Neurological Institute - Cleveland Clinic · Neurological Institute’s expansion in the past few...
Transcript of Neurological Institute - Cleveland Clinic · Neurological Institute’s expansion in the past few...
Neurological Institute
Year in review | 2012
Contents
02 Chairman’s Letter
04 neurological institute Overview
08 Highlights from Our Centers
EEG-Correlated fMRI: A Promising Tool in the Multimodal Evaluation of Refractory Epilepsy
Rollout of Research and Tech Innovations Takes the Fight to Athletic Brain Injuries
Visualizing Glioblastomas Intraoperatively as a Way to Maximize Resection
Making Freedom from Disease Activity an Achievable Goal in Multiple Sclerosis
Taking on Subarachnoid Hemorrhage Across Multiple Research Fronts
22 research and Clinical innovation
Spine Carepath Embeds Evidence-Based Care Strategy into the EMR
Using Advanced Neuroimaging to Pinpoint the Singularities of Blast-Related TBI
StudyChartsNewTerritoryinProfilingPredictorsofObstructiveSleepApneainEpilepsy
A New Tool for Alzheimer Evaluation — And Counseling to Support It
26 neurological institute Leadership and Staff
32 Locations
32 Cleveland Clinic information and resources
Cover image Visualization of a glioblastoma resection margin under blue light following use of 5-aminolevulinic acid demonstrates the presence of residual tumor cells (pink). See article on pages 16-17.
clevelandclinic.org /neuroscience
C L E V E L A N D C L I N I C N E U R O L O G I C A L I N S T I T U T E
Dear Colleagues,
Recent issues of our Year in Review have highlighted the
Neurological Institute’s expansion in the past few years. From
the creation of new disease-specific centers to the opening of
our Lou Ruvo Center for Brain Health location in Las Vegas to
the expansion of specialized services at our community hospi-
tals and our Florida site, our reach has grown substantially.
In view of this, a key focus for the Neurological Institute in
2012 was on maximizing connectivity and standardizing care
at the highest level across our many treatment settings. A big
part of these efforts are the carepaths we have developed for
a growing number of neurological conditions. Carepaths are
evidence-based care models that are embedded in the elec-
tronic medical record (EMR) to guide clinicians through the
care process for a specific condition. The aim is to reduce
harmful or needlessly expensive practice variation and ensure
evidence-based care for all patients.
Concussion and spine care are among the multiple condi-
tions for which we have developed carepaths, as discussed
on pages 14-15 and 23. And our sights are set on a carepath
for relapsing-remitting multiple sclerosis once we achieve
our goal of forging consensus on an operational definition of
disease-free status, as detailed on page 19.
The abovementioned piece on concussion care is a good
example of the centrality of technology to these efforts to
standardize evidence-based care across multiple settings.
This past year saw wide deployment of the Cleveland Clinic
Concussion (C3) mobile application for baseline function
testing in thousands of young athletes across Northeast Ohio
who now can be assessed for concussion with the C3 app
immediately after a head injury during play.
This type of applied technology solution offers the scal-
ability needed to gain maximum value from our Concussion
Carepath. We have been vigorously pursuing other ways to
enhance connectivity and scale up our expertise through
information technology. One example is spotlighted on page
25, where we explain our use of telemedicine to offer the
genetic counseling expertise of Cleveland Clinic’s Center for
Personalized Genetic Healthcare to patients at our Las Vegas
location whose results on a novel neuroimaging test indicate
neuritic plaque levels consistent with possible Alzheimer
disease.
In addition to reducing variability of care, our carepaths are
integrated with our Knowledge Program© interactive database
to allow us to mine the EMR and continually monitor out-
comes. This gives us an unprecedented window into which
treatments are working, which workups are truly needed and
similar issues that will fuel tomorrow’s clinical innovations —
the stuff of future issues of this publication.
For now, I invite you to review the 2012 developments that
we spotlight in these pages, which also include the following:
• Pioneering work combining EEG and fMRI to better
understand the brain regions involved in epileptic activity
• Initial results from the most comprehensive study to date of
chronic traumatic encephalopathy in professional fighters
• Our leading role in a trial of 5-ALA to enhance intraopera-
tive visualization of glioblastomas during resection
• A confluence of research efforts to blunt the impact of
subarachnoid hemorrhage
I welcome your comments and ideas for potential collabora-
tion in the year ahead.
Michael T. Modic, MD, FaCrChairman, Cleveland Clinic Neurological [email protected]
2 3
“A key focus for the Neurological Institute in 2012 was
on maximizing connectivity and standardizing care at
the highest level across our many treatment settings.”
Michael T. Modic, MD, FaCr
C L E V E L A N D C L I N I C N E U R O L O G I C A L I N S T I T U T E
Neurological Institute Overview
The multidisciplinary Cleveland Clinic Neurological Institute
includes more than 300 medical, surgical and research
specialists dedicated to the diagnosis, treatment and reha-
bilitation of adult and pediatric patients with disorders of
the brain and central nervous system.
The institute is anchored by specialized, disease-specific
centers. Each center incorporates a multidisciplinary
approach to the diagnosis and management of a particular
disease or group of diseases, combining the expertise of
physicians and allied health professionals to foster collabo-
ration and improve patient access.
The institute comprises four departments — Neurology,
Neurological Surgery, Psychiatry and Psychology, and
Physical Medicine and Rehabilitation — that integrate
resident training, academics and research.
U.S. News & World Report’s “America’s Best Hospitals”
survey consistently ranks our neurology and neurosurgery
programs among the top 10 in the nation. For us, 2012 is
no exception. We maintain the top ranking in Ohio for neu-
rology/neurosurgery and pediatric neurology/neurosurgery.
expert, Specialized Diagnosis
Neurological Institute physicians draw on advanced diag-
nostic capabilities and experience. Our imaging services
include structural and functional MRI, CT, PET, myelogra-
phy, diagnostic cerebral/spinal angiography, interventional
neuroradiology, and carotid and transcranial Doppler ultra-
sonography. Since 2008, nearly 600 studies have been
performed in our magnetoencephalography laboratory. Our
neuroimaging staff subspecializes in disease entities such
as epilepsy and cerebrovascular disease, ensuring accurate,
in-depth interpretations.
Additional diagnostic tools are found in our epilepsy moni-
toring units, sleep laboratories, neuropsychological testing
facilities, electromyography laboratory and cutaneous nerve
laboratory.
The Latest Treatment Modalities
Patients find leading-edge treatment options at the
Neurological Institute, where we continue to advance such
innovations as deep brain stimulation, laser interstitial ther-
mal therapy for brain tumors, epilepsy surgery, stereotactic
spine radiosurgery, endovascular treatment of cerebral
aneurysms and vascular malformations, and neuroendos-
copy. Joint Commission certification as a Primary Stroke
Center and accreditation by the American Academy of
Sleep Medicine are just two reflections of our commitment
to provide the most advanced, highest-quality care to our
patients.
relevant research
We conduct research directly related to conditions expe-
rienced by our patients, including translational research
and clinical trials of drug and device interventions. In
2011, some 229 clinical research projects involving 6,227
patients were under way in the Neurological Institute.
Neurologically based research grants and contract awards
totaled nearly $12 million.
Convenient Care in the Community
We are committed to making access to world-class care
convenient for all patients. Neurological Institute services
are available at Cleveland Clinic community hospitals and
family health centers throughout Northeast Ohio, as well
as in Nevada and Florida. As a result, patients can easily
54
The institute comprises four departments — Neurology,
Neurological Surgery, Psychiatry and Psychology, and
Physical Medicine and Rehabilitation — that integrate
resident training, academics and research.
neurological institute Centers
Center for Behavioral Health
Lou Ruvo Center for Brain Health
Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center
Cerebrovascular Center
Concussion Center
Epilepsy Center
Center for Home Care and Community Rehabilitation
Mellen Center for Multiple Sclerosis Treatment and Research
Center for Neuroimaging
Neurological Center for Pain
Center for Neurological Restoration
Neuromuscular Center
Center for Pediatric Neurology and Neurosurgery
Department of Physical Medicine and Rehabilitation
Center for Regional Neurosciences
Sleep Disorders Center
Center for Spine Health
C L E V E L A N D C L I N I C N E U R O L O G I C A L I N S T I T U T E
access specialists who treat the most complex neurological
conditions. This approach is predicated on the notion that
those we serve are entitled to a uniformly high level of care
and that location should never be an issue.
