Neuroscience Outlook

VOL. 10 | ISSUE 2

NEUROSCIENCE OUTLOOK

News and research from the Departments of Neurology and Neurosurgery at georgia regents neuroscience center

STROKE: EXPLORING NOVEL THERAPIES Bone marrow-derived stem cells promote recovery after stroke

FROM THE CHAIRMEN

DEPARTMENT NEWS

Welcome to another expanded issue of Neuroscience Outlook from both the Neurosurgery and the Neurology departments. Our publication schedule has changed from twice a year to three times a year, i.e., every four months.

In this issue we feature news items from our departments, including the recent awards to the Neurology department for teaching, and to individual members of both departments for teaching, patient care, and research, respectively.

Also newsworthy was a recent $66 million gift to the institution from one of the graduates of the Medical College of Georgia at Georgia Regents University. Additionally, William E. Mayher III, M.D., a 1970 graduate of the Neurosurgery department and board member of the MCG Foundation, was honored with a boardroom dedication and portrait unveiling.

In the research spotlight, we describe a variety of important clinical trials in acute stroke being conducted by our clinical faculty. In the clinical spotlight, we focus on minimally invasive surgery for lumbar disc disease and a minimally invasive approach to the clivus. The academic output of our departments is also chronicled.

Cargill H. Alleyne Jr., M.D. Professor and Marshall Allen Distinguished Chair of Neurosurgery calleyne@gru.edu gru.edu/neurosurgery

David C. Hess, M.D. Professor and Presidential Distinguished Chair of Neurology dhess@gru.edu gru.edu/neurology

NEUROSCIENCE OUTLOOK A publication of the Georgia Regents University Departments of Neurology and Neurosurgery Editor-in-chief: Cargill H. Alleyne Jr., M.D. Editor: Phil Malkinson Illustrations: Colby Polonsky, M.S. Contributors: David C. Hess, M.D., Askiel Bruno, M.D., Jeffrey A. Switzer, D.O., Jonathan Tuttle, M.D., Arturo Solares, M.D., John Vender, M.D.

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The Medical College of Georgia at Georgia Regents University was fortunate to receive a $66 million gift from the late J. Harold Harrison, M.D. Dr. Harrison was a 1948 graduate of the Medical College of Georgia and a vascular surgeon from Kite, Ga. This gift, one of the largest ever received by a U.S. medical school, is directed to fund student scholarships and endowed chairs for faculty.

Dr. Harrison and his wife have already contributed $10 million to the construction of a new Education Commons named in his honor.

award corner

The Department of Neurology was awarded the Outstanding Clinical Science Teaching Department from the Class of 2013.

Three faculty members from the Neurosurgery and Neurology departments (Drs. S. Dion Macomson, Elizabeth Sekul, and Jeffrey Switzer) won awards from the MCG faculty senate for teaching, patient care, and research, respectively.

Drug Warning

Study co-authored by faculty leads to FDA warning

Morris Cohen, M.D., (Department of Neurology) was a co-author of a prospective NIH study of cognitive outcomes after fetal exposure to antiepileptic drugs [Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD Study): A Prospective Observational Study. Lancet Neurology, March 12 (3):244–252, 2013; the NEAD, now MONEAD, group]. Based upon this study, the FDA has placed a warning on Valproic acid use in the treatment of migraines in women who are pregnant.

Honored Alumnus

Neurosurgery alumnus honored with Boardroom dedication

William E. Mayher III, M.D., a retired neurosurgeon and 1964 graduate of MCG and 1970 graduate of the Department of Neurosurgery, was honored in April by the Medical College of Georgia Foundation with the dedication of an Executive Boardroom and a portrait unveiling. Dr. Mayher is a board member of MCG Foundation and was its former Chairman. He has provided many years of dedicated service to the institution and has been a great friend and contributor to the Department of Neurosurgery. His portrait was painted by Georgia Regents University Emeritus Associate Professor of Medical Illustration David Mascaro.

Photos by L.B. Schnuck

Cargill H. Alleyne Jr., M.D., and David C. Hess, M.D.

