bluuebunny/crossref_metadata_2025 huggingface dataset:
The IL-4 and IL-13 pseudomonas exotoxins: new hope for brain tumor therapy
Authors: Shimamura Takeshi , Husain Syed R. , Puri Raj K.
Published: January 2008

✓ Targeting cell surface receptors with cytotoxins or immunotoxins provides a unique opportunity for brain tumor therapy. The authors have discovered that receptors for two cytokines, interleukin (IL)-4 and IL-13, are overexpressed on tumor biopsy samples and on cell lines derived from a variety of human tumors, including brain tumors. These investigators have demonstrated that the structure of these cytokine receptors on tumor cells is different from that found on normal immune cells. In human solid tumor cells, IL-4 binds to two chains (IL-4Rα and IL-13Rα1), whereas IL-13 binds to three chains in many solid tumor cells, including glioma cells (to IL-4Rα, IL-13Rα1, and IL-13Rα2). To target IL-4Rs and IL-13Rs, the authors generated two recombinant fusion cytotoxins composed of IL-4 or IL-13 and a mutated form of pseudomonas exotoxin (PE), which for simplicity are called IL4-PE and IL13-PE in this paper. These chimeric cytotoxins are highly toxic in vitro to human tumor cell lines and primary cell cultures, including glioma cells, and in vivo to animal models of human tumors, including gliomas. In contrast, normal cells, including immune, endothelial, and brain cells, are spared from their cytotoxic effects. Based on numerous preclinical studies, IL13-PE (also known as IL13-PE38QQR or cintredekin besudotox) has been tested in four Phase I/II clinical trials. The agent IL13-PE was administered intracranially by using convection-enhanced delivery (CED). The drug was delivered through catheters placed either directly into the tumor bed or in the peritumoral region after resection of the lesion. The CED of IL13-PE was fairly well tolerated, with a reasonable benefit/risk profile for treatment of patients with glioma. Based on Phase I/II clinical trials, the Phase III Randomized Evaluation of CED of IL13-PE Compared to Gliadel Wafer with Survival Endpoint Trial (also known as the PRECISE Trial) in patients with initial recurrence of glioblastoma multiforme has recently been completed. Patients are being monitored for safety of the agents, duration of overall survival, and quality of life.
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.
J. Lawrence Pool, M.D.: a pioneer in vascular neurosurgery
Authors: Zacharia Brad E. , Mocco J , Komotar Ricardo J. , Solomon Robert A. , Quest Donald O.
Published: January 2008

✓ The authors detail the life and career of Dr. J. Lawrence Pool, as well as his significant contributions to the field of cerebrovascular neurosurgery. The discipline of cerebrovascular neurosurgery is a young and dynamic field, which underwent rapid and substantial growth during the middle of the twentieth century. As the chairman of the Department of Neurological Surgery at the Neurological Institute of New York, Dr. J. Lawrence Pool was instrumental in the development of new techniques and devices that would ultimately result in decreased mortality rates and improved results from complex cerebrovascular procedures. Passion, ingenuity, and a pioneering spirit fueled Dr. Pool, whose introduction of the operating microscope and use of temporary clip occlusion during aneurysm repair revolutionized the field of cerebrovascular neurosurgery.
The history and present status of deep hypothermia and circulatory arrest in cerebrovascular surgery
Authors: Rothoerl Ralf Dirk , Brawanski Alexander
Published: January 2008

✓ After the development of deep hypothermia and circulatory arrest for cardiothoracic procedures in the late 1950s, this technique was adopted by several neurosurgeons as an aid to complex cranial surgery. Woodhall and colleagues described its first use for a neurosurgical procedure in 1960. Although their case did not involve a cerebrovascular procedure, the technique was subsequently used for the surgical treatment of cerebrovascular lesions, especially complex and giant aneurysms as well as large and solid hemangioblastomas. At the beginning, incorporation of this technique into common neurosurgical practice was impeded by several factors. For example, postbypass coagulopathy had been a serious source of morbidity. Furthermore, the need for cooperation among multiple subspecialities and the requirements for expensive equipment had further limited the availability of this technique. Subsequent improvements in the technique and advances in the equipment designed for cardiopulmonary bypass have led to its more widespread use starting in the 1980s. Hypothermic circulatory arrest has been described in several reports as a safe and useful tool in the treatment of large and giant aneurysms. Nevertheless, improvements in endovascular procedures and further refinement in skull base surgical techniques have limited the indications for circulatory arrest and deep hypothermia. The authors describe the history of hypothermia and circulatory arrest, its implementation in cerebrovascular surgery, and the changes in indications for and results of its use over time.
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.
History of surgery for cerebrovascular disease in children. Part I. Intracranial arterial aneurysms
Authors: Blount Jeffrey P. , Oakes W. Jerry , Tubbs R. Shane , Humphreys Robin P.
Published: January 2008

