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Sam Safavi-Abbasi, Mehmet Senoglu, Nicholas Theodore, Ryan K. Workman, Alireza Gharabaghi, Iman Feiz-Erfan, Robert F. Spetzler and Volker K. H. Sonntag

Object

The authors conducted a study to evaluate the clinical characteristics and surgical outcomes in patients with spinal schwannomas and without neurofibromatosis (NF).

Methods

The data obtained in 128 patients who underwent resection of spinal schwannomas were analyzed. All cases with neurofibromas and those with a known diagnosis of NF Type 1 or 2 were excluded. Karnofsky Performance Scale (KPS) scores were used to compare patient outcomes when examining the anatomical location and spinal level of the tumor. The neurological outcome was further assessed using the Medical Research Council (MRC) muscle testing scale.

Results

Altogether, 131 schwannomas were treated in 128 patients (76 males and 52 females; mean age 47.7 years). The peak prevalence is seen between the 3rd and 6th decades. Pain was the most common presenting symptom. Gross-total resection was achieved in 127 (97.0%) of the 131 lesions. The nerve root had to be sacrificed in 34 cases and resulted in minor sensory deficits in 16 patients (12.5%) and slight motor weakness (MRC Grade 3/5) in 3 (2.3%). The KPS scores and MRC grades were significantly higher at the time of last follow-up in all patient groups (p = 0.001 and p = 0.005, respectively).

Conclusions

Spinal schwannomas may occur at any level of the spinal axis and are most commonly intradural. The most frequent clinical presentation is pain. Most spinal schwannomas in non-NF cases can be resected totally without or with minor postoperative deficits. Preoperative autonomic dysfunction does not improve significantly after surgical management.

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Seref Dogan, Sam Safavi-Abbasi, Nicholas Theodore, Steven W. Chang, Eric M. Horn, Nittin R. Mariwalla, Harold L. Rekate and Volker K. H. Sonntag

Object

The authors evaluated the mechanisms and patterns of thoracic, lumbar, and sacral spinal injuries in a pediatric population as well as factors affecting the management and outcome of these injuries.

Methods

The records of 89 patients (46 boys and 43 girls; mean age 13.2 years, range 3–16 years) with thoracic, lumbar, or sacral injuries were reviewed. Motor vehicle accidents were the most common cause of injury. Eighty-two patients (92.1%) were between 10 and 16 years old, and seven (7.9%) were between 3 and 9 years old. Patient injuries included fracture (91%), fracture and dislocation (6.7%), dislocation (1.1%), and ligamentous injury (1.1%). The L2–5 region was the most common injury site (29.8%) and the sacrum the least common injury site (5%). At the time of presentation 85.4% of the patients were neurologically intact, 4.5% had incomplete injuries, and 10.1% had complete injuries. Twenty-six percent of patients underwent surgery for their injuries whereas 76% received nonsurgical treatment. In patients treated surgically, an anterior approach was used in six patients (6.7%), a posterior approach in 16 (18%), and a combined approach in one (1.1%). Postoperatively, six patients (26.1%) with neurological deficits improved, one of whom recovered fully from an initially complete injury.

Conclusions

Thoracic and lumbar spine injuries were most common in children older than 9 years. Multilevel injuries were common and warranted imaging evaluation of the entire spinal column. Most patients were treated conservatively. The prognosis for neurological recovery is related to the initial severity of the neurological injuries. Some pediatric patients with devastating spinal cord injuries can recover substantial neurological function.

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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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Vassilios G. Varsos, Theodore M. Liszczak, Dae Hee Han, J. Philip Kistler, Juan Vielma, Peter McL. Black, Roberto C. Heros and Nicholas T. Zervas

✓ Angiographic spasm of cerebral arteries was produced in dogs by successive injections of cisternal blood 48 hours apart. Angiograms were taken before and after each cisternal injection. There was progressively greater angiographic vasospasm of the basilar artery. Intravenous aminophylline, 10 mg/kg/hr, reversed vessel constriction on the 1st and 3rd day after one injection of cisternal blood. On the 5th day after two blood injections (on Day 1 and Day 3), intravenous aminophylline, nifedipine (1 mg/kg), and intra-arterial bolus injection of 2 mg/kg papaverine failed to reverse the constriction. The intractable constriction produced in this model resembles that found in patients. The calcium antagonist, nifedipine, is as ineffective as the more traditional vasodilators in reversing vasospasm in this model.

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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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Nestor G. Rodriguez-Martinez, Amey Savardekar, Eric W. Nottmeier, Stephen Pirris, Phillip M. Reyes, Anna G. U. S. Newcomb, George A. C. Mendes, Samuel Kalb, Nicholas Theodore and Neil R. Crawford

OBJECTIVE

Transvertebral screws provide stability in thoracic spinal fixation surgeries, with their use mainly limited to patients who require a pedicle screw salvage technique. However, the biomechanical impact of transvertebral screws alone, when they are inserted across 2 vertebral bodies, has not been studied. In this study, the authors assessed the stability offered by a transvertebral screw construct for posterior instrumentation and compared its biomechanical performance to that of standard bilateral pedicle screw and rod (PSR) fixation.

METHODS

Fourteen fresh human cadaveric thoracic spine segments from T-6 to T-11 were divided into 2 groups with similar ages and bone quality. Group 1 received transvertebral screws across 2 levels without rods and subsequently with interconnecting bilateral rods at 3 levels (T8–10). Group 2 received bilateral PSR fixation and were sequentially tested with interconnecting rods at T7–8 and T9–10, at T8–9, and at T8–10. Flexibility tests were performed on intact and instrumented specimens in both groups. Presurgical and postsurgical O-arm 3D images were obtained to verify screw placement.