Key components in our regional network include:
• Cleveland Clinic Neurological Institute at Lakewood
Hospital and Cleveland Clinic Neurological Institute at
Hillcrest Hospital, providing comprehensive services
throughout the community
• 120 acute inpatient rehabilitation beds at facilities across
Northeast Ohio
• A team of more than 750 specialty-trained therapists at
more than 45 locations offering physical medicine and
rehabilitation services
• Cleveland Clinic at Home, within the Center for Home
Care and Community Rehabilitation, bringing in-home
and distance healthcare to individuals in an expansive
area encompassing 14 Ohio counties and providing
home infusion/pharmacy services in eight states
integrated nursing
Nurses in the Neurological Institute rank as respected
members of the care team. They are encouraged to offer
their input to physicians and administrators and to engage
in problem-solving and process improvement. Patients
benefit from this integration through improved coordination
of care and shared provider goals.
Nurses with at least two years’ experience in the institute
can aspire to certification in neuroscience nursing. These
subspecialists staff areas such as the neurological intensive
care unit and neurological stepdown units that treat the
most complex patients.
Each November, Cleveland Clinic’s “Innovations in
Neuroscience” conference convenes in Cleveland. One of
its goals is to foster increased provider collaboration among
attendees, which include nurses, physician assistants and
medical assistants.
neurological institute volume, 2011
Patients
Total outpatient visits 186,666
Admissions 16,597
Inpatient days 100,469
Procedures
Surgical/interventional 9,684
Neuroimaging studies 76,556
Pioneering the Collection of Data and Outcomes
The Neurological Institute’s Knowledge Program© has
captured data from more than 1 million self-administered
patient questionnaires. One of the world’s first interactive
clinical patient databases, the Knowledge Program is dem-
onstrating its value as it evolves, with collection and cor-
relation of electronic information on patient health status,
quality of life and outcomes.
We are aggregating this patient-generated data with
information from other sources — such as imaging results,
information collected during patient encounters and data
from our growing number of condition-specific clinical
carepaths — to optimize clinical decision-making, quality
improvement and research opportunities.
All these data are accessible to physicians through an
interface with the patient’s electronic medical record. The
Knowledge Program is proving to be among our most con-
structive tools for delivering individualized care to improve
outcomes and quality of life, in line with Cleveland Clinic’s
guiding principle: Patients First.
research Funding, 2011
Grant and contract research dollars funding neurological investigations in the Neurological Institute totaled nearly $12 million.
New clinical research projects 70
Total active clinical research projects 229
Staff leading clinical research projects 59
New patients enrolled in clinical 1,362 research projects
Total patient enrollment in clinical 6,227 research projects
Federal grants and contracts 66
Nonfederal grants and contracts 186
76
N E U R O L O G I C A L I N S T I T U T EC L E V E L A N D C L I N I C
above Schematic illustration of an EEG spike predominantly involving EEG electrodes recording from the left frontal and central regions of the patient’s brain. During simultaneously recorded EEG/fMRI, correlation is sought between the time of EEG spike and the brain activation pattern.
above Schematic illustration of cortical activation revealed with functional MRI within the left basal frontal lobe and anterior insula. Areas of interest are super-imposed on sagittal and axial images of the patient’s structural MRI. Red indicates activation; green indicates deactivation.
The use of scalp electroencephalography (EEG) simultane-
ously with functional magnetic resonance imaging (fMRI)
allows measurement of electrical brain activity in correla-
tion with the hemodynamic response in the brain. Known
as EEG-correlated fMRI, or simply EEG/fMRI, this nonin-
vasive multimodal neuroimaging technique is being used
at Cleveland Clinic’s Epilepsy Center in an effort to better
understand the pathophysiologic mechanisms and patterns
of epileptic activities, particularly the generators of interictal
discharges (spikes).
Cleveland Clinic is one of only a few clinical centers in the
United States to employ EEG/fMRI, which currently serves
as a research tool in the study of brain regions involved at
the time of epileptic activity.
Eventually, EEG/fMRI may become clinically valuable as
a multimodal tool for evaluating individuals with epilepsy,
including patients whose seizures are difficult to control
with medications and in whom identifying the seizure
focus is challenging. Localizing the brain regions that show
changes in neuronal activity during interictal spikes through
the use of fMRI may one day enhance the evaluation of
surgical candidates and may help guide surgical strategies
in patients with refractory seizures.
The software used to execute simultaneous EEG and fMRI
has been approved by the U.S. Food and Drug Adminis-
tration for research applications. Cleveland Clinic is in a
unique position to validate the clinical use of EEG/fMRI
because of the high volume of evaluations and surgeries it
performs in patients with seizures refractory to medications.
a Spatiotemporal Snapshot of Brain activity
Integrating data obtained from EEG/fMRI may provide a
spatiotemporal snapshot of brain activity that is not avail-
able through either modality alone (see images on facing
page). With EEG, temporal resolution is excellent because it
directly measures electrical activity in the brain, but spatial
resolution is poor. Therefore, the accuracy of EEG in local-
izing the neuronal source from measurements of voltages at
the scalp is limited. In contrast, spatial localization of brain
activity is much better with fMRI, but temporal resolution
is poor. These differing profiles make the two techniques
complementary for measuring brain function.
With EEG/fMRI, MRI-compatible EEG electrodes are
attached to the patient’s head outside the MRI scanner.
Once the patient enters the scanner, these electrodes
are connected to an amplifier in the MRI suite and to a
recording computer outside the scanner room using a
fiber-optic cable. This configuration helps to ensure patient
safety during acquisition of the EEG/fMRI study.
Because patients must be placed inside the scanner for
this procedure, the duration of the recording is limited
to about one hour, so capturing activity during an actual
seizure is rare. This duration is usually sufficient, however,
to capture several interictal epileptic spikes and record the
timing of these activities. The simultaneous acquisition of
data using EEG and fMRI allows measurement of blood
oxygen levels in specific brain regions to be correlated with
the spike activity, offering evidence of the origin and spread
pattern of each spike. The hemodynamic response in the
brain is referred to as the blood-oxygen-level-dependent
EEG-Correlated fMRI: A Promising Tool in the Multimodal Evaluation of Refractory Epilepsy
98
N E U R O L O G I C A L I N S T I T U T EC L E V E L A N D C L I N I C
(BOLD) effect. Multiple spikes originating from the same
brain region provide important localizing information and
represent a strong indication that the epilepsy is focal and
potentially amenable to surgical therapy.
Cleaning Up Signal artifacts
The EEG recording environment in the MRI scanner is
electromagnetically noisy because of the inductive effects
of strong switching magnetic gradient fields. Removing arti-
facts from the EEG recording can be accomplished through
several methods that use software to filter or clean up the
signal (see images above). The EEG tracing is reviewed to
determine the exact timing of epileptic spikes. The timing is
right EEG data after artifact removal showing normal brain activity during wakefulness along with eye movement potentials, which are distributed, as expected, over the most anterior frontal EEG electrodes.
Left Raw EEG data acquired in a 3T Siemens MRI scanner before artifact removal.
then correlated to changes in the fMRI BOLD signal, which
measures the corresponding hemodynamic response.
Studies of focal epileptic spikes caused by different types
of brain pathologies have shown reliable activations in
the fMRI BOLD signal within the expected location of the
epileptogenic focus. In addition, these studies reveal areas
of activation and deactivation at locations distant from the
Left BOLD response recorded during an EEG/fMRI session. At the time of interictal epileptic spikes, the left anterior insula showed prominent cortical activation (circle), localizing the metabolic origin of the spikes. The posterior BOLD changes are expected in some patients undergoing EEG/fMRI and are not directly related to the origin of the patient’s epilepsy.
right EEG recorded simultaneously with the fMRI, with artifacts removed offline. The spike predominantly involved EEG electrodes recording from the left temporal region of the patient’s brain, concordant with the cortical activation shown by fMRI.
pathological focus, and thus provide a unique glimpse into
the underlying networks of brain activity. The significance
of distant responses in the study of brain connectivity and
pathological epileptic networks is one of the issues under
active investigation at Cleveland Clinic’s Epilepsy Center.