✓ Intracranial aneurysms are rare in children, and their origins and treatment methods tend to be different from those in these same entities in adults. These lesions tend to be congenital or to have an infectious or traumatic origin. In the current paper the authors trace the historical evolution of the diagnosis and treatment of intracranial aneurysms in children. Based on the literature, these lesions appear to occur in children in less than 3% of all series. The literature also supports the suggestion that symptoms from these aneurysms are often from mass effect and that giant aneurysms and lesions in the posterior cranial fossa are relatively more common in children than in adults. The termination of the carotid artery and the anterior cerebral artery seem to be disproportionately common sites of aneurysm formation in this cohort. Interestingly, surgical outcomes in children appear to be moderately better than in adults. Based on the literature, the claim can be made that a multidisciplinary approach to the management of such aneurysms can yield good outcomes in a very high percentage of children treated.
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.
Cavernoma of the foramen of Monro
Authors: Longatti Pierluigi , Fiorindi Alessandro , Perin Alessandro , Baratto Vittorio , Martinuzzi Andrea
Published: January 2008

✓The authors report on a patient who presented with an intraventricular mass located at the level of the foramen of Monro. The clinical presentation and neuroimaging appearance of the mass led to an initial diagnosis of colloid cyst. A neuroendoscopic approach offered a direct view of the ventricular lesion, which was found to be a cavernous angioma partially occluding the foramen of Monro. The lesion was then removed using microsurgery. In this report the authors highlight possible pitfalls in the diagnosis of some lesions of the third ventricle, and the possible advantages of using a combined endoscopic and microsurgical technique when approaching such lesions.
Resection of a left insular cavernoma aided by a simple navigational tool
Authors: Esposito Vincenzo , Paolini Sergio , Morace Roberta
Published: January 2008

✓The management of cavernous malformations of the brain is markedly influenced by the location of the lesions themselves. In the last decade, resection of cavernomas arising in the dominant insular lobe has been deemed safe only with the guidance of neuronavigation. Most navigation equipment, however, shares some minor drawbacks, including costs, longer operating time, and a variable loss of accuracy due to intraoperative brain shift. In this paper the authors present the case of a left dominant insular cavernoma that was successfully removed using a novel form of navigation that they call magnetic resonance imaging–based corticotopography. This technique, which is unaffected by the brain shift phenomenon, provided a simple and inexpensive alternative to standard neuronavigation. Selected cases of subcortical brain lesions could be conveniently approached using the same technique.
Are cavernous sinus hemangiomas and cavernous malformations different entities?
Authors: Gonzalez L. Fernando , Lekovic Gregory P. , Eschbacher Jennifer , Coons Stephen , Porter Randall W. , Spetzler Robert F.
Published: January 2008

✓Cavernous hemangiomas that occur within the cavernous sinus (CS) are different from cerebral cavernous malformations (CMs) clinically, on imaging studies, and in their response to treatment. Moreover, CMs are true vascular malformations, whereas hemangiomas are benign vascular tumors. Because of these differences, the authors suggest that these two entities be analyzed and grouped separately. Unfortunately, despite these differences, much confusion exists in the literature as to the nature, behavior, and classification of these two distinct lesions. This confusion is exacerbated by subtle histological differences and the inconsistent use of nomenclature. The authors use the term “cavernous malformation” to refer to intraaxial lesions only; they prefer to use the term “cavernous sinus hemangioma” to refer to extraaxial, intradural hemangiomas of the CS.
The use of botulinum toxin therapy for lower-extremity spasticity in children with cerebral palsy
Authors: Criswell Susan R. , Crowner Beth E. , Racette Brad A.
Published: January 2008

