bluuebunny/crossref_metadata_2025 huggingface dataset:
Suboccipital burr holes and craniectomies
Authors: Ribas Guilherme C. , Rhoton Albert L. , Cruz Oswaldo R. , Peace David
Published: January 2008

Object

The goal of this study was to delimit the external cranial projection of the transverse and sigmoid sinuses, and to establish initial strategic systematized burr hole sites for lateral infratentorial suboccipital approaches based on external cranial landmarks particularly related to the lambdoid, occipitomastoid, and parietomastoid sutures.

Methods

The external cranial projection of the transverse and sigmoid sinuses was studied through their external outlining obtained with the aid of multiple small perforations made from inside to outside along the inner margins of the sinuses of 50 paired temporoparietooccipital regions in 25 dried adult human skulls. The burr hole placement was studied by evaluating the supratentorial, over-the-sinuses, and infratentorial components of 1-cm-diameter openings made at strategic sites identified in the initial part of the study, which was performed in another 50 paired temporoparietooccipital regions.

The asterion and the midpoint of the inion–asterion line were found to be particularly related to the inferior half of the transverse sinus; the transverse and sigmoid sinuses' transition occurs 1 cm anteriorly to the asterion across the parietomastoid suture, and the most superior part of the sigmoid sinus is located anteriorly to the occipitomastoid suture, with its posterior margin crossing this suture posteriorly to the most superior aspect of the mastoid process, which is located at the most superior level of the mastoid notch. Burr holes made at the midpoint of the inion–asterion line, at the asterion, 1 cm anterior to the asterion, just inferiorly to the parietomastoid suture, and over the occipitomastoid suture at the most superior level of the mastoid notch are appropriate to expose the inferior half of the transverse sinus at its midpoint, the inferior half of the transverse sinus at its most lateral aspect, the transverse and sigmoid sinuses' transition, and the posterior margin of the basal aspect of the sigmoid sinus, respectively.

Conclusions

These findings allow an estimation of the transverse and sigmoid sinuses' external cranial projection. The asterion and the most posterior part of the parietomastoid suture constitute a suitable initial burr hole site at which to perform an upper or asterional suboccipital craniectomy to expose the superior aspect of the cerebellopontine angle (CPA). The occipitomastoid suture at the most superior aspect of the mastoid notch constitutes an adequate initial burr hole site at which to perform a basal suboccipital craniectomy to expose the lower portion of the CPA. The sites can be used together as initial burr hole sites to perform wide suboccipital exposures, because they already constitute natural infratentorial lateral limits.
Transpetrosal approaches to the posterior fossa
Authors: Tummala Ramachandra P. , Coscarella Ernesto , Morcos Jacques J.
Published: January 2008

Resection of the petrous temporal bone to various degrees provides different levels of access to lesions of the posterior fossa. Although their nomenclature can be confusing, the numerous variants of the transpetrosal approaches can be classified broadly into anterior and posterior groups. The posterior transpetrosal approaches include the retro-labyrinthine, translabyrinthine, and transcochlear, whereas the ones in the anterior group are extensions of the basic middle fossa approach. Both the anterior and posterior approaches have the potential of exposing the cerebellopontine angle and the petroclival region.

The posterior approaches are based on the standard mastoidectomy and involve resection of the petrous bone to various degrees. This results in progressively increased exposure anteriorly, but comes at the expense of hearing in the translabyrinthine approach and of hearing and facial strength in the transcochlear approach.

In contrast, the middle fossa approaches spare the lateral petrous bone and involve resection of the medial petrous bone to various degrees. All of the middle fossa approaches are designed to preserve hearing. Extensions of the middle fossa approaches involve resection of bone within the Kawase rhomboid and division of the tentorium to provide exposure of the posterior fossa.
Spontaneous motor cortex encephalocele presenting with simple partial seizures and progressive hemiparesis
Authors: Fountas Kostas N. , Smith Joseph R. , Jenkins Patrick D. , Murro Anthony M.
Published: January 2008

Several cases of congenital or acquired temporal encephaloceles have been reported in the literature as the causative mechanism of simple and/or complex partial seizures. In this report the authors describe a rare case of spontaneous parietal encephalocele presenting with simple partial seizures and progressively increasing contralateral upper-extremity motor deficit. The unusual anatomical location of an encephalocele associated with seizures and the delayed seizure onset represent distinctive characteristics in this case. Preoperative imaging included surface electroencephalography, computerized tomography, and brain magnetic resonance imaging. Frameless neuronavigation and intraoperative cortical mapping were used to aid resection of the encephalocele, and the dural and bone defects were reconstructed. The surgical outcome in this case was excellent, and the patient has remained seizure free. The pertinent literature is reviewed in this report.
Stem cell therapies for malignant glioma
Authors: Ehtesham Moneeb , Stevenson Charles B. , Thompson Reid C.
Published: January 2008

