N EWY ORK–PRESBYTERIAN

NeuroscienceAffiliated with COLUMBIA UNIVERSITY COLLEGE OF PHYSICIANS & SURGEONS and WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY August 2003

Deep Brain Endovascular Surgery Stimulation Surgery Shows Promising Results for Parkinson’s Disease iseases and malformations of the eep brain stimulation, the pow- brain’s endovascular system— erful new modality for treating Donce treatable only by invasive Dthe disabling motor symptoms and complicated surgical procedures— of Parkinson’s disease and other move- are increasingly being treated essentially ment disorders, has become the proce- from within using a procedure known as dure of choice at the Center for endovascular surgical neuroradiology. Movement Disorders Surgery at “We’re brain plumbers,” noted Philip Columbia Presbyterian Medical Center, Meyers, MD. “If the pipes are leaking, and at the Center for Stereotactic and we plug the leak; if the pipes are Functional Neurosurgery at NewYork clogged, we unclog them. All joking Weill Cornell Medical Center. It has aside, endovascular surgical neuroradiol- largely supplanted tissue ablation proce- ogy is a very important and rapidly dures, which had been the standard as growing specialty in major medical cen- recently as the 1990s. ters across the United States.” “We have converted, almost totally, With an array of high-tech tools— from doing lesions to stimulator glues, coils, tubes, balloons, and even see Deep Brain Stimulation, page 5 tiny “umbrellas”—researchers at NewYork-Presbyterian Hospital are, as Dr.Meyers would say, “plumbing” the INSIDE depths of the brain’s blood vessels. Along the way, their innovations and Computed Tomography Perfusion studies have made them recognized Engineering advances and continued research world leaders in the treatment of stroke, have made CT perfusion scanners better aneurysms, arteriovenous malforma- diagnostic tools for the ER setting 2 tions, and carotid stenting for opening Gene Therapy the neck’s plaque-choked artery. Researchers have launched the first human “One of the biggest and most dramatic clinical study investigating the efficacy of gene things we do is to take care of intracra- 4therapy in the treatment of neurologic disorders nial aneurysms, ruptured or unrup- Noninvasive Radiotherapy tured,” said Howard A. Riina, MD. Painless and noninvasive radiotherapy is being “The endovascular way of treating explored as an alternative to neurosurgery for aneurysms is by coiling them.” Aneurysm, before and after: 6patients with intractable temporal lobe epilepsy Developed in 1990 by Guido Guglielmi, The endovascular way of treating t-PA in Stroke Treatment MD, the Guglielmi Detachable Coil is a aneurysms involves the Guglielmi Researchers at NewYork–Presbyterian Hospital are tiny, flexible platinum coil placed into an Detachable Coil. By packing the seeking to expand the window for use of aneurysm via catheter. By packing the aneurysmal sac, the coil induces 7intravenous tissue plasminogen activator in stroke aneurysmal sac, it induces clotting and clotting and scarring to remove the see Endovascular, page 11 aneurysm from circulation. Emergency Treatments for Cerebral Hemorrhage Studies are revealing opportunities to provide patients suffering from intracerebral hemmorhage 9with more than supportive care in the ER NNeuroscienceEWY ORK–PRESBYTERIAN Computed Tomography Perfusion: Improving Stroke Diagnosis and Treatment

troke’s status as the third leading valuable uses for CT perfusion—acute cause of death in the United States stroke evaluation in the ER and treat- Shas served to spur researchers to ment of the post-stroke patient in the find safe and effective tools for its diag- intensive care unit. nosis and treatment. To some, computed “CT perfusion changes can be seen tomography (CT) scans have often been sooner after stroke onset than CT low- seen as somewhat of a “down and dirty” density changes, allowing earlier diagnosis radiologic tool when compared to and treatment,” said Dr. DeLa Paz. He positron emission tomography (PET) added that the technology is also useful in scans, single-photon–emission CT scans, monitoring the reduction of blood flow to and magnetic resonance imaging (MRI). the brain that may be produced by pro- Thanks to engineering advances and gressive vasospasm, which can result from continued research, much of which is subarachnoid hemorrhage. being done at NewYork-Presbyterian Dr.Sanelli believes that CT perfusion Hospital, CT perfusion scanners now helps physicians to better “estimate the show numerous advantages over other risk of developing vasospasm and diagnostic tools, particularly in the A CT angiogram shows right middle stroke” by providing actual numbers for diagnosis and safer treatment of emer- cerebral artery occlusion with large such parameters as cerebral blood flow parietal collaterals. gency room and intensive care unit and mean transit time. She admits that patients already in stroke or facing on very aggressive drips that can’t be catheter angiography is the gold stan- cerebral hemorrhage. interrupted, the enclosed MRI tube can dard for vasospasm evaluations, but it is According to Pina C. Sanelli, MD, present a major obstacle,” added Igor also an invasive procedure, which pres- while PET scans have remained the Ougorets, MD. “By comparison, CT ents increased risks for patients. As a gold standard for the evaluation of cere- perfusion makes it easier to prepare the result, NewYork Weill Cornell Medical bral blood flow and brain metabolism patient and the exam takes about 30 Center has been involved for more than for many years, they have often been a seconds—versus 10 minutes in MRI— a year in a new institutional review nonviable option for analyzing the to perform. You also have full access to board–approved protocol to use CT stroke patient in the emergency room or the patient, so if something happens, the perfusion to “provide us with informa- intensive care unit after hours or on the doctor or the technician can jump in to tion as to when patients are developing weekend because of their limited avail- treat the patient, fix a line, etc. CT vasospasm and need an angio,” noted ability and the need for prior prepara- perfusion is definitely more user-friendly Dr.Sanelli. “We feel that with CT per- tion of the radioactive tracer. Therefore, for the critically ill patient.” fusion we can image areas of the brain she said, other modalities such as CT that may be undergoing end-vessel and magnetic resonance perfusion have Monitoring Vasospasm vasospasm.” Historically, this has been emerged as promising tools for physi- Led by Robert DeLa Paz, MD, neurol- difficult information to obtain, even cians.“When you’re dealing with some- ogists at Columbia Presbyterian Medical with catheter angiography. one connected to multiple lines and/or Center have discovered 2 increasingly The All-in-One Debate A critical question facing doctors who “CT perfusion changes can be seen sooner after stroke onset treat stroke patients is how much of the brain has been infarcted and how much is than computed tomography low-density changes, allowing still treatable ischemic penumbra. “If the earlier diagnosis and treatment.” diffusion-weighted imaging lesion is smaller than the perfusion-weighted —Robert DeLa Paz, MD imaging abnormality, there is a potentially treatable stroke penumbra,” said Dr. DeLa