✓ Hypertonicity is a leading cause of disability for children with cerebral palsy (CP). Botulinum toxin A (BTA) chemically denervates muscle tissue and is commonly used in the management of lower-extremity hypertonicity in children with CP because of its focal effects and wide safety margin. Randomized controlled trials have demonstrated that BTA injections in the ankle flexors, hamstrings, and adductors reduce spasticity and result in improved passive and active range of motion. In other studies, improvements in gait and measurements of functional outcome were found in appropriately selected children who had been injected with BTA. A multidisciplinary treatment approach that includes physical therapists, occupational therapists, orthotists, neurologists, physicians with expertise in performing botulinum toxin injections, orthopedic surgeons, and neurosurgeons is critical to optimize care in children with lower-extremity tone due to CP. In this paper, the authors propose treatment algorithms based on clinical presentation, detailed dosing, and technical information to optimize the treatment of these children. With a multidisciplinary approach, children with lower-extremity hypertonicity due to CP can experience improvements in muscle tone and function.
A review of orthopedic surgeries after selective dorsal rhizotomy
Authors: O'Brien Donncha F. , Park Tae Sung
Published: January 2008

✓ Selective dorsal rhizotomy (SDR) is an evidence-based treatment for cerebral palsy (CP) spasticity. During their lifetime, patients with CP spasticity may require orthopedic surgery for muscles and joints to correct physical deformities and provide a better quality of life. In this review, the authors discuss the timing of such orthopedic surgery, its necessity, and whether it is influenced by the performance of SDR. A review of findings from the authors' 19 years of experience yields the following conclusions: 1) that SDR reduces orthopedic surgery requirements when compared with historical controls; 2) that SDR performed in patients at a young age (2–4 years) can reduce future orthopedic surgery requirements; 3) that independent walkers and diplegic patients will have the smallest amount of orthopedic surgery post-SDR; and 4) that patients who need assistance walking and those with quadriplegia will have the greatest amount, although the frequency of orthopedic surgery for quadriplegic patients is not as high as popularly believed.
Selection of treatment modalities in children with spastic cerebral palsy
Authors: Steinbok Paul
Published: January 2008

✓ The purpose of this report was to outline the various options currently used for treatment of spastic cerebral palsy (CP) and to discuss factors involved in selecting the appropriate treatment modalities for the individual child. In a review of the literature and his personal observations, the author presents an outline of treatment options and the criteria for using each. Therapeutic options include the following: physiotherapy; occupational therapy; oral spasmolytic and antidystonic drugs; botulinum toxin injections; orthopedic procedures; continuous infusion of intrathecal baclofen (ITB); selective dorsal rhizotomy (SDR); and selective peripheral neurotomy. The most commonly used neurosurgical procedures are ITB pump placement and SDR, and these are discussed in the most detail. The author's personal schema for assessment of the child to determine the nature of the hypertonia, the impact of the hypertonia, and the appropriate therapeutic intervention is presented. There are factors that help guide the optimal treatment modalities for the child with spastic CP. The treatment of these children is optimized in the setting of a multidisciplinary team.
Intrathecal baclofen in the treatment of adult spasticity
Authors: Hsieh Joseph C. , Penn Richard D.
Published: January 2008

✓ Medical management of adult spasticity, a condition of increased muscle tone and deep tendon reflexes, is often challenging and complex. Oral medications such as baclofen often have unacceptable supraspinal side effects at effective doses. Intrathecal baclofen delivered by an implanted catheter and pump system provides good relief of spasticity while overcoming these limitations. In this paper the authors survey the use of oral and intrathecal baclofen therapy, detail the surgical process, and explain the risks and benefits of the procedure.
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

Object

In this study the authors provide an assessment of intrathecal baclofen (ITB) therapy and evaluate patient outcomes and satisfaction.

Methods

Records 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.

Conclusions

Intrathecal 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.
Endovascular treatment strategies for cerebral vasospasm
Authors: Mindea Stefan A. , Yang Benson P. , Bendok Bernard R. , Miller Jeffrey W. , Batjer H. Hunt
Published: January 2008

✓Cerebral vasospasm is a significant cause of morbidity and mortality in patients who have sustained a subarachnoid hemorrhage from aneurysm rupture. Symptomatic cerebral vasospasm is also a strong predictor of poor clinical outcome and has thus drawn a great deal of interest from cerebrovascular surgeons. Although medical management is the cornerstone of treatment for this condition, endovascular intervention may be warranted for those in whom this treatment fails and in whom symptomatic vasospasm subsequently develops. The rapid advancements in endovascular techniques and pharmacological agents used to combat this pathological state continue to offer promise in broadening the available treatment armamentarium. In this article the authors discuss the rationale and basis for using the various endovascular options for the treatment of cerebral vasospasm, and they also discuss the limitations, complications, and efficacy of these treatment strategies in regard to neurological condition and outcome.
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.
Natural antiinflammatory agents for pain relief in athletes
Authors: Maroon Joseph C. , Bost Jeffrey W. , Borden Meghan K. , Lorenz Keith M. , Ross Nathan A.
Published: January 2008