The prognosis for patients with malignant glioma, which is the most common primary intracranial neoplasm, remains dismal despite significant progress in neurooncological therapies and technology. This is largely due to the inability of current treatment strategies to address the highly invasive nature of this disease. Malignant glial cells often disseminate throughout the brain, making it exceedingly difficult to target and treat all intracranial neoplastic foci, with the result that tumor recurrence is inevitable despite aggressive surgery and adjuvant radiotherapy and/or chemotherapy. The use of neural stem cells (NSCs) as delivery vehicles for tumor-toxic molecules represents the first experimental strategy aimed specifically at targeting disseminated tumor pockets. Investigators have demonstrated that NSCs possess robust tropism for infiltrating tumor cells, and that they can be used to deliver therapeutic agents directly to tumor satellites, with significant therapeutic benefit. With the aim of developing these findings into a clinically viable technology that would not be hindered by ethical and tissue rejection–related concerns, the use of adult tissue–derived stem cells has recently been explored. These technologies represent important progress in the development of a treatment strategy that can specifically target disseminated neoplastic pockets within the brain. Despite encouraging results in preclinical models, however, there are significant impediments that must be overcome prior to clinical implementation of this strategy. Key among these are an inadequate understanding of the specific tropic mechanisms that govern NSC migration toward invasive tumor, and the need to refine the processes used to generate tumor-tropic stem cells from adult tissues so that this can be accomplished in a clinically practicable fashion. Despite these limitations, the use of stem cell therapies for brain tumors holds significant promise and may emerge as an important therapeutic modality for patients with malignant glioma.
What do neurosurgeons actually do? A statistical analysis of one neurosurgeon's entire career
Authors: Kirkpatrick Douglas B.
Published: January 2008

The author maintained prospective records on every patient he treated during the 26 years of his neurosurgical private practice. At the conclusion of his clinical career, he compiled this information in a formal database program and then analyzed the results for totals, trends, and interesting conclusions, which are presented herein.
Genetic characterization of commonly used glioma cell lines in the rat animal model system
Authors: Sibenaller Zita A. , Etame Arnold B. , Ali Mushtaq M. , Barua Manali , Braun Terry A. , Casavant Thomas L. , Ryken Timothy C.
Published: January 2008

Object

Animal models have been used extensively to discern the molecular biology of diseases and to gain insight into treatments. Nevertheless, discrepancies in the effects of treatments and procedures have been encountered during the transition from these animal models to application of the information to clinical trials in humans. To assess the genetic similarities between human gliomas and four cell lines used routinely in animal models, the authors used microarray technology to characterize the similarities and differences in gene expression.

Methods

To define the changes in gene expression, normal rat astrocytes were compared with four rat glioma cell lines (C6, 9L, F98, and RG2). The data were analyzed using two different methods: fold-change analysis and statistical analysis with t statistics. The gene products that were highlighted after intersecting the lists generated by the two methods of analysis were scrutinized against changes in gene expression reported in the literature. Tumorigenesis involves three major steps: the accumulation of genetic alterations, uncontrolled growth, and selected survival of transformed cells. The discussion of the results focuses attention on genes whose primary function is in pathways involved in glioma proliferation, infiltration, and neovascularization. A comparative microarray analysis of differentially expressed genes for four of the commonly used rat tumor cell lines is presented here.

Conclusions

Due to the variances between the cell lines and results from analyses in humans, caution must be observed in interpreting as well as in the translation of information learned from animal models to its application in human trials.
Bioinformatics approaches for detecting gene–gene and gene–environment interactions in studies of human disease
Authors: Ritchie Marylyn D.
Published: January 2008

Neurological and mental disorders occur often, with approximately 450 million people suffering from them worldwide. Like most other common diseases, neurological disorders are hypothesized to be highly complex, with interactions among genes and risk factors playing a major role in the process. In recent years it has become obvious that for common diseases there may be more complex interactions among genes with and without strong independent main effects. These effects are more difficult to detect using traditional methodologies.