2 Clinical debate has NewYork-Presbyterian Neuroscience is a publication of the Neuroscience Centers of NewYork- centered around whether Presbyterian Hospital. The Neuroscience Centers are at the forefront of research and practice in the diagnosis, treatment, and rehabilitation of neurologic disease. NewYork-Presbyterian Hospital it is possible for CT is located at Columbia Presbyterian Medical Center and NewYork Weill Cornell Medical Center. The Neuroscience Centers include the Neurological Institute at Columbia Presbyterian perfusion to provide both Medical Center and the NewYork Weill Cornell Neuroscience Institute, which are respectively diffusion-weighted affiliated with Columbia University College of Physicians & Surgeons and the Weill Medical College of Cornell University. imaging and perfusion- weighted imaging data. NewYork-Presbyterian Neuroscience Editorial Board:

M.Flint Beal, MD Michael O’Dell, MD Neurologist-in-Chief, NewYork- Associate Chief, Department of Presbyterian Hospital at NewYork Weill Rehabilitation Medicine, NewYork- Paz. “If diffusion-weighted imaging versus per- Cornell Medical Center Presbyterian Hospital at NewYork Weill fusion-weighted imaging is the same or larger, Anne Parrish Titzel Professor of Neurology Cornell Medical Center and Chairman, Department of Neurology, Associate Chief and Professor of we conclude the tissue’s blood supply has been Weill Medical College of Cornell University Rehabilitation Medicine, Weill Medical reduced too long or that the body has reperfused [email protected] College of Cornell University that tissue and we’re too late to do anything.” [email protected] Y. Pierre Gobin, MD Clinical debate in this area has centered Director, Division of Interventional Timothy Pedley, MD around whether it is possible for CT perfusion Neuroradiology, NewYork-Presbyterian Neurologist-in-Chief, NewYork- to provide both diffusion-weighted imaging Hospital at NewYork Weill Cornell Presbyterian Hospital at Columbia and perfusion-weighted imaging data alone Medical Center Presbyterian Medical Center (as postulated by Wintermark et al in Professor of Radiology in Neurological Henry and Lucy Moses Professor of Switzerland [Adv Neurol 2003;92:389-400]). Surgery, Weill Medical College of Neurology and Chairman, Department of Cornell University Neurology, Columbia University College of According to Dr. DeLa Paz, researchers at [email protected] Physicians & Surgeons Columbia Presbyterian Medical Center have [email protected] used Dr. Wintermark’s methods and failed to Sean Lavine, MD obtain “a reliable discrimination between the Co-Director, Neuroendovascular Services, Howard Riina, MD NewYork-Presbyterian Hospital at Columbia Attending Neurosurgeon, NewYork- two.” But at NewYork Weill Cornell Medical Presbyterian Medical Center Presbyterian Hospital at NewYork Weill Center, according to Dr. Sanelli, preliminary Assistant Professor of Neurological Surgery Cornell Medical Center data in this area have “demonstrated the relia- and Radiology, Columbia University College Assistant Professor of Neurological Surgery, bility and reproducibility of CT perfusion” of Physicians & Surgeons Neurology and Radiology, Weill Medical alone for delineating the cerebral infarct core, [email protected] College of Cornell University [email protected] making it a useful tool in analyzing stroke James Lieberman, MD patients in emergency situations. Physiatrist-in-Chief, NewYork-Presbyterian Robert Solomon, MD It should be noted that the more limited Hospital at Columbia Presbyterian Chairman and Director of Service, brain coverage provided by CT perfusion is Medical Center Department of Neurological Surgery, another consideration for making it reliable in H.K. Corning Professor and Chairman, NewYork-Presbyterian Hospital at Rehabilitation Medicine, Columbia Columbia Presbyterian Medical Center diffusion-weighted imaging and/or perfusion- University College of Physicians & Surgeons Byron Stookey Professor of Neurological weighted imaging differentiation. “Would I [email protected] Surgery, Columbia University College of like to have an 8-slice image of the brain as I Physicians & Surgeons Philip Meyers, MD do with MRI? Yes,” said Dr. Ougorets. “But I [email protected] Co-Director, Neuroendovascular Services, now have 4 slices with the CT perfusion NewYork-Presbyterian Hospital at Columbia Philip Stieg, PhD, MD where I used to have 1.” That said, Dr. Presbyterian Medical Center Neurosurgeon-in-Chief, Department of Ougorets added that he has no reason to Assistant Professor of Neurological Surgery Neurological Surgery, NewYork-Presbyterian believe that in a few years CT perfusion won’t and Radiology, Columbia University College Hospital at NewYork Weill Cornell give him those 8 slices. of Physicians & Surgeons Medical Center [email protected] Professor and Chairman, Department of Risking t-PA Neurological Surgery Weill Medical College of Cornell University Using CT perfusion to determine the viabili- [email protected] ty of intra-arterial delivery of tissue plasmino- gen activator (t-PA) is another area researchers at Columbia Presbyterian Medical Center have been exploring. The suggested timeline for safe and effective stroke treatment using www.nypneuro.org t-PA is within the first 3 hours after onset. see CT Perfusion, page 10