✓ Most athletes experience musculoskeletal injuries during their sports activity that require rest at a minimum, and occasionally injuries are severe enough to necessitate surgical repair. Neurosurgeons are often consulted for athletically sustained injuries and prescribe medications for the associated pain. The use of both over-the-counter and prescription nonsteroidal medications is frequently recommended, but recent safety concerns must now be considered. The authors discuss the biochemical pathways of nonsteroidal drugs and review the potentially serious side effects of these medications. They also review the use of natural supplements, which may be a safer, and often as effective, alternative treatment for pain relief.
The role of cadherins and catenins in gliomagenesis
Authors: Barami Kaveh , Lewis-Tuffin Laura , Anastasiadis Panos Z.
Published: January 2008

✓Cell–cell adhesion is a crucial process occurring during normal tissue development. Cadherins are calcium-dependent cell-surface adhesion molecules involved in cell–cell adhesion. They reorganize the actin cytoskeleton via interaction with the catenins. Modulation of the cadherin/catenin system plays a role in cell motility. Dysregulation of the cadherin/catenin assembly has been implicated in various cancers. In this review, the authors summarize all studies focusing on the role of cadherins and catenins in glioma formation. With the emergence of recent data regarding gliomas' putative cell of origin, elucidation of the role of cadherins/catenins in gliomagenesis will become important in devising new therapeutic approaches against such deadly cancers.
Neurosurgeons and their contributions to modern-day athletics: Richard C. Schneider Memorial Lecture
Authors: Dunn Ian F. , Dunn Gavin , Day Arthur L.
Published: January 2008

✓ Neurosurgeons in the last half-century have had considerable influence on modern-day athletics. In this article, the authors address the contributions made by neurosurgeons as clinician–scientists, particularly as these relate to the understanding and reduction of the incidence and severity of injury to the nervous system during athletic competition. American football has been a proving ground for the ability of the craniospinal axis to withstand and, in unfortunate cases, succumb to tremendous impact forces; in this way, it has served as a model for translational research and was the arena in which Dr. Richard Schneider made his greatest contributions to sports neurosurgery. Therefore, in his memory and in the spirit of the Schneider lectureship, the authors outline the notable contribution to modern-day athletics made by neurosurgeons as it applies to American football. Neurosurgeons have had considerable influence on reducing injury severity, and this cause has been championed by a few notable individuals whose efforts are discussed herein.
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.
An overview of concussion consensus statements since 2000
Authors: Cantu Robert C.
Published: January 2008

✓ More refereed publications on sports-related concussion have appeared since 2000 than in all previous years combined. Three international consensus statements, documents from the National Athletic Trainers' Association (NATA) and the American College of Sports Medicine (ACSM), and entire issues of the Clinical Journal of Sport Medicine and the Journal of Athletic Training have been devoted to this subject. The object of this article is to critique the consensus statements and NATA and ACSM documents, pointing out areas of controversy.
Return to contact sports after spinal surgery
Authors: Burnett Mark G. , Sonntag Volker K. H.
Published: January 2008

✓ Decisions regarding the return of injured athletes to contact sports after spinal surgery can be complicated. The authors offer a brief overview of the return-to-play guidelines used successfully at their institution for the past two decades when caring for professional and amateur athletes after spinal surgery.
Implications of the blood–brain barrier in primary central nervous system lymphoma
Authors: Jahnke Kristoph , Doolittle Nancy D. , Muldoon Leslie L. , Neuwelt Edward A.
Published: January 2008