In this manuscript the author introduces the concept of epistasis and the challenges associated with detecting it. Next, she briefly mentions a number of bioinformatics approaches that have been developed to deal with this issue. Multifactor dimensionality reduction is a methodology developed specifically to deal with the challenge of detecting interaction effects in the absence of statistically detectable main effects in studies of common disorders, such as Alzheimer disease or brain cancer. Finally, the author describes the future directions for this technique and related methodologies.
Relevance of high Ki-67 in pituitary adenomas
Authors: Prevedello Daniel M. , Jagannathan Jay , Jane John A. , Lopes M. Beatriz S. , Laws Edward R.
Published: January 2008

Pituitary adenomas are heterogeneous in growth rate, invasiveness, and recurrence. To understand the biological behavior of the individual adenoma more fully, cell proliferation markers such as monoclonal antibodies targeted against the Ki-67 antigen have been applied. The Ki-67 antigen is a protein related to cell proliferation and is expressed in cell nuclei throughout the entire cell cycle. The authors report the case of an extremely rapidly growing pituitary adenoma with cavernous sinus invasion. The lesion, which displayed a high Ki-67 labeling index (LI; 22%), was found in a 54-year-old woman who presented with diplopia and headaches. The patient underwent three transsphenoidal operations in less than 6 months and, ultimately, was treated with fractionated intensity-modulated radiation therapy. The relationships between high Ki-67 LIs and tumor recurrence, invasiveness, and growth velocity in pituitary adenomas are reviewed.
Subthalamic stimulation for Parkinson disease: determination of electrode location necessary for clinical efficacy
Authors: McClelland Shearwood , Ford Blair , Senatus Patrick B. , Winfield Linda M. , Du Yunling E. , Pullman Seth L. , Yu Qiping , Frucht Steven J. , McKhann Guy M. , Goodman Robert R.
Published: January 2008

Object

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) performed using intraoperative microelectrode recording (MER) to adjust electrode placement has become a widely used treatment for patients with advanced Parkinson disease (PD). Few studies have been conducted to examine the location of implanted electrodes relative to the intended target, and even fewer have been undertaken to investigate the degree to which variations in the location of these electrodes impacts their clinical efficacy. This study was performed to examine these issues.

Methods

The authors located 52 bilaterally implanted DBS electrode tips on postoperative magnetic resonance (MR) images obtained in 26 consecutive patients. Postoperative and preoperative planning MR images were merged to determine the DBS electrode tip coordinates relative to the midcommissural point. Surgical records listed the intended target coordinates for each DBS electrode tip. Clinical outcome assessment included the Unified PD Rating Scale (UPDRS) motor score at 1 year, standardized questionnaires, and routine follow-up visits.

The mean difference between electrode tip location and intended target for all 52 electrodes was less than 2 mm in all axes. Only one electrode was farther than 3 mm from the intended target, and this was the only electrode that had to be replaced due to lack of clinical efficacy (lack of tremor suppression); its reimplantation 4 mm more medially provided excellent tremor control. High correlation coefficients indicate that the MR imaging analysis accurately determined the anatomical location of the electrode tips. Blinded videotape reviews of UPDRS motor scores comparing effects of stimulation in patients who were “on” and “off” medication identified subgroups in whom there was minimal and maximal stimulation response. Patients in these subgroups had no differences between the MR imaging–determined actual electrode tip location and its intended location. Similarly, improvements of dyskinesias and severity of symptoms encountered during the wearing-off period for the drug did not correlate with variations of electrode tip location.

Conclusions

The findings in this study lead the authors to suggest that a DBS electrode placed anywhere within a 6-mm-diameter cylinder centered at the presumed middle of the STN (based on stereotactic atlas coordinates) provides similar clinical efficacy. Future studies may be warranted to evaluate prospectively the degree to which MER modification of the anatomically and/or image-determined target improves clinical efficacy of DBS electrodes.
Molecular genetics of supratentorial primitive neuroectodermal tumors and pineoblastoma
Authors: Li Mei Hua , Bouffet Eric , Hawkins Cynthia E. , Squire Jeremy A. , Huang Annie
Published: January 2008

The supratentorial primitive neuroectodermal tumors (PNETs) are a group of highly malignant lesions primarily affecting young children. Although these tumors are histologically indistinguishable from infratentorial medulloblastoma, they often respond poorly to medulloblastoma-specific therapy. Indeed, existing molecular genetic studies indicate that supratentorial PNETs have transcriptional and cytogenetic profiles that are different from those of medullo-blastomas, thus pointing to unique biological derivation for the supratentorial PNET. Due to the rarity of these tumors and disagreement about their histopathological diagnoses, very little is known about the molecular characteristics of the supratentorial PNET. Clearly, future concerted efforts to characterize the molecular features of these rare tumors will be necessary for development of more effective supratentorial PNET treatment protocols and appropriate disease models. In this article the authors review existing molecular genetic data derived from human and mouse studies, with the aim of providing some insight into the putative histogenesis of these rare tumors and the underlying transforming pathways that drive their development. Studies of the related but distinct pineoblastoma PNET are also reviewed.
The molecular epidemiology of gliomas in adults
Authors: Wrensch Margaret , Fisher James L. , Schwartzbaum Judith A. , Bondy Melissa , Berger Mitchel , Aldape Kenneth D.
Published: January 2008

