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UAB Insight 410 • 500 22 nd Street South 1530 3rd ave s birmingham al 35294-0104 NON-PROFIT ORG. U.S. POSTAGE PAID PERMIT NO. 1256 BIRMINGHAM, AL bY PhOne Contact UAB MIST at 1.800.822.6478 to schedule appointments or arrange for transport of patients 24 hours a day, 7 days a week. inFOrmaTiOn FOr YOUr PaTienT Please tell your patient to bring all pertinent insurance information. If your patients would like more information about our visiting hours and services, please advise them to log on to www.uabhealth.org for important information about their stay. They will find information on parking, accommodations, and guest and hospital services. An information packet will be sent to your patients telling them where to park and how to find the UAB Hospital admission office. If they are coming for an outpatient visit, we will see them in The Kirklin Clinic ® , located on 6th Avenue South between 20th and 21st streets. Online For more information visit the UAB Department of Neurology at www.uab.edu/neurology and the UAB Division of Neurosurgery at www.uab.edu/neurosurgery. UAB Referrals To refer a patient to the UAB Department of Neurology or the UAB Division of Neurosurgery:
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Page 1: UAB Referrals

School of Medicine

UAB Insight 410 • 500 22nd Street South 1530 3rd ave s birmingham al 35294-0104

NON-PROFIT ORG.U.S. POSTAGE

PA I DPERMIT NO. 1256BIRMINGHAM, AL

bY PhOneContact UAB MIST at 1.800.822.6478 to schedule appointments or

arrange for transport of patients 24 hours a day, 7 days a week.

inFOrmaTiOn FOr YOUr PaTienTPlease tell your patient to bring all pertinent insurance information.

If your patients would like more information about our visiting hours

and services, please advise them to log on to www.uabhealth.org for

important information about their stay. They will find information on

parking, accommodations, and guest and hospital services.

An information packet will be sent to your patients telling them where

to park and how to find the UAB Hospital admission office. If they are

coming for an outpatient visit, we will see them in The Kirklin Clinic®,

located on 6th Avenue South between 20th and 21st streets.

OnlineFor more information visit the UAB Department of Neurology at

www.uab.edu/neurology and the UAB Division of Neurosurgery at

www.uab.edu/neurosurgery.

UAB ReferralsTo refer a patient to the UAB Department of

Neurology or the UAB Division of Neurosurgery:

Page 2: UAB Referrals

InsightA New Approach to

Parkinson Disease

Multiple Sclerosis Advances

Intracranial Aneurysm Management at UAB

NeurosciencesAdvances in

ON NEUROSCIENCES: NEUROLOGY AND NEUROSURGERY

UAB Referrals

Page 3: UAB Referrals

E D i t O R S i N C h i E f Ray L. Watts, MD

James M. Markert, MD, MPh

M A N A G i N G E D i t O R S Kristen Riley, MD

tom Brannan

A S S O C i A t E E D i t O R S Emily Delzell

Peaches Scribner Kate tully

C R E A t i v E D i R E C t O R Ron Gamble

A R t D i R E C t O R Jessica huffstutler

i L L U S t R A t i O N Echo Medical Media

Published by the Uab health system

500 22nd street south birmingham, al 35233

©2009 by The board of Trustees of The University of alabama

for the University of alabama at birmingham. second class postage

paid by Uab bulk mail dept.

Postmaster: address changes to: UAB Insight

410 • 500 22nd street south 1530 3rd ave s

birmingham al 35294-0104

Or call the toll-free misT line: 1.800.822.6478

[email protected]

School of Medicine

w e l c O m eUab insighT On neUrOsciences

FALL 2009vOlUme 1, nUmber 1

Welcome to the first issue of UAB Insight on Neurosciences:

Neurology and Neurosurgery, created to keep you informed

about UAB’s neurology and neurosurgery services. Growth of

the neurosciences is a top priority at UAB, and new leadership is

driving innovative development in both clinical and laboratory

science departments.

The University of Alabama Health Services Foundation, the

faculty practice plan of UAB School of Medicine, is one of the

largest and most successful academic multispecialty clinics in

the nation. UAB ranks among the top 25 centers in the United

States in National Institutes of Health research funding, and our

goal is to continue growth in our research programs and stay

on the forefront of development of new treatments and cures

for major neurological diseases. We have strong institutional

and community commitments to support vigorous growth in

the neurosciences, and we are recruiting additional outstanding

faculty from the best universities and hospitals in the nation.

This magazine is designed to examine specific neurologic

disease entities and provide an update on the latest approaches to

caring for patients with these conditions. Each article is written

by UAB specialists with expertise in the disease discussed. These

experts provide the reader with their perspective on the condition,

current treatment options, and information on new and evolving

therapies that offer exciting opportunities to improve care and quality of life for patients.

There is strong collaboration between UAB’s Department of Neurology and Division of Neuro-

surgery. Open communication between neurologists and neurosurgeons in the areas of epilepsy,

cerebrovascular disease, movement disorders, and neuro-oncology creates an exceptional team

environment that offers greater opportunities for our scientists and physicians to make novel discov-

eries in basic and clinical research. This model partnership enhances our ability to provide the best

possible patient care by offering the latest combinations of medical and surgical treatments.

We in the neurosciences at UAB are working hard to maximize our communication with our

referring physicians. The Physician Ambassador Program allows referring physicians without a

UAB affiliation access to patient notes, letters, reports, and other data through a secure Internet

connection. We encourage each of you to take advantage of this excellent service. For more in-

formation please contact Physician Services at 1.800.822.6478.

We wish to continue to foster a collaborative approach to patient care that serves our patients

and their physicians, to everyone’s benefit. Thank you for reading our magazine. We look for-

ward to working with you in the future.