3 NNeuroscienceEWY ORK–PRESBYTERIAN Studying Gene Therapy in the Treatment of Neurologic Disorders

ISORDERS esearchers at NewYork- Nature Genetics (1994;8:148-154). procedures, bioengineered cells will

D Presbyterian Hospital have Adeno-associated virus subsequently renormalize neurochemical circuits R launched the first clinical study became and remains widely used in gene without damage to tissue or insertion investigating the safety and efficacy of therapy experiments. of an electronic device. A patient gene therapy in the treatment of neuro- The disabling motor symptoms of undergoes a stereotactic procedure after logic disorders in human patients. The Parkinson’s disease arise, it is believed, extensive imaging and preparation, Phase I trials, which involve surgical from excessive neuronal firing in con- which leaves within the brain only the

OVEMENT insertion of viral vectors into cells of the sequence of a chemical disturbance in modified adeno-associated virus. subthalamic nucleus, are targeting the brain due, in the last analysis, to Dr.Kaplitt and his colleagues M patients suffering from the major motor loss of dopaminergic neurons. One of planned the surgical intervention in symptoms of Parkinson’s disease. If suc- dopamine’s functions is to regulate out- detail and undertook animal studies, cessful, the therapy has broader implica- put of the inhibitory neurotransmitter the success of which led to efforts to tions for other neurologic and brain- known as gamma-aminobutyric acid. gain approval for human trials. The related disorders. Dr.Kaplitt and others believed that proposal advanced through the For Michael Kaplitt, MD, PhD, restoring gamma-aminobutyric acid to National Institutes of Health’s co–principal investigator on the study, the trials open a new chapter in his per- sonal research efforts in the area, which “The concept of using gene therapy for Parkinson’s disease date from the late 1980s. “The concept evolved over the course of more than a decade.” of using gene therapy for Parkinson’s disease evolved over the course of more —Michael Kaplitt, MD, PhD than a decade,” said Dr. Kaplitt. When he began looking into the con- cept at Rockefeller University in 1989, Dr.Kaplitt and his team—and several specific areas of the basal ganglia could, Recombinant DNA Advisory other groups—were seeking to develop in principle, reduce the motor symp- Commission, where it gained enthusi- workable viral delivery systems that tar- toms of Parkinson’s disease, and that astic support, and the FDA approved it geted the brain. All exploited the natu- this plausible long-term solution might in August 2002. Matthew J. During, ral infectivity of viruses together with be implemented by introducing modi- MD, co–principal investigator with Dr. recently developed tools of recombinant fied recombinant viruses equipped with Kaplitt and Professor of Molecular DNA research. They found that genes the gene that expresses the gamma- Medicine at the University of that produce specific enzymes could be aminobutyric acid–producing enzyme Auckland, in New Zealand, empha- inserted into viruses disposed by nature glutamic acid decarboxylase. sized that these Phase I trials are still to integrate cellular DNA. With this concept firmly in mind, Dr. experimental. “Our primary objective Adeno-associated virus, which Dr. Kaplitt and colleagues worked to devel- has been to stress patient safety above Kaplitt also studied, was one of a num- op a stereotactic procedure that would all else,” he said. “It is our hope that, ber of candidate vectors in the early deliver these viral vectors specifically to with this approach, our trial will help 1990s. Researchers found it had several the basal ganglia cells that could nor- demonstrate that gene therapy in the advantages for gene therapy. A harmless malize the gamma-aminobutyric acid brain can be both safe and effective.” virus, adeno-associated virus does not circuitry. Since the 1980s, neurosur- provoke antibodies or stimulate inflam- geons had enjoyed new success both in Michael Kaplitt, MD, PhD, is Surgical mation, and it is able to enter nondivid- targeting highly specific areas of the Director, Movement Disorders Group, ing cells such as neurons. After several brain and in treating symptoms by NewYork-Presbyterian Hospital at NewYork Weill Cornell Medical Center, and is years of work, Dr. Kaplitt and colleagues ablating tissue or, more recently, by Assistant Professor of Neurological Surgery at reported the first use of adeno-associat- employing deep brain stimulation. Weill Medical College of Cornell University. ed virus in the mammalian brain in Now, it is hoped that in place of these E-mail: [email protected].

