Features of the Month


UCLA Lecture 77
Intracranial Aneurysms


Neurocirugía Hoy, Vol. 6, Numero 20

Image of the Month

Table 1
The future of high-grade glioma: Where we are and where are we going

Dear Colleague,

On March 1, SNI celebrated completion of its 5th year of publication. In that time, SNI and its publications have grown to reach 30,000 individual readers a month, in 223 countries and territories. SNI publishes nine supplements, on topics ranging from spine and stereotaxis to neuroscience nursing. It has the highest circulation of any journal in its field. Our thanks to you, our readers, for this success. 

To continue building upon this success, we have been working over the past six months to develop and construct a significantly more user friendly and functional Web site. We expect the new site to be released later this month, and will make an announcement when it is available.

Following are some of the key papers since the last newsletter:

Current Concepts

"Concepts" is a bimonthly feature, in which an editorial board of young neurosurgeons selects key papers from the literature. The selected papers in this issue include: a) dendritic cell vaccination for GBM with early very promising results, b) separation (circumferential) surgery for metastatic epidural tumors to the spine followed by SRS with improved results over standard therapy, c) how many brain metastases should be treated with SRS? d) surgical stabilization of type II dens fractures in the elderly is better than non-surgical management, e) molecular sub-typing of meningiomas with implications for anatomical location, e) the value of BDNF in spinal cord injury. Zach Smith and Isaac Yang are the lead editors of this feature.

Neuro-Oncology:

Dan Silbergeld published the latest installment of SNI: Neuro-oncology. This supplement looks at 21st century approaches to malignant glioma. Also look at Wilson’s paper on the treatment choices for GBM, which we published last year.

1) Ene et al discuss that for "personalized therapy to work for GBMs, pharmacologic agents would not only be tailored to target the differences from patient to patient, but also the clonal diversity within each patient's tumor." Personalized therapy is treatment designed for each person and his/her unique genetic characteristics.

2) Chowdhary et al reviewed the progress in chemotherapy, surgery, and radiation for GBM. "Two-year survival rate in the RT+TMZ (Temozolomide) group was 26.5% compared with 10.4% in the RT alone group." More extensive surgery was correlated with longer survival, but those left with post-op deficits had a shorter survival. Only survival, not quality of life, is addressed. "Ultimately, in the future, multi-modality glioma therapy will be personalized for individual patients based on tumor grade as well as histological and molecular sub-types."

3) Mangraveti et al review the evidence for the use of Gliadel wafers in primary or recurrent GBMs. It appears that the wafers, which contain BCNU, a chemotherapeutic agent that diffuses into the brain, produce increased survival, which is even additive to TMZ and radiation.

4) Among the investigational therapies, immunotherapy was designed to avoid the toxicity of conventional Rx that produces damage to healthy brain and other tissues. Tumors have a microenvironment that inhibits immunologic cells from attacking the tumor cells. If this inhibitory system is shut down, the tumor cells become less aggressive. Researchers have developed a number of ways to stimulate the patient’s immune system to attack the tumor, by vaccines against the tumor cell or by giving the patient immune cells that attack tumor cells. Immunotherapy has been effective against systemic melanomas and shows promise in GBM as stated in this review paper by Suryadevara et al.

5) "Unlike diffusion-limited treatment used in wafers, Convection Enhanced Delivery (CED) provides a localized pressure gradient, enhancing interstitial drug distribution in GBMs," avoiding the natural restrictions of the blood brain barrier. With this technique, various anti tumor agents, mostly chemotherapeutic, can be infused into the tumor bed and forced to diffuse thru the tissue and reach further distances from the tumor in higher concentrations and without systemic toxicity. This process is called CED. The agents used in CED can be tracked by imaging. Technical issues related to drug delivery and catheter placement are being worked out. Some clinical trials have been done with positive results. Healy et all review this evidence.

6) Chiarellie et al discuss the potential of nanotechnology in glioma therapy. Nanomolecules are small man-made poly-molecules on the scale of 1-10x the size of a red cell, that has a 7 micron diameter. These nanomolecules can be designed in the laboratory to include a variety of chemotherapeutic, imaging, gene replacement, and tumor destructive elements. Nanoparticles appear to enter tumor cells, leading to the development of nanoparticles designed to enable better imaging and sensitivity to ultrasound for localized destruction of the cells. The nanomolecule can penetrate the blood brain barrier to reach its target. Nanotechnology is developmental but is projected to become a major force, not only in medicine, but also in other applications. Some are predicting that nanomolecules will have a larger impact on civilization than the development of the Internet. This short summary cannot do justice to the review, which should be read for more detail of this interesting technology.

