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Insights 2011 | 2012A publication of the Center for Behavioral Health

Revealing the Underlying Neural Mechanisms of Successful ECT

Advanced Neuroimaging

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3 inSiGhTS 2010 | 2011 ClEvEl ANdClINIC.ORg /NEUROSCIENCE

[ investigations ]

ClEvEl ANd ClINIC CENTER fOR BEHAvIORAl HEAlTH | 866.588.2264 1

Dear Colleagues,

2011 | 2012

Donald A. Malone Jr., MD

Medical Editor

Seabright McCabe

Managing Editor

Barbara Ludwig Coleman

Art Director, Designer

Sarah C. Delly

Marketing

Insights is written for physicians and

should be relied upon 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.

Cleveland Clinic is a nonprofit,

multispecialty academic medical

center, consistently ranked among the

top hospitals in America by U.S.News

& World Report. Founded in 1921,

it is dedicated to providing quality

specialized care and includes an

outpatient clinic, a hospital with more

than 1,300 staffed beds, an education

institute and a research institute.

clevelandclinic.org

© The Cleveland Clinic Foundation 2011

It is my privilege to introduce this edition of Insights, featuring advances

in clinical care and research within Cleveland Clinic Neurological Institute’s

Center for Behavioral Health. This issue focuses on research and clinical

programs we have developed and embedded into other Cleveland Clinic

institutes.

At Cleveland Clinic’s Taussig Cancer Institute, Isabel Schuermeyer, MD, has

formed a psychosocial oncology team, aimed at educating caregivers on the

signs of clinical depression in cancer patients and reducing the time it takes

for them to be seen by a mental health professional.

Kathy Coffman, MD, details the comprehensive psychological evaluation

developed for Cleveland Clinic’s groundbreaking face transplantation

procedure — a process critical for both selecting candidates and predicting

positive psychological outcomes.

Erik Beall, PhD, investigates advanced neuroimaging for discovering how

electroconvulsive therapy changes the brain, with the aim of developing a

biomarker that predicts a patient’s response to treatment.

At the Epilepsy Center, George Tesar, MD, presents an analysis of data

supporting routine screening and measurement of depression in epilepsy

patients to improve outcomes, and Tatiana Falcone, MD, takes psychological

intervention for youth with epilepsy into the schools and community with

Project COPE.

Still other advances in treatments, ranging from deep brain stimulation for

thalamic pain to ketamine infusion for the relief of treatment-resistant

depression, are highlighted in these pages.

In the meantime, our staff has published research in dozens of journals and

presented findings at more than 50 national and international conferences,

symposia and meetings this year. Their contributions continue to advance

Cleveland Clinic’s leadership role in clinical research and patient care.

I hope you enjoy Insights and, as always, I welcome your feedback.

Sincerely,

Donald A. Malone Jr., MD

Professor and Chairman, Department of Psychiatry and Psychology

Director, Center for Behavioral Health

Cleveland Clinic Neurological Institute

The multidisciplinary Neurological

Institute, one of 26 institutes at

Cleveland Clinic, is internationally

known for superior diagnosis and

treatment of neurological disorders

ranging from the common to the

most complex. More than 300

specialists combine clinical expertise,

academic achievement and innovative

research to accelerate the transfer of

investigational therapies unavailable

elsewhere, for the benefit of adult and

pediatric patients. The institute is

committed to improving outcomes

while treating patients with compassion

and respect.

W E L C O M E f R O M T h E C h a i R M a n

Insights

IN THIS ISSUE:

NEUROIMAgINg

2 Using Advanced Neuroimaging to detect Brain Changes in Electroconvulsive Therapy for depression

4 Case Study: A Successful Course of ECT

OUTCOMES

5 Selection Process and Psychological Outcomes in Face Transplantation

EMPOWERINg PATIENTS

8 Caring for Cognition: Neuropsychology in the Cancer Clinic

BAlANCINg RISK

10 Fast-Acting Antidepressant for Treatment-Resistant Depression

dEvElOPINg TREATMENTS

12 Deep Brain Stimulation to Modulate the Affective Component of Thalamic Pain Syndrome

TOWARd WEllNESS

14 Identifying depression in Epilepsy Patients for Better Outcomes

16 Psychosocial Predictors of Weight loss following Bariatric Surgery

COllABORATIvE CARE

18 Behavioral Health Interventions for Cancer Patients

20 Innovative Interventions for Youth with Epilepsy: Project COPE

CAREgIvINg

22 Comprehensive Care of Motor, Psychiatric and Cognitive deficits in Huntington’s disease

AlSO INSIdE:

24 Staff Listing

24 Publications

26 Presentations

29 Select Clinical Trials

BC Referrals

BC Resources for Physicians and Patients

On the cover: Imaging of an average brain response to a spatial working memory task performed by an Mdd patient, pre-ECT.

2 inSiGhTS 2011 | 2012 ClEvEl ANdClINIC.ORg /PSYCHIATRY

n E U R O i M a G i n G



Figure 1. At left, the average brain response to viewing unpleasant pictures in MDD patients before they have undergone ECT. At right, the average brain response to unpleasant pictures in the same patients after ECT. Orange corresponds to an increase in blood flow-related activity; blue corresponds to a decrease in activity.

Roughly 20 percent of patients do not respond acutely

to ECT and, among those who do, 40 percent do not

experience a sustained remission beyond six months.

Furthermore, possible side effects — including transient

memory loss and behavioral changes — are not negligible.

Inconsistencies in patients’ responses reflect the fact

that, despite its undeniable success, this historically

controversial therapy works by a mechanism that we

do not precisely understand. Thus, progress toward

improving treatment is limited, more than 25 years after

the National Institutes of Health Consensus Develop-

ment Conference Statement of 1985 asserted that “much

additional research is needed into the basic mechanisms

by which ECT exerts its therapeutic effects.”

Data from a preliminary, internally funded neuroimaging

study at Cleveland Clinic suggest significant changes in

functional brain activation, functional connectivity and

gamma aminobutyric acid (GABA) levels in response to

ECT. These findings appear to differ between respond-

ers and nonresponders to therapy. On the strength of

these early results, we believe advanced neuroimaging

techniques can detect changes in brain activity linked

with the therapeutic response to ECT. We have applied to

the National Institute of Mental Health and the National

Institute of Biomedical Imaging and Bioengineering with

a proposal to use state-of-the-art magnetic resonance

imaging (MRI) to better understand the underlying neural

mechanisms of successful ECT for major depression and

to investigate outcome biomarkers from a single pre-ECT

MRI session.

Preliminary findings

Seven ECT-naïve adult patients (four male and three female)

with treatment-resistant depression, for whom a clinical

decision to pursue ECT had already been made, were

recruited for our study. The subjects were scanned within

one week of their first course of ECT and again a few

weeks after their final ECT treatment. Informed consent

was obtained for the pre- and post-ECT scanning sessions.

Although functional MRI (fMRI) and functional connec-

tivity (fcMRI) have been used to study depression and the

treatment effect of antidepressant medications, our study

marks the first application of these imaging modalities to

investigate ECT. In each scanning session, patients per-

formed three fMRI tasks, developed with the assistance

of research neuropsychologist Katherine Koenig, PhD,

Staff at the Department of Diagnostic Radiology. Two

affective picture-viewing tasks required patients to view

neutral and unpleasant pictures from the International

Affective Picture System and press a button each time a

new picture was displayed (Figure 1). A two-back spatial

working memory task required subjects to follow a ball as

it moved among four boxes. The patients used two button

boxes to indicate the ball’s current location during the

rest phase and its location two presentations previously

during the task phase (Figure 2). Additional imaging was

acquired, including spectroscopic measurement in the

anterior cingulate cortex and whole-brain high angular

resolution diffusion tensor imaging (DTI).

A synopsis of our findings follows:

GABA restoration. A magnetic resonance spectroscopy

technique pioneered by Pallab K. Bhattacharyya, PhD,

Staff at the Department of Diagnostic Radiology, was used

to measure neuronal levels of GABA, the brain’s predomi-

nant inhibitory neurotransmitter. Numerous studies have

linked depression with reduced cortical GABA levels. We

observed significant post-ECT normalization of GABA

levels in the anterior cingulate cortex, a region implicated

in past depression studies and known to be involved in

attention and emotional regulation.

Activation volume decrease. Blood oxygenation level-

dependent contrast activation levels in response to

performance of all fMRI tasks decreased following

ECT, dramatically in the case of emotional activation.

The change in activation in the orbitofrontal cortex,

a region associated with depression and emotional

processing, correlated significantly with change in

the level of depression.

Using Advanced Neuroimaging to detect Brain Changes in Electroconvulsive Therapy for Depression

Unchanged white matter tract integrity. We recorded the

first probabilistic tractography-based observations of

white matter tract integrity by using high-direction DTI

before and after an acute series of ECT. Using transverse

diffusivity (water diffusing perpendicular to the primary

neuronal direction), we observed no significant change

in axonal integrity from pre- to post-ECT scanning, which

supports conclusions of prior studies on the safety of ECT.

Toward a Deeper Understanding

We plan to build on these early results in a new study that

will enroll 60 patients with major depressive disorder and

30 controls. The treatment group will be scanned pre- and

post-acute ECT and six months after the course of therapy

concludes; the control group will be scanned only once as

a baseline comparison. In particular, we seek to:

• Confirm and increase the specificity of our initial findings

on normalization of spectroscopic levels of cortical GABA

after successful ECT.

• Identify the acute and long-term effects of ECT on

abnormal functional and structural brain connectivity.

Our preliminary data suggest that structural connectivity

is unchanged by ECT, whereas functional connectivity

is dramatically altered. To understand a change in func-

tional connectivity, we need to confirm whether ECT

induces axonal damage and whether structural connectivity

is a measure of neuronal integrity. We propose to show

that ECT produces normalizing changes in functional

connectivity driven primarily by cortical, not white

matter, changes.

• Determine whether there are significant predictive

differences in MR imaging among nonresponders, acute

responders and sustained responders to ECT. We hypoth-

esize that using advanced imaging modalities (fMRI and

By Erik Beall, PhD

resting-state fMRI) in a single pre-ECT session will provide

us with a biomarker to predict early in the course of therapy

which patients will respond acutely and long-term, as

determined by the Hamilton Depression Rating Scale.

an Opportunity for improvement

A typical course of acute ECT involves a total of six to

12 sessions performed every other day, each combining

general anesthesia, motor paralysis with muscle relax-

ants, assisted ventilation and a brief seizure. A full course

of this invasive procedure ranges in cost from $6,000

to $15,000. As noted above, not all patients respond to

therapy, and some responders require repeat ECT. An

improved understanding of ECT would greatly benefit

public health by reducing the expense, the number of

unnecessary treatments, the delay in proceeding to

potentially more useful therapies for nonresponders,

and the risk of morbidity and discomfort.

Erik Beall, PhD, is a project staff member at Cleveland Clinic

Imaging Institute, with a joint appointment at Cleveland

Clinic Neurological Institute. He is also an assistant professor

at Cleveland Clinic’s Lerner College of Medicine. His primary

research interests are functional neuroimaging with MRI

and development of advanced MRI methods. He can be

reached at 216.445.6110 or at [email protected].

