Paul A. Gardner, Juan C. Fernandez-Miranda, Carl H. Snyderman and Eric W. Wang
George A. C. Mendes, Curtis A. Dickman, Nestor G. Rodriguez-Martinez, Samuel Kalb, Neil R. Crawford, Volker K. H. Sonntag, Mark C. Preul and Andrew S. Little
The primary disadvantage of the posterior cervical approach for atlantoaxial stabilization after odontoidectomy is that it is conducted as a second-stage procedure. The goal of the current study is to assess the surgical feasibility and biomechanical performance of an endoscopic endonasal surgical technique for C1–2 fixation that may eliminate the need for posterior fixation after odontoidectomy.
The first step of the study was to perform endoscopic endonasal anatomical dissections of the craniovertebral junction in 10 silicone-injected fixed cadaveric heads to identify relevant anatomical landmarks. The second step was to perform a quantitative analysis using customized software in 10 reconstructed adult cervical spine CT scans to identify the optimal screw entry point and trajectory. The third step was biomechanical flexibility testing of the construct and comparison with the posterior C1–2 transarticular fixation in 14 human cadaveric specimens.
Adequate surgical exposure and identification of the key anatomical landmarks, such as C1–2 lateral masses, the C-1 anterior arch, and the odontoid process, were provided by the endonasal endoscopic approach in all specimens. Radiological analysis of anatomical detail suggested that the optimal screw entry point was on the anterior aspect of the C-1 lateral mass near the midpoint, and the screw trajectory was inferiorly and slightly laterally directed. The custommade angled instrumentation was crucial for screw placement. Biomechanical analysis suggested that anterior C1–2 fixation compared favorably to posterior fixation by limiting flexion-extension, axial rotation, and lateral bending (p > 0.3).
This is the first study that demonstrates the feasibility of an endoscopic endonasal technique for C1–2 fusion. This novel technique may have clinical utility by eliminating the need for a second-stage posterior fixation operation in certain patients undergoing odontoidectomy.
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.
Rachid Assina, Tejas Sankar, Nicholas Theodore, Sam P. Javedan, Alan R. Gibson, Kris M. Horn, Michael Berens, Volker K. H. Sonntag and Mark C. Preul
Axonal regeneration may be hindered following spinal cord injury (SCI) by a limited immune response and insufficient macrophage recruitment. This limitation has been partially surmounted in small-mammal models of SCI by implanting activated autologous macrophages (AAMs). The authors sought to replicate these results in a canine model of partial SCI.
Six dogs underwent left T-13 spinal cord hemisection. The AAMs were implanted at both ends of the lesion in 4 dogs, and 2 other dogs received sham implantations of cell media. Cortical motor evoked potentials (MEPs) were used to assess electrophysiological recovery. Functional motor recovery was assessed with a modified Tarlov Scale. After 9 months, animals were injected with wheat germ agglutinin–horseradish peroxidase at L-2 and killed for histological assessment.
Three of the 4 dogs that received AAM implants and 1 of the 2 negative control dogs showed clear recovery of MEP response. Behavioral assessment showed no difference in motor function between the AAM-treated and control groups. Histological investigation with an axonal retrograde tracer showed neither local fiber crossing nor significant uptake in the contralateral red nucleus in both implanted and negative control groups.
In a large-animal model of partial SCI treated with implanted AAMs, the authors saw no morphological or histological evidence of axonal regeneration. Although they observed partial electrophysiological and functional motor recovery in all dogs, this recovery was not enhanced in animals treated with implanted AAMs. Furthermore, there was no morphological or histological evidence of axonal regeneration in animals with implants that accounted for the observed recovery. The explanation for this finding is probably multifactorial, but the authors believe that the AAM implantation does not produce axonal regeneration, and therefore is a technology that requires further investigation before it can be clinically relied on to ameliorate SCI.
Eric M. Horn, Nicholas Theodore, Rachid Assina, Robert F. Spetzler, Volker K. H. Sonntag and Mark C. Preul
Venous stasis and intrathecal hypertension are believed to play a significant role in the hypoperfusion present in the spinal cord following injury. Lowering the intrathecal pressure via cerebrospinal fluid (CSF) drainage has been effective in treating spinal cord ischemia during aorta surgery. The purpose of the present study was to determine whether CSF drainage increases spinal cord perfusion and improves outcome after spinal injury in an animal model.
Anesthetized adult rabbits were subjected to a severe contusion spinal cord injury (SCI). Cerebrospinal fluid was then drained via a catheter to lower the intrathecal pressure by 10 mm Hg. Tissue perfusion was assessed at the site of injury, and values obtained before and after CSF drainage were compared. Two other cohorts of animals were subjected to SCI: 1 group subsequently underwent CSF drainage and the other did not. Results of histological analysis, motor evoked potential and motor function testing were compared between the 2 cohorts at 4 weeks postinjury.
Cerebrospinal fluid drainage led to no significant improvement in spinal cord tissue perfusion. Four weeks after injury, the animals that underwent CSF drainage demonstrated significantly smaller areas of tissue damage at the injury site. There were no differences in motor evoked potentials or motor score outcomes at 4 weeks postinjury.
Cerebrospinal fluid drainage effectively lowers intrathecal pressure and decreases the amount of tissue damage in an animal model of spinal cord injury. Further studies are needed to determine whether different draining regimens can improve motor or electrophysiological outcomes.
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.
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.
L. Fernando Gonzalez, Neil R. Crawford, Robert H. Chamberlain, Luis E. Perez Garza, Mark C. Preul, Volker K. H. Sonntag and Curtis A. Dickman
Object. The authors compared the biomechanical stability resulting from the use of a new technique for occipitoatlantal motion segment fixation with an established method and assessed the additional stability provided by combining the two techniques.
Methods. Specimens were loaded using nonconstraining pure moments while recording the three-dimensional angular movement at occiput (Oc)—C1 and C1–2. Specimens were tested intact and after destabilization and fixation as follows: 1) Oc—C1 transarticular screws plus C1–2 transarticular screws; 2) occipitocervical transarticular (OCTA) plate in which C1–2 transarticular screws attach to a loop from Oc to C-2; and (3) OCTA plate plus Oc—C1 transarticular screws.
Occipitoatlantal transarticular screws reduced motion to well within the normal range. The OCTA loop and transarticular screws allowed a very small neutral zone, elastic zone, and range of motion during lateral bending and axial rotation. The transarticular screws, however, were less effective than the OCTA loop in resisting flexion and extension.
Conclusions. Biomechanically, Oc—C1 transarticular screws performed well enough to be considered as an alternative for Oc—C1 fixation, especially when instability at C1–2 is minimal. Techniques for augmenting these screws posteriorly by using a wired bone graft buttress, as is currently undertaken with C1–2 transarticular screws, may be needed for optimal performance.