James Markert, MD, MPh

Ray Watts, MD

Ray L. Watts, MDJohn N. Whitaker Professor and Chair of Neurology

James M. Markert, MD, MPHDirector and James Garber Galbraith Endowed Chair in Neurosurgery

Page 4: UAB Referrals

c O n T e n T s

neurology

neurosurgery

Uab at a glance

Advances in Neurosciences ............... 2

Multiple Sclerosis Advances ..............4

The Future of Stroke Medicine: UAB Advances Stroke Care, Education, and Research ...................6

NET SMART: Advancing Stroke Care Education ............................................ 7

Genetics: A New Approach to Parkinson Disease ..............................8

Amyotrophic Lateral Sclerosis: A Comprehensive Approach .............9

Aneurysms: Intracranial Aneurysm Management at UAB ...................... 10

Minimally Invasive Spinal Surgery: Techniques for Faster Recovery......12

Radiosurgery: Developing Optimal Plan for Patients ........................... 13

Neurology and Neurosurgery .........14

Multidisciplinary Research ..............15

Faculty ............................................16

Visit UAB Insight online (www.uabhealth.org/insight) to request a second issue of UAB Insight

on Neurosciences, request our other referring physician magazines, or to sign up for electronic

delivery. The site also offers breaking news, referring physician resources, and new faculty

announcements. It features videocasts of our physicians discussing the latest procedures

available at UAB, CME opportunities, information on the Ambassador Program for referring

physicians, and more.

U a b i n s i g h T O n l i n e

4

8 6

10

Page 5: UAB Referrals

2 Uab insighT On neUrOsciences • Fall 2009

Neurology/Neurosurgery

Advances in NeurosciencesDeveloping New Treatments and Cures for Neurological Disorders

UNIqUe AT UABConcurrent with unprecedented growth

in neurosciences during the last decade, UAB has launched broad initiatives to advance understanding and treatment of neurological disorders. These ongoing efforts transcend disciplines and draw on cooperation and expertise of numerous scientists and clinicians in multiple de-partments and labs. Because of these out-standing accomplishments, UAB research-ers and clinicians are well-positioned to create new drugs and therapeutic strate-gies that improve patients’ lives.

CNeT The Center for Neurodegeneration and

Experimental Therapeutics (CNET) accel-erates the translational process by moving basic scientific discoveries from the labo-ratory to clinical use as rapidly and safely as possible. This interface between UAB’s clinical enterprise and its exceptionally strong basic science program represents a unique synergistic strategy to advance dis-coveries in neurodegenerative conditions such as Parkinson disease, Alzheimer dis-ease, and amyotrophic lateral sclerosis — and make a difference in patient care.

AlzheIMer’S DISeASe reSeArCh CeNTer

The Alzheimer’s Disease Research Center (ADRC) was established in 1991 through a grant funded by the National Institutes of Health (NIH) and the Na-tional Institute on Aging. The ADRC is an interdisciplinary effort among UAB neurologists, psychiatrists, geneticists, and psychologists, providing comprehensive and diagnostic services for patients with Alzheimer disease and their families.

An important part of the center’s mis-sion is promoting research for the pre-vention and cure of Alzheimer disease Ray Watts, MD, and James Markert, MD, MPh

Page 6: UAB Referrals

Uab insighT On neUrOsciences • Fall 2009 3

UAB Medicine At a Glanceand related disorders. UAB Alzheimer disease scientists collaborate with re-searchers throughout the world through the Alzheimer’s Disease Neuroimaging Initiative, a multicenter, multiyear study aimed at determining if brain imaging techniques can diagnose early stages of Alzheimer disease, and the Alzheimer’s Disease Cooperative Study, which links research institutions across the country in scientific investigations of treatments un-likely to be supported by drug companies, such as a recently conducted study to in-vestigate the role of estrogen in Alzheimer disease. Center researchers also are ac-tively testing the latest Alzheimer disease treatments from international pharmaceu-tical companies to optimize care and forge a path to improved treatments.

CoMPreheNSIve NeUroSCIeNCe CeNTer

The Comprehensive Neuroscience Cen-ter (CNC) promotes and supports interdis-ciplinary neuroscience research, clinical care, and education at UAB, and is one of the first of its kind in the nation. Six areas of concentration reflect the direction of neuroscience discovery: neurodevelop-ment and neurogenetics; neurodegenera-tion and experimental therapeutics; neuro-regeneration and plasticity; behavioral and cognitive health; glial biology; and neuroimaging.

The CNC facilitates cross-campus initiatives that rapidly apply basic science discoveries to human neurologic and psy-chiatric diseases.

AlABAMA NeUroSCIeNCe BlUePrINT Core CeNTer

In 2005 the NIH Blueprint for Neuro-science Research awarded UAB one of its highly competitive grants to establish the Alabama Neuroscience Blueprint Core Center. This collaborative group of investigators from various disciplines uses genetically modified rodents and small laboratory animals to advance un-derstanding of nervous system function and dysfunction. The five research cores are: molecular engineering; cellular and molecular neuropathology; neuroimaging;

physiology and phenotyping; and cellular and synaptic physiology.

Dr. ray WattsDr. James [email protected]

FOr mOreinFOrmaTiOn

The 908-bed, state-of-the-art UAB Hospital offers exceptional care for patients in all disciplines, in addition to outstanding research and teaching programs.

The $350 million UAB Hospital North Pavilion is a high-technology facility with all-new operating rooms, intensive care units, and vascular catheterization, imaging, and interventional suites.

UAB Hospital’s Emergency Department covers almost a full square block and is the state’s only American College of Surgeons-accredited Level 1 Trauma Center.

UAB Hospital has a 26-bed neurological intensive care unit and a new neurosciences unit with hospital floor beds.

More than 24,000 neurological and 13,000 neurosurgical outpatient visits are made at The Kirklin Clinic® annually.

UAB neurosurgeons perform 3900 neurosurgical procedures each year.

More than 4000 neurology and neurosurgery hospital admissions per year represent the full spectrum of acute and tertiary referrals for neurological disorders.

UAB neurologists and neurosurgeons work closely with the outstanding divisions of Otolaryngology and Neuroradiology, as well as other closely allied departments such as Medicine, Psychiatry and Behavioral Neurobiology, Physical Medicine and Rehabilitation, Trauma, Radiation Oncology, and Anesthesiology.

15,000 square feet of new laboratory space for disease-related neuroscience research opened in June 2006.

UAB has 50 neurology faculty members and 16 neurosurgery faculty, including 13 full-time neurosurgeons.

UAB’s Comprehensive Stroke Unit has 20 beds for stroke patients.

