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Robert W. Ryan, Robert F. Spetzler and Mark C. Preul

In this historical review the authors examine the important developments that have led to the availability of laser energy to neurosurgeons as a unique and sometimes invaluable tool. They review the physical science behind the function of lasers, as well as how and when various lasers based on different lasing mediums were discovered. They also follow the close association between advances in laser technology and their application in biomedicine, from early laboratory experiments to the first clinical experiences. Because opinions on the appropriate role of lasers in neurosurgery vary widely, the historical basis for some of these views is explored. Initial enthusiasm for a technology that appears to have innate advantages for safe resections has often given way to the strict limitations and demands of the neurosurgical operating theater. However, numerous creative solutions to improve laser delivery, power, safety, and ergonomics demonstrate the important role that technological advances in related scientific fields continue to offer neurosurgery. Benefiting from the most recent developments in materials science, current CO2 laser delivery systems provide a useful addition to the neurosurgical armamentarium when applied in the correct circumstances and reflect the important historical advances that come about from the interplay between neurosurgery and technology.

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Ali A. Baaj, Juan S. Uribe, Fernando L. Vale, Mark C. Preul and Neil R. Crawford

Enthusiasm for cervical disc arthroplasty is based on the premise that motion-preserving devices attenuate the progression of adjacent-segment disease (ASD) in the cervical spine. Arthrodesis, on the other hand, results in abnormal load transfer on adjacent segments, leading to the acceleration of ASD. It has taken several decades of pioneering work to produce clinically relevant devices that mimic the kinematics of the intervertebral disc. The goal of this work is to trace the origins of cervical arthroplasty technology and highlight the attributes of devices currently available in the market.

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Charles J. Prestigiacomo and Mark C. Preul

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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

Object

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.

Methods

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.

Results

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.

Conclusions

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.

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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

Object

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.

Methods

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.

Results

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.

Conclusions

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.

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Eric M. Horn, Nicholas Theodore, Rachid Assina, Robert F. Spetzler, Volker K. H. Sonntag and Mark C. Preul

Object

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.

Methods

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.

Results

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.

Conclusions

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.

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Tejas Sankar, Rachid Assina, John P. Karis, Nicholas Theodore and Mark C. Preul

✓Mannitol is widely considered the hyperosmolar therapy of choice in routine neurosurgical practice for the reduction of intracranial pressure (ICP). The authors present a unique case of a patient with a large meningioma treated with mannitol, in which mannitol accumulation within the tumor and its surrounding parenchyma was shown using in vivo magnetic resonance spectroscopy (MRS). This rare appearance of mannitol on MRS was characterized by a wide-based peak at 3.8 ppm, which remained detectable several hours after the last dose. These findings provide the first in vivo evidence in support of the prevailing theory that mannitol leakage into the peritumoral edematous region may contribute to rebound increases in ICP and suggest that this phenomenon has the potential to occur in extraaxial tumors. Judicious use of mannitol in the setting of elevated ICP due to tumor may be indicated to avoid potentially deleterious side effects caused by its accumulation.

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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.

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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

Object

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.

Methods

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.

Results

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).

Conclusions

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.

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Mark C. Preul, Patrick K. Campbell, William D. Bichard and Robert F. Spetzler

Object

The authors evaluated whether a polyethylene glycol–based hydrogel sealant system improved dural closures with collagen-based duraplasty onlay grafts.

Methods

Dural defects 1.5 cm in diameter were created in 12 canines and repaired with one of two commercially available duraplasty onlay products. In six animals, hydrogel was applied onto the dural onlays, and the other six animals underwent duraplasty only. Before bone flap replacement, watertight closure was assessed. Before the animals were killed, the craniotomy was reopened, adhesions were rated by a neurosurgeon blinded to the treatment groups, and dural integrity was assessed using pressure testing.

Results

The animals that received the hydrogel sealant in addition to the duraplasty withstood intraoperative Valsalva maneuvers up to 20 cm H2O without cerebrospinal fluid (CSF) leakage. The duraplasty-only animals leaked CSF at spontaneous pressures (p = 0.0022). Postoperatively, all six duraplasty-only dogs developed CSF subcutaneous accumulations, compared with only one (16.7%) dog who underwent hydrogel application (p = 0.0152). At the time of harvesting (8 weeks after implantation), duraplasty-only dogs had extensive scarring between the bone flap and the dura mater (median adhesion score 4, range 3–4). The animals receiving hydrogel showed minimal scarring (median adhesion score 0.5, range 0–2). In hydrogel-treated dogs, the mean adhesion score was 82.6% lower than the scores in duraplasty-only animals (p = 0.0043). In animals receiving hydrogel, the mean dural leak pressure was 56.8 ± 2.5 cm H2O compared with 9.8 ± 3.8 cm H2O in duraplasty-only dogs (p = 0.0392). Application of the hydrogel was not associated with neurotoxicity, delayed healing, degenerative changes, or increased dura–cortex adhesions.

Conclusions

The hydrogel sealant applied to collagen-based dural grafts significantly reduced CSF leakage and functioned as an adhesion barrier. Such technology could be an important tool for cranial surgery.