Electroconvulsive therapy (ECT) is considered a uniquely powerful modality for treatment of major depressive disorder

(MDD), which has an estimated lifetime prevalence of 13 percent in the general population. With a remission rate

approximating 80 percent in the acute term, ECT has proved to be safe and effective for MDD patients when every

other intervention has failed.



Selection Process and Psychological Outcomes in Face Transplantation

By Kathy Coffman, MD

a face transplant is a medical procedure like no other, involving the body part most closely associated with identity.

facial transplantation is an extremely complex procedure that, unlike organ transplants, is life-enhancing, not life-saving.

it is a treatment of last resort after traditional reconstructive techniques have failed to restore function. never is it

undertaken for cosmetic reasons alone.

In 2008, a Cleveland Clinic surgical team performed the

first face transplant in the United States. It was the culmi-

nation of five years’ preparation, including comprehensive

consideration of medical, psychological and ethical issues.

At the time of the transplant, psychological outcomes

were not well known. Previous face transplant reports

had not quantitatively investigated issues such as body

image, mood changes and self-esteem. The Cleveland

Clinic team is the first to undertake a comprehensive

quantitative evaluation of a transplant patient.

Selection Criteria

Before being considered for face transplant, a patient

must have come to terms with his or her experience:

grieving the loss, adjusting to the injuries, recovering

from depression and post-traumatic stress disorder, and

completing rehabilitation. Contraindications for trans-

plant include poor medical compliance, end-stage organ

disease, major psychiatric illness and active addiction.

Assertive coping strategies, both in handling the injury

and in social encounters, are important for self-care and

social reintegration. Avoidant coping strategies — such

as not touching the face or not discussing the severity of

the injury — may decrease anxiety, but they also hinder

the positive coping and self-care needed for a successful

face transplant.

Candidates should have strong self-esteem not based

on appearance, and the goals that motivate them should

be physical and functional, not for cosmetic purposes

alone. A strong social support system is important to

post-procedure recovery, rehabilitation and reintegration

into the community.

Ethical issues

Because face transplant is experimental and is not

life-saving, the informed consent process must be

rigorous. In developing the first face transplant ethical

protocol, we considered many issues, including whether

the potential benefits of the surgery justified the risks.

Connie Culp, the candidate considered for the procedure,

had injuries that severely impaired her ability to speak,

smell, eat and socialize. Unlike previous face transplant

patients, she had undergone multiple reconstructive

attempts with limited success.

Cleveland Clinic has developed a comprehensive evaluation process for selecting face transplant candidates and

assessing their psychological and psychosocial outcomes.

O U T C O M E S


By Mayur Pandya, DO

A 45-year-old woman with a 10-year history of major depression and poor response to psychotherapy presented for evaluation. She reported some past benefit from a few medications, but, typically, the response was inadequate and/or temporary. Trials had consisted of various classes of antidepressants, including selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors, as well as combination and augmentation strategies.

In recent weeks, she had begun to experience a general sense of fear and apprehension, evidenced by nihilistic thinking and a guarded demeanor. She was subsequently admitted, and a course of electroconvulsive therapy (ECT) was initiated.

After the first week, her thinking became more grounded in reality, but she continued to display a blunted affect with psychomotor slowing. By the end of the second week, she had a brighter affect with less depression.

She was subsequently discharged and completed the ECT course as an outpatient. By the end of the third week, she was socializing with friends and family and denying any continued depressive symptoms.

Her total course consisted of 10 treatments, after which she was placed on a combination of fluoxetine and aripiprazole, with complete restoration of social, occupational and interpersonal functioning.

Mayur Pandya, DO, is Director of the comprehensive

HD clinic at Cleveland Clinic, and a staff member

at both Cleveland Clinic’s Center for Behavioral

Health and Center for Neurological Restoration.

His specialty interests include psychiatric and

behavioral issues in movement disorders, treatment-

resistant depression, obsessive-compulsive disorder

and medical education. He can be contacted at

216.445.5585 or at [email protected].

Case Study: A Successful Course of ECT

Figure 2. The top image shows the average brain response to performing a spatial working memory (short-term memory) task in MDD patients before they have undergone ECT. The image below shows the average brain response to the same task in the same patients after ECT. Orange corresponds to an increase in blood flow-related activity; blue corresponds to a decrease in activity during the task. The brain’s function for short-term memory appears to be unchanged by ECT.


O U T C O M E S


O U T C O M E S

Ms. Culp had realistic goals, consistent with what could

be achieved with the procedure: to be able to smell, speak

more understandably, eat food normally, experience less

pain and fewer hospitalizations, and look more normal.

She had signed an organ donor card, and had no guilt or

superstition about the transplant.

During several months of meetings with the care team

and bioethicists — which involved both information

disclosure and assessment of comprehension of the

procedure’s potential risks and benefits — Ms. Culp

demonstrated understanding of the surgery, its innova-

tive nature and its uncertainties, and affirmed that it was

consistent with her values. In light of all these factors,

we determined the transplant was justified.

Patient history

At the time of her evaluation in 2008, Ms. Culp, then

45, had undergone 27 procedures at Cleveland Clinic

since 2004, when her then-husband shot her in the face.

Though initially depressed, Ms. Culp showed resilience

and a strong capacity to cope with her disfigurement.

She took classes, ate in restaurants and actively engaged

people who made comments about her appearance to

educate them on her condition.

The clinical team was impressed by Ms. Culp’s conscien-

tious adherence to medical regimens and inspired by her

positive attitude and humor. She demonstrated that she

had the motivation to follow the demanding post-trans-

plant regimen and undergo an arduous rehabilitation. She

had strong social support from her sister and daughter.

Her psychiatric history included treatment for major

depression and post-traumatic stress disorder. Alcohol

abuse had been a problem, but she had been sober since

her injury. She was taking escitalopram, 10 mg daily;

zolpidem, 5 mg at bedtime; and lorazepam, 0.5 mg three

times daily. She had no history of inpatient psychiatric

admission or attempts to harm herself or others. There

was no family history of depression, bipolar disorder or

schizophrenia, though both parents were alcoholic.

Psychological Outcomes

As transplant psychiatrist, I formed a strong therapeutic

relationship with Ms. Culp, providing psychological

support before and after the procedure. To assess her

outcomes, several rating instruments were modified

specifically for facial transplantation. She has been

assessed at regular intervals since the transplant.

FACES: A Cleveland Clinic Assessment Tool for Face Transplant Candidates

The FACES assessment tool was developed by Cleveland Clinic’s multidisciplinary face transplant team as an objective scoring system for identifying the optimal face transplant candidate. It can be used as a prescreening and/or post-screening tool, in conjunction with an IRB-approved protocol for facial transplantation.

The first fACES category, functional status, assesses social stability with two validated social point scales — the Straus-Bacon Social Stability Score and the Karnofsky Performance Score — that have demonstrated prognostic value in screening candidates for organ transplantation.

The remaining four categories assess the candidate’s physical state: the extent of facial deficits (aesthetic deficits), fitness for surgery (comorbidities), the severity of the facial injury (exposed tissue), and previous head and neck surgeries (surgical history).

Her Beck Depression Inventory score dropped from

16 before the transplant to 6 at three months post-

transplant, while she was still taking escitalopram.

Her appearance self-rating jumped from 3/10 post-

injury to 7-8/10 one year after the transplant. Her

State-Trait Anxiety Inventory and Rosenberg Self-

Esteem Scale scores remained constant.

On the Psychosocial Adjustment to Illness Scale-

Self-Report (PAIS-SR), her scores have steadily

improved since the transplant, reflecting her social

reintegration. The PAIS-SR has been more useful than

the SF-36 or the World Health Organization Quality

of Life-BREF for assessing social reintegration and

psychological distress.

On the Physical Appearance State and Trait Anxiety

Scale-State rating scale, her score fell from 15 at two

weeks after transplant to 2 at 11 months postop-

erative. Her response to her appearance has been

influenced by others, especially her daughter, as

predicted by symbolic interaction theory. Contrary

to our prediction, adjusting to her new face has been

less difficult than adjusting to her injury. Her score

on Cleveland Clinic’s FACES-Perception of Teasing

Scale (see sidebar) indicated that teasing and verbal

abuse had decreased and that she was less bothered

by them.

Overall, Ms. Culp’s physical and psychological out-

comes have exceeded expectations. Her chronic facial

pain is gone and her eating and speech have greatly

improved. She has gradually gained sensation in her

face and is learning to identify smells. As predicted,

she does not resemble the donor. She leads an active

life, which includes educating people about domestic

violence and organ donation.

As the number of face transplants grows and patient

outcomes data increase, we can better assess whether

the long-term physical and psychological outcomes

of this medical innovation outweigh the risks of

immunosuppression.

Kathy Coffman, MD, is a staff member at Cleveland Clinic’s

Center for Behavioral Health, and has worked with trans-

plant patients for more than 20 years. Her specialty interests

include alcohol and drug abuse in liver transplant patients,

delirium, immunomodulatory effects of psychotropic drugs,

and central nervous system effects of scleroderma and

celiac disease. She can be reached at 216.444.8832 or at

[email protected].

Composite facial allograft, procured from the face transplant donor, contains soft tissues, bones and muscles as well as functional units of nose, upper lip and lower eyelids. Facial allograft inset is used for reconstruction of severe facial defect.

8 inSiGhTS 2011 | 2012 ClEvEl ANdClINIC.ORg /PSYCHIATRY ClEvEl ANd ClINIC CENTER fOR BEHAvIORAl HEAlTH | 866.588.2264 9

• Secondarymanifestationsofillness(fatigue,anemia,

metabolic derangements)

• Otherconditionsthatcanco-occur(dementia,stroke)

Once the underlying cause of the cognitive problem is

determined, the strategy and rationale for treatment

becomes clear. Treatment options might include:

• Pharmacotherapy,withthechoiceofagent(e.g.,

attention-enhancing memory- or mood-related) being

dependent on the neuropsychological profile

• Rehabilitationorothertherapy,withstrategiesdrawn

from the neuropsychological evaluation

• Cognitivesurveillance,withrepeatevaluationat

specified intervals

Neuropsychology plays a critical role in evaluating the

effectiveness of brain tumor treatments in clinical trials.

These clinical trials have shown that cognitive data can

be more sensitive to tumor progression than MR imag-

ing. Because cognitive abilities have such a tremendous

impact on quality of life, the use of cognitive data as an

endpoint in clinical trials is becoming more common.

The BBTC interdisciplinary team includes cognitive

evaluation in many of the ongoing clinical trials.

Caring for the Caregivers

The role of caregiver is stressful on many levels. Family

members cope with their own feelings of anxiety, grief

and loss, while maintaining hopefulness and providing

support for the patient. The mental and physical health

of the caregiver impacts overall survival and plays a tre-

mendous role in quality of life for the patient. Cognitive

symptoms impose a greater burden on caregivers than

do physical symptoms. For example, a 50-year-old gentle-

man started to show disinhibited and inappropriate

behavior several months before presenting to the BBTC

with a seizure. A high-grade glioma involving both frontal

lobes was identified. While making treatment decisions,

the nursing staff observed the wife and daughter of the

patient struggling with the change in his personality. The

neuropsychologist evaluated the patient, who showed

numerous signs of frontal lobe “executive” dysfunction,

including poor impulse control, disinhibition and per-

severation. The neuropsychologist provided feedback to

the patient and family. Together, they set ground rules to

implement in the home to reduce the conflicts. Perhaps

more important, the family came to understand that the

behavior changes were a symptom of the patient’s illness,

rather than signs of dislike or lack of caring.

