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Increased oxygen levels may enhance the radiosensitivity of brain metastases treated with stereotactic radiosurgery (SRS). This project administered hyperbaric oxygen (HBO) prior to SRS to assess feasibility, safety, and response.38 patients were studied, 19 with 25 brain metastases treated with HBO prior to SRS, and 19 historical controls with 27 metastases, matched for histology, GPA, resection status, and lesion size. Outcomes included time from HBO to SRS, quality-of-life (QOL) measures, local control, distant (brain) metastases, radionecrosis, and overall survival.The average time from HBO chamber to SRS beam-on was 8.3 ± 1.7 minutes. Solicited adverse events (AEs) were comparable between HBO and control patients; no grade III or IV serious AEs were observed. Radionecrosis-free survival (RNFS), radionecrosis-free survival before whole-brain radiation therapy (WBRT) (RNBWFS), local recurrence-free survival before WBRT (LRBWFS), distant recurrence-free survival before WBRT (DRBWFS), and overall survival (OS) were not significantly different for HBO patients and controls on Kaplan-Meier analysis, though at 1-year estimated survival rates trended in favor of SRS + HBO: RNFS - 83% vs 60%; RNBWFS - 78% vs 60%; LRBWFS - 95% vs 78%; DRBWFS - 61% vs 57%; and OS - 73% vs 56%. Multivariate Cox models indicated no significant association between HBO treatment and hazards of RN, local or distant recurrence, or mortality; however, these did show statistically significant associations (p 0.05) for: local recurrence with higher volume, radionecrosis with tumor resection, overall survival with resection, and overall survival with higher GPA.Addition of HBO to SRS for brain metastases is feasible without evident decrement in radiation necrosis and other clinical outcomes.

Spinal epidural abscess (SEA) is an uncommon yet serious infection, associated with significant morbidity and mortality. Patients diagnosed with SEA often require surgical interventions or critical care services that are not available at community hospitals and are therefore transferred to tertiary care centers. Little is known about the effects of interhospital transfer on acute outcomes for patients with SEA.To study the effects of interhospital transfer on acute outcomes for patients with SEA.Cross sectional analysis using the 2009 to 2017 National Inpatient Sample (NIS).Using the 2009 to 2017 NIS, we identified cases of SEA using ICD, Ninth, or Tenth Revision diagnosis codes 324.1G06.1.Our primary endpoint was in hospital mortality.The association between interhospital transfer and inpatient mortality was assessed using multivariable logistic regression to adjust for potential covariates. Patient and hospital factors associated with interhospital transfer were assessed in a secondary analysis.A total of 21.5% of patient with SEA were treated after transfer from another hospital. After adjusting for covariates, those who presented after transfer had higher odds of death during hospitalization (OR: 1.51, 95% CI 1.27-1.78, p.001). Transferred patients were significantly more likely to live in rural communities (11.4 % vs. 5.3 % for nontransferred patients).Interhospital transfer, which occurred more frequently in patients from rural hospitals, was associated with death even after controlling for disease severity. Addressing healthcare delivery disparities across the US, including across the rural-urban spectrum, will require better understanding of the observed increased mortality of interhospital transfer as a preventable source of in-hospital mortality for SEA.

Background Tumors that take up and metabolize 5-aminolevulinic acid emit bright pink fluorescence when illuminated with blue light, aiding surgeons in identifying the margin of resection. The adoption of this method is hindered by the blue light illumination, which is too dim to safely operate under and therefore necessitates switching back and forth from white-light mode. The aim of this study was to examine the addition of an optimized secondary illuminant adapter to improve usability of blue-light mode without degrading tumor contrast. Methods Color science methods were used to evaluate the color of the secondary illuminant and its impact on color rendering index as well as the tumor-to-background color contrast in data collected from 7 patients with high-grade gliomas (World Health Organization grade III and IV). A secondary illuminant adapter was built to provide 475–600 nm light the intensity of which can be controlled by the surgeon and was evaluated in 2 additional patients. Results Secondary illuminant color had opposing effects on color rendering index and tumor-to-background color contrast; providing surgeon control of intensity allows this trade-off to be balanced in real time. Demonstration in 2 high-grade glioma cases confirms this, showing that additional visibility adds value when intensity can be controlled by the surgeon. Conclusions Addition of a secondary illuminant may mitigate surgeon complaints that the operative field is too dark under the blue light illumination required for 5-aminolevulinic acid fluorescence guidance by providing improved color rendering index without completely sacrificing tumor-to-background color contrast.

BackgroundTumors that take up and metabolize 5-aminolevulinic acid (5-AlA) emit bright pink fluorescence when illuminated with blue light, aiding surgeons in identifying the margin of resection. The adoption of this method is hindered by the blue light illumination, which is too dim to safely operate under, and therefore, necessitates switching back and forth from white-light mode. This paper examines the addition of an optimized secondary illuminant adapter (SIA) to improve usability of blue-light mode without degrading tumor contrast.MethodsWe used color science methods to evaluate the color of the secondary illuminant and its impact on color rendering index (CRI) as well as the tumor-to-background color contrast (TBCC). A secondary illuminant adapter was built to provide 475-600 nm light the intensity of which can be controlled by the surgeon and was evaluated in two patients.ResultsSecondary illuminant color had opposing effects on color rendering index (CRI) and tumor to background color contrast (TBCC); providing surgeon control of intensity allows this trade-off to be balanced in real-time. Experience in two cases suggests additional visibility adds value.ConclusionThe addition of a secondary illuminant may mitigate surgeon complaints that the operative field is too dark under the blue light illumination required for 5-ALA fluorescence guidance by providing improved CRI without completely sacrificing TBCC.

To investigate the effect of exposure to a virtual reality (VR) environment preoperatively on patient-reported outcomes for surgical operations.There is a scarcity of well-developed quality improvement initiatives targeting patient satisfaction.We performed a randomized controlled trial of patients undergoing cranial and spinal operations in a tertiary referral center. Patients underwent a 1:1 randomization to an immersive preoperative VR experience or standard preoperative experience stratified on type of operation. The primary outcome measures were the Evaluation du Vecu de l'Anesthesie Generale (EVAN-G) score and the Amsterdam Preoperative Anxiety and Information (APAIS) score, as markers of the patient's experience during the surgical encounter.During the study period, a total of 127 patients (mean age 55.3 years, 41.9% females) underwent randomization. The average EVAN-G score was 84.3 (standard deviation, SD, 6.4) after VR, and 64.3 (SD, 11.7) after standard preoperative experience (difference, 20.0; 95% confidence interval, CI, 16.6-23.3). Exposure to an immersive VR experience also led to higher APAIS score (difference, 29.9; 95% CI, 24.5-35.2). In addition, VR led to lower preoperative VAS stress score (difference, -41.7; 95% CI, -33.1 to -50.2), and higher preoperative VAS preparedness (difference, 32.4; 95% CI, 24.9-39.8), and VAS satisfaction (difference, 33.2; 95% CI, 25.4-41.0) scores. No association was identified with VAS stress score (difference, -1.6; 95% CI, -13.4 to 10.2).In a randomized controlled trial, we demonstrated that patients exposed to preoperative VR had increased satisfaction during the surgical encounter. Harnessing the power of this technology, hospitals can create an immersive environment that minimizes stress, and enhances the perioperative experience.

