epilepsy-related mortality: an untold burden on public

Epilepsy-related Mortality:

An Untold Burden on Public Health

and PAME 2014 Preview

Presented by: David J. Thurman, MD, MPH

and

Jeffrey Buchhalter MD, PhD

Thank you to the Partners Against Mortality in Epilepsy

for making this webinar series possible.

http://www.aesnet.org/pame

Thank You to the PAME Steering Committee Members

• Co-Chair: Jeff Buchhalter, MD, PHD,

FAAN,

• Co-Chair: Gardiner Lapham, CURE

• Cyndi Wright, Epilepsy Foundation

SUDEP Institute

• Orrin Devinsky, MD

• Jeanne Donalty,

• Elizabeth Donner, MD, FRCPC

• Alica Goldman, MD, PhD

• Jane Hanna

• Cynthia Harden, MD

• Dale Hesdorffer, PhD

• Lawrence J. Hirsch, MD

• Tamzin Jeffs, MSc

• Vicki Kopplin

• Barbara L. Kroner, PhD, MPH, RN, APRN

• Kim Macher

• Lina Nashef, MBChB, MD, BC, CNRN

• Rosemary Panel

• George Richerson, MD, PhD

• Christina SanInocencio

• Paul Scribner

• Tess Sierzant, MS

• Elson So, MD

• Mark Stevenson, FACHE, CHIE

• Torbjörn Tomson, MD, PhD

• Vicky Whittemore, PhD

• Tom Stanton

• David Thurman, MD, MPH

• Michelle Welborn, PharmD

AES Staff:

• Jeffrey Melin, MEd., CMP

• Paul Levisohn, MD

• Elizabeth Kunsey, CMP

• Sandy Pizzoferrato

• Kathy Hucks

Register Now at:

www.aesnet.org/pame

Today’s Speakers

David J. Thurman, MD, MPH

Emory University School of Medicine

Atlanta, Georgia, U.S.A.

Jeffrey Buchhalter MD, PhD

Professor of Clinical Neurosciences & Pediatrics

University of Calgary, Faculty of Medicine

Director, Comprehensive Pediatric Epilepsy

Center

Alberta Children’s Hospital, Canada

Epilepsy-related Mortality:

An Untold Burden on Public Health

and PAME 2014 Preview

April 3, 2014

David J. Thurman, MD, MPH

and

Jeffrey Buchhalter MD, PhD

Partners Against Mortality in Epilepsy Conference – June 19-22, 2014

Epilepsy-related Mortality:

An Untold Burden on Public Health April 3, 2014

David J. Thurman, MD, MPH

Emory University School of Medicine

Atlanta, Georgia, U.S.A.

Partners Against Mortality in Epilepsy Conference – June 19-22, 2014

Disclosure

UCB, Inc. Consultant; grant support

Learning Objectives

• To understand the leading causes of death directly attributable to epilepsy

• To understand the relative incidence of deaths directly attributable to epilepsy

Acknowledgements

• Dale Hesdorffer

• Jeff Buchhalter

• Cindy Wright

• PAME

Questions for the Audience

Measures of Mortality

Epilepsy Mortality

• In general, the overall mortality risk (SMR)

among people with epilepsy appears 2–3 times

higher than among the general population

– People with epilepsy of unknown cause have only a

slight increase in mortality,

– People with epilepsy due to a known underlying

cause have substantially increased mortality.

T Tomson & L Forsgren, Lancet 2005; 365:557.

Epilepsy Mortality—Leading Causes

of Death in New-onset Epilepsy Cases

• Tumors 18 – 34%

• Cerebrovascular disease 14 – 17%

• Pneumonia 8 – 18%

• Suicide 1 – 9%

• Accidents 6% (?)

• Seizure-related 0 – 6%

T Tomson et al. Epilepsy Research 2004; 60:1-16.

Defining “Epilepsy-related”

Mortality

• Deaths from underlying CNS condition causing epilepsy

– Perinatal (e.g., cerebral palsy)

– Brain tumors

– Stroke

– Traumatic brain injury

– Progressive disease (e.g. Alzheimer disease)

• Deaths caused directly by epilepsy

– Sudden unexpected death in epilepsy (SUDEP)

– Status epilepticus with preexisting epilepsy

– Seizure-related injury (e.g., falls, drowning)

– Suicide

Understanding Epilepsy-related

Mortality

• The true incidence of epilepsy-related mortality

is unknown.

– U.S. national mortality records provide grossly

incomplete data on epilepsy

How Good Are U.S. Mortality Data? NCHS Vital Records, 2006-2011

Epilepsy-related deaths

Diagnosis ICD-10

codes

Ave.

Annual

Cases

Face validity

All Epilepsy-

assoc. deaths G40 930 Very Low

SUDEP ? G40 AND

(R96 or T71) 102 Very Low / ~5%?

Status

Epilepticus G40 AND G41 41 Very Low / ~10%?

How Good Are U.S. Mortality Data? NCHS Vital Records, 2006-2011

Epilepsy-related deaths

Diagnosis ICD-10

codes

Ave.