Unprecedented Gift MCG at Georgia Regents University receives $66 million gift

International Connections GRU Neurosurgery fosters collaboration with health care providers and patients from other countries The Neurosurgery department has always had strong international connections. Beginning in 2006, our faculty members have served as mentors for several visitors at varying levels of training (medical students, pre-residency fellows, practicing physicians, etc.) from a variety of countries around the world, including Haiti, El Salvador, Greece, India, Egypt, Saudi Arabia, Kuwait, and Pakistan. Within the last three years, Dr. Haroon Choudhri has performed complex spinal procedures on several international patients from the latter four countries as well as patients from Canada, Puerto Rico, Algeria, United Arab

Emirates, and Afghanistan. We expect the variety of international cases to expand in the future.

In addition, Georgia Regents University has recently collaborated with Jiangsu Province Department of Health in China for the purpose of enhancing collaboration in medicine, education, health science, and research. Specifically, an observership program will be established to facilitate the education of medical doctors and other health care professionals in this Chinese province. The department of Neurosurgery is one of a handful of departments that will participate in this program beginning in summer 2013.

The map below shows the variety of nations from which GRU Neurosurgery faculty members have mentored health care providers and treated patients.

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CLINICAL SPOTLIGHT

Minimally invasive spinal surgery

by Jonathan Tuttle, M.D.

Evaluating the efficacy of minimally invasive discectomies versus open discectomies

Figure 1. Muscle sparing approach showing the lamina that will be removed with a high speed drill.

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Minimally invasive spinal surgery provides the surgeon an alternative to open procedures for spinal disorders. The benefits ascribed to minimally invasive surgery include lower surgical blood loss, decreased length of stay, and lower risk of infection.

A recent meta-analysis compared randomized controlled trials to determine the efficacy of open versus minimally invasive discectomies.1 The study results will be discussed after a short case.

A 36-year-old man presented with a four-month history of low back pain radiating down his left lower extremity to the heel and lateral aspect of his foot. He had been previously treated with NSAIDs, muscle relaxants, and ultimately epidural steroid injections, but they produced no relief. He underwent a CT myelogram as he would not agree to an MRI of the lumbar spine.

He also underwent EMG/NCV studies.

His physical exam was significant for a left-sided straight leg raise and left ankle DTR ¼. The electrodiagnostic studies revealed a left S1 radiculopathy.

His CT myelogram (figure 2) showed a left-sided disc herniation at L5-S1.

A minimally invasive discectomy was planned after a discussion of the treatment options with the patient.

NEUROSCIENCE OUTLOOK  Volume 10 | Issue 2

Figure 2. CT myelogram of the lumbar spine showing a leftsided L5–S1 disc herniation with S1 nerve root compression.

The surgery was done through an incision about 2.5 centimeters long and about 2.5 centimeters to the left of midline. Fluoroscopy was used to place the initial dilator tube and dilate up to the working channel. A K-wire was not used, because some believe its use increases the chance of a durotomy.

The operating microscope was utilized (figures 3–6).

Figure 3. Enhanced view of the lamina after removal of interlaminar paraspinal muscle.

Figure 4. Laminectomy being performed using a cylindrical coarse diamond drill bit.

Figure 5. The traversing root is identified.

Figure 6. The traversing root is retracted and the extruded disc is removed.

Figure 7. Sagittal illustration depicting a single incision for a two level bilateral hemilaminectomy.

The surgery went well and the patient was discharged home later the same day. Immediately after surgery and at the initial follow-up visit six weeks later, he had complete resolution of his radicular pain. There was no durotomy and there was no evidence of a wound infection.

Dasenbrock et al. discussed the efficacy of minimally invasive discectomy (MID) compared to open discectomy (OD).1 They included six trials with a total of 837 patients (388 randomized to MID and 449 randomized to OD). The MID trials included one full endoscopy, and two trials with tubular retractor systems with a microscope.

In the OD group, two trials did not use the microscope and the third trial randomized the patients to MID or OD. The OD in the third trial allowed a microscope or no microscope, based upon randomization.