OBJECTIVE The molecular mechanisms behind cerebral aneurysm formation and rupture remain poorly understood. In the past decade, microRNAs (miRNAs) have been shown to be key regulators in a host of biological processes. They are noncoding RNA molecules, approximately 21 nucleotides long, that posttranscriptionally inhibit mRNAs by attenuating protein translation and promoting mRNA degradation. The miRNA and mRNA interactions and expression levels in cerebral aneurysm tissue from human subjects were profiled. METHODS A prospective case-control study was performed on human subjects to characterize the differential expression of mRNA and miRNA in unruptured cerebral aneurysms in comparison with control tissue (healthy superficial temporal arteries [STA]). Ion Torrent was used for deep RNA sequencing. Affymetrix miRNA microarrays were used to analyze miRNA expression, whereas NanoString nCounter technology was used for validation of the identified targets. RESULTS Overall, 7 unruptured cerebral aneurysm and 10 STA specimens were collected. Several differentially expressed genes were identified in aneurysm tissue, with MMP-13 (fold change 7.21) and various collagen genes (COL1A1, COL5A1, COL5A2) being among the most upregulated. In addition, multiple miRNAs were significantly differentially expressed, with miR-21 (fold change 16.97) being the most upregulated, and miR-143–5p (fold change −11.14) being the most downregulated. From these, miR-21, miR-143, and miR-145 had several significantly anticorrelated target genes in the cohort that are associated with smooth muscle cell function, extracellular matrix remodeling, inflammation signaling, and lipid accumulation. All these processes are crucial to the pathophysiology of cerebral aneurysms. CONCLUSIONS This analysis identified differentially expressed genes and miRNAs in unruptured human cerebral aneurysms, suggesting the possibility of a role for miRNAs in aneurysm formation. Further investigation for their importance as therapeutic targets is needed.

Objective Helicopter transport may shorten transportation times for emergent neurosurgical intervention. The usefulness of helicopter transport after spontaneous intraparenchymal hemorrhage is not well studied. This study seeks to clarify factors that are associated with urgent surgical intervention in patients with spontaneous intracerebral hemorrhage following helicopter transport. Methods Records were reviewed for patients with spontaneous intraparenchymal hemorrhage transported by helicopter to Dartmouth-Hitchcock Medical Center between January 2008 and December 2011. Records were evaluated for factors associated with emergent tertiary-level care intervention during the first 24 hours of admission. Results A total of 107 patients met inclusion criteria, with a mean age of 67.2 years. At presentation, 79 (75.24%) were hypertensive, 22 (21.57%) had an increased international normalized ratio, and 47 (45.19%) were intubated. Thirty-three patients (30.8%) underwent 1 or more neurosurgical interventions within 24 hours of arrival, with an additional 6 (5.6%) patients undergoing neurosurgical intervention after 24 hours after admission. On univariate analysis, age, Glasgow Coma Scale (GCS) score, and clot volume were significant predictors of neurosurgical intervention within 24 hours of interfacility helicopter transport. A lobar clot, presence of intraventricular hemorrhage, and presence of >1 cm of midline shift were also associated with neurosurgical intervention within 24 hours. On multivariate analysis, younger age, GCS score of 3–8, and lobar hemorrhage were independent predictors of neurosurgical intervention within 24 hours. Conclusions Two thirds of patients did not undergo any surgical intervention during the first 24 hours of admission after interfacility helicopter transfer. Factors associated with urgent neurosurgical intervention included younger age, low GCS score, and presence of lobar hemorrhage.

Prospective, 3:1 randomized, single-blind, multicenter investigational study.To assess the safety and efficacy of a low-swell spinal sealant when used as an adjunct to sutured dural repair compared with standard of care methods to obtain watertight dural closure in subjects undergoing spinal surgery.Watertight dural closure is paramount in spinal surgery to avoid complications of cerebrospinal fluid leak. Prior reports have proven the efficacy of a synthetic, absorbable polyethylene glycol (PEG) hydrogel sealant in spinal surgery compared with standard of care. Given the potential concerns of swelling in spinal applications, the hydrogel was modified to a low-swell formulation.The primary endpoint was success rate in obtaining intraoperative watertight dural closure in subjects receiving PEG hydrogel sealant versus a control group of subjects receiving any standard method designed to provide intraoperative watertight closure. Subjects were evaluated at discharge and at 30 and 90 days postprocedure for cerebrospinal fluid leaks, surgical site infections, and adverse events.Between May 2007 and May 2009, 98 subjects (74 PEG hydrogel spinal sealant, 24 control) were randomized at 14 clinical sites in the United States. Patients treated with the PEG hydrogel spinal sealant had a significantly higher rate of watertight closure than the control (98.6% vs. 79.2%, P = 0.003). No statistical differences were seen in postoperative cerebrospinal fluid, infection, and wound healing. No neurological deficits were seen attributable to the sealant.The low-swell PEG hydrogel spinal sealant evaluated in this study has been proven safe and effective for providing watertight closure when used as an adjunct to sutured closure of intentional durotomies during spinal surgery. PEG hydrogel sealants have again proved superior to other standard of care technologies for safe, efficacious dural closure.2.

Objective Although the primary goal of treatment of type II odontoid fracture is bony union, some advocate continued nonsurgical management of minimally symptomatic older patients who have fibrous union or minimal fracture motion. The risk of this strategy is unknown. We reviewed our long-term outcomes after dens nonunion to define the natural history of Type II odontoid fractures in elderly patients managed nonoperatively. Methods A retrospective chart review of 50 consecutive adults aged 65 or older with Type II odontoid fracture initially managed nonsurgically from 1998 to 2012 at a single tertiary care institution was conducted. Particular attention was paid to patients who had orthosis removal despite absent bony fusion. Patients were contacted prospectively by telephone and followed until death, surgical intervention, or last known contact. Results Fifty patients initially were managed nonsurgically; of these, 21 (42.0%) proceeded to bony fusion, 3 (6%) underwent delayed surgery for persistent instability, and 26 (52%) had orthosis removal despite the lack of solid arthrodesis on imaging. The last group had a median follow-up of 25 months (range 4–158 months), with 20 of 26 (76.9%) followed until death. Of these patients, 1 patient developed progressive quadriplegia and dysphagia 11 months after initial injury. Compared with patients with spontaneous union, patients with nonunion had shorter life expectancy, despite no significant differences between the groups with respect to age, sex, injury mechanism, radiographic variables, or follow-up duration. Conclusions Orthosis removal despite fracture nonunion may be reasonable in elderly patients with Type II dens fractures.

