bluuebunny/crossref_metadata_2025_split huggingface dataset:
Image-guided resection of high-grade glioma: patient selection factors and outcome
Authors: Litofsky N. Scott , Bauer Andrew M. , Kasper Rachel S. , Sullivan Cynthia M. , Dabbous Omar H. , _ _ 
Published: January 2008

Object
In patients with glioma, image-guided surgery helps to define the radiographic limits of the tumor to maximize safety and the extent of resection while minimizing damage to eloquent brain tissue. The authors hypothesize that image-guided resection (IGR) techniques are associated with improved outcomes in patients with malignant glioma.

Methods
Data recorded in 486 patients enrolled in the Glioma Outcomes Project were analyzed in this study. Demographic data and outcomes in patients who underwent IGR were compared with those in patients who underwent resection without IGR. Univariate analysis performed with chi-square testing was used to compare patient presentation, tumor characteristics, and death rates. Multivariate logistic regression was used to predict various outcome parameters.
Patients who underwent IGR were younger and had smaller, lower-grade tumors than those in whom IGR was not performed. They were more likely to present with seizure and normal consciousness. Unexpectedly, gross-total resection was performed in significantly fewer patients with IGR than in individuals without IGR. Patients with IGR were more likely to be discharged home with the ability to live independently, and they had a shorter duration of hospital stay than patients without IGR. Survival was significantly longer in patients who underwent IGR, but multivariate analysis showed that glioblastoma multiforme (GBM) and age accounted for these observations.

Conclusions
Selection bias occurs regarding patients who receive IGR; these biases include younger age, presentation with seizure and normal level of consciousness, tumor diameter less than 4 cm, and non-GBM on histopathological studies. Outcome appears to be improved in patients who undergo IGRs of high-grade gliomas. It is unclear if these improved outcomes are due to the selection of a more favorable patient population or to the IGR techniques themselves. It is likely that the full potential of image guidance in glioma surgery will not be realized until it is applied to a wider range of patients.
Efficacy of antiangiogenic targeted toxins against glioblastoma multiforme
Authors: Hall Walter A. , Vallera Daniel A. 
Published: January 2008

Object
Because the prognosis for patients with glioblastoma multiforme (GBM) remains poor, investigators have focused on developing new and more effective treatment modalities. Targeted toxins represent a new class of compounds composed of a potent protein toxin and a carrier ligand that will recognize cell surface antigens located on target tissue. A recombinant fusion protein was created that contains the translocation and catalytic portions of diphtheria toxin that are responsible for cell entry and killing, respectively, fused to the noninternalizing aminoterminal fragment portion of human plasminogen activator. This diptheria toxin–uPA fusion protein (DTAT) has the advantage over other fusion proteins of targeting malignant glioma cells and the endothelial cells of the neovasculature that express the urokinase-type plasminogen activator receptor (uPAR). Another protein, DTAT13, was synthesized to target uPAR on the neovasculature and the uPAR and interleukin-13 receptor-expressing GBM cells. The authors describe the in vitro and in vivo efficacy of DTAT and DTAT13 against GBM.

Methods
The in vitro cytotoxicity of DTAT and DTAT13 was measured using cell proliferation assays. In vivo studies were performed in which DTAT, DTAT13, or a control protein was injected directly into GBM flank tumors in athymic nude mice. Tumor volume was assessed over time and analyzed using the Student t-test. The systemic organ effects of DTAT and DTAT13 were examined functionally and histologically in tumor-free C57BL/6 mice.
In vitro, DTAT and DTAT13 were found to be highly potent and selective against U118MG, U87MG, and U373MG GBM cell lines and human umbilical vein endothelial cells. In vivo, DTAT and DTAT13 both caused a statistically significant (p < 0.05) regression of U87MG GBM flank tumors when administered every other day at 10 μg/day for five doses. No tumor regression was seen in control animals. Both DTAT and DTAT13 had little effect on histological findings in the liver, kidney, spleen, and lungs. Serum analysis did not demonstrate an effect on blood urea nitrogen levels, but liver alanine aminotransferase levels rose to statistically significant (p = 0.046) but not life-threatening levels. Also, DTAT13 was less toxic than DTAT in studies of mortality rates.

