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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


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


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

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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


(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.

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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


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.


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


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


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


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


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


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.


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


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


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


John Lee, MD

Joung Lee, MD

Erin Murphy, MD


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


Aamir Hussain, MD

Zulfiqar Hussain, MD

Rebecca Kuenzler, MD


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


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


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


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


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



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


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


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

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