bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unilateral intraputaminal glial cell line–derived neurotrophic factor in patients with Parkinson disease: response to 1 year each of treatment and withdrawal
Authors: Slevin John T. , Gash Don M. , Smith Charles D. , Gerhardt Greg A. , Kryscio Richard , Chebrolu Himachandra , Walton Ashley , Wagner Renee , Young A. Byron 
Published: February 2011

Object
Glial cell line–derived neurotrophic factor (GDNF) infused unilaterally into the putamen for 6 months was previously shown to improve motor functions and quality of life measures significantly in 10 patients with Parkinson disease (PD) in a Phase I trial. In this study the authors report the safety and efficacy of continuous treatment for 1 year or more. After the trial was halted by the sponsor, the patients were monitored for an additional year to evaluate the effects of drug withdrawal.

Methods
During the extended study, patients received unilateral intraputaminal infusion of 30 μg/day GDNF at a basal infusion rate supplemented with pulsed boluses every 6 hours at a convection-enhanced delivery rate to increase tissue penetration of the protein. When the study was stopped, the delivery system was reprogrammed to deliver sterile saline at the basal infusion rate of 2 μl/hour.
The Unified PD Rating Scale (UPDRS) total scores after 1 year of therapy were improved by 42 and 38%, respectively, in the “off” and “on” states. Motor UPDRS scores were also improved: 45 and 39% in the off and on conditions, respectively. Benefits from treatment were lost by 9 to 12 months after GDNF infusion was halted. At that time, the patients had returned to their baseline UPDRS scores and required higher levels of conventional antiparkinsonian drugs to treat symptoms. After 11 months of treatment, the delivery system had to be removed in one patient because of the risk of infection. In seven patients antibodies to GDNF developed, with no evidence of clinical sequelae. There was also no evidence of GDNF-induced cerebellar toxicity, as evaluated using magnetic resonance imaging analysis and clinical testing.

Conclusions
Unilateral administration of GDNF results in significant, sustained bilateral benefits. These improvements are lost within 9 months after drug withdrawal. Safety concerns with GDNF therapy can be closely monitored and managed.
A technique for minimally altering anatomically based subthalamic electrode targeting by microelectrode recording
Authors: Senatus Patrick B. , Teeple David , McClelland Shearwood , Pullman Seth L. , Yu Qiping , Ford Blair , McKhann Guy M. , Goodman Robert R. 
Published: February 2011

Object
Implantation of a subthalamic nucleus (STN) deep brain stimulation (DBS) electrode is increasingly recognized as an effective treatment for advanced Parkinson disease (PD). Despite widespread use of microelectrode recording (MER) to delineate the boundaries of the STN prior to stimulator implantation, it remains unclear to what extent MER improves the clinical efficacy of this procedure. In this report, the authors analyze a series of patients who were treated at one surgical center to determine to what degree final electrode placement was altered, based on readings obtained with MER, from the calculated anatomical target.

Methods
Subthalamic DBS devices were placed bilaterally in nine patients with advanced PD. Frame-based volumetric magnetic resonance images were acquired and then transferred to a stereotactic workstation to determine the anterior and posterior commissure coordinates and plane. The initial anatomical target was 4 mm anterior, 4 mm deep, and 12 mm lateral to the midcommissural point. The MERs defined the STN boundaries along one or more parallel tracks, refining the final electrode placement by comparison of results with illustrations in a stereotactic atlas.
In eight of 18 electrodes, the MER results did not prompt an alteration in the anatomically derived target. In another eight placements, MER altered the target by less than 1 mm and two of 18 electrode positions differed by less than 2 mm. The anterior–posterior difference was 0.53 ± 0.65 mm, whereas the medial–lateral direction differed by 0.25 ± 0.43 mm. The ventral boundary of the STN defined by MER was 2 ± 0.72 mm below the calculated target (all values are the means ± standard deviation). All patients attained clinical improvement, similar to previous reports.

