Tomorrow's Neurological Care. Today.
Transcript of Tomorrow's Neurological Care. Today.
NEUROLOGICAL INSTITUTE | 2007 ANNUAL REPORT
Tomorrow’s Neurological Care.
Today.
Cleveland Clinic’s Neurological Institute is a multidisciplinary institute that
combines all physicians and other healthcare providers in neurology, neurosurgery,
neuroradiology, the behavioral sciences and nursing who treat adult and
pediatric patients with neurological disorders. This structure allows for a disease-
specifi c, patient-focused approach to care. Our unique, fully integrated model
is benefi cial to our current standard of care, allows us to measure quality
and outcomes on a continual basis, and enhances our ability to conduct research.
CONTENTS 2 Chairman’s Welcome
4 Neurological Institute Overview
6 Education
10 Research
18 The Knowledge Program
OUR CENTERS OF CARE
20 Brain Tumor and Neuro-Oncology Center
28 Cerebrovascular Center
36 Epilepsy Center
44 Center for Headache and Pain
50 Mellen Center for Multiple Sclerosis Treatment and Research
58 Center for Neuroimaging
62 Center for Neurological Restoration
68 Neuromuscular Center
74 Center for Pediatric Neurology and Neurosurgery
84 Department of Psychiatry and Psychology
92 Sleep Disorders Center
98 Center for Spine Health
ADDITIONAL INFORMATION
108 Neurological Institute Staff
112 Upcoming Symposia
113 How to Refer Patients
113 Locations
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2 | WELCOME
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WELCOME | 3
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DEAR COLLEAGUES
A newly arriving staff member mentioned to me that he thought cognition should be the fi fth vital sign. Medical
school has taught us to check for temperature, pulse, blood pressure and respiratory rate. But a key sign of a healthy
brain is its ability to do its job: to think.
Today, cognitive disorders and their prevalence are a greater
problem than anyone ever anticipated they could be. As we
all live longer lives, we also encounter a greater magnitude of
cognitive problems, on a personal, professional and societal
level. At the same time, we also are at a unique age of discovery
regarding these disorders. We’re learning that cognitive disorders
can be identifi ed at a stage earlier than previously believed and
potentially be altered. We’re also learning that more precise
identifi cation of the problem and understanding of the mecha-
nisms behind the damage can help us combat this high price
of aging. We’re realizing that memory programs, physical and
occupational therapy, even more precise identifi cation of brain
anomalies causing cognitive disorders can help us to better keep
our mental capacities intact. We’ve also identifi ed that the risk
factors for dementia overlap with those relative to cardiovascular
disease.
At a place like Cleveland Clinic, where we routinely incorporate
multidisciplinary, disease-based care, within our Neurological
Institute, we feel we have the perfect breeding ground for a cog-
nitive disorders program. In 2007, we announced the creation
of our new Center for Brain Health, which will bring together
researchers, clinicians, therapists, surgeons, imaging special-
ists and a variety of other experts to continue to advance our
understanding of cognitive disorders and to provide the optimum
in care to patients who suffer from them.
The Center for Brain Health will share the unique attributes of
our other centers and departments, promoting collaboration
across all care providers, offering patients a complete continuum
of care and infusing education and research into all that we do.
In 2007, these centers and departments of the Neurological
Institute continued to enhance their facilities, technologies and
processes, which I am pleased to share with you here in our
2007 annual report.
Of particular note is our undertaking of the Knowledge Program,
which is an institute-wide effort to standardize our data collec-
tion within each patient’s electronic medical record to better
track outcomes and analyze data.
As we continue to evolve and enhance our institute, I look
forward to sharing with you updates regarding our new Center
for Brain Health, our Knowledge Program and other efforts to
improve patient care.
Sincerely,
Michael T. Modic, MD, FACR
Chairman, Neurological Institute
4 | OVERVIEW
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
CLEVELAND CLINIC NEUROLOGICAL INSTITUTE
OVERV IEW
The multidisciplinary Cleveland Clinic Neurological Insti-
tute (NI) includes more than 220 medical, surgical and
research specialists dedicated to the treatment of adult
and pediatric patients with neurological and psychiatric
disorders. The institute offers a disease-specifi c, patient-
focused approach to care. Our unique, fully integrated
model strengthens our current standard of care, allows
us to measure quality and outcomes on a continual basis,
and enhances our ability to conduct research.
U.S.News & World Report’s “America’s Best Hospitals”
survey consistently has ranked our neurology and neu-
rosurgery programs among the top 10 in the nation. Our
neurology, neurosurgery and psychiatry programs are also
ranked best in Ohio.
The institute model allows our patients to better access
the care they need through specialized, multidisciplinary,
disease-specifi c centers that integrate the expertise of
neurologists, neurosurgeons, psychiatrists, psychologists,
neuroradiologists, and others, into the comprehensive
care of a single disease:
° Center for Brain Health
° Brain Tumor and Neuro-Oncology Center
° Cerebrovascular Center
° Epilepsy Center
° Center for Headache and Pain
° Mellen Center for Multiple Sclerosis Treatment
and Research
° Center for Neurological Restoration
° Neuromuscular Center
° Center for Pediatric Neurology and Neurosurgery
° Sleep Disorders Center
° Center for Spine Health
Additionally, our Center for Neuroimaging and Depart-
ment of Psychiatry and Psychology provide care across
all our disease-based centers.
We provide care across the spectrum of neurological
disorders, including primary and metastatic tumors of
the brain, spine and nerves; pediatric and adult epilepsy;
headache, facial pain syndromes and associated disor-
ders; movement disorders such as Parkinson’s disease,
essential tremor and dystonia; cerebral palsy and spastic-
ity; hydrocephalus; metabolic and mitochondrial disease;
fetal and neonatal neurological problems; multiple sclero-
sis; stroke; cerebral aneurysms; brain and spinal vascular
malformations; carotid stenosis; intracranial atherosclero-
sis; nerve and muscle diseases, including amyotrophic
lateral sclerosis, peripheral neuropathy, myasthenia gravis
and myopathies; sleep disorders; and mental/behavioral
health disorders and chemical dependencies.
EXPERT, SPECIALIZED DIAGNOSIS
Our Neurological Institute physicians draw on advanced
diagnostic capabilities and experience.
Our imaging services include structural and functional
magnetic resonance imaging (MRI), computed tomogra-
phy (CT), positron emission tomography (PET), myelogra-
phy, diagnostic cerebral/spinal angiography, interventional
neuroradiology, and carotid and transcranial Doppler ultra-
sound. Our neuroimaging staff subspecializes in specifi c
220 Staff Physicians
134 Clinical Residentsand Fellows
17Research Fellows
27Advanced Practice Nurses
15 Physician Assistants
NI STAFF BY
THE NUMBERS
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disease entities, such as epilepsy and cerebrovascular
disease, ensuring accurate, in-depth interpretations.
Additional diagnostic tools are found in our epilepsy
monitoring units, sleep laboratories, neuropsychological
testing facilities, electromyography laboratory, autonomic
laboratory and cutaneous nerve laboratory.
THE LATEST TREATMENT MODALITIES
Patients can receive leading-edge treatment options at
the Neurological Institute, where we continue to advance
such innovations as deep brain stimulation (brain pace-
makers), epilepsy surgery, stereotactic spine radiosurgery,
blood-brain barrier disruption, endovascular treatment of
cerebral aneurysms and vascular malformations, and neu-
roendoscopy. Distinctive services such as our three-week
outpatient program for sufferers of chronic headaches
(IMATCH) and our Headache Infusion Suite provide
intensive therapy when it is needed. The Brain Tumor
and Neuro-Oncology Center’s Translational Therapeutics
Program is accelerating the process of bringing novel
therapeutic agents from the laboratory to the patient,
while maintaining the highest standards of effi cacy and
safety. Joint Commission certifi cation as a Primary Stroke
Center and accreditation by the American Academy of
Sleep Medicine are just two examples of our commitment
to providing the most advanced and highest quality of
care to our patients.
RELEVANT RESEARCH
We strive to conduct research directly related to condi-
tions experienced by our patients, including programs in
translational research, clinical trials of drug and device
interventions, neuroimaging research, epidemiology and
health outcomes, behavioral and psychiatric research,
and research into better diagnostic methods. More than
175 clinical research trials are under way at the Neuro-
logical Institute. In the area of basic science, a core of
internationally recognized neuroscientists with external
funding totaling $10 million annually conduct investiga-
tions at the Cleveland Clinic Lerner Research Institute.
CONVENIENT CARE IN THE COMMUNITY
We are committed to making access to world-class
care convenient for all patients — whether coming
to us from near or far. Our Neurological Institute Regional
Centers are a system-wide effort to extend our services
to regional hospitals and at Cleveland Clinic family health
centers throughout the community. In addition, Cleveland
Clinic neurologists oversee inpatient care at a number
of Cleveland Clinic hospitals. Our Sleep Disorders Center
has pioneered the idea of hotel-based sleep studies,
offering overnight studies at multiple locations throughout
the community for patients’ convenience and comfort.
INTEGRATED NURSING SERVICES
Nursing in the institute integrates inpatient and ambul-
atory nursing, enhancing the continuum of patient care.
This unique structure also lends itself to greater informa-
tion sharing and process improvement opportunities.
Through continuing education programs, we are able to
broaden nursing educational opportunities from basic
nursing instruction to subspecialization in neurological
nursing, much like our physician colleagues.
At Cleveland Clinic’s Neurological Institute, we are
dedicated to maximizing patient care outcomes and the
patient experience, and to advancing medical education
and research in all areas of neurology, neurosurgery and
psychiatry.
6 | EDUCATION
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
EDUCAT ION
CONTINUING MEDICAL EDUCATION
The Neurological Institute collaborates with Cleveland Clinic’s Center
for Continuing Education to offer a variety of programs to physicians.
The center is responsible for one of the largest and most diverse CME
programs in the world. In 2007, there were more than 8,500 partici-
pants in 195 Neurological Institute-sponsored CME programs. The
programs ranged from weekly grand rounds in neurosurgery, neurology,
epilepsy and psychiatry to week-long symposia that provided in-depth
updates about the latest treatment options or research results on a
variety of neurological-based topics.
In its mission to provide a wide array of fi rst-rate continuing medical
education opportunities to medical professionals throughout the world,
the center also offers neurology-based online CME credit. In 2007,
1,303 CME certifi cates were awarded for the completion of online neuro-
logical courses covering topics such as migraine headaches, depression
and multiple sclerosis.
RESIDENCIES AND FELLOWSHIPS
The Neurological Institute offers extensive opportunities in physi-
cian education and research. We take special pride in training future
practitioners. The institute offers more than 30 training programs in
neurology, neurosurgery, psychiatry and psychology. This includes core
residency ACGME-accredited programs in adult neurology, child neurol-
ogy, neurosurgery, adult psychiatry and child and adolescent psychiatry,
as well as ACGME-accredited subspecialty fellowships and non-accredit-
ed fellowships. In 2007, 170 clinical and research fellows and residents
were trained through our programs.
NI RESIDENCIES
Adult Neurology
Child and Adolescent Psychiatry
Child Neurology
Psychiatry
Neurosurgery
NI FELLOWSHIPS
Chronic Pain Rehabilitation
Clinical Neuroimmunology
Clinical Neurophysiology/EEG
Clinical Neurophysiology/EMG
Endovascular Neuroradiology
Epilepsy
Epilepsy Surgery
Functional and Restorative Neurosurgery
Headache
Health Psychology
Movement Disorders
Neurocritical Care
Neuromuscular Medicine
Neuropsychology
Neurosurgical Oncology
Pediatric Neurosurgery
Psychosomatic Medicine
Skull Base Surgery
Sleep Medicine
Spine Medicine
Spine Surgery
Vascular Neurology
The Neurological Institute is committed to providing quality medical education to physicians, nurses
and other medical professionals within the institute, as well as regionally, across the country and
all over the world. From continuing medical education to residencies and fellowships to our observer
program, education is incorporated into all aspects of our institute.
170 clinical and
research fellows
and residents
were trained
120 medical students
matriculated in
NI’s core and
elective programs
EDUCATION | 7
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8 | EDUCATION
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
Our training programs offer research opportunities for trainees who plan to pursue careers in
academic neurology, neurosurgery, and psychiatry and psychology. We offer fl exible programs
that foster individual interests. Trainees are expected to participate in basic and clinical re-
search projects and are encouraged to present their fi ndings at national meetings.
CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE
The Cleveland Clinic Lerner College of Medicine of Case Western Reserve University is a
unique medical school established in 2002 that sets new standards for the training of physi-
cian investigators through innovative approaches to the integration of basic science, research
and clinical medicine. Physicians within the Neurological Institute direct the basic neurosci-
ence curriculum in years one and two of the school. This includes organization of the content
and teaching of the topics in a problem-based learning format. In 2007, 76 Neurological
Institute staff members taught courses at the medical school.
Additionally, physicians within the Neurological Institute direct the neurology, neurosurgery
and psychiatry clinical curriculum, including basic rotations, acting internships and advanced
electives. Cleveland Clinic’s basic rotations in neurosciences have been rated by the medical
school students as the best in the city.
70
international observers
visited our centers
of excellence
8,588 participants in CME-accredited,
NI-sponsored programs
490
CME hours offered in
NI-sponsored programs
195 CME-accredited programs
offered by the NI
2007 NI
PUBLICATIONS
352 journal articles
64
book chapters
7
books
EDUCATION | 9
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Research is a thread that runs throughout the entire fi ve-year medical
school curriculum. Neurological Institute physicians and scientists
mentor a number of medical students with projects in the clinical and
basic neurosciences. Medical students are invited to present their
projects at the annual Neurological Institute Research Day, when
poster and platform presentations are given, and medical students,
residents and fellows compete for recognition awards.
INTERNATIONAL PHYSICIAN OBSERVER PROGRAM
International Physician Observers are foreign physicians selected
to visit a designated medical department at Cleveland Clinic. The
program exposes participants to the latest practices within a specialty
area through clinical interactions, operating room observations and
teaching conferences. In 2007, the Neurological Institute hosted 70
international observers to our centers of excellence.
2007 EDUCATIONAL
H IGHL IGHTS
° The Brain Tumor and Neuro-Oncology Center held
the fi rst international symposium on Stereotactic Body
Radiation Therapy and Stereotactic Radiosurgery
in Orlando, Fla.
° The Center for Spine Health held its week-long spine
review course in Cleveland and in Cairo, Egypt
° The Epilepsy Center attracted nearly 650 attendees
to its Epileptology Review course and the 17th Interna-
tional Epilepsy Symposium
° Our Department of Neurosurgery held a neuro-endo-
scopic surgery course in Beijing, China, for more than
200 participants
° The Department of Psychiatry and Psychology hosted
the second annual Post Traumatic Stress Disorder
Symposium for more than 230 mental healthcare
professionals
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NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
Conducting exceptional research has been an important part of
the mission of Cleveland Clinic since its inception in 1921. At
Cleveland Clinic, neurological research is conducted on three
levels:
° Fundamental, laboratory-based biomedical research, conducted
in the research institute
° Translational research that applies fi ndings from the laboratories
to our patients and clinical populations
° Patient-based clinical research aimed at developing new tests
or treatments, or aimed at understanding disease and its impact
INNOVATIONS
In 2007, the NI founded the Neurological Institute Community
of Collaborative Innovation (NICCI), a multidisciplinary group
of physicians, scientists and bioethicists from the Neurological
Institute, the Lerner Research Institute and the Department of
Bioethics. The group’s mission is to create and maintain a culture
of innovation within the institute, and to manage any associated
confl icts of interest. NI staff were active innovators in 2007, reg-
istering 21 inventions with the Cleveland Clinic Innovations offi ce
and receiving three patents and four licenses for their discoveries.
Three new spin-off companies were created in 2007 based on NI
technology: Autonomic Technologies, CardioNomic and ReVasc
Technologies.
GRANTS AND CONTRACTS
Neurological research conducted within the Neurological Insti-
tute, Lerner Research Institute and the Department of Neuroradi-
ology received strong support in 2007. Grant and research dollars
funding neurologic investigations totaled almost $14 million in
2007, including more than $9 million for laboratory-based re-
search and nearly $5 million for patient-based research. Funding
came from federal, state, local, corporate and private sources,
including more than 50 grants from the National Institutes of
Health.
RESEARCH
NOT-FOR-PROFIT SPONSORS
OF NI RESEARCH
ALS Association
American Cancer Society
American Epilepsy Society
American Parkinson Association
American Sleep Medicine Foundation
Centers for Disease Control
Consortium of Multiple Sclerosis Centers
Epilepsy Foundation
Metanexus Institute
Nancy Davis Foundation
National Brain Tumor Foundation
National Epifellows Foundation
National Library of Medicine
National Parkinson Foundation
NIH — Eunice Kennedy Shriver National Institute
of Child Health and Human Development
NIH — National Cancer Institute
NIH — National Institute of Allergy and
Infectious Diseases
NIH — National Institute of Mental Health
NIH — National Institute of Neurological Disor-
ders and Stroke
NIH — National Institute on Aging
National Multiple Sclerosis Society
Ohio Department of Development
Research Triangle Institute (RTI International)
Tuberous Sclerosis Alliance
U.S. Army Research Offi ce
U.S. Department of Energy
Wallace Clinical Trials Center
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PUBLICATIONS
Many notable discoveries were made, as evidenced by
the many manuscripts accepted by high-impact journals
in 2007. Institute researchers’ manuscripts appeared in
infl uential publications such as EMBO Journal, Journal
of the American Medical Association, Lancet, Nature,
Nature Neurosciences, New England Journal of Medi-
cine, Proceedings of the National Academy of Sciences
USA, and Science. In 2007, NI staff authored more
than 400 journal articles, book chapters and books.
LERNER RESEARCH INSTITUTE
The Lerner Research Institute is the basic science
research arm of Cleveland Clinic, housing all of our
laboratory-based and translational biomedical research.
A hallmark of the institute is its focus on disease-
oriented research, working to create new diagnostic
tools, treatments and therapies, in collaboration with
partners in the clinical institutes.
Thirty-six Lerner Research Institute scientists pursued
neurologically based research projects in 2007, including
10 Neurological Institute clinicians who also conducted
basic research in the Lerner Research Institute. This
structure of bringing laboratory-based and clinical
researchers together encourages translational research
— taking the discoveries made in the laboratory to the
patient’s bedside as quickly and safely as possible. The
environment of collaboration between basic and clinical
researchers has the more immediate effect of improving
patient care today.
Neurological investigations within Lerner Research In-
stitute are carried out in the departments of Biomedical
Engineering, Cell Biology and Neurosciences.
This fl uorescence microscopy depicts cells being generated from neural
stem cells, which can generate in vitro astrocytes, oligodendrocytes and
neurons according to the stimuli they are under. These cells are prime
candidates for stem cell transplantation therapies. Here, the green staining
is for the astrocyte marker glial fi brilary acidic protein and the red is the
oligodendrocyte precursor marker platelet-derived growth factor receptor-
alpha. Oligodendrocyte precursors (red) migrate away from the core while
astrocytes (green) proliferate without apparent migration.
Department of Neurosciences
The Department of Neurosciences, founded in 1994, is
chaired by Bruce Trapp, PhD, and comprises a core of
internationally recognized scientists. The department is
divided into several core groups that focus on funda-
mental aspects of brain function and the pathogenesis
of human disease. Strong basic science programs have
resulted in the development of animal models of human
diseases, which include rodents, zebrafi sh and primates.
Departmental researchers directly investigate the patho-
genesis of human central nervous system (CNS) diseases
and have developed a unique rapid autopsy program for
these studies. The overall goal of the department is to
elucidate the cause of nervous system diseases and to
develop therapeutics that stop or delay their progression.
The interactions between faculty in the departments of
neurosciences, neurology, neurological surgery, radiology
and behavioral medicine provide a unique environment
for reaching these goals.
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
12 | RESEARCH
A major strength of the department is developmental
neurobiology. Most faculty members have a research
program in brain development. These interests range
from stem/progenitor cells to the function of disease-
related genes including the amyloid precursor protein,
chemokines, myelin proteins, neurotransmitter receptors,
BACE1 and the reticulins.
The department is noted internationally for its program in
glial development, recently discovering a primitive neural
cell with stem-cell-like characteristics. These cells show
a remarkable capacity to generate new myelin in a rodent
model of human myelin disease. Other developments
include mouse and zebrafi sh lines in which cells of the
oligodendrocyte lineage express green fl uorescence
protein. The mice have become a common and valuable
resource in the glial research community. A major project
focuses on Akt signaling in oligodendrocytes, which in-
duces hypermyelination. Another recent discovery is the
identifi cation of a role for chemokines in oligodendrocyte
colonization of the developing rodent brain. Additional
current research includes cerebellar development,
especially migration of granule cells, and the use of both
rodent and zebrafi sh models to study the function of the
amyloid precursor protein during development.
The glial research program has close ties with physicians
in the Neurological Institute’s Mellen Center for Multiple
Sclerosis Treatment and Research. Studies conducted
here on the function of myelin proteins in mice have
demonstrated that long-term axonal survival depends
upon trophic support from myelin. As an extension of
these basic science studies, Cleveland Clinic research-
ers described axonal degeneration as a major cause of
neurological disability in MS patients. A rapid autopsy
program was developed for individuals with MS. A
unique aspect of these autopsies is a post mortem MRI
that has been instrumental in defi ning pathological cor-
relates of MRI abnormalities.
Current research in the neurodegenerative disease
program includes a strong focus on Alzheimer’s disease.
This includes investigations of molecular mechanisms
of neurodegeneration in Alzheimer’s disease, focusing
on the role of β-secretase, its interacting proteins and
modifi cation of its activity in disease pathogenesis; the
genetic, therapeutic and environmental factors modify-
ing Alzheimer’s disease pathogenesis using transgenic
mouse models of the disease; and the normal biologi-
cal functions of the amyloid precursor protein in both
zebrafi sh and mice and the implications these may have
for neurodegenerative disease mechanisms underly-
ing Alzheimer’s disease. Additional neurodegenerative
research includes the mechanisms of neuronal degen-
eration in amyotrophic lateral sclerosis (ALS) and the
pathogenesis of neurodegeneration in an animal model of
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RESEARCH | 13
ALS. Neuroimaging research within the section examines
the functional neuroimaging correlates of neurodegenera-
tive disease pathogenesis, including Alzheimer’s disease,
Parkinson’s disease and MS.
The Neuromodulation Research Center (NMRC) focuses
on the functional and physical changes in patients with
movement disorders, the mechanisms of deep brain
stimulation (DBS), and the development of new applica-
tions for DBS. The center incorporates investigators
from the institute’s departments of Neurosciences and
Biomedical Engineering as well as faculty from the Neu-
rological Institute and the Imaging Institute. The NMRC
is unique in that it uses a multidisciplinary approach to
understand how neurological diseases arise and progress
within the CNS. The NMRC then works to translate these
understandings into clinical therapeutic applications.