More than 200 clinical trials are underway in the Department of Neurology and the Division of Neurosurgery.

Neurology/Neurosurgery

Page 7: UAB Referrals

4 Uab insighT On neUrOsciences • Fall 2009

As the most common cause of non-traumatic neurological disability among young adults, multiple sclerosis (MS) con-tinues as a focus of the research efforts of clinicians and researchers around the world and at UAB. Research during the last 20 years has yielded important breakthroughs in understanding of this enigmatic disease. The most apparent results have been the proliferation of drugs that favorably modify the natural history of this once untreatable condition.

UAB’s Multiple Sclerosis Center and the Center for Neuroimmunology owe their success in part to John N. Whitaker, MD, chair of UAB’s Department of Neurol-ogy from 1985 to 2001. Whitaker made important contributions to MS research in both the clinic and the laboratory. His accomplishments include early participa-tion in the study of beta-interferon and the identification of biomarkers to monitor MS progression. Since Whitaker’s prema-ture death in 2001, UAB clinicians and researchers have continued to pursue his goals of providing exceptional clinical care while making strides to better understand and treat MS.

The UAB Multiple Sclerosis Center is staffed by two MS-fellowship trained neurologists, Khurram Bashir, MD, MPH, center director, and John R. Rinker II, MD, who joined the group in 2007. The UAB Multiple Sclerosis Center is one of the larg-est of its kind in the Southeast, providing comprehensive care to more 1300 patients with MS and related disorders. Every year UAB’s center provides consultation ser-vices to more than 500 new patients from Alabama and the Southeast, and center physicians and scientists regularly partici-pate in industry-sponsored clinical trials of investigational drugs targeting disease modification and treatment of MS-related symptoms.

Ancillary services offered through the UAB Multiple Sclerosis Center include

Multiple Sclerosis Advances

Neurology

Collaboration Between Clinical and Laboratory Sciences Is Key

Page 8: UAB Referrals

Uab insighT On neUrOsciences • Fall 2009 5

Neurology

advanced neuroimaging capabilities, outpatient infusion services, rehabilitation, neuropsychology, and baclofen pump im-plantation for refractory spasticity. Patients seen at UAB also have access to neuro-ophthalmologists and urologists.

In 2006 UAB expanded the clinical ser-vices it offers to the MS population with the founding of the Center for Pediatric Onset Demyelinating Disease (CPODD). Under the leadership of pediatric neurolo-gist Jayne M. Ness, MD, PhD, the Na-tional Multiple Sclerosis Society awarded CPODD the designation of Pediatric Mul-tiple Sclerosis Center of Excellence, one of only six such centers in the United States.

As part of the Pediatric Multiple Scle-rosis Network, CPODD has been funded for 5 years and has developed a multidis-ciplinary clinic that supports collaborative research with the other Centers of Excel-lence. Children seen at CPODD receive comprehensive, on-site care, including neurological care, school couseling, and the services of neuropsychologists, psy-chiatrists, rehabilitation specialists, and social workers.

Collaboration between the clinical and laboratory sciences is a key strength of MS research at UAB. To further solidify joint efforts to develop and evaluate novel MS therapies, UAB researchers recently applied for a Collaborative Multiple Scle-rosis Research Center Award through the National Multiple Sclerosis Society. The aim of the application is to support inter-disciplinary research on several projects involving clinical and laboratory research-ers from a number of disciplines.

Current examples of collaboration high-light strides underway at UAB. In 2008, Richard S. Jope, PhD, and Patrizia De Sarno, PhD, UAB Department of Psychia-try and Behavioral Neurology, published an article describing the immune modu-lating effects of lithium in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS (J Immunol. 2008;181[1]:338-345).

Lithium exerts anti-inflammatory effects through inhibition of GSK3, an enzyme with important immune regulatory func-tions. In a series of experiments, lithium successfully prevented relapses and func-

tional impairment in multiple forms of EAE. Since lithium has a decades-long history of safe use in humans for psychiat-ric indications, it is well suited to a clini-cal trial in MS, which is currently being planned by Rinker and colleagues.

In another interdisciplinary collabora-tion Scott R. Barnum, PhD, and Etty (Tika) Benveniste, PhD, established researchers in the MS field, and Peter H. King, MD, a newcomer to MS research, are working to find new therapeutic targets. King brings expertise in RNA-binding proteins, which are important in regulating expression of pro- and anti-inflammatory mediators in MS. These scientists’ goal is characterizing the relevance of RNA-binding proteins to MS specifically and assessing their plausi-bility as therapeutic targets.

Finally, the UAB School of Public Health has become increasingly important in UAB’s MS research endeavors, acting as the data coordinating center for a pivotal

National Institutes of Health-sponsored MS clinical trial (CombiRx) and in the admin-istration of a large patient-reported North American MS database (NARCOMS).

Gary R. Cutter, PhD, and Stacey S. Co-field, PhD, are closely involved with data management for CombiRx.

CombiRx investigates the effective-ness of combination therapy with daily glatiramer acetate and once weekly intra-muscular interferon beta-1a versus either agent alone in reducing relapse rates and disability accumulation. When the study concludes in 2012 it will be the first defini-tive trial to answer the question of whether combinations of approved immunomodula-tory drugs in MS are superior to single-agent therapy.

Dr. khurram BashirDr. John rinker iiDr. Jayne [email protected]

FOr mOreinFOrmaTiOn

UAB Multiple Sclerosis Center faculty and staff (L-R): Wille Whatley, RN; John Rinker ii, MD; Khurram Bashir, MD, MPh; and Beverly Layton, RN.

Page 9: UAB Referrals

6 Uab insighT On neUrOsciences • Fall 2009

Neurology

In January 2009 the Division of Cere-brovascular Disease opened the UAB Com-prehensive Stroke Unit, which centralizes stroke care within one unit of UAB Hospital. As a world leader in stroke care and preven-tion, the UAB Comprehensive Stroke Re-search Center provides the best patient care available and conducts cutting-edge clinical and basic research. The new unit offers one location for stroke patients with critical care needs and for those who are stable and need less complex medical and nursing care.