The results showed a few statistically insignificant differences. Operative time in the OD trials was an average of five minutes shorter. Estimated blood loss was less in one OD trial whereas four MID trials reported less blood loss. Although rare, surgical site infections were noted to be higher in the three studies that recorded the data, all with an OD approach. Subsequent reoperation for recurrent disc herniation, also insignificant, was more common in the MID group.

Figure 8. Axial illustration depicting lumbar stenosis and a herniated disc as well as the decompression pathway visualized through the tube.

Dasenbrock et al. reported one significant complication difference in their meta-analysis.

The incidental durotomy rate was statistically higher in the MID group. They listed possible causes, including limited visualization, poor depth perception, and a steep learning curve; however, they noted “many of the incidental durotomies” came from the doubleblinded study. In the double-blinded study, patients had a midline incision for either MID or OD, which the authors hypothesized could have limited visualization. With regards to the sequelae, persistent CSF leakage with subsequent reoperation was performed on two MID patients compared with three OD patients.

In regards to short- and long-term outcomes, Dasenbrock et al. reported the VAS scores were not significantly different between the MID and OD approaches. Likewise, the total complications were not significantly different between the two groups, MID versus OD. Ultimately, the results seem somewhat equivalent.

Figure 9. Axial view of a well decompressed spinal canal after bilateral laminectomies or discectomy through a unilateral approach.

1. Dasenbrock HH, Juraschek SP, Schultz LR, Witham TF, Sciubba DM, Wolinsky JP, Gokaslan ZL, Bydon A: The efficacy of minimally invasive discectomy compared with open discectomy: a meta-analysis of prospective randomized controlled trials. J Neurosurgery Spine. 16:452–62, 2012.

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CLINICAL SPOTLIGHT

Figure 1. Upper and middle clivus drilled-out.

Pituitary remains in situ.

AICA—Anterior inferior cerebellar artery; BA—Basilar artery; CN II—Optic nerve; CN III—oculomotor nerve; CN VI Abducens nerve; GC—Gasserian ganglion; ICA—Internal carotid artery; V1—Ophthalmic, V2—Maxillary, and V3—Mandibular branches of the trigeminal nerve

Minimally invasive approach to the clivus Navigating the clivus with an endonasal transclival approach

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The clivus is composed of the posterior/ inferior portion of the sphenoid bone and basilar portion of the occipital bone.

This anatomic region separates the nasopharynx from the posterior cranial fossa. Clival lesions are of varied pathology and clinical behaviors. Their location and proximity to critical structures make operative management challenging.

At our institution, the endoscopic endonasal approach has been adopted for selected pathologies. The standard approach involves

NEUROSCIENCE OUTLOOK  Volume 10 | Issue 2

by Arturo Solares, M.D., John Vender, M.D., and Cargill H. Alleyne Jr., M.D.

a posterior septectomy, some degree of ethmoidectomy, and wide sphenoidotomies extending laterally to the level of the medial pterygoid plates. The sphenoid septations are then removed with the understanding that these may lead to the carotid canal. Finally, the sphenoid floor is removed to the level of the clival recess.

With this exposure completed, vital landmarks are now readily identifiable, including the medial and lateral opticocarotid recesses (OCR), the carotid protuberance within the parasellar space,

FACULTY & STAFF UPDATES Cargill H. Alleyne Jr., M.D., (Department of Neurosurgery) gave an invited lecture (“Hereditary Hemorrhagic Telangiectasia: The Georgia Health Sciences University Experience”) at the Southern Neurosurgical Society meeting in Sarasota, Fla., in February. He was also a panel member of a breakfast seminar (“The safe operating room environment: How do we make it safe for the patient?”) at the American Association of Neurological Surgeons meeting in New Orleans in April.

Darrell W. Brann, Ph.D., (Department of Neurology) was awarded a VA Merit review grant (Principal Investigator, with Krishnan Dhandapani, Ph.D., as co-investigator) entitled “Role of NADPH Oxidase in TBI” (June 1, 2013– May 30, 2017).

Figure 2. Upper and middle clivus drilled-out. Pituitary has been transposed to expose the interpeduncular fossa.