✓ The optimal treatment of primary central nervous system lymphoma (PCNSL), a rare form of extranodal non-Hodgkin lymphoma, has yet to be defined. Whole-brain radiation therapy (WBRT) has limited efficacy as a single therapeutic modality and is associated with a high risk of delayed neurotoxicity. Methotrexate-based chemotherapy regimens yield poor drug penetration across the blood–brain barrier (BBB), thus necessitating administration of high doses with the concomitant risk of increased systemic and neurological toxicity. Combined-modality therapy (WBRT plus chemotherapy) can improve response and survival rates, yet it is associated with a high risk of neurotoxicity. The aim of chemotherapy in conjunction with BBB disruption is to maximize drug delivery to the brain and improve the agent's efficacy, while preserving neurocognitive function and minimizing systemic toxicity. Methotrexate-based chemotherapy regimens administered in conjunction with BBB disruption have shown promising results in PCNSL. Animal models of central nervous system lymphoma and drug neurotoxicity offer new possibilities to study the effects of various treatments on PCNSL and normal brain and can also help understand biological and pathophysiological aspects of this disease. Because the intact BBB is even less permeable to antibodies than it is to drugs, preclinical and clinical studies of monoclonal antibody delivery (for example, rituximab and 90Y ibritumomab tiuxetan) to the brain in conjunction with BBB disruption offer a new possibility to make these novel treatments more efficient against PCNSL. Regarding the evaluation of more sensitive and specific diagnostic imaging tools, iron oxide–based contrast agents for magnetic resonance imaging have shown promise for better differentiation of PCNSL from other white matter diseases.
Primary central nervous system lymphoma: presentation, diagnosis, and staging
Authors: Eichler April F. , Batchelor Tracy T.
Published: January 2008

✓ Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma that affects the brain, spinal cord, leptomeninges, and eyes. The clinical presentation and neuroimaging appearance of PCNSL differ in immunocompetent patients and in those with acquired immunodeficiency syndrome (AIDS). A magnetic resonance (MR) image of the brain in immunocompetent patients with PCNSL typically demonstrates one or more homogeneously enhancing lesions located in the periventricular white matter, characteristically spanning the corpus callosum. In patients with AIDS, multiple ring-enhancing lesions are more common. After neuroimages raising the suspicion of PCNSL are obtained, a definitive diagnosis should be established in both immunocompetent and AIDS patients by performing pathological analysis of cerebrospinal fluid (CSF), vitreous fluid, or a biopsy specimen. Brain biopsy sampling remains the gold standard for PCNSL diagnosis in all patients, although the possibility of establishing routine, minimally invasive diagnostic procedures in which Epstein–Barr virus polymerase chain reaction (PCR) analysis of the CSF and nuclear imaging are used is currently under investigation in the population of patients with AIDS. At the time of diagnosis, the patient should undergo further evaluation, which should include a physical examination, ophthalmic evaluation with a slit-lamp examination, serum lactate dehydrogenase levels, human immunodeficiency virus testing, computed tomography scans of the chest/abdomen/pelvis, bone marrow biopsy sampling, contrast-enhanced brain MR imaging, and lumbar puncture (LP). Testicular ultrasonography studies should be considered in men. In patients who cannot undergo LP or in those with evidence of spinal cord dysfunction, contrast-enhanced MR imaging of the entire spine should be considered.
Molecular pathogenesis of primary central nervous system lymphoma
Authors: Kadoch Cigall , Treseler Patrick , Rubenstein James L.
Published: January 2008

✓ Primary central nervous system lymphoma (PCNSL) is an aggressive form of non-Hodgkin lymphoma (NHL) typically associated with a worse prognosis than other localized extranodal lymphomas with similar histological characteristics. The defining feature of PCNSL is its confinement to the central nervous system (CNS), with proclivity for growth within the leptomeningeal as well as intraocular compartments. Primary CNS lymphoma rarely disseminates outside the CNS and accounts for less than 5% of all primary brain neoplasms. At least 95% of PCNSLs are of large B-cell histology, the most common subtype of NHL. Consistent with the trend seen in systemic NHLs, the incidence of PCNSL has markedly increased over the past three decades, both in immunocompromised and immunocompetent patients. Because PCNSL is relatively rare, the identification of molecular prognostic biomarkers and the definition of a standard therapeutic strategy have been challenging. The authors discuss the current knowledge of the molecular pathogenesis of CNS lymphomas and review the recent advances in gene expression profile analysis and identification of novel prognostic biomarkers.
Imaging of primary central nervous system lymphoma
Authors: Go John L. , Lee Sandy C. , Kim Paul E.
Published: January 2008

✓Primary central nervous system lymphoma (PCNSL) is an aggressive neoplastic process that occurs in both immuno-competent and immunocompromised patients. Over the past 30 years there has been a steady increase in the number of cases in both patient populations. The imaging features for the disease and demographic characteristics within these patient populations vary, and in this article the authors describe the salient features of these two groups.
Lymphomatous meningitis in primary central nervous system lymphoma
Authors: Chamberlain Marc C.
Published: January 2008