NMRC researchers were the fi rst to describe the effect
of stimulation in the subthalamic nucleus on the basal
ganglia thalamic circuit. The NMRC also has modeled
the effect of stimulation on neuronal tissue using fi nite
element models of neural tissue based on anatomi-
cal and electrophysiological data from primates with
Parkinsonism. Current research includes using quantita-
tive kinematic measures to assess the effects of DBS on
motor control and daily living experiences of Parkinson’s
disease (PD) patients, including the interaction between
cognitive and motor function and the effect of exercise
on PD motor symptoms; studying the mechanisms
of DBS using functional MRI to evaluate the network
changes that take place during DBS in PD patients;
studying mechanisms of DBS through imaging, modeling
and quantitative kinematic studies in dystonia and PD;
developing closed-loop systems for DBS programming;
and using chronic recording from cortical neurons to
develop prosthetic devices.
The Neuroinfl ammation Research Center (NIRC) con-
ducts multidisciplinary translational research to address
neuroinfl ammation in human disorders including MS,
Alzheimer’s disease, Parkinson’s disease, amyotrophic
lateral sclerosis (ALS) and stroke. The center includes an
internationally recognized initiative in MS that provides
DETECTING CHANGES IN BRAIN ACTIVATION
PATTERNS IN EARLY ALZHEIMER’S DISEASE
A team of investigators in the Neurological Institute
is studying changes in brain activation of healthy
older individuals (ages 65-85) who are genetically
at risk for developing Alzheimer’s disease (AD)
and individuals who have Mild Cognitive Impair-
ment (MCI), a condition that typically precedes the
diagnosis of AD. One goal of the study is to develop
an imaging biomarker that can detect the earliest
brain changes associated with AD. Nineteen MCI
patients, 19 genetically at-risk but healthy older
adults, and 19 healthy older adults not at-risk for
AD (Control) were administered a memory task
while undergoing functional magnetic resonance
imaging (fMRI). Results indicate that fMRI is sensi-
tive to detecting the earliest changes in AD, even
before patients become symptomatic. The goal is to
use this imaging technology to assess the effi cacy
of drugs designed to delay the onset of AD.
Studies supported by the NIH (NIA R01 AG022304).
Three groups of older participants, MCI patients, individuals at-
risk for developing AD, and healthy not-at-risk control subjects
were asked to discriminate names of famous individuals from
those of unfamiliar persons. The difference in brain activation
(Famous > Unfamiliar) is shown in blue. MCI and at-risk par-
ticipants exhibited greater brain activity than controls. Results
suggest that early AD-related changes require the brain to “work
harder” to achieve similar levels of task performance. (Rao SM,
et al. Submitted.)
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
14 | RESEARCH
a template for program development and exemplifi es
bench-to-bedside evolution. Our current focus includes
neuroimmunology, leukocyte traffi cking, blood-brain
barrier function, cytokine action and signaling, and
innate immune mechanisms (including Toll-like recep-
tors) in furtherance of the mission to understand how
the CNS interacts with the hematogenous compartment
and the peripheral nervous system. The center recently
established a program of study in a viral model of MS
and received grant support from the National Institute
of Allergy and Infectious Diseases/NIH for this research.
In 2007, the center developed a new mouse model of ce-
rebral vasospasm to study how infl ammatory cells in the
cerebrospinal fl uid precipitate ischemic stroke in patients
who have suffered subarachnoid bleeding. Other current
projects include the study of a novel mouse model of
microglial activation in Alzheimer’s disease, and a new
and more clinically relevant model of Duchenne muscular
dystrophy, which will be used to defi ne how infl amed
and dystrophic muscle becomes fi brotic.
Biomedical Engineering
Lerner Research Institute’s Biomedical Engineering
Department provides a forum in which engineers, basic
scientists and physicians can interact, seeking together
to apply engineering principles to solve biomedical
problems. Active research programs include biological
microelectromechanical systems (BioMEMS) and the
design and utilization of micro-computed tomography
(micro-CT), quantifying images of the brain in multiple
sclerosis, and recording and modeling the brain’s electri-
cal activity.
Biomedical imaging staff researchers work on a variety
of research projects that include clinical, microscopic
and small animal imaging applications. The primary goal
of these investigators is to develop novel imaging and
image post-processing techniques to detect, diagnose
and monitor the progression of disease and to evaluate
different treatment therapies. Research and development
within this group includes tissue characterization using
high-frequency intravascular ultrasound, 3D real-time
ultrasound and multimodality imaging, quantitative
analysis of tissue damage due to multiple sclerosis in MR
images of the brain, and 3D quantitative phenotyping in
micro-CT images of mice.
EVALUATING DEEP BRAIN STIMULATION WITH fMRI
Investigators from the Neurological Institute
and the Imaging Institute have collaborated
to study the effect of deep brain stimulation
(DBS) in patients with Parkinson’s disease
using functional MRI. The investigators are
determining how the brain is activated during
DBS for Parkinson’s disease. Early results
demonstrated a consistent pattern of brain
activation produced by stimulation within
the ipsilateral thalamus and globus pallidus.
These studies will lead to a better under-
standing of the relationship between brain
activation and DBS in Parkinson’s disease,
and will provide the necessary information
to maximize therapeutic benefi ts of this
treatment.
Studies Supported by the NIH (NINDS R01
NS052566-01A1).
Functional MRI obtained during active deep brain stimulation. Images A and B
demonstrate the activation pattern during unilateral right-sided activation. Image C
demonstrates activation during unilateral left-sided stimulation. Images are projected
using radiological convention. Phillips, et al. Radiology. 2006;239:209–216.
The overall goal of the department is to elucidate
the cause of nervous system diseases and to develop
therapeutics that stop or delay their progression.
The interactions between faculty in the departments
of neurosciences, neurology, neurological surgery,
radiology and behavioral medicine provide a unique
environment for reaching these goals.
A
B
C
CEREBROVASCUL AR CENTER | 15
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NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
16 | RESEARCH
Nanotechnologists use microelectronics, microfabrication
and micromachining technologies to improve medical di-
agnostics and therapies by reducing device size and cost.
Their collaborative studies involve engineering micro-/
nanometer-sized features for tissue engineering, protein
analyses, assays and cell interrogation. Among the ap-
plications being developed are miniaturized versions of
drug delivery systems, transducers for ultrasound images
and in situ telemetrically monitored pressure/temperature
sensors for minimally invasive surgery/follow-up.
The neural control group performs basic science and
clinical research related to neural control of movement.
The program focuses mainly at system level of the
central nervous system (CNS) as well as the muscular
system. Research interests include understanding CNS
plasticity/reorganization as a result of disease and medi-
cal intervention, and its relation with functional recovery.
Current projects include evaluating effects of deep
brain stimulation on lessening symptoms in Parkinson’s
disease and the underlying mechanisms using neural-
network simulation, and understanding CNS reorganiza-
tion in stroke and other neurological disorders using
neuroimaging and electrophysiological techniques.
Cell Biology
The Department of Cell Biology investigates the roles of
specifi c cell types in health and disease, researching cell
and molecular biology and infl ammation. Neurological-
INVESTIGATING BRAIN PATHOLOGY IN MULTIPLE SCLEROSIS
A team of investigators in the Neurological Institute and Lerner
Research Institute is studying changes in the brains and spinal cords of
patients with multiple sclerosis. One goal of the study is to develop more
informative imaging tools that can be used to monitor and treat MS
patients. In this study, regions of brain were selected from postmortem
MRIs of 10 multiple sclerosis patients, and classifi ed into MRI-defi ned
categories. One of the categories identifi ed swollen axons and axonal
loss, pathologies that are associated with neurological disability in MS.
Studies to characterize cellular and molecular changes in brain tissue are
continuing. We expect to gain improved understanding of mechanisms
leading to brain damage in MS patients, and improve methods to moni-
tor treatments for individual patients using noninvasive MRI methods.
Studies Supported by the NIH (NINDS PO1 NS38667).
Plot of percentage axonal area, axonal count and swelling index in each magnetic reso-
nance imaging group (gray bars denote T2-weighted imaging only; black bars denote
T2-weighted, T1-weighted and magnetization transfer ratio abnormal [T2T1MTR]) rela-
tive to the means for normal-appearing white matter (NAWM; hatched bars) regions.
Sd - standard deviation. Fisher E, et al. Ann Neurol. 2007;62:219–228.
countarea diameter
1.0
0.8
0.6
0.4
0.2
0.0
1.0
0.8
0.6
0.4
0.2
0.0
Fraction of NAWM (+s.d.)Fraction of NAWM (+s.d.)
NAWMT2-onlyT2T1MTR
Axonal Measurements By MRI Region Type
This histological image of a goat lumbar spine segment (stained with H&E
for an in vivo biocompatibility assessment of microelectromechanical
systems, or MEMS, materials) shows a cross-section of vertebral endplates
and disc, with the location of the MEMS chip in the void in the disc (arrow).
There is no evidence of infl ammatory or infectious cellular response, con-
fi rming the biocompatibility of the MEMS materials with living tissue.
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
RESEARCH | 17
based research currently being conducted includes
investigations of the blood-brain barrier, multiple drug re-
sistance, stroke and cerebrovascular damage, peripheral
markers of CNS damage, and molecular and proteomic
analysis of neurological disorders.
PATIENT-BASED RESEARCH
The Neurological Institute conducts research on condi-
tions experienced by our patients. Clinical research
protocols include programs in bench-to-bedside transla-
tional research, trials of drugs and devices, neuroimaging
research, epidemiology and health outcomes, behavioral
and psychiatric research, and investigations into better
diagnostic methods. More than 175 clinical research
protocols were active within the Neurological Institute
in 2007, including 44 newly opened studies. Patient-
based clinical research within the institute is conducted
by multidisciplinary research teams combining expertise
and clinical knowledge of investigators focusing on re-
search computing and informatics, clinical trial methods,
outcomes assessment and neuroimaging. Multidisci-
plinary teams that comprise of staff physicians, clinical
investigators of various professional disciplines, clinical
fellows, full-time research fellows, residents, nurses and
certifi ed research coordinators are supported by shared
enabling resources to coordinate study startup and
conduct, and to assist with study design, data capture
and analysis. Through a multidisciplinary, team approach
that uses central resources, we are able to generate new
knowledge that will create better treatment options for
our patients.
More than 1,600 patients were enrolled in clinical trials
at the Neurological Institute in 2007, including almost
700 newly enrolled patients, with more than 60 of our
staff members leading these trials. Research studies
covered the range of neurological conditions we treat, in-
cluding Alzheimer’s disease and dementia, spine disease,
brain tumors, epilepsy, headache and pain, multiple scle-
rosis, Parkinson’s disease and other movement disorders,
depression and affective disorders, nerve and muscle
disease, neuropediatrics and congenital disorders, sleep
disorders, stroke and neurocritical care.
2007 NI CLINICAL TRIAL HIGHLIGHTS
° Assessing the entry of chemotherapeutic agents into
brain metastases in women with breast cancer
° Evaluating selective, 5-lipoxygenase inhibition by Bo-
swellia serrata herbal medicine approach as an adjuvant
therapy in newly diagnosed and recurrent high grade
gliomas
° CONFIRM: comparing fumarate with Copaxone® in
patients with relapsing-remitting multiple sclerosis
° CARE-MS II: comparing two doses of alemtuzimab
(CAMPATH-1h) with Rebif® in patients with relapsing-
remitting multiple sclerosis
° Deep brain stimulation for obsessive-compulsive disorder
° Deep brain stimulation for the minimally conscious state
° Predictors of bipolar disorder recurrence in pregnancy
and the postpartum period
° Sensitivity of fMRI in identifying cognitive and functional
brain changes in preclinical Huntington’s disease
° Evaluating Duragen® plus adhesion barrier matrix to
minimize adhesions following lumbar discectomy
° Assessing changes in quality of life following surgery
versus medical management in persons with medically
intractable epilepsy
° IRIS: determining if pioglitazone is effective in lowering
the risk of stroke or myocardial infarction among non-
diabetic men and women with a recent ischemic stroke
and insulin resistance
Active trials 177
New trials 44
NI staff leading trials 64
2007 NI CLINICAL RESEARCH TRIALS AT A GLANCE
18 | THE KNOWLEDGE PROGRAM
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
At the core of the Knowledge Program is a redesign of
the way the Neurological Institute organizes the immense
amount of clinical information it has. “The project is an
institute-wide effort to change the way we collect data so
that it can be harvested and used,” explains neurologist
Irene Katzan, MD, who is directing the Knowledge Pro-
gram. “Our goal is to be able to look at data on both an
individual and group level to evaluate clinical treatment
over time and provide better care.”
One of the fi rst obstacles to be overcome was how to
make patient information that traditionally is gathered by
the nurse or physician during the clinical encounters more
readily available for future use. The Knowledge Program
is tackling this by utilizing a standardized format for enter-
ing information during patient visits. During the patient’s
appointment, all clinical information will be collected
and entered into the patient’s electronic medical record
in a standardized way, beginning with the evaluation of
incoming patients’ current health status. Obtaining infor-
mation on patients’ health using validated scales provides
means to determine how patients are doing and to better
judge responses to treatment.
“This is an electronic system in which patients complete
a self-administered questionnaire when they come in
for their appointment, prior to seeing the physician,”
Dr. Katzan explains. The health status measures will
include generic measures, such as the European Quality
of Life scale, as well as well-established disease-specifi c
scales such as the Headache Impact Test 6. “Establish-
ing a quantitative baseline will allow us to then look at
trends over time,” Dr. Katzan notes. Part of the process,
too, is ensuring that all physicians know how to access
the information to use it during each patient encounter.
The electronic patient questionnaires, which interface
with EPIC, Cleveland Clinic’s electronic medical record
software, are being rolled out center by center within the
Neurological Institute. By the end of 2008, they will be in
use institute-wide.
In addition, the Knowledge Program is in the process
of implementing a computer-adaptive testing system to
assess patients’ health status, in collaboration with a
National Institutes of Health initiative called the Patient-
Reported Outcomes Measurement Information System
(PROMIS). With this method, a computerized algorithm
determines the next best question in the series, based
upon prior responses from the patient. Dr. Katzan
describes this tool as “the future of patient-reported
outcomes assessment,” adding that it “creates a more
precise picture of what’s going on with the patient, using
fewer questions.”
At the other end of the patient care process, the
Neurological Institute needed a method to consistently
track outcomes of interventions, an essential element
in creating a meaningful database. Unfortunately, some
Neurological Institute patients are lost to follow-up due to
geographic distance or other reasons, Dr. Katzan says. To
THE KNOWLEDGE PROGRAM
Cleveland Clinic’s Neurological Institute treats more than 140,000 patients every year, making it one
of the busiest centers for neurological diagnosis and treatment in the United States. The Knowledge
Program is a visionary venture designed to leverage this patient volume to systematically analyze patient
care and improve outcomes for Neurological Institute patients.
THE KNOWLEDGE PROGRAM | 19
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
capture data on these patients, the Neurological Institute
plans to implement a simple but consistent and organized
telephone follow-up system. “This will make our patient
follow-up more systematic and ensure that the outcomes
information we capture is as accurate as possible.”
Dr. Katzan says.
By virtue of its complexity and scope, the Knowledge Pro-
gram is undoubtedly a bold concept, but Dr. Katzan notes
that the Neurological Institute is uniquely positioned to
make it a success due to its large patient population,
technological capabilities and organizational structure.
“We are one of the few institutions with all of the neces-
sary elements to implement such an ambitious database,
and we are leading the way,” she says. “Once we have all
of the pieces in place and operational, it is a matter of us-
ing the database for improving the quality and outcomes
of care.”
The Knowledge Program is a visionary venture
designed to leverage this patient volume to
systematically analyze patient care and improve
outcomes for Neurological Institute patients.
As part of the Knowledge Program, all Neurological Institute patients input their answers to standardized health questions prior to their appointments.
BRAIN TUMOR AND
NEURO-ONCOLOGYCENTER
22 | BRAIN TUMOR AND NEURO-ONCOLOGY CENTER
CLINICAL PROGRAMS
Neuro-oncologists, medical oncologists, neurosurgical oncologists, radiation oncologists,
neuropathologists, neuroradiologists and nurses in the Brain Tumor and Neuro-Oncology Cen-
ter (BTNC) collaborated in the treatment of more than 4,600 children and adults with brain
tumors and other related conditions in 2007.
Innovative and experimental nonsurgical treatments for life-threatening tumors, state-of-the-art
surgical techniques and targeted radiation neuro-oncology technologies applied in combi-
nation with molecular and chromosomal testing have positioned the Brain Tumor and Neuro-
Oncology Center at the forefront of individualized care for patients with brain tumors.
Clinical programs in the center include medical therapeutics, radiation therapy and neuro-
surgical treatment, as well as alternative methods for patients with a variety of benign and
malignant CNS conditions. The team at the BTNC cares for patients with gliomas, metastases,
pituitary and neuro-endocrine tumors, skull base tumors (meningiomas and schwannomas),
neurofi bromatosis and other phakomatoses, and primary central nervous system lymphoma.
NEURO-ONCOLOGY
BTNC neuro-oncology team members are experts in the use of medical therapeutics for the
treatment of brain tumors, including:
° Chemotherapy/growth modifi ers — traditional anti-tumor drugs as well as new agents
targeted at specifi c tumor modalities
° Immunotherapy — stimulating the patient’s immune system against tumor cells
° Intra-arterial chemotherapy with or without blood-brain barrier disruption — a procedure
in which chemotherapeutic agents are delivered to the brain through the bloodstream
with or without opening the normal barriers that may prevent those drugs from entering
the brain
° Alternative and complementary treatments — including dietary interventions and yoga
NEUROSURGICAL ONCOLOGY AND RADIATION NEURO-ONCOLOGY
BTNC surgeons, who pioneered computer-assisted stereotactic techniques for brain surgery in
the 1980s, have extended the scope of operable brain tumors through the use of leading-edge
technology, including:
° Stereotactic neurosurgery — computer-guided surgery that serves as a GPS system for
the brain, often using ‘fi ber tracking’ and functional MRI that allows the surgeon to see
the function and ‘wiring’ of the brain
° Minimally invasive as well as endoscopic and endoscopic-assisted surgical procedures
° Intraoperative magnetic resonance imaging (iMRI) — navigational guidance and monitor-
ing during tumor resection
° Convection-enhanced delivery — the slow, continuous infusion of drugs through the brain
to enhance drug delivery to brain tumors
° Intraoperative radiation therapy — uses the INTRABEAM®, a 50 kVp device placed in
the resection cavity of metastatic brain tumors to deliver a high local dose of radiation at
the time of surgery to prevent or delay the need for whole brain irradiation
° Fractionated radiotherapy — widespread exposure of the brain and tumor to repeated
low doses of radiation
Initial outpatient visits 465
Total outpatient visits 8,354
Admissions 906
Inpatient Days 4,075
Surgical Cases 935
2007 STATS
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
BRAIN TUMOR AND NEURO-ONCOLOGY CENTER | 23
° Brachytherapy — direct implantation of a radiation source within a tumor site
° Cranial radiosurgery — the delivery of high-intensity, focused radiation directly to mul-
tiple sites within the tumor using the Gamma Knife® or Novalis®. Gamma Knife® is used
for single treatments of small tumors; Novalis® is used for larger tumors.
° Spinal radiosurgery — the delivery of high-intensity, focused radiation directly to spinal
metastases employing the Novalis® shaped-beam platform.
FELLOWSHIPS
The BTNC offers several non-ACGME-accredited fellowships. These include two two-year fel-
lowships in neurosurgical oncology and a one-year fellowship in skull base surgery.
A fundamental goal of this combined clinical and research fellowship program is exposure to
the design and operation of clinical trials, as well as contribution to the neuro-oncology litera-
ture. Fellows are expected to participate in the design, IRB application process and manage-
ment of new clinical trials and to produce clinical trials and reports.
CLINICAL RESEARCH
In 2007, 374 patients were enrolled in clinical trials related to their diagnosis. In addition to its
own phase I-II trials, the BTNC participates in several national and international consortia, in-
cluding New Approaches to Brain Tumor Therapy (NABTT) sponsored by the National Cancer
Institute, Radiation Therapy Oncology Group (RTOG), American College of Surgeons Oncology
Group (ACoSOG) and Children’s Oncology Group (COG).
BTNC physicians have developed a reputation for national and international leadership in
neuro-oncology clinical trials. BTNC physicians serve as national and international principal
investigators on multiple RTOG and pharmaceutical industry trials.
Open adult clinical trials include studies of medications, radiation therapies, stereotactic radio-
surgery, chemotherapies, gene therapies, hormone therapies, blood-brain barrier disruption,
devices, intraoperative optical spectroscopy, dietary and herbal complementary and alternative
medicine and stress reduction for astrocytomas, glial tumors, lymphomas, metastases and
oligodendrogliomas.
Open child and adolescent protocols include studies of medications, chemotherapies, chemo-
radiation therapies, radiotherapies and second-look surgeries for malignant brain tumors, CNS
AT/RT, CNS embryonal tumors, ependymoma, NGGCT, gliomas, CNS germinomas, medullo-
blastomas, neurofi bromatosis type 1, astrocytomas and solid tumors.
The Brain Tumor and Neuro-Oncology Center’s new
Gamma Knife® Perfexion equipment is the most
technologically advanced model available, allowing for
treatment in a wider range of anatomical structures,
enhanced planning, use of all imaging modalities and
reduced treatment time.
The Brain Tumor and Neuro-Oncology
Center initiated a collaboration with
industry to develop laser interstitial
thermal therapy for brain tumors —
moving initial research from the pre-
clinical phase to a fi rst-in-man trial.
INNOVATION
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
24 | BRAIN TUMOR AND NEURO-ONCOLOGY CENTER
LABORATORY RESEARCH
The BTNC has two primary laboratories under the direction of Drs. Michael Vogelbaum and
Robert Weil. Current research focuses on molecular genetics, apoptosis, engineering, immu-
nology, progenitor cells and genomics/proteomics. In addition to basic research in these areas,
BTNC researchers in the Translational Therapeutics Program, directed by Michael Vogelbaum,
MD, PhD, perform preclinical testing of novel agents for treating brain tumors with the aim
of bringing these agents to clinical trials. The BTNC laboratories collaborate closely on basic
research projects with the Cancer Biology and Immunology departments in the Lerner
Research Institute.
Basic research projects in progress include:
° Mechanisms for sensitizing glioma cells to chemotherapy
° The role of STAT3 in the biology of gliomas
° Genetic alterations and biological characterization of primary cell cultures derived from
malignant gliomas
° Genetic alterations in GBMs (loss or gain of 19q, 1p and other novel alterations) and their
correlations with patient survival
° Development of a clinical assay for detection of deletions in CDKN2A, ARF, PTEN and
p53 genes in gliomas
° 7,5-lipoxygenase inhibition as an adjuvant glioma therapy
° Molecular biology of brain tumors
° Blood-brain barrier, tumor markers and human gliomas project
° Molecular pathology of gliomas: “glioma genotyping”
° Transcription factors and brain tumors
° Molecular genetic investigation of pituitary tumors
° Genetic polymorphism analyses of brain tumors
The Brain Tumor and Neuro-Oncology
Center had 56 active clinical trials in
2007.
RESE ARCH
The Brain Tumor and Neuro-Oncology Center surgical services include sophisticated intraoperative techniques such as
awake craniotomy, physiologic mapping, radiotherapy, navigation, ultrasound and MRI.