BA—Basilar artery; CN III—oculomotor nerve; CN VI Abducens nerve; ICA—Internal carotid artery; PCA—Posterior cerebellar artery; SCA—Superior cerebellar artery

the sellar face, clival recess, and strut of tuberculum bone overlying the superior intercavernous sinus (SIS). The clival dura is then exposed by drilling the posterior wall of the sphenoid sinus starting at the sella and working inferiorly. Adequate carotid exposure is paramount when the tumor extends laterally into the cavernous sinus. Following dural exposure and removal, the following structures are visualized (figures 1 and 2). This technique provides unparalleled visualization to lesions in the central skull base.

Sergei A. Kirov, Ph.D., (Department of Neurosurgery) gave two invited lectures. The first (“Evolution of astroglial and neuronal disruption in stroke and TBI revealed by in vivo two-photon imaging”) was at the Satellite Caribe Glia Symposium on Molecular Mechanisms of NeuronGlia Interactions at Universidad Central del Caribe in San Juan, Puerto Rico in January. The second (“Neurons, astrocytes and microglia in early stroke and brain trauma”) was at the University of Virginia, Center for Brain Immunology & Glia (BIG) Seminar Series in Charlottesville, Va., in April.

S. Dion Macomson, M.D., (Department of Neurosurgery) was awarded an Exemplary Teacher Award by the MCG Faculty Senate.

Elizabeth Sekul, M.D., (Department of Neurology) was awarded a Patient Care Award by the MCG Faculty Senate.

Krishnan Dhandapani, Ph.D., (Department of Neurosurgery) was awarded an NIH/ NINDS R03 grant (as co-investigator with John Vender, M.D.) entitled “NLRP3 inflammasome and TBI” (July 1, 2013–June 30, 2015). He was also co-investigator on the grant awarded to Darrell Brann, Ph.D. David C. Hess, M.D., (Department of Neurology) was an invited speaker at the Second International Conference on Regenerative Medicine at the Vatican in April. His presentation was “Cell therapy of stroke and traumatic brain injury.”

Jeffrey Switzer, D.O., (Department of Neurology) was awarded a Distinguished Faculty Award for Clinical Science Research by the MCG Faculty Senate.

John Vender, M.D., (Department of Neurosurgery) was awarded an NIH/ NINDS R03 grant (as co-investigator with Krishnan Dhandapani, Ph.D.) entitled “NLRP3 inflammasome and TBI” (July 1, 2013–June 30, 2015).

THANKS TO OUR DONORS Neurosurgery Georgia Neurological Surgery (in honor of William Ford, M.D.) Mr. & Mrs. Lint Eberhardt Mr. Kenneth Drake Royston Diagnostic Center

Carol Bachus Susan R. Kay Cargill H. Alleyne Jr., M.D.

Neurology Mrs. Eileen V. Brandon Nicholas Schlageter, M.D. Ms. Rachel Arnett ALS Association of Georgia Mrs. Mary Ruth Haworth Kapil Sethi, M.D. Georgia Power

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RESEARCH SPOTLIGHT

Stroke: Exploring novel therapies

Investigator-initiated clinical trials in acute stroke seek to develop treatment strategies to promote recovery

by David C. Hess, M.D., Askiel Bruno, M.D., and Jeffrey Switzer, D.O.

A primary goal of the Georgia Regents Comprehensive Stroke Center is to develop novel therapies and treatment strategies to lessen the long-term disability from stroke. Toward this end, we are currently conducting three novel clinical

trials, initiated by our local stroke experts.

The MultiStem trial is a phase 2, randomized, double-blind, placebo-controlled, dose-escalation trial of MultiStem®, intravenously-delivered allogeneic multipotent bone marrow stem cells for acute ischemic stroke. David Hess, M.D., Chairman of the Department of Neurology at GRU, is the principal investigator of MultiStem. This trial builds upon a substantial body of preclinical work at GRU and other institutions supporting the utility of cellbased therapies hours to days after stroke. Although the neurorestorative mechanisms of cell therapies are incompletely elucidated, MultiStem appears to work through an immunomodulatory effect, reducing the exodus of monocytes from the spleen to the site of brain injury that appear to aggravate the damage (figure 1). Further, it is encouraging that previous studies of multipotent bone marrow cells in myocardial infarction and graft-versus-host disease have demonstrated safety.

