epilepsy-related mortality: an untold burden on public
TRANSCRIPT
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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
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Thank you to the Partners Against Mortality in Epilepsy
for making this webinar series possible.
http://www.aesnet.org/pame
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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
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Register Now at:
www.aesnet.org/pame
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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
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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
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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
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Disclosure
UCB, Inc. Consultant; grant support
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Learning Objectives
• To understand the leading causes of death directly attributable to epilepsy
• To understand the relative incidence of deaths directly attributable to epilepsy
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Acknowledgements
• Dale Hesdorffer
• Jeff Buchhalter
• Cindy Wright
• PAME
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Questions for the Audience
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Measures of Mortality
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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.
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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.
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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
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Understanding Epilepsy-related
Mortality
• The true incidence of epilepsy-related mortality
is unknown.
– U.S. national mortality records provide grossly
incomplete data on epilepsy
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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%?
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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
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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
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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.
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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
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Summary: Estimated Annual SUDEP
Incidence Among People with Epilepsy
Best overall estimates:
• Rate 1.2/1000
• US cases (2014) ~2700
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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
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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.
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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.
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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)
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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
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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
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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
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Summary: Excess Mortality from Epilepsy –
United States, 2014
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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
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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)
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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
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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.)
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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
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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
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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.
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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
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Disclosure
Name of Commercial
Interest
Type of Financial
Relationship
Eisai, Ltd
Lundbeck, LLC
Upsher-Smith, Laboratories
Consultant
Consultant
Consultant
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Learning Objectives
• Understand the “inclusive structure” of the conference
• Understand the wide range of topics for the conference
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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
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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
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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
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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.
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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.
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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.
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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.
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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
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Q&A