Cervical Total Disc Replacement: Indications and Technique
Cervical total disc replacement devices have been marketed in the United States (US) since 2007, with abundant level 1 evidence published on the treatment. Adherence to the strict inclusion/exclusion criteria and the surgical technique training of the US clinical trials remains the consistent and conservative approach to patient selection and implantation technique. However, patient selection and surgical technique remain debated among US surgeons as the published data and available cervical total disc replacements continue to grow. (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - September 17, 2021 Category: Neurosurgery Authors: Pierce Nunley, Kelly (Frank) Van Schouwen, Marcus Stone Source Type: research

Cervical Total Disc Replacement: Novel Devices
This article reviews the available literature for novel cervical total disc replacement devices, including ones which are available inside and outside of the United States. It includes biomechanical consideration as well as design characteristics and clinical data when available. (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - September 17, 2021 Category: Neurosurgery Authors: Richard D. Guyer, Joseph L. Albano, Donna D. Ohnmeiss Source Type: research

Cervical Spine Surgery
Three procedures dominate surgical management of degenerative cervical spine disorders: posterior cervical laminoforaminotomy (PCF), cervical total disc replacement (CTDR), and anterior cervical discectomy and fusion (ACDF). Together they provide a 360 ° approach to degenerative cervical spine disease that help surgeons reach the correct treatment decisions. ACDF, CTDR, and PCF are effective procedures for the treatment of a broad range of degenerative cervical disorders. Minimally invasive technique, outpatient setting, motion preservation, and adjacent segment disease should be taken into consideration in the surgica...
Source: Neurosurgery Clinics of North America - September 17, 2021 Category: Neurosurgery Authors: Vincent Rossi, Tim Adamson Source Type: research

Cervical Total Disc Replacement
Cervical total disc replacement (CTDR) has gained popularity over the last 2  decades. It is a motion-preserving option to ACDF and is becoming more popular with patients and surgeons alike. Understanding complications that are unique to CTDR is crucial to performing successful, durable surgery. Careful patient selection and meticulous surgical technique are key to reducing complications associated with the surgery. Patient’s should be followed closely after surgery with routine flexion/extension x-rays for early detection of any complications that may occur. Most complications can be observed with close follow-...
Source: Neurosurgery Clinics of North America - September 17, 2021 Category: Neurosurgery Authors: Richard L. Price, Domagoj Coric, Wilson Z. Ray Source Type: research

Lumbar Total Disc Replacement
This article reviews the history and current trends in use for lumbar toral disc arthroplasty for degenerative disc disease treatment. Furthermore, indications, contraindications, and complications management are discussed. (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - September 17, 2021 Category: Neurosurgery Authors: Daniel Franco, Garrett Largoza, Thiago S. Montenegro, Glenn A. Gonzalez, Kevin Hines, James Harrop Source Type: research

Update on Spinal Arthroplasty
The majority of this Update on Motion Preservation Technologies is dedicated to cervical arthroplasty, owing to the quicker and more pervasive adoption of total disc replacement (TDR) devices in the cervical spine. The disparity in acceptance of this novel technology is multifactorial, but lies largely in the familiarity of the anterior cervical approach to spine surgeons as well as the straightforward nature of the diagnosis of cervical radiculopathy. Conversely, the anterior lumbar approach is more precarious, generally requiring an exposure surgeon, and the surgical treatment of mechanical low-back pain remains somewhat...
Source: Neurosurgery Clinics of North America - September 17, 2021 Category: Neurosurgery Authors: Domagoj Coric Tags: Preface Source Type: research

Update on Motion Preservation Technologies
NEUROSURGERYCLINICS OF NORTH AMERICA (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - September 17, 2021 Category: Neurosurgery Authors: Domagoj Coric Source Type: research

Copyright
ELSEVIER (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - September 17, 2021 Category: Neurosurgery Source Type: research

Contributors
RUSSELL R. LONSER, MD (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - September 17, 2021 Category: Neurosurgery Source Type: research

Contents
Domagoj Coric (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - September 17, 2021 Category: Neurosurgery Source Type: research

Forthcoming Issues
Syndromic Neurosurgery (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - September 17, 2021 Category: Neurosurgery Source Type: research

