Dr. Hani Malone

Resident Dr. Hani Malone and Dr. Michael Kaiser from the Spine Center are currently conducting clinical research to determine the optimal treatment strategies for patients presenting with cervical spondylotic myelopathy (CSM), a degenerative process of the neck that can lead to neurological deficits and impaired quality of life.

Dr. Kaiser is currently chairman of the Guidelines Committee for the AANS/CNS Joint Section of Spine and Peripheral Nerve Disorders, the function of which is to establish standardized treatment paradigms for various spinal disorders based on the best available medical evidence.

Dr. Hani Malone is one the rising stars in the Columbia University neurosurgical residency program, who had developed a strong interest in spine surgery and promises to be a future leader in this field.

CSM is the most common cause of myelopathy (injury to the spinal cord) in adults older than 55 years, often causing progressive disability and compromising the patient’s quality of life. Patients will often present with hand numbness, loss of dexterity, gait instability, and compromised urinary control.

The goal of surgery for CSM is to relieve pressure on the spinal cord and prevent further injury, while maintaining spinal stability.  Surgeons have developed a number of different approaches to treat CSM, but the optimal surgical approach for a given patient remains an area of debate.

In order to establish the best treatment alternatives, Drs. Malone and Kaiser have been reviewing the clinical experience of the Columbia University spine surgeons over the past 8 years, where over 500 patients with CSM have been treated.

Development of a prospective patient database has become a national initiative, with the hope that such data will define specific patient characteristics that can be used to determine the optimal surgical approach.

This is particularly true with CSM since there are a number of surgical alternatives that may be considered. In addition to stabilizing and improving neurological function, maintaining and/or restoring the optimal spinal configuration is a major surgical objective to minimize chronic pain, prevent progressive deformities, and maximize quality of life.

Dr. Michael Kaiser

This research is ongoing and Drs. Malone and Kaiser will be submitting the preliminary work presentation at upcoming national neurosurgical meetings, including the AANS/CNS Joint Section on Disorders of the Spine and Peripheral Nerves and the AANS Annual Meeting.

“I was involved in several symposia which allowed us to present some of the latest work we are doing at Columbia to advance the field,” Says Dr. Bruce.

He was active in five different sessions as: Speaker at a symposium about Maximizing Extent of Resection in Primary Brain Tumors; Moderator at a Scientific Session on Tumors; Moderator at the Joint Section Session on Tumors; Discussant on a Panel about the Prevalence and Natural History of Pineal Cysts in Adults; And Panelist for a discussion on the Spectrum of Adjuvant Therapy for Brain Tumors.

“The conference provided a good update on all of the newest developments in neurosurgery.” Says Dr. Bruce, “ I am completing my term as Chairman of the Tumor Section where we have been productive. The brain tumor field has been very active in trying to develop new treatments for patients.”

He spoke about his lab‘s recently completed convection enhanced delivery trial of topotecan. The trial, led by Dr. Bruce at the Bartoli Brain Tumor Laboratory is described as follows:

-a multidisciplinary NIH-funded Phase I trial for brain tumor patients using a novel strategy that delivers chemotherapy directly into the tumor. A chemotherapy drug, Topotecan, is slowly pumped into the tumor and surrounding brain tissue through catheters that have been stereotactically implanted. This strategy, known as convection enhanced delivery, significantly increases the amount of drug that enters the tumor and avoids systemic side effects since the drug remains only in the brain. Bartoli Brain Tumor Laboratory

The results of the trial showed, “Significant anti-tumor activity as described by radiographic changes and prolonged overall survival with minimal drug associated toxicity,” Says Dr. Bruce. They also extablished a maxiumum tolerated dose for future phase II studies.

Congratulations to Dr. Bruce and everyone at the Bartoli Brain Tumor Lab on the completion of this important trial!

Imagine a war zone where the entire army has shown up to fight the enemy but for some reason won’t shoot.  For this war to be won, whatever is keeping the soldiers from fighting needs to be found and stopped.  This is the situation researchers have recently discovered in their fight against  malignant gliomas, a common type of brain tumor.  Dr. Richard C. E. Anderson from the Pediatric Neurosurgery Center recently presented this research at the American Society of Pediatric Neurosurgeons‘ Annual Meeting.

According to Dr. Anderson, the impetus for this research is the difficulty in treating this kind of cancer.  He says, “despite surgery, radiation, and chemotherapy, the prognosis can still be poor.”

He and a multicenter group of researchers have found that the presence of glioma tumor cells does trigger a large immune response in the body.  However, at some point in the tumor’s development, the immune cells sent in to fight become inhibited, leaving the deadly tumor to grow unrestricted.  He and his colleagues are trying to find out why, and exactly how, this is happening in the hopes of  somehow bolstering the patient’s own immune system to fight this deadly invader.