A 34-year-old right-handed female presented to the emergency department with a worsening headache, neck stiffness, intermittent abnormal sensation, and right arm weakness. Shortly after arrival, she had a generalized tonic-clonic seizure. A noncontrast head computed tomography scan revealed a right-sided, low-attenuating, lobulated mass ipsilateral to her arm symptoms. Magnetic resonance imaging revealed an abnormal signal throughout the subarachnoid space and increased fluid-attenuated inversion recovery sequence signal contralateral to the mass. This presentation suggested a false localization sign of sensory and motor disturbance ipsilateral to the mass likely caused by cyst rupture and sebum spread contralateral, causing cortical irritation (evidenced by increased fluid-attenuated inversion recovery sequence signal). During mass resection, sebum was visible throughout the subarachnoid space. The patient had an uneventful recovery from surgery and has been seizure free since the resection with steady improvement of symptoms. This case highlights the importance of avoiding cyst rupture of dermoid cysts.

Purpose Radiation therapy following resection of a brain metastasis increases the probability of disease control at the surgical site. We analyzed our experience with postoperative stereotactic radiosurgery (SRS) as an alternative to whole-brain radiotherapy (WBRT), with an emphasis on identifying factors that might predict intracranial disease control and overall survival (OS). Methods and Materials We retrospectively reviewed all patients through December 2008, who, after surgical resection, underwent SRS to the tumor bed, deferring WBRT. Multiple factors were analyzed for time to intracranial recurrence (ICR), whether local recurrence (LR) at the surgical bed or “distant” recurrence (DR) in the brain, for time to WBRT, and for OS. Results A total of 49 lesions in 47 patients were treated with postoperative SRS. With median follow-up of 9.3 months (range, 1.1-61.4 months), local control rates at the resection cavity were 85.5% at 1 year and 66.9% at 2 years. OS rates at 1 and 2 years were 52.5% and 31.7%, respectively. On univariate analysis (preoperative) tumors larger than 3.0 cm exhibited a significantly shorter time to LR. At a cutoff of 2.0 cm, larger tumors resulted in significantly shorter times not only for LR but also for DR, ICR, and salvage WBRT. While multivariate Cox regressions showed preoperative size to be significant for times to DR, ICR, and WBRT, in similar multivariate analysis for OS, only the graded prognostic assessment proved to be significant. However, the number of intracranial metastases at presentation was not significantly associated with OS nor with other outcome variables. Conclusions Larger tumor size was associated with shorter time to recurrence and with shorter time to salvage WBRT; however, larger tumors were not associated with decrements in OS, suggesting successful salvage. SRS to the tumor bed without WBRT is an effective treatment for resected brain metastases, achieving local control particularly for tumors up to 3.0 cm diameter.

This study compares the functional outcomes of nevus intermedius impairment following surgery, radiation, or observation for the treatment of vestibular schwannoma.Retrospective cohort study.Tertiary care medical center.We retrospectively examined 141 charts of patients with a vestibular schwannoma seen in the Dartmouth-Hitchcock Acoustic Neuroma Clinic between 2012 and 2014. Seventy-one patients underwent intervention (including radiation) as their primary treatment, and 70 were treated with observation. As part of routine care, patients were interviewed at clinic visits and with a questionnaire assessing nervus intermedius impairment.At presentation, 25 patients (19%) reported nervus intermedius impairment. Most common disturbances were xerophthalmia (dry eyes, 13%) and dysgeusia (taste alteration, 7.6%). Postintervention, 35 patients (53%) had ≥1 symptoms of nervus intermedius dysfunction, which is increased in comparison with patients in the observation group (17 patients, 26.5%, P.05). Twelve intervention patients had symptoms resolve postoperatively, making no long-term difference between the observation and intervention groups (P = .20). Motor function of the facial nerve postoperatively is correlated with nervus intermedius symptoms. Surgical approaches were compared with radiation therapy, and no significant difference in nervus intermedius outcomes was found.This study demonstrates the clinical importance of monitoring nervus intermedius symptoms, since a high percentage of all patients undergoing intervention will be symptomatic during management. Patients with motor dysfunction are at a higher risk of developing nervus intermedius sequelae and need close follow-up. Although impairment is common, many symptoms will improve over time with no long-term difference between intervention patients and those under observation.

Purpose To analyze 2 factors that influence timing of radiosurgery after surgical resection of brain metastases: target volume dynamics and intracranial tumor progression in the interval between surgery and cavity stereotactic radiosurgery (SRS). Methods and Materials Three diagnostic magnetic resonance imaging (MRI) scans were retrospectively analyzed for 41 patients with a total of 43 resected brain metastases: preoperative MRI scan (MRI-1), MRI scan within 24 hours after surgery (MRI-2), and MRI scan for radiosurgery planning, which is generally performed ≤1 week before SRS (MRI-3). Tumors were contoured on MRI-1 scans, and resection cavities were contoured on MRI-2 and MRI-3 scans. Results The mean tumor volume before surgery was 14.23 cm 3 , and the mean cavity volume was 8.53 cm 3 immediately after surgery and 8.77 cm 3 before SRS. In the interval between surgery and SRS, 20 cavities (46.5%) were stable in size, defined as a change of ≤2 cm 3 ; 10 cavities (23.3%) collapsed by >2 cm 3 ; and 13 cavities (30.2%) increased by >2 cm 3 . The unexpected increase in cavity size was a result of local progression (2 cavities), accumulation of cyst-like fluid or blood (9 cavities), and nonspecific postsurgical changes (2 cavities). Finally, in the interval between surgery and SRS, 5 cavities showed definite local tumor progression, 4 patients had progression elsewhere in the brain, 1 patient had both local progression and progression elsewhere, and 33 patients had stable intracranial disease. Conclusions In the interval between surgical resection and delivery of SRS, surgical cavities are dynamic in size; however, most cavities do not collapse, and nearly one-third are larger at the time of SRS. These observations support obtaining imaging for radiosurgery planning as close to SRS delivery as possible and suggest that delaying SRS after surgery does not offer the benefit of cavity collapse in most patients. A prospective, multi-institutional trial will provide more guidance to the optimal timing of cavity SRS.

Object Accurate discrimination between tumor and normal tissue is crucial for optimal tumor resection. Qualitative fluorescence of protoporphyrin IX (PpIX), synthesized endogenously following δ-aminolevulinic acid (ALA) administration, has been used for this purpose in high-grade glioma (HGG). The authors show that diagnostically significant but visually imperceptible concentrations of PpIX can be quantitatively measured in vivo and used to discriminate normal from neoplastic brain tissue across a range of tumor histologies. Methods The authors studied 14 patients with diagnoses of low-grade glioma (LGG), HGG, meningioma, and metastasis under an institutional review board–approved protocol for fluorescence-guided resection. The primary aim of the study was to compare the diagnostic capabilities of a highly sensitive, spectrally resolved quantitative fluorescence approach to conventional fluorescence imaging for detection of neoplastic tissue in vivo. Results A significant difference in the quantitative measurements of PpIX concentration occurred in all tumor groups compared with normal brain tissue. Receiver operating characteristic (ROC) curve analysis of PpIX concentration as a diagnostic variable for detection of neoplastic tissue yielded a classification efficiency of 87% (AUC = 0.95, specificity = 92%, sensitivity = 84%) compared with 66% (AUC = 0.73, specificity = 100%, sensitivity = 47%) for conventional fluorescence imaging (p < 0.0001). More than 81% (57 of 70) of the quantitative fluorescence measurements that were below the threshold of the surgeon's visual perception were classified correctly in an analysis of all tumors. Conclusions These findings are clinically profound because they demonstrate that ALA-induced PpIX is a targeting biomarker for a variety of intracranial tumors beyond HGGs. This study is the first to measure quantitative ALA-induced PpIX concentrations in vivo, and the results have broad implications for guidance during resection of intracranial tumors.

