem cells in disease states such as spinal cord injury has demonstrated that the cells' proliferative potential may be greatly upregulated in response to appropriate growth signals and exogenously applied trophic factors. Further understanding of the potential of such multipotent cells and the mechanisms responsible for creating a favorable microenvironment for them may lead to additional therapeutic alternatives in the setting of neurological diseases. These therapies would require no exogenous stem cell sources and thus would avoid the ethical and moral considerations regarding their use. In this review the authors provide a brief overview of the enhancement of endogenous stem cell proliferation following neurological insult.