RESULTS

The mean range of motion (ROM) per motion segment with transvertebral screws spanning 2 levels compared with the intact condition was 66% of the mean intact ROM during flexion-extension (p = 0.013), 69% during lateral bending (p = 0.015), and 47% during axial rotation (p < 0.001). The mean ROM per motion segment with PSR spanning 2 levels compared with the intact condition was 38% of the mean intact ROM during flexion-extension (p < 0.001), 57% during lateral bending (p = 0.007), and 27% during axial rotation (p < 0.001). Adding bilateral rods to the 3 levels with transvertebral screws decreased the mean ROM per motion segment to 28% of intact ROM during flexion-extension (p < 0.001), 37% during lateral bending (p < 0.001), and 30% during axial rotation (p < 0.001). The mean ROM per motion segment for PSR spanning 3 levels was 21% of intact ROM during flexion-extension (p < 0.001), 33% during lateral bending (p < 0.001), and 22% during axial rotation (p < 0.001).

CONCLUSIONS

Biomechanically, fixation with a novel technique in the thoracic spine involving transvertebral screws showed restoration of stability to well within the stability provided by PSR fixation.

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Jacob B. Archer, Hai Sun, Phillip A. Bonney, Yan Daniel Zhao, Jared C. Hiebert, Jose A. Sanclement, Andrew S. Little, Michael E. Sughrue, Nicholas Theodore, Jeffrey James and Sam Safavi-Abbasi

OBJECT

This article introduces a classification scheme for extensive traumatic anterior skull base fracture to help stratify surgical treatment options. The authors describe their multilayer repair technique for cerebrospinal fluid (CSF) leak resulting from extensive anterior skull base fracture using a combination of laterally pediculated temporalis fascial-pericranial, nasoseptal-pericranial, and anterior pericranial flaps.

METHODS

Retrospective chart review identified patients treated surgically between January 2004 and May 2014 for anterior skull base fractures with CSF fistulas. All patients were treated with bifrontal craniotomy and received pedicled tissue flaps. Cases were classified according to the extent of fracture: Class I (frontal bone/sinus involvement only); Class II (extent of involvement to ethmoid cribriform plate); and Class III (extent of involvement to sphenoid bone/sinus). Surgical repair techniques were tailored to the types of fractures. Patients were assessed for CSF leak at follow-up. The Fisher exact test was applied to investigate whether the repair techniques were associated with persistent postoperative CSF leak.

RESULTS

Forty-three patients were identified in this series. Thirty-seven (86%) were male. The patients’ mean age was 33 years (range 11–79 years). The mean overall length of follow-up was 14 months (range 5–45 months). Six fractures were classified as Class I, 8 as Class II, and 29 as Class III. The anterior pericranial flap alone was used in 33 patients (77%). Multiple flaps were used in 10 patients (3 salvage) (28%)—1 with Class II and 9 with Class III fractures. Five (17%) of the 30 patients with Class II or III fractures who received only a single anterior pericranial flap had persistent CSF leak (p < 0.31). No CSF leak was found in patients who received multiple flaps. Although postoperative CSF leak occurred only in high-grade fractures with single anterior flap repair, this finding was not significant.

CONCLUSIONS

Extensive anterior skull base fractures often require aggressive treatment to provide the greatest long-term functional and cosmetic benefits. Several vascularized tissue flaps can be used, either alone or in combination. Vascularized flaps are an ideal substrate for cranial base repair. Dual and triple flap techniques that combine the use of various anterior, lateral, and nasoseptal flaps allow for a comprehensive arsenal in multilayered skull base repair and salvage therapy for extensive and severe fractures.

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Henry Brem, M. Stephen Mahaley Jr., Nicholas A. Vick, Keith L. Black, S. Clifford Schold Jr., Peter C. Burger, Allan H. Friedman, Ivan S. Ciric, Theodore W. Eller, Jeffrey W. Cozzens and James N. Kenealy

✓ Malignant gliomas have been difficult to treat with chemotherapy. The most effective agent, BCNU (carmustine), has considerable systemic toxicity and a short half-life in serum. To obviate these problems, a method has been developed for the local sustained release of chemotherapeutic agents by their incorporation into biodegradable polymers. Implantation of the drug-impregnated polymer at the tumor site allows prolonged local exposure with minimal systemic exposure. In this Phase I–II study, 21 patients with recurrent malignant glioma were treated with BCNU released interstitially by means of a polyanhydride biodegradable polymer implant. Up to eight polymer wafers were placed in the resection cavity intraoperatively, upon completion of tumor debulking. The polymer releases the therapeutic drug for approximately 3 weeks.

Three increasing concentrations of BCNU were studied; the treatment was well tolerated at all three levels. There were no adverse reactions to the BCNU wafer treatment itself The average survival period after reoperation was 65 weeks for the first dose group, 64 weeks for the second dose group, and 32 weeks for the highest dose group. The overall mean survival time was 48 weeks from reoperation and 94 weeks from the original operation. The overall median survival times were 46 weeks postimplant and 87 weeks from initial surgery. Eighteen (86%) of 21 patients lived more than 1 year from the time of their initial diagnosis and eight (38%) of 21 patients lived more than 1 year after intracranial implantation of the polymer. Frequent hematology, blood chemistry, and urinalysis tests did not reveal any systemic effect from this interstitial chemotherapy.

Since the therapy is well tolerated and safe, a placebo-controlled clinical trial has been started. The trial will measure the effect of the second treatment dose on survival of patients with recurrent malignant glioma.

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