In cadaveric studies and recently in one adult patient the occipital condyle has been studied as an option to allow bone purchase by fixation devices. In the current case the authors describe the use of occipital condyle screws in a child undergoing occipitocervical fixation. To the best of the authors' knowledge this case is the first reported instance of this technique in a pediatric patient. This girl had a history of posterior fossa decompression for Chiari malformation Type I when she was 22 months of age. When she was 6 years old she presented with neck pain on flexion and extension of her head. Magnetic resonance imaging in flexion and extension revealed occipitocervical instability. She underwent an occiput to C-2 posterior arthrodesis with bilateral screw placement in the occipital condyles, C-2 lamina, and C-1 lateral masses. Postoperatively, she was neurologically intact. Computed tomography demonstrated a stable construct, and her cervical pain had resolved on follow-up.

Background: Construct failure is an uncommon but well-recognized complication following anterior cervical corpectomy and fusion (ACCF). In order to screen for these complications, many centers routinely image patients at outpatient visits following surgery. There remains, however, little data on the utility of such imaging. Methods: The electronic medical record of all patients undergoing anterior cervical corpectomy and fusion at Dartmouth-Hitchcock Medical Center between 2004 and 2009 were reviewed. All patients had routine cervical spine radiographs performed perioperatively. Follow-up visits up to two years postoperatively were analyzed. Results: Sixty-five patients (mean age 52.2) underwent surgery during the time period. Eighteen patients were female. Forty patients had surgery performed for spondylosis, 20 for trauma, three for tumor, and two for infection. Forty-three patients underwent one-level corpectomy, 20 underwent two-level corpectomy, and two underwent three-level corpectomy, using an allograft, autograft, or both. Sixty-two of the fusions were instrumented using a plate and 13 had posterior augmentation. Fifty-seven patients had follow-up with imaging at four to 12 weeks following surgery, 54 with plain radiographs, two with CT scans, and one with an MRI scan. Unexpected findings were noted in six cases. One of those patients, found to have asymptomatic recurrent kyphosis following a two-level corpectomy, had repeat surgery because of those findings. Only one further patient was found to have abnormal imaging up to two years, and this patient required no further intervention. Conclusions: Routine imaging after ACCF can demonstrate asymptomatic occurrences of clinically significant instrument failure. In 43 consecutive single-level ACCF however, routine imaging did not change management, even when an abnormality was discovered. This may suggest a limited role for routine imaging after ACCF in longer constructs involving multiple levels.

Although there is agreement on the oncologic management of patients with glioma, few guidelines exist to standardize other aspects of care, including supportive care.A quality improvement (QI) project was chartered to improve the care provided to patients with glioma. A multidisciplinary team was convened and identified 10 best-practice measures. Using a plan-do-study-act framework, the team brainstormed and implemented various improvement interventions between June 2011 and October 2012. Statistical process control charts were used to evaluate progress. A dashboard of quality measures was generated to allow for ongoing measurement and reporting.The retrospective assessment phase consisted of 43 patients with diagnosis of glioma. A manual medical record review for these patients showed that compliance with 10 best-practice measures ranged from 23% to 100%. Several factors contributed to less-than-ideal process performance, including poor communication among disciplines and lack of familiarity with the larger system of care. After implementing improvement interventions, performance was measured in 96 consecutive patients with glioma. The proportion of patients who met criteria for 10 practice measures significantly improved (pre-QI work, 63%; post-QI work, 85%; P = .003). The largest improvement was observed in the measure assessing for preoperative notification of the neuro-oncology program (pre-QI work, 39%; post-QI work, 97%; P.001).QI principles were used by a multidisciplinary team to improve the quality of care for patients with glioma during the perioperative period. Leadership involvement, ongoing dialogue across departments, and reporting of system performance were important for sustaining process improvements.

The use of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence has shown promise as a surgical adjunct for maximizing the extent of surgical resection in gliomas. To date, the clinical utility of 5-ALA in meningiomas is not fully understood, with most descriptive studies using qualitative approaches to 5-ALA-PpIX.To assess the diagnostic performance of 5-ALA-PpIX fluorescence during surgical resection of meningioma.ALA was administered to 15 patients with meningioma undergoing PpIX fluorescence-guided surgery at our institution. At various points during the procedure, the surgeon performed qualitative, visual assessments of fluorescence by using the surgical microscope, followed by a quantitative fluorescence measurement by using an intraoperative probe. Specimens were collected at each point for subsequent neuropathological analysis. Clustered data analysis of variance was used to ascertain a difference between groups, and receiver operating characteristic analyses were performed to assess diagnostic capabilities.Red-pink fluorescence was observed in 80% (12/15) of patients, with visible fluorescence generally demonstrating a strong, homogenous character. Quantitative fluorescence measured diagnostically significant PpIX concentrations (cPpIx) in both visibly and nonvisibly fluorescent tissues, with significantly higher cPpIx in both visibly fluorescent (P.001) and tumor tissue (P = .002). Receiver operating characteristic analyses also showed diagnostic accuracies up to 90% for differentiating tumor from normal dura.ALA-induced PpIX fluorescence guidance is a potential and promising adjunct in accurately detecting neoplastic tissue during meningioma resective surgery. These results suggest a broader reach for PpIX as a biomarker for meningiomas than was previously noted in the literature.

Object. The authors reviewed their series of patients to quantify clinical and radiographic complications in those who underwent a posterior lumbar interbody fusion (PLIF) procedure in which a threaded interbody cage (TIC) was implanted. Methods. Sixty-seven patients underwent a posterior lumbar interbody fusion procedure in which a TIC was used. The authors excluded patients who underwent procedures in which other instrumentation was used or a nondorsal approach was performed. Fifteen percent of the cases (10 patients) were complicated by laceration of the dura. In three cases, bilateral implantation could not be performed. The average blood loss was 670 ml for all cases, and blood transfusion was required in 25% of the cases (17 patients). The rate of minor wound complication was 4.5% (three patients). One patient died. The average period of hospitalization was 4.25 days. Twenty-eight patients (42%) experienced significant low-back pain 3 months postoperatively, and in 10 (15%) of these cases it persisted beyond 1 year. In 10 patients postoperative radiculopathy was demonstrated, and magnetic resonance imaging revealed epidural fibrosis in six patients, arachnoiditis in one, and a recurrent disc herniation in one. One patient incurred a permanent motor deficit with sexual dysfunction. Pseudarthrosis was suggested radiographically with evidence of motion on lateral flexion—extension radiographs (10 cases), lucencies around the implants (seven cases), and posterior migration of the cage (two cases). Additional procedures (in 14 patients) consisted primarily of transverse process fusion with pedicle screw and plate augmentation for persistent back pain and radiographically demonstrated signs of spinal instability. In two patients with radiculopathy, migration of the TIC required that it be removed. Graft material that extruded from one implant necessitated its removal. In one patient scarectomy was performed. Conclusions. Our high incidence of TIC-related complications in PLIF is inconsistent with that reported in previous studies.