1110
R L
N E U R O L O G I C A L I N S T I T U T E
B
A
Rollout of Research and Tech Innovations Takes the Fight to Athletic Brain Injuries
As sports-related head injuries garner more and more pub-
lic attention, researchers and clinicians across Cleveland
Clinic’s Neurological Institute are pursuing multiple initia-
tives to better understand these injuries and curb their
impact. One initiative is a large, unprecedented study
exploring how repeated blows to the head contribute to
neurodegenerative disease in professional fighters. Another
is the broad deployment of an inexpensive technology
solution to take the guesswork out of concussion assess-
ment in youth athletes. Both initiatives began yielding
important practical payoffs in 2012.
Professional Fighters Study: Brain Changes Surface
Long Before Symptoms
The link between repetitive head trauma and the neuro-
degenerative condition known as chronic traumatic
encephalopathy is not new, but little is known about the
condition’s natural history or risk factors.
To fill that knowledge gap, researchers with Cleveland
Clinic Lou Ruvo Center for Brain Health launched the
Professional Fighters Brain Health Study (PFBHS) in
2011. The trial is combining annual MRI studies with
computerized cognitive and mood testing, speech sample
analysis and other tests in a large group of professional
fighters (boxers and mixed martial arts athletes) for at least
four years. It has several aims:
• To examine the cumulative effects of repetitive injuries to
the brain in real time
• To assess the earliest and most subtle signs of brain
injury via MRI and other clinical measures
• To determine which factors make development of chronic
neurodegenerative disorders more likely
• To identify fighters who are progressing to long-term
neurodegenerative disease
In 2012, lead researcher Charles Bernick, MD, Associate
Medical Director of the Lou Ruvo Center for Brain Health,
presented one-year PFBHS findings from 146 fighters —
more than had ever been collected in a single research
report. This level of recruitment was made possible by the
center’s location in Las Vegas, billed as the “fight capital of
the world,” and trial enrollment continues to grow.
The one-year results showed that structural changes were
detectable in the brain even before any cognitive symptoms
appeared. Specific findings included the following:
• Greater numbers of fights and years of professional
fighting are associated with lower volumes of several
cortical and subcortical structures, but only after five
years of professional fighting.
• A much higher threshold is needed to show a
relationship between the number of fights and reduced
performance levels, such as decreased speed in
processing information.
Although these initial findings need to be confirmed longitu-
dinally, they are consistent with what is known so far about
subclinical disease in neurodegenerative conditions such as
Alzheimer disease and Parkinson disease.
Indeed, results of the PFBHS may ultimately guide the use
of MRI monitoring to identify degenerative brain disease
before cognitive symptoms surface in a wider population
subjected to repeated head blows, including young athletes
Above MRI methods that measure the strength of functional connections in the brain among professional fighters show a reduction in connection strength between the executive region (A) and the motor-control region (B) with fight exposure.
1 3
C L E V E L A N D C L I N I C N E U R O L O G I C A L I N S T I T U T E
and combat soldiers. Meanwhile, Lou Ruvo Center for
Brain Health researchers say their findings may start to
guide professional fighting’s regulatory agencies in how to
better protect their athletes, including when to require brain
evaluation.
Changing the Trajectory of Sports Concussion Care
Even broader and more immediate impact is resulting from
the Cleveland Clinic Concussion (C3) application for the
Apple® iPad® 2, a validated tool for convenient point-of-care
assessment of concussion symptoms in athletes.
In 2012, Cleveland Clinic athletic trainers used the C3
iPad app to conduct baseline assessments of motor
and cognitive function in nearly 6,000 high school and
college athletes across Northeast Ohio who play contact
sports. After baseline data are collected, the C3 app
can be deployed in the locker room or on the sidelines
for immediate objective assessment for concussion if an
athlete sustains a head injury during play.
The C3 app was designed to collect objective data on
motor and cognitive functions affected by concussion and
to provide those data to clinicians in a meaningful way that
permits interaction with the data. An athlete’s balance and
postural stability are assessed while he or she performs
clinical balance tests with an iPad strapped to the waist
(see image). Other relevant functions are assessed by the
app in other ways, such as trail-making tests conducted on
the iPad with a stylus.
The app-based assessment generates a “performance
polygon” plot (see image) that visually displays the extent
of impairment (vs. baseline) across various functional
domains as well as the speed of recovery in each domain
over continued follow-up. This plot pinpoints the areas of
most concern and helps guide therapy over time, says Jay
L. Alberts, PhD, lead developer of the C3 app and Director
of Cleveland Clinic’s Concussion Center.
In addition to the nearly 6,000 student athletes who
underwent baseline functional assessment, the C3 app was
made available in 2012 for post-injury assessment among
above “Performance polygon” plot generated by the C3 app for an athlete who sustained a head injury in May 2012. The colored tracings indicate performance in several functional domains at baseline (outer ring), at the time of injury (innermost ring) and at various points of follow-up after injury.
an additional 6,000 young athletes who are managed by
Cleveland Clinic athletic trainers but who play noncontact
sports or were not yet scheduled for baseline assessment.
Cleveland Clinic’s next aim is to explore broader deployment
of the C3 app for coordinated use by schools and hospi-
tals across the country, along with the Cleveland Clinic
Concussion Carepath, an online evidence-based protocol
above The Cleveland Clinic Concussion (C3) app prompts athletic trainers to systematically elicit essential information about a head injury on the sidelines.
right The C3 app assesses balance and postural stability while the athlete performs balance tests with an iPad attached to the waist.
1514
to reduce variability of care and improve patient outcomes.
Because the app is highly transferable and designed for an
affordable, widely used device, its potential for dissemina-
tion is great. When used with an evidence-based protocol
like the Concussion Carepath, it holds the promise of taking
much of the guesswork out of concussion management for
athletes around the nation.
C L E V E L A N D C L I N I C N E U R O L O G I C A L I N S T I T U T E
Cleveland Clinic’s Rose Ella Burkhardt Brain Tumor and
Neuro-Oncology Center is investigating fluorescence-guided
resection of glioblastoma using 5-aminolevulinic acid
(5-ALA), a prodrug that causes fluorescent porphyrins to
accumulate in the cells of malignant gliomas.
When 5-ALA is administered orally, it is taken up by
malignant glioma cells, which convert it to protoporphyrin
IX. Protoporphyrin IX fluoresces pink under blue light,
thereby offering the potential to identify residual tumor cells
intraoperatively.
Cleveland Clinic received permission from the U.S. Food
and Drug Administration to conduct a phase 2 study com-
paring 5-ALA with intraoperative MRI for tumor visualiza-
tion with the endpoint of completeness of tumor resection
in patients with suspected new or recurrent glioblastoma or
suspected upgraded glioblastoma.
The extent of bulk tumor resection has been shown to
correlate with prognosis in glioblastoma. Because most
recurrences of glioblastoma are at the margin of surgical
resection, identifying and removing all of the bulk or
contrast-enhancing tumor is expected to delay recurrence
and potentially improve outcomes.
Intraoperative MRI is used at some centers in an effort to
remove all contrast-enhancing tumor, but it requires signifi-
cant capital expenditure for the MRI and room modifica-
tions and it provides only a snapshot in time. Moreover,
obtaining images intraoperatively is cumbersome and
time-intensive, as it requires interruption of the procedure
and the need to re-establish the surgical field.
In contrast, fluorescence-guided resection with 5-ALA
provides information on a continuous basis, is easy to
perform, requires only a modification to existing surgical
microscopes and does not interrupt the procedure. A
potential drawback to 5-ALA is that its efficacy requires
direct visibility of fluorescent areas, so that a layer of
normal tissue may obscure the appearance of tumor cells
or an angle of vision without direct line of sight may lead to
incomplete tumor cell removal.