Caring for Cognition: Neuropsychology in the Cancer Clinic

By Michael Parsons, PhD, aBPP

A neuropsychologist specializes in brain function with

a background in psychology and training in functional

neuroanatomy, clinical psychology and mental health

care. At Cleveland Clinic, a neuropsychologist with

expertise in brain tumors, cancer treatment and cogni-

tive function can see every patient and consult with the

caregiving team. Neuropsychology improves the quality

of care, helps with clinical decision-making, provides

education and support for caregivers, and provides

holistic care.

improving Quality of Life for the Patient

For patients, symptoms are often difficult to understand,

and can be extremely frightening and often embarrass-

ing. For example, one patient reported strange symptoms

to his physician, and a neuropsychologist was consulted.

The patient explained that while driving to the appoint-

ment, he noticed the same person in multiple cars. He

became anxious and frightened, and his wife was uncer-

tain how to handle the situation. The neuropsychologist

determined that the patient was experiencing prosopag-

nosia, a deficit in the ability to recognize faces. His brain

tumor, a high-grade glioma, was situated in an area of the

brain critical for the recognition of faces (Figure 1).

The neuropsychologist explained the nature of the symp-

tom and provided strategies for how to identify important

people in his life by listening to their voices, looking at

their clothing, or watching their gait. The patient left not

only with a treatment plan for his brain tumor, but with

a better understanding of his symptoms and the reassur-

ance that he was not “crazy,” as he had feared.

This scenario illustrates how neuropsychologists broaden

the spectrum of care and help the patient and family to

understand what is happening. This improves the quality

of life for patients who are trying to maximize the quantity

of life. Other examples of the role of neuropsychology in

patient care include:

• Identificationofcognitivedeficitsforoccupationalor

educational accommodations

• Documentationfordisabilityorotherlegalissues(e.g.,

guardianship)

• Identificationofcognitivedeficitsthatraisesafety

concerns (e.g., supervision at home, ability to operate

cars or machinery)

neuropsychology is integral to Treatment of Brain Tumors

Neuropsychological evaluation gives objective data to

the treatment team about brain function. Neurocogni-

tive data can predict tumor grade, detect progression of

cancer and predict the cognitive risk of treatments. The

Burkhardt Brain Tumor Center (BBTC) has a neuropsy-

chological evaluation program that can screen patients

at the time of diagnosis and again at regular intervals

during treatment. This rigorous approach allows us to

discriminate among the many factors that can contribute

to cognitive symptoms in brain cancer:

• Primarymanifestationofbraintumor

• Sideeffectsoftreatment

• Consequencesofaffectivedistress

The Growing importance of neuropsychology in the Care of Brain Tumors

During the past decades, our capacity to treat brain

cancers has improved significantly, resulting in longer

survival times for even the most dire of diagnoses. As we

continue to make progress, the cognitive issues and their

impact on quality of life will grow in importance. At the

BBTC, we have integrated neuropsychology to broaden

our care to patients and their caregivers.

Michael Parsons, PhD, ABPP, is a staff member in Cleveland

Clinic’s Center for Behavioral Health and Cleveland Clinic’s

Rose Ella Burkhardt Brain Tumor and Neuro-Oncology

Center. He specializes in evaluating cognitive changes due

to head injury, brain tumors and cognitive diseases such

as dementia. He can be contacted at 216.445.3322 or at

[email protected].

E M P O W E R i n G P a T i E n T S E M P O W E R i n G P a T i E n T S

a brain malignancy is a devastating and life-changing event with an arduous course of treatment, a grim prognosis

and all the anxieties inherent in a terminal illness. Diagnosis is often sudden in a previously healthy person. Treat-

ment decisions occur in the first few days and weeks, and patients are left reeling, trying to recover from the shock

of diagnosis and the side effects of surgery or other treatment. Cognitive issues may seem a relatively minor concern,

but more than 90 percent of patients experience some cognitive problems during the course of the treatment,

making them one of the most common problems with brain tumors. Many patients fear “living as a vegetable” more

than they fear the possibility of death. To address these issues, Cleveland Clinic’s Rose Ella Burkhardt Brain Tumor

and neuro-Oncology Center has integrated neuropsychology into patient care.

Figure 1. Brain images showing the resection site of a patient with prosopagnosia. The patient was unable to discriminate between faces, resulting in confusion and distress. Neuropsychological evaluation revealed the nature of the deficit and relieved the anxiety.


symptoms. To further investigate the efficacy and safety of

ketamine for this use, we are planning to initiate a small

study of patients with TRD who are eligible for ECT but

who do not desire to undergo that mode of treatment. We

plan to enroll 10 to 20 patients and report the effects of a

low-dose series of ketamine infusions over 12 months in

these patients.

Roman Dale, MD, is Director of Adult Inpatient Psychiatric

Services at Cleveland Clinic’s Lutheran Hospital, and a

staff member at Cleveland Clinic’s Center for Behavioral

Health. His specialty interests include psychosis, neuropsy-

chiatry, and the use of neuromodulation treatments in

mood disorders. He can be reached at 216.363.2473 or at

[email protected].

Fast-Acting Antidepressant for Treatment-Resistant Depression

Major depressive disorder is a significant public health problem with a lifetime prevalence of about 17 percent of the

adult U.S. population. Conventional pharmacologic therapy, which requires weeks or months to elicit an adequate

therapeutic response, produces full remission in only one-third of patients with major depression. Patients who fail to

respond to several adequately dosed pharmacologic interventions are classified as treatment resistant (TRD) and pose

a serious clinical challenge. Traditionally, electroconvulsive therapy (ECT) has been used for these patients, but it is

successful only in about two-thirds of TRD patients, and it carries the risk of short-term cognitive and memory problems.

a growing body of evidence has shown that ketamine initiates a rapid antidepressant response in patients with TRD.

By Roman Dale, MD

Glutamate and Treatment-Resistant Depression

Glutamate is the most abundant excitatory neurotrans-

mitter in the brain. A complex, integrated system, includ-

ing glial astrocyte cells, modulates synaptic neuronal

glutamate transmission through multiple receptors,

particularly N-methyl-D-aspartate (NMDA) and alpha-

amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid

(AMPA). A substantial amount of research has been

conducted that implicates glutamatergic abnormalities

in both major depression and bipolar depression. Altered

glutamate levels have been observed in both plasma

and cerebrospinal fluid; and imaging studies, including

magnetic resonance spectroscopy, have shown regional

alterations. Further, postmortem studies have described

increased glutamate levels in the prefrontal cortex.

In addition, the glutamatergic system plays a critical role

in neuroplasticity (regulation of intracellular signaling,

gene expression, synaptic modification, transmitter

release and remodeling of axonal/dendritic architecture).

Other research has linked impairments in neuroplasticity

to mood disorders and in particular, it has been suggested,

to chronic TRD.

Why Use Ketamine for Treatment-Resistant Depression?

Studies in animal models and clinical case reports have

shown that administration of a low dose of intravenous

ketamine (0.5 mg/kg of ideal body weight) — a high-affinity

NMDA receptor antagonist and AMPA agonist — infused

over 40 minutes, initiates a rapid antidepressant response

within hours (Figure 1). Placebo-controlled trials have

reported a high success rate in TRD patients diagnosed

with major depression and bipolar depression. The effect

of acute ketamine infusion therapy is transient, with

relapse occurring in two to 13 days. However, there are

now case reports of long-term repeat ketamine infusions

providing sustained remission in TRD patients.

The exact mechanism of action is unclear, but according

to one rat lab study, ketamine increased spine density

and synaptic formation. Through “second messengers,”

ketamine quickly activated “mammalian target of

rapamycin” (mTOR), a protein kinase, in the prefrontal

cortex. Blocking mTOR showed that it was the essential

component needed for the neuroplastic increase in

spine and synaptic formation that was observed when

ketamine was administered.

Questions and the future

The potential for ketamine to be a therapeutic option

for this population of patients is exciting and, hopefully,

further investigation will lead to the development of

effective oral agents. Of clinical concern is that ketamine

has some possible adverse effects, including the risk of

psychosis, impaired cognitive ability and a potential

for abuse.

Many issues remain to be addressed. Finding the optimal

dose and duration of infusion to maximize therapeutic

effects while minimizing adverse events is critical. Further

investigation into the mechanism of action, identifica-

tion of responders, level of medical monitoring to ensure

safety, frequency of “maintenance” infusions and long-term

side effects of mTOR activation is needed. At Lutheran

Hospital, a Cleveland Clinic community hospital, we have

already observed a few patients with severe TRD in whom

repeat ketamine administration successfully improved

B a L a n C i n G R i S K

Ketamine

PrefrontalCortex

Improved behavior indicators

Increased synaptic activity

Dendritic spinal growth

NMDAreceptors AMPA

receptors

Increase in Akt / intracellular ERK

4E-BP1 p70S6K

Activation of mTOR

© CCF 2011

+

S U G GE S T E D R E A DI NG

1. Diazgranados N, Ibrahim L, Brutsche N, Newberg A,

Kronstein P, et al. A randomized add-on trial of an

N-methyl-D-aspartate antagonist in treatment-resis-

tant bipolar depression. Arch Gen Psychiatry 2010 Aug;

67(8):793-802.

2. Li N, Lee B, Liu R-J, Banasr M, Dwyer JM, et al. mTOR-

dependent synapse formation underlies the rapid

antidepressant effects of NMDA antagonists. Science

2010 Aug;329(5994):959-964.

3. Machado-Vieira R, Manji HK, Zarate CA. The role of the

tripartite glutamatergic synapse in the pathophysiology

and therapeutics of mood disorders. The Neuroscientist

2009 Oct;15(5):525-539.

4. Messer M, Haller IV, Larson P, Pattison-Crisostomo J,

Gessert CE. The use of a series of ketamine infusions

in two patients with treatment-resistant depression.

J Neuropsychiatry Clin Neurosci. 2010;22(4):442-444.

5. Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R,

et al. A randomized trial of an N-methyl-D-aspartate

antagonist in treatment-resistant major depression.

Arch Gen Psychiatry 2006 Aug; 63(8):856-864.

Figure 1. The pathway of ketamine’s antidepressant action has been tested in rat models. Increased mobility during a forced swim test was one of three behaviors observed in a recent study.

R EF E R E NC E S


D E v E L O P i n G T R E a T M E n T S


Deep Brain Stimulation to Modulate the Affective Component of Thalamic Pain Syndrome

By Donald a. Malone Jr., MD, and andre G. Machado, MD, PhD

Researchers in Cleveland Clinic’s Neurological Institute

are collaborating to investigate a novel approach for

managing severe, refractory central pain syndrome

that builds upon our understanding of chronic pain

pathways and research into a surgical therapy for

selected psychiatric disorders.

Depression Research Lays Groundwork

Chronic pain has not only a somatosensory sphere,

but also an affective and cognitive component that is

important, as proposed by Melzack’s neuromatrix theory.

In our ongoing investigation, we are evaluating whether

deep brain stimulation (DBS) of the ventral anterior limb

of the internal capsule and the adjacent ventral striatum

(VC/VS) will modulate the affective component of thalamic

pain syndrome and, consequently, reduce pain-related

disability.