Conclusions
Both DTAT and DTAT13 might have potential for clinical application against GBM because of their ability to target both the tumor cells and neovasculature simultaneously with an absence of serious systemic side effects. The discovery that DTAT13 was less toxic than DTAT indicated that the bispecific fusion protein might target a broader subset of antigenetically diverse patients with tumors while reducing the systemic exposure to toxin that would be necessary if two agents were administered separately.
Convection-enhanced delivery of therapeutics for brain disease, and its optimization
Authors: Raghavan Raghu , Brady Martin L. , Rodríguez-Ponce María Inmaculada , Hartlep Andreas , Pedain Christoph , Sampson John H. 
Published: January 2008

✓ Convection-enhanced delivery (CED) is the continuous injection under positive pressure of a fluid containing a therapeutic agent. This technique was proposed and introduced by researchers from the US National Institutes of Health (NIH) by the early 1990s to deliver drugs that would otherwise not cross the blood–brain barrier into the parenchyma and that would be too large to diffuse effectively over the required distances were they simply deposited into the tissue. Despite the many years that have elapsed, this technique remains experimental because of both the absence of approved drugs for intraparenchymal delivery and the difficulty of guaranteed delivery to delineated regions of the brain. During the first decade after the NIH researchers founded this analytical model of drug distribution, the results of several computer simulations that had been conducted according to more realistic assumptions were also published, revealing encouraging results. In the late 1990s, one of the authors of the present paper proposed the development of a computer model that would predict the distribution specific to a particular patient (brain) based on obtainable data from radiological images. Several key developments in imaging technology and, in particular, the relationships between image-obtained quantities and other parameters that enter models of the CED process have been required to implement this model. Note that delivery devices need further development.
In the present paper we review key features of CED as well as modeling of the procedure and indulge in informed speculation on optimizing the direct delivery of therapeutic agents into brain tissue.
The history of neurosurgical procedures for moyamoya disease
Authors: Reis Cassius V. C. , Safavi-Abbasi Sam , Zabramski Joseph M. , Gusmão Sebastião N. S. , Spetzler Robert F. , Preul Mark C. 
Published: January 2008

✓ Almost 50 years of research on moyamoya disease (1957–2006) has led to the development of a variety of surgical and medical options for its management in affected patients. Some of these options have been abandoned, others have served as the basis for the development of better procedures, and many are still in use today. Investigators studying moyamoya disease during this period have concluded that the best treatment is planned after studying each patient's presenting symptoms and angiographic pattern.
The surgical procedures proposed for the treatment of moyamoya disease can be classified into three categories: direct arterial bypasses, indirect arterial bypasses, and other methods. Direct bypass methods that have been proposed are vein grafts and extracranial–intracranial anastomosis (superficial temporal artery–middle cerebral artery [STA–MCA] anastomosis and occipital artery–MCA anastomosis). Indirect techniques that have been proposed are the following: 1) encephaloduroarteriosynangiosis; 2) encephalomyosynangiosis; 3) encephalomyoarteriosynangiosis; 4) multiple cranial bur holes; and 5) transplantation of omentum. Other options such as cervical carotid sympathectomy and superior cervical ganglionectomy have also been proposed. In this paper the authors describe the history of the development of surgical techniques for treating moyamoya disease.
Supratentorial cerebral cavernous malformations: clinical, surgical, and genetic involvement
Authors: D'Angelo Vincenzo Antonio , De Bonis Costanzo , Amoroso Rosina , Calì Alessandro , D'Agruma Leonardo , Guarnieri Vito , Muscarella Lucia Anna , Zelante Leopoldo , Bisceglia Michele , Scarabino Tommaso , Catapano Domenico 
Published: January 2008

Object
Although there is general agreement on the methods of treatment for symptomatic supratentorial cerebral cavernous malformations (CMs) located in noneloquent areas, some controversy exists regarding the management of cerebral CMs that are asymptomatic and/or located in eloquent or deep areas. Moreover, recent advances in genetic findings could influence both standard clinical management and the follow-up strategy in affected individuals. Thus, the objective of this study was to develop, based on the authors' experience and a literature review, a management algorithm to deal with supratentorial cerebral CMs.

