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Jeffrey M. Toth, Mei Wang, Joshua Lawson, Jeffrey M. Badura, and Kimberly Bailey DuBose

OBJECTIVE

The objective of this study was to evaluate bone grafts consisting of rhBMP-2 on an absorbable collagen sponge with a ceramic composite bulking agent, rhBMP-2, directly on a ceramic-collagen sponge carrier or iliac crest bone graft (ICBG) in combination with local bone graft to effect fusion in a multisegmental instrumented ovine lumbar intertransverse process fusion model.

METHODS

Thirty-six sheep had a single treatment at 3 spinal levels in both the right and left intertransverse process spaces. Group 1 sheep were treated with 7.5 cm3 of autograft consisting of ICBG plus local bone for each intertransverse process space. For Groups 2–4, 4 cm3 of local bone was placed within the intertransverse process space followed by 4.5–5 cm3 of the rhBMP-2 graft material. Group 2 animals received 1.5 mg/cm3 rhBMP-2 on an absorbable collagen sponge with a commercial bone void filler consisting of Type I lyophilized collagen with a biphasic hydroxyapatite/β-tricalcium phosphate ceramic with local bone. Group 3 animals received 0.75 mg/m cm3 of rhBMP-2 on a collagen ceramic sponge carrier with local bone. Group 4 animals received 1.35 mg/cm3 of rhBMP-2 on the same collagen ceramic sponge carrier with local bone. Sheep were euthanized 6 months postoperatively. Manual palpation, biomechanical testing, CT, radiography, and undecalcified histology were performed to assess the presence of fusion associated with the treatments.

RESULTS

All animals in Groups 2–4 that received grafts containing rhBMP-2 achieved radiographic and CT fusion at all 3 levels. In Group 1 (bone autograft alone), only 19% of the levels demonstrated radiographic fusion, 14% resulted in possible radiographic fusion, and 67% of the levels demonstrated radiographic nonfusion. Biomechanical testing showed that Groups 2–4 demonstrated similar stiffness of the L2–5 segment in all 6 loading directions, with each of the 3 groups having significantly greater stiffness than the autograft-only group. In Group 1, only 2 of 18 levels were rated as achieving bilateral histological fusion, with an additional 3 levels showing a unilateral fusion. The majority of the treated levels (13/18) in Group 1 were scored as histological nonfusions. There were no histological nonfusions in Groups 2 through 4. All 18 levels in Group 2 were rated as bilateral histological fusions. A majority (34/36) of the levels in Group 3 were rated as bilateral histological fusions, with 2 levels showing a unilateral fusion. A majority (35/36) of the levels in Group 4 were rated as bilateral histological fusions, with 1 level showing a unilateral fusion.

CONCLUSIONS

In the ovine multilevel instrumented intertransverse process fusion model, rhBMP-2 was able to consistently achieve CT, radiographic, biomechanical, and histological fusion. Compared with ICBG, the gold standard for bone grafting, rhBMP-2 was statistically superior at achieving radiographic and histological fusion.

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Domagoj Coric, Praveen V. Mummaneni, Vincent Traynelis, and Jeffrey Wang

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Erratum

Conversion of external ventricular drains to ventriculoperitoneal shunts after aneurysmal subarachnoid hemorrhage: effects of site and protein/red blood cell counts on shunt infection and malfunction

Stylianos Rammos, Jeffrey Klopfenstein, Lori Augspurger, Huan Wang, and Jennifer Poston

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Tony R. Wang, Shayan Moosa, Robert F. Dallapiazza, W. Jeffrey Elias, and Wendy J. Lynch