✓Lymphomatous meningitis (LM) due to primary central nervous system (CNS) lymphoma is an uncommon problem in neurooncology and can occur at time of diagnosis or recurrence. Notwithstanding frequent focal signs and symptoms, LM is a disease affecting the entire neuraxis, and therefore staging and treatment need to encompass all cere-brospinal fluid (CSF) compartments. Central nervous system staging of LM includes contrast agent–enhanced cranial computed tomography (CT) or Gd-enhanced magnetic resonance (MR) imaging, Gd-enhanced spinal MR imaging, CT myelography, and radionuclide CSF flow study. Treatment of LM includes involved-field radiotherapy of bulky or symptomatic disease sites and intra-CSF drug therapy. The inclusion of concomitant systemic therapy can benefit patients with LM and can obviate the need for intra-CSF chemotherapy. At present, intra-CSF drug therapy is confined to three chemotherapeutic agents (methotrexate, cytosine arabinoside, and thiotepa) administered by a variety of schedules either by intralumbar or intraventricular drug delivery. Although treatment of LM is palliative and the expected median survival of patients is 4 to 6 months, it often provides stabilization and protection from further neurological deterioration. In patients with primary CNS lymphoma, CNS prophylaxis has been recommended (using a combination of high-dose systemic chemotherapy and intra-CSF chemotherapy), but the strategy remains controversial because high-dose systemic methotrexate is commonly used as an adjuvant therapy. Patients with primary CNS lymphoma at high risk as defined by positive CSF cytology or neuroradiography consistent with LM may benefit from the inclusion of intra-CSF chemotherapy.
Selective enhancement of cellular oxidative stress by chloroquine: implications for the treatment of glioblastoma multiforme
Authors: Toler Steven M. , Noe Dennis , Sharma Amarnath
Published: January 2008

✓ Chloroquine is used in the treatment of malaria, a disease caused by infection with the parasite Plasmodium. Although chloroquine appears to possess diverse pharmacological activity, its plasmodicidal activity results from augmentation of parasite oxidative stress. Chloroquine also appears to augment oxidative stress in metabolically active mammalian cells, including human astroglial cells. The authors propose that chloroquine may augment oxidative stress induced by radiotherapy in the treatment of glioblastoma multiforme, enhancing therapeutic efficacy. Such an effect would be consistent with the known pharmacological effects of chloroquine observed in Plasmodium. Other selective redox agents, such as tempol and artemisinin, should be investigated clinically for therapeutic benefit when coadministered with combined radio- and chemotherapy for cancer.
Silicate-substituted calcium phosphate as a bone void filler after kyphoplasty in a young patient with multiple compression fractures due to osteogenesis imperfecta variant
Authors: Hardenbrook Mitchell A. , Lombardo Sergio R.
Published: January 2008

✓Kyphoplasty can be used to treat compression fractures resulting from a variety of causes. The use of polymethyl methacrylate (PMMA) in conjunction with kyphoplasty has many risks and potential complications, however, particularly in the younger patient population. Silicate-substituted calcium phosphate (Actifuse Synthetic Bone Graft; Apatech, Ltd.) is an alternative to PMMA that provides immediate pain relief and the ability to heal and incorporate within the vertebral body.
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.
Spinal cord stimulation: indications and outcomes
Authors: Lee Anthony W. , Pilitsis Julie G.
Published: January 2008

✓Spinal cord stimulation (SCS) is the most commonly used implantable neurostimulation modality for management of pain syndromes. In this paper the authors describe the current indications for SCS and its efficacy in the treatment of those diseases. Specifically, the literature on patient selection and outcomes after SCS for failed–back surgery syndrome (FBSS), refractory angina pectoris, peripheral vascular disease, and complex regional pain syndrome (CRPS) Type I was reviewed. Effective pain relief was obtained in 60 to 80% of patients with FBSS and CRPS Type I. Furthermore, these patients had significant improvements in quality of life (QOL) and a significantly greater chance of returning to work than patients who did not undergo SCS. The use of SCS in patients with inoperable angina (that is, refractory angina pectoris) resulted in significant decreases in chest pain and hospital admissions as well as increased exercise duration, with less morbidity than with open procedures that were performed for pain control only. Patients with inoperable PVD also demonstrated significant improvements in pain relief, QOL, and limb mobility. Reported complications were mostly related to hardware and were relatively minor. Review of randomized controlled studies supports the use of SCS as an effective treatment modality for pain associated with FBSS, refractory angina pectoris, peripheral vascular disease, and CRPS Type I.