Funded by a $1.5 million grant from the National

Institutes of Health, this pioneering approach marks the

first use of DBS of the VC/VS for management of central

pain. It is informed by the work of multicenter collabora-

tive research, including Cleveland Clinic, which has

evaluated stimulation of the VC/VS for treatment of

disabling depression and obsessive-compulsive disorder

(OCD). Based on encouraging data, the Food and Drug

Administration approved DBS in 2009 for use in refractory

OCD under a humanitarian device exemption.

Our Cleveland Clinic team partnered with colleagues

from Brown Medical School and Massachusetts General

Hospital to evaluate DBS of the VC/VS in patients with

chronic, severe, treatment-resistant depression, a more

common condition. Our initial experience in this area

demonstrated that it is possible to modulate the brain

circuits related to control of mood. Moreover, this work

suggests that targeting the VC/VS region is safe. Further

research on DBS in larger populations with treatment-

resistant depression is under way.

a new neuromodulatory approach for Thalamic Pain

Surgery, including deep brain stimulation, for patients

with refractory pain has been attempted over many years,

but the most effective option has yet to be determined.

DBS of the periventricular gray area, sensory thalamus or

motor cortex showed some promise in a small number of

patients with refractory pain disorders, but tended to fail

more in patients with central pain syndromes. Results

were far from the consistency seen in DBS for movement

disorders or in other neuromodulatory approaches for

peripheral neuropathic syndromes.

Our double-blind study is enrolling 10 patients with

central pain who have experienced severe pain for

more than six months and are considered refractory

to treatment attempts with conventional medications

and other surgical procedures. These patients will

undergo bilateral DBS surgery, with implantation under

sedation of one lead on either side of the brain. Each

lead has four contacts placed from dorsal to ventral

positions (Figure 1).

Programming titration of the leads occurs after implan-

tation. Stimulation parameters will be adjusted while

patients are questioned regarding mood, anxiety and

suffering to indicate whether we are effectively modulating

the neural circuits of the brain that process mood and

the affective sphere of pain, while minimizing possible

side effects.

After initial titration, patients will be randomized to

receive three months of active or sham stimulation

and then crossed over for an additional three months.

Monthly evaluations will determine the effectiveness of

DBS. Following the six-month evaluation period, patients

will undergo 18 months of open-label stimulation.

The Pain Disability Index is the primary outcome measure,

but the visual analog scale wil also be used along with

other scales. The intent is not to focus primarily on how

much DBS can alleviate pain intensity — which can be

difficult to measure in patients with chronic pain — but,

rather, to evaluate how much DBS of the VC/VS region can

alleviate pain-related suffering and disability.

Donald A. Malone Jr., MD, is Chairman of the Department

of Psychiatry and Psychology and Director of Cleveland

Clinic’s Center for Behavioral Health. He also serves as

Director of the Psychiatric Neuromodulation Center. His

research interests include deep brain stimulation for

psychiatric disorders. He can be contacted at 216.444.5817

or at [email protected].

Andre G. Machado, MD, PhD, is Director of the Center for

Neurological Restoration at Cleveland Clinic. His specialty

interests are deep brain stimulation for Parkinson’s disease,

essential tremor, dystonia and other movement disorders,

as well as emerging deep brain stimulation therapies for

central pain, obsessive-compulsive disorder, depression and

stroke rehabilitation. He can be contacted at 216.444.4270

or at [email protected]. S U G GE S T E D R E A DI NG

S U G GE S T E D R E A DI NG

1. Machado AM, Haber S, Sears N, et al. functional topography of the ventral striatum and anterior limb of the internal capsule determined by electrical stimulation of awake patients. Clin Neurophysiol. 2009 Nov;120(11):1941-48.

2. Malone dA Jr. Use of deep brain stimulation in treatment- resistant depression. Cleve Clin J Med. 2010 Jul;77(Suppl 3):S77-S80.

3. Melzack R. Pain and the neuromatrix in the brain. J Dent Educ. 2001;65(12):1378-1382.

Figure 1. In this view, DBS leads are targeted at the striatum ventral to the anterior commissure. The trajectory courses through the anterior limb of the internal capsule. The head of the caudate nucleus on the left side and the globus pallidus on the right side are labeled.

D E v E L O P i n G T R E a T M E n T S

Central thalamic pain syndrome is an often-severe form of chronic pain, usually caused by damage to the central

nervous system as a result of stroke or traumatic injury of the brain or spinal cord. The pain is usually described as

constant, often characterized by burning or aching. Typically, it affects one entire side of the body but some patients

have predominant pain in the upper or lower extremities. Symptoms may not appear for weeks or months after the

initial injury or trauma, complicating diagnosis and treatment.


Identifying depression in Epilepsy Patients for Better Outcomes

By George E. Tesar, MD

In 400 B.C.E., Hippocrates wrote On the Sacred Disease,

a paper exploring what is now known as epilepsy.

Physicians once believed the disorder was spiritual or

demonic in nature — divine or evil beings fought over a

person’s soul, causing the seizures and visions. Modern

doctors certainly have a better understanding of epilepsy,

yet a few mysteries still cloak the disease. One of these

present enigmas concerns the comorbidity of epilepsy

and depression.

Hippocrates also recognized the coexistence of the two

disorders. A number of common psychiatric disorders

prevalent in the general population (anxiety, attention-

deficit/hyperactivity, and psychoses) are four to five times

more common in patients with epilepsy, with published

rates of depression from 20 to 50 percent.

Despite these findings, depression often goes undetected

and untreated. Time factors, focus on the epilepsy, and

patient reluctance to identify depression as a problem

contribute. The treatment of depression in primary care

has been studied extensively, and it has been well-estab-

lished that detection of depression does not by itself

improve treatment outcome; care services must be designed

to facilitate treatment. The KP, focused on detection and

serial measurement of outcomes, is therefore a necessary

first step, although insufficient by itself, in tackling this

problem in patients with epilepsy.

In 2007, the Epilepsy Center was among the first of the

Neurological Institute’s 18 centers to start collecting KP

data. The process involves data collection — mostly from

the patients — at the point of care. When checking in for

an appointment, the patient is asked to complete center-

specific questionnaires. Responses are entered by the

patient (or an assistant) on a touch-screen tablet computer.

The tablet is then returned to desk personnel for up-load-

ing of the collected data so it can be viewed in Epic,

the Clinic’s electronic medical record, allowing the

patient’s clinician access to survey responses during the

clinical encounter.

Each center selects survey instruments specific to the

needs of its patients. All Neurological Institute patients,

including those of the Epilepsy Center, complete two

questionnaires: the European Quality of Life-5 Dimen-

sions short form and the Patient Health Questionnaire

(PHQ-9), a diagnostic scale ranked from 0 to 27 that

assesses presence and severity of depression symptoms.

Used extensively in primary care, the scale is designed to

detect major depressive disorder (MDD) as defined in the

Diagnostic and Statistical Manual of the American

Psychiatric Association. Scores of 10 or higher have been

shown to correlate with MDD. In the Epilepsy Center,

patients complete a number of other survey instruments,

including the Liverpool Seizure Severity Scale and the

Quality of Life in Epilepsy Scale, a 10-point scale

evaluating overall satisfaction in life.

Recently we performed a retrospective review of these

data in a sample of 2,015 patients who made 5,732 visits

to the Epilepsy Center from January 1, 2009, to December

31, 2009. Seventy percent accounted for one or more

visits, with 2 percent attending eight or more appoint-

ments. The analysis included demographic data as well

as driving status, epilepsy type (focal, generalized or

undefined), number of anti-epileptic drugs and antide-

pressant medication use.

Four hundred seventy-six patients (23.6 percent)

suffered from at least a moderate degree of self-rated

depression. Two hundred forty-six (12.2 percent) rated

their depressive symptoms as moderate, 142 (7 percent)

as moderate-to-severe, and 88 (4.4 percent) as severe.

According to the National Institute of Mental Health,

the 12-month prevalence of depression in the adult

general population is 6.7 percent, with a mean lifetime

prevalence of 16.5 percent.

T O W a R D W E L L n E S S T O W a R D W E L L n E S S

at Cleveland Clinic, physicians treating patients with epilepsy regularly use the neurological institute’s Knowledge

Program (KP) to assess psychiatric comorbidities commonly associated with epilepsy. Depressive disorders are

the most common. Routine depression screening and serial measurement of depression provide valuable data

toward understanding the relationship between epilepsy and depression and optimal treatment, promoting better

overall outcomes.

Predictors of clinically significant depression included

being older, African-American, single and unable to

drive. These data were presented at the 64th Annual

Meeting of the American Epilepsy Society in late 2010 and

are being prepared for publication.

As far as we know, this is the largest study of depression

detection in epilepsy patients using a highly efficient,

clinically relevant survey tool. Our results focus on the

importance of detection as a first step.

Because some patients are offended by the “depression”

label, it is imperative that doctors approach any discus-

sion of the problem with sensitivity. Epileptologists have

become increasingly sophisticated in their detection and

management of depression as more attention has been

devoted to it in the literature and here at Cleveland Clinic.

The problems already cited that interfere with optimal

management have encouraged us to develop strategies

promoting seamless integration of epilepsy and psychiat-

ric services. Plans are under way to increase trainee

exposure to and involvement in this exciting example

of integrated healthcare.

George E. Tesar, MD, is Director, Psychiatry Residency

Program at Cleveland Clinic’s Center for Behavioral Health,

and a staff member at Cleveland Clinic Epilepsy Center.

His specialty interests include emergency psychiatry, anxiety

and epilepsy psychiatry, mood disorders, consultation-liaison

psychiatry, and neuropsychiatry. He can be reached at


The mean PHQ-9 score improved from 7.9 (± 0.3) at the initial visit to 6.0 (± 0.3) at the last follow-up visit, reflecting a 25 percent reduction in depression score severity (P < 0.0001). The standard box plots reflect the median and the 25th and 75th quartiles. N = adult epilepsy patients treated with medications only and with greater than six months of follow-up. Mean duration of follow-up was 12.4 months.

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10

0

27

PHQ-9 ScoreDepression

ImprovedInitial Follow-up

Visit


T O W a R D W E L L n E S S


Psychosocial Predictors of Weight Loss Following Bariatric Surgery

By Leslie J. heinberg, PhD

The behavioral health team of psychologists at Cleveland

Clinic’s Bariatric and Metabolic Institute has a robust

research and clinical program designed to better identify

and treat psychosocial risk factors related to poorer

outcomes. Rather than conceptualizing such factors as

clear-cut contraindications, we attempt to manage and

minimize these risks so that the majority of patients can

reach surgery and achieve their goals. The following

reflects a sample of the research being conducted by our

behavioral health team.

We examined postoperative excess weight loss in 106

patients who underwent laparoscopic sleeve gastrectomy,

comparing patients who met criteria for a current mood

disorder with those who did not have a psychiatric

diagnosis.3 Although marked weight loss in the first year

was experienced by both groups, patients with a mood

disorder had lost significantly less excess weight at one-,

three-, six- and nine-month follow-up (Figure 1). These

results highlight the importance of psychiatric assess-

ment in bariatric patients. Those with current or lifetime

histories of mood disorder may need additional pre- and

postoperative care to improve outcomes.