Critically ill patients stay in the same room with the same care team from admis-sion to discharge, avoiding the need to transfer from one unit to another as their condition improves. This continuum of care helps the medical team establish better com-munication with patients and family.

“We are calling it a ‘universal concept stroke unit,’ and it is one of the first in the world,” says Andrei V. Alexandrov, MD, the inaugural director of the UAB Compre-hensive Stroke Research Center. “It is es-sentially a one-stop unit with more than 60

highly specialized interdisciplinary prac-titioners. We are able to provide state-of-the-art evidence-based care and conduct cutting-edge clinical research, all aimed at enhancing outcomes for stroke patients and reducing stroke and disability inci-dence worldwide. This universal concept stroke unit is a great improvement for pa-tients who, in the past, have been shuffled from one unit to another with a different set of caregivers in each area.”

Extensive treatment options are an ex-ceptional feature of the UAB Comprehen-sive Stroke Unit. A particular emphasis is 24-hour access to acute reperfusion thera-pies, such as the clot-busting medication tissue plasminogen activator and interven-tional catheter-based procedures including thrombectomy, clot aspiration, and stent-ing. A stroke team of multidisciplinary neurointerventionalists use the unit as a dedicated base to provide these therapies.

Patients travel to UAB from Alabama and Southeastern states, including Tennessee, Georgia, Louisiana, Mississippi,

and the Florida panhandle. Approximately 800 patients visit UAB for stroke treatment each year. The new unit is expected to in-crease that number significantly.

The Division of Cerebrovascular Dis-ease recently received a $500,000, 5-year grant from the National Institutes of Health to advance research on novel diag-nosis strategies and treatments for stroke.

The Comprehensive Stroke Research Center will grow in faculty and staff in the coming years to better meet the needs of the public. With the development of new treatments and preventive therapies, the center’s ultimate goal is lowering the num-ber of stroke cases and improving health outcomes for stroke patients in the South-east and throughout the world.

The Future of Stroke MedicineUAB Advances Stroke Care, Education, and Research

Dr. anDrei alexanDrovDr. ivan lopezDr. Damon [email protected]

FOr mOreinFOrmaTiOn

(L-R) Damon Patterson, MD; Andrei Alexandrov, MD, inaugural director of the UAB Comprehensive Stroke Research Center; and Anne Alexandrov, PhD, RN, CCRN.

Page 10: UAB Referrals

Uab insighT On neUrOsciences • Fall 2009 7

Neurology

Stroke is the leading cause of per-manent disability in adults and the third leading cause of death in the United States. It affects more than 700,000 Americans each year. Another estimated 300,000 are diagnosed with transient ischemic attack, a high-risk stroke precursor. Current pre-ventive services are inadequate, and as a result, stroke contributes significantly to health care costs. These costs will continue to increase unless medical practitioners are prepared to treat and preserve neurological function in emergency situations.

With an aim of improving stroke out-comes and reducing costs, UAB has part-nered with Arizona State University to serve as the clinical validation site for the world’s first online postgraduate neurovascular fel-lowship education and advanced training

program, called NET SMART (Neurovascu-lar Education and Training in Stroke Man-agement and Acute Reperfusion Therapy).

NET SMART was originally developed by UAB acute health specialist Anne W. Alexandrov, PhD, RN, CCRN, with funding from the Health Resource Services Admin-istration of the US Department of Health and Human Services. NET SMART’s objective is to increase stroke patients’ access to evidence-based acute stroke ser-vices through the widespread availability of advanced practice nurses (APNs) — nurse practitioners and clinical nurse special-ists — who have completed postmaster’s graduate neurovascular fellowship training, rendering them capable of expanding neu-rologist coverage in emergency departments and other acute hospital settings.

Depending on their state licensure and scope of practice, NET SMART fellows will be prepared for roles that could include diag-nosing a variety of acute stroke presentations through neuroimaging interpretation (multi-modal computed tomography, magnetic reso-nance imaging, transcranial Doppler imaging, and angiography), and clinical localization by neurovascular territory; establishing stroke mechanism; acute intravenous thrombolysis and intra-arterial treatment decision making; stroke risk factor analysis and treatment deci-sion making for secondary stroke prevention; treatment decision making for complication prevention; and clinical and administrative stroke leadership.

The program has enrolled more than 65 APNs from 22 states. These specialty educated and trained professionals have produced an average 7% increase in tissue plasminogen activator treatment rates, with a solid, safe clinical performance record. Some of the nation’s top stroke neurolo-gists, including UAB’s Andrei V. Alexan-drov, MD, director of the UAB Compre-hensive Stroke Research Center, oversee the curriculum supporting NET SMART, which undergoes regular updates to incor-porate the rapid changes in stroke science.

August 2009 marks the launch of NET SMART MD, a new program designed as an in-depth fellowship-like emersion pro-gram for physicians interested in expanding their acute stroke knowledge and skills through a flexible, online, self-paced train-ing program. Also launched in August was NET SMART Jr, a program designed to provide continuing education in acute stroke management to hospital nursing staff. NET SMART Jr combines assessment, manage-ment, and stroke center leadership content with customizable clinical skills and testing methods. The program offers more than 50 continuing education credits.

For more information or to enroll, please visit www.netsmart-stroke.com or contact Anne Alexandrov at [email protected].

NET SMARTAdvancing Stroke Care Education

Dr. anDrei alexanDrovDr. anne [email protected]

FOr mOreinFOrmaTiOn

Page 11: UAB Referrals

8 Uab insighT On neUrOsciences • Fall 2009

Neurology

With a fresh approach and innova-tive techniques, UAB has become a leader in the pursuit of discoveries of better treat-ments, and ultimately a cure, for Parkinson disease (PD). PD is a neurodegenerative disorder in which loss of neurons in the substantia nigra cause a movement disorder in the midstages of the disease.

PD is the second most common neuro-degenerative disorder after Alzheimer disease, and more than 1.5 million Ameri-cans may suffer symptoms, with 40,000 to 60,000 new cases diagnosed annually. Currently available treatments can lessen effects of the disease, particularly in its early stages, but there are no therapies that slow neurodegeneration.