BACKGROUND Epidural hematoma usually stems from trauma, yet it may occur from other etiologies, including neoplasms. We present a case of small cell lung carcinoma with focal hemorrhagic central nervous system metastasis producing an epidural hematoma, and review the associated literature. CLINICAL PRESENTATION A 67-year-old man was undergoing chemotherapy for small cell carcinoma of the lung. Acute neurologic deterioration resulted from a large parietal epidural hematoma of non-traumatic origin. INTERVENTION The clot was evacuated via craniotomy with marked improvement in his clinical state. Metastatic tumor was present in the scalp, muscle, bone, and dura. No gross brain invasion was apparent. CONCLUSIONS This case illustrates the wisdom of including metastatic disease in the differential diagnosis of intracranial hemorrhage. Even epidural hematoma may result from metastatic cancer. The prevalence of lung carcinoma and the aging of the population may produce an increased appearance of this phenomenon. Appropriate evaluation and rapid intervention will aid the patient in both the acute and long-term phases, and should improve the quality of survival.

Background: Antiestrogens are effective in the treatment of estrogen receptor (ER) positive breast carcinoma. The use of antiestrogen therapy in pituitary adenomas, however, has not been explored. This study attempted to identify a population who may benefit from antiestrogen therapy.

Background context There is a persistent trend for more outpatient lumbar discectomies in the United States. Purpose To investigate the characteristics of the patients selected for ambulatory procedures. Study design Retrospective cohort study. Patient sample Forty-seven thousand one hundred twenty-five patients who underwent outpatient and 102,592 patients undergoing inpatient lumbar discectomies and were were registered in the State Ambulatory Surgery Database (SASD) and State Inpatient Database (SID), respectively, for New York, California, Florida, and North Carolina from 2005 to 2008. Outcome measures Rate of outpatient procedures, 30-day readmissions, and hospital charges. Methods We performed a retrospective cohort study involving patients who underwent outpatient and inpatient lumbar discectomies and were registered in SASD and SID, respectively, for New York, California, Florida, and North Carolina from 2005 to 2008. Logistic regression models were used to demonstrate the association of socioeconomic factors with the odds of undergoing an outpatient procedure. Results Male gender (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.03–1.08), private insurance (OR, 1.93; 95% CI, 1.86–2.01), lower Charlson Comorbidity Index (OR, 4.04; 95% CI, 3.17–5.16), and higher volume hospitals (OR, 1.06; 95% CI, 1.04–1.08) were significantly associated with outpatient procedures. Higher income (OR, 0.83; 95% CI, 0.81–0.85), older age (OR, 0.996; 95% CI, 0.995–0.997), coverage by Medicaid (OR, 0.89; 95% CI, 0.83–0.96), African Americans (OR, 0.65; 95% CI, 0.60–0.70), and other minority races were associated with decreased odds of outpatient procedures. The rate of 30-day postoperative readmissions was higher among inpatients. Institutional charges were significantly lower for outpatient lumbar discectomies. The median charge for inpatient surgery was $24,273 as compared with $11,339 for the outpatient setting (p Conclusions Access to ambulatory lumbar discectomies appears to be more common for younger, white, male patients, with private insurance and less comorbidities, in the setting of higher volume hospitals. Further investigation is needed in the direction of mapping these disparities for appropriate resource utilization.

The association of surgical duration with the risk of surgical site infection (SSI) has not been quantified in neurosurgery. We investigated the association of operative duration in neurosurgical procedures with the incidence of SSI.We performed a retrospective cohort study involving patients who underwent neurosurgical procedures from 2005 to 2012 and were registered in the American College of Surgeons National Quality Improvement Project registry. To control for confounding, we used multivariable regression models and propensity score conditioning.During the study period there were 94,744 patients who underwent a neurosurgical procedure and met the inclusion criteria. Of these patients, 4.1% developed a postoperative SSI within 30 days. Multivariable logistic regression showed an association between longer operative duration with higher incidence of SSI (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.16-1.20). Compared with procedures of moderate duration (third quintile, 40th-60th percentile), patients undergoing the longest procedures (80th percentile) had higher odds (OR, 2.07; 95% CI, 1.86-2.31) of developing SSI. The shortest procedures (20th percentile) were associated with decreased incidence of SSI (OR, 0.72; 95% CI, 0.61-0.83) compared with those of moderate duration. The same associations were present in propensity score adjusted models and models stratified by subgroups of cranial, spinal, peripheral nerve, and carotid procedures.In a cohort of patients from a national prospective surgical registry, longer operative duration was associated with increased incidence of SSI for neurosurgical procedures. These results can be used by neurosurgeons to inform operative management and to stratify patients with regard to SSI risk.

This preliminary study demonstrates the vital role that magnetic resonance imaging plays in the study of neuronal grafts in a nonhuman primate model of Huntington's disease. MRI scans were used to accurately locate and stereotactically lesion the anterior putamen of an adult rhesus monkey, thereby mimicking the anatomical and biochemical changes in Huntington's disease. Follow-up scans were utilized to confirm correct placement of the lesion and to stereotactically implant primate fetal neuronal tissue precisely into the lesion. Additionally, MRI appeared capable of imaging the fetal striatal grafts in rhesus monkeys. While the precise cellular composition of growing grafts was not identifiable on MRI scans, differentiation between normal, lesioned, and engrafted tissue was possible. Correlation of the magnetic resonance images of the grafted regions with actual graft tissue in perfused sections of the brain was shown. The use of magnetic resonance imaging, as indicated in these neuronal implantation studies, allows for a wide variety of future research possibilities where noninvasive and precise localization of the graft is mandated.

Accurate discrimination between tumor and normal tissue is crucial for optimal tumor resection. Qualitative fluorescence of protoporphyrin IX (PpIX), synthesized endogenously following δ-aminolevulinic acid (ALA) administration, has been used for this purpose in high-grade glioma (HGG). The authors show that diagnostically significant but visually imperceptible concentrations of PpIX can be quantitatively measured in vivo and used to discriminate normal from neoplastic brain tissue across a range of tumor histologies.The authors studied 14 patients with diagnoses of low-grade glioma (LGG), HGG, meningioma, and metastasis under an institutional review board-approved protocol for fluorescence-guided resection. The primary aim of the study was to compare the diagnostic capabilities of a highly sensitive, spectrally resolved quantitative fluorescence approach to conventional fluorescence imaging for detection of neoplastic tissue in vivo.A significant difference in the quantitative measurements of PpIX concentration occurred in all tumor groups compared with normal brain tissue. Receiver operating characteristic (ROC) curve analysis of PpIX concentration as a diagnostic variable for detection of neoplastic tissue yielded a classification efficiency of 87% (AUC = 0.95, specificity = 92%, sensitivity = 84%) compared with 66% (AUC = 0.73, specificity = 100%, sensitivity = 47%) for conventional fluorescence imaging (p0.0001). More than 81% (57 of 70) of the quantitative fluorescence measurements that were below the threshold of the surgeon's visual perception were classified correctly in an analysis of all tumors.These findings are clinically profound because they demonstrate that ALA-induced PpIX is a targeting biomarker for a variety of intracranial tumors beyond HGGs. This study is the first to measure quantitative ALA-induced PpIX concentrations in vivo, and the results have broad implications for guidance during resection of intracranial tumors.