Previously, our team developed the Cleveland Clinic

Behavioral Rating System (CCBRS)4 as a multidimensional

tool for the psychological assessment of presurgical

bariatric candidates. Our more recent work examined

whether psychological ratings were associated with

nonspecific complications and regret one month post-

operatively in 139 bariatric patients. We found that

patients who endorsed significant nausea and/or regretted

having surgery had received significantly lower social

support ratings on the CCBRS. Further, patients reporting

dehydration had been rated significantly lower on

adherence. The results demonstrated that ratings at the

time of psychological evaluation may help identify

patients’ nonspecific complications, nonadherence with

fluid intake and postoperative regret. We hope our future

work will help inform treatment recommendations and

postoperative intervention for patients determined to be

at risk.

Another area of interest is the impact of past problematic

alcohol or drug use on postbariatric surgery outcomes.

Research indicates that a lifetime history of any substance

use disorder is significantly higher in weight loss surgery

candidates than the population base rate.5 Forty-five

patients with a history of substance abuse/dependence

were compared with 386 patients without a substance

abuse/dependence history. The groups did not differ in

type of surgery or body mass index (BMI) change at one- and

three-month follow-up. However, after we controlled for

their baseline BMI, patients with a substance abuse history

had significantly greater BMI reductions at six-, nine- and

12-month follow-up. Thus, somewhat surprisingly, patients

with a substance abuse/dependence history had greater

BMI reductions from six months onward. Our results

indicate that a history of substance abuse/dependence

should not be considered a surgical contraindication,

and may demonstrate a patient’s ability to make significant

lifestyle changes.

Bariatric behavioral health is a relatively new field and

much of the research is in its infancy. Our collaborative,

multidisciplinary team at Cleveland Clinic affords us

the opportunity to add to the knowledge base and help

optimize outcomes for our patients.

Leslie J. Heinberg, PhD, is Director of Behavioral Services

for the Bariatric and Metabolic Institute at Cleveland

Clinic and Associate Professor of Medicine at Cleveland

Clinic Lerner College of Medicine of Case Western Reserve

University. Her specialty interests include obesity,

disordered eating behaviors and body image. She can be

contacted at 216.445.1986 or at [email protected].

R EF E R E NC E S

1. Garb J, Welch G, Zagarins S, Kuhn J, Romanelli J.

Bariatric surgery for the treatment of morbid obesity:

a meta-analysis of weight loss outcomes for laparo-

scopic adjustable gastric banding and laparoscopic

gastric bypass. Obes Surg. 2009 Oct;19(10):1447-1455.

2. Magro DO, Geloneze B, Delfini R, Pareja BC, Callejas F,

Pareja JC. Long-term weight regain after gastric bypass:

a 5-year prospective study. Obes Surg. 2008 Jun;18(6):

648-651.

3. Semanscin-Doerr D, Windover A, Ashton K, Heinberg

LJ. Mood disorders in laparoscopic sleeve gastrectomy

patients: does it affect early weight loss? Surg Obes

Relat Dis. 2010 Mar 4;6(2):191-196.

4. Heinberg L J, Ashton K, Windover A. Moving beyond

dichotomous psychological evaluation: the Cleveland

Clinic Behavioral Rating System for weight loss surgery.

Surg Obes Relat Dis. 2010 Mar 4;6(2):185-190.

5. Heinberg LJ, Ashton K. History of substance abuse

relates to improved postbariatric body mass index

outcomes. Surg Obes Relat Dis. 2010 Jul-Aug;6(4):417-421.

T O W a R D W E L L n E S S

Figure 1. Patients with lifetime mood disorders lost excess body weight more slowly in the first month post-surgery, but were able to catch up to patients with no psychiatric diagnoses at three- and six-month follow-ups. However, these patients were not able to maintain this weight loss progress over longer periods of time, losing significantly less percentage excess weight loss at nine- and 12-month follow-ups.

Features of depressive disorders, such as memory and concentration problems, may be affecting post-surgical outcomes. Additionally, they may overeat to manage their mood, or may lack energy or motivation to engage in physical activity. Many anti-depressant medications also have weight gain as a side effect.

10

20

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40

50

12 mo9 mo6 mo3 mo1 mo

Bariatric surgery is the most effective treatment for severe obesity and is associated with the most sustained weight

loss.1 Yet bariatric surgery requires permanent lifestyle change, and a sizable minority of patients experience suboptimal

weight loss (< 50 percent of excess body weight) or weight regain.2 although various putative biological mechanisms have

been investigated to explain these outcomes, the majority of empirical findings support psychosocial and behavioral

factors. Such factors include resumption of overeating (particularly loss-of-control eating), lack of physical activity,

psychiatric comorbidity, eating psychopathology and problems with behavioral adherence.


Nonadherent behaviors, such as failure to show up for

appointments, take prescribed medications or follow

the treatment plan are also indicators of depression or

anxiety. We attempt to determine the underlying cause

and work to resolve the situation.

The interdisciplinary, multispecialty approach at Cleveland

Clinic is an ideal setting to address the psychosocial

aspects of a patient’s cancer care. Our clinic is based in

Taussig Cancer Institute, where we work closely with

oncologists, a team of eight social workers, with support

from nutritionists, and with access to services that provide

spiritual support. The institute’s recent emphasis on

psychosocial oncology has resulted in greater collabora-

tion among practitioners of all disciplines, and our goal

is to significantly reduce wait time for referrals for these

services, when necessary, referring patients to providers

beyond the Cleveland Clinic health system.

Cancer patients who suffer from

depression have higher pain levels,

longer hospital stays and impaired

quality of life when compared to

non-depressed cancer patients.

Depression can be successfully

treated, but the first step is making

the diagnosis.


C O L L a B O R a T i v E C a R E

Cancer patients who suffer from depression have higher

pain levels, longer hospital stays and impaired quality of

life when compared to non-depressed cancer patients.

Depression can be successfully treated, but the first step

is making the diagnosis.

Fortunately, a recent educational emphasis on psycho-

oncology has resulted in a major philosophical change

based in part on animal model research demonstrating

that cancer, regardless of its location, can change the

brain chemistry to a distressed state. Thus, it is not only

the stress of cancer that causes depression; the disease

itself may be causing chemical changes in the brain,

resulting in higher rates of depression and anxiety.

To address this population’s unique emotional needs,

the Psychosocial Oncology team at Cleveland Clinic’s

Taussig Cancer Institute is developing an approach,

including a social work triage clinic to facilitate access

to psychosocial services, ensuring that patients do not

become lost in the system and suffer further distress.

Plans include a protocol designed for timely referrals

to the staff psychiatrist, social workers or other mental

health professionals if the patient’s insurance coverage

is outside our network.

Several valid screening tools for identifying depression

exist, including the PHQ-9 depression screen and the

Distress Thermometer, developed by the National

Comprehensive Cancer Network to address physical,

emotional and spiritual health and family problems,

as well as practical problems related to housing, child

care and transportation. These tools provide an extremely

helpful, nonjudgmental way to identify underlying issues.

We are currently administering these tools to patients

referred for psychiatric evaluation within the Taussig

Cancer Institute.

Behavioral Health Interventions for Cancer Patients

Depression is a disabling comorbidity affecting 20 to 47 percent of cancer patients, while another 22 percent experience

anxiety. Yet, caregivers frequently overlook the symptoms, missing an opportunity to improve patients’ quality of life and

increase medical adherence. it is estimated that depressed patients are three times more likely to be non-adherent.

By isabel Schuermeyer, MD

Our Psychosocial Oncology Program continues to

educate caregivers on clinical symptoms seen in

depression. Annual seminars and smaller group

sessions focus on how depression and/or anxiety can

affect compliance, how to ask patients about their

mood, and how to appropriately use and evaluate

antidepressants and dosing.

One of the results has been that oncologists and other

healthcare providers are becoming increasingly comfort-

able discussing psychosocial issues and recognize when

a patient has depression. The Psychosocial Oncology

Program is working toward the goal of making sure

distressed patients never have to wait more than one

week to be seen by a mental health professional.

Increasingly, oncologists include documentation about

depression and ask us to help clarify specific cases,

especially when patients are resistant to an intervention

by a mental health specialist. While most of our oncolo-

gists are comfortable treating depression or anxiety, our

program has experienced a significant increase in referrals.

My own referrals are often those who fail initial treatment

of depression or who are experiencing non-depressive

disorders, such as steroid-induced mania, psychosis,

memory impairment, fatigue or organic personality change.

Inevitably, barriers remain. Some medical professionals

are uncomfortable or lack training in mental health

problems related to cancer patients. Popular culture

portrays these patients as “warriors” who do everything

they can to beat cancer, and patients may be afraid to

admit depression because they do not want to appear

weak. In addition, some physicians harbor the misconcep-

tion that all cancer patients are depressed, that depression

is normal and treatment does not help. Finally, physicians

may be unsure of how to diagnose depression, may not

take the time to screen their patients or may fail to

monitor patients if they do prescribe antidepressants.

The interdisciplinary, multispecialty

approach at Cleveland Clinic is

an ideal setting to address the

psychosocial aspects of a patient’s

cancer care. Our clinic is based in

Taussig Cancer Institute, where

we work closely with oncologists,

a team of eight social workers,

with support from nutritionists,

and with access to services that

provide spiritual support.

A significant component of cancer care is recognition

that depression and anxiety must be aggressively treated

because individuals with high levels of distress manifest

slower recovery and increased morbidity and mortality.

All cancer patients should be screened for psychosocial

issues with the goal of enhancing their treatment

adherence and improving their quality of life.

Isabel Schuermeyer, MD, is a staff psychiatrist at Cleveland

Clinic’s Center for Behavioral Health. Her specialty interests

include psycho-oncology and treatment of patients with

psychiatric complications from neurological disorders

and cancer. She can be contacted at 216.444.5965 or at

[email protected].





Innovative Interventions for Youth with Epilepsy: Project COPE

By Tatiana falcone, MD

Lifetime prevalence of depression in the general population

is about 3.7 to 6.7 percent, but in patients with epilepsy it

can be as high as 22 percent. Higher rates of depression

are also reported in younger patients with epilepsy. Suicidal

ideation is another major problem for patients with

epilepsy, with a rate nearly double that of the general

population, at around 25 percent. Previous studies linked

suicidal ideation to antiepileptic medications; however,

further research demonstrated that it was related to the

high incidence of depression and the time between the

first symptoms and referral for treatment.

Further, a survey of mental health problems in the general

population found that only 4 percent of youth struggle

compared to nearly 17 percent of youth with epilepsy.1-3

Services for these children and their families vary

according to different state regulations, but even when

fully available, most families do not discover or access

such services during early stages when they are most

effective. The most important factor determining access

to healthcare is insurance coverage. In Ohio, children

residing in households with income less than 200 percent

of the federal poverty level are eligible for Medicaid, but

in 2008, only 6.2 percent of children with special health

care needs (CSHCN) in Ohio were insured.4,5

Project COPE (Collaboration for Outreach and Prevention

Education for Children with Epilepsy) was funded with

a generous contribution by the Health Resources and

Services Administration (HRSA) Maternal and Child

Health Bureau to conduct a needs assessment of 359

families. We learned from the survey that parents deeply

felt that a lack of access to educational services was a

major barrier for youth with epilepsy. Some of the parents

expressed a complete lack of knowledge of any of the

educational services available for youth with epilepsy.

They also reported difficulty being good advocates for

their children at school.