Cervical Total Disc Replacement: Expanded Indications
This article analyses the current available evidence supporting the expanded indication of cTDR to 3- and 4-level disc disease, either stand-alone or adjacent to fusion, from a less stringent European perspective. (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - July 30, 2021 Category: Neurosurgery Authors: Óscar L. Alves Source Type: research

Cervical Total Disc Replacement
The first US Food and Drug Administration (FDA) approval for cervical total disc replacement (CTDR) was issued in 2007. Since then, 8 more artificial discs have been granted FDA approval for single-level CTDR. Two of these have also been approved for 2-level CTDR. All devices are indicated for levels C3 to C7 for symptomatic patients with radiculopathy or myelopathy caused by disc herniation or spondylosis unresponsive to conservative management. Trials have shown noninferiority of CTDR compared with anterior cervical decompression and fusion in their overall success. Hybrid surgery and CTDR of 3 or more levels are not FDA...
Source: Neurosurgery Clinics of North America - July 30, 2021 Category: Neurosurgery Authors: Mohamad Bydon, Giorgos D. Michalopoulos, Mohammed Ali Alvi, Anshit Goyal, Kingsley Abode-Iyamah Source Type: research

Cervical Total Disc Replacement
Degenerative disc disease and associated cervical spondylosis or stenosis are common conditions encountered in clinical practice. These conditions may cause progressive cervical radicular or myelopathic symptoms leading to significant impairment. Although anterior cervical discectomy and fusion (ACDF) has been a reliable surgical treatment of cervical myelopathy and radiculopathy, but limitations include loss of cervical range of motion, the concern for adjacent segment degeneration and disease, pseudoarthrosis, complications related to the choice of intervertebral graft, dysphagia, as well as standard anterior cervical ap...
Source: Neurosurgery Clinics of North America - July 30, 2021 Category: Neurosurgery Authors: Gregory Callanan, Kristen E. Radcliff Source Type: research

Biomechanics of Cervical Disc Arthroplasty Devices
Prosthesis design has an influence on the quantity and quality of postoperative motion after cervical disc arthroplasty. Prostheses with built-in resistance to angular and translational motion may have an advantage in restoring physiologic motion. The ability of a prosthesis to work with remaining bony and soft tissues to restore motion and load-sharing is a function of the kinematic degrees of freedom DOF, axis of rotation for a given motion, and device stiffness. How these characteristics allow the prosthesis to work with the patient's anatomy will determine whether the prosthesis is successful at restoring motion and mi...
Source: Neurosurgery Clinics of North America - July 30, 2021 Category: Neurosurgery Authors: Avinash G. Patwardhan, Robert M. Havey Source Type: research

Adjacent-Segment Disease Following Spinal Arthroplasty
Intuitively, the introduction of artificial discs into spinal surgery offered the promise of reducing the incidence of adjacent segment (AS) reoperation compared with fusion. Several early clinical studies reported nonstatistically significant differences in AS disease between total disc replacement and fusion. Given the relatively low rate of AS reoperation ( ∼1%–2% per year) following fusion, any appropriately powered study designed to demonstrate a statistically significant difference compared with arthroplasty would require thousands of patients and/or long-term follow-up (>5  years). Therefore, these...
Source: Neurosurgery Clinics of North America - July 30, 2021 Category: Neurosurgery Authors: Jonathan M. Parish, Anthony M. Asher, Domagoj Coric Source Type: research

Posterior Lumbar Facet Replacement and Arthroplasty
There is an ongoing desire for the development of motion-preserving facet replacement devices as an alternative to rigid fixation in hopes of better preserving the natural kinematics of the lumbar spine. Theoretically, such a construct would simultaneously address pain associated with spinal instability and prevent abnormal load distribution and adjacent segment degeneration. Several such devices have been developed including the Anatomic Facet Replacement System, the Total Facet Arthroplasty System, and the Total Posterior Arthroplasty System. Of these devices, none have yet proven to be more efficacious than rigid fixati...
Source: Neurosurgery Clinics of North America - July 30, 2021 Category: Neurosurgery Authors: Ben Jiahe Gu, Rachel Blue, Jang Yoon, William C. Welch Source Type: research