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
BRAIN TUMOR AND NEURO-ONCOLOGY CENTER | 25
2003 20052004 2006 2007
6
5
4
3
2
1
0
6
5
4
3
2
1
0
12
10
8
6
4
2
0
12
10
8
6
4
2
0
DaysDays Number of DeathsNumber of Deaths
Target LOSMean LOSActual MortalityExpected Mortality
Supratentorial Craniotomy: Inpatient Mortality and Length of Stay
2003 2004 2005 2006 2007
100
80
60
40
20
0
100
80
60
40
20
0
100
80
60
40
20
0
100
80
60
40
20
0
Percent SurvivalPercent Survival Number of SurgeriesNumber of Surgeries
30-Day Survival180-Day Survival# of Surgeries
Infratentorial Craniotomy: Survival
2003 2004 2005 2006 2007
5
4
3
2
1
0
5
4
3
2
1
0
1.0
0.8
0.6
0.4
0.2
0
1.0
0.8
0.6
0.4
0.2
0
DaysDays Number of DeathsNumber of Deaths
Mean LOSTarget LOSActual MortalityExpected Mortality
Pituitary Surgery: Inpatient Mortality
Expected deaths are based on
APR-DRGs, which adjust for the
severity of the patient population.
Thirty and 180-day survival remained
robust in 2007 for infratentorial cran-
iotomies at 100 and 96.2 percent.
There have been no inpatient deaths
following pituitary surgery in the past
fi ve years. Target length of stay (LOS)
is calculated based on APR-DRGs,
which adjust for the severity of the
patient population.
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
OUTCOMES HIGHLIGHTS
JOE CASE
Age: 33
Hometown: Uniontown, Ohio
Diagnosis: Glioblastoma
Treatment: Initial surgery and radiation therapy
with concurrent temozolomide, additional
temozolomide for fi ve days out of every
28 days for 12 cycles, and daily dosing of
erlotinib (Tarceva®) for three years.
Dizziness wasn’t enough to slow down Joe Case, a busy business owner who had not seen
a doctor in years. As hearing and visual disturbances set in, however, Mr. Case knew it was
time to seek help. CT and MR imaging confi rmed a tumor, but surgery at a local hospital
failed to remove it entirely. He made the commitment to get the best care he possibly could,
and found people to drive him more than an hour to Cleveland Clinic every day for six weeks
for radiation therapy. Afterward, he joined a trial of Tarceva®, a lung cancer chemotherapy
drug being studied in glioblastoma. Three years later, the tumor hasn’t grown. Case, who is
married and has a 1½-year-old son, stays more active than ever, and just participated in the
American Brain Tumor Association’s annual 5K race.
“Next to my wife and family, Cleveland Clinic has been my godsend. I tell anyone who has
any cancer problems not to waste their time anywhere else. I don’t have the words to praise
Cleveland Clinic enough for the fact that I am still here. My doctors and nurses are like
family to me now.”
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
BRAIN TUMOR AND NEURO-ONCOLOGY CENTER | 27
PUBLICATION HIGHLIGHTS
Marko NF, Weil RJ, Toms SA. Nanotechnology in proteomics. Expert Rev Proteomics. 2007
Oct;4(5):617-626.
Nathoo N, Ugokwe K, Chang AS, Li L, Ross J, Suh JH, Vogelbaum MA, Barnett GH. The role
of (111)indium-octreotide brain scintigraphy in the diagnosis of cranial, dural-based menin-
giomas. J Neurooncol. 2007 Jan;81(2):167-174.
Videtic GMM, Adelstein DJ, Mekhail TM, Rice TW, Stevens GHJ, Lee SY, Suh JH. Validation
of the RTOG recursive partitioning analysis (RPA) classifi cation for small-cell lung cancer-only
brain metastases. Int J Radiat Oncol Biol Phys. 2007 Jan 1;67(1):240-243.
Vogelbaum MA. Convection enhanced delivery for treating brain tumors and selected neuro-
logical disorders: symposium review. J Neurooncol. 2007 May;83(1):97-109.
More than 300 physicians and physi-
cists have been trained on Gamma
Knife® technology through the Brain
Tumor and Neuro-Oncology Center.
EDUCATION
2003 2004 2005 2006 2007
100
80
60
40
20
0
100
80
60
40
20
0
300
240
180
120
60
0
300
240
180
120
60
0
Percent SurvivalPercent Survival Number of DeathsNumber of Deaths
30-Day Survival180-Day Survival# of Procedures
Stereotactic Radiosurgery: Survival
The number of Gamma Knife® cases
peaked in 2007 despite a six-week
hiatus for upgrading to the Gamma
Knife® PerfexionTM. Thirty and 180-
day survival for Gamma Knife® were
97.6 and 91.3 percent respectively
with the highest 180-day survival in
the last fi ve years.
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
OUTCOMES HIGHLIGHTS
28 | CEREBROVASCUL AR CENTER
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
CEREBROVASCULARCENTER
CEREBROVASCUL AR CENTER | 29
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
30 | CEREBROVASCUL AR CENTER
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
CLINICAL PROGRAMS
Cleveland Clinic’s Cerebrovascular Center offers a unique mix of physician subspecialties deliv-
ering endovascular therapy and cutting-edge care of the highest quality with proven successful
outcomes. The quality stroke care that we deliver places an emphasis on aggressive acute
stroke intervention and multi-modality therapy of brain aneurysms and AVMs. In addition,
there is strength in stroke prevention through our vascular neurology team, with leverage on
outcomes research.
Endovascular approaches are standard of care, and our advanced imaging capabilities will
guide treatment decisions. Patients also receive comprehensive care in our 16-bed neurointen-
sive care unit staffed by neurointensivists, inpatient nursing and dedicated mid-level praction-
ers. Our Cerebrovascular Center received re-certifi cation as a Primary Stroke Center in 2007.
We provide patients effi cient, high-quality care for acute stroke, coupled with excellent patient
outcomes and shorter lengths of stay. With a case severity index in the top 2.2 percent in the
United States, the Cerebrovascular Center performed better than national comparisons for
inpatient mortality, length of stay and hospital costs in 2007.
Long-term, risk-factor modifi cation programs are available through the Cerebrovascular Center
in conjunction with physical medicine and rehabilitation services.
Cerebrovascular disease states we treat include:
Carotid Occlusive Disease (Stenosis)
Cleveland Clinic specialists are leaders in carotid endarterectomy and carotid angioplasty for
this disease with outcomes that surpass national averages.
Cerebral Aneurysms
Treatment of ruptured and unruptured brain aneurysms and arteriovenous malformations
(AVMs) continues to outnumber all other cerebrovascular surgical procedures. In addition to
microsurgical clipping, endovascular neurosurgeons also use detachable coils, intracranial self-
expanding stents and new embolic agents to treat aneurysms and AVMs.
Initial outpatient visits 515
Total outpatient visits 4,135
Admissions 1,138
Inpatient Days 6,568
Surgical Cases 1,057
2007 STATS
The Neurological Institute’s dedicated, 16-bed neurointensive care unit is staffed by a team of neurologists, neurosurgeons,
specially trained nurses, respiratory therapists, nutritionists and pharmacists, all under the direction of neurointensivists.
The unit is equipped for intracranial pressure monitoring, continuous EEG/Evoked Potential monitoring, transcranial Doppler
ultrasound monitoring, and brain tissue oxygenation and metabolism monitoring.
CEREBROVASCUL AR CENTER | 31
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
Arteriovenous Malformations (AVMs)
The center provides multidisciplinary consultation and treatment for these disorders, including
microsurgical resection, embolization and Gamma Knife® stereotactic radiosurgery.
2007 Cerebrovascular Center highlights:
° In collaboration with hospitals across the Cleveland area, we are working to increase the
number of Joint Commission-certifi ed stroke sites and provide coverage where needed
° We developed the Temporary Endovascular Bypass technology for stroke treatment
° We completed the world’s largest-ever study of intracranial atherosclerotic disease
FELLOWSHIPS
Neurointensive Care
Four two-year fellowships are available in neurointensive care. The fellowship provides com-
prehensive training in neurointensive care, medical and surgical intensive care and vascular
neurology. There is an active clinical research program including therapeutic hypothermia and
neuromonitoring. This fellowship is the only UCNS-approved Neurological Intensive Care Unit
fellowship in the region, and is one of the fi rst nine programs in the country to receive this
certifi cation.
Vascular Neurology
Two ACGME-accredited one-year fellowships in vascular neurology are offered for those who
desire further subspecialty training in this area.
Endovascular Neuroradiology
The Cerebrovascular Center offers two ACGME-accredited two-year fellowships in endovascu-
lar neuroradiology. The fellowships provide trainees an organized, comprehensive, supervised,
full-time educational experience in neuro-endovascular surgery/interventional neuroradiology
(NES/INR). This experience includes the management of patients with neurological disease,
In 2007, the Cerebrovascular Center
opened a state-of-the-art angiography
room that allows for endovascular and
open craniotomy treatment of patients
with cerebrovascular disease.
INNOVATION
The Cerebrovascular Center’s new neurovascular intervention and operating suite is designed for traditional microsurgical
procedures as well as for advanced, highly technical endovascular procedures.
32 | CEREBROVASCUL AR CENTER
the performance of NES/INR procedures, and the integration of NES/INR therapy into the
clinical management of patients.
CLINICAL RESEARCH
Current clinical trials offered through Cleveland Clinic’s Cerebrovascular Center include:
° Phase III, randomized, multicenter, open label clinical trial to examine whether a com-
bined intravenous (IV) and intra-arterial (IA) approach to recanalization is superior to
standard IV rt-PA (Activase®) alone when initiated within three hours of acute ischemic
stroke onset
° NeuroThera® Effectiveness and Safety Trial (NEST-2), a phase III, randomized, multi-
center, double-blind, controlled study to assess safety and effectiveness of the treatment
of ischemic stroke with the NeuroThera® Laser system within 24 hours from stroke onset
° Carotid occlusion surgery study (COSS) for symptomatic carotid occlusion
° IRIS trial to determine if pioglitazone, compared with placebo, is effective in lowering the
risk for stroke or myocardial infarction among non-diabetic men and women with a recent
ischemic stroke and insulin resistance
° Long-term cardiac complications of subarachnoid hemorrhage
° Percutaneous mechanical hematoma evacuation of spontaneous intracranial hemorrhage
° Matrix and Platinum Science (MAPS) trial for cerebral aneurysm embolization comparing
two FDA-approved embolic coil types for safety and effi cacy
° Trial for patients who have had a stroke or TIA possibly related to a patent foramen ovale
(CLOSURE-I)
° Warfarin vs. Aspirin (WARCEF) in reduced cardiac ejection fraction
° Use of rimonabant vs. placebo in patients with multiple cardiovascular risk factors and
abdominal obesity to show reduction of cerebrovascular events (CRESCENDO)
In 2007, the Cerebrovascular Center
completed the 160-patient, fi ve-center
U.S. Multicenter Wingspan Registry.
RESE ARCH
The Cerebrovascular Center has one of the highest stroke-related patient volumes in North America, seeing more than 3,200
stroke patients annually.
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
CEREBROVASCUL AR CENTER | 33
2003 2004 2005 2006 2007
200
100
0
200
100
0
EndovascularMicrosurgery
Number of ProceduresNumber of Procedures
Treatment of Unruptured Aneurysms
2003 2004 2005 2006 2007
150
100
50
0
150
100
50
0
EndovascularMicrosurgery
Number of ProceduresNumber of Procedures
Treatment of Ruptured Aneurysms
Discharge Status
2007 DISCHARGE STATUS UNRUPTURED ANEURYSMS RUPTURED ANEURYSMS
Home 80% 37%
Home Health 5% 5%
Acute Rehab 3% 14%
Skilled Nursing Facility 1% 19%
Expired 1% 19%
Other 5% 18%
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
OUTCOMES HIGHLIGHTS
The Cerebrovascular Center offers
four different fellowships for training in
advanced cerebrovascular care.
EDUCATION
TERESA MARTENS
Age: 23
Hometown: Higginsville, Missouri
Diagnosis: Symptomatic moyamoya disease
Treatment: Bypass surgery and encephalo-
duroarteriomyosynangiosis (EDAMS)
Teresa Martens was having a series of mini-strokes, but she was busy with school and plan-
ning her wedding, so she ignored them. When she fi nally went to see a local neurologist, he
wanted to do a brain biopsy, which would have required her to shave her head. As a bride
to be, she was quite hesitant. Meanwhile, her insurance company noticed all the tests she
was having and called to suggest she travel to Cleveland Clinic to see Peter Rasmussen, MD.
She agreed, and was diagnosed, treated and ready to go home within 10 days of arriving in
Cleveland. Today, she feels great and is back to her busy life.
“This was such a scary thing to go through. I really needed answers and hope. Since my
treatment, I have talked with a few people who know someone who is suffering from similar
mini-stroke-like episodes, and I always refer them to Cleveland Clinic. I even carry the
phone number to Cleveland Clinic in my cell phone to have ready to hand out! Without
Cleveland Clinic, I really could have suffered irreversible brain damage.”
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
CEREBROVASCUL AR CENTER | 35
PUBLICATION HIGHLIGHTS
Fiorella D, Levy EI, Turk AS, Albuquerque FC, Niemann DB, Aagaard-Kienitz B, Hanel RA,
Woo H, Rasmussen PA, Hopkins LN, Masaryk TJ, McDougall CG. US multicenter experi-
ence with the wingspan stent system for the treatment of intracranial atheromatous disease:
periprocedural results. Stroke. 2007 Mar;38(3):881-887.
Fiorella D, Woo HH. Emerging endovascular therapies for symptomatic intracranial atheroscler-
otic disease. Stroke. 2007 Aug;38(8):2391-2396.
Fiorella D, Chow MM, Anderson M, Woo H, Rasmussen PA, Masaryk TJ. A 7-year experience
with balloon-mounted coronary stents for the treatment of symptomatic vertebrobasilar intrac-
ranial atheromatous disease. Neurosurgery. 2007 Aug;61(2):236-242; discussion 242-243.
Katzan IL, Dawson NV, Thomas CL, Votruba ME, Cebul RD. The cost of pneumonia after
acute stroke. Neurology. 2007 May 29;68(22):1938-1943.
Kerber CW, Wanke I, Bernard J Jr, Woo HH, Liu MW, Nelson PK. Rapid intracranial
clot removal with a new device: the alligator retriever. AJNR Am J Neuroradiol. 2007
May;28(5):860-863.
Kirsch J, Rasmussen PA, Masaryk TJ, Perl J, II, Fiorella D. Adjunctive rheolytic thrombectomy
for central venous sinus thrombosis: technical case report. Neurosurgery. 2007 Mar;60(3):E-
77-E578.
Levy EI, Turk AS, Albuquerque FC, Niemann DB, Aagaard-Kienitz B, Pride L, Purdy P, Welch
B, Woo H, Rasmussen PA, Hopkins LN, Masaryk TJ, McDougall CG, Fiorella DJ. Wingspan
in-stent restenosis and thrombosis: incidence, clinical presentation, and management. Neuro-
surgery. 2007 Sep;61(3):644-650.
Levy EI, Mehta R, Gupta R, Hanel RA, Chamczuk AJ, Fiorella D, Woo HH, Albuquerque FC,
Jovin TG, Horowitz MB, Hopkins LN. Self-expanding stents for recanalization of acute cerebro-
vascular occlusions. AJNR Am J Neuroradiol. 2007 May;28(5):816-822.
Lin R, Svensson L, Gupta R, Lytle B, Krieger D. Chronic ischemic cerebral white matter dis-
ease is a risk factor for nonfocal neurologic injury after total aortic arch replacement. J Thorac
Cardiovasc Surg. 2007 Apr;133(4):1059-1065.
Turk AS, Rowley HA, Niemann DB, Fiorella D, Aagaard-Kienitz B, Pulfer K, Strother CM. CT
angiographic appearance of in-stent restenosis of intracranial arteries treated with the Wing-
span stent. AJNR Am J Neuroradiol. 2007 Oct;28(9):1752-1754.
Turner RD, Gonugunta V, Kelly ME, Masaryk TJ, Fiorella DJ. Marginal sinus arteriovenous
fi stulas mimicking carotid cavernous fi stulas: diagnostic and therapeutic considerations. AJNR
Am J Neuroradiol. 2007 Nov;28(10):1915-1918.
Wallace RC, Karis JP, Partovi S, Fiorella D. Noninvasive imaging of treated cerebral aneu-
rysms, part I: MR angiographic follow-up of coiled aneurysms. AJNR Am J Neuroradiol. 2007
Jun;28(6):1001-1008.
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
EPILEPSY CENTER
38 | EPILEPSY CENTER
CLINICAL PROGRAMS
Adult and Pediatric Epilepsy
Cleveland Clinic’s Epilepsy Center is one of the leading epilepsy programs in the world. In
2007 our team again saw one of the largest patient volumes in the world in outpatient clinics
and evaluated nearly 1,000 adult and pediatric patients in two dedicated, state-of-the-art
epilepsy monitoring units equipped with digital video-EEG technology.
Specialized neuroimaging services include advanced high-resolution magnetic resonance imag-
ing (MRI using specialized imaging techniques), functional magnetic resonance imaging (fMRI),
magnetic resonance spectroscopy (MRS), ictal single-photon-emission computed tomography
(SPECT) and positron emission tomography (PET). Cleveland Clinic’s Epilepsy Center recently
opened the fi rst clinical magnetoencephalography (MEG) program in northeastern Ohio to
further assist in the diagnosis and workup of patients with epilepsy. With advanced MEG
equipment and world-renowned research scientists in the fi eld of clinical and applied neuro-
physiology, we are introducing state-of-the-art noninvasive diagnostic abilities that will enable
our physicians and staff to manage the most complex and challenging epilepsy cases.
Our Pediatric Epilepsy Program is one of the world’s premier programs for children and
adolescents who are affected with epilepsy. Combining a multidisciplinary approach towards
the most advanced monitoring and treatment with compassion and caring, Cleveland Clinic’s
program achieves excellent patient outcomes. Pediatric patients are evaluated in the newly
expanded Pediatric Epilepsy Monitoring Unit and in the Pediatric and Neonatal ICUs.
Initial outpatient visits 809
Total outpatient visits 9,536
Admissions 1,175
Inpatient Days 6,015
Surgical Cases 227
2007 STATS
The Epilepsy Center’s pediatric services include a child-friendly, self-contained, eight-bed pediatric epilepsy monitoring unit,
a dedicated pediatric epilepsy staff and one of the most experienced epilepsy surgery programs in the country.
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
EPILEPSY CENTER | 39
Epilepsy Surgery
Our Epilepsy Surgery Program for adults and children with medication-resistant epilepsy is
one of the foremost programs of its kind in the world. Cleveland Clinic was one of the fi rst
institutions in the world to perform brain mapping for pre-surgical evaluation in epilepsy.
Performing more than 200 surgeries annually, including nearly 90 pediatric epilepsy proce-
dures, our surgeons have expertise in the leading treatments for surgical epilepsy, including
extra-temporal surgery, hemispherectomy, lesionectomy, temporal lobectomy and vagal nerve
stimulation. In addition, Cleveland Clinic Epilepsy Center is the only program in the state of
Ohio to offer a new investigational technique of computer-assisted responsive neurostimula-
tion (RNS, NeuroPace®) for select patients with focal epilepsy who failed various antiepileptic
medications and are not resective surgery candidates.
Cognitive Behavioral Program
This multidisciplinary, comprehensive cognitive and behavioral program provides psychosocial
assistance to patients with seizures at various stages of the patient’s evaluation and treatment.
By bringing together epileptologists, psychiatrists, neuropsychologists, social workers and
rehabilitation specialists, the program seeks to care for the full spectrum of physical, mental,
emotional, social and practical needs and issues that affect the lives of our epilepsy patients.
FELLOWSHIPS
The Epilepsy Center’s education programs offer in-depth exposure to our comprehensive ap-
proach to the diagnosis and management of adults and children with epilepsy, including surgi-
cal and investigational treatments. The aim of our program is the most comprehensive training
of future academic epileptologists and epilepsy surgeons. Our graduates have played and will
continue to play an integral role in treatment and innovation in epilepsy.
Currently, our approved educational/training programs consist of the following:
° Five one-year fellowships in clinical neurophysiology/EEG, which provide an intensive
experience in EEG and evoked potentials in the diagnosis and management of epilepsy
° Five one-year non-ACGME epilepsy fellowships
° A one-year surgical epilepsy fellowship
The Epilepsy Center installed the fi rst
clinical MEG (magnetoencephalogram)
system in Ohio. The MEG will improve
noninvasive localization of the seizure
focus in patients who suffer from
intractable epilepsies.
INNOVATION
The Pediatric Epilepsy Support Group is led by a pediatric epileptologist and provides families of children with epilepsy a
venue for education, discussion and camaraderie.
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
40 | EPILEPSY CENTER
CLINICAL RESEARCH
The many facets of epilepsy are refl ected in the scope of the Epilepsy Center’s clinical
research. Some of the areas currently being studied through clinical trials include:
° The genetics of epilepsy
° Hormone therapy for women with seizures
° Development of novel treatment techniques
° Responsive neurostimulation (RNS) with the NeuroPace® trial
° Clinical drug trials
° Physiologic markers and characterization of depressive subtypes in treatment-
refractory epilepsy
LABORATORY RESEARCH
Cleveland Clinic Lerner Research Institute and Epilepsy Center scientists are pursuing basic
and translational research that aids in the understanding of the neurological basis for epilepsy
and potential molecular-level interventions for the disease. Some of our current areas of
research include:
° Molecular genetics and cellular mechanisms of epilepsy
° Molecular and cellular mechanisms of resistance to antiepileptic medications
° Application of deep brain stimulation in epilepsy
In 2007, 411 patients were enrolled
in clinical trials through the Epilepsy
Center.
RESE ARCH
The Epilepsy Center’s monitoring units use digital video-EEG technology to accurately locate seizure origin.
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
EPILEPSY CENTER | 41
0 21 3Time since surgery (years)
4
1.0
0.8
0.6
0.4
0.2
0.0
1.0
0.8
0.6
0.4
0.2
0.0
Probability of seizure freedomProbability of seizure freedom
0 21 3Time since surgery (years)
1.0
0.8
0.6
0.4
0.2
0.0
1.0
0.8
0.6
0.4
0.2
0.0
Probability of seizure freedomProbability of seizure freedom
0 21 3 4 5 6 7 8 9 1110Time since surgery (years)
1.0
0.8
0.6
0.4
0.2
0.0
1.0
0.8
0.6
0.4
0.2
0.0
Probability of seizure freedomProbability of seizure freedom
0 654321 9 10 117 8Time since surgery (years)
1.0
0.8
0.6
0.4
0.2
0.0
1.0
0.8
0.6
0.4
0.2
0.0
Probability of seizure freedomProbability of seizure freedom
Long-Term Seizure Freedom Following Frontal Lobe Surgery for Epilepsy (n=119 surgeries from 1997-2007)
Seizure Freedom Following Hemispherectomy for Epilepsy (n=65 surgeries from 2004-2006)
Seizure Freedom Following Temporal Lobectomy for Epilepsy (n=474 surgeries from 1997-2007)
Seizure Freedom Following Posterior Quadrant Resections for Epilepsy (n=60 surgeries from 1997-2007)
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
OUTCOMES HIGHLIGHTS
RUSSELL BROOKER
Age: 2
Hometown: Lowell, Ohio
Diagnosis: Epilepsy
Treatment: Hemisphrectomy
Russell began having seizures at 2 weeks old. A trip to the local emergency room and a stay
in a Columbus hospital didn’t yield any answers. The seizures returned about six months
later, along with pneumonia. A doctor in Columbus advised Russell’s parents to take their
worsening child to Cleveland Clinic, where he was taken to the ICU immediately due to
complications with his breathing. William Bingaman, MD, and colleagues removed Russell’s
right hemisphere over the course of two surgeries. Russell has been completely seizure-free
ever since and undergoes therapy to improve his left-side motor skills.