In this paper the authors highlight recent findings from molecular epidemiology studies of glioma origin and prognosis and suggest promising paths for future research. The reasons for variation in glioma incidence according to time period of diagnosis, sex, age, ancestry and ethnicity, and geography are poorly understood, as are factors that affect prognosis. High-dose therapeutic ionizing irradiation and rare mutations in highly penetrant genes associated with certain rare syndromes—the only two established causes of glioma—can be called upon to explain few cases. Both familial aggregation of gliomas and the inverse association of allergies and immune-related conditions with gliomas have been shown consistently, but the explanations for these associations are inadequately developed or unknown. Several bio-markers do predict prognosis, but only evaluation of loss of 1p and 19q in oligodendroglial tumors are incorporated in clinical practice. Ongoing research focuses on classifying homogeneous groups of tumors on the basis of molecular markers and identifying inherited polymorphisms that may influence survival or risk. Because most cases of glioma have yet to furnish either an environmental or a genetic explanation, the greatest potential for discovery may lie in genomic studies in conjunction with continued evaluation of environmental and developmental factors. Large sample sizes and multidisciplinary teams with expertise in neuropathology, genetics, epidemiology, functional genomics, bioinformatics, biostatistics, immunology, and neurooncology are required for these studies to permit exploration of potentially relevant pathways and modifying effects of other genes or exposures, and to avoid false-positive findings. Improving survival rates for patients harboring astrocytic tumors will probably require many randomized clinical trials of novel treatment strategies.
Modeling medulloblastoma with genetically engineered mice
Authors: Fults Daniel W.
Published: January 2008

Medulloblastoma is a malignant tumor that arises in the cerebellum in children, presumably by transformation of granule neuron precursor cells. In vivo models of medulloblastoma in genetically engineered mice have shown that activation of signal transduction pathways that stimulate proliferation and inhibit differentiation of neural progenitor cells during cerebellar development initiate medulloblastoma formation. Activation of the Sonic hedgehog (Shh)/Patched signaling pathway in the postnatal cerebellum is sufficient to induce medulloblastoma in mice. Activation of the phos-phatidylinositol 3–kinase (PI3K) signaling pathway by insulin-like growth factor–II, inactivation of the p53 tumor suppressor protein, loss of DNA damage repair mechanisms, and ectopic expression of Myc oncoproteins cooperate with Shh/Patched signaling to enhance tumor formation in mice. Ectopic expression of alpha and beta interferons in the developing brain also induces Shh–mediated medulloblastoma formation, suggesting a possible role for antiviral response in the genesis of medulloblastoma. By revealing which cell signaling proteins can initiate medulloblastoma formation, mouse models have enabled investigators to identify molecular targets for designing new therapies. Small-molecule inhibitors of the Shh/Patched and PI3K pathways are potential chemotherapeutic agents for patients with medulloblastoma.
Medulloblastoma: mouse models and novel targeted therapies based on the Sonic hedgehog pathway
Authors: Piedimonte Leandro R. , Wailes Ian K. , Weiner Howard L.
Published: January 2008

Understanding molecular pathways, signaling cascades, and genetic alterations activated during tumorigenesis is essential for the development of targeted cancer treatments. In children, tumors of the central nervous system are thought to arise from progenitor cells that show considerable temporal and spatial heterogeneity in a developmental environment that is different from that of the adult. Investigating the molecular basis of pediatric tumors is critical because it is likely to generate novel treatments. Animal models have brought many important advances in this field. In this review the authors discuss the mouse models based on the Sonic hedgehog pathway, which have provided a better knowledge of the genetic and molecular alterations of medulloblastoma.
Endoscopic third ventriculostomy
Authors: Jallo George I. , Kothbauer Karl F. , Abbott I. Rick
Published: January 2008