Annual

Cases

Face validity

Drowning (G40 OR R56.8)

AND (W65-W74) 172 Low

Suicide G40 AND

(X60-X84) 2 Very Low

MV & Transport

Accidents G40 AND (V01-

V99) 8 Very Low

Falls G40 AND (W00-

W19) 28

Very Low

Sudden Unexpected Death in

Epilepsy (SUDEP)

• Definition: sudden, unexpected, non-traumatic

death in person with epilepsy, w/o evidence of

structural or toxicological cause of death

• Many problems accurately identifying SUDEP cases

for epidemiologic studies, e.g.:

– Many MDs & coroners unfamiliar with SUDEP

– Death certificate data very inadequate

– Insufficient resources for medical examiner

investigations

Summary: Studies of SUDEP Incidence

0.4 0.9

1.5

6.2

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

9.0

10.0

Children All Pop'n Clinics Refractory

An

nu

al

Rate

per

1000 P

WE

Median estimates in red

Data sources:

“Children” – 5 population-based studies of incidence among children < 18 years

“All Population” – 5 coroner/ME studies of incidence in general populations, all ages

“Clinics” – 7 studies of epilepsy clinic populations or hospital series of patients with epilepsy

“Refractory” – 6 studies of patients with treatment resistant epilepsy in clinical trials, etc.

SUDEP Occurrence by Age

• Limited data

• Lower risk in young

children

• Higher risk in

adolescents, young

adults, middle-aged

• Occurrence in older

adults appears lower

Terrence CF et al., 1975

Summary: Estimated Annual SUDEP

Incidence Among People with Epilepsy

Best overall estimates:

• Rate 1.2/1000

• US cases (2014) ~2700

Lifetime Risk Model—SUDEP in the

General Population of People w/ Epilepsy

• Assumptions:

• Childhood onset, no life-limiting comorbid disease

• Overall annual incidence 1.2/1000

• Peak incidence age 30

• Cumulative Incidence: 8% at age 75

Method of Sasieni PD & Adams J. Am J Epidem 1999;149(9):869-875

Fatal Status Epilepticus (SE):

In General Population • Most cases of fatal SE are acutely ill people

with no history of epilepsy. Major causes:

– infections, stroke, hypoxic and metabolic brain

disease

• Estimates of fatal SE occurrence vary widely.

– Highest estimate is 9 to 17 / 100,000 annually*

– Median estimate is 0.94 / 100,000 annually†

– Corresponds to ~3000 deaths in U.S. annually

– U.S. mortality data incomplete: ~1100/year

*See DeLorenzo RJ et al. J Clin Neurophysiol. 12:316-25, 1995 † See Rosenow F. et al. Epilepsia. 48 Suppl 8:82-4, 2007.

See also Govoni V et al. European Neurology. 59(3-4):120-6, 2007.

Fatal Status Epilepticus: Among People with Epilepsy

Population-based

Follow-up Studies Ages Cases Ann. Rate/1000

Ackers, 2011 (UK) 0-18 6 0.22

Camfield, 2002 (Nova Scotia) 0-36 1 0.11

Sillanpaa, 2010 (Finland) 0-55 4 0.46

Total 0-55 11 0.25 (0.13-0.46)

Limitation: study populations mainly children and young adults

with childhood-onset epilepsy; older adults not represented.

Estimated Fatal SE among

People with Epilepsy – U.S., 2014

• Est. rate/105 fatal SE 24.7 (13.0 – 45.7)

• Est. U.S. number PWE 2,269,640

• Est. Cases fatal SE in PWE 561 (295 – 1037)

Drowning among

People with Epilepsy

• UK pop’n-based study† 15.3 SMR*

• Meta-analysis of 51 cohorts† 18.7 SMR

• Applying SMR of 15.3 to U.S. population:

– Est. 423 drowning deaths among PWE

– Est. 395 attributable to epilepsy (“excess”)

*Standardized mortality ratio †Bell et al., 2008

Suicide among PWE Community-based or General Clinical Population Studies

Study Locality SMR 95% C.I.

Hauser, 1980 Minnesota, USA 3.0 0.6-8.8

Lhatoo, 2001 UK 1.1 0.03-6.0

Mohanraj, 2006 Scotland, UK 2.7 0.6-7.8

Nilsson, 1997 Sweden 3.5 2.6-4.6

Rafnsson, 2001 Iceland 5.0 1.4-12.8

Median 3.0

See Bell et al., Epilepsia 2009; 50:1933-42

Estimating Epilepsy-associated

Suicide Occurrence

• Suicides per 100,000 population in U.S. 12.4*

• Predicted suicides in PWE if SMR=1 272

• Predicted suicides in PWE if SMR=3 820

• ‘Excess’ suicides in PWE 547

*Calculated from data from U.S. Centers for Disease Control and Prevention

Summary: Excess Mortality from Epilepsy –

United States, 2014

Major Caveats: Estimates of Excess Mortality from Epilepsy

• The preceding estimates are based on:

– extrapolations from small numbers of studies of

limited populations, representing few localities

– case finding is likely to be incomplete in many or

most of these studies

• Substantial potential bias using estimates of

risk from these studies

• These are ‘provisional’ estimates that are

probably ‘conservative.’