Cleveland Clinic is one of only about 10 centers in the
United States to investigate the use of 5-ALA for resection
of brain tumors.
The study at Cleveland Clinic is led by Michael Vogelbaum,
MD, PhD, Associate Director of the Burkhardt Brain Tumor
Center. Forty patients with glioblastoma deemed to be surgi-
cal candidates based on current neurosurgical standards of
care are being enrolled. Patients undergoing fluorescence-
guided resection of tumor will receive a single oral dose of
5-ALA two to four hours before the scheduled surgery.
The primary objective involves comparing the volume of tis-
sue removed with 5-ALA-guided resection vs. the measured
enhancing tumor evaluated on a preoperative MRI. Patients
will be assessed for completeness of tumor resection one
to two days after surgery using gadolinium-enhanced brain
MRI. Tumor progression will be assessed subsequently with
images obtained when clinically indicated.above Visualization of a glioblastoma resection margin under blue light following use of 5-ALA demonstrates the presence of residual tumor cells (pink). This visualization is of the same margin shown in the inset. As a result of this enhanced visualization, additional resec-tion was performed until the margin was cleared of bulky disease.
Visualizing Glioblastomas Intraoperatively as a Way to Maximize Resection
inset Intraoperative image of a glioblastoma resection (the same as in accompanying image) using conventional white-light microscopy. A portion of the bulk tumor has been removed, and the margin is being evaluated. It is not obvious from this image whether or not resect-able tumor is present.
1716
N E U R O L O G I C A L I N S T I T U T E
The prospect of achieving freedom from disease activity
in relapsing-remitting multiple sclerosis (MS) is potentially
within reach, given advancements in the ability to monitor
disease activity and the emergence and expanded use of
potent disease-modifying therapies.
To date, freedom from MS disease activity has been a ther-
apy goal defined only in the clinical trial setting. Adoption of
this treatment target in clinical practice will mean overcom-
ing challenges, including the need for agreement on how to
define the target and accurately measure response to MS
therapies. Nevertheless, consensus is building that defini-
tively stopping MS activity early in the disease course is a
worthwhile and achievable patient management goal.
Cleveland Clinic’s Mellen Center for Multiple Sclerosis
Treatment and Research is a leading proponent of this
concept. To that end, the Mellen Center hosted an MS
Experts Consensus Summit in September 2012, bringing
together more than 50 experts in MS to focus on the use of
existing monitoring tools and treatment strategies to achieve
disease-free status in relapsing-remitting MS.
The summit heralded the beginning of an attempt to
standardize the monitoring tools on which an operational
definition of freedom from MS disease activity can be
constructed. Over the course of two days in Cleveland,
summit faculty discussed methods for measuring and
monitoring disease activity and treatment efficacy. Several
key concepts emerged:
• A consensus definition is needed to serve as a treatment
target for appropriate patients in the clinic as well as to
drive research on the concept of disease-free status.
• Multiple objective measures are candidates for inclusion
in a definition of disease-free status, including relapse
counts/recovery, the Expanded Disability Status Scale,
MRI with and without quantitative analysis, a timed 25-
foot walk, optical coherence tomography, and emerging
biomarkers in the blood and cerebrospinal fluid.
• There is a high level of interest in using patient-reported
outcomes to expand the patient’s role in defining the
treatment target and measuring health status.
Cleveland Clinic’s Neurological Institute is uniquely posi-
tioned to monitor the stability of MS and the effectiveness
of disease-modifying therapies over time, thanks to its
Knowledge Program© database. The Knowledge Program
collects patient-reported measures (e.g., health status,
quality of life, symptoms) at every visit, aggregates these
data with clinician-collected measures (e.g., laboratory
and imaging results) and embeds them in the electronic
medical record (EMR). This transforms the EMR from a
simple repository for physicians’ notes and test results into
a dashboard of clinical tools with which Cleveland Clinic
neurologists can design patient management plans.
The goal is to use an operational definition of disease-
free status in relapsing-remitting MS as the basis for a
carepath — a comprehensive care interface embedded
in the EMR — to provide treatment guidance, feedback
and real-time reminders that empower neurologists to help
patients bring their disease activity to a standstill.
Making Freedom from Disease Activity an Achievable Goal in Multiple Sclerosis
Cleveland Clinic multiple sclerosis (MS) specialist Robert Bermel, MD, leads a discussion at the MS Experts Consensus Summit held at Cleveland Clinic in September 2012. The summit was convened to advance identification of monitoring tools and treatment strategies to achieve freedom from disease activity in relapsing-remitting MS.
19
N E U R O L O G I C A L I N S T I T U T E
Taking on Subarachnoid Hemorrhage Across Multiple Research Fronts
Subarachnoid hemorrhage (SAH) often results from rupture
of an aneurysm in the brain. While it’s a potentially devas-
tating disease in its own right, SAH also brings a number
of complications that can lead to further brain damage.
Physician researchers in the Neurological Institute’s Cerebro-
vascular Center are joining forces to conduct broad-based
studies into aneurysmal SAH and its potential complications.
Platelets and SaH Outcomes
The effect of platelet aggregation on functional outcomes in
patients with SAH is being evaluated by Jennifer Frontera,
MD. Recently, she discovered elevations in markers of
platelet activation and inflammation during the first 72
hours after aneurysm rupture, which suggests that platelet
activation is involved in early brain injury.
The role of microthrombosis after aneurysmal SAH as a
contributor to early cerebral injury is the focus of a research
grant awarded to Dr. Frontera by the American Heart Asso-
ciation. If microclot formation is found to be a significant
player in early damage after SAH, its attenuation by early
antiplatelet therapy might represent a new treatment para-
digm. Discovering the optimal timing and intensity of such
therapy to discourage rebleeding, an unwanted side effect
of antiplatelet therapy, is of paramount importance.
innate immune Mechanisms in vasospasm after SaH
The pathways by which neutrophil infiltration and activation
lead to delayed cerebral injury as a complication of SAH are
being explored by J. Javier Provencio, MD, a Cerebrovas-
cular Center neurointensivist who also works in the Lerner
Research Institute’s Neuroinflammation Research Center.
Support for Dr. Provencio’s work on this type of delayed
cerebral injury (also called vasospasm) includes a grant
from the National Institute of Neurological Disorders and
Stroke. His laboratory is studying preclinical models of SAH
to understand the immune mechanisms responsible for
delayed deterioration, with the hope of developing immune-
based treatments to prevent or treat this complication.
His laboratory is also collaborating with Neurological
Institute neuropsychologist and researcher Cindy Kubu,
PhD, to conduct studies of patients with SAH in order to
evaluate the role of inflammation in the long-term cognitive
deficits seen after SAH.
iron Overload in iCH and SaH
The release of iron into the brain has been shown to be a
mechanism of injury in intracerebral hemorrhage (ICH), a
disease related to, but different from, SAH. The Cerebro-
vascular Center is involved in a multicenter national trial of
early deferoxamine mesylate, an iron chelator, for treatment
of brain injury secondary to ICH. As a corollary to this study,
Joao Gomes, MD, is investigating whether iron accumula-
tion is similarly involved in the pathogenesis of early brain
injury following SAH in humans. If it is, this may open the
door to acute administration of desferoxamine as a potential
strategy for preserving neurons in patients with SAH.
a Broad Mix of neurointensive investigations
These three physician researchers form the core of a
larger neurointensive care group that includes five other
neurointensivists who all have research and quality proj-
ects based in Cleveland Clinic’s neurointensive care unit.
By sharing clinical data and lab resources, these neuro-
intensive care researchers are rapidly working toward
treatments for some of the most deadly and debilitating
diseases of the brain.
After a cerebral aneurysm ruptures in the large arteries of the brain, blood under arterial pressure spills into the subarachnoid space (arrows).
Cleveland Clinic researchers are exploring the role of micro-thrombosis after aneurysmal SAH as a contributor to early cerebral injury.
