neurological institute - cleveland clinic

Neurological Institute2013 YEAR IN REVIEW

CONTENTS1 Neurological Institute Overview

4 Welcome from the Chairman

HIGHLIGHTS FROM OUR CENTERS

6 Advent of 7T MRI Scanner Elevates Neuroimaging Research Abilities, Aspirations

10 Novel Approaches to Refractory Epilepsy: Bringing New Hope to Diverse Patients in Need

14 Virtual Reality System Ushers in New Era of Immersive, Multisensory Rehab in a Controlled Environment

18 Deploying Personalized Medicine for Smarter Therapeutic Targeting of Brain Tumors

20 Teaming with the NFL Players Association to Promote Brain Health of Retired Athletes

INNOVATIONS IN BRIEF

24 Proliferation of Care Paths Transforms Care Culture and Promotes Consistent, Evidence-Based Treatment Decisions

26 Brain-Computer Interface Technology: Helping Restore Function After Neurologic Injury

27 Alzheimer Disease Trials Program Takes a ‘Multiple Shots on Goal’ Approach

28 ‘Hyperacute’ MRI Protocol Results in Fewer — but More Effective — Endovascular Stroke Interventions

29 NIH Grant Helps Chart Synaptic Wiring in the Autism Brain

30 Neurological Institute Staff

34 Resources for Physicians

On the cover: High-resolution T2-weighted image from Cleveland Clinic’s new 7T MRI scanner. See story on page 6.

CLEVELAND CLINIC NEUROLOGICAL INSTITUTE | 1

Cleveland Clinic Neurological InstituteWHO WE ARE, HOW WE WORK TOGETHER

Cleveland Clinic’s multidisciplinary Neurological Institute includes more than 300

medical, surgical and research specialists dedicated to the diagnosis, treatment and

rehabilitation of adults and children with brain and CNS disorders.

The institute is structured into

four departments — Neurology,

Neurological Surgery, Physical

Medicine and Rehabilitation,

and Psychiatry and Psychology

— that oversee education

and training, and coordinate

activities across our condition-

based centers.

DEPARTMENTS

CENTERS

PHYSICIANS

OUR INSTITUTE MODEL allows patients to access

care through 15 specialized, condition-specific centers.

Each center incorporates a multidisciplinary approach to the

diagnosis and management of a particular condition or group

of conditions.

NEUROLOGICAL INSTITUTE DEPARTMENTS AND CENTERS

Department of Neurology

Department of Neurological Surgery

Department of Physical Medicine and Rehabilitation

Department of Psychiatry and Psychology

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

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

Center for Regional Neurosciences

Sleep Disorders Center

Center for Spine Health

2 | YEAR IN REVIEW 2013

$13M IN RESEARCH GRANTS, 7,500+ TRIAL ENROLLEES

Our clinical services are complemented by a robust research program that fosters innovation and

collaboration. Neurological Institute physicians and scientists work closely with colleagues in the Lerner

Research Institute, Cleveland Clinic’s basic science research arm, to pursue laboratory-based and

translational research in addition to our hundreds of ongoing clinical trials. We recently enhanced our

neuroimaging research capabilities across multiple conditions with acquisition of a 7T MRI scanner.

200,000+ PATIENT VISITS,

17,700+ ADMISSIONSAcross our more than 200,000 annual

patient visits and more than 17,700 annual

admissions, the Neurological Institute

manages the most common to the most

complex disorders of the brain and CNS. For

patients with challenging conditions in need

of leading-edge treatments, our physicians

and surgeons are regularly advancing

innovations in specialty areas including:

› Epilepsy surgery and SEEG

› Stereotactic radiosurgery

› Deep brain stimulation

› Laser interstitial thermal therapy for

brain tumors

› Endovascular treatment of cerebral

aneurysms and vascular malformations

› Neuroendoscopy

› Concussion assessment and management

1 MILLION VISITS’ WORTH OF HEALTH STATUS MEASURESThe Neurological Institute is dedicated to data-

informed clinical care. Our Knowledge Program

interactive data collection platform, now in

its seventh year, has captured health status

measure (HSM) data from more than 1 million

patient visits. At every outpatient visit, HSMs

are administered to patients electronically, while

providers report outcomes during the usual

medical documentation process.

We aggregate these patient- and provider-

generated data with information from other

sources — such as imaging results and

data from the growing number of care paths

embedded in our electronic medical record

system — to optimize clinical decision-making,

quality improvement and research. The result

is better care for communities and individuals

alike. Better and broader data means more

effective and efficient care at the population

level. For individual patients, our data-

informed approach to caregiving means we can

choose our tools wisely and wield them more

confidently to deliver the best outcome possible.


3-STATE PRESENCE = ACCESS, REACHWe are committed to making access to the most advanced neurological 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 Las Vegas and in Weston, Fla. As a result, patients can

access our specialists within a couple hours’ flight time from almost any spot in the continental U.S.

Key components of our broad regional network include 120 acute inpatient rehabilitation beds at

Cleveland Clinic facilities across Northeast Ohio and a team of more than 750 specialty-trained therapists

at more than 45 locations offering physical medicine and rehabilitation services.

LAS VEGAS LOU RUVO CENTER FOR BRAIN HEALTH MAIN CAMPUS

CLEVELANDCLINIC

WESTONCLEVELAND CLINICFLORIDA

NEUROLOGICAL INSTITUTE VITAL STATISTICS (2012)

206,760 Annual outpatient visits

17,731 Annual admissions

114,297 Annual inpatient days

9,769 Annual surgical/interventional procedures

77,218 Annual neuroimaging studies

266 Staff physicians

149 Clinical residents and fellows

20 Research fellows

NEUROLOGICAL INSTITUTE RESEARCH FUNDING (2012)

$12.96M Total grant and contract research funding

63 Federal grants and contracts

181 Nonfederal grants and contracts

237 Active clinical research projects

77 New clinical research projects (initiated 2012)

58 Staff leading clinical research projects

7,580 Patients enrolled in clinical research projects


MICHAEL T. MODIC, MD, FACRCHAIRMAN, CLEVELAND CLINIC NEUROLOGICAL INSTITUTE


Dear Colleagues,

The age of high-definition healthcare is here.

Breakthroughs in visualization and big data are

enabling us to see more and do more than ever

before, with payoffs in research and the clinical

care of our patients.

This edition of the Neurological Institute’s Year in

Review is rich with examples:

7-tesla MRI. The Neurological Institute is

proud to have completed installation of a 7T

MRI scanner in 2013, enabling us to conduct

neuroimaging research at spatial resolutions up

to five times greater than those possible at regular

field strengths. The story on page 6 outlines our

planned uses of the scanner and the daunting

engineering efforts behind its installation.

Immersive virtual environments for rehab and

research. 2013 also saw the continent’s first

nonmilitary installation of the CAREN 6-degrees-

of-freedom treadmill here at the Neurological

Institute. As detailed on page 14, this platform

allows us to safely challenge patients through

immersive ambulatory courses simulating nearly

any scenario from real life. We’ve been busy

deploying the treadmill for rehabilitation, research

and clinical analysis purposes in Parkinson disease,

multiple sclerosis and a growing list of other

clinical applications.

Expanded genomic profiling of brain tumors. In

2013 the Neurological Institute made personalized

medicine much more of a reality for patients with

select brain tumors by offering expanded genomic

profiling. By testing tumors for thousands of

genetic abnormalities that could impact therapy,

the expanded profiling empowers our specialists to

advise patients in a more personalized way on the

treatment course that’s best for them. Details are

on page 18.

Additional examples profile the Neurological

Institute’s expanding collection of EMR-embedded

care paths designed to generate data for ongoing

quality improvement (page 24) and our burgeoning

research efforts in brain-computer interface

technology and their potential rehabilitative payoffs

(page 26).

As advances in technology and computing allow

us to see more and do more, opportunities for

cooperation, collaboration and data sharing will

only increase. I invite you to review the past year

with us in these pages and contact me if our

initiatives may intersect with yours in ways that

might benefit all our patients.