The survey further found that 70 percent of our patients

(191 of 274) felt that they had very little understanding of

epilepsy and felt sad, frustrated and overwhelmed after

hearing the diagnosis. Many of their concerns were related

to quality of life, poor seizure control and psychiatric

comorbidities.

In an attempt to bridge the gap between lack of access

to services and early recognition of mental health

comorbidities in youth with epilepsy, a program was

designed as part of Project COPE to help this youth

population and their parents.

Parental sessions focused on:

• Breakingdownbarriers(perceptions,stigmasand

misconceptions about epilepsy and mental health)

• Recognizingthewarningsignsofbehavioraland

health issues that children with epilepsy face

• Effectivelyparentingateenagerwhohasepilepsy

• Encouragingahealthymind

Teen sessions focused on:

• Livingwithepilepsyandtheimportanceofemotional

wellness

• Developingahealthyteenidentity

• Socialproblemsolving

• Takingresponsibilityforwellness

We will be collecting outcome indicators to assess quality

of life, psychiatric comorbidities (anxiety, depression,

suicidal tendencies), coping, and parenting styles in this

group of patients and parents both before and after the

program. Three interventions will be delivered every year

for three years.

An additional program aimed at decreasing bullying at

inner-city schools is currently being developed to target

some of the classrooms where youth with epilepsy attend.

There are important, under-recognized, unmet needs in

youth with epilepsy. Psychoeducation is an important

part of the strategy for helping families cope with some

of the comorbidities these patients face. Although many

services are provided in our communities, parents and

children often do not know about these services and fail

to take advantage of them. Engaging providers to discuss

the services with families will help parents gain access

to mental health services. Together, we can help decrease

the stigma associated with this disease and improve

access to mental health services for youth with epilepsy.


Tatiana Falcone, MD, is a staff member at both Cleveland

Clinic Epilepsy Center and Cleveland Clinic’s Center

for Behavioral Health. Dr. Falcone is doing research in

psychiatric comorbidities in epilepsy and biomarkers in

mood disorders and schizophrenia. She can be reached at


R EF E R E NC E S

1. Austin JK, Caplan R. Behavioral and psychiatric

comorbidities in pediatric epilepsy: toward an

integrative model. Epilepsia. 2007; 48:1639-1651.

2. Plioplys S, Dunn DW, Caplan R. 10-year research

update review: psychiatric problems in children with

epilepsy. J Am Acad of Child & Adol Psych. 2007;46:

1389-1402.

3. Hampton T. Experts describe “spectrum” of epilepsy.

JAMA; 2010:303(4):313-314.

4. Ohio Family Health Survey. Health Policy Institute

of Ohio. 2008. http://grc.osu.edu/ofhs.

5. Goodie A, Fairbrother G, Simpson L, Mandel K. Profile

of children with special health care needs in Ohio.

OFHS. Child Policy Research Center. p1-53 http://www.

cincinnatichildrens.org/assets/0/78/1067/1395/1833/

1835/9810/306c09d5-1af0-4f21-ac0a-8ebb0457728f.pdf.

0

20

40

60

80

100

MoodIssues

CognitiveProblems

LearningProblems

BehaviorProblems

ADHD

Despite all the advances in epilepsy research, the quality of life for children with epilepsy, even for those who reach

seizure freedom, is not as high as it should be. Young people with epilepsy have increased mental health needs compared

with the general population.


C a R E G i v i n G


Comprehensive Care of Motor, Psychiatric and Cognitive deficits in Huntington’s disease

By Mayur Pandya, DO

Huntington’s disease (HD) is a neurodegenerative illness

with an autosomal-dominant mode of genetic inheritance,

making it both a family burden and a generational curse.

Confirmatory diagnosis is made through DNA genetic

testing of cytosine-adenine-guanine (CAG) repeat lengths,

with 40 or more repeats being diagnostic (Figure 1). The

average life span is 10 to 20 years following the onset of

symptoms, with a deteriorating course. In light of this

relatively rapid decline and the degree of impact from one

generation to the next, the need for comprehensive care

for patients and families is paramount.

an assault on Body and Mind

HD has three primary domains of deficit: motor,

psychiatric and cognitive. Chorea is the distinguishing

and most closely associated motor symptom, although

some patients may present with an absence of voluntary

movements, as with parkinsonism and dystonia. The

risk of falls from the changes in volitional movement is

a source of significant distress and concern for patients

and families, especially when other deficits arise.

The psychiatric and cognitive symptoms may be as, if

not more, debilitating than the motor symptoms in HD.

Psychiatric deficits may range from affective symptoms

(depression, anxiety, mania) to thought and perceptual

disturbances (delusional ideation, auditory or visual

hallucinations) to changes in behavior (disorganization,

apathy). Cognitively, patients with HD develop a dysex-

ecutive syndrome, characterized initially by difficulties

with planning, organizing and cognitive flexibility, but

relentlessly progressing to global dementia. Many new

HD patients may present for psychiatric care prior to

diagnosis, as these symptoms typically predate the onset

of motor symptoms.

Comprehensive Care Model

At Cleveland Clinic, we offer an HD clinic to address the

multifactorial domains of illness that present in HD. This

multidisciplinary clinic provides comprehensive care

for patients and families dealing with this disease. Our

team comprises healthcare providers from neurology,

psychiatry, neuropsychology, genetics, physical therapy,

occupational therapy and speech therapy, who work in a

coordinated fashion to assess the physical, emotional,

cognitive and behavioral needs of patients with Hunting-

ton’s disease. We address issues such as chorea, depression,

nutritional needs and swallowing disorders as well as

practical concerns such as safety in the home. In the

more advanced stages, a discussion of end-of-life manage-

ment and comfort is a necessary and important aspect

of care.

One advantage of a comprehensive care model is the

ability to provide a wide range of services to patients and

families at each visit in the most efficient way possible.

The structure of our HD clinic allows for face-to-face

discussions and debriefings among providers after each

patient visit. Genetic counseling helps to address the

complex issues that arise when individuals first consider

genetic testing. The opportunity to educate and to offer

emotional and psychological support to both patients

and families is invaluable.

C a R E G i v i n G

“…there seems to exist some hidden power, something that is playing tricks, as it were, upon the will…”

– George Huntington, MD

Community Collaboration

In addition to offering opportunities for participation

in clinical research trials, our team at Cleveland Clinic

is in the process of joining a more extensive program of

collaborative care through the formation of a Northeast

Ohio Coalition for Huntington’s Disease. Through an

alliance with the local Huntington’s Disease Society of

America chapter and various community agencies and

resources, we aim to create a uniform standard of clinical

care for all patients with Huntington’s disease and to

provide equal opportunities for participation in clinical

trials, educational initiatives and HD community efforts,

regardless of where patients seek medical care.

Currently, there are three active HD trials at Cleveland

Clinic: PREDICT-HD, CREST-E and 2CARE. The goal of

the PREDICT-HD study is to define the earliest biological

and clinical features of HD to help design future studies

of experimental drugs aimed at slowing or postponing

the onset in healthy persons at risk for developing HD.

CREST-E and 2CARE are drug trials (creatinine and

CoQ10, respectively) looking at the ways to slow the

progression of HD.

Future collaborative projects include working in close

contact with our parallel multidisciplinary HD clinic at

Cleveland Clinic Lou Ruvo Center for Brain Health in

Las Vegas, as well as participation in a worldwide initative

called ENROLL-HD, which is a prospective registry study

aimed at accelerating the development of therapies for

HD by compiling uniform clinical data and biological

samples and building a comprehensive database of

HD information.

Our hope is that these collaborative efforts will culminate

in standardized care and therapeutic advances that lead,

in turn, to neuroprotective discoveries and potentially

disease-modifying or arresting therapies for this

devastating condition.

Mayur Pandya, DO, is Director of the comprehensive HD

clinic at Cleveland Clinic , and a staff member at both

Cleveland Clinic’s Center for Behavioral Health and

Cleveland Clinic’s Center for Neurological Restoration. His

specialty interests include psychiatric and behavioral issues

in movement disorders, treatment-resistant depression,

obsessive-compulsive disorder and medical education. He

can be contacted at 216.445.5585 or at [email protected].

Figure 1. The present research efforts in HD aim to target the proposed mechanisms of pathogenesis and degeneration, believed to be a result of mutant Huntingtin (HTT) protein generated from abnormal CAG repeat length expansion on the HTT gene. Research studies at Cleveland Clinic, such as 2CARE and CREST-E, aim to investigate the antioxidative effects in hopes of discovering neuroprotective benefits.

The haunting and enigmatic nature of huntington’s disease is captured in this statement taken from Dr. huntington’s

1872 address at Meigs and Mason academy of Medicine in Middleport, Ohio. as a result of his classic description, the

disorder was later named after him.

Staff Listing

Center for Behavioral Health

Donald a. Malone Jr., MD

Director, Center for Behavioral Health

Professor and Chairman, Department of Psychiatry and Psychology

Susan albers-Bowling, PsyD

Kathleen ashton, PhD

Joseph M. austerman, DO

Joseph Baskin, MD

Scott Bea, PsyD

Minnie Bowers, MD

Dana Brendza, PsyD

Karen Broer, PhD

Robyn Busch, PhD

Kathy Coffman, MD

Gregory Collins, MD

Edward Covington, MD

Roman Dale, MD

Syma Dar, MD

Beth Dixon, PsyD

Judy Dodds, PhD

Michelle Drerup, PhD

Jung El-Mallawany, MD

Tatiana falcone, MD

Lara feldman, DO

Darlene floden, PhD

Kathleen franco, MD

Margo funk, MD

John P. Glazer, MD

Lilian Gonsalves, MD

J. Robert Gribble, PhD

Jennifer haut, PhD, aBPP-Cn

Leslie heinberg, PhD

Kelly huffman, PhD

Karen Jacobs, DO

Joseph W. Janesz, PhD, LiCDC

amir Jassani, PhD

Jason Jerry, MD

Regina Josell, PsyD

Elias Khawan, MD

Patricia Klaas, PhD

Olga Kostenko, MD

Steven Krause, PhD, MBa

Cynthia S. Kubu, PhD, aBPP-Cn

Michael McKee, PhD


P U B L i C a T i O n S

2010 – 2011

Publications of the Center for Behavioral Health

Journal Publications

Baldessarini RJ, Viguera AC. Perinatal screening for

depression. Am J Obstet Gynecol. 2010 Aug;203(2):e16.

Bangdiwala SI, Brown SS, Cunningham FG, Dean TM,

Frederiksen M, Hogue CJ, King TL, Lukacz ES, McCullough

LB, Nicholson W, Petit NF, Probstfield JL, Viguera AC, Wong

CA, Zimmet SC. NIH consensus development conference

draft statement on vaginal birth after cesarean: new

insights. NIH Consens State Sci Statements. 2010 Mar 10;27:3.

Bea SM. Some thoughts about thoughts and mental health. Bar

J Cleve Metropolitan Bar Assoc. 2011;3(6):33-34.

Busch RM, Floden D, Lineweaver TT, Chapin JS, Unnwongse K,

Wehner T, Diaz-Arrastia R, Najm IM. Effect of APOE 4 allele

on hippocampal and brain volume in intractable temporal

lobe epilepsy. Epilepsy Behav. 2011 May;21:88-90.