Researchers at UAB are working to change that. Andrew B. West, PhD, the John A. and Ruth R. Jurenko Research Scholar, and his team of researchers in the UAB Center for Neurodegenerative and Experimental Therapeutics are using clues from human genetic studies to radically alter the way researchers think about the molecular basis of PD.

Research into specific genetic causes of PD is relatively new. Before 1997 investigators focused primarily on iden-tification of environmental factors that might be responsible for diseases, such as chemicals and pathogens. These studies provided insight but have not indentified specific molecules that might cause PD. In the last 10 years scientists have identi-fied several genes that are now thought to be important in PD susceptibility.

The most common known cause of PD are mutations in the LRRK2 gene. Muta-tions in LRRK2, first discovered in PD patients in 2004, can account for up to 30% of PD cases in certain populations, such as Ashkenazi Jews and North African Arabs, although a smaller percentage of patients from most Western populations might be expected to have known mutations.

New studies suggest the protein pro-duced by the LRRK2 gene has kinase activity that potentially regulates the func-tion of other proteins and is typically in-volved in cell signaling pathways. In 2005 West and colleagues found that the most

common PD-associated gene mutations in LRRK2 cause an increase in LRRK2 kinase activity, suggesting this activity may play a central role in PD pathogenesis. This finding led to great excitement: kinases are often modifiable by small molecules, and thus drugs might exist that target LRRK2 and provide neuroprotection in PD.

After 5 years of dedicated research, West is considered one of the world’s leading experts in LRRK2. His research objective is developing the tools needed to find com-pounds that safely inhibit LRRK2 activity. He also hopes his research leads to an un-derstanding of how LRRK2 causes PD. To accomplish his objectives, West is working to develop new animal models that reliably emulate the unique characteristics of PD. Models in current use are largely centered on anatomic features of PD, but West aims to create a genetic model to explore the link between LRRK2 and neurodegeneration.

Developing this model is a challenge. LRRK2 is extremely large compared with most proteins and is difficult to transport with conventional methods, West says. “Mov-ing LRRK2 protein into neurons to create relevant model systems may be like trying to move a boulder with a shovel. We’re trying to invent a bulldozer that handles LRRK2 with ease.” The bulldozer he needs might be a new viral system West and scientists in UAB’s Gene Therapy Center are creating.

Another key to discovering drugs that target LRRK2 involves direct visualization of LRRK2 activity in living cells. West is creating a molecular tracking device to detect LRRK2 activity. Understanding this process will give researchers a clearer pic-ture of how LRRK2 causes PD and how to inhibit disease progression.

West firmly believes that a cure is pos-sible. With support from the National Insti-tutes of Health, the Michael J. Fox Foun-dation, the American Parkinson’s Disease Association, and private donations West and the research community are closer to finding a cure than anyone thought possible just a few years ago.

Dr. DaviD stanDaertDr. anDreW [email protected]

FOr mOreinFOrmaTiOn

Genetics

Below: A mouse neuron growing in a dish that contains PD-associated LRRK2 (green signal), and may have early changes in activity that will give insight into the molecular basis of PD. Left: Andrew West, PhD, in his laboratory.

A New Approach to Parkinson Disease

Page 12: UAB Referrals

Uab insighT On neUrOsciences • Fall 2009 9

Neurology

Amyotrophic lateral sclerosis (ALS), a degenerative disease of motor neurons, leads to progressive weakness, and ultimately, death. As there is no cure, this disease exacts a heavy emotional and financial toll from patients and their families.

ALS patients present a dilemma for treat-ing physicians because of the many clinical problems that emerge during the course of the disease. These problems intersect with many clinical subspecialties, and addressing them requires a team approach. ALS also challenges researchers with its elusive etiol-ogy. UAB has brought together clinicians and researchers in a multidisciplinary ALS Center to address these issues.

The center is involved in a continuum of efforts from scientific bench to clinical bedside. Such translational medicine is key to a successful program. Patients receive the best possible care and have access to clinical trials of the latest ALS treatments. Clinician-scientists in the center, already recognized as outstanding researchers, have the opportunity to draw on the wealth of scientific expertise at UAB and focus it on solving the obstacles of ALS while translat-ing discoveries into therapies.

The close association with interdisciplin-ary programs such as the Center for Neuro-degeneration and Experimental Therapeu-tics and the Comprehensive Neuroscience Center ensures the best possible environ-ment for success. Services and research initiatives at the ALS Center include:

ALS Clinic: The clinic provides compre-hensive care for ALS and related diseases. It provides ongoing care for ALS patients and coordinates services from a variety of disciplines, including occupational and physical therapy, gastroenterology, and pul-monary medicine. UAB neurologist Gwen C. Claussen, MD, has participated in two major clinical trials of ALS therapies (Rilutek, a glutamate blocker; and Myotrophin, which sustains motor neurons) and the center is in a prime position to participate in future trials. This clinic, one of the largest of its kind in the

region, is a major referral center for patients with suspected ALS in the Southeast.

Muscle Histopathology and Electro-myography Laboratories: Muscle biopsy analysis is a cornerstone in evaluation of ALS and related diseases. The histology lab interprets more than 400 muscle and 125 nerve biopsies annually; about 40 of these are ALS-related. The electromyography lab provides comprehensive electrodiagnostic evaluation of patients with suspected ALS. Physicians who are board certified in clini-cal neurophysiology and electrodiagnostic medicine perform more than 2500 studies yearly.

ALS Clinical Database: With the as-sistance of the Eleanor and Lou Gehrig MDA/ALS Multidisciplinary Care Center at Columbia University in New York, UAB neurologist Angela Young Achong, MD, has worked with information technology experts at UAB to develop a comprehen-sive database to track clinical information for all patients seen in the ALS clinic. The database allows close monitoring of clinical parameters, which can improve the quality of patient care, and facilitates monitoring of clinical responses in therapeutic trials.

Basic ALS Research Labora-tory: Research in this lab is supported by independent grants from the National Institutes of Health and Department of Veterans Affairs. UAB neurologist and principal investigator Peter H. King, MD, is a neuromuscular specialist who trained in molecular biology at Duke University. Liang Lu, MD, PhD, is the recent recipi-

ent of a prestigious K08 award for ALS research from the National Institute of Neurological Disorders and Stroke. Lu’s and King’s laboratory efforts have yielded novel insight into mechanisms of growth factor regulation in ALS. Motor neurons are dependent on growth factors for sur-vival, and their research has identified an abnormality in RNA regulation that encodes these growth factors. Their work holds great promise for advancing research and identi-fying new therapies.