Respectfully,

MICHAEL T. MODIC, MD, FACR

Chairman, Cleveland Clinic Neurological Institute [email protected]

WELCOME FROM THE CHAIRMAN


Cleveland Clinic installed a 7-tesla

MRI scanner on its main campus in

2013, making it one of only 13 medical

centers in the U.S. with 7T MRI

scanning abilities.

The new scanner’s more than doubling

in field strength (relative to the previous

3T standard) permits researchers to

produce in vivo body images at spatial

resolutions up to five times greater

than those possible at clinical field

strengths. Its images can approach the

spatial resolution of CT scans while

maintaining the superior soft-tissue

contrast of MRI. Because of FDA

restrictions on the clinical use of MRI

scanners with field strengths above

4T, the new scanner will be used for

biomedical research purposes.

NEW WINDOWS INTO BRAIN RESEARCH

“With this 7T imaging facility, we can

begin to explore brain function and

structure at an unprecedented level,”


Advent of 7T MRI Scanner Elevates Neuroimaging Research Abilities, Aspirations

says Mark Lowe, PhD, Cleveland

Clinic’s Director of High-Field MRI,

whose team finalized installation

of the scanner in December. “The

advantage of MRI has always been its

ability to study the brain as a system.

This greatly enhances that ability by

allowing us to simultaneously study the

brain both as a system and at nearly

microscopic scales.”

The new scanner’s enhanced imaging

research capabilities are still being

explored and prioritized. For one,

functional MRI is likely to be improved,

as the higher field strength will allow

for its performance at very high spatial

and temporal resolution, which will

open up new areas of investigation in

neuropsychiatry and other research

areas.

“We will be working to develop magnetic

resonance spectroscopic imaging

(MRSI) sequences suited for ultra-high


High-resolution T2-weighted image

from the 7T MRI scanner showing detail

in the hippocampus and other structures.

Spatial resolution: 400 microns in-plane.

Acquisition time: 4 minutes.


fields to take advantage of the increased

spatial and spectral resolution they

provide,” notes Amit Anand, MD, Vice

Chairman for Research in Cleveland

Clinic’s Center for Behavioral Health.

Extremely high-resolution diffusion

tensor imaging of the hippocampus with

the 7T scanner may permit discovery of

novel biomarkers in Alzheimer disease

and other cognitive disorders.

Areas of epileptogenic focus are

normally too small to identify with

standard MRI, but one hope is that

these foci will be able to be localized

with 7T imaging, enabling more precise

surgical removal of seizure-producing

brain areas.

When it comes to brain tumors, the

high spatial resolution and contrast-

to-noise ratio of 7T imaging will

allow for superior definition of tumor

boundaries within the brain. In

musculoskeletal imaging, it has already

been demonstrated that the higher

field strength permits better imaging of

cartilage.

MOVING INTO MULTINUCLEAR MRI

Previously, all whole-body MRI scanners

at Cleveland Clinic produced images

based on proton excitation. Protons are

the most abundant nuclei in the human

body and by far the most common ones

used in MRI imaging. However, other

nuclei in the body occur naturally in a

form that can be studied with MRI.

Beyond its high field strength, the

new 7T system is the first whole-body

MRI scanner at Cleveland Clinic with

multinuclear imaging capability. In

addition to producing images that

provide anatomic or functional detail

from protons, the scanner can yield

information on metabolic processes

using other nuclei, such as sodium,

phosphorus and carbon. This capability

permits the study of more-complex

processes, such as cell metabolism.

“This facility puts Cleveland Clinic at the

forefront of biomedical research with

MRI,” says Dr. Lowe. “It will keep us

very competitive for research dollars

for years to come while also creating

good opportunities across our regional

biomedical research community.”

“The advantage of MRI has always been its ability to study the brain as a system. This greatly enhances that ability by allowing us to simultaneously study the brain both as a system and at nearly microscopic scales.”

— MARK LOWE, PhD


The Scanner’s Journey and Installation: No Small Engineering Feat

Installation of the 7T MRI scanner began in July, and image

production started by September. Installation, including the opening

of a 7T MRI facility adjacent to the Mellen Center for Multiple

Sclerosis Treatment and Research, was complete before year’s end.

The magnet at the heart of the 7T system was constructed to

order by its manufacturer, Siemens Healthcare, over 18 months.

Behind this long production window is the enormous amount of

superconducting wire (see “By the Numbers” sidebar) needed to

produce the magnet.

To maintain field strength, the wire must be kept very cold,

requiring large amounts of liquid helium for cooling. At 80,000

pounds, the magnet had to be shipped by boat from its production

site in Oxford, England, taking three weeks to cross the Atlantic

Ocean. Because the helium would boil away during a journey of

that length, the magnet was shipped warm and then cooled at

Cleveland Clinic over several weeks. Another several weeks were

needed to pump current through the magnet to get it up to field

strength. The overall process was slowed by the worldwide helium

shortage of the past two years.

Once the magnet was up to field strength, Siemens engineers

needed 90 days to finish installation of the electronics necessary

to produce high-quality images. Physicists from Cleveland Clinic’s

Imaging Institute then performed final tuning to customize the

scanner facility for the specific research needs desired.

7T SCANNER BY THE NUMBERS

5-FOLD Potential increase in

spatial resolution (vs.

clinical field strengths)

$10.5 MILLIONCleveland Clinic’s

investment in the

scanner

80,000 Weight (in pounds) of the

scanner’s magnet

350 Length (in miles) of tin-

niobium wire needed to

construct the magnet

20,000 Amount of liquid helium

(in liters) necessary to cool

the magnet


Jorge Gonzalez-Martinez, MD, PhD, one of the Neurological Institute neurosurgeons who implants

the RNS neurostimulator and performs laser ablation for patients with refractory epilepsy.


Two of the newest treatment options

for patients with refractory epilepsy

— the NeuroPace® RNS® System

neurostimulator and laser ablation —

differ in important ways. The RNS

neurostimulator, a promising option for

patients who are not good candidates

for surgery, could potentially be offered

to hundreds of thousands of epilepsy

patients. Laser ablation, in contrast, is

a potent intervention but is appropriate

for a more modest subset of patients —

those with small, localized lesions deep

in the brain.

One thing the two novel modalities have

in common is that Cleveland Clinic’s

Epilepsy Center was at the forefront of

their testing and/or adoption — and has

insights to share from early experience

in their use.

NEUROSTIMULATOR STOPS SEIZURES BEFORE THEY START

The RNS neurostimulator received

FDA clearance in November 2013 for

treatment of medically refractory partial

seizures in adults with no more than

two epileptogenic foci. Clinical trials

demonstrated a 50 percent or greater

reduction in seizure frequency in more


Novel Approaches to Refractory Epilepsy: Bringing New Hope to Diverse Patients in Need

than half of patients two years after

device implantation.

Cleveland Clinic was one of the centers

participating in the pivotal trials,

implanting the device in seven patients.

Some have had the device in place

for six to seven years. As of its FDA

approval date, the neurostimulator had

been placed in 256 patients, with some

being treated for more than eight years.

The battery-powered RNS

neurostimulator is implanted in the

cranium anywhere on the cortex where

seizures are originating. It works by

monitoring electrical activity in the

brain. If abnormal activity is detected,

the device sends electrical impulses

to the seizure focus via leads, helping

prevent seizure onset. The impulses are

imperceptible to the patient.

Cranially implanted

RNS neurostimulator

connected to one or two

leads placed at seizure

foci. Illustration courtesy

of NeuroPace Inc.


Unlike open-loop devices (e.g., those

used in vagal nerve stimulation) that

provide constant electrical stimulation,

the RNS neurostimulator’s novel

closed-loop design allows it to deliver

stimulation only when needed.

WHAT IT MEANS FOR PATIENTS

The device provides hope for patients

with disabling and medically refractory

epilepsy who cannot undergo surgery

because the focal areas cannot be

resected or are too far apart. “These

are patients who have no other resort,

and this device offers them new hope

for seizure reduction,” says Dileep Nair,

MD, an epileptologist in Cleveland

Clinic’s Epilepsy Center.

Dr. Nair believes about 20 to 30

percent of patients with medically

refractory epilepsy may benefit from

the RNS neurostimulator. He notes that

those with bitemporal lobe epilepsy

benefit most.