Methods
The authors retrospectively reviewed the clinical data related to 118 patients who underwent surgery for symptomatic supratentorial cerebral CMs at their institution. Twenty-eight of 118 patients harbored multiple lesions, and nine of these 28 patients had a clinically positive familial history. Genetic investigations were performed in 89 patients (75%).

Conclusions
Surgery for supratentorial cerebral CMs in noneloquent locations is safe and curative. In cerebral CMs located in deep and eloquent areas and with symptoms including progressive neurological deficits, evidence of hemorrhage, and uncontrolled seizures, surgical treatment according to an integrated plan based on frameless stereotactic guidance and functional magnetic resonance imaging is recommended and results in acceptably low morbidity. The data support the need for long-term imaging follow up in all patients, careful preoperative vascular studies to detect associated venous anomalies, and the importance of genetic mutational analysis. The DNA screening protocol will change the care of family members of patients with familial forms of cerebral CMs, because affected asymptomatic family members may benefit by early detection of lesions. At the same time, the exclusion of family members who are not carriers of the mutation as members of the population at risk reduces the economic and psychological burden of clinical and instrumental monitoring.
Clinical presentation and optimal management for intramedullary cavernous malformations
Authors: Jallo George I. , Freed Diana , Zareck Michelle , Epstein Fred , Kothbauer Karl F. 
Published: January 2008

Object
Intramedullary cavernous malformations (CMs) account for approximately 5% of all intraspinal lesions. The purpose of this study was to define the spectrum of presentation for spinal intramedullary CMs and the results of microsurgery for these benign but clinically progressive lesions.

Methods
Retrospective chart review was performed in 26 patients with histologically diagnosed CMs. All patients had undergone preoperative magnetic resonance (MR) imaging studies. All patients were treated with a laminectomy and microsurgical resection of the malformation.

Conclusions
The MR imaging findings are diagnostic for intramedullary CMs; these lesions abut a pial surface and have a characteristic imaging pattern. Spinal intramedullary CMs present with either an acute onset of neurological compromise or a slowly progressive neurological decline. Acute neurological decline occurs secondary to hemorrhage inside the spinal cord. Chronic progressive myelopathy occurs due to microhemorrhages and resulting gliotic reaction to blood products. Surgery and total removal of the lesion tends to halt progression of symptoms.
Intrathecal baclofen therapy and multiple sclerosis: outcomes and patient satisfaction
Authors: Vender John R. , Hughes Mary , Hughes Betsy D. , Hester Sydney , Holsenback Stephen , Rosson Brenda 
Published: January 2008

ObjectIn this study the authors provide an assessment of intrathecal baclofen (ITB) therapy and evaluate patient outcomes and satisfaction.MethodsRecords for patients with multiple sclerosis who were selected as candidates for ITB therapy were reviewed for their response to test dose, surgical technique, surgery- and pump-related complications, and short- and long-term response to therapy. Family and caregiver assessments of the value of ITB therapy were also reviewed.ConclusionsIntrathecal baclofen therapy is safe and effective. Most patients and caregivers express satisfaction with the therapy and would recommend it to other patients. Spasm frequency appears to be the single most common variable positively affected by therapy.
Update on evidence for a genetic predisposition to cerebral vasospasm
Authors: Khurana Vini G. , Fox Douglas J. , Meissner Irene , Meyer Fredric B. , Spetzler Robert F. 
Published: January 2008