MultiStem is the first intravenously delivered allogeneic cell therapy to be tested in stroke, and it has several features that suggest potential generalizability to a substantial number of stroke patients. Targeting the “neurorestorative window,” patients are enrolled between 24 and 36 hours after stroke onset, and the inclusion criteria include recipients of tPA who have not had substantial improvement. In addition, since the cell source is allogeneic, as opposed to autologous, it can be prepared as an “off the shelf ” product, allowing for potential storage at most community hospitals.

A total of 136 subjects will be randomized. If MultiStem® is safe and there is a signal of efficacy, a late-stage phase 2b–3 trial is planned.

Figure 1. These bone marrow-derived stem cells migrate to the spleen, where they prevent activation of splenocytes. They also reduce activation of other white blood cells, including lymphocytes.

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SHINE (Stroke Hyperglyecemia Network Effort) is a phase 3, randomized, blinded, multicenter trial that will determine the safety and efficacy of standard versus intensive glucose control with insulin in hyperglycemic acute ischemic stroke patients.

The trial is sponsored by the NIH (NINDS) and represents the collaboration of co-investigators from GRU (Askiel Bruno, M.D.), University of Virginia, and University of Texas Southwestern.

While hyperglycemia occurs commonly in acute ischemic stroke (~40 percent) and is associated with worse clinical outcomes, whether or not intensive glucose control with IV insulin improves clinical outcome is not established. Preclinical and clinical data have suggested potential benefit from tight glucose control in the setting of brain ischemia.

However, these benefits must be balanced against the risks of hypoglycemia. In SHINE, 1,400 hyperglycemic acute ischemic stroke patients presenting within 12 hours of symptom onset will be randomly assigned to continuous IV infusion of insulin or standard therapy (sliding scale subcutaneous insulin) for three days (figure 2). This trial will provide important novel information about preferred management of acute ischemic stroke patients with hyperglycemia.

It will determine the potential benefits and risks of intensive glucose control during acute stroke.

MACH (Minocycline in Acute Cerebral Hemorrhage) is an American Heart Association, SE Affiliate-sponsored pilot trial of minocycline for the treatment of intracerebral hemorrhage.

Jeffrey Switzer, D.O., is the principal investigator.

Unfortunately, there are currently no established effective treatments for intracerebral hemorrhage, a disease with a mortality of 40 percent and with few survivors who achieve long-term independence.

Following hemorrhage, blood constituents and their degradation products cause direct toxic injury to neurons and supporting tissue, and trigger a secondary inflammatory response. These pathways result in acute cell death, blood-brain barrier disruption, and edema, followed long-term by tissue loss and permanent neurologic deficits. Several key mediators, including matrix metalloproteinases (MMP-9), iron, and activated microglia/ macrophages, have been identified. Minocycline, a so-called “dirty drug,� has been proposed as a putative therapy for hemorrhage patients. With a long track record as an antibiotic and several promising trials of neuroprotection in ischemic stroke, a short course of treatment should be safe and tolerable in intracerebral hemorrhage. Importantly, minocycline is a potent inhibitor of matrix metalloproteinases, an iron chelator, and suppresses the inflammatory response post-stroke (figure 3).

Figure 2 . When there is hyperglycemia, insulin is given either subcutaneously or intravenously during acute ischemic stroke for up to three days. These two treatment options will be compared according to functional outcomes.

In this pilot study, we will determine whether minocycline reduces MMP-9, serum iron, and inflammation (IL-6) in ICH patients, and we will evaluate hemorrhage growth, perihematomal edema, and clinical outcome. Finally, an important additional rationale for studying minocycline in intracerebral hemorrhage is that if shown to be safe, it could be initiated in the pre-hospital setting (prior to neuroimaging and the differentiation of ischemic stroke from ICH), permitting ultra-early treatment and possibly increasing the likelihood of benefit for both ICH and ischemic stroke patients.

Figure 3. Proposed pathophysiologic targets of minocycline in intracerebral hemorrhage

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PUBLICATIONS & PRESENTATIONS

January–April 2013 Publications Strelzik J, Carroll JE Neonatal intraventricular hemorrhage.