• More research is needed

The Sudden Death in the Young Registry: An NIH-CDC Surveillance Initiative

• Funds provided Oct. 2013 to plan

development of a multi-state Sudden Death in

the Young (SDY) Registry.

• Joint collaboration of NIH and CDC:

– NHLBI (Nat’l Heart, Lung, and Blood Institute)

– NINDS (Nat’l Institute for Neurological Disorders

and Stroke)

– CDC Chronic Disease Center (Division of

Reproductive Health and Division of Population

Health/Epilepsy Program)

The SDY Registry (cont.)

• Goals:

– Define incidence of SDY

– Risk factors

– Help set future research priorities

• Focus – sudden cardiac death and

SUDEP in children and young adults up

to age 24 years

The SDY Registry (cont.)

• Infrastructure

– Coordinating center - Michigan Public

Health Institute

– State health agencies, child death review

panels, medical examiners

– Expansion of CDC Sudden Unexpected

Infant Death Case Registry (currently 9

states.)

The SDY Registry (cont.)

• First steps, 2014

– Establishment of SDY Advisory Committee

– Establish operational case definitions, data

elements for collection, general protocol(s)

– CDC Grant Announcement in Spring 2014

• eligible network participants: state or major

metropolitan public health agencies

Future Research Needs

• Expand surveillance of PWE to include

SUDEP, SE, and fatal injury—all ages

– Incidence and risk factors

• Clinical cohort studies of people w/ epilepsy

– Prospective incidence and risk factor data

– Participate in tissue registries

• Voluntary registry

– risk factor data and tissue registries

Impact on Clinical Care and Practice

• There is an appreciable increased risk of premature death that can be directly attributed to epilepsy.

• Many or most of these deaths may be preventable.

• Patients and their families should be counselled accordingly, emphasizing measures that can be taken to reduce risk.

Preview of PAME 2014

April 3, 2014

Jeffrey Buchhalter MD, PhD

Professor of Clinical Neurosciences & Pediatrics

University of Calgary, Faculty of Medicine

Director, Comprehensive Pediatric Epilepsy Center

Alberta Children’s Hospital

Partners Against Mortality in Epilepsy Conference – June 19-22, 2014

Disclosure

Name of Commercial

Interest

Type of Financial

Relationship

Eisai, Ltd

Lundbeck, LLC

Upsher-Smith, Laboratories

Consultant

Consultant

Consultant

Learning Objectives

• Understand the “inclusive structure” of the conference

• Understand the wide range of topics for the conference

USA Chronology

• 2006- AES and EF individually recognize need for

SUDEP movement- Task Force

• June 2007- Task Force meeting, C.U.R.E. &

NINDS became partners

• Nov 2008- NINDS SUDEP Workshop

• Mar 2009- SUDEP Coalition

• Oct 2010- CDC Mortality in Epilepsy project

• Jun 2012- Partners Against Mortality in Epilepsy

Intent of the conference, then & now

• Provide an opportunity for all those involved in SUDEP to meet & exchange information. To learn from each other

• Provide a state-of-the-art “snapshot” of SUDEP activities

• Advocacy

• Basic science

• Clinical/translational science

• Education

• Lay/bereaved

Structure of the conference

• Overall meeting

• Integrated (Clinical & basic science, advocacy, education)

• Each day, each topic addressed

• Attempt to have related topics

• Sessions

• Intend to make content accessible to all

• Intend to provide maximal opportunities for interaction with attendees, participation

PAME Goals

• Prevent mortality in epilepsy through a

rigorous scientific meeting that:

– Promotes understanding of the latest

developments in SUDEP and epilepsy

mortality research,

– Stimulates ideas and collaborations to

advance discovery,

– Hastens efforts to increase public awareness

and education for professionals and people

living with epilepsy.

PAME Objectives- Clinicians

• Strengthen the capacity of health care

providers to discuss epilepsy-mortality

broadly and SUDEP specifically, identify

risk factors, communicate prevention

strategies

• Address gaps in care for people with

epilepsy and provide strategies for

improvement.

PAME Objectives- Researchers

• Identify progress made in epilepsy

mortality and SUDEP research and

direction for future research as well as

funding and collaboration opportunities.

• Build collaborations across medical

disciplines and among families/advocates

to bolster research opportunities and

participation.

PAME Objectives-Families and Advocates

• Provide a forum to learn about the latest in epilepsy

mortality, especially SUDEP research.

• Enable the advancement of SUDEP awareness and

education by facilitating collaborations.

• Allow opportunity to share stories and support one

another.

PAME 2014 Session Topics

• Epidemiology of Mortality and Surveillance

Efforts

• Basic Mechanisms: Autonomic, Cardiac,

Respiratory, Sleep

• Genetics

• Epilepsy & Grief

• Devices, Treatment & Prevention

• Awareness & Advocacy Activities

Q&A