✓ Considerable evidence links cerebral vasospasm to the decreased bioavailability of endothelial nitric oxide synthase (eNOS) after aneurysmal subarachnoid hemorrhage (SAH). In recent studies from the cardiology literature, researchers have suggested that a genetic predisposition to coronary vasospasm might develop as the result of a T-786C single nucleotide polymorphism (SNP) in the eNOS gene. The authors of this study attempted to determine if there may be a similar genetic predisposition toward cerebral vasospasm.
The authors prospectively identified 28 patients with Fisher Grade 3 SAH from a group of 51 consecutive patients with ruptured intracranial saccular aneurysms. Genomic DNA was isolated from a peripheral blood sample obtained with permission from each patient. Gene microarray technology was used to assay the samples for the presence and distribution of certain key eNOS gene polymorphisms. Clinical, radiological, and genomic data were analyzed. The finding of eNOS T-786C SNP could be used to significantly differentiate between the presence and severity of cerebral vasospasm (p = 0.04).
The findings from this preliminary study support similar findings in the coronary vasospasm literature as well as the hypothesis that a predisposition toward cerebral vasospasm may be related partially to genetic factors, which needs to be confirmed in a larger study. Such gene-based information may be important in rapidly identifying patients at increased risk of vasospasm after SAH, independent of their Fisher grade. In this article, the authors review key studies in this area.
Dissociation between vasospasm and functional improvement in a murine model of subarachnoid hemorrhage
Authors: Mesis Rachel G. , Wang Haichen , Lombard Frederick W. , Yates Robert , Vitek Michael P. , Borel Cecil O. , Warner David S. , Laskowitz Daniel T. 
Published: January 2008

Object
The efficacy of nimodipine was examined in a murine model of subarachnoid hemorrhage (SAH). End points included the diameter of the lumen of the middle cerebral artery (MCA) and behavioral outcome. An apolipoprotein E (apoE)–mimetic peptide, acetyl-AS-Aib-LRKL-Aib-KRLL-amide, previously shown to have promise in this model was tested both alone and in combination with nimodipine. The effects of carboxyamidotriazole (CAI), a non–voltage-gated calcium channel blocker, were explored using the same animal paradigm.

Methods
Experimental SAH was induced in male C57B1/6J mice. For 3 days postoperatively, behavioral analyses were performed. In the first experiment, the mice were treated with vehicle or with low- or high-dose CAI for 3 days. In the second experiment, the mice were treated with vehicle, high- and low-dose nimodipine, and/or the apoE-mimetic peptide. On postoperative Day 3 each mouse was killed and perfused. Following this, the right MCA was removed and its lumen measured.
Mice that received nimodipine demonstrated significant behavioral improvements when compared with vehicle-treated mice, but there was no clear dose-dependent effect on MCA diameter. Administration of the apoE-mimetic peptide was associated with improved functional performance and a significant reduction in vasospasm. Mice that received high-dose CAI performed worse on functional tests, despite a significant increase in the diameters of their MCA lumina.

Conclusions
These results demonstrate a dissociation between vasospasm and neurological outcomes that is consistent with findings of previous clinical trials.
Evidence-based cerebral vasospasm management
Authors: Weyer George W. , Nolan Colum P. , Macdonald R. Loch 
Published: January 2008

✓Cerebral vasospasm and delayed cerebral ischemia remain common complications of aneurysmal subarachnoid hemorrhage (SAH), and yet therapies for cerebral vasospasm are limited. Despite a large number of clinical trials, only calcium antagonists have strong evidence supporting their effectiveness. The purpose of this work was to perform a systematic review of the literature on the treatment of cerebral vasospasm.
A literature search for randomized controlled trials of therapies used for prevention or treatment of cerebral vasospasm and/or delayed cerebral ischemia was conducted, and 41 articles meeting the review criteria were found. Study characteristics and primary results of these articles are reviewed.
Key indicators of quality were poor when averaged across all studies, but have improved greatly over time. The only proven therapy for vasospasm is nimodipine. Tirilazad is not effective, and studies of hemodynamic maneuvers, magnesium, statin medications, endothelin antagonists, steroid drugs, anticoagulant/antiplatelet agents, and intrathecal fibrinolytic drugs have yielded inconclusive results.
The following conclusions were made: nimodipine is indicated after SAH and tirilazad is not effective. More study of hemodynamic maneuvers, the effectiveness of other calcium channel antagonists such as nicardipine delivered by other routes (for example intrathecally), magnesium, statin drugs, endothelin antagonists, and intrathecal fibrinolytic therapy is warranted. There is less enthusiasm for the study of steroid drugs and anticoagulant/antiplatelet agents because they entail more risks and investigations so far have shown little evidence of efficacy. The study of rescue therapy such as balloon angioplasty and intraarterial vasodilating agents will be difficult. The quality of clinical trials should be improved.
Subdural hematomas in boxing: the spectrum of consequences
Authors: Miele Vincent J. , Bailes Julian E. , Cantu Robert C. , Rabb Craig H. 
Published: January 2008