Interest in the therapy is high, as

more than 50 patients were on a

waiting list for device implantation at

Cleveland Clinic when it was approved

in November. Their ability to benefit

depends on “ensuring that we know

exactly where their seizures are coming

from,” says Dr. Nair, which puts a

premium on experience in device

implantation and seizure localization.

MORE APPLICATIONS AHEAD

The device comes with a programmer

that enables the treating physician to

noninvasively program the detection

and stimulation parameters. The

programmer also can display the

patient’s brain electrical activity

(electrocorticogram) in real time.

“The RNS neurostimulator is always

monitoring brain activity, so having it

implanted is like constantly being in

the epilepsy monitoring unit,” explains

Dr. Nair. “It has a range of diagnostic

abilities.”

Beyond diagnostic applications, he

envisions eventual use of the device

(and similar neurostimulators in

development) for delivering anti-

epileptic medications directly to a

specific portion of the brain to reduce

the agents’ side effects.

“A device like this represents a kind

of brain-machine interface that may

benefit patients with other forms of

neurological disease,” says Dr. Nair.

“This technology is going to lead into

several new avenues of therapy.”

LASERS FOR MINIMALLY INVASIVE ABLATION OF SMALL, FOCAL LESIONS

Throughout 2013, while the RNS

neurostimulator was nearing regulatory

approval, Cleveland Clinic neurosurgeon

Jorge Gonzalez-Martinez, MD, PhD, was

steadily building his experience base

in the use of another therapy recently

cleared by the FDA — laser ablation.

Cleveland Clinic is one of a handful of

epilepsy centers nationwide employing

the procedure.

Laser ablation represents a less

invasive, less costly and potentially

safer alternative to more traditional

forms of surgery for refractory epilepsy

arising from small, localized brain

regions. “Laser therapy is a good first-

step surgery to try if the lesions are

small and deep in the brain,” says Dr.

Gonzalez-Martinez.

The advantages of laser ablation relative

to resective surgery include:


• Minimal invasiveness. No craniotomy is

required, and the incision is typically

just 3 mm in diameter.

• Less tissue damage. Ablation of the

target tissue is precise and localized,

avoiding removal of nonepileptogenic

brain tissue and theoretically reducing

complications and adverse effects. No

radiation is involved.

• Shorter hospital stays. Patients are

typically discharged the day after

laser ablation. Compared with the

five- or six-day stay often required

with craniotomy, this should translate

to lower overall treatment costs.

The primary disadvantage is that laser

therapy is restricted to patients with

small lesions.

The utility of laser ablation is enhanced

when the seizure foci are located with

stereoelectroencephalography (SEEG)

and when intraoperative MRI is used

for real-time monitoring of intracranial

pathology. These measures, which can

reduce the need for reoperation, are

THE NEW TREATMENT OPTIONS AT A GLANCE

Advantages Drawbacks Most likely to benefit/ ideal candidates

RNS neuro-stimulator

• Can be placed anywhere on cortex where seizures originate

• Stimulation is imperceptible to patient

• Can be implanted for months, years or lifetime

• No brain tissue removed, so no associated decrease in brain function

• Provides ongoing monitoring of brain activity, with potential diagnostic utility

• Not approved for use in patients under age 18

• Reduces, but does not eliminate, seizures

• Nearly half of patients do not achieve significant improvement

• Patients with implant cannot undergo MRI, electroconvulsive therapy or transcranial magnetic stimulation

• Patients who cannot/will not undergo surgery

• Patients with bitemporal lobe epilepsy

• Patients in whom vagal nerve stimulation has failed

Laser ablation

• Less invasive than resective surgery (no craniotomy)

• Less tissue damage than with resective surgery, with potential for reduction in adverse effects

• Shorter hospital stay (typically 1 day vs. 5-6 days), with resulting cost savings

• Appropriate only for patients with small lesions deep in brain

• Pediatric patients with hypothalamic hamartoma

• Patients with tuberous sclerosis or mesial temporal sclerosis

• Patients with unsuccessful prior resective surgery

• Patients hesitant about resective surgery

typically used during laser ablation at

Cleveland Clinic, says Dr. Gonzalez-

Martinez. Robotic assistance is

considered as well to optimize the

precision of laser placement.

“We typically follow patients for six

months after laser surgery to determine

treatment success,” Dr. Gonzalez-

Martinez notes. While volumes at

Cleveland Clinic are currently too small

for robust outcomes analysis, only one

patient to date has required reoperation

with craniotomy and resection.

Cleveland Clinic has begun enrolling

patients in a multicenter trial evaluating

the efficacy of laser ablation for

temporal lobe epilepsy marked by

mesial temporal sclerosis.

Intraoperative MRI showing

laser ablation in progress

in a patient with epilepsy,

with isothermal areas

located in the right frontal

periventricular region.


Imagine a patient with Parkinson

disease undergoing physical therapy for

neuromuscular re-education. Instead of

walking in a straight line on a treadmill

surrounded by the sights and sounds

of a therapy suite or biomechanics lab,

she has the experience of walking along

a gravel path. The path feels rocky

and uneven beneath her feet, twisting,

turning and meandering uphill and

down. Surrounded on all sides by trees,

a blue sky and chirping birds, with

the gravel making a crunching sound

underfoot, the patient’s senses are

immersed in navigating this challenging

walk.

Despite all the sights and sounds,

the patient’s experience is a virtual

one, taking place in a controlled, safe

environment on Cleveland Clinic’s main

campus. This scenario is repeated

regularly since the installation of the

new CAREN (Computer Assisted

Rehabilitation Environment) system

at Cleveland Clinic in mid-2013. The

system, manufactured by Amsterdam-

based Motek Medical, is a high-tech

medical and research platform that


Virtual Reality System Ushers in New Era of Immersive, Multisensory Rehab in a Controlled Environment

allows clinicians to view and analyze

patients’ balance, locomotion and

coordination. It serves as a valuable tool

for rehabilitation, clinical analysis and

research.

“We want physical therapy to challenge

patients, but it’s always a question of

how to do so in a safe environment,”

says Jay Alberts, PhD, who is leading

Cleveland Clinic’s CAREN system

initiative. “The CAREN system puts

us on the leading edge by enabling us

to safely challenge patients through

different courses in an immersive virtual

environment.”

Cleveland Clinic’s acquisition of the

CAREN system, which was funded by

a grant from the state of Ohio, marks

the first nonmilitary installation of the

platform in North or South America.

HOW IT WORKS

The foundation of the CAREN platform

is a “6 degrees of freedom” motion base

that turns and moves up and down

or left and right. The base is topped

with force plates or an instrumented


treadmill, and the system has real-

time motion capture capabilities that

integrate visual projection and surround

sound. Not only can patients experience

walking on a path, they can navigate a

boat deck, stroll through an airport or

simulate just about any scenario from

real life — all under close monitoring

(and while harnessed for safety).

“Challenges can be customized, with

levels of difficulty automatically based

on patient performance,” explains Dr.

Alberts, who is Director of Cleveland

Clinic’s Concussion Center and a

researcher in the Department of

Biomedical Engineering. “The system

registers and reacts more quickly

than human perception, making

microadjustments and even going into a

soft shutdown as needed.”

The system allows for the registration,

evaluation, clinical analysis and

rehabilitation of balance, including

the body’s visual, auditory, vestibular,

tactile and proprioceptive systems. Its

software merges data from all hardware

components, enabling measurable and

quantifiable evaluation, rehabilitation

and research, leading to constantly

monitored progression.

“Beyond the virtual immersion features,

the system is a complete biomechanics

laboratory — in a quarter of the size

of a traditional lab,” Dr. Alberts says.

“It measures EMG muscle activation

patterns in real time, helping identify

where a patient may have a deficiency

and what can be done to improve it.”

COLLABORATIVE BY DESIGN

With the CAREN system, neurologists,

rehabilitation specialists, orthopaedists,

occupational therapists and

physiotherapists can collaborate with

one another — and with researchers in

biomechanical engineering, pediatrics,

mental health and other disciplines —

to both evaluate patients’ functional

behavior and help restore or improve

that function. A computer scientist

rounds out the interdisciplinary mix,

Challenges can be customized, with levels of difficulty automatically based on patient performance.


writing code to customize virtual scenes

and experiences beyond those provided

with the system.