The traditional treatment for all forms of hydrocephalus has been the implantation of ventricular shunt systems; however, these systems have inherent tendencies toward complications such as malfunction and infection. A significant advance in the treatment of hydrocephalus has been the evolution of endoscopy. The recent technological advances in this field have led to a renewed interest in endoscopic third ventriculostomy as the treatment of choice for obstructive hydrocephalus. Although several different endoscopes are available, the authors favor a rigid one to perform a blunt fenestration of the third ventricle floor. This description of the technique stresses the nuances for successful completion of this procedure.
Future uses of mesenchymal stem cells in spine surgery
Authors: Helm Gregory A. , Gazit Zulma
Published: January 2008

Stem cells are currently being studied for use in numerous clinical applications, ranging from neurodegenerative diseases to cardiac insufficiency. The use of mesenchymal stem cells (MSCs) in spine surgery is also compelling, especially with the increasing age of the general population. In this review the authors discuss the use of MSCs for intervertebral disc repair and regeneration and for use in spinal arthrodesis procedures. Clearly, the routine use of cellular therapies by spine surgeons to improve outcome after a variety of surgical procedures is rapidly approaching.
A brief history of endoscopic transsphenoidal surgery—from Philipp Bozzini to the First World Congress of Endoscopic Skull Base Surgery
Authors: Doglietto Francesco , Prevedello Daniel M. , Jane John A. , Han Joseph , Laws Edward R.
Published: January 2008

Since its inception, one of the major issues in transsphenoidal surgery has been the adequate visualization of anatomical structures. As transsphenoidal surgery evolved, technical advancements improved the surgical view of the operative field and the orientation. The operating microscope replaced Cushing's headlight and Dott's lighted speculum retractor, and fluoroscopy provided intraoperative imaging. These advances led to the modern concept of micro-surgical transsphenoidal procedures in the early 1970s.

For the past 30 years the endoscope has been used for the treatment of diseases of the sinus and, more recently, in the surgical treatment of pituitary tumors. The collaboration between neurological and otorhinolaryngological surgeons has led to the development of novel surgical procedures for the treatment of various pathological conditions in the skull base.

In this paper the authors review the history of the endoscope—its technical development and its application—from the first endoscope described by Philipp Bozzini to the First World Congress of Endoscopic Skull Base Surgery held in 2005 in Pittsburgh, Pennsylvania. Specifically, in this review the history of endoscopy and its application in endonasal neurosurgery are presented.
Thoracoscopic spine surgery for decompression and stabilization of the anterolateral thoracolumbar spine
Authors: Amini Amin , Beisse Rudolf , Schmidt Meic H.
Published: January 2008

The anterior thoracolumbar spine can be exposed via a variety of approaches. Historically, open anterolateral or pos-terolateral approaches have been used to gain access to the anterior thoracolumbar spinal column. Although the exposure is excellent, open approaches are associated with significant pain and respiratory problems, substantial blood loss, poor cosmesis, and prolonged hospitalization. With the increasing use of the endoscope in surgical procedures and recent advances in video-assisted thoracoscopic surgery, minimally invasive thoracoscopic spine surgery has been developed to decrease the morbidity associated with open thoracotomy. The purpose of this article is to illustrate the surgical technique of a minimally invasive thoracoscopic approach to the anterolateral thoracolumbar spine and to discuss its potential indications and contraindications in patients with diseases involving the anterior thoracic and lumbar regions.
Endoscopic third ventriculostomy for tumor-related hydrocephalus in a pediatric population
Authors: Ray Pulak , Jallo George I. , Kim R. Y. H. , Kim Bong-Soo , Wilson Sean , Kothbauer Karl , Abbott Rick
Published: January 2008

Object

Endoscopic third ventriculostomy (ETV) has become a common alternative for managing hydrocephalus in select patients. Nevertheless, there is still controversy regarding the indications for ETV as the primary procedure, given its variable success rates. The purpose of this study is to review the authors' experience with ETV for a variety of patients.

Methods

A total of 43 children underwent ETV between July 1992 and June 2003. Their medical records, operative reports, and imaging studies, when available, were retrospectively reviewed with regard to outcome, complications, and patency rate. Treatment failure was defined as the need to place a shunt within 4 weeks of performing ETV in the patient.

There were 20 male and 23 female patients with a mean age of 9.6 years (range 8 weeks–21 years). The overall success rate was 69.8%, and the mean follow-up duration was 24.6 months. Six patients underwent eight repeated ETVs at a mean interval of 25 months, with a patency rate of 62.5% after the second procedure. Only two surgeries were aborted for anatomical reasons. The highest success rates (100% in each instance) were achieved for obstructive hydrocephalus resulting from midbrain/tectal tumor (four patients) and pineal tumor (three patients).