The Natural History of Spinal Cord Injury
The natural history of spinal cord injury is in a state of flux. Our knowledge about the prevalence, epidemiology, and natural history spinal cord injury is in evolution. In this article, we summarize these considerations to provide a state-of-the-art synopsis of the neurologic outcomes of this condition. (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - May 28, 2021 Category: Neurosurgery Authors: Alexander F. Haddad, John F. Burke, Sanjay S. Dhall Source Type: research

Spinal Cord Injury Management on the Front Line
This article discusses the important strategies in caring for patients with SCI that are supported with significant literature. (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - May 28, 2021 Category: Neurosurgery Authors: Christopher Wilkerson, Andrew T. Dailey Source Type: research

Hypothermia for Acute Spinal Cord Injury
Neuroprotection after acute spinal cord injury is an important strategy to limit secondary injury. Animal studies have shown that systemic hypothermia is an effective neuroprotective strategy that can be combined with other therapies. Systemic hypothermia affects several processes at the cellular level to reduce metabolic activity, oxidative stress, and apoptotic neuronal cell death. Modest systemic hypothermia has been shown to be safe and feasible in the acute phase after cervical spinal cord injury. These data have provided the impetus for an active multicenter randomized controlled trial for modest systemic hypothermia...
Source: Neurosurgery Clinics of North America - May 28, 2021 Category: Neurosurgery Authors: Aditya Vedantam, Allan D. Levi Source Type: research

Spinal Cord Injury: Journey of Discovery
I am grateful to John Hurlbert, Russ Lonser, and Dan Resnick for asking me to participate in this important issue on spinal cord injury (SCI). John and I have known each other for a long time. He was a superb research fellow in my SCI lab, and an excellent resident on my neurosurgical service. I am honored to write this introductory article, and my goal is to portray for readers some of the excitement I experienced and the important milestones in SCI management and research that I was privileged to witness. (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - May 28, 2021 Category: Neurosurgery Authors: Charles H. Tator Tags: Introduction Source Type: research

Current State of the Art in Spinal Cord Injury
NEUROSURGERYCLINICS OF NORTH AMERICA (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - May 28, 2021 Category: Neurosurgery Authors: John Hurlbert Source Type: research

Copyright
ELSEVIER (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - May 28, 2021 Category: Neurosurgery Source Type: research

Contributors
RUSSELL R. LONSER, MD (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - May 28, 2021 Category: Neurosurgery Source Type: research

Contents
John Hurlbert (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - May 28, 2021 Category: Neurosurgery Source Type: research

Forthcoming Issues
Update on Motion Preservation  Technologies (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - May 28, 2021 Category: Neurosurgery Source Type: research

Targeting Central Nervous System Regeneration with Cell Type Specificity
There have been tremendous advances in identifying cellular and molecular mechanisms constraining axon growth and strategies have been developed to overcome regenerative failure. However, reproducible and meaningful functional recovery remains elusive. An emerging reason is that neurons possess subtype-specific activation requirements. Much of this evidence comes from studying retinal ganglion cells following optic nerve injury. This review summarizes key neuropathologic events following spinal cord injury, and draws on findings from the optic nerve to suggest how a similar framework may be used to dissect and manipulate t...
Source: Neurosurgery Clinics of North America - May 11, 2021 Category: Neurosurgery Authors: Mark A. Anderson Source Type: research

Preface
This issue of Neurosurgery Clinics of North America focuses on one of the most long-lasting, life-altering conditions known to our specialty: spinal cord injury (SCI). Since the inaugural issue in 1990, Neurosurgery Clinics of North America has been publishing quarterly state-of-the-art updates intended to keep students, researchers, and surgeons on the cutting edge of information specific to our discipline. In acknowledging this 30-year legacy, it is fitting we recognize and dedicate this issue to a world-renowned student, researcher, and clinical master, who has dedicated his career to the pursuit of Spinal Cord Injury, ...
Source: Neurosurgery Clinics of North America - May 11, 2021 Category: Neurosurgery Authors: John Hurlbert, Allan D. Levi, Michael Fehlings Source Type: research

Diagnostic Imaging in Spinal Cord Injury
In the evaluation of spinal trauma, diagnostic imaging is of paramount importance. Computed tomography (CT), flexion/extension radiographs, and MRI are complementary modalities. CT is typically obtained in the initial setting of spinal trauma and provides detailed information about osseous structures. MRI provides detailed information about structural injury to the spinal cord. Diffusion tensor imaging provides microstructural information about the integrity of the axons and myelin sheaths, but its clinical use is limited. Novel imaging techniques may be better suited for the acute clinical setting and are under developmen...
Source: Neurosurgery Clinics of North America - May 8, 2021 Category: Neurosurgery Authors: Saman Shabani, Briana P. Meyer, Matthew D. Budde, Marjorie C. Wang Source Type: research