“Protocols and programs currently being

developed using CAREN are leading the

creation of groundbreaking rehabilitation

techniques,” Dr. Alberts notes.

ENGAGING FOR PATIENTS, EMPOWERING FOR CLINICIANS AND RESEARCHERS

Since patients began using the CAREN

system in September, their reaction

has been enthusiastic. “Patients like

the system’s gamelike and interactive

features,” says Dr. Alberts. “From our

standpoint, it offers the best of both

worlds — it’s engaging for patients

while measuring outcomes in a highly

systematic, objective way.”

So far the system has been used

primarily for patients with Parkinson

disease and multiple sclerosis, but

it has many more potential clinical

applications, including the diagnosis

and treatment of various neuromuscular

and other neurological conditions. Plans

are underway to use the system in

the Concussion Center, including for

facilitation of return-to-play decisions

for concussed athletes.

The system is also at the heart of

translational research efforts. “Using

the CAREN system for research will

help us clinically, and clinical utilization

certainly complements our research

efforts,” Dr. Alberts says.

The system also will facilitate

development of mobile applications

by validating measurements taken

using mobile devices. “We can use

information learned from the system

and transfer a pared-down version to

a mobile app,” Dr. Alberts explains.

“We’re working on customized multiple

sclerosis and Parkinson disease apps,

and data from the CAREN system

should allow us to develop them much

more quickly.”

Personalized medicine services

have been part of the toolbox of the

Neurological Institute’s Rose Ella

Burkhardt Brain Tumor and Neuro-

Oncology Center since 1999, when 1p

chromosome deletion testing was first

offered. After adding more and more

such services in the ensuing years, the

center decided in 2013 to begin offering

patients with select brain tumors the

option of having their tumor tissue

undergo genomic profiling to test for

thousands of genetic abnormalities that

could potentially impact their treatment.

“As we’ve offered more personalized

medicine over the years, we’ve reached

the point where it clearly makes sense

to perform personalized tumor testing

for genetic abnormalities in some

cases rather than offer just a few

specific tests,” says Gene Barnett, MD,

MBA, Director of the Burkhardt Brain

Tumor Center, which works closely

with Cleveland Clinic’s Taussig Cancer

Institute.

KNOWLEDGE IS POWER

The Burkhardt Brain Tumor Center

offers genomic profiling primarily


Deploying Personalized Medicine for Smarter Therapeutic Targeting of Brain Tumors

for patients with new or recurrent

glioblastoma, or atypical or malignant

meningioma. It can provide a more

rational basis on which to choose drug

therapies, be they conventional or

investigational, by offering data about

particular characteristics that a patient’s

tumor may have.

“The genomic profiling is looking for

specific pathways within the tumor

that we might target,” Dr. Barnett

explains. “The results can help us

avoid treatments that are not predicted

to be helpful while suggesting other

treatments that are more likely to be in

the patient’s best interest.” Historically,

he says, patients have been treated

with a standard drug paradigm or

an investigational therapy without

knowledge of whether their specific

tumor would or would not benefit from

that approach.

The tissue analysis uses next-generation

sequencing to assess for hundreds of

known cancer genes, and results are

available in two to three weeks. The

process requires an adequate amount

of tumor tissue, so testing cannot

be performed for all eligible patients,


particularly if they have had a needle

biopsy. However, in some cases

more invasive or larger biopsies can

be performed so that tissue can be

submitted for comprehensive testing.

The testing is very sensitive in finding

many types of gene abnormalities,

Dr. Barnett says. In some cancers,

nearly two-thirds of all tissue samples

assessed are found to have at least one

actionable gene alteration.

Because the profile is of the tumor, not

the patient’s own genome (genetic

makeup), it does not necessarily provide

any information about heritability of the

patient’s condition.

THE FUTURE IS COMING FAST

The Burkhardt Brain Tumor Center is

one of a select number of prominent

centers across the country performing

genomic profiling of brain tumors to

guide treatment. “We are recognizing

that an important part of the future lies

in molecular testing of these tumors,”

Dr. Barnett says.

That future will likely include changes

to clinical guidelines to incorporate

genomic testing guidance, he adds, but

more experience and information are

needed first. “This type of testing may

very well become part of the standard of

care for management of certain tumors,

but we’re not there yet.”

Cleveland Clinic is contributing to the

insights needed in the interim through

participation in a clinical trial of genomic

testing across a number of tumor types,

including malignant meningiomas and

other brain tumors.

Meanwhile, Dr. Barnett and his Burkhardt

Brain Tumor Center colleagues are

focused on refining this personalized

medicine service to their patients and

assessing its benefits, as there is of

course no guarantee that it will generate

results useful for guiding therapy for any

given patient.

“In some patients, the results have

suggested new routes of treatment we

would not have considered on our own,”

Dr. Barnett says. “But it’s too early to say

how effective it is.”



Nearly every month brings new

reports raising concern over the

potential long-term consequences of

repeated head impacts in football. In

response, Cleveland Clinic has teamed

with the National Football League

Players Association (NFLPA) in an

unprecedented program to assess and

improve the brain health and overall

well-being of retired NFL players.

The program, called The Trust,

offers former players physical and

neurological evaluations followed by a

comprehensive ongoing plan to relieve

symptoms, restore function and improve

cognitive skills.

Cleveland Clinic will host players at

three sites — in Cleveland, at Cleveland

Clinic Florida in Weston, Fla., and at

Cleveland Clinic Lou Ruvo Center for

Brain Health in Las Vegas. Players

can also choose to visit the two other

medical centers participating in The

Trust: the University of North Carolina in

Chapel Hill, N.C., or Tulane University

in New Orleans.


Teaming with the NFL Players Association to Promote Brain Health of Retired Athletes

“Former NFL players are at increased

risk for neurological disease,” says Jay

Alberts, PhD, Director of Cleveland

Clinic’s Concussion Center. “The

program’s goal is to identify potential

problems — physical, neurological or

cognitive — sooner, which may lead

to earlier interventions and treatments.

In response, we’re developing a sort of

brain health and restoration center.”

IN-DEPTH INITIAL ASSESSMENT

Players who choose to take part in the

program visit one of the participating

sites for two days of assessment starting

with a comprehensive medical exam

that includes determining the player’s

injury history, functional symptoms and

personal concerns. That’s followed by

a battery of tests, an MRI of the brain,

cognitive evaluations, psychological

interviews and balance assessments.

Non-neurological tests and interventions

(internal medicine exam, wellness

screening, nutrition counseling and

life skills consultation) round out the

initial visit.


The tests draw on Cleveland Clinic

innovations in concussion assessment,

including the Cleveland Clinic

Concussion App for the iPad®, which

evaluates postural stability and motor

and cognitive function.

FOLLOW-UP BASED ON THE ‘NEUROLOGICAL PASSPORT’

After their initial visit, players are

given a personalized treatment plan

customized to their individual needs.

The plan includes communication

between the player and his local

healthcare team via phone, computer,

videoconferencing or other methods.

“This population needs a comprehensive

evaluation and treatment approach,”

says Dr. Alberts. “Each player will

leave with his own ‘neurological

passport’ that outlines exactly where

he is cognitively and neurologically. If

changes occur after he goes home,

we can intervene in a systematic and

strategic way.”

The aim is to practice some degree of

anticipatory medicine, he adds, with

the assistance of emerging distance

health offerings (see sidebar, next page).

“The cumulative effect of repeated

collisions and resultant brain trauma

can manifest as cognitive impairment,

decreased motor functioning, incessant

pain and psychological/behavioral

issues including irritability, impaired

insight and impulse control, paranoia,

violent outbursts, and even suicide,”

notes Charles Bernick, MD, Associate

Medical Director of the Lou Ruvo Center

for Brain Health. “By taking a proactive

approach, this program is helping

retired players be assessed, diagnosed

and treated before symptoms arise or

grow too serious.”

YIELDING INSIGHTS BEYOND RESEARCH

While the program is clinical in

nature and not a research project,

opportunities to do research may be

considered by the NFLPA in the future.

“Even as the program now stands, we

will learn a lot about caring for these

players,” Dr. Alberts notes, “and some

of that may translate to caring for other

patients with similar histories.”

