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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
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
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