Primate fetal neostriatal neurons were implanted into the ibotenic acid-lesioned primate striatum and the animals were allowed to survive for 8 months. Light microscopic examination of the transplanted tissue demonstrated that the grafts were between 1.0 and 1.5 mm in diameter. The transplants were highly gliotic, but contained both normal appearing and degenerating neurons. At the electron microscopic level, the transplanted neurons displayed ultrastructural features identical to those of medium spiny, medium aspiny, and large aspiny striatal neurons. However, the majority of the grafted neurons showed evidence of degeneration. The grafts' neuropil demonstrated numerous glial processes, as well as mature axodendritic and axospinous synapses, Although this study was limited to only two graft recipients, the degenerative changes seen in the long-term primate allografts suggest that extension of these techniques into the clinical selling may be premature at the present time.

✓ Cerebral vasospasm continues to be the leading treatable cause of morbidity and mortality following aneurysmal subarachnoid hemorrhage. In this preliminary anecdotal series of 12 patients who were candidates for balloon angioplasty, vasospasm was treated instead with intra-arterial papaverine. Eight patients had marked angiographic reversal of the arterial narrowing following papaverine infusion, four of whom showed dramatic reversal of profound neurological deficits. Two patients deteriorated clinically 5 days after the initially successful papaverine infusions. In both, repeat angiography demonstrated severe recurrent vasospasm, which was partially reversed with a second intra-arterial papaverine treatment. Two patients developed focal neurological deficits during papaverine infusion, which resolved spontaneously over several hours after cessation of the intra-arterial infusion. Arterial narrowing in the posterior circulation and middle cerebral artery distribution appeared to be more responsive to papaverine infusion than was spasm in the anterior cerebral arteries. The infusion of 300 mg of papaverine over 1 hour seemed to be an adequate and safe dose to effect these angiographic and clinical improvements.

Primate fetal striatal neurons were transplanted into the ibotenic acid lesioned rhesus monkey striatum. Ten weeks after transplantation the monkeys were transcardially perfused and graft tissue was histologically stained, Golgi impregnated, and processed for electron microscopy. The monkeys received magnetic resonance imaging (MRI) scans before lesioning, after lesioning, and ten weeks after transplantation to noninvasively study the striatal grafts. The study demonstrated that fetal striatal grafts, measuring up to 0.4 × 0.8 cm, can survive for extended periods of time in the non-human primate. Hematoxylin-eosin stained sections of the transplant demonstrated that neuronal, glial, vascular, and lymphocytic cells were present in the graft. The majority of the neurons had somatic diameters between 8 and 20 μm and were characterized by nuclei containing multiple nucleoli. A few neurons within the graft had somatic diameters up to 40 μm. These larger neurons exhibited more mature cytoplasm containing a moderate amount of Nissl substance. Some of the blood vessels within the graft were surrounded by a large number of plasma cells, but there was no evidence of hemorrhage or necrosis. Bielschowsky staining and Golgi impregnation of the transplanted tissue demonstrated that there were neurons at various degrees of differentiation. Some of the neurons had varicose dendrites, growth cones, and filopodia, which are all characteristics of immature neurons, while others had a much more mature appearance, including a moderate number of dendritic spines. Some of these neurons had an appearancetypical of differentiating “medium spiny” neurons of the normal striatum. Electron microscopic analysis of the transplanted tissue and individual Golgi-impregnated neurons within the transplant confirmed that there were developing neurons within the graft. These neurons had an increased nuclear-to-cytoplasmic ratio and had nuclei containing multiple nucleoli. The neuropil surrounding these neurons was loosely organized and contained large areas of extracellular space. The neuropil exhibited developing dendrites, numerous growth cones, and mature synapses. In summary, the study demonstrated that fetal striatal allografts can survive for up to three months in the rhesus monkey and undergo normal differentiation as assessed by Golgi impregnation and electron microscopy.

Stereotactic implantation of fetal brain regional anlage into adult host brain (“brain transplantation”) appears to be an increasingly viable strategy for therapy of neurodegenerative diseases. We have studied implantation of fetal striatum into adult striatum, previously lesioned by neurotoxic amino acid injection, as a model for transplantation therapy of Huntington's disease. The beginning of behavioral recovery to apomorphine is not apparent until 6.5 months after implantation. By 4 months after implantation cerebral blood flow through the implants appears equal to that in the intact contralateral striatum. At this time, cerebral glucose utilization is reduced in the implants but increases following apomorphine treatment. The development of D1 and D2 dopamine (DA) receptors is markedly deficient in the striatal grafts at both 4 and 6.5 months after implantation. Very little D2 radioligand binding was observed in the grafts at either time point; D1 receptors appeared in a patchy fashion by 6.5 months at densities approaching normal striatum. In situ hybridization of D2 dopamine receptor mRNA demonstrated robust hybridization signal in normal striatum and accumbens but no signal in 6.5-month-old striatal grafts. Adenylate cyclase (AC) activity, examined with high-affinity [3H]forskolin binding, also appeared in patches similar to D1 receptors at 6.5 months. In contrast, protein kinase C activity, labeled with [3H]phorbol ester, was very apparent in the grafts at both time points. Higher and generally homogenous densities of muscarinic cholinergic receptors, assessed with [3H]QNB binding, develop in the grafts, but there appear to be few functioning cholinergic terminals, as measured by [3H]hemicholinium binding. Our data demonstrate that very few D1 or D2 DA receptors develop in fetal striatal neurons removed from E15–16 embryos and subsequently implanted into adult ibotenic acid-lesioned striata. The lack of D2 receptor development appears to derive from lack of transcription of the D2 receptor gene. By 6.5 months, D1 receptor sites and AC activity both appear in discrete patches, consistent with the known in vitro association of D1 receptors with stimulation of AC activity. In this model, the majority of graft protein kinase C activity, to the extent that it is labeled with [3H]phorbol ester, is not associated with DA receptors. DA receptor development in fetal striatal implants may require coimplantation of DA neurons.