4 OVEMENT ISORDERS M D 5 see Deep Brain Stimulation, page 12 ing deep brain stimulation, the r llman, MD, handles the same duties esbyterian Medical Center, and by Dr. aplitt at NewYork Weill Cornell Weill aplitt at NewYork Once the electrode is anchored in the is anchored Once the electrode Du urgery. is itself The surgical procedure lavicle. (This can be done on the same A patient undergoing deep brain A patient undergoing stimulation surgery:inserts The surgeon through burr electrodes into the brain holes in the skull. The electrodes reach their targets with the help of magnetic resonance imaging and brain mapping with microelectrodes. patient remains awake and helps the patient remains surgical placement electrode team guide by answering various questions con- cerning symptoms and sensations. For patients with bilateral symptoms, elec- insertiontrode is performed on both sides of the brain. brain, its lead is attached to the inside of the skull, is and a connecting wire laid in behind the ear and neck, leading to the chest, a battery-operated where implantable pulse generator is placed in a surgically pocket created beneath the c performed by Dr. or Guy Goodman McKhann, MD, at Columbia Pr K Medical Center. done by Shaik Ubaid, MD. Seth Pu Disorders at the Center for Movement S Candidates for deep brain stimulation usually sufferCandidates for deep brain stimulation from the disease that arise in advanced motor symptoms of Parkinson’s of initial diagnosis. most patients within 5 to 10 years Like the lesion-based procedures that Like the lesion-based procedures Crucialbrain of deep success to the unctional Neurosurgery, is this work ounger patients tend to have the best esults, advanced age alone is not a con- Blair Ford, MD, can almost always ben- if they deep brain stimulation efit from in good general health.are Although y r traindication to surgery. it has largely replaced, deep brain stimu- operation in lation is a stereotactic which a coordinate system enables the surgeon to target a specific location in the brain with millimeter-by-millimeter accuracy. However, instead of tissue lesions that reduce ablation to create motor symptoms, the surgeon inserts burr into the brain through electrodes holes in the skull. Brain mapping proce- placement of the proper to ensure dures performed are by neurolo- stimulators gists with expertise technique. in this At the Center for Stereotactic and F stimulation are comprehensive patient comprehensive are stimulation screening, preparation, education, and postoperative care. and preoperative for deep brainCandidates stimulation usually motor the advanced suffer from that disease symptomsof Parkinson’s arise in most patients within 5 to 10 years of initial diagnosis. Although these invariablypatients are helped at first by levodopa—still medication the standard disease—their response for Parkinson’s to the drug eventually becomes prob- lematic or unpredictable, and other medications to help. fail Sometimes a dose of levodopa will fail to control symptoms only or work intermittently, “wearingwith spells of off ” levodopa as ceases to work, during which patients become stiff or unable to move. Other rapid motor fluctu- patients suffer from dyskinesias,ations or from the most dis- abling of motor symptoms, that involves involuntary muscle contractions in the extremities, head, or trunk. at Patients this stage of the disease,to according y approved by the Food and Drug the Food by y approved ll imulation kinson’s disease patients for whom kinson’s r er the past few years indicates that dministration (FDA) in 2002 after dministration (FDA) Fu Michael Kaplitt, MD, PhD, who per- tereotactic and Functional Neurosur- and Functional tereotactic ated lesion-based techniques that for Blair Ford, MD, consults with a disease patient: “The care for Parkinson’s these patients needs to be comprehensive, and optimally carried out in a context an accumulation of where there’s expertise, clinical experience, and institutional resources.” considerable in the lay media coverage press, has rapidly deep brain stimulation defined a new standard of care among Pa signif- medication has ceased to provide icant relief. is Deep brain stimulation not a cure, but for the rightthe patients can substantiallyprocedure reduce qualitymotor symptoms and improve of life.that can be postopera- A procedure tively and adjusted to indi- programmed vidual patients, deep brain stimulation has quietly and rapidly supplanted thal- amotomy and pallidotomy, 2 sophisti- c state-of- the past 2 decades represented the-art surgery for advanced Parkinson’s disease. These procedures, although quite frequently effective, carry various of riskdegrees that deep brain stimula- tion largely avoids. gery, added, of our experience “all that ov better tolerated than are stimulators effects.”lesions and have longer-lasting A implants,” according to Robert Goodman, MD. Center for at the forms the procedure S continued from page 1 continued Deep BrainDeep St NNeuroscienceEWY ORK–PRESBYTERIAN Investigating Noninvasive Radiotherapy in Temporal Lobe Epilepsy