Pathophysiology of Spinal Cord Injury
Spinal cord injury (SCI) triggers a complex cascade of molecular and cellular events that leads to progressive cell loss and tissue damage. In this review, the authors outline the temporal profile of SCI pathogenesis, focusing on key mediators of the secondary injury, and highlight cutting edge insights on the alterations in neural circuits that largely define the chronic injury environment. They bridge these important basic science concepts with clinical implications for informing novel experimental therapies. Furthermore, emerging concepts in the study of SCI pathogenesis that are transforming fundamental research into i...
Source: Neurosurgery Clinics of North America - May 7, 2021 Category: Neurosurgery Authors: Laureen D. Hachem, Michael G. Fehlings Source Type: research

Central Cord Syndrome Redefined
This article reviews the historical origins of central cord syndrome (CCS), the mechanism of injury, pathophysiology, and clinical implications. CCS is the most common form of incomplete spinal cord injury. CCS involves a spectrum of neurologic deficits preferentially affecting the hands and arms. Evidence suggests that in the twenty-first century CCS has become the most common form of spinal cord injury overall. In an era of big data and the need to standardize this particular diagnosis to unite outcome data, we propose redefining CCS as any adult cervical spinal cord injury in the absence of fracture/dislocation. (Source...
Source: Neurosurgery Clinics of North America - May 7, 2021 Category: Neurosurgery Authors: Mauricio J. Avila, R. John Hurlbert Source Type: research

Acute, Severe Traumatic Spinal Cord Injury
We discuss 2 evolving management options for acute spinal cord injury that hold promise to further improve outcome: pressure monitoring from the injured cord and expansion duraplasty. Probes surgically implanted at the injury site can transduce intraspinal pressure, spinal cord perfusion pressure, and cord metabolism. Intraspinal pressure is not adequately reduced by bony decompression alone because the swollen, injured cord is compressed against the dura. Expansion duraplasty may be necessary to effectively decompress the injured cord. A randomized controlled trial called DISCUS is investigating expansion duraplasty as a ...
Source: Neurosurgery Clinics of North America - May 7, 2021 Category: Neurosurgery Authors: Samira Saadoun, Marios C. Papadopoulos Source Type: research

Pharmacologic and Cell-Based Therapies for Acute Spinal Cord Injury
This article provides a review of current pharmacologic and cell-based modalities used for the management of acute spinal cord injury (SCI). The literature search was focused on clinical trials performed in the United States and Canada. Despite the significant advance in research, there is no definitive treatment option for SCI. Instead, existing pharmacologic and cell-based modalities provide only minimal neurologic recovery benefits. This can be attributed to the complex pathophysiology of SCI and spinal cord regeneration. Further research is imperative to better understand these mechanisms and discover definitive treatm...
Source: Neurosurgery Clinics of North America - May 7, 2021 Category: Neurosurgery Authors: Nikolay L. Martirosyan Source Type: research

Brain-Computer Interface, Neuromodulation, and Neurorehabilitation Strategies for Spinal Cord Injury
This article briefly introduces these broad areas of active research and lays out some of the current evidence for their use for patients with spinal cord injury. (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - May 7, 2021 Category: Neurosurgery Authors: Iahn Cajigas, Aditya Vedantam Source Type: research

Spinal Cord Injury Clinical Classification Systems
Spinal cord injury (SCI) remains a challenging disease in terms of surgical decision-making and improving neurologic outcome. As we have now entered a new era founded on routine “big data” capture, more advanced and meaningful yet simplified SCI classification systems and outcome measurement tools would be helpful to determine the efficacy of potential therapeutics in future clinical trials and registries. The proposed classification herein focuses on gross sensorimotor , sacral function below the injured level via an easy-to-use scoring system yielding grades 1 to 4 of injury severity. Such an optimized SCI sc...
Source: Neurosurgery Clinics of North America - May 6, 2021 Category: Neurosurgery Authors: Wyatt L. Ramey, Jens R. Chapman Source Type: research