Conclusions
In this series of patients, microelectrode mapping of the STN altered the anatomically based target only slightly. Because it is not clear whether such minor adjustments improve clinical efficacy, a prospective clinical comparison of MER-refined and anatomical targeting may be warranted.
Stereotactic radiosurgery for glioblastoma: a final report of 31 patients
Authors: Masciopinto Jeffery E. , Levin Allan B. , Mehta Minesh P. , Rhode Blair S. 
Published: February 2011

✓ From February 1989 to December 1992, 31 patients who presented with an initial pathological diagnosis of glioblastoma multiforme underwent tumor debulking or biopsy, stereotactic radiosurgery, and standard radiation therapy as part of their primary treatment. Presenting characteristics in the 22 men and nine women included a median age of 57 years, Karnofsky Performance Scale score median of 80, and median tumor volume of 16.4 cm3.
Stereotactic radiosurgery delivered a central dose of 15 to 35 Gy with the isocenter location, collimator size, and beam paths individualized by means of three-dimensional software developed at the University of Wisconsin. The peripheral isodose line varied from 40% to 90% with a median of 72.5% and a mode of 80%. The mean follow-up period was 12.84 months with a median of 9.5 months. Statistical analysis was performed using Kaplan—Meier analysis and log-rank comparison of risk factor groups.
The parameters of age, initial Karnofsky Performance Scale score, and biopsy were significantly different in patient survival from debulking; but no difference was noted between single and multiple isocenters and patterns of steroid requirement. Radiographic recurrences were divided by location into the following categories: central (within central stereotactic radiosurgery dose), 0; peripheral (within 2 cm of central dose), 19; and distant (> 2 cm), 4. There is no evidence of recurrence in five surviving patients. Actuarial 12-month survival was 37%, with a median survival of 9.5 months. These values are similar to previous results for surgery and standard radiotherapy alone.22 The results suggest that the curative value of radiosurgery is significantly limited by peripheral recurrences.
The role of minocycline in the treatment of intracranial 9L glioma
Authors: Weingart Jon D. , Sipos Eric P. , Brem Henry 
Published: February 2011

✓ This study was designed to explore the question of whether minocycline, a semisynthetic tetracycline shown to inhibit tumor-induced angiogenesis, could control the growth of the rat intracranial 9L gliosarcoma. Minocycline was tested alone and in combination with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in vivo. Treatment was started at the time of intracranial implantation of 9L gliosarcoma into male Fischer 344 rats, 5 days later, or after tumor resection.
Minocycline was delivered locally with a controlled-release polymer or systemically by intraperitoneal injection. Systemic minocycline did not extend survival time. Local treatment with minocycline by a controlled-release polymer implanted at the time of tumor implantation extended median survival time by 530% (p < 0.001) compared to treatment with empty polymer. When treatment was begun 5 days after tumor implantation, minocycline delivered locally or systemically had no effect on survival. However, after tumor resection, treatment with locally delivered minocycline resulted in a 43% increase in median survival time (p < 0.002) compared to treatment with empty polymer. Treatment with a combination of minocycline delivered locally in a controlled-release polymer and systemic BCNU 5 days after tumor implantation resulted in a 93% extension of median survival time compared to BCNU alone (p < 0.002). In contrast, treatment with a combination of systemic minocycline and BCNU did not increase survival time compared to systemic BCNU alone. These results demonstrate that minocycline affects tumor growth when delivered locally and suggest that minocycline may be a clinically effective modulator of intracranial tumor growth when used in combination with a chemotherapeutic agent and surgical resection.
Phineas among the phrenologists: the American crowbar case and nineteenth-century theories of cerebral localization
Authors: Barker Fred G. 
Published: February 2011