esearchers at NewYork- and eventual neoplasms—remains. In Presbyterian Hospital’s Center addition, for reasons that are still R for Movement Disorders unclear, patients only gradually become Surgery believe painless, noninvasive free of seizures. While the effects of radiotherapy can become a viable alter- neurosurgery are immediate, benefits native to neurosurgery for patients with from the gamma knife in epilepsy intractable temporal lobe epilepsy. appear over several months. “This treatment may prove just as Temporal lobe epilepsy patients in the effective as surgery for at least some of current study, when offered the gamma the patients that we treat,” says Robert knife option, still decided on invasive Goodman, MD. Dr. Goodman and his surgery approximately half the time. “By surgical team are currently participating A CT scan of a patient with temporal the time they’re being recommended for in a multicenter study to determine the lobe epilepsy–induced left medial surgery, they want to have it yesterday,” effectiveness of gamma knife radio- temporal sclerosis. said Dr. Goodman. “So if we suggest surgery in temporal lobe epilepsy, with treat vascular abnormalities and brain treatment with radiation, which takes 9 preliminary results expected within a tumors for which resection is not an to 10 months, they don’t want that year. The research is supported by the option. With improved understanding delay.” In addition, he added, these National Institutes of Health. of brain structure and neurochemical patients are often relatively young and Surgery remains the accepted treat- interactions, the gamma knife is cur- may also have concerns about long-term ment for patients with refractory tem- rently on track to treat several move- adverse effects of radiation. poral lobe epilepsy. Dr. Goodman’s ment disorders, including Parkinson’s Use of the gamma knife for temporal study offers patients the radiologic disease. To date, the procedure has been lobe epilepsy does not rule out subse- option as an alternative to conventional used to treat temporal lobe epilepsy in a quent neurosurgery if the patient does surgery. The larger aim is to discover small number of cases in Europe and not become seizure-free. As with other whether and to what extent the gamma the United States. forms of surgery, if successful, the knife can effectively eliminate symptoms Epilepsy affects about 1 million people gamma knife may have other advan- while reducing or avoiding the risks of in the United States, an estimated tages. A current hypothesis holds that functional impairment that come with 100,000 of whom become candidates for surgery may confer a neuroprotective invasive neurosurgery. surgery when medication fails to ade- benefit, and some evidence suggests that “We might learn we can eliminate the quately control seizures. Lesionectomy patients who become seizure-free at a seizure potential without eliminating all and other operations, ranging from cura- young age avoid a variety of associated of the function in the part of the brain tive to palliative, aim to reduce or elimi- psychologic and psychosocial problems. operated on,” noted Dr. Goodman. nate seizures. Aided by advances in brain If the gamma knife provides these bene- Gamma knife radiosurgery involves imaging, surgical procedures currently fits without the risks of invasive proce- use of a multi–million-dollar system (it enjoy high rates of success overall. But dures, it may become a widely used weighs 20 tons) that delivers highly with an estimated 1% mortality rate and alternative in a rapidly advancing field. focused beams of cobalt-60 radiation to postoperative complications as high as 3-dimensional pinpoint targets within 10% to 20%, a noninvasive alternative Robert Goodman, MD, is Surgical Director, Center for Movement the brain. Therapeutic benefits accrue would be welcome. Disorders Surgery, NewYork- over time, presumably due to radiation- Although painless and bloodless, Presbyterian Hospital at Columbia induced changes in cell function and gamma knife radiosurgery is not with- Presbyterian Medical Center, and is metabolism. Developed in Sweden in out risk. While the procedure has Assistant Professor of Neurological the 1960s, the instrument has been proved safe in other uses, concern for Surgery at Columbia University College employed for years by neurosurgeons— complications—including radiation of Physicians & Surgeons. E-mail: sometimes with outstanding success—to necrosis and edema, neurologic deficits, [email protected].

6 Expanding t-PA’s Use in Stroke Treatment eurosurgeons and interventional “There have also been some prelimi- where it deploys a self-expanding coni- neuroradiologists at NewYork- nary studies on using intra-arterial cal coil. The coil becomes so enmeshed NPresbyterian Hospital are at the urokinase,” said Dr. Lavine. The drug, in the clot that it can be dragged away forefront of efforts to widen the window approved by the FDA in October 2002 when the catheter is removed. of opportunity for treating stroke for treating clots in the heart, is already The MERCI I trial, involving 50 patients. The medical treatment current- ly approved by the FDA for hemorrhag- ic stroke—intravenous tissue plasmino- “There have also been some preliminary studies on using intra- gen activator, or t-PA—can be given arterial urokinase [in stroke treatment.] We’re hoping to only within the first 3 hours after the improve the chances of a good outcome by 30% to 50% onset of symptoms. As a result, only 2% to 3% of patients who can benefit from when it’s used in that 6-hour time frame.” the treatment actually receive it. —Sean Lavine, MD “If we get to them within those first 3 hours with intravenous t-PA, there’s a 30% improvement in morbidity and mor- tality,” said Sean Lavine, MD. Beyond 3 showing results comparable to those patients at 7 centers across the United hours, he added, the risk of the drug’s with intra-arterial t-PA when used in States, established that the device could causing a devastating hemorrhage in the the brain, he said. “We’re hoping to be safely used up to 8 hours after the brain outweighs any possible benefit. improve the chances of a good outcome onset of symptoms. In 52% of the cases, The need to find effective interven- by 30% to 50% when it’s used in that 6- the clot was successfully retrieved with tions beyond those first 3 hours couldn’t hour time frame,” he added. the device. Just 2% of patients had a be greater. Intracranial hemorrhage is Ultimately, though, “you would prefer major complication during the procedure. the third leading cause of death and the to not give any thrombolytic at all, Now in a Phase II trial at 20 centers primary cause of adult disability in the because even when delivered intra-arte- across the United States, the MERCI United States, making it the leading rially, it still raises the risk of bleeding,” device has been used on 80 patients. diagnosis for patients moving from hos- said Y. Pierre Gobin, MD. “We are reporting a 55% recanaliza- pitals to nursing homes. The standard To find a better way to clear neurologic tion rate of cerebral arteries,” Dr. Gobin strategy now used at NewYork- emboli, Dr. Gobin invented a device, the said. “Half of the patients that were Presbyterian Hospital’s advanced treat- Concentric Retriever, that is being exam- recanalized have a great recovery and are ment centers when patients show up ined in the Mechanical Embolus able to live independently.” within 3 to 6 hours after the onset of Removal in Cerebral Ischemia (MERCI) Dr.Lavine, who has been using the symptoms is the application of t-PA Trial at NewYork-Presbyterian Hospital. MERCI device, added, “I think it’s a promising, excellent idea. This device is one of the very few tools we have.” One Y. Pierre Gobin, MD, has developed the Concentric Retriever to challenge with using the device, he said, clear neurologic emboli. To use the system, neuroendovascular is that the coil needs to be stiff enough therapists guide a microcatheter beyond the site of the clot, to hang onto the clot yet flexible enough to negotiate the twists and turns of the where it deploys a self-expanding conical coil. The coil becomes neurovasculature. “To be effective, the so enmeshed in the clot that it can be dragged away when the device has to have some stiffness,” Dr. catheter is removed. Says Dr. Gobin, “When you reopen the Lavine explained. “But that comes at the expense of having more difficulty navi- artery this way, there’s almost no risk of hemorrhage.” gating to get it where you want it to go.” As a result, the MERCI device has evolved as neurosurgeons such as Dr. Lavine, Dr. Gobin, and others have directly to the site of the clot, via a radi- “It’s much better to open the artery gained experience with it. In the latest ologically guided catheter. Intra-arterial with a MERCI device,” Dr. Gobin incarnation, Dr. Gobin said, “we are t-PA has the added benefit of allowing said. “When you reopen the artery using a nitinol coil, a special metal made the physician to pump higher concen- with MERCI, there’s almost no risk of super-elastic material, to snare and trations of the drug into the confines of of hemorrhage.” remove the thrombus that is occluding the blockage than could ever be safely To use the mechanical system, neuro- the artery in the brain.” Nitinol, an alloy delivered to the entire body intra- endovascular therapists guide a micro- of nickel and titanium, is in a unique venously. catheter beyond the site of the clot, see t-PA, page 10