Cohen LS, Wang B, Nonacs R, Viguera AC, Lemon EL, Freeman

MP. Treatment of mood disorders during pregnancy and

postpartum. Psychiatr Clin N Am. 2010 Jun;33(2):273-93.

Cusin C, Evans KC, Carpenter LL, Greenberg BD, Malone DA,

Eskandar E, Dougherty DD. Deep brain stimulation for

treatment resistant depression: the role of the ventral

capsule/ventral striatum. Psychiatr Ann. 2010;40(10):496-502.

Diehl B, Piao Z, Tkach J, Busch RM, LaPresto E, Najm I,

Bingaman W, Duncan J, Lüders HO. Cortical stimulation

for language mapping in focal epilepsy: correlations with

tractography of the arcuate fasciculus. Epilepsia. 2010

Apr;51(4):639-646.

Fins JJ, Mayberg HS, Nuttin B, Kubu CS, Galert T, Sturm V,

Stoppenbrink K, Merkel R, Schlaepfer TE. Neuropsychiatric

deep brain stimulation research and the misuse of the

humanitarian device exemption. Health Aff. 2011

Feb;30(2):302-11.

Fins JJ, Schlaepfer TE, Nuttin B, Kubu CS, Galert T, Sturm V,

Merkel R, Mayberg HS. Ethical guidance for the management

of conflicts of interest for researchers, engineers and

clinicians engaged in the development of therapeutic deep

brain stimulation. J Neural Eng. 2011 Jun;8(3):033001. [Epub

ahead of print]

Floden D, Vallesi A, Stuss DT. Task context and frontal lobe

activation in the Stroop task. J Cogn Neurosci. 2011

Apr;23(4):867-879.

Fong JS, Jehi L, Najm I, Prayson RA, Busch RM, Bingaman W.

Seizure outcome and its predictors after temporal lobe

epilepsy surgery in patients with normal MRI. Epilepsia. 2011

Aug;52(8):1393-1401.

Frank DL, Khorshid L, Kiffer JF, Moravec CS, McKee MG.

Biofeedback in medicine: who, when, why and how? Ment

Health in Fam Med. 2010;7:85-91.

Greenberg BD, Gabriels LA, Malone DA, Rezai AR, Friehs GM,

Okun MS, Shapira NA, Foote KD, Cosyns PR, Kubu CS, Malloy

PF, Salloway SP, Giftakis JE, Rise MT, Machado AG, Baker KB,

Stypulkowski PH, Goodman WK, Rasmussen SA, Nuttin BJ.

Deep brain stimulation of the ventral internal capsule/

ventral striatum for obsessive-compulsive disorder:

worldwide experience. Mol Psychiatry. 2010 Jan;15:64-79.

Hicks C, Pandya M, Itin I, Fernandez HH. Valproate for the

treatment of medication-induced impulse-control disorders

in three patients with Parkinson’s disease. Parkinsonism

Relat Disord. 2011 Jun;17(5):379-81.

Joffe H, Petrillo LF, Koukopoulos A, Viguera AC, Hirschberg A,

Nonacs R, Somley B, Pasciullo E, White DP, Hall JE, Cohen

LS. Increased estradiol and improved sleep, but not hot

flashes, predict enhanced mood during the menopausal

transition. J Clin Endocrinol Metab. 2011 Jul;96(7):E1044-54.

Kovac S, Möddel G, Reinholz J, Alexopoulos AV, Syed T,

Koubeissi MZ, Schuele SU, Lineweaver T, Busch RM,

Loddenkemper T. Visual naming performance after ATL

resection: impact of atypical language dominance.

Neuropsychologia. 2010 Jun;48(7):2221-2225.

Lampert R, Hayes D, Annas G, Farley M, Goldstein N, Hamilton

R, Neal G, Kramer D, Muller P, Padeletti L, Pozuelo L,

Schoenfeld M, Vardas P, Wiegand D, Zeller R. HRS expert

consensus statement on the management of cardiovascular

implantable electronic devices (CIEDs) in patients nearing

end of life or requesting withdrawal of therapy. Heart

Rhythm. 2010 Jul;7(7):1008-1026.

Malone DA. Use of deep brain stimulation in treatment-

resistant depression. Cleve Clin J Med. 2010 Jul;77(3

Suppl):S77-80.

McKee MG. The burdens of caregiver stress: proceedings of the

2011 Heart-Brain Summit. Cleve Clinic J of Med. 2011 Aug;78(1

Suppl):S54-S64.

Muzina DJ, Malone DA, Bhandari I, Lulic R, Buadisch R, Keene

M. Rate of non-adherence prior to upward dose titration in

previously stable antidepressant users. J Affect Disord. 2011

Apr;130:46-52.

Newman CW, Sandridge SA, Bea SM, et al. Tinnitus: patients

do not have to ‘just live with it.’ Cleve Clin J Med. 2011

May;78(5):312-319.

Rajah MN, Crane D, Maillet D, Floden D. Similarities in the

patterns of prefrontal cortex activity during spatial and

temporal context memory retrieval after equating for task

structure and performance. NeuroImage. 2011 Jan;54(2):

1549-1564.

Wimbiscus M, Kostenko O, Malone D. MAO inhibitors: risks,

benefits and lore. Cleve Clin J Med. 2010 Dec;77(12):859-882.

Yoon DY, Dole A, Gonsalves L. Takotsubo (stress-induced)

cardiomyopathy in post-menopausal women.

Psychosomatics. 2011 Jul-Aug;52(4):375-378.

Zhang JP, Pozuelo L, Brennan DM, Hoar B, Hoogwerf BJ.

Association of SF-36 with coronary artery disease risk factors

and mortality: a PreCIS study. Prev Cardiol. 2010;13(3):

122-129.

Book Chapter

Brendza D. Taking a sexual history: if you don’t ask, your

patients probably won’t tell. In: Windover AK, Isaacson JH,

Pien L, Moore A, eds. Advanced Topics in Patient-Centered

Communication. OH; 2010:1-11.

Gene Morris, PhD

Kathryn Muzina, MD

Richard naugle, PhD

Mayur Pandya, DO

Michael Parsons, PhD

Leopoldo Pozuelo, MD

Kathleen Quinn, MD

Ted Raddell, PhD

Stephen Rao, PhD

Robert Rowney, DO

Balaji Saravanan, MD

Judith Scheman, PhD

isabel Schuermeyer, MD

Cynthia Seng, MD

Jean Simmons, PhD

Barry Simon, DO

Catherine Stenroos, PhD

David Streem, MD

amy Sullivan, PsyD

George E. Tesar, MD

Mackenzie varkula, DO

adele viguera, MD, MPh

John vitkus, PhD

Cynthia White, PsyD

Molly Wimbiscus, MD

amy Windover, PhD

P R E S E n T a T i O n S


2010 – 2011

Presentations of the Center for Behavioral Health

Albers S. The art of soothing yourself without food. Presented

at: Binge Eating Disorder Conference; March 31-April 1, 2011;

Scottsdale, Arizona.

Albers S. Mindful eating 101. Presented at: Florida Dietetic

Association Annual Symposium; July 17-20, 2011; Weston,

Florida.

Bongiolatti Bowen SR, Chapin JS, Busch RM, Haut JS, Klaas P,

Prayson RA, Bingaman WE. Left temporal resection in

pediatric epilepsy: neuropathology and memory outcome.

Presented at: 39th Annual International Neuropsychological

Society Meeting; February 2-5, 2011; Boston, Massachusetts.

Busch RM, Floden D, Lineweaver TT, Chapin JS, Unnwongse K,

Wehner T, Diaz-Arrastia R, Najm IM. APOE 4 is not related to

hippocampal or brain volume in patients with medically

intractable temporal lobe epilepsy. Presented at: 38th

Annual International Neuropsychological Society Meeting;

February 3-6, 2010; Acapulco, Mexico.

Busch RM, Frazier T, Diehl B, Alexopoulos A, Hamrahian A,

Unnwongse K, Naugle R, Kubu C, Tesar G, Najm I. Cortisol is

not related to depressive symptoms or mesial temporal

integrity in patients with medically intractable temporal

lobe epilepsy. Presented at: American Epilepsy Society

Meeting; December 3-7, 2010; San Antonio, Texas.

Chapin JS, Floden D, Busch RM, Klaas P, Naugle RI, Najm I.

Development of an equation to predict risk of verbal memory

decline after left temporal lobectomy. Presented at: 38th


February 3-6, 2010; Acapulco, Mexico.

Dixon BG, Schuermeyer I. Development of post-traumatic

stress disorder following a brain mass and secondary seizure

disorder. Presented at: American Psychosocial Oncology

Annual Conference; February 17-19, 2011; Anaheim,

California.

Falcone T. Bullying and epilepsy. Presented at: Annual Meeting

of the Epilepsy Association of Northeast Ohio; June 2011;

Cleveland, Ohio.

Falcone T, Bruce N, Fazio V, Janigro D. S100B as a marker for

suicidality in adolescents. Presented at: American Academy

of Child and Adolescent Psychiatry; October 26-31, 2010; New

York Hilton, New York.

Falcone T, Drexhage R, Steiner J, Dreshaj A, Franco K.

Inflammatory markers in psychiatric disorders. Presented

at: American Psychiatric Association Annual Meeting; May

14-18, 2011; Honolulu, Hawaii.

Falcone T, Fazio V, Franco K, Janigro D. Inflammatory markers

in youth with psychosis. Presented at: American Academy of

Child and Adolescent Psychiatry; October 26-31, 2010; New


Falcone T, Fazio V, Janigro D, Franco K. Inflammatory markers

in mood disorders in youth. Presented at: American Academy

of Child and Adolescent Psychiatry; October 26-31, 2010; New


Falcone T, Gallaher L, Blanks M, Rivera E, Sperry L. Needs

assessment for the epilepsy needs of the youth of Northeast

Ohio. Presented at: Learning Collaborative National Center

for Project Access, Epilepsy Foundation and Health

Resources and Services Administration; June 11-12, 2011;

Baltimore, Maryland.

Falcone T, Gallaher L, Kless B, Lachwani D. Preventing suicide

and bullying in adolescents. Presented at: ADAMHS Board;

May 2011; Cleveland, Ohio.

Falcone T, Gonsalves C, Steiner J, Uranova N. S100B in

psychiatric disorders. Presented at: Brazilian Society of

Neurosciences; September 8-11, 2011; Caxambu, Brazil.

Falcone T, Harris T. Suicide prevention and emotional

wellness. Presented at: Transformational Leadership in

Psychiatry; January 2011; St. Thomas, United States Virgin

Islands.

Falcone T, Kotagal P, McConville A. Psychiatric comorbidities

in patients with epilepsy. Presented at: School Nurses

Association of Ohio Annual Meeting; April 2011; Lakewood,

Ohio.

Falcone T, Schuermeyer I, Hatters S, Forgey M, Franco K. CL

issues across the life span. Presented at: American

Psychiatric Association Annual Meeting; May 14-18, 2011;

Honolulu, Hawaii.

Ferguson L, Busch RM, Lineweaver TT, Klaas P, Haut J.

Subjective versus objective memory in pediatric epilepsy:

caregivers’ memory ratings reflect objective memory

performance better than self-ratings. Presented at: American

Epilepsy Society Meeting; December 3-7, 2010; San Antonio,

Texas.