UNLABELLED: OBJECTIVE/IMPORTANCE: One of the most severe complications of craniosynostosis repair is dural sinus laceration. Massive hemorrhage and air embolism are potentially life-threatening sequelae that can result from such an event. The aberrant anatomy of patients with craniosynostosis only accentuates this risk, because separation of the calvaria from the underlying dura is often performed without direct visualization of the sinuses. METHODS: Three-dimensional computed tomography was combined with computed tomographic angiography in the preoperative assessment of patients with craniofacial abnormalities. RESULTS: A clear understanding of the dural sinus anatomy in relation to the overlying bony landmarks became available to the operating surgeon. Six patients underwent this procedure, with excellent visualization of the bony and sinus anatomy achieved in all cases. CONCLUSION: It is thought, that the benefit of combining these procedures has been significant by allowing the visualization of the dural sinus anatomy and overlying bony landmarks. This procedure conveys minimal concomitant morbidity or expense to the patient, yet offers valuable insight toward operative planning and complication avoidance.

✓Pituitary carcinoma is a rare tumor characterized by poor responsiveness to therapy, leading to early death. Reported responses to standard chemotherapy have only been anecdotal, with no single agent or combination demonstrating consistent efficacy in the treatment of patients with this disease. The authors report rare examples of a persistent response to cytotoxic chemotherapy in two patients with pituitary carcinoma. One patient was a 38-year-old man with visual field loss caused by a luteinizing hormone–secreting pituitary carcinoma that had recurred despite multiple surgeries and radiation therapy. Intradural metastases to the spine that had failed to respond to radiation therapy were pathologically confirmed. The second patient was a 26-year-old man with hyperprolactinemia from a prolactin-secreting pituitary tumor. Spine magnetic resonance images obtained to search for causes of neck pain showed a vertebral tumor, which was later confirmed through pathological analysis to be a metastatic pituitary carcinoma. His disease progressed despite radiation therapy, high-dose bromocriptine, and chemotherapy. Both patients were treated monthly with temozolomide, which was administered orally on the first 5 days of a 28-day cycle. The patient in the first case underwent all 12 treatment cycles without serious side effects, and his visual field deficits improved. The patient in the second case had undergone only 10 cycles when the drug was stopped because of his severe fatigue. Nonetheless, his pain disappeared and his serum prolactin concentration decreased. Both patients continue to have partial responses and have been employed full-time for more than 1 year after discontinuing temozolomide therapy. These two examples demonstrate that temozolomide may be effective in treating pituitary carcinomas and thus should be considered in the treatment algorithm for these difficult cases.

The transthoracic approach to herniated thoracic discs is an important procedure in the management of these uncommonly encountered lesions. Whereas posterior and posterolateral microsurgical approaches and thoracoscopic procedures have been widely advocated in the recent neurosurgical literature, the transthoracic operation continues to offer significant advantages in appropriately selected cases. The authors discuss the preoperative considerations, relevant anatomical structures, and surgical technique.

Object. Transsphenoidal surgery remains the optimal treatment for Cushing disease, but the definitions of surgical cure and failure remain debatable. In this study the authors evaluated serum cortisol levels in patients before and after they underwent transsphenoidal surgery to elucidate the patterns of cortisol decrease and the optimal time and criteria for determining surgically induced remission. Methods. Twenty-seven patients were evaluated throughout an 8-month period. Serum cortisol levels were obtained before surgery and at 6-hour intervals postoperatively. No exogenous steroid medications were administered until after cortisol sampling was discontinued, following diagnosis of remission. Twenty-one (78%) of 27 cases were labeled initial surgically induced remissions. Twenty-two (81%) of 27 cases were deemed surgically induced remissions at follow-up examination. Following surgery, initial remissions and failures demonstrated divergent patterns of cortisol levels. No patient whose condition was deemed an initial surgically induced remission has experienced definitive relapse of disease since discharge. One patient whose condition was initially deemed a surgical failure, eventually was found to exhibit surgically induced remission without further intervention. Conclusions. Given such findings, exogenous steroid medications do not appear to be required for patients until after the determination of remission. During the 1st postoperative day, there is a time period during which serum cortisol values significantly differ between the categories of surgically induced remissions and surgical failures. Surgically induced remissions were identified when postoperative values of cortisol were lower than preoperative midnight levels and when absolute values of cortisol were less than 10 µg/dl. In a small proportion of patients remission on a delayed basis may also be demonstrated. These data allow for a simple and rapid determination of postoperative remission in patients undergoing transsphenoidal surgery for Cushing disease.

Object. The authors undertook a study to explore the predisposing risk factors, frequency of occurrence, and clinical implications of kyphosis following laminectomy for cervical spondylotic myelopathy (CSM). Methods. Preoperative radiological studies were available in 46 patients with CSM who had undergone laminectomy. Records were reviewed to obtain demographic data and operative reports. Preoperative radiographs were assessed to determine spinal alignment. In a follow-up interview the authors established clinical outcome and patient satisfaction. Postoperative cervical alignment and mobility was also determined by assessing lateral neutral, flexion, and extension x-ray films. Preoperatively, the cervical spine was shown to be kyphotic in four (9%) of 46, straight in 20 (43%) of 46, and lordotic in 22 (48%) of 46 patients. Nine (21%) of 42 patients with either straight or lordotic alignment demonstrated in the preoperative period developed kyphosis after surgery. Kyphosis developed in six (30%) of 20 patients in whom straight spinal alignment was demonstrated preoperatively and in only three (14%) of 22 patients in whom lordosis was found preoperatively. Clinically, 13 (29%) of 45 patients improved and 19 (42%) of 45 remained unchanged after an average 4-year follow-up period; 36 (80%) patients believed that their surgery was successful (one patient, who was mentally retarded, could not respond to the follow-up questionnaire). Spinal alignment was not predictive of outcome; cervical mobility as demonstrated on flexion and extension, however, correlated with improved functional performance (p = 0.005). Conclusions. Kyphosis may develop in up to 21% of patients who have undergone laminectomy for CSM. Progression of the deformity appears to be more than twice as likely if preoperative radiological studies demonstrate a straight spine. In this study, clinical outcome did not correlate with either pre- or postoperative sagittal alignment.

BACKGROUND Cushing's disease causes significant pathological changes throughout the body as a result of elevated cortisol levels. Very few systematic investigations have focused on the morphologic effects of hypercortisolism on the central nervous system. The validity of using premature cerebral atrophy as a diagnostic tool for Cushing's disease remains unknown. METHODS This study includes 63 patients with Cushing's disease who were evaluated and treated at the University of Virginia Medical Center. Radiologists randomly compared these individuals with age- and sex-matched controls in a blinded protocol, assessing the degree of cerebral atrophy on computed tomography and magnetic resonance scans. RESULTS Patients with Cushing's disease showed significant premature atrophy when compared with controls. This trend continued after subdividing the groups based on age and duration of symptoms except in the following groups: age greater than 60, duration of symptoms less than 1 year, and symptoms lasting between 4-5 years. CONCLUSIONS Excluding the three aforementioned groups, the hypercortisolemic state manifested in patients with Cushing's disease promotes the premature development of cerebral atrophy, which can be identified on routine radiologic imaging and may assist in the clinical diagnosis of the condition.