7

Emergency Treatments for Cerebral Hemorrhage ntracerebral hemorrhage represents centers, Dr. Mayer and his colleagues rhage and subarachnoid hemorrhage,” 15% of all strokes in the United have been involved in a Phase II study he said, adding that conventional cooling IStates. It is also among the deadliest enrolling 46 patients. The study’s pur- blankets have been shown to be ineffec- and most disabling forms of stroke. pose is to evaluate the risks and benefits tive in reducing fever for these patients. More than 40% of intracerebral hemor- of a combination therapy: placing the Dr.Mayer and his colleagues are cur- rhage patients die within 6 months or catheter and “examining the potential rently conducting a clinical trial of the suffer devastating impairment. efficacy of direct intraventricular throm- Medivance Arctic Sun Cooling System. Unfortunately, there are still no effec- bolytic therapy using tissue plasminogen The device seems to normalize body tem- tive treatments—including surgery—for activator.” Because there is overwhelm- perature more effectively than conven- intracerebral hemorrhage or other forms ing evidence that clotted blood can be tional cooling blankets. A hydrogel poly- of cerebral hemorrhage. Nevertheless, toxic, he added, “the hope is that by mer provides enhanced contact with the researchers at NewYork-Presbyterian effectively lysing the clot and promoting patient’s skin, allowing the water-circulat- Hospital say, studies are revealing its clearance, patients will suffer less ing blankets to stick to the body and thus opportunities for physicians to provide damage due to reduced duration of con- maintaining the cooling process more their patients with more than just sup- tact with potential toxic blood elements effectively than conventional means. portive care. (e.g., hemoglobin and thrombin).” “It’s about pushing the envelope, find- ing better ways to treat the patients,” Only Preliminary Results said Stephan A. Mayer, MD. “We’re At NewYork Weill Cornell Medical looking for the cutting-edge protocols.” Center, Igor Ougorets, MD, is currently Dr.Mayer points to 2 ongoing trials using a treatment method that involves exploring therapies to help patients cope controlling hyperglycemia in his with hemorrhage. Physicians at Columbia patients. “Some animal studies have Presbyterian Medical Center are looking indicated that hyperglycemia produces A head CT scan demonstrating a left-sided at recombinant factor VIIa as a possibility more neuro-injury in ischemic tissue,” basal ganglia hemorrhage (left). A follow- for arresting ongoing bleeding in intrac- he explained. “The problem is that in all up CT obtained after the patient further erebral hemorrhage emergency room these areas all we have is preliminary deteriorated (right) shows significant patients. In fact, Columbia Presbyterian data. We don’t yet have the study that enlargement of the hematoma. Medical Center is part of a worldwide, takes neuro-injured patients on a tightly multicenter trial testing the potential effi- controlled glucose level and compares cacy of recombinant human coagulation them with a group that was not con- “Using regular cooling blankets, factor VIIa as an ultra-early hemostatic trolled to see if the glucose control patients’ body temperature remains over therapy for brain hemorrhage. changes the neurological outcome.” 101°F,” said Dr. Mayer. “With this sys- The preliminary dose escalation safety To date, according to Dr. Ougorets, tem, they go right down to normal, and study, which treated 86 patients, offered treatment protocols for hemorrhage stay there.” The unexpected benefit of “some indication of efficacy,” said Dr. have not been based on the results of the system, he added, seems to be that Mayer. Because of those results, the randomized trials but on the personal “effective treatment of fever can produce department has initiated a proof-of- experience of neurologists in the field. clear and dramatic improvements in concept trial with a target enrollment of All the researchers hope to change that, intracranial pressure levels, and in 240 (it now has 186). That trial started however, with their recent efforts. patients’ levels of consciousness.” in January. Researchers at Columbia Presbyterian Looking at Body Temperature Stephan A. Mayer, MD, is Director of the Medical Center are also exploring “Everyone agrees that overall tempera- Neurological Intensive Care Unit, NewYork- Presbyterian Hospital at Columbia options for treating a subset of intra- ture control has to be done,” said Dr. Presbyterian Medical Center, and is Assistant cerebral hemorrhage patients: patients Ougorets. “The problem is that we don’t Professor of Neurological Surgery at with intraventricular hemorrhage. have clear-cut trials showing that it Columbia University College of Physicians Current procedure calls for inserting a actually makes a difference in the out- & Surgeons. E-mail: [email protected]. ventricular catheter, noted Dr. Mayer, come of our patients.” but physicians in the Neurological Another critical issue is the treatment Igor Ougorets, MD, is Director of the Intensive Care Unit recognize that of fever in patients with hemorrhagic Neurological Intensive Care Unit, NewYork- “simply placing a catheter may be life- stroke, according to Dr. Mayer. “Body Presbyterian Hospital at NewYork Weill saving, but otherwise doesn’t appear to temperature elevations are independently Cornell Medical Center, and is Assistant Professor of Neurological Surgery at Weill substantially benefit patients.” correlated with death and poor functional Medical College of Cornell University. That’s why, in conjunction with other outcomes after both intracerebral hemor- E-mail: [email protected].