Drug addiction represents a significant public health concern that has high rates of relapse despite optimal medical therapy and rehabilitation support. New therapies are needed, and deep brain stimulation (DBS) may be an effective treatment. The past 15 years have seen numerous animal DBS studies for addiction to various drugs of abuse, with most reporting decreases in drug-seeking behavior with stimulation. The most common target for stimulation has been the nucleus accumbens, a key structure in the mesolimbic reward pathway. In addiction, the mesolimbic reward pathway undergoes a series of neuroplastic changes. Chief among them is a relative hypofunctioning of the prefrontal cortex, which is thought to lead to the diminished impulse control that is characteristic of drug addiction. The prefrontal cortex, as well as other targets involved in drug addiction such as the lateral habenula, hypothalamus, insula, and subthalamic nucleus have also been stimulated in animals, with encouraging results. Although animal studies have largely shown promising results, current DBS studies for drug addiction primarily use stimulation during active drug use. More data are needed on the effect of DBS during withdrawal in preventing future relapse. The published human experience for DBS for drug addiction is currently limited to several promising case series or case reports that are not controlled. Further animal and human work is needed to determine what role DBS can play in the treatment of drug addiction.

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Jeffrey M. Toth, Kevin T. Foley, Mei Wang, Howard B. Seim III, and A. Simon Turner

OBJECTIVE

This study was designed with the following research objectives: 1) to determine the efficacy of facet fusion with recombinant human bone morphogenetic protein–2 (rhBMP-2) on an absorbable collagen sponge (ACS) in an ovine lumbar facet fusion model; 2) to radiographically and histologically compare the efficacy of lumbar facet fusion with rhBMP-2/ACS to facet fusion with an iliac crest bone graft (ICBG); and 3) to biomechanically compare lumbar facet fusion with rhBMP-2/ACS to lumbar posterolateral fusion (PLF) with ICBG.

METHODS

The efficacies of the 3 treatments to induce fusion were evaluated in an instrumented ovine lumbar fusion model. Eight sheep had 10 cm3/side ICBG placed as an onlay graft for PLF at L2–3. At the adjacent L3–4 level, 0.5 cm3/side ICBG was placed for facet fusion. Finally, 0.5 cm3/side rhBMP-2/ACS (0.43 mg/ml) was placed for facet fusion at L4–5. CT scans were obtained at 2, 4, and 6 months postoperatively with 2 reviewers conducting an evaluation of the 6-month results for all treated spinal levels. All 8 sheep were killed at 6 months, and all posterolateral instrumentation was removed at this time. The spines were then sectioned through L3–4 to allow for nondestructive unconstrained biomechanical testing of the L2–3 and L4–5 segments. All treated spinal levels were analyzed using undecalcified histology with corresponding microradiography. Statistical comparisons were made between the treatment groups.

RESULTS

The PLF with ICBG (ICBG PLF group) and the rhBMP-2 facet fusion (rhBMP-2 Facet group) treatment groups demonstrated similar levels of stiffness, with the rhBMP-2 Facet group having on average slightly higher stiffness in all 6 loading directions. All 8 levels in the autograft facet fusion treatment group demonstrated CT radiographic and histological fusion. All 8 levels in the rhBMP-2 Facet group showed bilateral CT radiographic and histological fusion. Six of 16 rhBMP-2/ACS-treated facet defects demonstrated small intraosseous hematomas or seromas. Four of the 8 levels (50%) in the ICBG PLF treatment group demonstrated bilateral histological fusion. Three of 8 levels in the ICBG PLF treatment group showed unilateral fusion. One of the 8 levels in the ICBG PLF treatment group demonstrated bilateral histological nonfusion.

CONCLUSIONS

Both rhBMP-2/ACS and autograft demonstrated 100% efficacy when used for facet fusion in the instrumented ovine model. However, the ICBG PLF treatment group only demonstrated a 50% bilateral fusion rate. Biomechanically, the ICBG PLF and rhBMP-2 Facet groups demonstrated similar stiffness in all 6 loading directions, with the rhBMP-2 Facet group having on average slightly higher stiffness in all directions.