The Current Landscape of Immune Checkpoint Blockade in Glioblastoma
The glioblastoma tumor microenvironment is highly immunosuppressed. This immunosuppressive state is engineered by inhibitory molecules secreted by tumor cells that limit activation of immune effector cells, drive T-cell exhaustion, and enhance the immunosuppressive action of tumor-associated myeloid cells. Immunotherapeutic approaches have sought to combat glioblastoma microenvironment immunosuppression with agents such as immune checkpoint inhibitors. Although immune checkpoint blockade in glioblastoma has yielded disappointing results thus far, there is significant interest in the combination of immune checkpoint blockad...
Source: Neurosurgery Clinics of North America - March 27, 2021 Category: Neurosurgery Authors: Oluwatosin O. Akintola, David A. Reardon Source Type: research

Metabolic Vulnerabilities in Brain Cancer
Glioblastomas (GBMs) exhibit altered metabolism to support a variety of bioenergetic and biosynthetic demands for tumor growth, invasion, and drug resistance. Changes in glycolytic flux, oxidative phosphorylation, the pentose phosphate pathway, fatty acid biosynthesis and oxidation, and nucleic acid biosynthesis are observed in GBMs to help drive tumorigenesis. Both the genetic landscape of GBMs and the unique brain tumor microenvironment shape metabolism; therefore, an understanding of how both intrinsic and extrinsic factors modulate metabolism is becoming increasingly important for finding effect targets and therapeutic...
Source: Neurosurgery Clinics of North America - March 27, 2021 Category: Neurosurgery Authors: Danielle Morrow, Jenna Minami, David A. Nathanson Source Type: research

Novel Radiation Approaches
The standard of care treatment for glioblastoma is surgical resection followed by radiotherapy to 60  Gy with concurrent and adjuvant temozolomide with or without tumor-treating fields. Advanced imaging techniques are under evaluation to better guide radiotherapy target volume delineation and allow for dose escalation. Particle therapy, in the form of protons, carbon ions, and boron neutron captur e therapy, are being assessed as strategies to improve the radiotherapeutic ratio. Stereotactic, hypofractionated, pulsed-reduced dose-rate, and particle radiotherapy are re-irradiation techniques each uniquely suited for di...
Source: Neurosurgery Clinics of North America - March 27, 2021 Category: Neurosurgery Authors: Rupesh Kotecha, Martin C. Tom, Minesh P. Mehta Source Type: research

Morphologic and Molecular Aspects of Glioblastomas
The definition of glioblastomas has continually evolved from a reliance on strict morphologic features to a combination of histologic and molecular criteria, as the understanding of the genetic basis of these tumors expands. Modern pathologic workup of glioblastomas includes intraoperative evaluations with tissue-sparing techniques, histologic assessment with immunohistochemical markers, and comprehensive molecular characterization aiming at personalized targeting of genetic abnormalities. Machine learning analysis of DNA methylation profiles is a breakthrough technology that has bolstered central nervous system tumor clas...
Source: Neurosurgery Clinics of North America - March 27, 2021 Category: Neurosurgery Authors: Osorio Lopes Abath Neto, Kenneth Aldape Source Type: research

Brain Tumor Vaccines
Peptide and dendritic cell vaccines activate the immune system against tumor antigens to combat brain tumors. Vaccines stimulate a systemic immune response by inducing both antitumor T cells as well as humoral immunity through antibody production to cross the blood –brain barrier and combat brain tumors. Recent trials investigating vaccines against peptides (ie, epithelial growth factor receptor variant III, survivin, heat shock proteins, or personalized tumor antigens) and dendritic cells pulsed with known peptides, messenger RNA or unknown tumor lysate tar gets demonstrate the potential for therapeutic cancer vacci...
Source: Neurosurgery Clinics of North America - March 27, 2021 Category: Neurosurgery Authors: Justin Lee, Benjamin R. Uy, Linda M. Liau Source Type: research

Glioblastoma, Part II: Molecular Targets and Clinical Trials
NEUROSURGERY CLINICS OF NORTH AMERICA (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - March 27, 2021 Category: Neurosurgery Authors: Linda M. Liau Source Type: research

Copyright
ELSEVIER (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - March 27, 2021 Category: Neurosurgery Source Type: research