Each player leaves with his own ‘neurological passport’ that outlines exactly where he is cognitively and neurologically.


NE X T STEPS:

Diving into Distance Health

As Cleveland Clinic’s participation in The Trust evolves, it will provide increasing

opportunities to assess new distance health offerings.

“We will be developing and refining additional mobile apps for program participants to use

after they return home to keep us connected with their progress,” says Dr. Alberts. He cites

Cleveland Clinic’s existing “MyHealth: Spine” app (in beta testing) and additional apps for

motor and cognitive training as examples.

“The aim is to begin to practice anticipatory or predictive medicine,” he says. For example,

if a retired NFL player began showing signs of depression or motor function changes via a

mobile app he was regularly using, the healthcare team at his Cleveland Clinic site could

catch those changes via serial monitoring before the condition became more serious.

Additionally, the app could be programmed with a predictive algorithm to recommend

interventions to the player once the depressive or functional changes began occurring at a

potentially concerning rate.

“The result will be more personalized medicine that doesn’t require one-on-one visits with a

provider,” notes Dr. Alberts.

Ultimate goals include translating these distance health offerings to other, larger patient

groups and potentially making the Cleveland Clinic distance health apps available to non-

Cleveland Clinic sites participating in The Trust.


INNOVATIONSIN BRIEF

Proliferation of Care Paths Transforms Care Culture and Promotes Consistent, Evidence-Based Treatment Decisions

The journey from volume-based to value-based care requires clear

pathways. That was the idea behind the Neurological Institute’s

recent efforts to produce a collection of disease-specific Cleveland

Clinic Care Paths.

Now, two years and a couple dozen care paths into the initiative, the

institute has found that care paths provide more than just a road map

to evidence-based and efficient care. The process of developing them

is a cultural transformation in itself. “Our caregivers are being engaged

across the care continuum to solve problems in multidisciplinary,

patient-centered ways that promote value over the volume-based

tradition,” says Neurological Institute Chairman Michael T. Modic, MD.

Much More than Guidelines

Cleveland Clinic Care Paths are more than just practice guidelines.

They are instead process-based tools designed for translation into the

electronic medical record (EMR) to guide clinical work flow and assist

providers in making guidelines operational.

Care paths start as evidence- or consensus-based guides developed

by multidisciplinary teams of clinical experts for the management of

a specific condition (see sample work flow excerpt). The aim is to

standardize care around the best evidence, clearly identify meaningful

outcomes of care and identify relevant process metrics.

The care paths are then analyzed for opportunities for practice

transformation and efficiencies. “We are using care paths as the

organizing principle to align our services to reduce unnecessary

variation from the most evidence-based, patient-focused and efficient

standard of care,” explains Dr. Modic. One focus is to match patients

to the most appropriate level of clinician for their needs at various

stages of care. For instance, initial management of acute back pain

without red flags may be best provided by a specialized physical

therapist or nurse practitioner rather than a medical spine specialist,

who is engaged for more persistent or complicated cases.

› NEUROLOGICAL INSTITUTE CARE PATHS TO DATE

Completed

› Low back pain

› Radiculopathy

› Neck pain

› Obstructive sleep apnea

› Concussion

In review and/or piloting

› Headache

› Epilepsy

› Multiple sclerosis

› Delirium

› Glioblastoma multiforme

› Alzheimer disease

› Hemorrhagic stroke

› Transient ischemic attack

› Ischemic stroke

› Post-acute stroke management

› Physical therapy for low back pain

In development

› Brain metastases

› Depression

› Vertebral fracture

› Fibromyalgia

› Autonomic disorders

› Pediatric headache

› Insomnia

› Spine metastases

› Multiple sclerosis comprehensive care

› Spine surgery

› Chronic pain

› Normal pressure hydrocephalus


Providervisit

Symptoms/complaints

Screening questions • STOP-BANG • ESS • Wellness widget • ISI

Testing?

Significantcomorbidities or

other sleepcomplaints?

PolysomnographyHome sleep

testing

PAP treatmentindicated

High clinicalsuspicion

High clinicalsuspicion

PositiveNegative NegativePositive

Future re-evaluation vs. need for sleep

medicine consultation

Future re-evaluation vs. need for sleep

medicine consultation

Yes

Yes

No No

Positive Negative

Excerpt of a work flow from the Obstructive Sleep Apnea Care Path. This portion focuses on deciding when to use home sleep testing vs. polysomnography.

Following care process analysis, care paths are

piloted for work flow studies and improvements

at select Cleveland Clinic health system facilities.

Then they are translated into the EMR to guide

— and ideally improve — clinical work flow. This

is achieved through standardized documentation

templates, order sets, and clinical decision-support

and predictive analytical tools.

Embedding care paths in the EMR enables

outcomes and process monitoring, such as the

ability to generate condition-specific metrics for

individual physicians, departments and facilities to

drive continuous quality improvement.

“The aim is to standardize and measure care across

time, venues and provider types,” says Dr. Modic.

“But we are finding that participation in care path

development is transforming our teams to work

together in new ways that optimize outcomes over

cost — in other words, to deliver value-based care.”

28 Care Paths and Counting

As of late 2013, the Neurological Institute had

28 disease-specific care paths completed or

under development (see list on page 24). The

initiative has since spread to the overall Cleveland

Clinic enterprise, with 67 care paths currently in

development or completed organizationwide.

Next steps include exploring opportunities to make

Cleveland Clinic Care Paths available to outside

providers and health systems.


Brain-Computer Interface Technology: Helping Restore Function After Neurologic InjuryBrain-computer interface (BCI) systems allow a person to communicate — through analysis and

modulation of brain signals — with a device such as a computer, robotic arm or a variety of other

machines. When used by patients with spinal cord injury, stroke or other neurological diseases, these

systems (also known as brain-machine interface technology) allow individuals to perform activities that

have become difficult or impossible to do because of their injury or disease.

BCI systems function by analyzing signals in the brain that are produced during an intention to perform a

function, such as grasping an object. The electrical signals generated during this “motor imagery” are then

processed using a computer-based algorithm and delivered as a command to a device that performs the

function originally intended by the patient. Thus, using a BCI system, a patient with arm paralysis is able

to grasp an object, using a prosthetic arm, simply by thinking about doing so.

Cleveland Clinic’s Center for Neurological Restoration, in collaboration with researchers from Case Western

Reserve University, has begun an initiative to research ways to enhance the brain signals generated during

motor imagery. By improving the specificity of cortical signals generated during various motor imagery

tasks, they hope to improve the efficiency and safety of using BCI devices, allowing the devices to move

out of the laboratory setting and be considered for day-to-day use.

Darlene Lobel, MD, who is leading the initiative for Cleveland Clinic, says her team expects preliminary

research results beginning in 2014.

The sequence of steps involved in using BCI technology to stand to walk from a sitting position.

›


Alzheimer Disease Trials Program Takes a ‘Multiple Shots on Goal’ ApproachCurrent therapies for Alzheimer disease (AD) produce modest improvement in symptoms and a temporary

delay in cognitive decline. They do not affect the underlying biological processes leading to cell death.

To address the urgent need for new therapies, especially disease-modifying therapies, Cleveland Clinic

Lou Ruvo Center for Brain Health has developed one of the largest U.S. clinical trials programs for AD

therapeutics. We are taking a “balanced matrix” approach, investigating agents that target diverse

mechanisms of action, address multiple stages of AD, and come in a variety of formulations. Specifically,

we have underway:

• Three trials assessing various approaches to AD prevention

• Four trials of interventions in patients with very early AD

• Thirteen trials of interventions for more severe dementia in patients with AD

Similarly, we are pursuing studies of interventions that take on AD in three different ways, as detailed in

the figure below:

• Disease-modifying therapies that target amyloid plaques

• Disease-modifying therapies that address nonamyloid targets, such as neurofibrillary tangles

• Therapies that treat or improve AD’s symptomatic manifestations

We are carrying out this broad program through a network of four trial sites with extensive national reach.

The Lou Ruvo Center for Brain Health has locations in Las Vegas; at Cleveland Clinic’s main campus in

Cleveland; in Lakewood, Ohio, outside of Cleveland; and in Weston, Fla. These sites form a unique AD

clinical trials consortium that matches patient location with available studies, extending the ability to

enroll patients and accelerate therapeutic testing.