Ford P, Kubu CS. Ethics of control in DBS: consent and control

centered in patients’ values. Presented at: Annual American

Academy of Neurology Meeting; April 10-17, 2010; Toronto,

Ontario.


Ford P, Yee K, Kubu CS. Quality of life surgeries, patient values

and data: epilepsy surgery as a paradigm. Presented at: Brain

Matters 2 Conference; May 25-27, 2011; Montreal, Canada.

Foster M, Busch RM. The relationship of executive function

and working memory with recognition of emotion in

patients with temporal lobe epilepsy. Presented at: The

Cleveland Clinic Foundation Neurological Institute Research

Day; May 2011; Cleveland, Ohio.

Frank D, Baumann M, Khorshid L, Liebenstein M, Grossman-

McKee A, Kiffer J, McKee MG, Moravec CS. Biofeedback in

heart failure patients awaiting transplantation. Presented at:

Association for Applied Psychophysiology and Biofeedback

Annual Meeting; March 9-12, 2011; New Orleans, Louisiana.

Frank D, Baumann M, Liebenstein M, Khorshid L, Bolwell G,

Kiffer J, Tang W, Young JB, Starling RC, McKee MG, Moravec

CS. Biofeedback training in patients with advanced heart

failure. Presented at: Heart Failure Society of America

Annual Meeting; September 19, 2011; Boston,

Massachusetts.

Gale JT, Baker KB, Cash SS, Machado AG, Dougherty DD,

Stypulkowski P, Rezai A, Eskandar EN, Malone DA. Cortical

evoked potentials in response to deep brain stimulation for

depression. Presented at: Society of Biological Psychiatry;

May 2010; New Orleans, Louisiana.

Glazer JP, Fritz GK, Dyer CA. Changing illness beliefs in a

pediatric/child psychiatric day hospital setting: three cases.

Presented at: American Academy of Child and Adolescent

Psychiatry Annual Meeting; October 28, 2010; New York, New

York.

Khawam E. Depression, mood and behavior in living with MS.

Presented at: National MS Society “What’s Hot in MS”

Conference; October 9, 2010; Cleveland, Ohio.

Khawam E. Psychiatric aspects of MS. Presented at: Mellen

Center Update on Multiple Sclerosis Conference; June 24,

2011; Cleveland, Ohio.

Khawam E, Pandya M, Pozuelo L. Outpatient psychosomatic

medicine: the trainee’s perspective. Presented at: Academy of

Psychosomatic Medicine 57th Annual Meeting; November

11, 2010; Marco Island, Florida.

Klaas P, Mosher J. Mapping cortical responses in epilepsy

patients using MEG. Presented at: International

Neuropsychological Society Mid-Year Meeting; July 6-10,

2011; Auckland, New Zealand.

Klaas P, Tuxhorn I, Busch RM, Haut J, Bowen S. Gender

differences and memory performance in children with left

TLE. Presented at: American Epilepsy Society Meeting;

December 3-7, 2010; San Antonio, Texas.

Kubu CS. Outcomes following deep brain stimulation for

Parkinson’s disease: patients’ perspectives on control.

Presented at: Guidance for Responsible Research and

Application Meeting; January 2011; Bonn, Germany.

Kubu CS, Ford PJ. Beyond mere symptom relief: patients’

values and goals in deep brain stimulation for the treatment

of Parkinson’s disease. Presented at: Brain Matters 2

Conference; May 25-27, 2011; Montreal, Canada.

Lewis C, Tesar G, Dale RM. The role of carnitine

supplementation for valproate-induced hyperammonemic

encephalopathy in the psychiatric setting. Presented at:

Ninth International Conference on Bipolar Disorder; June

9-11, 2011; Pittsburgh, Pennsylvania.

Lewis C, Tesar G, Dale RM. Valproate-induced

hyperammonemia in patients with psychiatric diagnosis at

Lutheran Hospital between 2005-2009. Presented at: Ninth

International Conference on Bipolar Disorder; June 9-11,

2011; Pittsburgh, Pennsylvania.

Lineweaver TT, Haut JS, Kalman C, Ferguson L, Bongiolatti

Bowen S, Busch RM. Does mother know best? Self-reports

and parent-reports of memory in pediatric epilepsy patients

at two time points. Presented at: 39th Annual International

Neuropsychological Society Meeting; February 2-5, 2011;

Boston, Massachusetts.

Lujan JL, Chaturvedi MS, Malone DA, Rezai AR, McIntyre CC.

Axonal pathways activated by deep brain stimulation for

neuropsychiatric disorders and their correlation to

therapeutic outcomes. Presented at: Society for

Neuroscience; October 2009; Chicago, Illinois.

Malone DA, Beall EB, Sakaie KE, Szymkowicz S, Muzina DJ,

Dale RM, Phillips MD, Lowe MJ. White matter tract integrity

is not impaired by electroconvulsive therapy. Presented at:

Annual Meeting of International Society for ECT and

Neurostimulation; May 2011; Honolulu, Hawaii.

McKee MG, Moravec CS. Biofeedback for chronic disease.

Presented at: Bakken Heart Brain Institute Annual Meeting;

March 2011; Kona, Hawaii.

Menon U, Jehi L, Humbel D, Busch R, Tesar G, Najm I.

Psychiatric comorbidities and health care usage in patients

with non-epileptic seizures. Presented at: The Cleveland

Clinic Foundation Neurological Institute Research Day; May

2011; Cleveland, Ohio.

Muzina DJ, Keene M, Malone DA, Lulic R, Baudisch R,

Bhandari I. Rate of non-adherence prior to upward dose

titration in previously stable antidepressant users. Presented

at: Institute on Psychiatric Services; October 2010; Boston,

Massachusetts.

C



Pozuelo L. Behavioral risk factors and cardiovascular disease.

Presented at: Second Latin American Heart and Brain

Meeting; June 2011; Buenos Aires, Argentina.

Pozuelo L. Brain heart connections: fact or fiction? Presented

at: Cleveland Clinic Hot Topics in Healthcare; September

24-25, 2010; Las Vegas, Nevada.

Pozuelo L. Managing patients with high power devices:

discussion of the psychosocial issues and care plans.

Presented at: Allied Healthcare Professional Symposium;

May 2010; Denver, Colorado.

Pozuelo L. Patient provider connection panel discussion.

Presented at: Women and Heart Disease Summit,

Minneapolis Heart Institute Foundation; April 29-30, 2010;

Minneapolis, Minnesota.

Pozuelo L. Psychiatric aspects of syncope. Presented at: Heart

Rhythm Society 31st Annual Scientific Session; May 12-15,

2010; Denver, Colorado.

Pozuelo L. Psychological impacts of shocks: having a shock

plan in place. Presented at: 32nd Annual Scientific Sessions,

Heart Rhythm Society; May 4-7, 2011; San Francisco,

California.

Pozuelo L. Psychosocial and psychiatric interventions to

improve quality of life for children and adults with ICDs.

Presented at: Scientific Session, American Heart Association;

November 13-17, 2010; Chicago, Illinois.

Pozuelo L. Quality of life and cardiovascular implantable

electronic devices. Presented at: Ethics of the Heart: Ethical

and Policy Challenges in the Treatment of Advanced Heart

Failure; October 8-9, 2010; Philadelphia, Pennsylvania.

Pozuelo L. Update in med-psych issues and the problem

patient. Presented at: Sixth Annual Midwestern Hospital

Medicine Conference; October 7-9, 2010; Chicago, Illinois.

Ramirez M, Lineweaver TT, Naugle R, Busch RM. Memory

outcome following temporal lobectomy in epilepsy patients

with bilateral mesial temporal sclerosis. Presented at: 39th


February 2-5, 2011; Boston, Massachusetts.

Sarkis RA, Floden D, Busch RM, Chapin J, Kalman C, Jehi L,

Najm I. Predictors of decline in verbal fluency after frontal

lobe epilepsy surgery. Presented at: American Epilepsy

Society Meeting; December 3-7, 2010; San Antonio, Texas.

Streem D. The challenge of outcome measurement in

addiction treatment. Presented at: Association of Recovery

Schools Annual Meeting; July 21, 2011; Cleveland, Ohio.

Strober LB, Busch RM, Chapin JS, Tesar G, Viguera A, Najm I.

Beyond endorsement: a closer look at how seizure activity

and antiepileptic medication side effects impact patients’

reports of depression. Presented at: 38th Annual

International Neuropsychological Society Meeting; February

3-6, 2010; Acapulco, Mexico.

Strober LB, Busch RM, Chapin JS, Tesar G, Viguera A, Najm I.

Psychometric properties of the Beck Depression Inventory-II

(BDI-II), Beck Depression Inventory-Fast Screen (BDI-FS) and

Center for Epidemiological Studies-Depression (CES-D) in an

epilepsy sample: are our present measures sufficient?

Presented at: 38th Annual International Neuropsychological

Society Meeting; February 3-6, 2010; Acapulco, Mexico.

Wimbiscus M, Mehta A, Falcone T. Psychosis and violence in

children. Presented at: American Academy of Child and

Adolescent Psychiatry; October 26-31, 2010; New York Hilton,

New York.

C L i n i C a L T R i a L S

Select Clinical Trials

Assessing Reliable Cognitive Change in Children Following Epilepsy Surgery

PURPOSE: The goal of this study is to develop reliable methods for assessing cognitive change in children with epilepsy. Specifically, we are examining how children with epilepsy perform on neuropsychological tests over time in order to develop tools to more effectively evaluate the effects of treatments such as epilepsy surgery. This information will help neuropsychologists inform parents and physicians about the cognitive risk associated with surgery and assist with prediction of overall learning and behavioral outcomes. Furthermore, clinicians can use this information to more accurately identify cognitive and school abilities requiring intervention following surgery. This study includes children with epilepsy, regardless of whether epilepsy surgery is being considered.

ELiGiBiLiTY: Participants must be 6 to 16 years of age; have a history of seizures for at least one year, as evidenced on EEG recordings; be fluent in English; have no history of neurosurgical interventions or neurodegenerative disorders; and have not undergone neuropsychological testing within the past six months.

PRinCiPaL invESTiGaTORS: Jennifer Haut, Phd, and Robyn Busch, PhD

RESEaRCh COORDinaTORS: Colleen Kalman, 216.444.5952, [email protected]; lisa l. ferguson, 216.444.5111, [email protected]

Controlled Trial of Deep Brain Stimulation for Obsessive-Compulsive Disorder

PURPOSE: The goal of this controlled trial is to determine the effectiveness of deep brain stimulation (DBS) on patients who have treatment-resistant obsessive-compulsive disease (OCD). The study includes three months of active vs. sham DBS in which participants are blinded as to which group they are in. Following the three-month blinded phase, all subjects in the clinical trial will receive active DBS stimulation.

ELiGiBiLiTY: Subjects must be between the ages of 18 and 75 years old with a documented history of treatment-resistant OCD. Subjects must have had OCD for at least five years. Subjects will have failed to improve with traditional treatments of medication and exposure therapy. Subjects cannot have a history of psychosis or schizophrenia.

PRinCiPaL invESTiGaTOR: Donald Malone, MD

RESEaRCh COORDinaTOR: Elizabeth Olszewski, 216-444-1179, [email protected]

Documents

Insights - Cleveland Clinic · patients to improve outcomes, and Tatiana Falcone, MD, takes psychological intervention for youth with epilepsy into the schools and community with