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Robert T. Buckley, Anthony C. Wang, John W. Miller, Edward J. Novotny, and Jeffrey G. Ojemann

OBJECTIVE

Laser ablation is a novel, minimally invasive procedure that utilizes MRI-guided thermal energy to treat epileptogenic and other brain lesions. In addition to treatment of mesial temporal lobe epilepsy, laser ablation is increasingly being used to target deep or inoperable lesions, including hypothalamic hamartoma (HH), subependymal giant cell astrocytoma (SEGA), and exophytic intrinsic hypothalamic/third ventricular tumors. The authors reviewed their early institutional experience with these patients to characterize clinical outcomes in patients undergoing this procedure.

METHODS

A retrospective cohort (n = 12) of patients undergoing laser ablation at a single institution was identified, and clinical and radiographic records were reviewed.

RESULTS

Laser ablation was successfully performed in all patients. No permanent neurological or endocrine complications occurred; 2 (17%) patients developed acute obstructive hydrocephalus or shunt malfunction following treatment. Laser ablation of HH resulted in seizure freedom (Engel Class I) in 67%, with the remaining patients having a clinically significant reduction in seizure frequency of greater than 90% compared with preoperative baseline (Engel Class IIB). Treatment of SEGAs resulted in durable clinical and radiographic tumor control in 2 of 3 cases, with one patient receiving adjuvant everolimus and the other receiving no additional therapy. Palliative ablation of hypothalamic/third ventricular tumors resulted in partial tumor control in 1 of 3 patients.

CONCLUSIONS

Early experience suggests that laser ablation is a generally safe, durable, and effective treatment for patients harboring HHs. It also appears effective for local control of SEGAs, especially in combination therapy with everolimus. Its use as a palliative treatment for intrinsic hypothalamic/deep intraventricular tumors was less successful and associated with a higher risk of serious complications. Additional experience and long-term follow-up will be beneficial in further characterizing the effectiveness and risk profile of laser ablation in treating these lesions in comparison with conventional resective surgery or stereotactic radiosurgery.

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Alexander D. Wang, Jeffrey Cone, Lindsay Symon, and Izabel E. Costa e Silva

✓ Somatosensory evoked responses to median nerve stimulation have been recorded during the management of subarachnoid hemorrhage from intracranial aneurysms. The type of measurement was central conduction time (CCT), the time interval between the N14 peak (at C-2) and the N20 peak (at the cortex). Significant differences were found between patients with aneurysms in clinical Grade 4 and normal individuals, although there was no significant difference between most aneurysm patients in Grades 1 through 3. The prolongation of CCT was found of prognostic value. Significant prolongation (mean plus two standard deviations) from the normal period of 5.4 ± 0.4 msec was found significantly useful to predict a less than satisfactory outcome (a patient with neurological signs or disabled) at 2 months, and these differences were detectable as early as 48 hours postoperatively. Differences between conduction time in the two hemispheres could also be used prognostically, although the significance of the differences did not appear until 48 to 72 hours after surgery, and was in any event less than that of CCT.

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Stylianos Rammos, Jeffrey Klopfenstein, Lori Augsburger, Huan Wang, Anne Wagenbach, Jennifer Poston, and Giuseppe Lanzino

Object

The purpose of this study was to determine the incidence of shunt infection in patients with subarachnoid hemorrhage (SAH) after converting an external ventricular drain (EVD) to a ventriculoperitoneal (VP) shunt using the existing EVD site. The second purpose was to assess the risk of shunt malfunction after converting the EVD to a permanent shunt irrespective of the cerebrospinal fluid (CSF) protein and red blood cell (RBC) counts.

Methods

Data obtained in 80 consecutive adult patients (18 men and 62 women, mean age 60.8 years, range 33–85 years) who underwent direct conversion of an EVD to a VP shunt for post-SAH hydrocephalus between August 2002 and March 2007 were retrospectively reviewed. In each patient, the existing EVD site was used to pass the proximal shunt catheter. In no patient was VP shunt insertion delayed based on preoperative RBC or protein counts.