✓Boxing is a violent sport in which every participant accepts the risk of brain damage or death. This sport has been linked to acute neurological injury and chronic brain damage. The most common life-threatening injury encountered by its participants is subdural hematoma (SDH), and the most feared consequence of chronic insult to the nervous system is dementia pugilistica, or punch drunkenness. Although advances in imaging and neuropsychological testing have improved our ability to diagnose these injuries, the unprecedented sensitivity and wide availability of these modalities have increased the detection of mild cognitive impairment and small, asymptomatic imaging abnormalities. The question has thus been raised as to where on the spectrum of these injuries an athlete should be permanently banned from the sport.
In this report the authors describe six boxers who were evaluated for SDH sustained during participation in the sport, and who experienced remarkably different outcomes. Their presentations, clinical courses, and boxing careers are detailed. The athletes ranged in age from 24 to 55 years at the time of injury. Two were female and four were male; half of them were amateurs and half were professionals. Treatments ranged from observation only to decompressive craniectomy. Two of the athletes were allowed to participate in the sport after their injury (one following a lengthy legal battle), with no known sequelae. One boxer died within 48 hours of her injury and at least two suffered permanent neurological deficits. In a third, dementia pugilistica was diagnosed 40 years later, and the man died while institutionalized.
Reflections on 40 years as a sideline physician
Authors: Nugent G. Robert 
Published: January 2008

Object
In this study the author presents his personal observations concerning football injuries in a historical perspective with additional literature citations.

Methods
Aspects of brachial plexus and cervical spine injuries, neurapraxia, face mask infractions, concussion, acute subdural hematoma (SDH), and the so-called second-impact syndrome are addressed.

Conclusions
The list of conclusions presented in this paper is as follows: there is more than one kind of brachial plexus injury; wedging of cervical vertebrae may be normal; neurapraxia presents a problem for return to play; face mask injuries are rarely serious; definitions of concussion vary; acute SDH requires immediate transfer to a hospital; and the second-impact syndrome may be a myth to some.
Is clear cell sarcoma a malignant form of psammomatous melanotic schwannoma?
Authors: Şengöz Ahmet , Taşdemiroğlu Erol , Togay Halit 
Published: January 2008

✓The authors present a case of clear cell sarcoma (CCS) in which the tumor originated in the S-1 nerve root and had been previously diagnosed as psammomatous melanotic schwannoma (PMS). This is the third case of a spinal nerve root origin for CCS reported in the English-language literature. The similar histogenesis of CCS and malignant melanoma supports the hypothesis that biological agents or immunotherapy are potentially important areas of investigation.
The patient underwent S1–3 laminectomy and gross-total resection of the mass lesion. The border of the resection was extended 1 cm distal to the tumor margin. The postoperative period was uneventful. The new histopathological diagnosis was CCS (malignant melanoma of soft tissue). Despite total resection, the patient returned with disseminated disease at the 18-month follow-up visit. His follow-up magnetic resonance image of the lumbar spine revealed sacral L5–S3 involvement of the vertebral bodies along with disseminated cauda equina seeding.
A CCS originating from peripheral nerves is quite rare. The histopathological and immunohistochemical appearance of CCSs resembles those of PMSs. Surgery should be the first choice of treatment.