MedLink Neurology Jan 29, 2013 Hess DC, Hoda MN, Bhatia K Remote limb preconditioning and postconditioning: Will it translate into a promising treatment for acute stroke?

PMID: 2333996, Stroke 44:1191-7, 2013 Smitherman AD, Woodall MN, Alleyne CH, Rahimi SY Open surgical management of a ruptured intracranial aneurysm in KlippelTrenaunay-Weber syndrome.

BMJ Case Reports, Jan 2013 [doi:10.1136/ bcr-2012-0006857] Samuel TA, Parikh, J, Sharma S, Giller CA, Sterling K, Kapoor S, Pirkle C, Jillella A Recurrent adult choroid plexus carcinoma treated with highdose chemotherapy and syngeneic stem cell (bone marrow) transplant.

J Neurol Surg A Cent Eur Neurosurg 1–6, 2013 Sword J, Masuda T, Croom D, Kirov SA Evolution of neuronal and astroglial disruption in the pericontusional cortex of mice revealed by in vivo two-photon imaging.

Brain 136: 1446-1461, [Epub ahead of print; (2013) Mar 6], 2013 Meador KJ, Baker GA, Browning N, Cohen MJ, Bromley RL, ClaytonSmith J, Kalayjian LA, Kanner A, Liporace JD, Pennell PB, Privitera M, Loring DW Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD Study): A Prospective Observational Study.

Lancet Neurology 12:244-252, 2013 Switzer JA, Demaerschalk BM, Xie J, Liangyi F, Villa KF, Wu EQ Cost-effectiveness of hub-and-spoke telestroke networks for the management of acute ischemic stroke from the hospitals’ perspectives.

Circ Cardiovasc Qual Outcomes 6:18-26, 2013 Howard G, Cushman M, Howard VJ, Kissela BM, Kleindorfer DO, Moy CS, Switzer J, Woo D Risk factors for intracerebral hemorrhage: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

Stroke 44:1282-1287, 2013 Alleyne CH Angiography, ed: Kountakis SE Encyclopedia of Otolaryngology, Head and Neck, Springer, 2013:167–172

Afferent signals (blue) travel along the Trigeminal nerve (V1) to brainstem structures where it splits into direct (red) and indirect pathways (green) that exit via the facial nerve (CN VII) to the Orbicularis Oculi. Each pathway generates separate waveforms that can be recorded by specialized nerve stimulation techniques. (Hartmann JE, The blink reflex)

Alleyne CH Arteriovenous malformations, ed: Kountakis SE Encyclopedia of Otolaryngology, Head and Neck, Springer, 2013:186–191

Vender JR, Youssef PP Lateral skull base epidermoids, ed: Kountakis SE Encyclopedia of Otolaryngology, Head and Neck, Springer, 2013:1448–1454

Rivner MH Transcranial magnetic stimulation of facial nerve, ed: Kountakis SE Encyclopedia of Otolaryngology, Head and Neck, Springer, 2013:2845–2847

Hartmann JE The blink reflex, ed: Kountakis SE Encyclopedia of Otolaryngology, Head and Neck, Springer, 2013:337–341

Rivner MH Nerve excitability test, ed: Kountakis SE Encyclopedia of Otolaryngology, Head and Neck, Springer, 2013:1840–1842

Rivner MH Maximum stimulation test, ed: Kountakis SE Encyclopedia of Otolaryngology, Head and Neck, Springer, 2013:1590–1592

Hartmann JE Electromyography, ed: Kountakis SE Encyclopedia of Otolaryngology, Head and Neck, Springer, 2013:738–743

Rivner MH Evoked EMG, ed: Kountakis SE Encyclopedia of Otolaryngology, Head and Neck, Springer, 2013:841–846

Names in blue indicate faculty members in the Georgia Regents University Neurosurgery or Neurology department.

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Presentations Kirov SA Evolution of astroglial and neuronal disruption in stroke and TBI revealed by in vivo two-photon imaging.

Satellite Caribe Glia Symposium on Molecular Mechanisms of NeuronGlia Interactions In Vivo and In Vitro.