2 1
C L E V E L A N D C L I N I C N E U R O L O G I C A L I N S T I T U T E
Research and Clinical Innovation
Cleveland Clinic’s Neurological Institute carries out a robust
research program that fosters a culture of innovation and
collaboration. Physician investigators and scientists pursue
laboratory-based research whose findings are applied to
improve patient care. In 2011, we were awarded nearly
$12 million in neurologically based research grants and
contracts and had 229 clinical research projects actively
under way.
In addition to the innovations featured in the preceding
pages, below are snapshots of other innovative Neurologi-
cal Institute initiatives that saw significant developments in
2012 and will continue to evolve in the years ahead.
Spine Carepath embeds evidence-Based
Care Strategy into the eMr
Fragmented, variable and costly: Despite the recent pro-
liferation of clinical practice guidelines for managing back
pain, treatment of back pain remains fragmented among
multiple providers, varies widely from evidence-based
recommendations, and too often involves inappropriate use
of expensive therapies and imaging tools.
To address the stubbornly poor compliance with spine
care guidelines, Cleveland Clinic’s Center for Spine Health
has developed the Cleveland Clinic Spine Carepath, an
evidence-informed algorithmic strategy for managing back
pain that is embedded in the electronic medical record
(EMR). Key elements of care are captured in structured
documentation (“clinical notes”) in the EMR, and diagnostic
and therapeutic orders are recorded in a retrievable data set.
This design allows retrospective study of the process of care
and its impact on clinical outcomes. The Spine Carepath’s
utility for outcomes research is further enhanced by its link-
age with Cleveland Clinic’s Knowledge Program© database,
which elicits patient-reported validated outcome measures
at appropriate points throughout the course of care.
The carepath provides an opportunity to reduce potentially
harmful variability in spine care while improving patient
outcomes and reducing inappropriate or premature use of
medical resources. The latter may reduce the cost of care
and improve value. And because the carepath systemati-
cally analyzes process and outcomes data to continually
re-evaluate and revise its clinical algorithm, it will keep
itself on its toes — and ensure that patients get the most
up-to-date, value-driven care.
Imaging positive?
Non-spine specialty referral
Yes
Surgical care
Conservative care
Psych
Yes
No
No
Pre-op
Follow-up (> 12 weeks)
Sufficient progress?
Continue treatment
No
No
Yes
Operating room
Post-op
Yes
Follow-upSufficient progress?
Specialty referral
Follow-up (6–12 weeks)
Medication (muscle relaxant/
NSAID)
Education
Activity as tolerated/
self-care
Manipulation
Sufficient progress?
Physicaltherapy
Treatment plan
w/ imaging
Continue treatment
Yes
No
Education
Medication (muscle relaxant/
NSAID)
Activity as tolerated/
self-care
Manipulation
Follow-up (< 4 weeks)
Treatment plan
Sufficient progress?
Continue treatment
Yes
Treatment plan
No
Reassess;red flags?
Refer to initial visit
Yes
No No
LOW BACK PAIN work flow
s
t
t
t t
t
t
t
t
t
t
t
t
t
t
t
t
t
t
Interventional careYes
t
t t t t t
tt
t
t
t
t
t
t
t
t
s
s
t
s
t
Refer to initial visit
Reassess;red flags?
Yes
Below A portion of the Spine Carepath’s recommended work flow for low back pain.
2 3 2 2
In our most recent reporting year, the Neurological
Institute had 229 clinical research projects — involving
6,227 patients — actively under way.
C L E V E L A N D C L I N I C N E U R O L O G I C A L I N S T I T U T E
Using advanced neuroimaging to Pinpoint the
Singularities of Blast-related TBi
Traumatic brain injury (TBI) following explosive blasts
in military combat is different from other forms of TBI,
but insight into exactly how it differs has been limited.
Cleveland Clinic’s Schey Center for Cognitive Neuroimaging
is one of a select group of research centers to win fund-
ing from the U.S. Department of Defense to study blast-
induced TBI in military personnel in order to sort out those
differences and how best to treat them.
The differences in blast-induced TBI are thought to
stem from changes in air pressure caused by the blast.
Conventional MRI has failed to elucidate the resulting dam-
age to both gray and white matter in the brain. In response,
Cleveland Clinic researchers have been using advanced
neuroimaging techniques — functional MRI with diffu-
sion tensor imaging and high-angular-resolution diffusion
imaging — to identify biomarkers that may continue to
indicate TBI-related neural changes long after the injured
individual’s cognitive function has returned to near normal.
They are combining these imaging studies with compre-
hensive neuropsychological testing in a controlled study of
160 individuals, including active-combat military person-
nel with and without blast-induced TBI and civilians with
mechanical TBI and other traumatic injuries. Neuroimaging
is conducted at least one year after TBI to help ensure that
relatively permanent neural changes are being measured.
Data collection ended in the last few months of 2012.
While image analysis is continuing into 2013, initial
findings appear to provide preliminary evidence that
neural changes from blast-induced TBI are different from
neural changes from civilian brain injuries. Cleveland
Clinic researchers are using similar imaging techniques
in longitudinal studies to identify imaging biomarkers in
people genetically at risk for Alzheimer disease and to study
patients in the preclinical stages of Huntington disease.
Study Charts New Territory in Profiling Predictors
of Obstructive Sleep apnea in epilepsy
Early diagnosis of obstructive sleep apnea (OSA) is a focus
of Cleveland Clinic’s Sleep Disorders Center, but the diagno-
sis of OSA can be fraught with complexities in populations
with neurologic disease. Since OSA is a contributor to poor
seizure control in epilepsy patients, early OSA diagnosis
and treatment can yield clear payoffs in this population.
To better understand the predictors of OSA in epilepsy,
researchers from the Sleep Disorders Center and the
Epilepsy Center recently teamed to assess cross-sectional
OSA prevalence and predictors in 130 consecutive adults
with epilepsy using polysomnography, structured interviews
fMRI studies show a difference in brain activation in the inferior temporal gyrus (circled orange region) between blast-induced TBI and mechanical TBI.
and subjective assessments. Their study, the first to explore
OSA predictors using polysomnography in patients un-
selected for epilepsy severity or sleep disorder symptoms,
was published in Epilepsy & Behavior (2012;25:363-367).
A full 30 percent of study participants had OSA (apnea-
hypopnea index [AHI] ≥ 10) and 16 percent had severe
OSA (AHI ≥ 15), rates that are markedly higher than those
in the general population. The risk for OSA increased with
age and higher doses of anti-epileptic drugs regardless of
gender, body mass index and seizure frequency. Some tra-
ditional OSA risk factors, such as male gender and higher
body mass index, were found to be stronger predictors of
the severity of OSA than of the presence of OSA.
While noting that their observational study requires confir-
mation in longitudinal trials, the Cleveland Clinic researchers
concluded that these findings support implementation of
routine OSA screening in adult epilepsy clinics.
a new Tool for alzheimer evaluation —
and Counseling to Support it
When the FDA approved the radiopharmaceutical Amyvid™
in April, it became possible for the first time to determine
the brain’s density of the neuritic plaques implicated in
Alzheimer disease (AD) without brain biopsy or autopsy
exam. Cleveland Clinic Lou Ruvo Center for Brain Health is
one of a limited number of centers across the country using
Amyvid, and it’s setting itself apart even more by the coun-
seling it offers patients after they undergo Amyvid testing.
Amyvid is approved for use with PET imaging of the brain
to estimate beta-amyloid neuritic plaque density in adults
with cognitive impairment who are being evaluated for AD.
A negative scan indicates sparse to no neuritic plaques
and is inconsistent with an AD diagnosis. A positive scan
indicates moderate to frequent plaques but does not estab-
lish a diagnosis of AD because while these plaque levels
are found in patients with AD, they may also be present in
patients with other types of cognitive impairment and in
older people with normal cognition. For this reason, PET
scanning with Amyvid is an adjunct to other diagnostic
evaluations for AD.