7) In one of the most exciting papers in the supplement, Sutherland et al describe their use of robotic technology in the treatment of gliomas, which can be combined with intraoperative MR, but used continuously by distant manipulation of surgical tools being constantly directed to tumor cells and away from fiber tracts. The effects of brain shift are avoided. This is a very innovative application of robotics to neurosurgery, and will lead to applications beyond glioma surgery.

8)  In the final paper in this supplement, "The future of high-grade glioma: Where we are and where are we going," Le Ruhn et al have done an excellent job of summarizing the relevant drug and radiation trials and correlating their outcomes with the known tumor markers. This is a superb review and indicates that histological data needs to be supplemented by the molecular characterization of anaplastic gliomas and GBMs, and is very important in determining the types and outcomes of various therapies to prolong survival. It is the first study that I have read that also considers quality of life. This is the best paper I have read summarizing the status of high-grade glioma therapy from all the clinical trials. These approaches make a major advance in the treatment of these tumors.

Dr. Silbergeld and the authors of the papers in this supplement have done an outstanding job reporting on present and future treatments for high-grade gliomas.

Trauma

In patients with traumatic brain injury, Ramakrishnan et al found a trend of more seizure activity after decompressive craniectomy compared to traditional craniotomy -- suggesting a need for longer antiepileptic treatment.

Vascular

Katsuno et al describe a new approach to low position basilar aneurysms without sacrificing temporal veins. "The modified anterior temporal approach allows a wider operating field within the retro-carotid space, without sacrificing any vessels, and permits a safer posterior clinoidectomy [that provides more visualization] for aneurysm clipping in patients with low-position aneurysms of the basilar complex." Read the methods section for a detailed explanation of the technique. In their dissection, the pterional muscle is reflected posteriorly to provide room anteriorly to the tip of the temporal lobe and sylvian fissure. This is a very interesting approach.

Almeida et al review the management of posterior fossa arteriovenous malformations. The authors quote from the work of Hernesniemi and colleagues that "posterior fossa AVMs have an annual rate of rupture of 11.6% in the first 5 years after admission, with a cumulative rupture rate of 45% in the first 5 years, as compared with an annual rate of 4.3% and a cumulative 5 years rate of 19% for supratentorial AVMs." The authors conclude, "current data supports the role of microsurgery as the gold standard treatment for cerebellar AVMs. Brainstem AVMs are usually managed with radiotherapy and endovascular therapy; microsurgery is considered in cases of pial brainstem AVMs… Total obliteration rates after SRS range from 44% to 73% over 3-4 years based on MRI or angiography studies." Favorable outcomes are reported in surgical studies. What ever happens to those patients whose AVMs are not obliterated with SRS?

Spine and Spinal Cord: Re-anastomosing the Spinal Cord

Sergio Canavero has written an editorial on re-anastomosing a severed spinal cord, which follows his previous paper on head transplantation in animals. Robert White, a neurosurgeon in the USA, published a set of experiments performed in the 70s-90s on head transplantation in dogs, but he was not able to find a solution to fusing separated spinal cords. Canavero now writes about reconnecting a severed spinal cord. He quotes Bucy from his work with the pyramidal tracts, "The pyramidal tract … is not essential to useful control of the skeletal musculature… In the absence of the corticospinal fibers, other fiber systems, particularly some … multineuronal pathways pass through the mesencephalic tegmentum, are capable of producing useful, well-coordinated, strong and delicate movements of the extremities."  Canavero uses this idea of multiple interneuronal connections for the motor system in solving the severed spinal cord challenge. First, he sharply severs the spinal cord, and then uses fusogen/sealants to promote fusion of the severed axons. Next, he applies electrical stimulation across the spinal cord gap to stimulate these short neural connections to become reconnected. He writes, "This means that a sufficient number of axonal proximal stumps get fused with the distal counterparts in such a way to ensure appropriate electrophysiological conduction, likely the result of tight axonal packing. This number is likely low (10-15%), and yet enough for recovery, reflecting the potential for substantial plasticity in the injured CNS." This is science at its most visionary. Yet, if we think that we will live to 100 and beyond by the end of the 21st century, and that predictions are being made that we will be able to transfer information between brains of humans, thereby shortening the time of learning and experience, why would Sergio’s ideas be so unusual?

Skull Base Surgery, Repair Techniques

Reinard et al describe their approach to repair of the cranial base in complex skull base cases. "The layered reconstruction of large anterior cranial fossa defects resulted in postoperative CSF leak in only 5% of the patients and represents a simple and effective closure option for skull base surgeons." The low CSF leak rate is impressive. Read the methods section for details of their approach.

Anatomy for Neurosurgeons

There are two very practical papers by Tubbs et al on "Superficial cortical landmarks for localization of the hippocampus: Application for temporal lobectomy and amygdalohippocampectomy" and "External cortical landmarks and measurements for the temporal horn: Anatomic study with application to surgery of the temporal lobe."  They are self-explanatory.