“We have adopted a ‘multiple shots on goal’ strategy for AD therapeutics, since only about 5 percent

of investigational drugs for CNS diseases ultimately succeed in clinical testing and come to market,”

explains Jeffrey Cummings, MD, ScD, Director of the Lou Ruvo Center for Brain Health. “As we diversify

the therapies tested and enhance our trials network, we are raising the likelihood of the breakthrough

treatment successes so urgently needed in AD.”

Targeting Alzheimer Disease on Three Fronts

›

The three broad focus

areas of the Lou Ruvo

Center for Brain Health

clinical trials program

for AD, with examples of

therapies being assessed

in each.

Amyloid disease-modifying therapies

• Bexarotene • Immunotherapy • BACE inhibitor

Nonamyloid disease-modifying therapies

• Resveratrol • Pioglitazone

Symptomatic therapies

• Dextromethorphan/quinidine • Transcranial magnetic stimulation • Axona®


‘Hyperacute’ MRI Protocol Results in Fewer — but More Effective — Endovascular Stroke Interventions

It’s a clinical curiosity: Endovascular stroke therapy (EST) has demonstrated effective recanalization rates

and a good safety profile for patients with acute ischemic stroke caused by large vessel occlusion, but

most clinical trials have failed to show that EST improves clinical outcomes.

Specialists in Cleveland Clinic’s Cerebrovascular Center suspected that suboptimal patient selection is to

blame for the disconnect. Specifically, they speculated that the traditional tools for patient selection, CT

and CT angiography (CTA), do not sufficiently reveal brain tissue viability in this population that does not

achieve recanalization with or is ineligible for IV tPA.

That suspicion prompted these clinicians to implement a “hyperacute” MRI protocol to perform pretreatment

MRI on EST-eligible acute stroke patients with large vessel occlusion to assist in patient selection.

“We hypothesized that adding pretreatment MRI to determine the core infarct volume before interventions

could improve patient selection and, in turn, improve outcomes,” explains M. Shazam Hussain, MD,

FRCP(C), Head of Cleveland Clinic’s Stroke Program in the Cerebrovascular Center.

He and colleagues conducted a retrospective analysis of outcomes before and after implementation of the

protocol at Cleveland Clinic in April 2010. Acute stroke patients with large vessel occlusion who were

considered for EST — including mechanical thrombectomy and/or intra-arterial thrombolysis — were

identified over 28-month periods before and after protocol implementation. Those before the protocol (n

= 88) were selected based on CT/CTA; those after the protocol (hyperacute MRI group; n = 179) were

selected based on CT/CTA and MRI.

Dr. Hussain’s team found that nearly 50 percent fewer evaluated patients ended up receiving EST in

the hyperacute MRI group compared with the pre-protocol group. The hyperacute MRI group also had

statistically significantly better modified Rankin Scale scores at 30 days, both overall and among those

who underwent EST, compared with the pre-protocol group. On adjusted multivariate analysis, EST was

associated with significantly better outcomes and lower mortality in the hyperacute MRI period than

during the pre-protocol period.

The analysis, which has been accepted for publication in Stroke, was in press at the time of this writing.

“Our use of hyperacute MRI in patients with acute large vessel occlusion appears to have reduced utilization

of EST and was accomplished without significant delay in the start of intervention,” says Dr. Hussain. “This

approach may aid in patient selection for EST, although further confirmatory study is needed.”

›

Left: Noncontrast head CT

without evidence of an acute

infarct despite left middle

cerebral artery (MCA) syndrome

on examination. Right: Axial

diffusion trace MRI in the same

patient within 20 minutes,

showing infarction of the entire

left MCA territory.


NIH Grant Helps Chart Synaptic Wiring in the Autism Brain

Bruce Trapp, PhD, is shining light on the autism brain — literally.

Years ago, Dr. Trapp, Chairman of the Department of Neurosciences in Cleveland Clinic’s Lerner Research

Institute, found a way to make astrocyte cells glow fluorescently. This allowed him to study how astrocytes

are generated in the developing brain and how they associate with synapses in the adult brain. It is well

established that astrocyte processes surround and modulate the function of synapses. Now, with help from

a $1.97 million grant from the National Institute of Mental Health, the Trapp lab will study how astrocytes

respond to altered synapses in the autism brain.

Previous studies have shown that both synapses and astrocytes are altered in brains with autism. To date,

however, the two structures have not been investigated in a single study. “With this grant, we will be able

to chart the wiring of the synapses and determine if the associations of astrocyte processes with synapses

are altered in the autism brain,” explains Dr. Trapp.

By lighting up astrocytes, as they plan to do in their study, researchers in the Trapp lab will be able to

map the cells’ appearance and determine, for example, whether they are malformed. In brain areas with

altered astrocytes, the researchers will establish the relationship between astrocytes and synapses using

three-dimensional electron microscopy. “We are fortunate to have one of the world’s few 3-D electron

microscopes,” says Dr. Trapp. “We will be performing a detailed connectome study on small regions of the

autism brain.”

While he doesn’t suspect that mapping astrocytes will be a silver bullet for curing autism, Dr. Trapp

believes this research will help pave the way to a treatment. “We hope to identify therapeutic targets and

share the data to generate future research.”

›


STAFFCLEVELAND CLINIC NEUROLOGICAL INSTITUTE

NEUROLOGICAL INSTITUTE LEADERSHIP

Michael T. Modic, MD, FACR Chairman, Neurological Institute

William Bingaman, MD Institute Vice Chairman, Clinical Areas

Richard Rudick, MD Institute Vice Chairman, Research and Development

Stephen Samples, MD Institute Vice Chairman, Regional Neurosciences

Edward C. Benzel, MD Chairman, Department of Neurological Surgery

Kerry Levin, MD Chairman, Department of Neurology

Donald A. Malone Jr., MD Chairman, Department of Psychiatry and Psychology

Frederick Frost, MD Chairman, Department of Physical Medicine and Rehabilitation

Thomas Masaryk, MD Chairman, Department of Diagnostic Radiology

Bruce Trapp, PhD Chairman, Department of Neurosciences

Jocelyn Bautista, MD Institute Quality Improvement Officer

Adrienne Boissy, MD Institute Patient Experience Officer

CENTERS AND DEPARTMENTS

Center for Behavioral Health

Donald A. Malone Jr., MD Director

Manish Aggarwal, MD

Veena Ahuja, MD

Amit Anand, MD

Kathleen Ashton, PhD

Joseph M. Austerman, DO

Florian Bahr, MD

Sarah Banks, PhD, ABPP-CN

Joseph Baskin, MD

Scott Bea, PsyD

Aaron Bonner-Jackson, PhD

Adam Borland, PsyD

Minnie Bowers-Smith, MD

Susan Albers Bowling, PsyD

Robert Brauer, DO

Dana Brendza, PsyD

Karen Broer, PhD

Robyn Busch, PhD

Kathy Coffman, MD

Gregory Collins, MD

Edward Covington, MD

Horia Craciun, MD

Roman Dale, MD

Syma Dar, MD

Sara Davin, PsyD, MPH

Ketan Deoras, MD

Beth Dixon, PsyD

Judy Dodds, PhD

Michelle Drerup, PsyD

Jung El-Mallawany, MD

Emad Estemalik, MD

Tatiana Falcone, MD

Lara Feldman, DO

Darlene Floden, PhD

Kathleen Franco, MD

Margo Funk, MD

Harold Goforth, MD

Lilian Gonsalves, MD

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

Xavier Jimenez, MD

Daniel Jones, PhD

Regina Josell, PsyD

Elias Khawam, MD

Patricia Klaas, PhD

Steven Krause, PhD, MBA

Cynthia S. Kubu, PhD, ABPP-CN

Richard Lightbody, MD

Jane Manno, PsyD

Manu Mathews, MD

Michael McKee, PhD

Douglas McLaughlin, DO

Julie Merrell, PhD

Amit Mohan, MD

Gene Morris, PhD

Douglas Moul, MD

Donna Munic-Miller, PhD

Kathryn Muzina, MD

Richard Naugle, PhD

Mayur Pandya, DO

Michael Parsons, PhD

Leopoldo Pozuelo, MD

Kathleen Quinn, MD

Ted Raddell, PhD

Laurel Ralston, DO

Stephen Rao, PhD

Joseph Rock, PsyD

Michael Rosas, MD

Robert Rowney, DO

Judith Scheman, PhD

Isabel Schuermeyer, MD

Cynthia Seng, MD

Jean Simmons, PhD

Barry Simon, DO

Catherine Stenroos, PhD

David Streem, MD

Amy Sullivan, PsyD

Giries Sweis, PsyD

George E. Tesar, MD

Mackenzie Varkula, DO

Adele Viguera, MD, MPH

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


Charles Bernick, MD

Aaron Bonner-Jackson, PhD

Le Hua, MD

Gabriel Léger, MD

Justin Miller, PhD


Jagan Pillai, MD, PhD

Alexander Rae-Grant, MD

Stephen Rao, PhD Director, Schey Foundation Center for Advanced Cognitive Function