“If we hadn’t gone to Cleveland Clinic, Russell wouldn’t be here today,” says Russell’s mother.
“They saved my son’s life. It was so scary, but they explained everything so well and made us
feel like they were going to fi x it. And they did.”
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
EPILEPSY CENTER | 43
PUBLICATION HIGHLIGHTS
Busch RM, Lineweaver TT, Naugle RI, Kim KH, Gong Y, Tilelli CQ, Prayson RA, Bingaman W,
Najm IM, Diaz-Arrastia R. ApoE-epsilon4 is associated with reduced memory in long-standing
intractable temporal lobe epilepsy. Neurology. 2007 Feb 6;68(6):409-414.
Gonzalez-Martinez JA, Bingaman WE, Toms SA, Najm IM. Neurogenesis in the postnatal
human epileptic brain. J Neurosurg. 2007 Sep;107(3):628-635.
Gonzalez-Martinez JA, Srikijvilaikul T, Nair D, Bingaman WE. Longterm seizure outcome in
reoperation after failure of epilepsy surgery. Neurosurgery. 2007 May;60(5):873-880.
Gupta A, Chirla A, Wyllie E, Lachhwani DK, Kotagal P, Bingaman WE. Pediatric epilepsy
surgery in focal lesions and generalized electroencephalogram abnormalities. Pediatr Neurol.
2007 Jul;37(1):8-15.
Janigro D, Awasthi S, Awasthi YC, Sharma R, Yadav S, Singhal SS, Hallene K. RLIP76 in AED
drug resistance. Epilepsia. 2007 Jun;48(6):1218-1219.
Jehi LE, Najm I, Bingaman W, Dinner D, Widdess-Walsh P, Luders H. Surgical outcome and
prognostic factors of frontal lobe epilepsy surgery. Brain. 2007 Feb;130(Pt 2):574-584.
Loddenkemper T, Moddel G, Schuele SU, Wyllie E, Morris HH III. Seizures during intracarotid
methohexital and amobarbital testing. Epilepsy Behav. 2007 Feb;10(1):49-54.
Loddenkemper T, Holland KD, Stanford LD, Kotagal P, Bingaman W, Wyllie E. Developmental
outcome after epilepsy surgery in infancy. Pediatrics. 2007 May;119(5):930-935.
Marchi N, Angelov L, Masaryk T, Fazio V, Granata T, Hernandez N, Hallene K, Diglaw T, Franic
L, Najm I, Janigro D. Seizure-promoting effect of blood-brain barrier disruption. Epilepsia.
2007 Apr;48(4):732-742.
Matsumoto R, Nair DR, LaPresto E, Bingaman W, Shibasaki H, Luders HO. Functional
connectivity in human cortical motor system: a corticocortical evoked potential study. Brain.
2007 Jan;130(Pt 1):181-197.
Schuele SU, Bermeo AC, Alexopoulos AV, Locatelli ER, Burgess RC, Dinner DS, Foldvary-
Schaefer N. Video-electrographic and clinical features in patients with ictal asystole.
Neurology. 2007 Jul 31;69(5):434-441.
Wehner T, LaPresto E, Tkach J, Liu P, Bingaman W, Prayson RA, Ruggieri P, Diehl B. The value
of interictal diffusion-weighted imaging in lateralizing temporal lobe epilepsy. Neurology. 2007
Jan 9;68(2):122-127.
Widdess-Walsh P, Jehi L, Nair D, Kotagal P, Bingaman W, Najm I. Subdural electrode analysis
in focal cortical dysplasia: predictors of surgical outcome. Neurology. 2007 Aug 14;69(7):660-
667.
Widdess-Walsh P, Kotagal P, Jehi L, Wu G, Burgess R. Multiple auras: clinical signifi cance and
pathophysiology. Neurology. 2007 Aug 21;69(8):755-761.
Wyllie E, Lachhwani DK, Gupta A, Chirla A, Cosmo G, Worley S, Kotagal P, Ruggieri P, Binga-
man WE. Successful surgery for epilepsy due to early brain lesions despite generalized EEG
fi ndings. Neurology. 2007 Jul 24;69(4):389-397.
The Epilepsy Center hosted its
17th International Epilepsy Symposium
in June 2007.
EDUCATION
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44 | CEREBROVASCUL AR CENTER
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
CEREBROVASCUL AR CENTER | 45
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
CENTER FOR
HEADACHE AND PAIN
46 | CENTER FOR HEADACHE AND PAIN
CLINICAL PROGRAMS
The Center for Headache and Pain offers a unique, interdisciplinary approach to headache
management involving specialists in adult neurology, pediatric neurology, internal medicine,
psychology, nursing, physical therapy and nutrition. Effective preventive and abortive treat-
ment for migraine, tension headache and cluster headache frequently involves a combination
of pharmacologic agents, behavioral therapy, psychotherapy, nutrition, physical therapy and
other modalities.
The infusion program is devoted to intravenous infusions specifi c for headaches and provides
urgent, inpatient-type care to patients who would otherwise have visited an emergency room.
In 2007, infusion patient volume continued to increase. This allowed for the successful out-
patient treatment of many otherwise stable headache patients who suffered episodes of acute
exacerbations of pain as well as the initiation of treatment for the many patients with chronic
headache disorders. The infusion program also provided an accessible site for initiation of
analgesic research studies and analgesic treatment, including detoxifi cation from medications
that perpetuate headaches.
The Cleveland Clinic Center for Headache and Pain also has pioneered home care infusion
nursing, which has allowed patients to remain in the comfort of familiar surroundings while
receiving aggressive medical therapy.
Additionally, Cleveland Clinic has been one of the early adopters of botulinum type A therapy
for headache, and this service has attained steady growth since the headache program was
created in 2004. Patient referrals for this treatment continued to expand in 2007.
In 2007, the Center for Headache and Pain initiated the IMATCH Program (Interdisciplinary
Method for the Assessment and Treatment of Chronic Headache). This three-week program
was designed to provide a multidisciplinary approach to the diagnosis and intensive treat-
ment of longstanding, functionally disabling headache disorders. It incorporates the fusion and
coordination of a number of invaluable services for this impaired patient population, including
behavioral management, intensive physical therapy, medical management (including the infu-
sion room) and education, and has treated nearly 100 patients to date. Treatment focuses on
enabling patients to regain normal functioning that has been lost due to pain. While pain may
not be eliminated completely, patients are taught how to manage the pain so that it does not
consume their lives.
Initial outpatient visits 862
Total outpatient visits 13,315
2007 STATS
The Center for Headache and Pain
established the IMATCH (Interdisci-
plinary Method for the Assessment
and Treatment of Chronic Headache)
program for adults with chronic
headaches. One of only a few in
the country, IMATCH is an intensive,
multidisciplinary outpatient program
for patients who have exhausted other
treatment options.
INNOVATION
The Center for Headache and Pain utilizes biofeedback to teach patients how to control symptoms of chronic headache.
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
CENTER FOR HEADACHE AND PAIN | 47
Current Average Least Worst
Pain Ratings (0=no pain; 10=worst possible pain)
10
8
6
4
2
0
10
8
6
4
2
0
AdmissionDischarge
DASS Stress Scale DASS Anxiety Scale DASS Depression
35
30
25
20
15
10
5
0
35
30
25
20
15
10
5
0
Emotional functioning scoresEmotional functioning scores
AdmissionDischarge
Pain Disability Headache Dizziness Neck Disability
100
80
60
40
20
0
100
80
60
40
20
0
Disability scoresDisability scores
AdmissionDischarge
Pain Outcome Following IMATCH (n=36)
Stress, Anxiety and Depression Following IMATCH (n=36)
Functional Status Following IMATCH (n=36)
Pain scores (mean + s.d.) decrease following
the IMATCH (Interdisciplinary Method for the
Assessment and Treatment of Chronic Headache)
Program. N=36 patients completing the three-
week program in 2007.
Measures of stress, anxiety, and depression all
decrease following IMATCH, indicating improve-
ment. Mean DASS-42 (Depression, Stress and
Anxiety Scale) subscale scores are plotted with
their standard deviations.
Disability scores improve (higher scores indicate
greater levels of disability) following completion
of the IMATCH program.
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
OUTCOMES HIGHLIGHTS
HALLIE NEWHOUSE
Age: 23
Hometown: New Alexandria, Penn.
Diagnosis: Migraines with and without aura,
restless legs syndrome and iron defi ciency
Treatment: The IMATCH program
(Interdisciplinary Method for the Assessment
and Treatment of Chronic Headache), a
three-week intensive multidisciplinary
outpatient program that includes neurology,
psychology, nutrition and physical therapy
Ms. Newhouse started having chronic migraines when she was 13 years old. They contin-
ued as she went to college, and she even had to take one semester off when her headaches
caused her to miss classes too frequently. She saw 15 neurologists in Pennsylvania over
the years searching for relief. When she read about Cleveland Clinic’s IMATCH program on
the Internet, she went to Cleveland right away. She experienced signifi cant relief within one
week of beginning the program and, importantly, is now able to function through the rare
headaches that she does get. She recently graduated from college after making the Dean’s
List two semesters in a row and is going to graduate school soon.
“This program absolutely put my life back on track. I am a functioning adult now. I was
taking 29 pills a day; now I take only six. I recently went eight months without a headache.
I had one this winter but I didn’t end up in the hospital, which is a big improvement for me.
Cleveland Clinic changed my life.”
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
CENTER FOR HEADACHE AND PAIN | 49
FELLOWSHIPS
Two one-year clinical/research fellowships in headache are available, one in adult headache
and another in pediatric headache medicine. This training program provides signifi cant experi-
ence in the diagnosis and management of adult and pediatric headache disorders, inpatient
headache management, ancillary treatment techniques such as biofeedback and stress
management, and the design and execution of headache research protocols. This is a non-
ACGME position, but has been accredited by the UCNS and AAN and AHS. After one year the
applicant may sit for the UCNS-accredited board examination.
CLINICAL RESEARCH
For headache sufferers, access to clinical trials of the newest, potentially effective pharmaco-
logic agents is an important attribute of the Cleveland Clinic Center for Headache and Pain.
Some of the current trials include:
° Comparison of an investigational oral drug with placebo for the treatment of moderate or
severe headache
° Neurogenetic studies of migraine headache
° Comparison of an investigational oral drug with placebo for the treatment of early mi-
graine headache
° Comparison of an investigational oral drug with placebo for the treatment of an acute
menstrual migraine
° Measurement of psychophysical markers in patients with a variety of headaches
PUBLICATION HIGHLIGHTS
Kapural L, Stillman M, Kapural M, McIntyre P, Guirgius M, Mekhail N. Botulinum toxin occipi-
tal nerve block for the treatment of severe occipital neuralgia: a case series. Pain Pract. 2007
Dec;7(4):337-340.
Spears RC, Ifthikharuddin S. New-onset headache from cerebral venous thrombosis.
Headache. 2007 Feb;47(2):275-276.
The Center for Headache and Pain
had 37 patients enrolled in clinical
trials in 2007.
RESE ARCH
More than 600 participants received
CME credit for Cleveland Clinic’s
online “Update on Migraine Headache”
course.
EDUCATION
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
0-24 50-74 75-10025-49
Percent Pain Reduction
100
80
60
40
20
0
100
80
60
40
20
0
Percent of PatientsPercent of Patients
Pain Reduction with Infusion Therapy (n=198)
Percent of patients reporting various levels of pain reduction following
infusion therapy. More than 60 percent of patients reported a 50 percent
or greater reduction in pain immediately after treatment.
MELLEN CENTER FOR
MULTIPLE SCLEROSISTREATMENT AND RESEARCH
52 | MELLEN CENTER FOR MULTIPLE SCLEROSIS TREATMENT AND RESEARCH
CLINICAL PROGRAMS
As one of the leading centers in the world for the diagnosis and management of multiple
sclerosis (MS), the Mellen Center includes a comprehensive array of clinical programs related
to its core mission.
Medical Programs
The core team includes neurologists, advanced practice nurses and physician assistants. The
Infusion Center, in its recently expanded 15-chair setting, has seen a 30 percent increase
in volume with the reintroduction of natalizumab (Tysabri®), a monthly infusion therapy for
relapsing forms of MS. The medical program also has been enhanced by the addition of Dr.
Alexander Rae-Grant to the staff.
Imaging Program
Two large grants were awarded by the National Multiple Sclerosis Society: one is to study
the clinical and imaging characteristics of damage to the hippocampus, which is a commonly
injured brain region supporting memory; the other is to further study functional connectiv-
ity in white matter, which is known to be impaired in MS patients and may lead to reduced
cognitive and memory function. Methodological development work was published observing
a correlation between white matter disease burden and functional connectivity, as well as a
novel method to determine fi ber direction within diseased white matter.
Comprehensive Care Program
We are refocusing our comprehensive care program using the Chronic Care Model developed
by Edward Wagner at the MacColl Institute. To that end we are enhancing the educational
opportunities on our website, offering programs for patients who are newly diagnosed and
conducting the “Mellen Center Learning Series” that is intended to help participants improve
their overall wellness and self-management strategies for living with MS.
Initial outpatient visits 749
Total outpatient visits 20,301
2007 STATS
The Mellen Center utilizes tests like timed gait trials and visual acuity testing to track patients’ disease progress and symp-
tom management.
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
Rehabilitation Program
The clinical activity of the rehabilitation and spasticity clinic continues to expand. Additional
equipment has been added to the therapy program to assess patient balance and the effec-
tiveness of wheelchair seating and selection. We continue to improve and validate the Mellen
Center Gait Test to improve sensitivity to change and safety of the patient.
FELLOWSHIPS
The Mellen Center offers four non-ACGME-approved fellowships in clinical neuroimmunology.
Fellows have the option of focusing clinical work/rehabilitation in a one-year program or on
clinical trials, MRI or clinical research in a two-to-three year program.
As one of the premier centers in the world for treatment and research related to multiple
sclerosis, the Mellen Center provides fellows with an unparalleled opportunity to experience
a comprehensive clinical multiple sclerosis program and participate in a world-class research
program.
CLINICAL RESEARCH
The Mellen Center staff and the individuals who come here for care maintain a strong partner-
ship in MS research. Research is aimed at unraveling the complexities of MS. The staff is
dedicated to understanding the effects and causes of the disease, improving its management
and working toward a cure. Researchers investigate more effective supportive care, better
rehabilitation techniques and more effective medical therapies.
Current studies of new MS therapies include: fi ngolimod (FTY-720) in both relapsing-remitting
and primary progressive MS, fumarate (BG-12), fampridine (4-aminopyridine), double-dose
glatiramer acetate (Copaxone), alemtuzimab (CAMPATH-1h), ocrelizumab, glatiramer acetate
(Copaxone) combined with interferon beta-1a (Avonex), laquinimod, atacicept and atorvastatin
(Lipitor), each of which may provide new treatment options for MS patients. Mellen Center
physicians occupy leadership positions in all of these multinational trials.
MELLEN CENTER FOR MULTIPLE SCLEROSIS TREATMENT AND RESEARCH | 53
The Mellen Center utilized Diffusion
Tensor Imaging as a noninvasive
MRI-based technique to measure
remyelination.
INNOVATION
Physical therapists at the Mellen Center develop personalized treatments to help MS patients improve their strength, gait
and overall function.
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
54 | MELLEN CENTER FOR MULTIPLE SCLEROSIS TREATMENT AND RESEARCH
Some of our ongoing non-treatment studies include:
° A clinical trial of a web-based self-monitoring program, which aims to develop the Inter-
net for use in patient self-management
° Diffusion tensor MR imaging studies of natalizumab (Tysabri®) and corticosteroids (Solu-
Medrol®), which will develop new imaging markers of degeneration
° A biomarker study of interferon beta-1a (Avonex) therapy, which hopes to predict who
will respond to therapy
° A functional MRI study of hand movements in MS, which aims to understand how the
brain re-organizes after injury from MS
° Studies of optical coherence tomography, which seek to develop a new approach to
monitor neural degeneration
° A 15-year follow-up of patients in the pivotal trial of interferon beta-1a (Avonex®) in
relapsing-remitting MS
LABORATORY RESEARCH
Neurologists at the Mellen Center collaborate with researchers at major medical centers, uni-
versities and the NIH in sophisticated laboratory research. The dual focus of this research is
to contribute to the understanding of the underlying disease process in MS and to advance our
knowledge of currently available treatments. Signifi cant grants to the Mellen Center from agen-
cies such as the NIH and the National Multiple Sclerosis Society refl ect the Mellen Center’s
exemplary standing as a nationally recognized center for laboratory research.
Current areas under study include:
° mechanisms responsible for myelin and nerve cell destruction in MS patients
° cellular and molecular biology of infl ammation, myelin formation and regeneration
° investigation of laboratory models of MS
In 2007, the Mellen Center received
$1,296,884 for research through
grants and contracts.
RESE ARCH
The Mellen Center offers a monthly
lunch-and-learn series for newly
diagnosed patients and their families
that reviews the disease, its symptoms
and treatment options.
EDUCATION
The center’s 1.5 Tesla MR scanner provides images of MS lesions in the brain and spinal cord to track disease state and
responsiveness to treatment.
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
MELLEN CENTER FOR MULTIPLE SCLEROSIS TREATMENT AND RESEARCH | 55
Before After
Treatment
4
3
2
1
0
4
3
2
1
0
Spasticity ScoreSpasticity Score
Modifi ed Ashworth Scale Following Intrathecal Baclofen Therapy (n=17)
Before After
Treatment
4
3
2
1
0
4
3
2
1
0
Spasm Frequency ScoreSpasm Frequency Score
Spasm Frequency Following Intrathecal Baclofen Therapy (n=17)
Effect on symptoms Effect on function
100
80
60
40
20
0
100
80
60
40
20
0
Percent Patients Reporting Treatment EffectivenessPercent Patients Reporting Treatment Effectiveness
First follow-up visitLast follow-up visit
Botox® Treatment Effectiveness (n=47)
Spasticity scores on the Modifi ed Ashworth
Scale (0=no increase in tone, 4=severe
increase in tone) at baseline and after ITB
therapy. There was a statistically signifi cant
(p<0.001, paired t-test) reduction in spastic-
ity after treatment. Average follow-up for the
17 patients was 167 days.
Spasm Frequency Scale scores (0=no
spasms, 4=more than 10 spasms/hour)
at baseline and at most recent follow-up
visit. There was a statistically signifi cant
(p<0.001, paired t-test) reduction in spasm
frequency after treatment. Average follow-up
for the 17 patients was 167 days.
Percent of patients reporting treatment
effectiveness following Botox® therapy for
focal spasticity. Patients were assessed
at fi rst follow-up visit (three months after
initial treatment) and subsequently every
three months. Average last follow-up was six
months, with a range up to 12 months. The
average follow-up period for the 47 patients
who continued treatment is 170 days. The
average dose injected at the most recent
session was 360 units of botulinum toxin A.
Most patients reported benefi t with treat-
ment both on symptoms and function, and
the results were stable over time.
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
OUTCOMES HIGHLIGHTS
PATRICIA SUBSTELNY
Age: 39
Hometown: Cleveland Heights, Ohio
Diagnosis: Multiple Sclerosis
Treatment: Monthly natalizumab (Tysabri®)
infusions for MS and botulinum toxin
injections for leg spasticity and tightness
every three months.
Patricia Substelny was a busy Human Resources professional by day and an aerobics
instructor by night 11 years ago when she started to have problems with her eyes and
weakness in her legs. The diagnosis of MS came one month before her wedding in the fall of
1997. Although today she is no longer able to be employed, she is active as a volunteer with
the MS Society and other local charities, which she actually fi nds to be more fulfi lling.
“It is a true partnership at the Mellen Center. I am the patient and I am responsible for
taking my medication and doing my exercises, but I really feel like I am on a team with the
doctors and nurses. We are all working toward the same goal. They are just as happy as I
am when I am doing well and just as concerned when I am not.”
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
MELLEN CENTER FOR MULTIPLE SCLEROSIS TREATMENT AND RESEARCH | 57
PUBLICATION HIGHLIGHTS
Cohen JA, Rovaris M, Goodman AD, Ladkani D, Wynn D, Filippi M. Randomized, double-
blind, dose comparison study of glatiramer acetate in relapsing-remitting MS. Neurology. 2007
Mar 20;68(12):939-944.
Dutta R, McDonough J, Chang A, Swamy L, Siu A, Kidd GJ, Rudick R, Mirnics K, Trapp BD.
Activation of the ciliary neurotrophic factor (CNTF) signalling pathway in cortical neurons of
multiple sclerosis patients. Brain. 2007 Oct;130(Pt 10):2566-2576.
Fisher E, Chang A, Fox RJ, Tkach JA, Svarovsky T, Nakamura K, Rudick RA, Trapp BD.
Imaging correlates of axonal swelling in chronic multiple sclerosis brains. Ann Neurol. 2007
Sep;62(3):219-228.
Fox RJ, Lee JC, Rudick RA. Optimal reference population for the multiple sclerosis functional
composite. Mult Scler. 2007 Aug;13(7):909-914.
Hahn JS, Pohl D, Rensel M, Rao S. Differential diagnosis and evaluation in pediatric multiple
sclerosis. Neurology. 2007 Apr 17;68(16 Suppl 2):S13-S22.
Marrie RA, Cutter G, Tyry T, Vollmer T, Campagnolo D. Disparities in the management of mul-
tiple sclerosis-related bladder symptoms. Neurology. 2007 Jun 5;68(23):1971-1978.
Rudick RA, Miller D, Hass S, Hutchinson M, Calabresi PA, Confavreux C, Galetta SL, Giovan-
noni G, Havrdova E, Kappos L, Lublin FD, Miller DH, O’Connor PW, Phillips JT, Polman CH,
Radue EW, Stuart WH, Wajgt A, Weinstock-Guttman B, Wynn DR, Lynn F, Panzara MA.
Health-related quality of life in multiple sclerosis: effects of natalizumab. Ann Neurol. 2007
Oct;62(4):335-346.
Ransohoff RM. Natalizumab for multiple sclerosis. N Engl J Med. 2007 Jun 21;
356(25):2622-2629.
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
58 | CEREBROVASCUL AR CENTER
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
CEREBROVASCUL AR CENTER | 59
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
CENTER FOR
NEUROIMAGING
60 | CENTER FOR NEUROIMAGING
CLINICAL PROGRAM
The Center for Neuroimaging includes specialists in structural and functional imaging of the
central nervous system for the diagnosis of neurological lesions, injury or metabolic disease.
Subspecialization in specifi c disease entities (e.g., epilepsy and cerebrovascular disease) ensures
accurate, in-depth, relevant interpretations. Across the Cleveland Clinic health system, the
Center for Neuroimaging supervises and interprets more than 60,000 CT scans and more than
50,000 MR scans each year. The normal turn-around time for reports is two to three hours,
with daily quality checks performed according to American College of Radiology guidelines.