Results

The mean period of external ventricular drainage before VP shunt placement was 14.1 days (range 3–45 days). No patient suffered ventriculitis. The mean perioperative CSF protein level was 124 mg/dl (range 17–516 mg/dl). The mean and median perioperative RBC values in CSF were 14,203 RBCs/mm3 and 4600 RBCs/mm3 (range 119–290,000/mm3), respectively. No patient was lost to follow-up. The mean follow-up duration was 24 months (range 2–53 months). Three patients (3.8%) had shunt malfunction related to obstruction of the shunt system after 15 days, 2 months, and 18 months, respectively. There were no shunt-related infections. No patient suffered a clinically significant hemorrhage from ventricular catheter placement after VP shunt insertion.

Conclusions

In adult patients with aneurysmal SAH, conversion of an EVD to a VP shunt can be safely done using the same EVD site. In this defined patient population, protein and RBC counts in the CSF do not seem to affect shunt survival adversely. Thus, conversion of an EVD to VP shunt should not be delayed because of an elevated protein or RBC count.

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Martin H. Pham, Vivek A. Mehta, Neil N. Patel, Andre M. Jakoi, Patrick C. Hsieh, John C. Liu, Jeffrey C. Wang, and Frank L. Acosta

The Dynesys dynamic stabilization system is an alternative to rigid instrumentation and fusion for the treatment of lumbar degenerative disease. Although many outcomes studies have shown good results, currently lacking is a comprehensive report on complications associated with this system, especially in terms of how it compares with reported complication rates of fusion. For the present study, the authors reviewed the literature to find all studies involving the Dynesys dynamic stabilization system that reported complications or adverse events. Twenty-one studies were included for a total of 1166 patients with a mean age of 55.5 years (range 39–71 years) and a mean follow-up period of 33.7 months (range 12.0–81.6 months). Analysis of these studies demonstrated a surgical-site infection rate of 4.3%, pedicle screw loosening rate of 11.7%, pedicle screw fracture rate of 1.6%, and adjacent-segment disease (ASD) rate of 7.0%. Of studies reporting revision surgeries, 11.3% of patients underwent a reoperation. Of patients who developed ASD, 40.6% underwent a reoperation for treatment. The Dynesys dynamic stabilization system appears to have a fairly similar complication-rate profile compared with published literature on lumbar fusion, and is associated with a slightly lower incidence of ASD.

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Jeffrey E. Arle, Craig Morriss, Zhiyue J. Wang, Robert A. Zimmerman, Peter G. Phillips, and Leslie N. Sutton

Recent studies have explored characteristics of brain tumors by means of magnetic resonance spectroscopy (MRS) to increase diagnostic accuracy and improve understanding of tumor biology. In this study, a computer-based neural network was developed to combine MRS data (ratios of N-acetyl-aspartate, choline, and creatine) with 10 characteristics of tumor tissue obtained from magnetic resonance (MR) studies, as well as tumor size and the patient's age and sex, in hopes of further improving diagnostic accuracy.

Data were obtained in 33 children presenting with posterior fossa tumors. The cases were analyzed by a neuroradiologist, who then predicted the tumor type from among three categories (primitive neuroectodermal tumor, astrocytoma, or ependymoma/other) based only on the data obtained via MR imaging. These predictions were compared with those made by neural networks that had analyzed different combinations of the data. The neuroradiologist correctly predicted the tumor type in 73% of the cases, whereas four neural networks using different datasets as inputs were 58 to 95% correct. The neural network that used only the three spectroscopy ratios had the least predictive ability. With the addition of data including MR imaging characteristics, age, sex, and tumor size, the network's accuracy improved to 72%, consistent with the predictions of the neuroradiologist who was using the same information. Use of only the analog data (leaving out information obtained from MR imaging), resulted in 88% accuracy. A network that used all of the data was able to identify 95% of the tumors correctly. It is concluded that a neural network provided with imaging data, spectroscopic data, and a limited amount of clinical information can predict pediatric posterior fossa tumor type with remarkable accuracy.