✓ In 1848, Mr. Phineas Gage suffered destruction of his left frontal lobe in a unique fashion: passage of a metal rod through his head after a freak explosion. His change in character after the accident is the index case for personality change due to frontal lobe damage. Yet, from 1848 to 1868, it was widely believed among American physicians that he was mentally intact. The case was used as evidence against phrenology, a crude precursor of modern cerebral localization theories.The two original reports of the case by Drs. John Harlow (Gage's physician) and Henry J. Bigelow show subtle differences in attitude toward Gage's posttraumatic character change. In his 1848 report, Harlow promised a further communication that would address Gage's “mental manifestations.” Bigelow's article portrayed Gage as fully recovered. Although delayed by 20 years, Harlow's second report rapidly changed the perception of the case in the medical community, as reflected by contemporary citations.The educational backgrounds of Harlow and Bigelow are examined to explain their differing attitudes toward the case. Harlow's interest in phrenology prepared him to accept the change in character as a significant clue to cerebral function which merited publication. Bigelow had learned that damage to the cerebral hemispheres had no intellectual effect, and he was unwilling to consider Gage's deficit significant. Although Bigelow's paradigm was initially more influential, Harlow's more closely matched emerging theories of cerebral localization. His version of the case was used by David Ferrier as the keystone in the first modern theory of frontal lobe function, and this is how the case is remembered today.
Neurosurgery, “neurospine,” and neuroscience: a vital synergy?
Authors: Nowitzke Adrian 
Published: February 2011

A fundamental dilemma that faces both neurosurgery in general and the subspecialty field of spine surgery is the question of whether those who trained in the former and now work in the latter should maintain their links with their origins and remain under the broader umbrella of neurosurgery, or whether they should develop their own organizational structure and identity separate from organized neurosurgery. This challenge raises many questions with respect to future potential for growth and development, professional identity, and collegiality.
This paper is an edited version of an invited speech to the 2007 Annual Meeting of the Joint Section on Disorders of the Spine and Peripheral Nerves. It uses the concept of synergy to review relevant history and explore possible future options for neurosurgery, neurospine, and neuroscience. An example from medical politics is used to illustrate the importance of perspective in approaching these questions, and examples of current therapeutic cutting-edge endeavors highlight the need for team-based behavior that takes a broad view.
The premise of the paper is that while individual and specialty aspirations need to be acknowledged, considered, and managed, the results from truly working together will be greater than the sum of the individual efforts—synergy.
Neurological symptoms and deficits in adults with scoliosis who present to a surgical clinic: incidence and association with the choice of operative versus nonoperative management
Authors: Smith Justin S. , Fu Kai-Ming , Urban Peter , Shaffrey Christopher I. 
Published: February 2011

Object
Adults with scoliosis often present with neurological symptoms and deficits. However, the incidence of these findings and how they may affect treatment decisions have not been clearly defined. The purpose of this study was to quantify the prevalence of neurological symptoms and deficits in adults with scoliosis presenting to a surgical clinic, and to assess for an association between these factors and the decision to pursue operative treatment.

Methods
In this study, the authors document the Oswestry Disability Index (ODI), radiographic findings, and the incidences of back pain, neurological symptoms (radiculopathy and claudication), and neurological deficits (weakness, myelopathy, and bowel/bladder dysfunction) and correlate these with operative versus nonoperative management. Pain was assessed using the visual analog scale (VAS) score. Of 207 patients, 25% underwent surgery.

Results
Incidences of back pain (VAS score > 0 points) and radiculopathy (VAS score > 0) were 99 and 85%, respectively. The incidences of severe (VAS score > 5) back pain and radiculopathy were 66 and 47%, respectively. Neurological symptoms and deficits included weakness in 8% of patients, claudication in 9%, myelopathy in 1%, and bowel/bladder dysfunction in 3%. Patients with severe radiculopathy had greater mean ODI scores (p < 0.001) and reduced lumbar lordosis (p = 0.04) and were more likely to have de novo scoliosis (p = 0.009). Patients who underwent surgery had higher ODI scores (p < 0.001) and a greater incidence of severe radiculopathy (p = 0.006), weakness (p < 0.001), and neurogenic claudication (p = 0.003). Factors associated with operative management on multivariate analysis included weakness (p < 0.001), severe radiculopathy (p = 0.02), and sagittal imbalance (p = 0.03).