Matsushima et al write about the "Absence of the superior petrosal veins and sinus: Surgical considerations." In cases in which the superior petrosal sinus and veins are absent, care should be directed to preserving the collateral drainage through the galenic and tentorial tributaries.

Neurosurgical Education:

Healthcare in Africa
Mansouri et al evaluated the reasons for delay of neurosurgical care in a Kenyan hospital. Hydrocephalus and neural tube defects accounted for 2/3 of the admissions. Delays in primary care accounted for more than 2/3 of the causes late admissions. Neural tube defects were recognized early and referred more quickly. The authors concluded, "Improvement in primary care physicians' knowledge base, implementation of a triage and referral process, and development of community-based funding strategies can potentially reduce these delays." With the help of outside volunteers from other countries, these problems have the potential to be solved.

Surgical Simulation
Bohm and Arnold review the literature on surgical simulation methods in use. This paper is a nice review of the status of the field. SNI stands ready to provide supplements or content that would facilitate this process and make this information more widespread. 

Programming for Physicians
Pieter Kubben, SNI’s IT Editor, will be starting a programming course for physicians shortly.

Bioethics, Aging, Neurosurgery and its Future

In its ongoing effort to examine controversial subjects, SNI explores a recent paper on limiting life to the age of 75 by Emanuel. Miguel Faria, an Associate Editor in Chief of SNI, in his Editorial, "Bioethics and why I hope to live beyond age 75 attaining wisdom!: A rebuttal to Dr. Ezekiel Emanuel's 75 age limit," provides a response to "the government planners, supported by the ever-accommodating bioethicists, who posit that with increasing longevity and augmentation of the population of American elderly, more drastic actions will be required to prevent the bankruptcy of the public financing of medical care. They believe, therefore, that outright government-imposed euthanasia, not only for the terminally ill but also for the inconvenient infirm and the superfluous elderly, will become necessary."

This subject is a very important one for physicians and neurosurgeons to understand, as it has major implications for the practice of medicine. Recently, Dr. Ezekiel Emanuel, whose paper was quoted by Faria, proposed this idea. Emanuel stated that people should not be allowed to live beyond the age of 75, as they are no longer productive for society, and consume resources needed by those younger. Emanuel is one of the architects of Obamacare.

Other evidence to support the contrary point of view was stated by University of Chicago economist, Gary Becker, who wrote that the greatest achievement of the 20th century was the doubling of life expectancy. The futurist, R. Naam, listed the worldwide advances in the last 150 years, including: 1) the rising life expectancy, 2) massive reduction in poverty, 3) increasing education of the masses, 4) the rapid access to information (cell phone usage has grown from 0 to 4 billion in 20 years), 5) the doubling of democracies since 1970, 6) the discovery of huge resources of energy, 7) the increased productivity of food from smaller amounts of land, 8) the exploration of space, 9) the potential to harness the sun’s energy, and to desalinate the ocean water for the increasing world population, and 10) the recent finding of the potential of life on another planet similar to earth.  These are all spectacular achievements. In his article in The Futurist, Naam states that with these changes, people are demanding more control over their lives and more individual freedom. These examples are not the story of limited resources and human potential. They signal the creativity, imagination, and determination of individuals of all ages, who, when liberated, will make great achievements for humankind in solving its challenges. The papers cited in this newsletter, particularly, provide a view of the huge potential available through the creativity of neurosurgeons and other scientists.

So, Emanuel and Faria present two opposing views of the future and how society can cope with this challenge. One projects the idea of the acceptance of limited resources that must be centrally controlled in all ways. The other idea supports the unlimited opportunities to solve the challenges faced by our civilizations under a system of individual liberty and competition. That is the fundamental conflict that has been going on for centuries as civilization has evolved. Because of the nature of individuals to want freedom, no centrally controlled system has survived, as recorded by Durant and Durant. [The Lessons of History. New York: Simon and Schuster; 1968. p. 109.] Corruption is the threat to all theoretical systems of governance, including democracy. Which system will provide the best healthcare for the people? That is your decision. SNI is presenting the controversy that will affect your life and the practice of medicine.



Watch for Nancy Epstein’s new spine supplement in the coming weeks, and also Tony DeSalles' stereotactic supplements in the next 60 days.

Also enjoy the new additions to the UCLA 100 series of lectures, the new additions to the Russian Journal of Neurosurgery for our Russian-speaking readers, and a new edition of HOY! for our Spanish-speaking readers.

SNI thanks Arbor Pharmaceuticals for its support of the Neuro-oncology supplement, and also our major supporter, Elekta. This is your journal. You can comment on any of the content. I am open to all suggestions and ideas on how we can make SNI Publications better for you and your colleagues. Write to me at jamesausman@mac.com.



James I. Ausman, MD, PhD,
Editor in Chief,
Surgical Neurology International





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