Contributors
DANIEL K. RESNICK, MD, MS (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - March 27, 2021 Category: Neurosurgery Source Type: research

Contents
Linda M. Liau (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - March 27, 2021 Category: Neurosurgery Source Type: research

Neurosurgery Clinics of North America
Current State of the Art in Spinal Cord Injury (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - March 27, 2021 Category: Neurosurgery Source Type: research

Glioblastoma: Molecular Mechanisms and Clinical Trials
Despite growing basic research on the molecular genetics and mechanisms of brain tumor biology and new clinical trials for brain tumors, glioblastoma has remained a formidable foe. In this issue of Neurosurgery Clinics of North America, an authoritative panel of researchers and clinicians critically reviews the current state-of-the-field to provide a comprehensive guide to modern molecular considerations and clinical trials for glioblastoma, with hopes of enhancing future research in this area. The contributors detail many of the key laboratory experiments and clinical protocols that are currently being investigated, integ...
Source: Neurosurgery Clinics of North America - March 27, 2021 Category: Neurosurgery Authors: Linda M. Liau Tags: Preface Source Type: research

Pediatric Gliomas
Next-generation sequencing of pediatric gliomas has revealed the importance of molecular genetic characterization in understanding the biology underlying these tumors and a breadth of potential therapeutic targets. Promising targeted therapies include mTOR inhibitors for subependymal giant cell astrocytomas in tuberous sclerosis, BRAF and MEK inhibitors mainly for low-grade gliomas, and MEK inhibitors for NF1-deficient BRAF:KIAA fusion tumors. Challenges in developing targeted molecular therapies include significant intratumoral and intertumoral heterogeneity, highly varied mechanisms of treatment resistance and immune esc...
Source: Neurosurgery Clinics of North America - February 18, 2021 Category: Neurosurgery Authors: Sophie M. Peeters, Yagmur Muftuoglu, Brian Na, David J. Daniels, Anthony C. Wang Source Type: research

Molecularly Targeted Clinical Trials
Glioblastoma remains incurable despite advances in surgery, radiation, and chemotherapy, underscoring the need for new therapies. The genetic heterogenicity, presence of redundant molecular pathways, and the blood-brain barrier have limited the applicability of molecularly targeted agents. The therapeutic benefit seen with a small subset of patients suggests, however, that patient selection is critical. Recent investigations show that molecularly targeted synthetic lethality is a promising complementary approach. The article provides an overview of the challenges of molecularly targeted therapy in adults with glioblastoma,...
Source: Neurosurgery Clinics of North America - February 18, 2021 Category: Neurosurgery Authors: Matthew A. Smith-Cohn, Orieta Celiku, Mark R. Gilbert Source Type: research

Therapeutic Delivery to Central Nervous System
Therapies for glioblastoma face several physiologic hurdles. The blood-brain barrier (BBB) and blood-brain-tumor barrier (BTB) present impediments to therapeutic delivery of drugs to the central nervous system. Strategies to disrupt or bypass the native BBB are necessary to deliver therapeutic agents. Techniques to bypass the BBB/BTB include implantable controlled-release polymer systems, intracavitary drug delivery, direct injection of viral vectors, and infusion via convection-enhanced delivery. Ideal methods and agents to accomplish the goal providing survival benefit are yet to be determined. Further development of met...
Source: Neurosurgery Clinics of North America - February 18, 2021 Category: Neurosurgery Authors: Katherine E. Kunigelis, Michael A. Vogelbaum Source Type: research

CAR T Cells
Chimeric antigen receptor T (CAR-T) cells, an immunotherapy that demonstrates marked success in treatment of hematologic malignancies, are an emergent therapeutic for patients with glioblastoma (GBM). GBM CAR-T trials have focused on targeting well-characterized antigens in the pathogenesis of GBM. Early stage trials demonstrate initial success in terms of safety and tolerability. There is preliminary evidence of antitumor activity and localization of the CAR-T product to tumoral sites. There are mixed results regarding patient outcomes. Ongoing GBM CAR-T trials will target novel antigens, explore CAR-T combination therapy...
Source: Neurosurgery Clinics of North America - February 18, 2021 Category: Neurosurgery Authors: Thilan Tudor, Zev A. Binder, Donald M. O ’Rourke Source Type: research