Conclusions
Neurological symptoms and deficits are common among adults with scoliosis. Development of neurological symptoms and/or deficits is strongly associated with the decision to pursue operative treatment.
An unusual case of spinal column metastasis after orthotopic transplantation for cardiac sarcoma
Authors: McLoughlin Gregory S. , Sciubba Daniel M. , Ali S. Kaiser , Weinkauf Justin G. , Fourney Daryl R. 
Published: February 2011

The authors describe a patient who underwent orthotopic cardiac transplantation after an undifferentiated cardiac sarcoma was diagnosed. While receiving immunosuppressive therapy, the patient developed spinal column metastases and cauda equina syndrome requiring surgical decompression and stabilization. This occurred despite an exhaustive search for metastatic disease prior to the transplantation. To the authors' knowledge, this represents the first reported case of an undifferentiated cardiac sarcoma metastasis to the spine.
This previously healthy 18-year-old woman presented with a myocardial infarction. Investigations revealed a left atrial tumor, which was resected. Following local recurrence, the patient underwent extensive studies to rule out systemic disease. Orthotopic heart–lung transplantation was then performed. While receiving postoperative immunosuppressive therapy the patient presented with cauda equina syndrome secondary to metastatic tumor compression at the L-5 level.
Despite a comprehensive screening process to exclude metastatic disease prior to transplantation, spinal metastases occurred while this patient was receiving immunosuppressive therapy. This represents a previously unreported and clinically significant complication for undifferentiated cardiac sarcoma.
Stem cell delivery by lumbar puncture as a therapeutic alternative to direct injection into injured spinal cord
Authors: Neuhuber Birgit , Barshinger Alissa L. , Paul Courtney , Shumsky Jed S. , Mitsui Takahiko , Fischer Itzhak 
Published: February 2011

Object
Using cellular transplants to treat spinal cord injury is a promising therapeutic strategy, but transplants grafted directly into the injury site can further damage the already compromised cord. To avoid additional trauma and to simplify translation to the clinic, it is advantageous to use less invasive delivery methods.

Methods
The authors compared the efficacy of intrathecal cell delivery at the lumbar region (lumbar puncture [LP]) to direct injection into a thoracic contusion injury using a mixed population of lineage-restricted neural precursor cells.

Results
Direct injection resulted in a higher volume of neural precursor cells located throughout the injury site, whereas fewer LP-delivered cells accumulated at the dorsal aspect of the injured cord. Both grafting methods were neuroprotective, resulting in reduction of injury size and greater tissue sparing compared with controls. Functional recovery was evaluated by assessing motor and bladder function. Animals that received cells via direct injection performed significantly better in the open-field locomotor test than did operated controls, while LP-treated animals showed intermediate recovery of function that did not differ statistically from that of either operated controls or directly injected animals. Bladder function, however, was significantly improved in both directly injected and LP-treated animals.

Conclusion
Grafting of stem cells via LP resulted in localized accumulation of cells at the injury site, neuroprotection, and modest recovery of function. Further optimization of the LP procedure by increasing the number of cells that are delivered and determining the optimal delivery schedule may further improve recovery to levels comparable to direct injection.
Surgical management of primary and metastatic sarcoma of the mobile spine
Authors: Rao Ganesh , Suki Dima , Chakrabarti Indro , Feiz-Erfan Iman , Mody Milan G. , McCutcheon Ian E. , Gokaslan Ziya , Patel Shreyaskumar , Rhines Laurence D. 
Published: February 2011