UAB’s programs combine outstand-ing facilities with clinical expertise in all aspects of ALS management. This setting provides patients with effective and com-passionate care, and the dynamic interaction between basic and clinical research creates an environment of hope for people with this devastating disease.

Amyotrophic Lateral SclerosisA Comprehensive Approach

Dr. angela achongDr. gWen claussenDr. peter kingDr. liang [email protected]

FOr mOreinFOrmaTiOn

(L-R) Liang Lu, MD, Peter King, MD, and Gwen Claussen, MD.

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Neurosurgery

The Cerebrovascular Service at UAB is a major regional referral cen-ter for the management of patients with unruptured intracranial aneurysms and individuals with subarachnoid hemorrhage (SAH). It also is currently the highest vol-ume center in Alabama for management of intracranial aneurysms. In 2008, nearly 400 patients with unruptured aneurysms were referred to UAB, and 58 patients with SAH were admitted. A total of 158 patients underwent craniotomy for aneurysm, and 79 had endovascular treatment of an intra-cranial aneurysm.

UAB’s Cerebrovascular Service includes Winfield S. Fisher III, MD, and Mark R. Harrigan, MD. Fisher trained with the emi-nent aneurysm surgeon Charles M. Drake,

MD, and Harrigan has completed fellow-ships in neurointervention with L. Nelson Hopkins III, MD, in Buffalo and in cere-brovascular surgery with Fisher. UAB neu-roradiologist Joel K. Cure, MD, provides expertise in aneurysm imaging with mag-netic resonance angiography (MRA) and computed tomography angiography (CTA). Patients also benefit from the Cerebrovas-cular Service’s full-time team of nurses and nurse practitioners.

A complete range of surgical options is available for treatment of aneurysms, in-cluding standard microsurgical craniotomy and clipping techniques, as well as skull-base approaches and bypass procedures. After aneurysm surgery, all patients at UAB undergo routine follow-up catheter

AneurysmsIntracranial Aneurysm Management at UAB

Winfield fisher iii, MD, and Mark harrigan, MD

CtA of aneurysm prior to clipping (top), and 3-dimensional angiogram image after clipping (bottom).

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Neurosurgery

angiography to ensure complete aneurysm obliteration with preservation of the parent arteries. At UAB an average of only one patient per year is returned to the operating room for clip repositioning.

In the neurointerventional realm, UAB remains on the cutting edge. A latest-gen-eration Philips Neurointerventional Suite is equipped for 3-dimensional angiography, 3-dimensional roadmapping, and CT scan-ning during neurointerventional proce-dures. State-of-the-art aneurysm coiling techniques are supplemented with stent- assisted coiling and with balloon-remod-eling techniques when needed. UAB pres-ently has Institutional Review Board (IRB) approval for use of the Neuroform and Enterprise stents for treatment of wide-necked aneurysms.

To date, UAB’s cumulative experience with stent-assisted coiling includes 58 cases, with excellent clinical results (modi-fied Rankin Scale score of 0 or 1) in 57 of those cases (98%).

ClINICAl reSeArChThe UAB Cerebrovascular Service also

is actively involved in clinical research. Fisher is the UAB principal investigator (PI) for the International Study of Unrup-tured Aneurysms, an ongoing landmark trial of the natural history of and treatment for intracranial aneurysms. Harrigan is the PI for four IRB-approved research proto-cols involving aneurysm patients.

UAB employs advanced 3-dimensional CTA and MRA to image intracranial aneu-rysms. High-resolution 60-slice CTA has replaced catheter angiography in most cases. CTA is just as accurate as digital subtraction angiography in the imaging of most aneu-rysms and can provide additional informa-tion about anatomy and bony structures.

Three-dimensional MRA has evolved and now is used for surveillance imaging of most coiled aneurysms, obviating the need for catheter angiography for routine posttreatment follow-up.

For management of patients with SAH, the Cerebrovascular Service is supported by a 26-bed neurosurgical intensive care unit and a full-time Neurocritical Care Service staffed by the UAB Department

of Anesthesiology. UAB specialists use CT perfusion cerebral blood flow imaging and transcranial Doppler ultrasonography for diagnosis and management of cerebral vasospasm, and intracranial angioplasty and intra-arterial drug infusion are used for patients with medically refractory symptomatic vasospasm.

three-dimensional angiogram prior to coiling (left) and after stent-assisted coiling (right) of a basilar apex aneurysm. Arrows indicate proximal stent markers in the basilar artery.

Angiograms done before (left) and after (right) endovascular treatment for symptomatic cerebral vasospasm.

Dr. WinfielD fisherDr. mark [email protected]

FOr mOreinFOrmaTiOn

Giant intracranial aneurysm that will require vessel reconstruction.

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12 Uab insighT On neUrOsciences • Fall 2009

Neurosurgery

UAB’s Division of Neurosurgery proudly offers minimally invasive spinal surgery as an alternative to conventional spinal surgery. The primary goal in em-ploying this technique is to accomplish the same objectives as conventional spinal sur-gery through a less traumatic approach that preserves surrounding soft tissue.

During surgery fluoroscopy is used to guide the surgeon to the exact location of interest. By utilizing a small surgical field, tissue damage is greatly reduced. The technique allows surgeons to split lumbar paraspinous muscles along their natural longitudinal divisions.

A series of soft tissue dilators are used to create a tunnel through the targeted musculature. A tubular retractor is inserted over the dilators and functions as an access portal to the spinal column at the level of interest and as a working channel through which decompression and fusion or instru-mentation procedures can be performed.

At UAB surgeons utilize minimally invasive spinal surgery in the treatment of herniated disks within the cervical, tho-racic, or lumbar spine and in thoracic and lumbar degenerative disk disease, lumbar spondylolisthesis, thoracic or lumbar spinal stenosis, degenerative lumbar deformities, and traumatic lumbar spinal conditions. Published data and UAB’s institutional ex-perience show minimally invasive surgery is comparable to conventional surgery in symptom relief for these pathologies.