Background and importance Comminuted sacral fractures present significant challenges for operative management. Open and percutaneous sacroiliac screws have been used for stabilization but carry not insignificant rates of complications, including wound infection for the former and malposition and neurological injury for the latter. We report the use of a novel mini-open lumbar-ilium fixation for stabilization of a patient with a comminuted sacral fracture. Clinical presentation A 33-year-old man with intact neurologic function was admitted after a fall of approximately 25 ft. A comminuted sacral fracture was diagnosed. The patient was unable to tolerate conservative management because of pain in upright positions. The patient was taken to the operating room for stabilization with a "mini-open" procedure involving L4 and L5 pedicle screws and bilateral iliac screws. Four 2-in paramedian incisions were made overlying the L4-L5 facet joints and medial to the sacroiliac joints. Minimally invasive retractors were placed to expose bony landmarks. L4-L5 pedicle screws and bilateral iliac screws were placed with minimal fluoroscopic guidance. Titanium rods were tunneled inferior-superiorly between incisions and affixed to screw heads. Total operative time was approximately 3.5 hours. The patient remained neurologically intact and had an uncomplicated recovery. One-year follow-up computed tomography showed successful healing of the sacrum. Conclusion We report the first case of a mini-open procedure to treat a comminuted sacral fracture. Use of this procedure offers a straightforward method for sacral stabilization with minimal blood loss and minimal radiation exposure. If indicated, this method could be combined with decompressive procedures.

OBJECTIVE : An optimal method for spinal fusion would induce rapid growth of bone via an osteoconductive and osteoinductive implant. This study examines the spinal fusion enhancement potential of some osteoconductive and osteoinductive biomaterials. METHODS : Four similar canines received unilateral posterolateral fusions on the left side at T13-L1 and L4-L5 and on the right side at L2-L3 and L6-L7. The experiments were grouped as follows : Group A, autogenous bone harvested from the iliac crest ; Group B, autogenous bone and collagen ; Group C, no implant ; and Group D, autogenous bone, collagen, and recombinant human bone morphogenetic protein-2. Radiographic assessment, three-dimensional computed tomographic volumetric analysis, and biomechanical testing were performed at each level. RESULTS : For Groups A and B, the fusions demonstrated moderate bone formation at 6 and 12 weeks postoperatively. Group D fusions exhibited earlier and more dramatic increases in volume and radiodensity and eventually were comparable in size to the vertebral bodies. Average fusion volumes computed from three-dimensional computed tomographic analysis were : Group A = 1.243 cc, Group B = 0.900 cc, Group C = 0.000 cc, and Group D = 6.668 cc (P = 0.003 compared to Group A). Group D exhibited flexion and extension biomechanical properties much greater than controls. The addition of recombinant human bone morphogenetic protein-2 consistently yielded the strongest fused segments and, on average, enhanced extension stiffness by 626% and flexion stiffness by 1120% over controls. CONCLUSION : The most advantageous spinal fusion implant matrix consisted of recombinant human bone morphogenetic protein-2, autogenous bone, and collagen. Future investigators, however, need to examine the appropriate quantities of the individual components and clarify the efficacy of the matrix for the various types of spinal fusion approaches.

✓ A new surgical technique for the treatment of lumbar spinal stenosis features extensive unilateral decompression with undercutting of the spinous process and, to preserve stability, uses contralateral autologous bone fusion of the spinous processes, laminae, and facets. The operation was performed in 29 patients over a 19-month period ending in December of 1991. All individuals had been unresponsive to conservative treatment and presented with low-back pain in addition to signs and symptoms consistent with neurogenic claudication or radiculopathy. Nine had undergone previous lumbar decompressive surgery. The minimum and mean postoperative follow-up times were 2 and 2 1/2 years, respectively. The mean patient age was 64 years; only two patients were younger than 50 years of age.Of the patients with neurogenic claudication, 69% reported complete pain relief at follow-up review. Of those with radicular symptoms, 41% had complete relief and 23% had mild residual pain that was rated 3 or less on a pain—functionality scale of 0 to 10. For the entire sample, this surgery decreased pain from 9.2 to 3.3 (p < 0.0001) on the scale. Sixty-nine percent of patients were satisfied with surgery. Low-back pain was significantly relieved in 62% of all patients (p < 0.0001). Low-back pain relief correlated negatively with number of levels decompressed (p < 0.05). To assess fusion, follow-up flexion/extension radiographs were obtained, and no motion was detected at the surgically treated levels in any patient.The results suggest that this decompression procedure safely and successfully treats not only the radicular symptoms caused by lateral stenosis but also the neurogenic claudication symptoms associated with central stenosis. In addition, the procedure, by using contralateral autologous bone fusion along the laminae and spinous processes, can preserve stability without instrumentation.

The retinal afferents to the basal optic nucleus in the frog, Rana Pipiens, were labeled anterogradely with biocytin and subsequently studied at the electron microscopic level. Labeled synaptic terminals in the nucleus varied in size from 0.5 microns to 2.0 microns and made symmetric synaptic contacts with large and small dendrites, although very rare axospinous and axosomatic contacts were also demonstrated.

Cerebral vasospasm continues to be the leading treatable cause of morbidity and mortality following aneurysmal subarachnoid hemorrhage. In this preliminary anecdotal series of 15 patients who were candidates for balloon angioplasty, vasospasm was treated instead with intra-arterial papaverine. Ten patients had marked angiographic reversal of the arterial narrowing following the papaverine infusion. Five of these patients showed dramatic reversal of profound neurologic deficits following papaverine treatment. Two patients clinically deteriorated five days after the initial successful papaverine infusions. In both, repeat angiograms demonstrated severe recurrent vasospasm which was partially reversed with a second intra-arterial papaverine treatment. Three patients developed focal neurologic deficits during papaverine infusion which spontaneously resolved over several hours after cessation of the intraarterial infusion. Arterial narrowing in the posterior circulation and middle cerebral artery distribution appeared to be more responsive to papaverine infusion than spasm in the anterior cerebral arteries. The infusion of 300 mg of papaverine over one hour seemed to be an adequate and safe dose to effect these angiographie and clinical improvements.

✓ Several types of adjustable clamp have been widely utilized to gradually occlude the carotid artery for the treatment of various intracranial vascular lesions. A fairly large number of patients, many of whom have not been adequately followed, have these clamps still in place. The authors report two patients, initially treated with a Crutchfield clamp for an intracranial aneurysm, in whom carotid artery system revascularization occurred through the clamp many years later, leading to continued filling of the aneurysm. Recommendations are given on monitoring patients with Crutchfield clamps in order to minimize long-term complications.

Numerous methods have been utilized in the past to study the retinofugal pathway at both the light and electron microscopic levels. However, many of these techniques have technical drawbacks that make them difficult to use in electron microscopic studies. We present herein a method for utilizing the anterograde tracer biocytin to study the retinal pathways at both the light and electron microscopic levels. Biocytin is an especially useful tracer since it clearly labels very small axons and boutons in addition to the larger fibers. In addition, the synaptic ultrastructure is left intact and the technique can be utilized in numerous double-labeling neuroanatomical studies.