Universidad Central del Caribe, San Juan, Puerto Rico, January 2013

intracerebral hemorrhage.

Comprehensive Stroke Management Update, Hilton Head, S.C., April 2013

Alleyne CH Hereditary Hemorrhagic Telangiectasia.

The Georgia Health Sciences University Experience. Southern Neurosurgical Society Meeting, Sarasota, Fla., February 2013

Switzer JA PFOs: Statin Controversy?: Separating the wheat from the chaff.

Comprehensive Stroke Management Update, Hilton Head, S.C., April 2013

Alleyne CH Update on subarachnoid hemorrhage and intracranial aneurysms.

Comprehensive Stroke Management Update, Hilton Head, S.C., April 2013 Bruno A TIA and Stroke: Clinical diagnosis and misdiagnosis.

Comprehensive Stroke Management Update, Hilton Head, S.C., April 2013 Bruno A Decisions in the management of carotid artery disease.

Comprehensive Stroke Management Update, Hilton Head, S.C., April 2013 Bruno A Stroke in the young.

Switzer JA Stroke Centers and Telestroke: An Evolving Landscape.

Comprehensive Stroke Management Update, Hilton Head, S.C., April 2013

Management Update, Hilton Head, S.C., April 2013

Switzer JA Special issues in atrial fibrillation and stroke.

Comprehensive Stroke Management Update, Hilton Head, S.C., April 2013

Nichols FT Endovascular revascularization therapy update.

Comprehensive Stroke Management Update, Hilton Head, S.C., April 2013

Vender JR Malignant cerebral edema: from ventriculostomy to hemicraniectomy.

Comprehensive Stroke Management Update, Hilton Head, S.C., April 2013

Nichols FT PFOs: To close or not to close? and other evolving issues in cardioembolic stroke.

Comprehensive Stroke Management Update, Hilton Head, S.C., April 2013

Alleyne CH Subarachnoid hemorrhage and unruptured intracranial aneurysms: Emphasis on diagnosis and early treatment plan.

Primary Care and Family Practice Symposium, Augusta, Ga., April 2013

Genealogical chart of a family with HHT treated at GRU. (Alleyne CH, Hereditary Hemorrhagic Telangiectasia)

Comprehensive Stroke Management Update, Hilton Head, S.C., April 2013 Hess DC The borderlands of intravenous thrombolysis.

Comprehensive Stroke Management Update, Hilton Head, S.C., April 2013 Hess DC The challenge of psychogenic stroke.

Comprehensive Stroke Management Update.

Hilton Head, S.C., April 2013 Hess DC The de-Alzheimerization of dementia: The role of ischemia in dementia.

Comprehensive Stroke

Ramesh S Contemporary management of

Alleyne CH The safe operating room

environment: How do we make it safe for the patient?

American Association of Neurological Surgeons Meeting, New Orleans, La., April 2013 Alleyne CH, Shields J, Kimbler DE, Dhandapani KM Lipopolysaccharide upregulates aquaporin-4 expression in mouse cortical astrocytes via PI3K gamma-dependent mechanisms.

American Association of Neurological Surgeons Meeting, New Orleans, La., April 2013 (poster) Hess DC Cell therapy of stroke and traumatic brain injury.

Second International Conference on Regenerative Medicine, Vatican City, April 2013 Kirov SA Neurons, astrocytes and microglia in early stroke and brain trauma.

University of Virginia, Center for Brain Immunology & Glia (BIG) Seminar Series, Charlottesville, Va., April 2013 Viers A, Allen M, Alleyne CH Historical vignette: George W. Smith, M.D. (1916–1964).

American Association of Neurological Surgeons Meeting, New Orleans, La., April 2013 (poster)

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As a regional referral center for the Southeastern U.S., the Georgia Regents Neuroscience Center of Excellence includes the area’s largest, most diverse team of adult and pediatric neurologists and neurosurgeons, including renowned experts in Parkinson’s disease, stroke, ALS, MS, functional and cerebrovascular neurosurgery, and complex spine surgery. To make an online referral, visit gru.edu/referral.