Minimally invasive surgery offers the advantages of a less-invasive procedure, reduced intraoperative blood loss, and a smaller surgical scar. These benefits lead to earlier postoperative ambulation, decreased in-hospital use of narcotic medications, and, ultimately, to shorter hospital stays. Less-invasive procedures also facilitate surgery for obese or overweight individuals who would ordinarily be denied surgery

because of associated technical challenges and surgical morbidity.

The incidence of surgical infections and postoperative cerebrospinal fluid pseudo-meningoceles or fistulas is greatly reduced with minimally invasive procedures. At UAB surgeons have yet to encounter a surgical wound infection related to mini-mally invasive decompression or fusion procedures. Surgeons believe this is due to a smaller surgical incision, minimal soft tissue disruption, and the absence of a sub-stantial postoperative dead space, which is often encountered in conventional surgery.

UAB neurosurgeons encourage referring neurologists and neurosurgeons to con-sider this novel approach to treating spinal disease and are confident patients will be pleased with their overall experience and surgical outcome.

Minimally Invasive Spinal SurgeryTechniques for Faster Recovery

Dr. mamerhi okorDr. patrick pritcharDDr. melissa [email protected]

FOr mOreinFOrmaTiOn

fig. 1. Access is gained to the spinal column using a series of graduated dilators.

fig. 2. tubular retractor is used to gain access to the spinal column.

fig. 3. Actual lumbar surgery using a minimally invasive tubular retractor as would be used in decompression or fusion.

Fig. 1

Fig. 2

Fig. 3

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Neurosurgery

UAB’s Radiosurgery Program is a recognized national leader in providing quality comprehensive care and using state-of-the-art technology. Starting in 1992 with a linear accelerator, the program improved treatment delivery with the addition of the Leksell Gamma Knife.

Radiation and oncologists and neurosur-geons work together closely, and as of 2008 have formulated treatment plans for more than 3800 patients.

The Leksell Gamma Knife is a highly advanced technology that delivers 201 co-balt radiation beams to one point. The pre-cise dose planning delivers radiation to the targeted lesion, sparing surrounding healthy tissue. For some patients the Gamma Knife is not an option because of the location or size of their tumors. In those cases, a ste-reotactic treatment plan often is achieved with hypo-fractionated radiation.

For extracranial central nervous system tumors, stereotactic body radiation therapy (SBRT) allows precise delivery of high- energy X-rays to tumor targets throughout the body. The Tomotherapy Unit at The

Kirklin Clinic® at Acton Road and the Var-ian Clinac iX linear accelerator with Rapid-Arc at the Wallace Tumor Institute treat spinal tumors as well as lesions in the lung, liver, and other body sites.

UAB was the first institution in the United States to treat patients with volumetric arc therapy (RapidArc, Varian Medical Sys-tems, Palo Alto, CA). The system provides high-quality computed tomography images with greatly shortened treatment times, reducing potential for patient movement between imaging and radiation delivery. The ability to safely and precisely deliver radiation to multiple body sites lets UAB’s Radiosurgery Program physicians treat the patient as a whole, not just as a single organ system.

As treatment options for metastatic tu-mors increase, it is important for medical oncologists, radiation oncologists, and sur-geons to be aware of all the available treat-ment options, including research trials. At UAB, patient treatment plans are discussed in multidisciplinary tumor conferences to ensure the most advanced treatment plan for

each patient. This allows for coordination between chemotherapy, radiation, and surgi-cal treatment.

In addition to malignant tumors, benign tumors such as meningiomas, schwanno-mas, and pituitary tumors are treated with Gamma Knife radiosurgery. While these lesions have traditionally been treated with surgical resection, many patients prefer the noninvasive treatment provided by radio-surgery.

The neurosurgical team — Barton L. Guthrie, MD; James M. Markert, MD, MPH; Kristen O. Riley, MD; and Winfield S. Fisher III, MD — also have vast ex-perience using the Gamma Knife to treat trigeminal neuralgia and complex brain vascular malformations.

RadiosurgeryDeveloping Optimal Plan for Patients

Dr. Bart guthrieDr. James markertDr. WinfielD fisherDr. kristen [email protected]

FOr mOreinFOrmaTiOn

CNS Benign CNS Malignant Trigeminal Neuralgia Vascular

Patient volume varies by disease, and in 2008, patients were treated as indicated above.

Since 1992 radiosurgery procedures have increased from 11 patients to nearly 400 patients per year.

Patient Volume by Disease Number of Patients Treated at UAB

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Neurology/Neurosurgery

UAB Neurology and Neurosurgery at a Glance

DIvISIoN oF NeUroSUrGerYServICeS, ProGrAMS, AND CeNTerS

Brain Tumor ServiceNeuro-oncology Research Program

Cerebrovascular Service

Spine Service Minimally Invasive Surgical Program

Functional/Movement Disorders Service

Pediatric Service

Fellowship in Pediatric Neurosurgery

Gamma Knife ServiceUAB Gamma Knife Center

Comprehensive Epilepsy Center

Neurotrauma Service

Peripheral Nerve/Brachial Plexus Service

Resident Education Program

General Neurosurgery Service

DePArTMeNT oF NeUroloGYDIvISIoNS, ProGrAMS, AND CeNTerS

Center for Neurodegeneration and Experimental Therapeutics

Division of Cerebrovascular DiseaseComprehensive Stroke Research Center

Division of EpilepsyEpilepsy CenterUAB-HSF Magnetoencephalography Laboratory

Division of Memory Disorders and Behavioral NeurologyAlzheimer’s Disease Center

Division of Movement DisordersParkinson Disease and Movement Disorder Research ProgramParkinson Disease Information and Referral Center

Division of Neuro-oncology

Division of Neuropsychology

Division of Neuroimmunology and Multiple SclerosisCenter for NeuroimmunologyMultiple Sclerosis Center

Division of Neuromuscular Disease

Neurology Residency Program

General Neurology Program Neurology Fellowship Programs Medical Student Education Program