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 Director

Manmeet Ahluwalia, MD

Lilyana Angelov, MD


Toomas Anton, MD

Samuel Chao, MD

Kambiz Kamian, MD

John Lee, MD

Joung Lee, MD

Alireza Mohammadi, MD

Erin Murphy, MD

Michael Parsons, PhD

David Peereboom, MD

Pablo Recinos, MD

Violette Recinos, MD

Jeremy Rich, MD

Steven Rosenfeld, MD, PhD

Isabel Schuermeyer, MD

Glen Stevens, DO, PhD

John Suh, MD

Tanya Tekautz, MD

Jose Valerio-Pascua, MD

Michael Vogelbaum, MD, PhD

Jennifer Yu, MD, PhD

Cerebrovascular Center

Peter Rasmussen, MD Director

Mark Bain, MD

Dhimant Dani, MD

Megan Donohue, MD

Erin Dyer, MD

Abeer Farrag, MD

Darlene Floden, PhD

Neil Friedman, MBChB

Jennifer Frontera, MD

Joao Gomes, MD

Stephen Hantus, MD

Ferdinand Hui, MD

M. Shazam Hussain, MD

Damir Janigro, PhD

Irene Katzan, MD, MS

Zeshaun Khawaja, MD

Ajit Krishnaney, MD

John Lee, MD

Mei Lu, MD, PhD

Gwendolyn Lynch, MD

Edward Manno, MD

Thomas Masaryk, MD

Laurie McWilliams, MD

J. Javier Provencio, MD


Andrew Russman, MD

Susan Samuel, MD

Gabor Toth, MD

Ken Uchino, MD

Dolora Wisco, MD

Epilepsy Center

Imad Najm, MD Director

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

Paul Ford, PhD

Nestor Galvez-Jimenez, MD

Jorge Gonzalez-Martinez, MD, PhD

Ajay Gupta, MD

Stephen Hantus, MD

Jennifer Haut, PhD

Lara Jehi, MD

Stephen E. Jones, MD, PhD

Patricia Klaas, PhD

Prakash Kotagal, MD

Deepak Lachhwani, MBBS, MD

Chetan Malpe, MD

John Mosher, PhD

Ahsan Moosa Naduvil Valappil, MD

Dileep Nair, MD

Richard Naugle, PhD

Silvia Neme-Mercante, MD

Elia Pestana Knight, MD

Adriana Rodriguez, MD

Paul Ruggieri, MD

Norman So, MD

Andrey Stojic, MD, PhD

George E. Tesar, MD

Guiyun Wu, MD

Elaine Wyllie, MD

Zhong Ying, MD, PhD

General Adult Neurology


C. Daniel Ansevin, MD

Kristin Appleby, MD

Dina Boutros, MD

Thomas E. Gretter, MD

Zulfiqar Hussain, MD

Kuruvilla John, MD

Richard Lederman, MD, PhD

Nimish Thakore, MD

Roya Vakili, MD

Robert Wilson, DO

Mellen Center for Multiple Sclerosis Treatment and Research

Richard Rudick, MD Director

Robert Bermel, MD

Francois Bethoux, MD

Adrienne Boissy, MD

Jeffrey Cohen, MD

Devon Conway, MD

Robert Fox, MD

Juliet Hou, MD

Le Hua, MD

Keith McKee, MD

Deborah Miller, PhD

Manikum Moodley, MD, FCP, FRCP

Daniel Ontaneda, MD

Alexander Rae-Grant, MD

Megan Rahmlow, MD

Richard M. Ransohoff, MD

Mary Rensel, MD

Lael Stone, MD

Amy Sullivan, PsyD

Timothy West, MD

Mary Willis, MD

Center for Neuroimaging

Paul Ruggieri, MD Director

Aliye Bricker, MD

Todd M. Emch, MD

Ramin Hamidi, DO

Virginia Hill, MD

Rebecca Johnson, MD

Stephen E. Jones, MD, PhD

Brooke Lampl, DO

Daniel Lockwood, MD

Mark Lowe, PhD

Michael Martinez, MD

Thomas Masaryk, MD

Parvez Masood, MD

Manoj Massand, MD

Michael T. Modic, MD

Doksu Moon, MD

Stuart Morrison, MD, MBChB, FRCP

Ellen Park, MD

Michael Phillips, MD

Alison Smith, MD

Todd Stultz, DDS, MD

Andrew Tievsky, MD

Jawad Tsay, MD

Unni Udayasankar, MD

Neil Vachhani, MD

Esben Vogelius, MD

Neurological Center for Pain

Edward Covington, MD Director

Cynthia Bamford, MD

Eric Baron, DO

Neil Cherian, MD

Sarah Davin, PsyD

Emad Estemalik, MD

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

Anwar Ahmed, MD

Jay Alberts, PhD

Kristin Appleby, MD

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

Darlene A. Lobel, MD, FAANS

Donald A. Malone Jr., MD

Sean Nagel, MD

Mayur Pandya, DO

Ela B. Plow, PhD, PT

Joseph Rudolph, MD

Stewart Tepper, MD

Ryan Walsh, MD, PhD

Neuromuscular Center

Kerry Levin, MD Director

Kara Browning, MD


Joshua Gordon, MD


Rebecca Kuenzler, MD

Yuebing Li, MD, PhD

Mei Lu, MD, PhD


John Morren, MD

Erik Pioro, MD, PhD

David Polston, MD

Robert Shields Jr., MD

Steven Shook, MD

Jinny Tavee, MD

Nimish Thakore, MD

Jennifer Ui, MD

Pediatric and Congenital Neurosurgery

Stephen Dombrowski, PhD

Mark Luciano, MD, PhD


Center for Pediatric Neurology

Kerry Levin, MD Interim Director


Gary Hsich, MD

Irwin Jacobs, MD

Kambiz Kamian, MD

Sudeshna Mitra, MD


Sumit Parikh, MD

A. David Rothner, MD

Tanya Tekautz, MD

Department of Physical Medicine and Rehabilitation

Frederick Frost, MD Chairman and Executive Director, Cleveland Clinic Rehabilitation and Sports Therapy