ObjectSarcomas of the spine are a challenging problem due to their frequent and extensive involvement of multiple spinal segments and high recurrence rates. Gross-total resection to negative margins, with preservation of neurological function and palliation of pain, is the surgical goal and may be achieved using either intralesional resection or en bloc excision. The authors report outcomes of surgery for primary and metastatic sarcomas of the mobile spine in a large patient series.MethodsA retrospective review of patients undergoing resection for sarcomas of the mobile spine between 1993 and 2005 was undertaken. Sarcomas were classified by histology study results and as either primary or metastatic. Details of the surgical approach, levels of involvement, and operative complications were recorded. Outcome measures included neurological function, palliation of pain, local recurrence, and overall survival.ResultsEighty patients underwent 110 resections of either primary or metastatic sarcomas of the mobile spine. Twenty-nine lesions were primary sarcomas (36%) and 51 were metastatic sarcomas (64%). Intralesional resections were performed in 98 surgeries (89%) and en bloc resections were performed in 12 (11%). Median survival from surgery for all patients was 20.6 months. Median survival for patients with a primary sarcoma of the spine was 40.2 months and was 17.3 months for patients with a metastatic sarcoma. Predictors of improved survival included a chondrosarcoma histological type and a better preoperative functional status, whereas osteosarcoma and a high-grade tumor were negative influences on survival. Multivariate analysis showed that only a high-grade tumor was an independent predictor of shorter overall survival. American Spinal Injury Association scale grades were maintained or improved in 97% of patients postoperatively, and there was a significant decrease in pain scores postoperatively. No significant differences in survival or local recurrence rates between intralesional or en bloc resections for either primary or metastatic spine sarcomas were found.ConclusionsSurgery for primary or metastatic sarcoma of the spine is associated with an improvement in neurological function and palliation of pain. The results of this study show a significant difference in patient survival for primary versus metastatic spine sarcomas. The results do not show a statistically significant benefit in survival or local recurrence rates for en bloc versus intralesional resections for either metastatic or primary sarcomas of the spine, but this may be due to the small number of patients undergoing en bloc resections.
Reduction of hypoxia by perfluorocarbon emulsion in a traumatic spinal cord injury model
Authors: Schroeder Jason L. , Highsmith Jason M. , Young Harold F. , Mathern Bruce E. 
Published: February 2011

Object
Few therapies have consistently demonstrated effectiveness in preserving O2 delivery after spinal cord injury (SCI). Perfluorocarbons (PFCs) offer great promise to carry and deliver O2 more efficiently than conventional measures. The authors investigated the use of Clark-type microelectrodes to monitor spinal cord oxygenation directly (intraparenchymal [IP] recording) and indirectly (cerebrospinal fluid [CSF] recording) in the context of SCI, O2 therapy, and PFC treatment.

Methods
After placement of a subdural/CSF Licox probe in rats, incremental increases in the fraction of inspired O2 (FiO2) up to 100% were administered to establish a dose-response curve. The probe was then placed in the parenchyma of the same animals for a second dose-response curve. In a second study, rats with CSF or IP probes underwent SCI with the NYU Impactor and treatment with O2, followed by administration of PFC, or saline in the control group.

Results
All animals in the first experiment responded to the FiO2 dose increase, with changes in PO2 evident in both CSF and IP levels. The SCI in the second experiment caused a marked drop in PO2 from a mean of 21.4 to 10.4 mm Hg, with most animals dropping to less than half their preinjury value. All animals responded to 100% O2 treatment. Every animal that received PFCs showed significant improvement, with a mean increase in PO2 of 23.3 mm Hg. Only 1 saline-treated animal showed any benefit. Oxygen values in the PFC treatment group reached up to 6 times the normal level.

Conclusions
Oxygen levels in SCI show a profound drop almost immediately postinjury. Administration of PFCs combined with 100% O2 therapy can reverse tissue hypoxia and holds promise for reducing ischemic injury.