At Cleveland Clinic, patients who have a positive scan or
carry an AD diagnosis are offered the services of the Center
for Personalized Genetic Healthcare, the clinical arm of
Cleveland Clinic’s Genomic Medicine Institute. Patients can
take advantage of genetic counseling for education on the
genetics of AD and what it means for them and their family
members. Genetic testing, and why it may or may not be
appropriate, can also be discussed. Novel telemedicine
offerings allow patients evaluated at the Lou Ruvo Center
for Brain Health location in Las Vegas to seamlessly access
the genetic counselors the same way that patients in
Cleveland do.
PET imaging with Amyvid in a healthy brain (left) and an Alzheimer disease brain (right).
2 52 4
N E U R O L O G I C A L I N S T I T U T EC L E V E L A N D C L I N I C
Center for Behavioral Health
Donald A. Malone Jr., MD Chairman, Department of Psychiatry and PsychologyDirector, Center for Behavioral Health
Susan Albers Bowling, PsyD
Amit Anand, MD
Brian Appleby, MD
Kathleen Ashton, PhD
Joseph M. Austerman, DO
Joseph Baskin, MD
Scott Bea, PsyD
Aaron Bonner-Jackson, PhD
Minnie Bowers-Smith, MD
Robert Brauer, DO
Dana Brendza, PsyD
Karen Broer, PhD
Robyn Busch, PhD
Kathy Coffman, MD
Gregory Collins, MD
Edward Covington, MD
Roman Dale, MD
Syma Dar, MD
Sara Davin, PsyD, MPH
Ketan Deoras, MD
Beth Dixon, PsyD
Judy Dodds, PhD
Jung El-Mallawany, MD
Tatiana Falcone, MD
Lara Feldman, DO
Darlene Floden, PhD
Kathleen Franco, MD
Margo Funk, MD
Lilian Gonsalves, MD
J. Robert Gribble, PhD
Jennifer Haut, PhD, ABPP-CN
Justin Havemann, MD
Leslie Heinberg, PhD
Kelly Huffman, PhD
Karen Jacobs, DO
Joseph W. Janesz, PhD, LICDC
Amir Jassani, PhD
Jason Jerry, MD
Regina Josell, PsyD
Elias Khawam, MD
Patricia Klaas, PhD
Steven Krause, PhD, MBA
Cynthia S. Kubu, PhD, ABPP-CN
Richard Lightbody, MD
Manu Mathews, MD
Michael McKee, PhD
Douglas McLaughlin, DO
Amit Mohan, MD
Gene Morris, PhD
Kathryn Muzina, MD
Richard Naugle, PhD
Mayur Pandya, DO
Michael Parsons, PhD
Leo Pozuelo, MD
Kathleen Quinn, MD
Ted Raddell, PhD
Stephen Rao, PhD
Michael Rosas, MD
Robert T. Rowney, DO
Balaji Saravanan, MD
Judith Scheman, PhD
Isabel Schuermeyer, MD
Cynthia Seng, PhD
Jean Simmons, PhD
Barry Simon, DO
Catherine Stenroos, PhD
David Streem, MD
Amy Sullivan, PsyD
Giries W. Sweis, PsyD
George E. Tesar, MD
Mackenzie Varkula, DO
Adele Viguera, MD
John Vitkus, PhD
Kelly Wadeson, PhD
Cynthia White, PsyD
Molly Wimbiscus, MD
Amy Windover, PhD
Lou Ruvo Center for Brain Health
Jeffrey Cummings, MD, ScD Director, Lou Ruvo Center for Brain Health
Brian Appleby, MD
Sarah Banks, PhD
Charles Bernick, MD
Aaron Bonner-Jackson, PhD
Gabriel Leger, MD
Donna Munic-Miller, PhD
Richard Naugle, PhD
Michael Parsons, PhD
Jagan Pillai, MD, PhD
Alexander Rae-Grant, MD, FRCP(C)
Stephen Rao, PhD, ABPP-CNDirector, Schey Foundation Center for Advanced Cognitive Function
Patrick Sweeney, MD
Babak Tousi, MD
Po-Heng Tsai, MD
Ryan Walsh, MD, PhD
Timothy West, MD
Dylan Wint, MD
Xue (Kate) Zhong, MD, MSc
Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center
Gene Barnett, MD, MBA, FACS Director, Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center
Manmeet Ahluwalia, MD
Lilyana Angelov, MD, FRCS(C)
Toomas Anton, MD
Samuel Chao, MD
Kambiz Kamian, MD
StaffLeadership
NEuROLOGICAL INSTITuTE CHAIRMEN
Michael T. Modic, MD, FACR Chairman, Neurological Institute
William Bingaman, MD Vice Chairman, Clinical Areas, Neurological Institute
Richard Rudick, MD Vice Chairman, Research and Development, Neurological Institute
Edward Benzel, MD Chairman, Department of Neurological Surgery
Frederick Frost, MD Chairman, Department of Physical Medicine and RehabilitationDirector, Center for Home Care and Community Rehabilitation
Kerry Levin, MD Chairman, Department of Neurology
Donald A. Malone Jr., MD Chairman, Department of Psychiatry and Psychology Director, Center for Behavioral Health
Thomas Masaryk, MD Chairman, Department of Diagnostic Radiology
Bruce Trapp, PhD Chairman, Department of Neurosciences, Lerner Research Institute
2 72 6
N E U R O L O G I C A L I N S T I T U T EC L E V E L A N D C L I N I C
John Lee, MD
Joung Lee, MD
Erin Murphy, MD
Michael Parsons, PhD
David Peereboom, MD
Violette Recinos, MD
Jeremy Rich, MD
Steven Rosenfeld, MD, PhD
Glen Stevens, DO, PhD
John Suh, MD
Tanya Tekautz, MD
Jose Valerio-Pascua, MD
Michael Vogelbaum, MD, PhD, FACS
Robert Weil, MD
Jennifer Yu, MD, PhD
Cerebrovascular Center
Peter Rasmussen, MD Director, Cerebrovascular Center
Mark Bain, MD
Dhimant Dani, MD
Erin Dyer, MD
Abeer Farag, MD
Neil Friedman, MBChB
Jennifer Frontera, MD
Joao Gomes, MD
Ferdinand Hui, MD
M. Shazam Hussain, MD, FRCPC
Irene Katzan, MD, MS
John Lee, MD
Mei Lu, MD, PhD
Gwendolyn Lynch, MD
Edward Manno, MD
Thomas Masaryk, MD
Laurie McWilliams, MD
J. Javier Provencio, MD, FCCM
Andrew Russman, DO
Susan Samuel, MD
Gabor Toth, MD
Ken Uchino, MD
Epilepsy Center
Imad Najm, MD Director, Epilepsy Center
Badih Adada, MD
Andreas Alexopoulos, MD, MPH
Jocelyn Bautista, MD
William Bingaman, MD
Juan Bulacio, MD
Richard Burgess, MD, PhD
Robyn Busch, PhD
Tatiana Falcone, MD
Nancy Foldvary-Schaefer, DO, MS
Joanna Fong, MD
Paul Ford, PhD
Nestor Galvez-Jimenez, MD
Jorge Gonzalez-Martinez, MD, PhD
Ajay Gupta, MD
Stephen Hantus, MD
Jennifer Haut, PhD, ABPP-CN
Lara Jehi, MD
Stephen E. Jones, MD, PhD
Patricia Klaas, PhD
Prakash Kotagal, MD
Deepak Lachhwani, MBBS, MD
Chetan Malpe, MD
John Mosher, PhD
Dileep Nair, MD
Richard Naugle, PhD
Silvia Neme-Mercante, MD
Adriana Rodriguez, MD
Paul Ruggieri, MD
Norman So, MD
Andrey Stojic, MD, PhD
George E. Tesar, MD
Guiyan Wu, MD
Elaine Wyllie, MD
Zhong Ying, MD, PhD
Center for Home Care and Community Rehabilitation
Frederick Frost, MD Director, Center for Home Care and Community Rehabilitation
Raghavendra Allareddy, MD
Young Doo Chang, MD
Michael Felver, MD
Eiran Gorodeski, MD, MPH
Mona Gupta, MD
Terence Gutgsell, MD
Mohammed Ahmed Khan, MD
Do Gyun Kim, MD
Anu Shrestha, MD
Ethel Smith, MD
Maidana Vacca, MD
William Zafirau, MD
Mellen Center for Multiple Sclerosis Treatment and Research