Richard Aguilera, MD

Jay Alberts, PhD

Melissa Alvarez-Perez, MD

Keerthi Atluri, MD

Sree Battu, 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

Jane Manno, PsyD

Carey Miklavcic, DO


Matthew Plow, PhD

Anantha Reddy, MD

Michael Schaefer, MD

Patrick Schmitt, DO

Dan Shamir, MD

Patrick Shaughnessy, MD

Yana Shumyatcher, MD

Kelly Wadeson, PhD

Center for Regional Neurosciences


Jeremy Amps, MD

C. Daniel Ansevin, MD

Toomas Anton, MD

Kristin Appleby, MD

Eric Baron, DO

Samuel Borsellino, MD

Dina Boutros, MD

Luzma Cardoma, MD

A. Romeo Craciun, MD

Carrie Diulus, MD

Megan Donohue, MD

Atef Eltomey, MD

Todd Francis, MD, PhD

Naila Goenka, MD

Joshua Gordon, MD

Raqeeb Haque, MD

Dulara Hussain, MD


Kambiz Kamian, MD

Robert Kosmides, MD

Don K. Moore, MD

Tiffany Perry, MD

Sheila Rubin, MD

Teresa Ruch, MD

Joseph Rudolph, MD

Andrey Stojic, MD, PhD

Nimish Thakore, MD

Jennifer Ui, MD

Roya Vakili, MD

Simona Velicu, MD

Robert Wilson, DO

Joseph Zayat, MD

Sleep Disorders Center

Nancy Foldvary-Schaefer, DO, MS Director

Loutfi Aboussouan, MD

Charles Bae, MD

A. Romeo Craciun, MD

Ketan Deoras, MD

Michelle Drerup, PsyD

Sally Ibrahim, MD

Krystyna Kolaczynski, MD

Alan Kominsky, MD

Jyoti Krishna, MD

Megan Lavery, PsyD

Reena Mehra, MD, MS

Omar Minai, MD

Douglas Moul, MD, MPH, FAASM

Silvia Neme-Mercante, MD

Carlos Rodriguez, MD

Frederick Royce Jr., MD

Jessica Vensel-Rundo, MD, MS

Harneet Walia, MD

Tina Waters, MD

Center for Spine Health

Gordon Bell, MD Director

Daniel Mazanec, MD Associate Director

Jeremy Amps, MD

Lilyana Angelov, MD

Toomas Anton, MD

Adam Bartsch, PhD

Edward Benzel, MD

William Bingaman, MD

Samuel Borsellino, MD

Edwin Capulong, MD

Edward Covington, MD

Russell DeMicco, DO

Carrie Diulus, MD

Alef Eltomy, MD

Michael Eppig, MD

Todd Francis, MD, PhD

Frederick Frost, MD


Kush Goyal, MD

Raqeeb Haque, MD

Garett Helber, DO

Augusto Hsia Jr., MD

Iain Kalfas, MD

Kambiz Kamian, MD

Tagreed Khalaf, MD

Ajit Krishnaney, MD

Andre Machado, MD, PhD

Jahangir Maleki, MD, PhD

Manu Mathews, MD

E. Kano Mayer, MD

Robert McLain, MD

Don Moore, MD

Thomas Mroz, MD

R. Douglas Orr, MD

Tiffany Perry, MD

Anantha Reddy, MD

Teresa Ruch, MD

Judith Scheman, PhD

Richard Schlenk, MD

Santhosh Thomas, DO, MBA

Deborah Venesy, MD

Fredrick Wilson, DO

Adrian Zachary, DO, MPH

COLLABORATIVE DEPARTMENTS

Section for Neurosurgical Anesthesia, Department of General Anesthesiology, Anesthesiology Institute

Rafi Avitsian, MD Section Head

Sekar Bhavani, MD

Matvey Bobylev, MD

Zeyd Ebrahim, MD

Hesham Elsharkawy, MD

Ehab Farag, MD

Samuel Irefin, MD

Paul Kempen, MD, PhD

Reem Khatib, MD

Mariel Manlapaz, MD

Marco Maurtua, MD

Antonio Ramirez, MD

Stacy Ritzman, MD

Leif Saager, MD

David Traul, MD, PhD

Guangxiang Yu, MD

Department of Neurosciences, Lerner Research Institute

Bruce Trapp, PhD Chairman

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

Department of Biomedical Engineering, Lerner Research Institute

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

Department of Cell Biology, Lerner Research Institute

Damir Janigro, PhD

Nicola Marchi, PhD

Department of Anatomic Pathology, Pathology & Laboratory Medicine Institute

Richard Prayson, MD

Susan Staugaitis, MD, PhD

CLEVELAND CLINIC FLORIDA

Badih Adada, MD

Michelle Dompenciel, MD

Néstor Gálvez-Jiménez, MD, MSc, MS (HSA), FACP

Danita Jones, DO

Tarannum Khan, MD

Ramon Lugo-Sanchez, MD

Chetan Malpe, MD

Ryan McTaggart, MD

Graham Mouw, MD, FAANS, FACS

Linda Pao, MD

Megan Rahmlow, MD

Adriana Rodriguez, MD

Richard Roski, MD

Virgilio D. Salanga, MD

Efrain Salgado, MD

Alexandra Soriano Caminero, MD

Po-Heng Tsai, MD

CLEVELAND CLINIC NEVADA

Jeffrey Cummings, MD, ScD Director, Lou Ruvo Center for Brain Health


Charles Bernick, MD

Le Hua, MD

Gabriel Leger, MD

Justin Miller, MD


Ryan Walsh, MD, PhD

Timothy West, MD

Dylan Wint, MD

Xue (Kate) Zhong, MD, MSc

YEAR IN REVIEW STAFF

Managing Editor, Glenn Campbell

Art Director, Chip Valleriano

Principal Photography, Russell Lee Yu Kwan Lee Steve Travarca

Principal Illustration, Amanda Mendelsohn Mark Sabo

For address changes

or more information

about Cleveland Clinic’s

Neurological Institute,

please contact:

Cleveland Clinic

9500 Euclid Ave./AC311

Cleveland, OH 44195

216.448.1022

[email protected]

clevelandclinic.org/

neuroscience

Cleveland Clinic is a

nonprofit academic medical

center ranked among the

nation’s top hospitals

(U.S. News & World

Report), where more than

3,000 physicians in 120

specialties collaborate to

give every patient the best

outcome and experience.

clevelandclinic.org

Year in Review is written for

physicians and should be

relied on for medical

education purposes only. It

does not provide a complete

overview of the topics

covered and should

not replace the independent

judgment of a physician

about the appropriateness

or risks of a procedure for a

given patient.

©The Cleveland Clinic

Foundation 2013


24/7 ReferralsReferring Physician Hotline 855.REFER.123 (855.733.3712) clevelandclinic.org/refer123

Live help connecting with our specialists, scheduling and confirming appointments, and resolving service-related issues.

Hospital Transfers 800.553.5056

Stay Connected to Cleveland Clinic on …

Physician Directory. View our staff at clevelandclinic.org/staff.

Same-Day Appointments. Cleveland 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).

Track Your Patients’ Care Online. Establish a secure online DrConnect account for real-time information about your patients’ treatment at Cleveland Clinic at clevelandclinic.org/drconnect.

Critical Care Transport Worldwide. To arrange for a critical care transfer, call 216.448.7000 or 866.547.1467. For STEMI (ST elevated myocardial infarction), acute stroke, ICH (intracerebral hemorrhage) or aortic syndrome transfers, call 877.379.CODE (2633). Learn more at clevelandclinic.org/criticalcaretransport.

CME Opportunities: Live and Online. Visit ccfcme.org to learn about the Cleveland Clinic Center for Continuing Education’s convenient, complimentary learning opportunities.

Outcomes Data. View Outcomes books at clevelandclinic.org/outcomes.

Clinical Trials. We offer thousands of clinical trials for qualifying patients. Visit clevelandclinic.org/clinicaltrials.

Executive Education. Learn about our Executive Visitors’ Program and two-week Samson Global Leadership Academy immersion program at clevelandclinic.org/executiveeducation.

ABOUT CLEVELAND CLINIC

Cleveland Clinic is an integrated healthcare delivery system with local, national and international reach. At Cleveland Clinic, more than 3,000 physicians and researchers represent 120 medical specialties and subspecialties. We are a nonprofit academic medical center with a main campus, eight community hospitals, more than 75 northern Ohio outpatient locations (including 16 full-service family health centers), 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 2013, 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 in heart care for the 19th consecutive year.

DOWNLOAD OUR NEW PHYSICIAN REFERRAL APP!

With our free Physician Referral App, you can view all our specialists and get in touch immediately with one click of your iPhone®, iPad®, or Android™ phone or tablet.

Download today at the App Store or Google Play.

RESOURCES FOR PHYSICIANS

Contacting us is now easier than ever.

Great things happen when a medical center puts patients first.

Visit clevelandclinic.org/ClevelandClinicWay for details or to order a copy.

The Cleveland Clinic WayBy Toby Cosgrove, MD, CEO and President of Cleveland Clinic

The Cleveland Clinic Foundation 9500 Euclid Avenue / AC311Cleveland, OH 44195

13-NEU-591

neurological institute - cleveland clinic

Documents