Conclusions

The ETV procedure is an effective management tool for obstructive hydrocephalus in children. It should be considered the primary procedure, rather than ventriculoperitoneal shunts, in carefully selected children. The success rate is dependent on the origin of the hydrocephalus.
Cowden disease and Lhermitte–Duclos disease: an update
Authors: Robinson Shenandoah , Cohen Alan R.
Published: January 2008

Object

Cowden disease is a rare autosomal-dominant phacomatosis and cancer syndrome that is associated with Lhermitte–Duclos disease (LDD), also called dysplastic cerebellar gangliocytoma.

Methods

In this review the authors summarize the additions to the literature during the past 5 years, with emphasis on new case reports and advances in imaging and molecular biology. Adult-onset LDD is now considered pathognomonic for Cowden disease.

Approximately 220 cases of LDD have been reported. Magnetic resonance imaging in patients with LDD is often diagnostic, and imaging studies have facilitated accurate diagnosis and contributed to the improved outcome in affected patients. Cowden disease and other rare, related disorders, such as Bannayan-Riley-Ruvalcaba, Proteus, and Proteus-like syndromes, are often caused by mutations of the PTEN gene.

Conclusions

Because of the high incidence of systemic cancer in patients with Cowden disease, it is important for neurosurgeons to recognize the association between this disease and LDD and to refer affected patients for appropriate cancer screenings and interventions.
Focal cortical dysplasia: a review of pathological features, genetics, and surgical outcome
Authors: Wang Vincent Y. , Chang Edward F. , Barbaro Nicholas M.
Published: January 2008

Focal cortical dysplasia (FCD) is found in approximately one-half of patients with medically refractory epilepsy. These lesions may involve only mild disorganization of the cortex, but they may also contain abnormal neuronal elements such as balloon cells. Advances in neuroimaging have allowed better identification of these lesions, and thus more patients have become surgical candidates. Molecular biology techniques have been used to explore the genetics and pathophysiological characteristics of FCD. Data from surgical series have shown that surgery often results in significant reduction or cessation of seizures, especially if the entire lesion is resected.
Familial intracranial ependymomas
Authors: Dimopoulos Vassilios G. , Fountas Kostas N. , Robinson Joe Sam
Published: January 2008

Familial cases of intracranial ependymomas have been well documented in the literature. The authors present two cases from a family in which three members harbored intracranial ependymomas. A 54-year-old man with fourth ventricular ependymoma underwent resection of the tumor followed by radiation therapy. His son presented at age 36 years with a fourth ventricular tanycytic ependymoma and underwent total resection of the ependymoma with postoperative radiation therapy. The father's sister had been treated at another institution for a posterior fossa ependymoma. The association of ependymomas with molecular genetic alterations in chromosome 22 has been previously described. Further investigation of the genetic influences may lead to better therapeutic approaches for this relatively rare clinicopathological entity.
Cervical spine clearance after trauma in children
Authors: Anderson Richard C. E. , Kan Peter , Hansen Kris W. , Brockmeyer Douglas L.
Published: January 2008

Object

Currently, no diagnostic or procedural standards exist for clearing the cervical spine in children after trauma. The purpose of this study was to determine if reeducation of nonneurosurgical personnel and initiation of a new protocol based on the National Emergency X-Radiography Utilization Study criteria could safely increase the number of pediatric cervical spines cleared of suspected injury without a neurosurgical consultation.

Methods

Data regarding cervical spine clearance in children (ages 0–18 years) after trauma protocol activation at Primary Children's Medical Center between 2001 and 2005 were collected and reviewed. Radiographic and clinical methods of clearing the cervical spine as well as the type and management of injuries were determined for two time frames: Period I (January 2001–December 2003) and Period II (January 2004–July 2005).

Between 2001 and 2003, 95% of 936 cervical spines were cleared of suspected injury by the neurosurgical service. Twenty-one ligamentous injuries (2.2%) and 12 fracture–dislocations (1.3%) were detected, with five patients requiring surgical stabilization (0.5%). Between January 2004 and July 2005, 507 (68%) of 746 cervical spines were cleared by nonneurosurgical personnel. Six ligamentous injuries (0.8%) and 10 fracture–dislocations (1.3%) were identified, with three patients (0.4%) requiring surgical stabilization. No late injuries were detected in either period.