Neuroimaging also functions in cooperation with the Cerebrovascular Center to provide
cerebrovascular ultrasound, angiography and interventional neuroradiology services. The latter
includes more than 3,000 cerebral angiograms per year, as well as state-of-the-art manage-
ment of acute stroke, internal/external carotid artery embolizations, Guglielmi detachable coil
occlusion of intracranial aneurysms, treatment of vasospasm and atherosclerotic occlusive
disease, and carotid artery stenting.
FELLOWSHIPS
Two ACGME-accredited fellowships are available: endovascular surgical neuroradiology and
diagnostic neuroradiology. The endovascular fellowship provides trainees an organized, com-
prehensive, supervised, full-time educational experience and is available to candidates with
appropriate prior training in neurosurgery, neuroradiology and stroke neurology. The diagnostic
neuroradiology program is open to suitable radiology candidates and provides a broad experi-
ence with state-of-the-art imaging equipment across all modalities for the evaluation of adult
and pediatric disorders of the brain and spine.
PUBLICATION HIGHLIGHTS
Beall EB, Lowe MJ. Isolating physiologic noise sources with independently determined spatial
measures. Neuroimage. 2007 Oct 1;37(4):1286-1300.
Bhattacharyya PK, Lowe MJ, Phillips MD. Spectral quality control in motion-corrupted single-
voxel J-difference editing scans: An interleaved navigator approach. Magn Reson Med. 2007
Oct;58(4):808-812.
Gandour J, Tong Y, Talavage T, Wong D, Dzemidzic M, Xu Y, Li X, Lowe M. Neural basis of fi rst
and second language processing of sentence-level linguistic prosody. Hum Brain Mapp. 2007
Feb;28(2):94-108.
Kapural L, Mekhail N, Bena J, McLain R, Tetzlaff J, Kapural M, Mekhail M, Polk S. Value of
the magnetic resonance imaging in patients with painful lumbar spinal stenosis (LSS) undergo-
ing lumbar epidural steroid injections. Clin J Pain. 2007 Sep;23(7):571-575.
Modic MT, Ross JS. Lumbar degenerative disk disease. Radiology. 2007 Oct;245(1):43-61.
Modic MT. Degenerative disc disease: genotyping, MR imaging and phenotyping. Skeletal
Radiol. 2007 Feb;36(2):91-93.
Obuchowski NA, Schoenhagen P, Modic MT, Meziane M, Budd GT. Incidence of advanced
symptomatic disease as primary endpoint in screening and prevention trials. AJR Am J Roent-
genol. 2007 Jul;189(1):19-23.
Sakaie KE, Lowe MJ. An objective method for regularization of fi ber orientation distributions
derived from diffusion-weighted MRI. Neuroimage. 2007 Jan 1;34(1):169-176.
Total CT brain scans 60,000
Total MR brain procedures 50,000
Total cerebralangio procedures 3,000
Studies performed on main campus, Cleveland Clinic family health centers and affi liated hospitals, estimated
2007 STATS
In 2007, the Center for Neuroimaging
obtained the fi rst mobile CT head scan-
ner in the state of Ohio.
INNOVATION
The Center for Neuroimaging received
a three-year, $768,000 grant from the
National Multiple Sclerosis Society in
2007 to study diffusion tensor imaging
changes within the hippocampus and
fornix and their relationship to memory
in patients with MS.
RESE ARCH
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
CEREBROVASCUL AR CENTER | 61
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
DALE WESSELL
Age: 67
Hometown: Fort Walton Beach, Fla.
Diagnosis: Stroke due to carotid
dissection
Treatment: Emergency carotid artery
stenting
Dale Wessell and his wife were up from Florida visiting family for the holidays. On Christ-
mas Eve, while driving from Oberlin to Elyria to go shopping, his vision suddenly became
blurred. He pulled over to let his wife, Debbie, drive, and was near crawling just to get to the
passenger seat. A former nurse, Debbie recognized the symptoms of stroke and rushed to a
nearby Oberlin hospital. Doctors there confi rmed an evolving stroke, initiated treatment and,
recognizing an impending catastrophe, summoned an emergency helicopter. Upon arrival
at Cleveland Clinic, Mr. Wessell was unable to speak and paralyzed on the right side; his
family was told he might not survive. He was rushed to the operating room for emergency
treatment, where he was found to have a carotid dissection, a spontaneous injury to the in-
ner wall of the artery to the left side of the brain. With the consent of his wife and emergent
approval from the institutional review board, an experimental fl exible stent was used to
re-open the artery before signifi cant permanent damage to the brain. Several hours later, he
was able to speak and move his entire body again. Today, he is completely recovered.
“Thank the Lord I was near Cleveland when this happened. They did an awesome job and
saved my life. Afterward, the doctors answered all my questions and never made me feel
like they had another patient in the world. They gave me as much time as I needed. I can’t
say enough about my care. It was miraculous.”
62 | CEREBROVASCUL AR CENTER
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
CENTER FOR
NEUROLOGICALRESTORATION
CEREBROVASCUL AR CENTER | 63
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
64 | CENTER FOR NEUROLOGICAL RESTORATION
CLINICAL PROGRAMS
Movement Disorders
A team of experts including renowned neurologists, neurosurgeons, researchers and a host
of support personnel offers the latest proven treatments for people with movement disorders,
including Parkinson’s disease, essential tremor and dystonia. Our surgical team is world-
renowned for performing deep brain stimulation (DBS) surgeries and has experience with
more than 1,200 DBS implants. This group also has expertise in the surgical management of
spasticity. Various medication clinical trials as well as gene therapy surgical trial programs are
under way.
Psychiatric Disorders
The Center for Neurological Restoration (CNR) team of neurosurgeons, psychiatrists and
psychologists has been involved in studies using DBS for treating obsessive-compulsive dis-
order and major depression for the past seven years with promising outcomes. Patients with
disabling OCD and depression are being actively enrolled in these studies. The center also
performs vagal nerve stimulation for medically refractory depression.
Chronic Pain
For more than a decade, our neurosurgical surgeons have provided surgical management of
chronic pain conditions including failed back surgery syndrome, RSD, CRPS, facial pain, stroke
pain and other chronic pain disorders. Various surgical procedures including lesioning and the
implantation of intrathecal infusion pumps, spinal cord stimulators, peripheral nerve stimula-
tors, cranial nerve stimulators and brain stimulators are performed for patients.
FELLOWSHIPS
Surgical Fellowship: Deep brain stimulation surgery is an area of specialty training available
with a one-year and two-year fellowship in functional and restorative neurosurgery. One fellow
is accepted for intensive training in surgery for the management of movement disorders such
as Parkinson’s disease, dystonia and spasticity; chronic pain; psychiatric disorders; and other
central nervous system disease states. In addition, fellows gain experience in peripheral and
central neurostimulation, intra-axial medication delivery and ablative procedures for pain and
movement disorders.
Medical Fellowship: For those interested in the medical management of movement disorders,
a one-year and two-year fellowship in movement disorders is offered. Two fellows are ac-
cepted for this intensive program, which includes exposure to all of the movement disorders
seen in our clinics. The depth and breadth of our program provides fellows with an unparal-
leled experience in the diagnosis and management of all aspects of these complex disorders.
CLINICAL RESEARCH
Clinical research interests in the center are focused on refi ning the use of DBS in movement
disorders and expanding its application to other problems. Current clinical trials available
relate to:
° Application of deep brain stimulation to psychiatric disorders, including depression and
obsessive-compulsive disorder
Initial outpatient visits 326
Total outpatient visits 6,499
Admissions 333
Inpatient Days 1,475
Surgical Cases 489
2007 STATS
The Center for Neurological
Restoration implanted the fi rst deep
brain stimulator in a patient
with severe traumatic brain injury,
demonstrating behavioral improvement
from a minimally conscious state.
INNOVATION
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
° Evaluation of functional MRI in patients with implanted neurostimulators
° Development of frameless techniques for deep brain stimulator placement
° Development of cortical interfaces for neural prostheses
° Multidisciplinary assessment of severe brain injury and application of deep brain stimula-
tion to treat cognitive disorders following severe brain injury
° Deep brain stimulation for pain
LABORATORY RESEARCH
Scientists at Cleveland Clinic’s Lerner Research Institute are involved in several major projects
related to deep brain stimulation and neurological restoration:
° Cerebellar stimulation for recovery of motor function following cortical strokes
° Corpus callosum stimulation for recovery of functions following subcortical strokes
° Effects of chronic electrical stimulation of the subthalamic nucleus on tissue integrity
° The effectiveness of deep brain stimulation of intralaminar nuclei of thalamus in a model
of focal cortical seizures induced by intracortical penicillin and generalized seizures
induced by intraperitoneal PTZ (pentylenetetrazole) in adult rats
° Effi cacy of subthalamic nucleus stimulation using variable wave-form external pulse gen-
erator (VWEPG) in ameliorating Parkinsonism in 6-hydroxydopamine-lesioned hemipar-
kinsonian rats
PUBLICATION HIGHLIGHTS
Birdno MJ, Cooper SE, Rezai AR, Grill WM. Pulse-to-pulse changes in the frequency of
deep brain stimulation affect tremor and modeled neuronal activity. J Neurophysiol. 2007
Sep;98(3):1675-1684.
Butson CR, Cooper SE, Henderson JM, McIntyre CC. Patient-specifi c analysis of the volume of
tissue activated during deep brain stimulation. Neuroimage. 2007 Jan 15;34(2):661-670.
Deogaonkar M, Walter BL, Boulis N, Starr P. Clinical problem solving: fi nding the target.
Neurosurgery. 2007 Oct;61(4):815-824; discussion 824-825.
Kuncel AM, Cooper SE, Wolgamuth BR, Grill WM. Amplitude- and frequency-dependent
changes in neuronal regularity parallel changes in tremor with thalamic deep brain stimulation.
IEEE Trans Neural Syst Rehabil Eng. 2007 Jun;15(2):190-197.
Lee JYK, Deogaonkar M, Rezai A. Deep brain stimulation of globus pallidus internus for dysto-
nia. Parkinsonism Relat Disord. 2007 Jul;13(5):261-265.
Machado A, Azmi H, Deogaonkar M, Rezai A. MRI-guided procedures for the management of
chronic pain. Tech Reg Anesth Pain Manag. 2007 Apr;11(2):113-119.
Machado A, Ogrin M, Rosenow JM, Henderson JM. A 12-month prospective study of gas-
serian ganglion stimulation for trigeminal neuropathic pain. Stereotact Funct Neurosurg.
2007;85(5):216-224.
Schiff ND, Giacino JT, Kalmar K, Victor JD, Baker K, Gerber M, Fritz B, Eisenberg B, O’Connor
J, Kobylarz EJ, Farris S, Machado A, McCagg C, Plum F, Fins JJ, Rezai AR. Behavioural
improvements with thalamic stimulation after severe traumatic brain injury. Nature. 2007 Aug
2;448(7153):600-603.
CENTER FOR NEUROLOGICAL RESTORATION | 65
The Center for Neurological Restora-
tion, in collaboration with the Center
for Headache and Pain, investigated
stimulation of the spheno-palatine
ganglia for treatment of severe cluster
and migraine headaches.
RESE ARCH
The Center for Neurological Restoration
held a one-day symposium on move-
ment disorders in 2007 for physicians
and nurse practitioners, addressing
restless legs syndrome, pharmacologi-
cal management of Parkinson’s disease,
and surgical therapies for advanced
Parkinson’s disease, dystonia and es-
sential tremor.
EDUCATION
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
DIANE HIRE
Age: 54
Hometown: Norwalk, Ohio
Diagnosis: Severe intractable depression
Treatment: Deep brain stimulation surgery
Diane Hire struggled with unrelenting depression for 20 years. Every morning, her fi rst
thought was that she would be able to go back to bed in 16 hours. She tried a variety of
treatments, but none provided sustained relief. One day, a therapist she was seeing heard
a lecture by Donald Malone, MD, about deep brain stimulation at Cleveland Clinic and sent
Ms. Hire’s records to him. She had surgery with Ali Rezai, MD, in November 2006; the de-
vice was activated in January 2007. Today, Ms. Hire is excited to wake up and enjoys talk-
ing to people, reading, working around the yard and house, and just being active — things
she hadn’t done in decades.
“Before, I was just a walking dead person. Only my body was alive. I didn’t know if I even
knew how to be well anymore. But I couldn’t ask for kinder, gentler people than Dr. Malone
and Dr. Rezai. They were so responsive and always had my best interest at heart. Because
of them, I am now 180 degrees away from where I was. My life is changed completely.”
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
CENTER FOR NEUROLOGICAL RESTORATION | 67
Parkinson’sDisease
Tremor Dystonia Other
80
60
40
20
0
80
60
40
20
0
20062007
Deep Brain Stimulation (DBS) procedures
Bilateral DBS, N=28 Unilateral DBS, N=27
Type of Surgery
80
60
40
20
0
80
60
40
20
0
UPDRS Motor ScoresUPDRS Motor Scores
Stimulation onStimulation off
Improvement in Motor Scores with DBS
Bilateral DBS, N=28 Unilateral DBS, N=27
Type of Surgery
100
80
60
40
20
0
100
80
60
40
20
0
Percent Improvement in Motor Function Following DBS for Parkinson’s Disease
Improvement in motor functioning in
Parkinson’s disease with deep brain
stimulation. Motor functioning is
measured with the Unifi ed Parkin-
son’s Disease Rating Scale, Part III
(Motor Subscale). Motor scores are
shown with the stimulator in the on
and off states.
Percent improvement on Unifi ed
Parkinson’s Disease Rating Scale
(UPDRS), Part III (Motor Subscale)
following deep brain stimulation
treatment for Parkinson’s Disease.
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
OUTCOMES HIGHLIGHTS
NEUROMUSCULARCENTER
70 | NEUROMUSCUL AR CENTER
CLINICAL PROGRAM
Treating neuromuscular diseases such as amyotrophic lateral sclerosis (ALS), peripheral nerve
injury, myasthenia gravis and myopathies requires a unique combination of medical expertise
and compassion. Specialists in the Neuromuscular Center successfully achieve this blend and
strive to apply the latest technology to help patients optimize their quality of life and minimize
their disability. To assist in the accurate diagnosis of these disorders, our specialists rely on
diagnostic modalities such as electrodiagnosis (e.g., EMG); autonomic testing; and muscle,
nerve and skin biopsies to supplement the history and physical examination.
FELLOWSHIPS
A one-year, ACGME-accredited fellowship is available in neuromuscular medicine, and a one-
year ACGME-approved fellowship is offered in clinical neurophysiology/EMG. Fellows have the
opportunity to gain experience in the range of neuromuscular diseases, as well as training in
the EMG laboratory, the autonomic disorders laboratory (tilt table, valsalva and pupillometry
testing), the quantitative sensory testing laboratory (QST, QSART and thermoregulatory sweat
testing), the quantitative muscle testing laboratory, and the histopathology laboratory for
epidermal nerve fi ber analysis in skin.
CLINICAL RESEARCH
Physicians in the Neuromuscular Center are engaged in a number of clinical and translational
research projects focused on improving the treatment of this cluster of diseases. Our patients
have the opportunity to participate in new drug trials sponsored by pharmaceutical companies
and the National Institutes of Health (NIH). Some of the current protocols include:
° Recombinant methionyl human brain-derived neurotrophic factor (r-metHuBDNF) in
patients with ALS
° SR 57746A in patients with ALS
° Topiramate in ALS
° Celebrex® in patients with ALS
° The ALS Care Program: a database resource for measuring and improving ALS outcomes
° AVP-923 (dextromethorphan/quinidine) in the treatment of patients with pseudobulbar affect
° High-dose CoQ10 in ALS
° Arimoclomol in a single patient with ALS
° IGIV chromatography (IGIV-C) 10 percent treatment in subjects with chronic infl amma-
tory demyelinating polyneuropathy
LABORATORY RESEARCH
Researchers in the Department of Neurosciences in Cleveland Clinic’s Lerner Research
Institute are dedicated to advancing the understanding of the genetic basis of neuromuscular
diseases. Examples of basic research related to neuromuscular diseases include:
° Genetic therapy utilizing genes for neural growth factors and anti-apoptotic intracellular
proteins for treatment of neuromuscular disorders
° Identifi cation of molecular pathways leading to degeneration of motor neurons in ALS
° Incorporation of the WLDS mutation to delay axonal degeneration
° Exploration of mechanisms and potential therapies for treating muscle infl ammation and
fi brosis associated with Duchenne muscular dystrophy
Initial outpatient visits 771
Total outpatient visits 8,121
2007 STATS
The Neuromuscular Center added
thermoregulatory sweat testing to
our battery of autonomic and quantita-
tive sensory testing, allowing more
sophisticated diagnosis of autonomic
and small fi ber neuropathic disorders.
INNOVATION
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
NEUROMUSCUL AR CENTER | 71
Total SFSN SFSN exclusivelyby skin bx
250
200
150
100
50
0
250
200
150
100
50
0
Number of ProceduresNumber of Procedures
Skin Biopsy for Small Fiber Sensory Neuropathy
Mean VAS atBaseline
Mean VAS atLast Follow-up
Mean Changein VAS
50
40
30
20
10
0
-10
50
40
30
20
10
0
-10
Pain ScoresPain Scores
Treatment of Painful Peripheral Neuropathy (N=42)
Cleveland Clinic is one of a few medical centers with a cutane-
ous nerve laboratory to facilitate evaluation of small fi ber sensory
neuropathy (SFSN). In 2007, we performed skin biopsies with
intraepidermal nerve fi ber density evaluation for 233 patients. One
hundred and seventy eight patients (76 percent) were diagnosed
with SFSN based on the biopsy results. In 79 patients (44 percent)
the diagnosis was made exclusively by skin biopsy. Our data are
consistent with reports by other medical centers that skin biopsy is
a valuable diagnostic tool and is more sensitive than electrophysi-
ological studies for diagnosing SFSN.
Of 42 patients with painful peripheral polyneuropathy followed for
up to one year, 60 percent showed improvement in visual-analog
pain scores (VAS) with various treatment modalities.
Patients showed an average improvement (reduction in pain scores)
of 25 percent. This compares to an average improvement of 12 to
42 percent in published studies of treatment of neuropathic pain.
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
OUTCOMES HIGHLIGHTS
CATHLEEN WAGNER
Age: 53
Hometown: Columbiana, Ohio
Diagnosis: Myasthenia gravis
Treatment: Thymectomy and
immunosuppressant therapy
Cathleen Wagner began having weakness in her neck and arms, drooping eyelids and dif-
fi culty speaking. Her primary care doctor accurately diagnosed myasthenia gravis and sent
her to a local neurologist, who ordered a CT scan. This revealed a coexisting thymoma, and
Ms. Wagner’s neurologist then referred her to Cleveland Clinic neurologist Kerry Levin, MD.
Because Ms. Wagner had a history of cardiac arrhythmia, surgery was riskier. Cleveland
Clinic thoracic surgeons, however, were able to successfully remove the thymoma and
Dr. Levin began a treatment regime to treat her myasthenia gravis. Today her condition is
managed with immunosuppression — and she is back at her rigorous job as a kindergarten
teacher.
“Dr. Levin takes such a personal interest. He really listens and wants to know what is going
on. He always takes in account the fact that I spend all day with little kids when we are
making decisions about my care and is never willing to settle for ‘good enough.’ When I
told him I was having trouble smiling, he didn’t dismiss that as something I would just have
to live with. He insisted we could get me back to 100 percent. He has never given up.”
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
NEUROMUSCUL AR CENTER | 73
Neuromuscular Center research is
exploring mechanisms and potential
therapies for treating muscle infl am-
mation and fi brosis associated with
Duchenne muscular dystrophy.
RESE ARCH
The Neuromuscular Center has trained
three fellows per year in EMG and
neuromuscular disease for the last 20
years, and has continuously trained
residents, fellows and observers in our
EMG lab since 1975.
EDUCATION
PUBLICATION HIGHLIGHTS
Bello-Haas VD, Florence JM, Kloos AD, Scheirbecker J, Lopate G, Hayes SM, Pioro EP,
Mitsumoto H. A randomized controlled trial of resistance exercise in individuals with ALS.
Neurology. 2007 Jun 5;68(23):2003-2007.
Chemali KR, Zhou L. Small fi ber degeneration in post-stroke complex regional pain syndrome I.
Neurology. 2007 Jul 17;69(3):316-317.
Lederman RJ. Tremor in instrumentalists: Infl uence of tremor type on performance. Med Probl
Perform Art. 2007 Jun;22(2):70-73.
Levin KH. Nonsurgical interventions for spine pain. Neurol Clin. 2007 May;25(2):495-505.
Polston DW. Cervical radiculopathy. Neurol Clin. 2007 May;25(2):373-385.
Robertson J, Sanelli T, Xiao S, Yang W, Horne P, Hammond R, Pioro EP, Strong MJ. Lack of
TDP-43 abnormalities in mutant SOD1 transgenic mice shows disparity with ALS. Neurosci
Lett. 2007 Jun 13;420(2):128-132.
Tavee J, Mays M, Wilbourn AJ. Pitfalls in the electrodiagnostic studies of sacral plexopathies.
Muscle Nerve. 2007 Jun;35(6):725-729.
Zhou L, Kitch DW, Evans SR, Hauer P, Raman S, Ebenezer GJ, Gerschenson M, Marra CM,
Valcour V, Diaz-Arrastia R, Goodkin K, Millar L, Shriver S, Asmuth DM, Clifford DB, Simpson
DM, McArthur JC. Correlates of epidermal nerve fi ber densities in HIV-associated distal sen-
sory polyneuropathy. Neurology. 2007 Jun 12;68(24):2113-2119.
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
74 | CEREBROVASCUL AR CENTER
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
CENTER FOR
PEDIATRIC NEUROLOGYAND NEUROSURGERY
CEREBROVASCUL AR CENTER | 75
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
76 | CENTER FOR PEDIATRIC NEUROLOGY AND NEUROSURGERY
CLINICAL PROGRAMS
Child neurologists and neurosurgeons at Cleveland Clinic provide family-integrated, com-
prehensive, advanced care in the diagnosis and treatment of children with a wide array of
neurological disorders. U.S.News & World Report recently ranked Cleveland Clinic’s pediatric
neurology and neurosurgery services among the top four programs in the country.
PEDIATRIC NEUROLOGY
Our staff members — all board-certifi ed in both pediatrics and neurology — are committed
to providing the highest quality clinical care, research, teaching and training in the pediatric
neurosciences. This is achieved through collaboration with Cleveland Clinic pediatric subspe-
cialists in every medical and surgical fi eld to offer the most advanced care and individualized
treatment for a wide range of pediatric neurological conditions. The center includes dedicated
disease-based clinical programs:
The Pediatric Neuromuscular Disease Program diagnoses and treats such conditions as
muscular dystrophy, spinal muscular atrophy, congenital myopathies and myasthenia gravis,
hereditary neuropathies and other polyneuropathies using advanced techniques including
specialized DNA tests, pediatric EMG and neuropathological examination of nerve and muscle
biopsies. Affected children have access to the latest therapies, including drug trials, plasma-
pheresis and immunoglobulin infusion when indicated.