9 NNeuroscienceEWY ORK–PRESBYTERIAN “On the engineering side, it can be the result will one day mean a revolution t-PA very exciting to work with smart materi- in the treatment of cerebral infarction. continued from page 7 als like that,” Dr. Lavine said. That day can’t come soon enough for the Both he and Dr. Gobin emphasized estimated 750,000 people in the United class of materials known as shape memo- that the procedure remains experimental. States who suffer a stroke each year. ry alloys. After being heat treated while But Dr. Gobin predicted that it will in a particular position, it can be bent eventually become the treatment of Y. Pierre Gobin, MD, is Director of the and distorted, then reheated to regain its choice at hospitals specializing in the Division of Interventional Neuroradiology, NewYork-Presbyterian Hospital at NewYork original shape. Thus, the device can be treatment of stroke. “Most treatments Weill Cornell Medical Center, and is advanced within a microcatheter inside for stroke will be mechanical, with a Professor of Radiology in Neurological the cerebral artery occluded by the clot. MERCI device,” he said. If this is true, Surgery at Weill Medical College of Cornell University. Email: [email protected].

Sean Lavine, MD, is Co-Director of Neuroendovascular Services, NewYork- Current work at NewYork-Presbyterian Hospital could one day Presbyterian Hospital at Columbia mean a revolution in the treatment of cerebral infarction. That Presbyterian Medical Center, and is day can’t come soon enough for the estimated 750,000 Assistant Professor of Neurological Surgery, and is Radiology at Columbia University people in the United States who suffer a stroke each year. College of Physicians & Surgeons. E-mail: [email protected].

not correlated with a measure of poten- CT Perfusion tially salvageable tissue. Using CT per- continued from page 3 fusion to determine how much viable brain exists and to generate constructive “Would I like to have an Delivery even 5 or 6 hours out escalates maps of cerebral blood flow, blood vol- 8-slice image of the brain the risk of hemorrhage dramatically, ume, and mean transit time is a boon to as I do with MRI? Yes. But from 5% to as much as 30% or 40%. doctors treating stroke patients. Having served on some of the safety “Clinical science will only get you so I now have 4 slices with committees analyzing the 3-hour far,” said Dr. Ougorets. “You need addi- the computed tomography “deadline,” Dr. DeLa Paz believes this tional information to appreciate what’s where I used to have 1.” to be an artificial timeline that can be happening to the brain tissue.” expanded. The key is using intra-arteri- —Igor Ougorets, MD al administration of t-PA versus intra- Robert DeLa Paz, MD, is Director of Neuroradiology, NewYork-Presbyterian venous delivery. Using an intra-arterial Hospital at Columbia Presbyterian catheter, he explained, “the lysis of Medical Center, and is Professor of occluding thrombus in the cerebral ves- Radiology at Columbia University sels and reconstitution of blood flow to College of Physicians & Surgeons. the ischemic brain” may be achieved in E-mail: [email protected]. only 20 or 30 minutes. That, he says, means that intra-arterial delivery of t-PA Igor Ougorets, MD, is Director of the Pina C. Sanelli, MD, is Assistant could begin as much as 4 or 5 hours Neurological Intensive Care Unit, Attending Physician, NewYork- after onset and still provide effective NewYork-Presbyterian Hospital at Presbyterian Hospital at NewYork Weill NewYork Weill Cornell Medical Cornell Medical Center, and is results with a low risk of hemorrhage. Center, and is Assistant Professor of Assistant Professor of Radiology, However, intra-arterial delivery of t-PA Neurological Surgery at Weill Medical Neuroradiology Division at Weill carries a much higher risk of hemor- College of Cornell University. E-mail: Medical College of Cornell University. rhage than intravenous delivery if it is [email protected]. E-mail: [email protected].