Conclusions

The protocol used has been effective in enabling detection of cervical spine injuries in children after trauma, with the new protocol increasing by more than 60% the number of cervical spines cleared by nonneurosurgical personnel. Reeducation with establishment of the new protocols can safely facilitate clearance of the cervical spine by nonneurosurgical personnel after trauma.
Anterior approach to the subaxial cervical spine in children: a brief review
Authors: Baron Eli M. , Loftus Christopher M. , Vaccaro Alexander R. , Dominique Devanand A.
Published: January 2008

✓ Although it was originally developed to address degenerative problems, including disc herniations and cervical spondylotic myelopathy in the adult population, the anterior approach to the subaxial spine has proven to be useful for select indications in the pediatric population. The authors review indications for surgery, bone grafting, and instrumentation as they pertain to children.
Odontoid synchondrosis fractures in children
Authors: Fassett Daniel R. , McCall Todd , Brockmeyer Douglas L.
Published: January 2008

Object

Odontoid synchondrosis fractures, although rare in the overall incidence of spinal trauma, are one of the more common fractures in young children. The goal of this study was to evaluate the demographic data, incidence of neurological deficits, treatment strategies, and outcomes in a combined series of odontoid synchondrosis fractures treated at the authors' institution and reported in other series.

Methods

In a retrospective chart review, the authors identified four odontoid synchondrosis fractures treated at their hospital since January 2000; these were combined with cases reported in six other series in the literature, yielding a total of 55 patients. Data regarding the patients' age, sex, delayed diagnosis, odontoid displacement, neurological deficits, treatment, and fusion status were collected.

The patients' ages ranged from 9 months to 7 years (mean 2.8 years), with neither sex predominating. Diagnosis was delayed in eight cases. The orientation of the odontoid fracture was reported for 36 patients, with 94% experiencing anterior displacement. Spinal cord injury (SCI) was noted in 15 patients, including 11 with complete injuries and eight with SCI at the cervicothoracic junction. Forty-two (93%) of 45 patients with fractures initially treated with external immobilization attained fusion. Eight patients were treated with surgery; four initially, with no attempt at conservative therapy, three after failed halo immobilization, and one after nonunion because of delayed diagnosis.

Conclusions

Odontoid synchondrosis fractures can be difficult to diagnose. In children younger than 7 years of age who present with neck pain or neurological deficits attributable to SCI, this fracture should be suspected. Given the high rate of fusion attained with conservative therapy, it is recommended for most synchondrosis fractures, although surgery may be warranted for individual cases.
Paramedian approach for transforaminal lumbar interbody fusion with unilateral pedicle screw fixation
Authors: Tuttle Jonathan , Shakir Ahmed , Choudhri Haroon Fiaz
Published: January 2008

✓ Lumbar fusion is a commonly performed procedure for a variety of pathological conditions, and it is frequently used in the treatment of degenerative lumbar instability that is refractory to medical management. Pedicle screws and interbody devices have been used for internal fixation to promote arthrodesis, prevent nonunion, and facilitate early mobilization. Recently, attempts have been made to reduce the morbidity associated with lumbar fusion by using a variety of minimally invasive techniques. Many minimally invasive lumbar fusion procedures require specialized retractors, implants, image guidance systems, or insertion instruments. Other minimally invasive techniques are primarily applied to an ideal patient population (thin, healthy, and with no previous surgery). The authors describe their experience with a paramedian approach for minimally invasive transforaminal lumbar interbody fusion (TLIF) with unilateral pedicle screw (PS) fixation. This procedure requires only standard implants, instruments, and retractors, with direct visualization for all aspects of the procedure. The authors describe encouraging early results in a challenging patient population in which there was a high incidence of obesity, medical comorbidities, and previous surgery at the same level. The paramedian approach for TLIF performed using unilateral lumbar PSs has yielded successful outcomes in this series of 47 patients, and further study of this technique may help define its role as a minimally invasive procedure for spinal fusion.
Clinical and radiographically/neuroimaging documented outcome in transforaminal lumbar interbody fusion
Authors: Houten John K. , Post Nicholas H. , Dryer Joseph W. , Errico Thomas J.
Published: January 2008

Object

Although transforaminal lumbar interbody fusion (TLIF) is an increasingly popular surgical technique, there are a limited number of studies in which investigators have stratified outcome data with respect to surgical indications or documented radiographically proven and clinical results with respect to disc space height (DSH). The authors conducted a study to evaluate the long-term outcomes after TLIF with respect to surgical indication and radiographic/neuroimaging results.