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Neurology/Neurosurgery

The Multidisciplinary research Team

Neurology

Movement Disorders Rebecca McMurray, 205.996.4034 / [email protected]

Epilepsy Nancy Cohen, 205.934.7244 / [email protected]

Cerebrovascular Disorders April Sisson, 205.975.7571 / [email protected]

Neuroimmunology Beverly Layton, 205.934.1885 / [email protected]

Neuromuscular Mary Ward, 205.934.2120 / [email protected]

Headache Silvia Weibelt, 205.996.7944 / [email protected]

Memory Disorders Pamela trull, 205.934.0496 / [email protected]

Neurosurgery

Neuro-oncology Beth Casey, 205.934.1848 / [email protected]

Cerebrovascular Disorders Beth Casey, 205.934.1848 / [email protected]

Movement Disorders Stephanie Guthrie, 205.996.4033 / [email protected]

Memory Disorders Denise Ledlow, 205.934.6223 / [email protected]

Neurotrauma/Traumatic Brain Injury Blair MacDowell, 205.934.0994 / [email protected] Adrianne McCullars, 205.934.2334 / [email protected]

Spinal Stenosis Meredith Owens, 205.481.7938 / [email protected]

the UAB Department of Neurology and the Division of Neurosurgery work collaboratively with experts from multiple disci-plines, including vascular surgery and endovascular therapy, radiation oncology, physical medicine and rehabilitation, and oth-ers, to produce cutting-edge approaches and newer treatment options for a wide variety of conditions.

in addition to offering a strong clinical effort to improve patients’ quality of life, UAB is home to a large network of scientists working in partnership at all levels. these translational researchers are dedicated to discovering novel approaches and solu-tions that improve patient outcomes while preserving health care resources.

Research efforts in these areas span a broad spectrum of treatments that utilize device, pharmacologic, biologic, and gene therapies. UAB’s Department of Neurology and Division of Neurosurgery currently have more than 200 active clinical trials. for more information, please contact the appropriate coordinator (see below).

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16 Uab insighT On neUrOsciences • Fall 2009

Neurology/Neurosurgery

UAB Faculty at a GlanceGrowth is key to the success of the neurosciences at UAB. In the past 5 years we have doubled our neurology faculty, which now has more than 50 physicians and researchers. The Division of Neurosurgery has 16 faculty members, including 13 full-time neurosurgeons.

DePArTMeNT oF NeUroloGY

Movement DisordersRay L. Watts, MD, John N. Whitaker Professor and Chair of NeurologyDavid G. Standaert, MD, PhD, John and Juanelle Strain Professor and Vice Chair of NeurologyErwin B. Montgomery Jr, MD, Dr. Sigmund Rosen Scholar in Neurology Leon S. Dure, MD Paul R. Atchison, MD Yuqing Li, PhDAnthony P. Nicholas, MD, PhD Natividad P. Stover, MD

Andrew B. West, PhD, John A. and Ruth R. Jurenko Research Scholartalene A. Yacoubian, MD, PhD, Parkinson’s Association of Alabama Scholar in Parkinson’s Researchharrison Walker, MD Michelle Gray, PhD, Dixon Scholar in NeuroscienceRyan R. Walsh, MD, PhD, Francis and Ingeborg Heide Schumann Fellow in Parkinson’s Disease ResearchAmy W. Amara, MD, PhD, Francis and Ingeborg Heide Schumann Fellow in Parkinson’s Disease Researchvictor Sung, MD, fellow

EpilepsyR. Edward faught Jr, MD Martina Bebin, MD, MPA Robert C. Knowlton, MD, MSPhJennifer L. DeWolfe, DO Nita A. Limdi, PharmD, PhD, MSPh A. LeBron Paige, MD Lawrence ver hoef, MD Rotem Elgavish, MD, PhD

Memory DisordersDaniel C. Marson, JD, PhDLindy E. harrell, MD, PhD Roy C. Martin, PhD

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Neurology/Neurosurgery

UAB Faculty at a Glance

Neuro-oncologyJames M. Markert, MD, MPh, Director and James Garber Galbraith Endowed Chair in NeurosurgeryBarton L. Guthrie, MDKristen O. Riley, MDM. Renee Chambers, DvM, MD

Neuro-oncology ResearchG. Yancey Gillespie, PhDCorinne Griguer, PhD

Functional and Movement DisordersBarton L. Guthrie, MD

CerebrovascularWinfield S. fisher iii, MDMark R. harrigan, MD

EpilepsyKristen O. Riley, MD

SpineMark N. hadley, MD, Patsy W. and Charles A. Collat Endowed Chair in NeurosurgeryMamerhi O. Okor, MDPatrick R. Pritchard, MDthomas G. Spurlock, DC

General (including spine)M. Renee Chambers, DvM, MD

Pediatric (including spina bifida, brain tumors, craniofacial disorders, epilepsy, and spine disorders)W. Jerry Oakes, MD, Dan L. Hendley Chair in Pediatric NeurosurgeryJeffrey P. Blount, MDCurtis J. Rozzelle, MDJohn C. Wellons iii, MD

DePArTMeNT oF SUrGerY, DIvISIoN oF NeUroSUrGerY

David G. Clark, MD h. Randall Griffith, PhD Miller Piggott, MSW Erik Roberson, MD, PhD, Virginia B. Spencer Scholar in NeuroscienceKristen L. triebel, PsyD

Neuro-oncologyL. Burt Nabors, MD hassan fathallah-Shaykh, MD, PhD Xiaosi “Stan” han, MD, PhDCheryl Ann Palmer, MD

NeuromuscularShin J. Oh, MD Peter h. King, MD Gwen Claussen, MD Angela Young Achong, MD Liang Lu, MD, PhD Marla Morgan, MD Esther A. Suswam, PhD

HeadacheJohn f. Rothrock, MD J. ivan Lopez, MD

Cerebrovascular Andrei v. Alexandrov, MD J. ivan Lopez, MDDamon Patterson, MDAnne W. Alexandrov, PhD, RN, CCRNAaron Anderson, MD

Neuroimmunology Khurram Bashir, MD, MPh John R. Rinker ii, MD

General NeurologyJohn C. Brockington, MD