The troops used by the immune system to fight this cancer are specific white blood cells called Tumor Associated Microglia/Monocytes or TAMs.  According to Anderson, “They are found at a much higher frequency than any other immune cell in the presence of malignant gliomas” and inherently they are, “capable of destroying these tumor cells.”  But in laboratory tests, “TAMS are significantly impaired in the presence of malignant gliomas.”  If fully functional, the TAMS would secrete a cancer cell destroying agent called TNF-alpha.  Instead, they sit there like soldiers who have been ordered not to release any bullets.

Dr. Anderson explains further, “The TAMs do not secrete the TNF-alpha in the presence of glioma cells, not simply because the entire system is blocked, but rather there is some specific pathway to cause this, and that is what we’re trying to figure out!”

He and his colleagues have found a specific gene within the TAMs that is activated, or up-regulated, when these kinds of tumor cells are present.  When a gene is up-regulated, it becomes more sensitive or develops more receptors to be effected by an agent acting on it.  What that agent is, researchers are trying to find out.

As they know more, Anderson says they can, “attempt to reverse functional impairment of TAMs by using siRNA, blocking antibodies, or medications to inhibit up-regulation of these genes.”

Dr. Anderson is hopeful.  He says, “these initial findings are a huge clue in the continuing fight against this deadly cancer.” He and his fellow researchers now know that the soldiers are there, it’s just a matter of freeing up the troops to do battle.

People involved in this research are: at Columbia University, Richard Anderson, Shinji Shimato, Benjamin Kennedy, Mike Castelli, Peter Canoll, and Jeffrey Bruce; at Harvard University, David Anderson and Alex Kostianovsky; and at Erinyes Biotechnologies, Lisa Maier.

The basilar artery is a large blood vessel located at the base of the brain that is formed when two of the major suppliers of oxygen rich blood, the vertebral arteries, come together at the back of the brain.

Because our brain is such a vital structure, the human body has given it a redundant blood supply.  That means that if one vessel in the brain gets blocked off, blood can be automatically re-routed.  This happens basically in two ways.  First, all the major arteries to the brain come together in the middle to form a circle (the Circle of Willis) and collectively can feed the whole brain. This way blood can be re-routed from the other major vessels if one fails.

The brain also has what is called collateral circulation.  Collateral blood vessels are normally closed but when a larger vessel gets blocked they can open up and re-rout the blood between vessels.  Over time these tiny vessels will grow and become permanent.

Sometimes a surgeon needs to block an artery on purpose.  This may be the case when it supplies an oddly shaped or giant aneurysm that is at risk of bursting.  A giant aneurysm  (larger than 2.5 cm in diameter) in the basilar artery can be particularly hard to treat however, because of  its location.  It lies deep in the skull near parts of the brain that control vital functions like breathing and heart rate.

An aneurysm occurs when the wall of a blood vessel grows weak and starts to balloon out.  These enlarged areas of the vessel are at risk of bursting and causing a brain bleed.  They can also be a problem if the increase in size presses on vital brain structures .

A number of surgical methods are used to treat them.  Because they are often balloon like in shape, they can be clipped at the neck and closed off.  Once it is no longer fed with blood, the aneurysm shrinks away.  More recently surgeons have been able to insert a coil into the aneurysm itself using minimally invasive endovascular techniques.

The problem with oddly shaped and giant aneurysms is that they often don’t have a distinct “neck” that can be clipped or they are just too big to be reliably coiled.   Surgeons are seeing that the rate of recurrence of these kinds of aneurysm after these procedures are not always optimal.  When this is the case, clipping off the basilar artery itself can be the most effective and least risky procedure.

Researchers in the Cerebrovascular Center combed through old charts from the last 22 years and found all the patients who had gone through this procedure.  They had records of these patients during the procedure, at their one month and one year follow-ups, and up to 18 years after.  They wanted to see how patients fared over all, especially in terms of neurological symptoms (indications of brain damage) and recurrence of the aneurysm.

The results were exceptional.  At the one month follow-up, 80% of the patients studied had no neurological problems.  Upon long term follow-up (an average of 3.5 years) none of the patients had any lasting deficits.  In fact, one patient who had weakness in his arms and legs before surgery was completely normal by his 2 year follow up.

According to the authors, ”No patients suffered a recurrence of symptoms or necessitated re-operation. No patients suffered a hemorrhage at any point after occlusion, and of the 4 patients who presented with a subarachnoid hemorrhage, none suffered a re-bleed.”

Based on their research, they also outlined a number of patient criteria for optimal outcome.  First of all they said, ”Patients were considered for surgical occlusion of the basilar artery if direct surgical or endovascular intervention was not considered safe.” Then they considered, ” failure of previous treatments, size of the aneurysm, neck to dome ratio, incorporation of major vessels in the neck of the aneurysm, and position of the thalamoperforates (specific surrounding blood vessels).”