Methods

Thirty-three consecutive TLIF-treated patients underwent follow-up investigation for a mean of 37 months. Isthmic spondylolysis was present in eight patients, recurrent disc herniation in 14, and degenerative disc disease (DDD) in 11. The operative technique involved the placement of interbody structural allograft, pedicle screw instrumentation, and morcellized autograft in the anterior interbody space and the contralateral intertransverse gutter. Surgery was performed at L4–5 in 16 patients, L5–S1 in 14, L3–4 in two, and both L4–5 and L5–S1 in one patient.

Preoperative symptoms were back pain (in 91% of cases), leg pain (in 94%), sensory loss (in 67%), and motor deficits (in 30%). Postoperatively, back pain was improved in 67% of the patients, unchanged in 27%, and worsened in 7%. Leg pain improved in 80% of patients, was unchanged in 10%, and worsened in 10%. Outcome, as measured using the Prolo Functional and Economic Scales, improved from a score of 4.9 to 7. In patients with spondylolysis and recurrent disc herniation outcomes were better than in those with DDD only. There was no correlation of outcome with symptom duration, patient age, or level of surgery. In an independent review of pre- and late postoperative radiographs no significant differences in lordosis angles, Cobb angles, or DSHs were found. Fusion occurred in all cases.

Conclusions

The TLIF procedure was associated with good clinical outcomes and a high fusion rate but no change in the DSH. Patients who present with spondylolysis and recurrent herniations experience better outcome than those with degenerative disease alone.
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.
Treatment options for glioblastoma
Authors: Chamberlain Marc C.
Published: January 2008

✓ Following the seminal trial conducted by the European Organisation for Research and Treatment of Cancer (EORTC) and the National Cancer Institute of Canada (NCIC), concurrent temozolomide and radiotherapy has become the new standard of care for patients with newly diagnosed glioblastoma multiforme (GBM). Investigation of emerging therapies (which are now used as salvage therapy) such as small-molecule inhibitors (for example, epidermal growth factor receptor inhibitors) and convection-enhanced delivery (CED) of targeted toxins (for example, interleukin-13/pseudo-monas exotoxin) is likely to build on the EORTC/NCIC treatment platform and will, it is hoped, improve survival rates in patients with GBM. The majority of adjuvant Phase I and II trials being conducted by the brain tumor consortia are based on the EORTC/NCIC treatment platform and have added a targeted therapy in an effort to find a promising synergistic treatment. Furthermore, researchers in the consortia are continuing to explore treatments for recurrent GBM, not otherwise eligible for local therapies, such as CED. The treatments under study include novel cytotoxic chemotherapy as well as small-molecule inhibitors; these are being assessed in a variety of Phase I or II trials.
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.
Recurrent glioblastoma multiforme: a review of natural history and management options
Authors: Hou Lewis C. , Veeravagu Anand , Hsu Andrew R. , Tse Victor C. K.
Published: January 2008

✓ Glioblastoma multiforme (GBM) is one of the most aggressive primary brain tumors, with a grim prognosis despite maximal treatment. Advancements in the past decades have not significantly increased the overall survival of patients with this disease. The recurrence of GBM is inevitable, its management often unclear and case dependent. In this report, the authors summarize the current literature regarding the natural history, surveillance algorithms, and treatment options of recurrent GBM. Furthermore, they provide brief discussions regarding current novel efforts in basic and clinical research. They conclude that although recurrent GBM remains a fatal disease, the literature suggests that a subset of patients may benefit from maximal treatment efforts. Nevertheless, further research effort in all aspects of GBM diagnosis and treatment remains essential to improve the overall prognosis of this disease.
Autophagy, the Trojan horse to combat glioblastomas
Authors: Lefranc Florence , Kiss Robert
Published: January 2008

✓ Malignant gliomas, among which glioblastomas constitute the largest group, are characterized by a dramatically diffuse infiltration into the brain parenchyma with, as a consequence, the fact that no patient with glioblastoma multiforme (GBM) has been cured to date. Migrating GBM cells are resistant to apoptosis (Type I programmed cell death), and thus to radiotherapy and conventional chemotherapy, because of the constitutive activation of several intracellular signaling pathways, of which the most important identified to date are the pathways controlled by phosphatidylinositol 3-kinase, Akt, and the mammalian target of rapamycin (mTOR). Migrating GBM cells seem to be less prone to resist autophagy (Type II programmed cell death), and disruption of the pathway controlled by mTOR induces marked autophagic processes in GBM cells. Temozolomide is the most efficacious cytotoxic drug employed today to combat glioblastoma, and this drug exerts its cytotoxic activity through proautophagic processes. Thus, autophagy represents a kind of Trojan horse that can be used to bypass, at least partly, the dramatic resistance of glioblastoma to radiotherapy and proapoptotic-related chemotherapy.