10 Endovascular NewYork-Presbyterian Hospital can investigator. Those numbers, he added, either cauterize the abnormal tangle of “look as good as surgery, maybe even continued from page 1 blood vessels, or deploy the new glue better, without having to perform sur- Neuracryl M that hardens slowly and gery.” Other studies of similar debris- scarring to remove the aneurysm from cir- smoothly. One of the hottest areas of catching devices include the Acculink culation. Research has shown that, com- research is the endoscopic widening of for Revascularization of Carotids in pared with surgery, the Guglielmi a plaque-clogged carotid artery, with High-Risk patients (ARCHeR) and the Detachable Coil treatment significantly the use of a stent to keep the artery Boston Scientific EPI: A Carotid lowers the risk of subsequent severe dis- clear. Until recently, the endovascular Stenting Trial for High-Risk Surgical ability or death from a ruptured aneurysm. method was used only for patients too Patients (BEACH). “The study was so overwhelmingly in sick to undergo surgery, because when According to Sean Lavine, MD, it’s favor of coiling that the safety commit- performed from within, the procedure still too early to tell which of the devices tee of the trial stopped enrolling new can dislodge plaque that would then will eventually be most effective—or patients,” said Y. Pierre Gobin, MD. travel up the bloodstream into the even whether any of them will ultimate- Dr.Gobin, who worked for 10 years brain, where it could cause a stroke. But ly prove safer than surgery. There are with Dr. Guglielmi at the University a new invention offers the possibility of “data on both sides,” Dr. Lavine said. California at Los Angeles, noted that revolutionary new safety: a tiny filter “Some say using the devices increases new designs and materials for the coil that opens like an umbrella downstream the risk of embolic events; others say are constantly being tested—including, from the stent to safely block any debris that it has dramatically reduced morbid- most recently, special coatings designed before it reaches the brain, while allow- ity. We are currently investigating the to speed the development of an ing blood to flow normally. benefit of these devices with active par- aneurysm-shutting clot. “It’s like a coffee filter for the blood, ticipation in trials such as ARCHeR, Another new technique for treating flowing into the brain when you’re BEACH, and CREST.” aneurysms involves the use of the reopening an artery in the neck,” Dr. Neuroform stent. “With certain com- Meyers said. “The filter catches any plex aneurysms, the Guglielmi debris generated during revasculariza- Y. Pierre Gobin, MD, is Director of the Detachable Coil alone may not be ade- tion of the brain’s arteries. The early Division of Interventional Neuroradiology, NewYork-Presbyterian Hospital at NewYork Weill Cornell Medical Center, and is Professor of Radiology in Neurological Surgery at Weill “The Neuroform stent is a self-expanding tube designed Medical College of Cornell University. Email: specifically for use in the brain to treat complex aneurysms in a [email protected]. way that was never possible before. Aneurysm coils can then Sean Lavine, MD, is Co-Director of be safely placed into the aneurysm without jeopardizing the Neuroendovascular Services, NewYork- Presbyterian Hospital at Columbia integrity of the main blood vessels.” Presbyterian Medical Center, and is Assistant Professor of Neurological Surgery and —Philip Meyers, MD Radiology at Columbia University College of Physicians & Surgeons. E-mail: [email protected].

Philip Meyers, MD, is Co-Director of quate,” said Dr. Meyers. “The evidence suggests that stent-supported Neuroendovascular Services, NewYork- Neuroform stent is a self-expanding angioplasty with filter protection of the Presbyterian Hospital at Columbia tube designed specifically for use in the brain’s blood supply may become a pre- Presbyterian Medical Center, and is Assistant brain to treat complex aneurysms in a ferred method of treatment over stan- Professor of Neurological Surgery and way never possible before. Aneurysm dard surgical endarterectomy.” Radiology at Columbia University College of coils can then be safely placed into the Researchers at NewYork-Presbyterian Physicians & Surgeons. E-mail: aneurysm without jeopardizing the Hospital are among the lead investiga- [email protected]. integrity of the main blood vessels.” tors in a multicenter trial of the proce- Howard A. Riina, MD, is Attending For the treatment of arteriovenous dure, called Carotid Revascularization: Neurosurgeon, NewYork-Presbyterian malformations, Dr. Meyers added, Endarterectomy versus Stent Trial Hospital at NewYork Weill Cornell Medical NewYork-Presbyterian Hospital is “one (CREST). In the early phases of the Center, and is Assistant Professor of of the largest treatment centers in the study, “the complication rate with pro- Neurological Surgery, Neurology and United States. It’s been one of the hos- tection is 2% for asymptomatic patients, Radiology at Weill Medical College of pital’s strengths for many years.” and 6% for patients with symptomatic Cornell University. E-mail: Neuroendovascular specialists at stenosis,” said Dr. Gobin, the principal [email protected].

11 Blair Ford, MD, is Medical Director turning on and adjusting the deep brain Deep Brain at the Center for Movement Disorders stimulator. Frequency, polarity, pulse Surgery, NewYork-Presbyterian Stimulation width, and voltage may all be adjusted. Hospital at Columbia Presbyterian continued from page 5 This process may take several visits over Medical Center, and is Associate weeks or even months. It is another rea- Professor of Clinical Neurology at son why Dr. Ford comes out strongly in Columbia University College of day as the electrode surgery, or some- favor of a comprehensive program like Physicians & Surgeons. He is also what later.) For bilateral operations, 2 that at Columbia Presbyterian Medical a scientific advisor to the Parkinson’s implantable pulse generators are Center. “The care for these patients Disease Foundation. E-mail: installed. Three types of deep brain needs to be comprehensive,” he main- [email protected]. stimulation can be performed: thalamic tained, “and optimally carried out in a Robert Goodman, MD, is Surgical Director, stimulation, subthalamic nucleus stimu- context where there’s an accumulation of Center for Movement Disorders Surgery, lation, and globus pallidus stimulation. expertise, clinical experience, and insti- NewYork-Presbyterian Hospital at Columbia Each type corresponds to a different tutional resources.” Presbyterian Medical Center, and is Assistant area in the brain where the stimulator is Dr.Kaplitt, MD, PhD, agreed with Professor of Neurological Surgery at placed, and each tends to alleviate spe- Dr.Ford on the importance of compre- Columbia University College of Physicians & cific symptom formations. Beginning in hensive expertise and training for deep Surgeons. E-mail: [email protected]. April 2003, Medicare agreed to cover brain stimulation. He emphasized the Michael Kaplitt, MD, PhD, is Surgical each of the 3 deep brain stimulation time and teamwork expended on each Director, Movement Disorders Group, procedures for patients who fulfill diag- patient in deciding whether a candidate NewYork-Presbyterian Hospital at NewYork nostic conditions. is suitable for surgery and in planning Weill Cornell Medical Center, and is Postoperative care after deep brain the procedure. “Collectively, it takes an Assistant Professor of Neurological Surgery at stimulation forms a crucial part of the enormous amount of experience in order Weill Medical College of Cornell University. entire procedure because it involves to get it right,” said Dr. Kaplitt. E-mail: [email protected].

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