Richard Rudick, MD Director, Mellen Center for Multiple Sclerosis Treatment and Research
Robert Bermel, MD
Francois Bethoux, MD
Adrienne Boissy, MD
Jeffrey Cohen, MD
Devon Conway, MD
Robert Fox, MD
Keith McKee, MD
Deborah Miller, PhD
Daniel Ontaneda, MD
Alexander Rae-Grant, MD, FRCP(C)
Richard M. Ransohoff, MD
Mary Rensel, MD
Lael Stone, MD
Amy Sullivan, PsyD
Timothy West, MD
Center for Neuroimaging
Thomas Masaryk, MD Director, Center for Neuroimaging
Paul Ruggieri, MD Head, Section of Neuroimaging
Todd M. Emch, MD
Nicholas Fetko, MD
Ramin Hamidi, DO
Virginia Hill, MD
Rebecca Johnson, MD
Stephen E. Jones, MD, PhD
Daniel Lockwood, MD
Mark Lowe, PhD
Parvez Masood, MD
Michael T. Modic, MD, FACR
Doksu Moon, MD
Michael Phillips, MD
Alison Smith, MD
Todd Stultz, DDS, MD
Andrew Tievsky, MD
Neurological Center for Pain
Edward Covington, MD Director, Neurological Center for Pain
Cynthia Bamford, MD
Eric Baron, MD
Neil Cherian, MD
Sarah Davin, PsyD
Kelly Huffman, PhD
Steven Krause, PhD, MBA
Jennifer Kriegler, MD
Jahangir Maleki, MD, PhD
Manu Mathews, MD
MaryAnn Mays, MD
Judith Scheman, PhD
Mark Stillman, MD
Giries W. Sweis, PsyD
Deborah Tepper, MD
Stewart Tepper, MD
Brinder Vij, MD
Center for Neurological Restoration
Andre Machado, MD, PhD Director, Center for Neurological Restoration
Anwar Ahmed, MD
Jay Alberts, PhD
Scott Cooper, MD, PhD
Hubert Fernandez, MD
Darlene Floden, PhD, ABPP-CN
John Gale, PhD
Michal Gostkowski, DO
Ilia Itin, MD
Cynthia S. Kubu, PhD, ABPP-CN
Richard Lederman, MD, PhD
Donald A. Malone Jr., MD
Cameron McIntyre, PhD
Mayur Pandya, DO
Ela B. Plow, PhD, PT
Joseph Rudolph, MD
Patrick Sweeney, MD
Ryan Walsh, MD, PhD
Neuromuscular Center
Kerry Levin, MD Director, Neuromuscular Center
Neil Friedman, MBChB
Aamir Hussain, MD
Zulfiqar Hussain, MD
Rebecca Kuenzler, MD
Richard Lederman, MD, PhD
Mei Lu, MD, PhD
Erik Pioro, MD, PhD
David Polston, MD
Robert Shields Jr., MD
Steven Shook, MD
Jinny Tavee, MD
Nimish Thakore, MD
Center for Pediatric Neurology and Neurosurgery
Elaine Wyllie, MD Director, Center for Pediatric Neurology
Mark Luciano, MD, PhD Director, Center for Pediatric Neurosurgery
Stephen Dombrowski, PhD
Gerald Erenberg, MD
Neil Friedman, MBChB
Debabrata Ghosh, MD, DM
Gary Hsich, MD
Irwin Jacobs, MD
Kambiz Kamian, MD
Sudeshna Mitra, MD
Manikum Moodley, MBChB, FCP, FRCP
Sumit Parikh, MD
Violette Recinos, MD
A. David Rothner, MD
Tanya Tekautz, MD
Center for Regional Neurosciences
Stephen Samples, MD Director, Center for Regional Neurosciences
Jeremy Amps, MD
C. Daniel Ansevin, MD
Toomas Anton, MD
Kristin Appleby, MD
Eric Baron, DO
Samuel Borsellino, MD
2 92 8
N E U R O L O G I C A L I N S T I T U T EC L E V E L A N D C L I N I C
Dina Boutros, MD
Devon Conway, MD
A. Romeo Craciun, MD
Carrie Diulus, MD
Megan Donohue, MD
Atef Eltomey, MD
Joanna Fong, MD
Todd Francis, MD
Joshua Gordon, MD
Amir Hussain, MD
Dulara Hussain, MD
Zulfiqar Hussain, MD
Kambiz Kamian, MD
Michael Mervart, MD
Sheila Rubin, MD
Teresa Ruch, MD
Joseph Rudolph, MD
Andrey Stojic, MD, PhD
Diana Tanase, MD, PhD
Nimish Thakore, MD
Howard Tucker, MD
Jennifer Ui, MD
Simona Velicu, MD
Ari Wilkenfeld, MD, PhD
Robert Wilson, DO
Joseph Zayat, MD
Department of Physical Medicine and Rehabilitation
Frederick Frost, MD Chairman, Department of Physical Medicine and Rehabilitation
Richard Aguilera, MD
Jay Alberts, PhD
Raghavendra Allareddy, MD
Melissa Alvarez-Perez, MD
Keerthi Atluri, MD
Sree Battu, MD
Michael Felver, MD
Kim Gladden, MD
Juliet Hou, MD
Lynn Jedlicka, MD
John Lee, MD
Yu-Shang Lee, PhD
Zong-Ming Li, PhD
Ching-Yi Lin, PhD
Vernon W.H. Lin, MD, PhD
Carey Miklavcic, DO
Ela B. Plow, PhD, PT
Matthew Plow, PhD
Anantha Reddy, MD
Michael Schaefer, MD
Patrick Schmitt, DO
Dan Shamir, MD
Yana Shumyatcher, MD
Vlodek Siemionow, PhD
Weidong Xu, MD, MS
General Adult Neurology
Kerry Levin, MD Chairman, Department of Neurology
C. Daniel Ansevin, MD
Kristin Appleby, MD
Dina Boutros, MD
Stefan Dupont, MD, PhD
Thomas E. Gretter, MD
Zulfiqar Hussain, MD
Richard Lederman, MD, PhD
Patrick Sweeney, MD
Diana Tanase, MD, PhD
Nimish Thakore, MD
Sleep Disorders Center
Nancy Foldvary-Schaefer, DO, MS Director, Sleep Disorders Center
Loutfi Aboussouan, MD
Charles Bae, MD
A. Romeo Craciun, MD
Ketan Deoras, MD
Michelle Drerup, PsyD
Joanna Fong, MD
Sally Ibrahim, MD
Alan Kominsky, MD
Jyoti Krishna, MD
Omar Minai, MD
Douglas Moul, MD, MPH, FAASM
Silvia Neme-Mercante, MD
Carlos Rodriguez, MD
Jessica Vensel-Rundo, MD, MS
Harneet Walia, MD
Tina Waters, MD
Center for Spine Health
Gordon Bell, MD Director, Center for Spine Health
Lilyana Angelov, MD, FRCS(C)
Adam Bartsch, PhD
Thomas Bauer, MD, PhD
Edward Benzel, MD
William Bingaman, MD
Edwin Capulong, MD
Alfred Cianflocco, MD
Edward Covington, MD
Russell DeMicco, DO
Carrie Diulus, MD
Michael Eppig, MD
Todd Francis, MD
Frederick Frost, MD
Augusto Hsia Jr., MD
Iain Kalfas, MD
Tagreed Khalaf, MD
Ajit Krishnaney, MD
Thomas Kuivila, MD
Andre Machado, MD, PhD
E. Kano Mayer, MD
Daniel Mazanec, MD
Robert McLain, MD
Thomas Mroz, MD
R. Douglas Orr, MD
Anantha Reddy, MD
Joseph Scharpf, MD
Judith Scheman, PhD
Richard Schlenk, MD
Santhosh Thomas, DO, MBA
Deborah Venesy, MD
Fredrick Wilson, DO
Adrian Zachary, DO, MPH
Neuroanesthesiology
Rafi Avitsian, MD Section Head, Neurosurgical Anesthesiology
Sekar Bhavani, MD
Matvey Bobylev, MD
Zeyd Ebrahim, MD
Hesham Elsharkawy, MD
Ehab Farag, MD, FRCA
Samuel Irefin, MD
Paul Kempen, MD, PhD
Reem Khatib, MD
Mariel Manlapaz, MD
Marco Maurtua, MD
Stacy Ritzman, MD
Leif Saager, MD
David Traul, MD, PhD
Guangxiang Yu, MD
Lerner Research Institute Department of Neurosciences
Bruce Trapp, PhD Chairman, Department of Neurosciences, Lerner Research Institute
Cornelia Bergmann, PhD
Jianguo Cheng, MD, PhD
John Gale, PhD
James Kaltenbach, PhD
Hitoshi Komuro, PhD
Bruce Lamb, PhD
Yu-Shang Lee, PhD
Ching-Yi Lin, PhD
Yoav Littner, MD
Sanjay W. Pimplikar, PhD
Erik Pioro, MD, PhD
J. Javier Provencio, MD, FCCM
Richard M. Ransohoff, MD
Susan Staugaitis, MD, PhD
Stephen Stohlman, PhD
Dawn Taylor, PhD
Riqiang Yan, PhD
Lerner Research Institute Biomedical Engineering
Jay Alberts, PhD
Yin Fang, PhD