The Pediatric Movement Disorders and Spasticity Program offers traditional medical and inno-
vative therapies, including botulinum toxin injections guided by electromyography, deep brain
stimulation, physical therapy, orthopaedic interventions, intrathecal baclofen infusion and
selective dorsal rhizotomy. Conditions treated include Tourette syndrome, ataxia, spasticity,
cerebral palsy and myelomeningocele.
The Pediatric/Adolescent Headache Program offers state-of-the-art patient care, education
and innovative research. The program provides expert evaluation and treatment of those af-
fected by both acute and chronic headaches, especially those with refractory headaches who
have failed previous attempts at therapy. In addition, a three-week inpatient rehabilitation
program is offered to those whose headaches have resulted in excessive school absences and
overuse of medication. Collaboration with other specialties including psychology and rehabili-
tation ensures positive outcomes. An infusion suite is available on an urgent/emergency basis
for those experiencing headache crises.
The Pediatric Neurometabolic and Genetic Disorders Program provides diagnosis and treat-
ment for the complex genetic and metabolic disorders that are the underlying basis of many
pediatric neurological and developmental issues. Areas of particular focus include central
nervous system white matter disorders, underlying genetic and metabolic disorders in the set-
ting of mental retardation and epilepsy, disturbances of mitochondrial oxidative phosphoryla-
tion and fatty acid oxidation, disorders of amino and organic acid metabolism, and lysosomal
storage diseases.
The Pediatric Cerebrovascular Disorders Program offers advanced imaging, including brain
MRI, MRA, cerebral angiogram and CT angiogram, as well as other comprehensive diagnostic
and therapeutic interventions for all forms of neonatal and childhood stroke. Children with
acute stroke are cared for in a pediatric intensive care unit staffed full-time by experienced
Initial outpatient visits 1,109
Total outpatient visits 7,623
Admissions 220
Inpatient Days 736
2007 STATS
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
pediatric intensivists in conjunction with our pediatric neurologists. Special areas of stroke
interest include children with central nervous system vasculitis, stroke associated with cardiac
disease or interventions, neonatal stroke and the vasculopathy of neurofi bromatosis.
The Pediatric Neurocardiology Program offers care for children with a wide variety of con-
genital and acquired heart diseases, including the management of associated neurological con-
ditions and complications of these disorders, as well as a comprehensive neuromuscular and
neurometabolic evaluation for children with unexplained cardiomyopathy or children undergo-
ing heart transplantation.
The Neonatal and Fetal Neurology Program offers prenatal consultation for a wide range of
neurological disorders detected in utero by fetal ultrasound, magnetic resonance imaging or
amniocentesis. Consultation and treatment also is provided for a variety of newborn conditions
including hypoxic-ischemic encephalopathy, neonatal seizures, stroke, CNS malformations,
brachial plexopathies and other newborn problems.
The Pediatric Neuro-Oncology Program specializes in the treatment of brain and spinal cord
cancer and offers sophisticated radiotherapies, including Gamma Knife® for brain tumors;
computer-assisted imaging for precise surgical planning, navigation and tumor resection; and
the most advanced chemotherapy as part of national study protocols.
The Neurocutaneous Disorders Program provides multidisciplinary care for a large popula-
tion of children with neurocutaneous disorders such as neurofi bromatosis, tuberous sclerosis
and Sturge-Weber syndrome. Cleveland Clinic received designation from the Children’s Tumor
Foundation as one of only 33 affi liate neurofi bromatosis clinics nationally.
CENTER FOR PEDIATRIC NEUROLOGY AND NEUROSURGERY | 77
The Center for Pediatric Neurology
and Neurosurgery developed the fi rst
Pediatric Multiple Sclerosis and White
Matter Disorders Clinic in Ohio in
collaboration with the Mellen Center.
INNOVATION
U.S.News & World Report recently ranked
Cleveland Clinic’s pediatric neurology and
neurosurgery services among the top four
programs in the country.
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
78 | CENTER FOR PEDIATRIC NEUROLOGY AND NEUROSURGERY
The Pediatric White Matter Disorders and Multiple Sclerosis Program offers advanced
diagnosis and treatment of multiple sclerosis and white matter disease in children. Distinction
between the many genetic, metabolic and acquired forms of pediatric white matter disease is
facilitated by collaboration with Pediatric Neurology team members who are world-renowned
specialists in the clinical and laboratory diagnosis of this group of disorders.
The Cyclic Vomiting Program provides expert evaluation and treatment for those individuals
with episodic unexplained vomiting. This program is one of only three in the country and the
only one in Northeast Ohio. The consultation includes evaluation by a neurometabolic special-
ist and metabolic gastroenterologist. Experts in pediatric headache, psychology and psychiatry
are an integral part of the team.
The Pediatric Epilepsy and Sleep Disorders Program provides comprehensive care for children
with epilepsy, often in the setting of complex neurological diseases. Sophisticated diagnosis of
pediatric seizure disorders and their underlying causes is available. Children with sleep disor-
ders receive state-of-the-art consultation and testing by pediatric sleep specialists.
Through the Community Pediatric Neurology Program, Cleveland Clinic pediatric neurologists
deliver clinical services in community settings including Hillcrest Hospital, Fairview Hospital
and Cleveland Clinic Wooster. These practices provide convenient access for patients and their
families in a community setting.
Pediatric neurologists at Cleveland Clinic are all board-certifi ed in both pediatrics and neurology.
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
CENTER FOR PEDIATRIC NEUROLOGY AND NEUROSURGERY | 79
PEDIATRIC AND CONGENITAL NEUROSURGERY
Cleveland Clinic’s pediatric and congenital neurosurgery services were one of the fi rst in the
country to emphasize the continuity of treatment of pediatric problems into adulthood, treating
congenital problems regardless of age. A variety of subspecialty programs are offered.
The center has broad experience in the treatment of brain and spinal cord malformations,
including Chiari malformation in children and adults. Surgical intervention for these congenital
abnormalities uses an innovative minimally invasive approach. Brain and spinal cord tumors are
biopsied and surgically resected in coordination with Pediatric Oncology and the Brain Tumor
and Neuro-Oncology Center using the latest localizing and minimally invasive techniques.
The latest technology, such as an adjustable antibiotic system, is offered for the treatment of
hydrocephalus in children and adults, resulting in an infection rate lower than national norms.
A $1 million study of outcomes for shunting in hydrocephalus is ongoing.
Our neuroendoscopy program has extensive experience in ventricular and extra ventricular
minimally invasive procedures. Advances include a combination of endoscopy with navigation
systems for complex procedures and resection of tumor masses. In 2007, the neuroendoscopic
program directed a neurosurgical course in Beijing, China, in a unique collaboration with
Peking Union Medical Center.
Cerebral palsy patients are seen in a unique multidisciplinary clinic for assessment, surgical
evaluation, follow- up and ongoing care. Combined neurosurgical and orthopaedic procedures
are performed to treat spasticity quickly and effectively. The section directs a course in the
treatment of spasticity and its regional therapies in children.
Center neurosurgeons and plastic surgeons collaborate in the treatment of craniofacial disor-
ders. Cleveland Clinic designed a pneumatic molding helmet that is utilized for more control
and fl exible head reshaping.
In our Aging Brain Clinic, specialists from multiple disciplines evaluate patients from around
the country with regard to dementia and normal pressure hydrocephalus.
FELLOWSHIPS
Pediatric neurosurgery offers a one-year, non-ACGME accredited fellowship in pediatric neuro-
surgery under the auspices of the Department of Neurosurgery. In the pediatric neurosurgery
fellowship, the focus is on learning the most advanced surgical treatments for hydrocephalus
and congenital abnormalities in children and adults. Minimally invasive techniques using
endoscopy are emphasized.
In addition to its certifi ed residency training program in Pediatric Neurology, Cleveland Clinic also
offers certifi ed subspecialty pediatric fellowships in Headache, Neuromuscular Disease, Sleep
Medicine and Epilepsy. These fellowships benefi t from collaboration with specialists in other cen-
ters throughout Cleveland Clinic, and are among only a few in the country that offer in-depth sub-
specialty training in the diagnosis and treatment of children and adolescents with these disorders.
CLINICAL RESEARCH
The Center for Pediatric Neurology and Neurosurgery participates in a range of clinical trials aimed
at improving management of a number of specifi c pediatric neurologic and neurosurgical disorders.
Pediatric neurology researchers are
exploring new ways to use MRI
and EEG to expand the potential pool
of pediatric candidates for epilepsy
surgery.
RESE ARCH
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
The pediatric neurology residency pro-
gram celebrated its 30th anniversary
in 2007, with more than 45 physicians
having graduated from the program.
We are one of only a few programs in
the country to offer a combined fi ve-
year training program that includes two
years of pediatrics training followed
by three years of pediatric neurology
training.
EDUCATION
80 | CENTER FOR PEDIATRIC NEUROLOGY AND NEUROSURGERY
Current clinical research includes:
Pediatric Neurology
° Ongoing coordination of the Ohio Pediatric Stroke Registry, the only pediatric state-based
registry in the country
° Ongoing participation in the International Pediatric Stroke Study (IPSS) collaborative
° Drug treatments in Duchenne muscular dystrophy and spinal muscular atrophy
Pediatric and Congenital Neurosurgery
° Treatment of children with spasticity: differences in intrathecal baclofen delivery
° Evaluation of new molding helmet in cranial abnormality
° Third ventriculostomy: outcome-related to CSF fl ow
° Neuroendsocopic-assisted chiari surgery compared with conventional standard surgical
approach
° Evaluating cognitive and neuropsychological effects of a study drug in children with par-
tial seizures
° Accelerator quantitation of imbalance in normal pressure hydrocephalus
° Treatment of children with chronic hydrocephalus
° Gait and balance in normal pressure hydrocephalus using the Medtronic Strata® Adjust-
able Valve and the Codman® Hakim™ Programmable Valve CSF content in normal pres-
sure hydrocephalus
° Developmental venous anomaly indices for patients undergoing lumbar drainage of CSF
for normal pressure hydrocephalus
LABORATORY RESEARCH
Basic research at Cleveland Clinic’s Lerner Research Institute that investigates the cellular and
molecular biology of brain development and neuronal and glial function contributes signifi -
cantly to advances in clinical care in pediatric neurology and neurosurgery.
Current basic research projects include:
° Oxygen delivery in hydrocephalus after surgical treatment
° Cerebrovascular and blood fl ow changes in chronic hydrocephalus
° CSF metabolite/cytokine expression in hydrocephalic CSF
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
Pediatric neurosurgeons at Cleveland Clinic
are some of the most experienced in the nation
for shunting pediatric hydrocephalus and adult
cases of normal pressure hydrocephalus.
CENTER FOR PEDIATRIC NEUROLOGY AND NEUROSURGERY | 81
2003 2004 2005 2006 2007
300
200
100
0
300
200
100
0
6
4
2
0
6
4
2
0
ProceduresProcedures DaysDays
Pediatric NeurosurgeryProceduresMean LOS
Pediatric Neurosurgery (<18 years)
Peds MIDAS HeadacheFrequency
RescueDoses
SchoolDays Missed
50
40
30
20
10
0
50
40
30
20
10
0
Visit 1Visit 2
Pediatric Headache (n=18)
New patientconsults
Diagnosis established viamuscle, genetic or CSF
350
300
250
200
150
100
50
0
350
300
250
200
150
100
50
0
Number of PatientsNumber of Patients
Neurometabolic Clinic Diagnostic Yield
Pediatric patients treated for headache showed an improve-
ment in PedsMIDAS (Migraine Disability Assessment Score),
headache frequency, and number of rescue medications
needed. The number of school days missed is one of the
questions included in the PedsMIDAS interview. N=18
pediatric patients with two PedsMIDAS scores an average of
three months apart.
In 2007 our Neurometabolic Clinic evaluated more than
300 patients presenting with unexplained neurologic and/or
developmental symptoms, and we were able to establish
a diagnosis in 125 patients, or 40 percent.
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
OUTCOMES HIGHLIGHTS
AIDAN VON GUNTEN
Age: 4
Hometown: Amherst, Ohio
Diagnosis: Left-side hemiparesis, due to
presumed perinatal ischemic stroke
Treatment: Physical and occupational
therapy and adaptive aquatics
When Aidan was about 3 months old, his mother, who works in early childhood intervention,
noticed that he was only reaching with his right hand. She watched him for about a month
before taking him to his Cleveland Clinic pediatrician. Aidan was referred to Cleveland Clinic
pediatric neurologist Neil Friedman, MB, ChB, who quickly began a comprehensive series of
diagnostic tests. An MRI demonstrated that a stroke had occurred, most likely before birth.
Aidan has been going for therapy to improve his balance and left-side strength for about
three years and today is a very social and active little boy. He plays soccer and many people
who interact with him are surprised to learn he has any limitations at all.
“The systematic approach of helping us right away gave us such a positive impression of
Cleveland Clinic,” says Aidan’s mom. “If our pediatrician hadn’t been so open to referring us
to Dr. Friedman right away and if we hadn’t gotten in to see such an excellent neurologist
so quickly, Aidan might not have gotten the help he needed so fast. Dr. Friedman is very
thorough and very comforting. He takes my concerns seriously and has always treated me
like a partner in Aidan’s care.”
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
CENTER FOR PEDIATRIC NEUROLOGY AND NEUROSURGERY | 83
° Dural substitutes
° Telemetric intracranial pressure measurement
° CSF circulation and solute clearance
° Intracranial pulse pressure changes in chronic hydrocephalus
° Study of the brain’s adaptation to chronic hypoxia hydrocephalus through stimulation of
VEGF and angiogenesis
° Study of cerebral hydro- and hemodynamic interaction to increase cerebral blood fl ow at
time of ischemic risks
PUBLICATION HIGHLIGHTS
Di X. Multiple brain tumor nodule resections under direct visualization of a neuronavigated
endoscope. Minim Invasive Neurosurg. 2007 Aug;50(4):227-232.
Di X, Luciano M. A novel endoscopic technique to suboccipital ecompression and atlas lamine-
ctomy for chiari malformation type I: technical note. WSJ. 2007;2(1):27-31.
Hinson JT, Fantin VR, Schonberger J, Breivik N, Siem G, McDonough B, Sharma P, Keogh I,
Godinho R, Santos F, Esparza A, Nicolau Y, Selvaag E, Cohen BH, Hoppel CL, Tranebjaerg L,
Eavey RD, Seidman JG, Seidman CE. Missense mutations in the BCS1L gene as a cause of the
Bjornstad syndrome. N Engl J Med. 2007 Feb 22;356(8):809-819.
Mathews CA, Jang KL, Herrera LD, Lowe TL, Budman CL, Erenberg G, Naarden A, Bruun RD,
Schork NJ, Freimer NB, Reus VI. Tic symptom profi les in subjects with Tourette syndrome
from two genetically isolated populations. Biol Psychiatry. 2007 Feb 1;61(3):292-300.
Mohyuddin T, Jacobs IB, Bahler RC. B-type natriuretic peptide and cardiac dysfunction in
Duchenne muscular dystrophy. Int J Cardiol. 2007 Jul 31;119(3):389-391.
Singh M, Jacobs IB, Spirnak JP. Nephrolithiasis in patients with Duchenne muscular dystro-
phy. Urology. 2007 Oct;70(4):643-645.
Turner RD, Rosenblatt SM, Chand B, Luciano MG. Laparoscopic peritoneal catheter place-
ment: results of a new method in 111 patients. Neurosurgery. 2007 Sep;61(3 Suppl):
167-172; discussion 172-174.
Warnke JP, Di X, Mourgela S, Nourusi A, Tschabitscher M. Percutaneous approach for
thecaloscopy of the lumbar subarachnoidal space. Minim Invasive Neurosurg. 2007
Jun;50(3):129-131.
Williams MA, McAllister JP, Walker ML, Kranz DA, Bergsneider M, Del Bigio MR, Fleming
L, Frim DM, Gwinn K, Kestle JRW, Luciano MG, Madsen JR, Oster-Granite ML, Spinella G.
Priorities for hydrocephalus research: report from a National Institutes of Health-sponsored
workshop. J Neurosurg. 2007 Nov;107(5 Suppl Pediatrics):345-357.
Wyllie E, Lachhwani DK, Gupta A, Chirla A, Cosmo G, Worley S, Kotagal P, Ruggieri P,
Bingaman WE. Successful surgery for epilepsy due to early brain lesions despite generalized
EEG fi ndings. Neurology. 2007 Jul 24;69(4):389-397.
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
84 | CEREBROVASCUL AR CENTER
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
CEREBROVASCUL AR CENTER | 85
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
DEPARTMENT OF
PSYCHIATRY AND PSYCHOLOGY
86 | DEPARTMENT OF PSYCHIATRY AND PSYCHOLOGY
CLINICAL PROGRAMS
The Department of Psychiatry and Psychology provides comprehensive adult, child and ado-
lescent mental health and chemical dependency services.
Adult Psychiatry
Inpatient and outpatient services are provided for the full range of adult psychiatric disorders.
The chief inpatient diagnoses are psychoses, alcohol and/or drug abuse, personality disorders
and mood disorders. The most common outpatient diagnoses treated are mood, anxiety and
somatoform disorders. Adult psychiatry also includes the Center for Psychiatric Neuromodula-
tion and the growing Mood Disorders Research Program.
Child and Adolescent Psychiatry
The department’s very active program in child and adolescent psychiatry offers outpatient and
crisis-oriented inpatient treatment. In the under 18 population, the leading inpatient diagnoses
in 2007 were psychoses, personality disorders, depression, anxiety disorders and DSM-IV
“childhood mental disorders,” including disruptive behavior disorders, pervasive developmen-
tal disorders, eating disorders and tic disorders. The top three diagnoses in 2007 among the
pediatric outpatient population were Attention Defi cit-Hyperactivity Disorder, mood disorders
and anxiety, and dissociative or somatoform disorders.
Section of Pain Medicine
The Section of Pain Medicine provides diagnosis and treatment of chronic pain and related
problems. It operates the Chronic Pain Rehabilitation Program, which is an interdisciplinary,
biopsychosocial rehabilitation program for patients with serious pain-related functional impair-
Initial outpatient visits 916
Total outpatient visits 47,497
Admissions 759
Inpatient Days 3,843
2007 STATS
Cleveland Clinic psychiatrists and psychologists participate in the team-based care of patients across the various Neurologi-
cal Institute centers and Cleveland Clinic institutes, incorporating mental and behavioral health services into the continuum
of patient care.
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
DEPARTMENT OF PSYCHIATRY AND PSYCHOLOGY | 87
ment or psychological distress. This all-day program provides inpatient care as well when
needed.
Psychosomatic Medicine
This section is staffed by psychiatrists, residents, a fellow in psychosomatic medicine and a
team of psychiatric occupational therapists who provide psychiatric consultation to hospital-
ized patients and their caregivers on medical and surgical units for psychiatric and neuro-
psychiatric disorders that occur during hospital admission. It is among the most active and
highly valued teaching services. The most common problems encountered include post-
operative delirium, mood disorders, adjustment disorders and assessment for either safety or
capacity, or both. Section staff also participate in the Epilepsy, Preventive Cardiology, Trans-
plant and Women’s Health centers and the Taussig Cancer Institute, as well as the Bakken
Heart-Brain Institute.
General and Health Psychology
Health psychologists provide behavioral assessment and treatment including biofeedback and
cognitive-behavioral, supportive and other types of psychotherapy on an outpatient basis.
Section members also serve important roles in Executive Health, the Center for Headache and
Pain, Bariatric Surgery and Women’s Health.
Neuropsychology
Specialists in this area work closely with physicians in other disciplines to provide neuropsy-
chological testing for patients with cognitive disturbance related to epilepsy, multiple sclerosis,
movement disorders, dementia, hydrocephalus, head injury and cardiothoracic surgery.
Alcohol and Drug Recovery Center
Our specialists in this area provide high-quality, multidisciplinary care and treatment for all
age groups with alcohol and drug abuse or addiction. Treatment is individualized to include
inpatient care, partial hospitalization and intensive or routine outpatient care or a combination
of these as needed to evaluate, detoxify and treat patients.
Psychiatric Neuromodulation Center
The Psychiatric Neuromodulation Center is a unique and distinctive feature of the depart-
ment’s collaboration with the Center for Neurological Restoration. It provides conventional and
innovative treatments to patients with psychiatric disorders refractory to common treatment
modalities. Patients with treatment-resistant depression or obsessive compulsive disorder in
particular can benefi t from evaluation and consultation with center physicians.
FELLOWSHIPS
Two comprehensive chronic pain rehabilitation fellowships are available through the Section
of Pain Medicine. Each fellow participates in the Chronic Pain Rehabilitation Program doing
biofeedback-assisted psychotherapy. Research primarily involves using our IRB-approved data
registry. Fellows also participate in couples and groups sessions, including a psychodynamic
group and CBT-based groups, as well as monthly aftercare.
The psychosomatic fellowship is a one-year training program, and involves rotations in
cardiology, oncology, transplantation and Women’s Health. In addition, the fellow may
The Department of Psychiatry and
Psychology developed and implement-
ed an SBAR modifi ed for psychiatry.
The SBAR (Situation, Background,
Assessment and Recommendation)
is a tool that is used to report to the
next shift, improving communication
between providers.
INNOVATION
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
88 | DEPARTMENT OF PSYCHIATRY AND PSYCHOLOGY
participate in research related to a topic of interest in consultation-liaison psychiatry.
The fellow also teaches residents and medical students, and provides supervision in the
Emergency Department. The fellow may also see patients for longitudinal follow-up in the
Psychosomatic Clinic with supervision from faculty.
The neuropsychology fellowship through the Association of Postdoctoral Programs in Clinical
Neuropsychology is a two-year program and is designed to provide specialty training in pediat-
ric or adult neuropsychology at the post-doctoral level.
CLINICAL RESEARCH
The department participates in multicenter clinical trials supported by the National Institutes
of Health (NIH), corporations and private foundations, as well as in-house trials conducted
exclusively at Cleveland Clinic. The primary focus of clinical trials is the development and
investigation of new pharmacological and other treatments for psychiatric disorders.
The Cleveland Clinic Mood Disorders Research Center is nearing the completion of the largest
double-blind, placebo-controlled trial of divalproex sodium to date in the acute treatment of
bipolar depression. The trial is being completed in collaboration with partners at Case Western
Reserve University.
Current child and adolescent psychiatry clinical trials include:
° First psychotic episode in children and adolescents, a four-year retrospective review
° S-100 B as a serum marker for early detection of infl ammation in psychotic children
° Cytokines in psychotic children
° Depression and epilepsy in childhood
° Infl ammatory markers in depression and epilepsy
° MRI fi ndings in temporal lobe epilepsy and depression
° A retrospective review of cognitive impact on epileptic children post-frontal lobectomy
Current psychology research includes:
° Cancer fatigue
° Facial allograft research and clinical protocol
° Palliative care and quality of life for those in long-term care
° Evaluation and treatment of tinnitus
° Strategies for managing patients with tinnitus
° Psychophysiologic remodeling of the failing human heart
° Heart-rate variability biofeedback in the treatment of early heart failure
° The health effects of spiritually focused meditation for people with acute leukemia
Current neuropsychology research includes:
° The role of cortisol dysregulation in depression and hippocampal dysfunction associated
with temporal lobe epilepsy
° An fMRI study of attention networks in multiple sclerosis
° Evaluating the risks and benefi ts associated with the application of deep brain stimulation
in the treatment of a variety of disorders such as Parkinson disease, tremor, dystonia,
pain, obsessive compulsive disorder, depression and neurocognitive disorders as a result
of brain injury
The new Cleveland Clinic Mood
Disorders Inpatient Unit includes an
IRB-approved research database as
part of the admissions process, which
helped to identify incorrect primary
diagnoses in 26 of the fi rst 100 admit-
ted adult patients in 2007.