It was also critically important, they said, that there was good collateral circulation.  This was tested before surgery using a balloon test occlusion as a kind of trial run. Surgeons get to see if it will be safe to block the vessel by inflating a balloon inside the artery to temporarily block the blood flow and see if it is re-routed.

Overall, the authors concluded that, ”Surgical occlusion of the basilar artery is an effective treatment option offering a high rate of angiographic cure in a single procedure for patients with complex basilar artery aneurysms,” and “for aneurysms of the upper third of the basilar artery, proximal surgical occlusion should be considered as an important treatment option along with direct surgical clipping and endovascular approaches.”

*The authors of this study, Complex Basilar Artery Aneurysms Treated with Surgical Basilar Occlusion: A Modern Series are: resident physicians Christopher P Kellner and Raqeeb Haque;  and from the Cerebrovascular Center, Dr. Philip M. Meyers, Dr. Sean D. Lavine, Dr. E. Sander Connolly, and the Department Chair Dr, Robert A. Solomon.

To learn more about the treatment of aneurysms see our blog, Results From First IML: Aneurysm Coiling V. Clipping Still A Toss Up, and Solomon’s Brain Aneurysm Primer Video.

The study entitled, Stenting versus Endarterectomy for Treatment of Carotid-Artery Stenosis (also called  Carotid Revascularization Endarterectomy vs. Stenting Trial or CREST) encompassed nearly 2500 patients from 116 medical centers across the United States and Canada.

Dr. Solomon says, “The Crest trial is, in my opinion, the largest and best study comparing endarterectomy and stenting for carotid artery disease.”

Stenting is a minimally invasive technique  where surgeons access the Carotid artery in the neck through an artery in the groin, then a stent, or piece of tubing, is placed inside the artery to ensure that it stays open.  Endarterectomy is a more traditional surgical procedure where the artery is opened and the plaque is removed.

Solomon continues, “The results [of CREST] are very consistent with previous trials. Most importantly, when compared to carotid endarterectomy, carotid stenting is associated with a higher periprocedural risk of stroke or death, a difference that was still significant at 4 years. The increased risk of stroke with stenting was offset by an increased risk of myocardial infarction in the endarterectomy patients, but stroke has much greater longterm health consequences than heart attack.”

The authors of this newly published research overall found little difference between these two procedures in terms of major outcome including, incidences of stroke, heart attack, and death. There were a couple of minor differences worth noting, however.

According to the authors, “The incidence of periprocedural stroke was slightly lower in the endarterectomy group than in the stenting group, whereas the incidence of myocardial infarction (heart attack) was lower in the stenting group.”

Also, they said that younger patients had, “a slightly better outcome with carotid-artery stenting and older patients having a better outcome with carotid endarterectomy.”

Dr. Solomon said, “My interpretation of the Crest Trial is that it supports the way we practice here at Columbia University Medical Center. Carotid endarterectomy is the preferred treatment for most patients with carotid stenosis, especially older patients with symptoms of carotid blockage. There are many instances where surgery is not ideal, such as patients with radiation induced stenosis, recurrent stenosis after previous endarterectomy, stenosis that is near the skull base, and certain medical conditions that contraindicate open surgery. In these patients we are gratified that stenting has been shown to be a reasonable alternative to open surgical treatment.”

Authors of this study also include: Paul Gigante; Justin Gorski; Mason Yeh; Sergei Sosunov; and Brian Y. Hwang.

Related basic science projects include an active collaboration with Dr. Carol Troy seeks to understand novel mechanisms of caspase-mediated post-ischemic neuronal cell death/survival.  In addition, recent laboratory studies are underway to study the role of the complement cascade, programmed cell death, and neurogenesis in spontaneous intracerebral hemorrhage, as well.

We have recently begun recruiting patients for an FDA-funded multicenter, phase II clinical trial aimed at assessing the safety of tiopronin in patients with aneurysmal subarachnoid hemorrhage(aSAH) and also to obtain preliminary data on the efficacy of tiopronin versus placebo in reducing serum and CSF 3AP levels in this stroke patient population. Collaborating principle investigators participating in this trial include Dr. Brian L. Hoh and Dr. J. Mocco from the Neurosurgery Department at the University of Florida, and also Dr. Louis J. Kim from the Neurosurgery Department at the University of Washington.

Other clinical research efforts include those concerning vascular re-activation of large and small cerebral vessels through the effects of subarachnoid hemorrhage and other trauma, and the auto-regulation of vessels in relation to arteriovenous malformations and other pathological vascular conditions.  In collaboration with Dr. Eric Heyer (Anesthesiology), the lab has also shown that possession of the ε4 allele of the ApoE gene (originally characterized in Alzheimer’s Diseases) is a risk factor for neurocognitive decline following carotid endarterectomy.  Researchers in the laboratory also play a pivotal role in the international effort to identify genes responsible for the formation of cerebral aneurysms.