Elizabeth Fisher, PhD
Aaron Fleischman, PhD
Zong-Ming Li, PhD
Cameron McIntyre, PhD
Ela B. Plow, PhD, PT
Matthew Plow, PhD
Vlodek Siemionow, PhD
Weidong Xu, MD
Lerner Research Institute Cell Biology
Damir Janigro, PhD
Nicola Marchi, PhD
Pathology and Laboratory Medicine InstituteAnatomic Pathology
Richard Prayson, MD
Cleveland Clinic Florida
Badih Adada, MD
Michelle Dompenciel, MD
Nestor Galvez-Jimenez, MD
Danita Jones, MD
Tarannum Khan, MD
Ramon Lugo, MD
Chetan Malpe, MD
Graham Mouw, MD, FAANS, FACS
Megan Rahmlow, MD
Adriana Rodriguez, MD
Richard Roski, MD
Virgilio D. Salanga, MD
Efrain Salgado, MD
Po-Heng Tsai, MD
Jose Valerio-Pascua, MD
Cleveland Clinic Nevada
Jeffrey Cummings, MD, ScD Director, Lou Ruvo Center for Brain Health
Brian Appleby, MD
Sarah Banks, PhD
Charles Bernick, MD
Gabriel Leger, MD
Donna Munic-Miller, PhD
Ryan Walsh, MD, PhD
Timothy West, MD
Dylan Wint, MD
Xue (Kate) Zhong, MD, MSc
313 0
C L E V E L A N D C L I N I C N E U R O L O G I C A L I N S T I T U T E
Editor: Glenn Campbell
Designer: Amy Buskey-Wood
Contributing writer: Wayne Kuznar
Photographers: Don Gerda, Stephen
Travarca, Tom Merce, Russell Lee,
Al Fuchs, Toni Greaves
Cleveland Clinic’s Neurological Institute has locations
throughout Northeast Ohio as well as in Weston, Fla., and
Las Vegas, Nev.
in northeast Ohio, the Center for Regional Neurosciences
brings together physicians and other healthcare providers at
more than 30 locations across the region to care for adults
and children with the most common to the rarest and most
complex neurological conditions:
• Cleveland Clinic’s main hospital campus
• Eight community hospitals, including comprehensive
neurological services at Lakewood Hospital and
Hillcrest Hospital
• A children’s hospital for rehabilitation
• Multiple family health centers
in Las vegas, Cleveland Clinic Lou Ruvo Center for Brain
Health offers highly specialized services in the diagnosis,
treatment and research of Alzheimer disease and other
neurocognitive disorders and collaborates with expert
centers in our Cleveland location in the management of
multiple sclerosis and movement disorders.
at Cleveland Clinic Florida, epileptologists diagnose
patients in a dedicated four-bed adult epilepsy monitoring
unit and collaborate with their colleagues in Cleveland
when surgical treatment is indicated. Programs for the
treatment of brain tumors, Alzheimer disease and dementia
are similarly linked.
Locations
FLORiDaWESTON
NEVaDa LaS VEgaS
OHiOCLEVELaND
About Cleveland Clinic
Cleveland Clinic is an integrated health-care delivery system with local, national and international reach. At Cleveland Clinic, 2,800 physicians represent 120 medical specialties and subspecialties. We are a main campus, 18 family health centers, eight community hospitals, Cleveland Clinic Florida, Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, Cleveland Clinic Canada, Sheikh Khalifa Medical City, and Cleveland Clinic Abu Dhabi.
In 2012, Cleveland Clinic was ranked one of America’s top 4 hospitals in U.S. News & World Report’s annual “America’s Best Hospitals” survey. The survey ranks Cleveland Clinic among the nation’s top 10 hospitals in 14 specialty areas, and the top hospital in three of those areas.
Resources for Physicians
referring Physician Center and HotlineCleveland Clinic’s Referring Physician Center has established a 24/7 hotline — 855.reFer.123 (855.733.3712) — to streamline access to our array of medical services. Contact the Referring Physician Hotline for information on our clinical specialties and services, to schedule and confirm patient appoint-ments, for assistance in resolving service-related issues, and to connect with Cleveland Clinic specialists.
Physician DirectoryView all Cleveland Clinic staff online at clevelandclinic.org/staff.
Track Your Patient’s Care OnlineDrConnect is a secure online service providing real-time information about the treatment your patient receives at Cleveland Clinic. Establish a DrConnect account at clevelandclinic.org/drconnect.
Critical Care Transport worldwideCleveland Clinic’s critical care transport teams and fleet of vehicles are available to serve patients across the globe.
• To arrange for a critical care transfer, call 216.448.7000 or 866.547.1467 (see clevelandclinic.org/criticalcare-transport).
• For STEMI (ST elevated myocardial infarction), acute stroke, ICH (intracere-bral hemorrhage), SAH (subarachnoid hemorrhage) or aortic syndrome transfers, call 877.379.CODe (2633).
Outcomes DataView clinical Outcomes Books from all Cleveland Clinic institutes at cleveland-clinic.org/outcomes.
Clinical TrialsWe offer thousands of clinical trials for qualifying patients. Visit clevelandclinic.org/clinicaltrials.
CMe Opportunities: Live and OnlineThe Cleveland Clinic Center for Continuing Education’s website offers convenient, complimentary learning opportunities. Visit ccfcme.org to learn more, and use Cleveland Clinic’s myCME portal (available on the site) to manage your CME credits.
executive educationCleveland Clinic has two education programs for healthcare executive leaders — the Executive Visitors’ Program and the two-week Samson Global Leadership Academy immersion program. Visit clevelandclinic.org/executiveeducation.
Same-Day appointmentsCleveland Clinic offers same-day appointments to help your patients get the care they need, right away. Have your patients call our same-day appointment line, 216.444.Care (2273) or 800.223.Care (2273).
Cleveland Clinic Information
Stay connected with us on
24/7 Referrals
referring Physician Hotline
855.reFer.123 (855.733.3712)
Hospital Transfers
800.553.5056
On the web at
clevelandclinic.org/refer123
Integrating Singular Care Across Multiple Sites
3 2
12-NEU-238
The Cleveland Clinic Foundation9500 Euclid Avenue / AC311Cleveland, Ohio 44195
Go green with Cleveland Clinictoday!
Use your device to connect to our medical professionals page and sign up to receive publications electroni-cally from Cleveland Clinic Neurological Institute.
To read the QR code with your device, find and download a reader from http://ccf.org/QRCodes.