RESE ARCH
More than 230 mental healthcare
professionals attended the Department
of Psychiatry and Psychology’s second
annual Post Traumatic Stress Disorder
symposium in 2007.
EDUCATION
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
DEPARTMENT OF PSYCHIATRY AND PSYCHOLOGY | 89
Admission Discharge 6 months 12 months
10
8
6
4
2
0
10
8
6
4
2
0
Pain Score (0=No Pain, 10=Worst possible pain)Pain Score (0=No Pain, 10=Worst possible pain)
20062007
Pain Intensity Following Chronic Pain Rehabilitation Program Treatment
12(N=11)
6(N=15)
3(N=15)
Time Since Surgery (Months)
1(N=15)
Baseline(N=15)
0
-10
-20
-30
-40
-50
-60
-70
0
-10
-20
-30
-40
-50
-60
-70
Percent Change in ScorePercent Change in Score
HDRSMADRS
Depressive Symptom Improvement with Deep Brain Stimulation in Highly Refractory Depression
Average BES Average Number ofBinge Eating Episodes
25
20
15
10
5
0
25
20
15
10
5
0
Before Treatment
After Treatment
Outcomes Following Binge Eating Therapy (n=81)
Mean pain scores decrease following en-
rollment in the Chronic Pain Rehabilitation
Program. Two hundred fi fty-nine patients
were admitted to the program in 2006 and
233 in 2007. Approximately 80 percent of
patients completed the program. Typical
treatment duration is 3.5 weeks.
Change in Montgomery-Asberg Depression
Rating Scale (MADRS) and Hamilton-24
Depression Rating Scale (HDRS) over time
for the subject population.
The patient average on the BES showed
a signifi cant reduction following group
treatment (p<.001). The average number
of binge eating episodes also showed a
signifi cant reduction following group treat-
ment (p < .001). Average patient satisfac-
tion was 4.52 (Very Satisfi ed to Extremely
Satisfi ed) on a scale of 1 (Extremely Dis-
satisfi ed) to 5 (Extremely Satisfi ed).
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
OUTCOMES HIGHLIGHTS
DAVID A ND DIANE RAGOZINE
Age: 57 and 55 years old
Hometown: Bristolville, Ohio
Diagnosis: Decades of chronic drug
and alcohol addiction
Treatment: Buprenorphine (Suboxone®)
maintenance therapy
This husband and wife spent years addicted to prescription drugs and alcohol. They tried
many times to stop, but nothing lasted. Mr. Ragozine fi nally went to see Gregory Collins, MD,
who put him on Suboxone®, which often is used as initial therapy, but less often offered
as long-term maintenance. Several months later, Mrs. Ragozine also sought help from
Dr. Collins. Today they are both clean and attend 12-step meetings with sponsors several
times a week. They continue to take Suboxone® daily.
“I was a slave to my addiction,” says Mr. Ragozine. “It took our money and our pride. Dr. Col-
lins really understands how hopeless narcotic addiction is and he’s been a miracle man for
us. His approach of combining the medication with intensive therapy is what saved us.”
“I was slowly dying and would be dead today if it weren’t for Dr. Collins’ help. My heart is not
heavy anymore. I don’t know what I would do without this treatment,” says Mrs. Ragozine.
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
DEPARTMENT OF PSYCHIATRY AND PSYCHOLOGY | 91
PUBLICATION HIGHLIGHTS
Fattal O, Link J, Quinn K, Cohen BH, Franco K. Psychiatric comorbidity in 36 adults with
mitochondrial cytopathies. CNS Spectr. 2007 Jun;12(6):429-438.
Ford PJ, Kubu CS. Ameliorating and exacerbating: surgical “prosthesis” in addiction. Am J
Bioeth. 2007 Jan;7(1):32-34.
Ford PJ, Boulis NM, Montgomery EB Jr, Rezai AR. A patient revoking consent during awake
craniotomy: an ethical challenge. Neuromodulation. 2007 Oct;10(4):329-332.
Keary TA, Frazier TW, Busch RM, Kubu CS, Lampietro M. Multivariate neuropsychologi-
cal prediction of seizure lateralization in temporal epilepsy surgical cases. Epilepsia. 2007
Aug;48(8):1438-1446.
Newport DJ, Calamaras MR, DeVane CL, Donovan J, Beach AJ, Winn S, Knight BT, Gibson
BB, Viguera AC, Owens MJ, Nemeroff CB, Stowe ZN. Atypical antipsychotic administration
during late pregnancy: placental passage and obstetrical outcomes. Am J Psychiatry. 2007
Aug;164(8):1214-1220.
Pearson KH, Nonacs RM, Viguera AC, Heller VL, Petrillo LF, Brandes M, Hennen J, Cohen
LS. Birth outcomes following prenatal exposure to antidepressants. J Clin Psychiatry. 2007
Aug;68(8):1284-1289.
Viguera AC, Koukopoulos A, Muzina DJ, Baldessarini RJ. Teratogenicity and anticonvulsants:
lessons from neurology to psychiatry. J Clin Psychiatry. 2007;68(Suppl)9:29-33.
Viguera AC, Whitfi eld T, Baldessarini RJ, Newport DJ, Stowe Z, Reminick A, Zurick A, Cohen
LS. Risk of recurrence in women with bipolar disorder during pregnancy: prospective study of
mood stabilizer discontinuation. Am J Psychiatry. 2007 Dec;164(12):1817-1824.
Viguera AC, Newport DJ, Ritchie J, Stowe Z, Whitfi eld T, Mogielnicki J, Baldessarini RJ, Zurick
A, Cohen LS. Lithium in breast milk and nursing infants: clinical implications. Am J Psychiatry.
2007 Feb;164(2):342-345.
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
92 | CEREBROVASCUL AR CENTER
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
CEREBROVASCUL AR CENTER | 93
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
SLEEP DISORDERSCENTER
94 | SLEEP DISORDERS CENTER
CLINICAL PROGRAM
The Sleep Disorders Center is accredited by the American Academy of Sleep Medicine. Our
clinical program continues to expand, refl ecting the widespread incidence of these disorders
in the population. To date, the center has performed more than 47,000 sleep studies. The
introduction of hotel-based sleep laboratories in 2005 strategically situated in the Greater
Cleveland region contributed signifi cantly to the center’s expansion throughout 2006 and
2007. Jyoti Krishna, MD, joined the center in 2007 as head of the pediatric sleep program.
Construction is under way for a new pediatric sleep clinic at our Fairhill location.
FELLOWSHIPS
Five one-year, ACGME-accredited fellowships are available with the center. Designed to
develop a range of competencies in sleep medicine, the fellowship provides trainees with
eligibility for the American Board of Sleep Medicine. Trainees are provided with a broad expo-
sure to sleep medicine including polysomnographic technology and the treatment of adult and
pediatric patients with sleep disorders, with a strong emphasis on clinical neurophysiology.
Initial outpatient visits 156
Total outpatient visits 11,690
2007 STATS
The Sleep Disorders Center established
a comprehensive Cognitive Behav-
ioral Program in 2007, incorporating
individual and group therapy for the
treatment of insomnia.
INNOVATION
Annually, more than 4,000 sleep studies are performed at our main center’s nine-bed lab and at hotel-based sleep labs
throughout the community.
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
SLEEP DISORDERS CENTER | 95
Before PAP After PAP
ESS ScoreESS Score
20
15
10
5
0
Sleep Apnea: Improvement in Sleepiness (n=60)
Before PAP After PAP
PHQ-9 ScorePHQ-9 Score
15
10
5
0
Sleep Apnea: Improvement in Depressive Symptoms (n=60)
No Insomnia Mild Moderate
Insomnia Category
Severe
Number of PatientsNumber of Patients
14
12
10
8
6
4
2
0
Before
After
Insomnia Sleep Skills Group
Sleepiness as measured with the Epworth Sleepiness
Scale (ESS) in sleep apnea patients seen from June to
December 2007, before and after PAP (positive airway
pressure) treatment. Higher scores indicate more
severe daytime sleepiness; PAP treatment reduced
sleepiness into the normal range (<10). Average dura-
tion of treatment was 86 days.
Depressive symptoms as measured with the Patient
Health Questionnaire (PHQ-9), in sleep apnea patients
seen from June to December 2007 also improved after
PAP treatment. PHQ-9 scores of 5-9 suggest mild
depression, <5 suggests minimal depression.
The Sleep Skills Group is a novel treatment for
insomnia started in 2007, one of the fi rst of its
kind in Northeast Ohio. After a fi ve-week session, 69
percent of participants had a signifi cant improvement
in insomnia, and 22 percent of participants no
longer had insomnia, as measured with the Insomnia
Severity Index.
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
OUTCOMES HIGHLIGHTS
EDWINA POLK
Age: 39
Hometown: Cleveland, Ohio
Diagnosis: Obstructive sleep apnea
Treatment: Continuous positive airway
pressure (CPAP)
Edwina Polk was helping countless people to fi nd the source of their sleeping problems
working as a polysomnography technologist at Cleveland Clinic’s Sleep Disorders Center. Yet
it took her a while to consider that her excessive tiredness could be due to a sleep disorder
of her own. She considered the diffi culty concentrating and remembering information to be
a way of life. Finally, when even adding extra sleep to her routine didn’t help, she decided to
undergo some of the tests she had administered so frequently to others. After going through
basic sleep tests and positional sleep therapy, her doctor found that a CPAP was just what
she needed. Now Ms. Polk enjoys having much more energy during the day and getting
things done.
“Cleveland Clinic solved my problems — I’m not tired during the daytime and I’m able to
concentrate. Now I’m able to get up and do all the things I need to do.”
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
SLEEP DISORDERS CENTER | 97
CLINICAL RESEARCH
Clinical studies in the Sleep Disorders Center include research into the causes of sleep
disorders, evaluation of innovative treatments and understanding co-morbidities and sleep
disorders. Current areas of research include:
° Major depressive disorder in sleep disorder patients
° Effects and prevalence of sleep apnea in bariatric surgery patients
° Finding the gene for restless legs syndrome
° Sleep disorders complicating epilepsy
° Use of wireless polysomnography in hospitalized patients
° Comparison of ambulatory and laboratory polysomnography for the diagnosis of obstruc-
tive sleep apnea
PUBLICATION HIGHLIGHTS
Mermigkis C, Chapman J, Golish J, Mermigkis D, Budur K, Kopanakis A, Polychronopoulos V,
Burgess R, Foldvary-Schaefer N. Sleep-related breathing disorders in patients with idiopathic
pulmonary fi brosis. Lung. 2007 May;185(3):173-178.
Mermigkis C, Kopanakis A, Foldvary-Schaefer N, Golish J, Polychronopoulos V, Schiza S,
Amfi lochiou A, Siafakas N, Bouros D. Health-related quality of life in patients with obstructive
sleep apnea and chronic obstructive pulmonary disease (overlap syndrome). Int J Clin Pract.
2007 Feb;61(2):207-211.
The Sleep Disorders Center collabo-
rated with Cleveland Clinic’s Cardiovas-
cular Surgery Department to study the
perioperative morbidity of sleep apnea.
RESE ARCH
Since 1995, when the accredited
clinical sleep medicine fellowship
began, the Sleep Disorders Center has
trained 54 clinical fellows who cur-
rently practice sleep medicine around
the world, including Korea, Singapore,
Saudi Arabia, Greece, Thailand and
Lebanon.
EDUCATION
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98 | CEREBROVASCUL AR CENTER
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
CEREBROVASCUL AR CENTER | 99
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
CENTER FOR
SPINE HEALTH
100 | CENTER FOR SPINE HEALTH
CLINICAL PROGRAMS
Specialists in neurosurgery, orthopaedic surgery and medical spine provide state-of-the-art
medical and surgical management for the full scope of back and spine problems.
The following highlights some of the subspecialty programs in the Center for Spine Health that
have achieved a national reputation:
Scoliosis and Kyphosis: Non-operative treatment typically involves bracing to temporarily
halt the worsening of the curve during a growth spurt. For spinal deformities approaching or
greater than 45 degrees associated with pain, functional impairment or severe cosmetic defor-
mity, spine stabilization surgery is performed. Surgeons employ spinal fusion in combination
with bone grafts and pedicle screws to stabilize the spine and correct the deformity. Whenever
possible, the procedure is performed in part or completely minimally invasively.
Spondylolisthesis: Nonsurgical treatment includes muscle relaxants, acetaminophen or anti-
infl ammatory agents in combination with physical therapy, non-aerobic exercise and stretching
to improve fl exibility of the trunk muscles. Spinal fusion and spinal instrumentation are recom-
mended in cases in which the spondylolisthesis causes neuropathy or incontinence.
Spinal Stenosis: Medical treatment options for spinal stenosis include nonsteroidal anti-infl am-
matory drugs (NSAIDs), intrathecal cortisone injections, exercise and physical therapy. We
also offer gabapentin and related drugs, the fi rst group of medications to provide an effective
nonsurgical treatment option for symptomatic lumbar stenosis with neurogenic claudication.
Surgical intervention is recommended when these measures are ineffective and pain interferes
with quality of life. Surgical treatment to permanently decompress the spinal canal includes
laminectomy with or without fusion, foraminotomy and spinal fusion with or without instru-
mentation.
Primary and Metastatic Spinal Tumors: Depending on the pathology and location of the tumor,
treatment options include analgesics and steroids to manage pain and infl ammation, brac-
ing to increase spinal stability, chemotherapy, radiation therapy, and/or surgical resection in
Initial outpatient visits 2,638
Total outpatient visits 30,977
Admissions 1,557
Inpatient Days 8,409
Surgical Cases 3,679
2007 STATS
Center for Spine Health surgeons offer spine stabilization surgery for both adult and pediatric cases of scoliosis, performing
the procedure using minimally invasive techniques whenever possible.
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
CENTER FOR SPINE HEALTH | 101
combination with spinal fusion. Embolization is performed as an adjunct to surgery for very
vascular tumors.
Mature Spine: The focus of the program is on conservative treatment for patients over age 60
experiencing chronic back pain. Options include pharmacologic and non-pharmacologic treat-
ments such as medications and supplements, physical, occupational and aquatic therapy, and
bracing.
Degenerative Spine: Conservative treatment is emphasized, including bed rest for acute pain,
stretching, low-impact exercise, pharmacologic therapy, spinal manipulation, heat and acu-
puncture. When pain is refractory to conservative treatments, surgical options may be used
and include laminectomy, spinal fusion or discectomy.
Cervical Fractures: Minor fractures frequently are treated with a cervical collar. Surgery is rec-
ommended for cases that involve neurological injury and the removal of a portion of bone to
relieve pressure on the spinal cord. More severe fractures may require manipulation or surgery
to restore the normal skeletal conformation. This may involve traction or surgery with bone
grafting and instrumentation.
Minimally Invasive Spinal Surgery: In certain cases of degenerative disease of the spine,
scoliosis, kyphosis, spinal column tumors, infection, fractures and herniated discs, minimally
invasive techniques may be used to speed recovery from surgery, minimize postoperative pain
and improve the fi nal outcome. The spine surgeons at Cleveland Clinic are leaders in the fi eld
and have been instrumental in advancing these techniques, including: spinal fusion, deformity
corrections (such as for scoliosis), repair of herniated discs, decompression of spinal tumors
and repair and stabilization of vertebral compression fractures.
Degenerative Diseases of the Spine: Degenerative diseases of the spine affect all regions of
the spine. Physicians at Cleveland Clinic provide state-of-the-art care that ranges from the
least invasive to complex surgical procedures to decompress neurological compression and/or
The Center for Spine Health offers medical
acupuncture to treat musculoskeletal and
spinal pain, as well as fatigue, stress and
muscle tension.
Stereotactic spine radiosurgery can deliver a very precisely targeted, high dose of radiation that can effectively control pain
or tumors in as little as a single session.
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
102 | CENTER FOR SPINE HEALTH
spinal instability or deformity. All treatments are individualized and may be multi-staged. The
most effective and least risky approaches are chosen on a case-specifi c basis.
FELLOWSHIPS
The Center for Spine Health offers a one-year fellowship in spine surgery that provides exper-
tise in diagnosing and treating all aspects of spinal disease, with emphasis on degenerative
disorders, adult deformity, complex reconstruction and revision techniques, and emerging
technologies. Surgical decision-making is emphasized as the fellow rotates through both ortho-
paedic and neurosurgical spine services. Laparoscopic and thoracoscopic minimally invasive
techniques, kyphoplasty and artifi cial disc techniques are taught. The fellow develops exper-
tise in applying both anterior and posterior spinal instrumentation systems. Fellows participate
in basic science and/or clinical research, and are expected to complete two research projects
over the course of the year.
The Center for Spine Health also offers a fellowship in spine medicine, training broadly compe-
tent specialists in this emerging specialty, focused on the evaluation and management of the full
spectrum of spine disorders. Fellows have the opportunity to develop outstanding clinical skills
grounded in an evidence-based framework. Fellows are exposed to a wide range of diagnostic
and therapeutic modalities including electrodiagnostics, acupuncture, manipulation, physical
The Center for Spine Health spine medicine fellowship focuses not only on procedural techniques, but also on spine well-
ness, surgical evaluations, imagery interpretation and pharmacologic therapies.
Center for Spine Health physicians
perform 1,600 interventional spine
procedures with center fellows as part
of the spine medicine fellowship.
EDUCATION
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
CENTER FOR SPINE HEALTH | 103
therapy, pain management and lumbar interventional spine procedures. Scholarly activity is
encouraged and expected. Fellows are active participants in clinical research and writing.
CLINICAL RESEARCH
Physicians in the Center for Spine Health participate in numerous clinical trials related to pain
management, advanced surgical techniques and new technology.
Current protocols include:
° Prospective outcomes evaluation of decompression with or without instrumented fusion
for lumbar stenosis with degenerative grade I spondylolisthesis (SLIP)
° Lumbar spine instability study: the role of fl exion/extension radiographs
° A prospective, randomized clinical investigation of the Cervitech, Inc. porous-coated mo-
tion artifi cial disc for stabilization of the cervical spine
° A chart review comparing surgical to conservative management in the treatment of type II
odontoid fractures among the elderly
° A retrospective, randomized controlled trial of duragen plus adhesion barrier matrix to
minimize adhesions following lumbar discectomy
° Cost savings in the operative room, standard radiographs vs. fl uoroscopy for localization
° A prospective, multicenter, randomized controlled study to compare the spinal sealant system
as an adjunct to sutured dural repair with standard of care methods during spinal surgery
° A multicenter, prospective, randomized, controlled clinical trial comparing the safety and
effectiveness of the Mobi-C prosthesis with conventional anterior cervical discectomy and
fusion in the treatment of symptomatic degenerative disc disease in the cervical spine
° The effectiveness of physical therapy for patients with lumbar spinal stenosis
° An assessment of P-15 bone putty in anterior cervical fusion with instrumentation inves-
tigational plan
° Determining the optimal surgical approach (ventral versus dorsal) for patients with multi-
level cervical spondylotic myelopathy
The Spine Research Laboratory actively develops investigations to address the problems Center for Spine Health physicians
encounter in the clinical setting.
The Center for Spine Health established
the Neurological Institute Collabora-
tive Community of Innovation (NICCI),
a new initiative designed to create,
promote and nurture a culture of cre-
ativity, innovation and teamwork in the
Neurological Institute.
INNOVATION
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104 | CENTER FOR SPINE HEALTH
LABORATORY RESEARCH
The research focus of the Spine Research Laboratory (SRL) is largely “translational” in its
emphasis on moving discoveries in basic science research to applications at the clinical level.
The close involvement of clinicians from Cleveland Clinic’s Center for Spine Health is a key
ingredient in maintaining this translational focus. The current “research portfolio” of the SRL
mirrors the interests of Center for Spine Health clinicians, and therefore incorporates the views
of surgical spine specialists (neurosurgical and orthopaedic) and medical spine specialists
(trained in physical medicine and rehabilitation, and osteopathic medicine).
The SRL has a number of ongoing, long-term research endeavors conducted under the aus-
pices of fi ve unique research pillars:
SpinalMEMS. Development of wireless, miniature pressure sensors that can be implanted
within an intervertebral disc and transmit real-time data for extended periods of time — pro-
viding clinicians with information as to the load-bearing, hydration and overall health of the
disc in response to different treatments and rehabilitation strategies.
Spine Biomechanics. Use of robotics technology to simulate changes in spinal neuromuscular
control strategies in response to pain.
Bone Bioengineering. Computational simulation of spinal bone remodeling and adaptive pro-
cesses in response to aging, trauma and disease.
Tissue Engineering. Development of animal models of intervertebral disc degeneration for
establishing causal links between disc degeneration, neoinnervation and pain.
Spinal Cord Injury. Development of biologic approaches to spinal cord regeneration following
traumatic injury.
Additionally, customized research projects are developed by medical students, residents and
fellows involved with the SRL.
A focus of the Spine Research Laboratory is bringing basic science investigations to clinical practice.
The Cleveland Clinic Center for Spine
Health spin-off company OrthoMEMS,
a microelectromechanical system, is
moving rapidly toward clinical trials
with its micro-pressure sensor, the
OrthoChip. The fi rst clinical application
of this battery-less, telemetric micro-
sensor will be for the assessment of
intervertebral disc function and the
more accurate determination of the
indications for and contraindications to
spine fusion surgery.
RESE ARCH
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
CENTER FOR SPINE HEALTH | 105
TumorTumor
CorrectionCorrection
DeformityDeformity
DecompressiveDecompressive
BiopsyBiopsy
ArthrodesisArthrodesis
0 400 600200 800
Number of Procedures
1,000
Type of ProcedureType of Procedure
Selected Spinal Procedures
Spinal deformity
Degenerative spine disease
Spinal fracture/trauma
Non-degenerative musculoskeletal-primary
Spinal tumor
Nervous system disorder
Spinal vascular malformation
10
8
6
4
2
0
10
8
6
4
2
0
DaysDays
Mean LOSTarget LOS
Mean Length of Stay (LOS) in Spinal Disorders
Spinal decompression remains the most
frequently performed procedure for spine
disease.
Target LOS is calculated based on APR-
DRGs, which adjust for the severity of the
patient population.
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
OUTCOMES HIGHLIGHTS
JO STEINHURST
Age: 84
Hometown: Cleveland, Ohio
Diagnosis: Spinal pain
Treatment: Medical acupuncture
Mrs. Steinhurst had injured her spine about 50 years ago when she was chasing her four-
year-old son and fell down the stairs. Years of physical therapy weren’t enough to ward off
the pain and she was forced to wear a leather and metal brace frequently to ease the pain.
Recently, she discovered medical acupuncture with Daniel Mazanec, MD, at Cleveland
Clinic’s Center for Spine Health and had immediate results. She now takes only over-the-
counter arthritis pills for her spinal injury because of the success of acupuncture.
“Nothing did for me what the fi rst go at acupuncture did. My back has not been as comfort-
able for most of my adult life as it is now. And, I have a physician doing it, which adds a
feeling of security. I go back every six to eight weeks for a ‘tune-up.’ The only regret I have
is that I waited until I was 84 to do this.”
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
CENTER FOR SPINE HEALTH | 107
PUBLICATION HIGHLIGHTS
Caron TH, Bell GR. Combined (tandem) lumbar and cervical stenosis. Semin Spine Surg.
2007 Mar;19(1):44-46.
Claybrooks R, Kayanja M, Milks R, Benzel E. Atlantoaxial fusion: a biomechanical analysis of
two C1-C2 fusion techniques. Spine J. 2007 Nov;7(6):682-688.
Covington E. Chronic pain management in spine disorders. Neurol Clin. 2007 May;25(2):539-
566.
Ferrara LA, Gordon I, Coquillette M, Milks R, Fleischman AJ, Roy S, Goel VK, Benzel EC. A
preliminary biomechanical evaluation in a simulated spinal fusion model. Laboratory investiga-
tion. J Neurosurg Spine. 2007 Nov;7(5):542-548.
Hwang SH, Kayanja M, Milks RA, Benzel EC. Biomechanical comparison of adjacent seg-
mental motion after ventral cervical fi xation with varying angles of lordosis. Spine J. 2007
Mar;7(2):216-221.
Kilincer C, Inceoglu S, Sohn MJ, Ferrara LA, Benzel EC. Effects of angle and laminectomy on
triangulated pedicle screws. J Clin Neurosci. 2007 Dec;14(12):1186-1191.
Krishnaney AA, Park J, Benzel EC. Surgical management of neck and low back pain. Neurol
Clin. 2007 May;25(2):507-522.
Mazanec D, Reddy A. Medical management of cervical spondylosis. Neurosurgery. 2007
Jan;60(1 Suppl 1):S43-S50.
Mohit AA, Orr RD. Percutaneous vertebral augmentation in osteoporotic fractures. Curr Opin
Orthop. 2007 May;18(3):221-225.
Orr RD, Postak PD, Rosca M, Greenwald AS. The current state of cervical and lumbar spinal
disc arthroplasty. J Bone Joint Surg Am. 2007 Oct;89 Suppl 3:70-75.
Steinmetz MP, Stewart TJ, Kager CD, Benzel EC, Vaccaro AR. Cervical deformity correction.
Neurosurgery. 2007 Jan;60(Suppl 1):S90-S97.
Stewart TJ, Schlenk RP, Benzel EC. Multiple level discectomy and fusion. Neurosurgery. 2007
Jan;60(1 Suppl 1):S143-S148.
Vadala G, Sowa GA, Smith L, Hubert MG, Levicoff EA, Denaro V, Gilbertson LG, Kang JD.
Regulation of transgene expression using an inducible system for improved safety of interverte-
bral disc gene therapy. Spine. 2007 Jun 1;32(13):1381-1387.
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
108 | NEUROLOGICAL INSTITUTE
Cleveland Clinic’s Neurological Institute is a multidisciplinary team of specialists offering innovative technology for diagnosis and treatment of all
neurological conditions affecting adult and pediatric patients. Because of our clinical expertise, academic achievement and innovative research,
the Neurological Institute has earned an international reputation for excellence.
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
NEUROLOGICAL INSTITUTE STAFF
NEUROLOGICAL INSTITUTE CHAIRMEN
Michael T. Modic, MD, FACRChairman, Neurological Institute
William Bingaman, MDVice Chairman, Clinical Areas, Neurological Institute
Richard Rudick, MD Vice Chairman, Research and Development, Neurological Institute
Edward Benzel, MDChairman, Department of Neurological Surgery
Kerry Levin, MDChairman, Department of Neurology
Thomas Masaryk, MDChairman, Department of Diagnostic Radiology
George Tesar, MDChairman, Department of Psychiatry and Psychology
Bruce Trapp, PhDChairman, Department of Neurosciences, Lerner Research Institute
CENTER FOR BRAIN HEALTH
Richard Rudick, MDInterim Director, Center for Brain Health
Richard Lederman, MD, PhD
Michael Parsons, PhD
Stephen Rao, PhDDirector, Schey Center for Cognitive Neuroimaging
Patrick Sweeney, MD
Janice Zimbelman, PT, PhD
BRAIN TUMOR AND NEURO-ONCOLOGY CENTER
Gene Barnett, MD, FACSDirector, Brain Tumor and Neuro-Oncology Center
Lilyana Angelov, MD, FRCS(C)
Samuel Chao, MD
Bruce H. Cohen, MD
Joung Lee, MD
David Peereboom, MD
Burak Sade, MD
John Suh, MD
Glen Stevens, DO, PhD
Tanya Tekautz, MD
Michael Vogelbaum, MD, PhD
Robert Weil, MD
CEREBROVASCULAR CENTER
Peter Rasmussen, MDDirector, Cerebrovascular Center
Rishi Gupta, MD
Irene Katzan, MD, MS
Gwendolyn Lynch, MD
Thomas Masaryk, MD
Shaye Moskowitz, MD, PhD
J. Javier Provencio, MD, FCCM
Vivek Sabharwal, MD
EPILEPSY CENTER
Imad Najm, MDDirector, Epilepsy Center
Andreas Alexopoulos, MD, MPH
Jocelyn Bautista, MD
William Bingaman, MD
Juan Bulacio, MD
Richard Burgess, MD, PhD
Robyn Busch, PhD
Jessica Chapin, PhD
Tatiana Falcone, MD
Nancy Foldvary-Schaefer, DO
Jorge Gonzalez-Martinez, MD, PhD
Ajay Gupta, MD
Stephen Hantus, MD
Jennifer Haut, PhD, ABPP-CN
Lara Jehi, MD
Patricia Klaas, PhD
Prakash Kotagal, MD
Deepak Lachhwani, MB.BS, MD
John Mosher, MD, PhD
Dileep Nair, MD
NEUROLOGICAL INSTITUTE | 109
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
Richard Naugle, PhD
Diosely Silveira, MD, PhD
George Tesar, MD
Ingrid Tuxhorn, MD
Elaine Wyllie, MD
CENTER FOR HEADACHE AND PAIN
Mark Stillman, MDDirector, Center for Headache and Pain
Cynthia Bamford, MD
Neil Cherian, MD
Steven Krause, PhD, MBA
Jennifer Kriegler, MD
Robert Kunkel, MD
MaryAnn Mays, MD
Roderick Spears, MD
Deborah Tepper, MD
Stewart Tepper, MD
MELLEN CENTER FOR MULTIPLE SCLEROSIS
TREATMENT AND RESEARCH
Richard Rudick, MDDirector, Mellen Center for Multiple Sclerosis Treatment and Research
Robert Bermel, MD
Francois Bethoux, MD
Adrienne Boissy, MD
Jeffrey Cohen, MD
Robert Fox, MD
Keith McKee, MD
Deborah Miller, PhD
Alexander Rae-Grant, MD, FRCP (C)
Richard M. Ransohoff, MD
Mary Rensel, MD
Lael Stone, MD
CENTER FOR NEUROIMAGING
Thomas Masaryk, MDDirector, Center for Neuroimaging
Manzoor Ahmed, MD
Todd M. Emch, MD
Stephen E. Jones, MD, PhD
Mark Lowe, PhD
Parvez Masood, MD
Doksu Moon, MD
Micheal Phillips, MD
Paul Ruggieri, MD
Alison Smith, MD
Todd Stultz, DDS, MD
Andrew Tievsky, MD
CENTER FOR NEUROLOGICAL RESTORATION
Ali Rezai, MDDirector, Center for Neurological Restoration
Anwar Ahmed, MD
Scott Cooper, MD, PhD
Milind Deogaonkar, MD
Darlene Floden, PhD
Ilia Itin, MD
Cynthia S. Kubu, PhD, ABPP-CN
Richard Lederman, MD, PhD
Andre Machado, MD, PhD
Donald Malone Jr., MD
Mayur Pandya, DO
Patrick Sweeney, MD
Jerrold Vitek, MD, PhD
NEUROMUSCULAR CENTER
Kerry Levin, MDDirector, Neuromuscular Center
Kamal Chémali, MD
Thomas E. Gretter, MD
Rebecca Kuenzler, MD
Richard Lederman, MD, PhD
Erik Pioro, MD, PhD
David Polston, MD
Robert Shields Jr., MD
Steven Shook, MD
Patrick Sweeney, MD
Jinny Tavee, MD
Lan Zhou, MD, PhD
CENTER FOR PEDIATRIC NEUROLOGY
AND NEUROSURGERY
Elaine Wyllie, MDDirector, Center for Pediatric Neurology
Mark Luciano, MD, PhDDirector, Center for Pediatric Neurosurgery
Bruce H. Cohen, MD
Xiao Di, MD, PhD
Stephen Dombrowski, PhD
Gerald Erenberg, MD
Neil Friedman, MB, ChB
Debabrata Ghosh, MD, DM
Gary Hsich, MD
Irwin Jacobs, MD
Manikum Moodley, MD
Sumit Parikh, MD
A. David Rothner, MD
Tanya Tekautz, MD
NEUROLOGICAL INSTITUTE STAFF
110 | NEUROLOGICAL INSTITUTE
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
DEPARTMENT OF PSYCHIATRY AND PSYCHOLOGY
George Tesar, MDChairman, Department of Psychiatryand Psychology
Susan Albers-Bowling, PsyD
Kathleen Ashton, PhD
Joseph M. Austerman, DO
Scott Bea, PsyD
Dana Brendza, PsyD
Karen Broer, PhD
Kumar Budur, MD
Robyn Busch, PhD
Jessica Chapin, PhD
Kathy Coffman, MD
Gregory Collins, MD
Edward Covington, MD
Roman Dale, MD
Beth Dixon, PsyD
Judy Dodds, PhD
Tatiana Falcone, MD
Darlene Floden, PhD
Kathleen Franco, MD
John P. Glazer, MD
Lilian Gonsalves, MD
Jennifer Haut, PhD, ABPP-CN
Leslie Heinberg, PhD
Karen Jacobs, DO
Joseph Janesz, PhD, LICDC
Regina Josell, PsyD
Elias Khawan, MD
Patricia Klaas, PhD
Steven Krause, PhD, MBA
Cynthia S. Kubu, PhD, ABPP-CN
Donald Malone Jr., MD
Michael McKee, PhD
Scott Meit, PsyD, MBA
Gene Morris, PhD
David Muzina, MD
Richard Naugle, PhD
Mayur Pandya, DO
Michael Parsons, PhD
Shannon Perkins, PhD
Leo Pozuelo, MD
Kathleen Quinn, MD
Ted Raddell, PhD
Judith Scheman, PhD
Isabel Schuermeyer, MD
Jean Simmons, PhD
Barry Simon, DO
Catherine Stenroos, PhD
David Streem, MD
Adele Viguera, MD
John Vitkus, PhD
Cynthia White, PsyD
Amy Windover, PhD
CENTER FOR REGIONAL NEUROLOGY
Stephen Samples, MDDirector, Center for Regional Neurology
A. Romeo Craciun, MDDirector, Stroke Center, Marymount Hospital
Sheila Rubin, MD
Jennifer Ui, MD
Joseph Zayat, MD
CENTER FOR REGIONAL NEUROLOGICAL SURGERY
Michael Mervart, MDDirector, Center for Regional Neurological Surgery
Samuel Borsellino, MD
Samuel Tobias, MD
SLEEP DISORDERS CENTER
Nancy Foldvary-Schaefer, DODirector, Sleep Disorders Center
Loutfi Aboussouan, MD
Kathleen Ashton, PhD
Charles Bae, MD
Kumar Budur, MD
Michelle Drerup, PsyD
Sally Ibrahim, MD
Alan Kominsky, MD
Prakash Kotagal, MD
Jyoti Krishna, MD
William Novak, MD
Carlos Rodriguez, MD
CENTER FOR SPINE HEALTH
Edward Benzel, MDDirector, Center for Spine Health
Gordon Bell, MD
Edwin Capulong, MD
Russell DeMicco, DO
Lars Gilbertson, PhD
Augusto Hsia Jr., MD
Serkan Inceoglu, PhD
Iain Kalfas, MD
Tagreed Khalaf, MD
Ajit Krishnaney, MD
NEUROLOGICAL INSTITUTE STAFF
NEUROLOGICAL INSTITUTE | 111
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
Paula Lidestri, MD
Daniel Mazanec, MD
Robert McLain, MD
Thomas Mroz, MD
R. Douglas Orr, MD
Judith Scheman, PhD
Richard Schlenk, MD
Michael Steinmetz, MD
Santhosh Thomas, DO, MBA
Fredrick Wilson, DO
Adrian Zachary, DO, MPH
NEUROANESTHESIOLOGY
Michelle Lotto, MDHead, Section of Neurosurgical Anesthesia
Zeyd Ebrahim, MDO.R. Clinical Director
Armin Schubert, MDChairman, Department of General Anesthesiology
Rafi Avitsian, MD
Ehab Farag, MD, FRCA
Mariel Manlapaz, MD
Marco Maurtua, MD
Vivek Sabharwal, MD
Gloria Walters, MD
LERNER RESEARCH INSTITUTE
DEPARTMENT OF NEUROSCIENCES
Bruce Trapp, PhDChairman, Department of Neurosciences, Lerner Research Institute
Cornelia Bergmann, PhD
Hitoshi Komuro, PhD
Bruce Lamb, PhD
Wendy Macklin, PhD
Sanjay W. Pimplikar, PhD
Richard M. Ransohoff, MDDirector, Neuroinfl ammation Research Center, Lerner Research Institute
Susan Staugaitis, MD, PhD
Stephen Stohlman, PhD
Jerrold Vitek, MD, PhD
Riqiang Yan, PhD
LERNER RESEARCH INSTITUTE
BIOMEDICAL ENGINEERING
Jay Alberts, PhD
Elizabeth Fisher, PhD
Aaron Fleischman, PhD
Cameron McIntyre, PhD
Shuvo Roy, PhD
LERNER RESEARCH INSTITUTE
CELL BIOLOGY
Damir Janigro, PhD
PATHOLOGY AND LABORATORY MEDICINE INSTITUTE
ANATOMIC PATHOLOGY
Richard Prayson, MD
NEWLY ARRIVING STAFF
Ferdinand Hui, MD
Bushra Malik, MD
NEUROLOGICAL INSTITUTE STAFF
2008 -2009 CONT INU ING MED ICAL EDUCAT ION
September 26-27, 2008Optimizing Function through Spasticity Management: Midwest Spasticity Conference 2008
COURSE DIRECTORS: Francois Bethoux, MD, and Mark Luciano, MD, PhD
Bertram Inn and Conference CenterAurora, Ohio
October 20-22, 2008Gamma Knife Perfexion — Update Training
COURSE DIRECTOR: Gene Barnett, MD
Cleveland Clinic Gamma Knife CenterCleveland, Ohio
October 30-31, 2008Neuroimaging in Traumatic Brain Injury
COURSE DIRECTORS: Stephen Rao, MD, and Harvey Lenin, PhD
InterContinental Hotel and Bank of America Conference CenterCleveland, Ohio
November 5-7, 200811th Annual Neuroscience Nursing Symposium
COURSE DIRECTOR: Kimberly Hunter
Hilton Garden Inn Hotel, Downtown ClevelandCleveland, Ohio
November 6-8, 2008Neuro-Oncology: Current Conceptsin conjunction with Mexican Neurosurgery, Neuro-Oncology, and Radiosurgery Societies
COURSE DIRECTOR: Gene Barnett, MD
Fiesta Americana Grand Los CabosLos Cabos, Mexico
November 21, 20083rd Annual Post Traumatic Stress Disorder Symposium
COURSE DIRECTORS: Joseph Janesz, PhD, and Bridget Dwyer, MA, PC
InterContinental Hotel and Bank of America Conference CenterCleveland, Ohio
December 1-5, 2008Gamma Knife Perfexion Training
COURSE DIRECTOR: Gene Barnett, MD
Cleveland Clinic Gamma Knife CenterCleveland, Ohio
December 4-7, 2008North American Neuromodulation Society 12th Annual Meeting
SCIENTIFIC PROGRAM DIRECTOR: Ali R. Rezai, MD
Mandalay Bay Resort and CasinoLas Vegas, Nev.
February 9-11, 2009Case Studies in Epilepsy Surgery
COURSE DIRECTORS: William Bingaman, MD, and Imad Najm, MD
The Silvertree HotelSnowmass Village, Colo.
February 20-22, 20093rd Annual International Symposium on Stereotactic Body Radiation Therapy and Stereotactic Radiosurgery
COURSE DIRECTORS: Lilyana Angelov, MD, Gene Barnett, MD, Edward Benzel, MD, Sam Chao, MD, and John Suh, MD
The Grand Floridian Resort and SpaLake Buenavista, Fla.
June 19-21, 2009Epileptology: Comprehensive Review and Practical Exercises
COURSE DIRECTORS: Andreas Alexopoulos, MD, Deepak Lachhwani, MD, and Imad Najm, MD
InterContinental Hotel and Bank of America Conference CenterCleveland, Ohio
June 22-24, 200918th International Cleveland Clinic Epilepsy Symposium: Epilepsy Surgery — Improving OutcomesCOURSE DIRECTORS: Imad Najm, MD and William Bingaman, MD
InterContinental Hotel and Bank of America Conference CenterCleveland, Ohio
112 | CONTINUING MEDICAL EDUCATION
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
All physicians are cordially invited to attend the following Cleveland Clinic Neurological Institute CME symposia and
ongoing programs:
Cleveland ClinicCelebrating 75 Years of Excellence in
CONTINUING MEDICAL EDUCATION
For more information, please visit clevelandclinic.org/neuroscience/CME.
CONTACT INFORMATION AND LOCATIONS | 113
CLEVEL ANDCLINIC.ORG /NEUROSCIENCE | 866.588.2264
CONTACT INFORMAT ION AND LOCAT IONS
General Patient Referral
24/7 hospital transfers or physician consults 800.553.5056
Neurological Institute Appointments/Referrals Toll-free 866.588.2264
On the Web at clevelandclinic.org/neuroscience
The Neurological Institute is a Cleveland Clinic-wide endeavor to provide world-class diagnosis and treatment to all patients — whether coming to us from near or far. Institute physicians see patients at Cleveland Clinic’s main campus, six Neurological Institute Regional Centers and nine Cleveland Clinic family health centers.
Please inquire about availability of specifi c services at each location when calling.
Main Campus
9500 Euclid Ave.Cleveland, Ohio 44195 866.588.2264
Neurological Institute Regional Centers
Euclid Hospital18901 Lake Shore Blvd.Euclid, Ohio 44119216.531.9000
Fairview Hospital18101 Lorain Ave.Cleveland, Ohio 44111216.476.7000
Hillcrest Hospital6780 Mayfi eld RoadMayfi eld Heights, Ohio 44124440.312.4500
Huron Hospital13951 Terrace RoadEast Cleveland, Ohio 44112216.761.3300
Lakewood Hospital14519 Detroit Ave.Lakewood, Ohio 44107216.521.4200
Lutheran Hospital1730 West 25th St.Cleveland, Ohio 44113216.696.4300
Cleveland Clinic Family Health Centers
Beachwood Family Health and Surgery Center26900 Cedar RoadBeachwood, Ohio 44122216.839.3000
Chagrin Falls Family Health Center551 E. Washington St.Chagrin Falls, Ohio 44022440.893.9393
Independence Family Health Center5001 Rockside RoadCrown Center IIIndependence, Ohio 44131216.986.4000
Lorain Family Health and Surgery Center 5700 Cooper Foster Park RoadLorain, Ohio 44053440.204.7400
Solon Family Health Center 29800 Bainbridge RoadSolon, Ohio 44139440.519.6800
Strongsville Family Health and Surgery Center 16761 SouthPark CenterStrongsville, Ohio 44136440.878.2500
Westlake Family Health Center 30033 Clemens RoadWestlake, Ohio 44145440.899.5555
Willoughby Hills Family Health Center 2570 SOM Center Rd.Willoughby Hills, Ohio 44094440.943.2500
Cleveland Clinic Wooster1739 Cleveland RoadWooster, Ohio 44691330.287.4500
This fall, Cleveland Clinic is introducing the future of healthcare with the opening of the Sydell and Arnold Miller Family Pavilion and the Glickman Tower.
These buildings, which represent the largest construction and philanthropy project in Cleveland Clinic history, embody the pioneering spirit and commitment to quality that defi ne Cleveland Clinic. These structures are a tangible expression of institutes, our new model of care that organizes patient services by organ and disease.
At 1 million square feet, the Miller Family Pavilion is the country’s largest single-use facility for heart and vascular care. The 12-story Glickman Tower, new home to the Glickman Urological & Kidney Institute, is the tallest building on Cleveland Clinic’s main campus. Both will help us improve patient experience by increasing our capacity and by consolidating services, so patients can stay in one location for their care.
With 278 private patient rooms, more than 90 ICU beds and a combined total of nearly 200 exam rooms and more than 90 procedure rooms, patients will have faster access to Cleveland Clinic cardiac and urological services.
For details, including a virtual tour, please visit meetthebuildings.com.
I N T R O D U C I N G
THE FUTURE OF HEALTHCARE
114 | OTHER NEWS
NEUROLOGICAL INSTITUTE 2007 ANNUAL REPORT
OUTCOMES DATA AVA IL ABLEThe latest outcomes data from Cleveland Clinic’s Neurological Institute are now available. Charts, graphs and tables illustrate the scope and volume of procedures performed in our institute each year. To view the outcomes books for the Neurological Institute and many other Cleveland Clinic institutes, visit clevelandclinic.org/quality/outcomes.
Cleveland Clinic’s neurology and neurosurgery programs are ranked sixth
in the nation and our pediatric neurology and neurosurgery services are ranked
fourth by U.S.News & World Report.
Innovative new
buildings improve patient
access, experience.
11
Outcomes | 2007
NeurologicalInstitute
The Neurological Institute is one of 26 institutes at Cleveland Clinic that group multiple specialties
together to provide collaborative, patient-centered care. The institute is a leader in treating the
most complex neurological disorders, advancing innovations such as deep brain stimulation, epilepsy
surgery, stereotactic spine radiosurgery and blood-brain barrier disruption. Annually, our staff of
more than 200 specialists serves 140,000 patients and performs 6,000 surgeries. Cleveland Clinic
is a nonprofi t multispecialty academic medical center, consistently ranked among the top hospitals
in America by U.S.News & World Report. Founded in 1921, it is dedicated to providing quality
specialized care and includes an outpatient clinic, a hospital with more than 1,000 staffed beds,
an education institute and a research institute.
Cleveland Clinic ©2008 | Design: Chip Valleriano | Editor: Christine Coolick | Principal Photography: Al Fuchs, Don Gerda, Neil Lantzy, Russell Lee, Yu Kwan Lee, Tom Merce, Steve Travarca
The Cleveland Clinic Foundation9500 Euclid Avenue / AC311Cleveland, OH 44195
Our neurology and neurosurgery services are ranked sixth in the nation and our pediatric neurology and
neurosurgery services are ranked fourth by U.S.News & World Report.