Plenary 2 Mortality in Children June 24, :30 a.m. - noon Moderator: Elizabeth Donner, MD, FRCP(C), The Hospital for Sick Children

Transcription

1 Plenary 2 Mortality in Children June 24, 216 1:3 a.m. - noon Moderator: Elizabeth Donner, MD, FRCP(C), The Hospital for Sick Children Parent Speaker: Shannon Bursick, MS and Joe Bursick The Facts about Mortality in Pediatric Epilepsy Anne Berg, PhD, Feinberg School of Medicine SUDEP in Children: Compare and Contrast with Adult Literature - Sanjeev Kothare, MD, NYU Langone Medical Center Lessons Learned in Sudden Unexpected Death in Childhood (SUDC) Research and Advocacy Laura Crandall, The SUDC Foundation Panel Discussion: Why is SUDEP reported to be less common in children?

2 215 AES Annual Meeting Disclosure Mortality in Pediatric Epilepsy: An Overview Anne T. Berg, PhD Lurie Children s Hospital Northwestern Feinberg School of Medicine Research Funding from NINDS CDC Pediatric Epilepsy Research Foundation Gozuetta Foundation/Emory University Dravet Syndrome Foundation Commercial Interests/Other Expert Witness, NBTY Inc. JUNE 216 Learning Objectives Following participation in this activity, learners should be able to Describe and explain the burden and causes of mortality In the first 2 decades of life in the general population In children and young people with epilepsy In the different types of pediatric epilepsies SMR Standardized mortality ratios (SMR) for people with epilepsy General Population Children Mortality Force of mortality and reasons for death vary By Country By subgroups Gender Socio economic status AGE! Population death rates by age US 213 death rate / 1, per year <1 year

3 215 AES Annual Meeting Cumulative mortality from birth Cumulative mortality in first 2 decades of life <~1% bsif.gc.ca/eng/oca bac/as ea/pages/mpsspc.aspx Proportional impact When deaths occur in young people, what are the most common reasons? 7 1% 6 9% 8% 5 7% 4 6% 5% 3 4% 2 3% 1 2% 1% % Death rate <1 1 to 4 5 to 9 1 to to 24 <1 to to 1 to to 24 Heart disease Suicide Cancer Resp Distress Infection Accidents Homicide SIDS/SUDC Perinatal Epilepsy associated mortality Relative force of mortality depends on overall force of mortality SMR 14 Children Forensic/SUDC Statistics Mortality in young people with epilepsy compared to the population rate/1,/year Mortality in 4 pediatric epilepsy cohorts and overall (Berg et al. Pediatrics 213) y.o Overall Mortality by age US population, 213, (NVSR, 216) Epilepsy associated mortality Relative force of mortality depends on overall force of mortality Epidemiology of epilepsy epidemiology of neurological morbidity

4 215 AES Annual Meeting Short cut definition Complicated Presentation ~25% Associated with recognized brain disorder Early life insults Infections Trauma Stroke Autoimmune Genetic (including structural) causes Neurodisability Uncomplicated Presentation ~75% No recognized associated brain disorder AND Neurologically, no impairment Neurotypical Epilepsy associated mortality Relative force of mortality depends on overall force of mortality Epidemiology of epilepsy epidemiology of neurological morbidity Force of mortality of epilepsy force of mortality of causes of epilepsy and their consequences Complicated vs Uncomplicated epilepsy presentations compared to general population rate/1,/year Mortality rates in 4 pediatric epilepsy cohorts and overall (Berg et al. Pediatrics 213) Overall Mortality rate by age US population, Standardized Mortality Ratio (SMR) Impact on mortality of Developmental Disability Without Epilepsy No Epilepsy Day, Neurology 25;65: Standardized Mortality Ratio (SMR) Impact on mortality of developmental disability with and without epilepsy No Epilepsy Epilepsy Standardized Mortality Ratio (SMR) Impact of epilepsy on mortality in people with developmental or comparable acquired disability 2.1 Epilepsy/NoEpilepsy Epilepsy/NoEpilepsy 5 Day, Neurology 25;65: Day, Neurology 25;65:

5 215 AES Annual Meeting Mortality in young people with epilepsy in the absence of neurodisability? Mortality rates in 4 pediatric epilepsy cohorts and overall (Berg et al. Pediatrics 213) rate/1,/year 595 Overall Mortality rate by age US population, 213 Distribution of types of pediatric epilepsies Type of Epilepsy 5 12% Non Syndromic Epilepsy Garden Variety Epilepsy Berg&Rychlik Epilepsia, 215 Distribution of types of pediatric epilepsies % All Mortality % % % 7 1 % 39 33% 56% Number and causes of death by type of epilepsy JAE JME + ~12% of pediatric epilepsies Nonsyndromic, uncomplicated ~4% of pediatric epilepsies Nonsyndromic, complicated ~ 15% of pediatric epilepsies 1 % 1% 33% Deaths from 4 cohort study 1 suicide (JAE) 2 SUDEP 1 status iatrogenic 2 cancer 1 suicide, 1 homicide 1 unknown 4 SUDEP 2 other sz related 2 accidental 1 suicide 18 other natural Non Syndromic Epilepsy Garden Variety Epilepsy Berg&Rychlik Epilepsia, 215 Encephalopathic epilepsies ~ 12% of pediatric epilepsies 56% 4 SUDEP 38 other natural (including device malfunction) 2 unknown Causes of death: young people in general and young people with epilepsy 9 8 1% 9% 7 6 8% 7% 5 6% 5% 4 4% 3 3% 2 2% 1 1% % Proportional impact Death rate medical device Heart disease Suicide Cancer Resp Distress Infection Accidents Homicide Seizure related SIDS/SUDC Perinatal Impact on Clinical Care and Practice Provide a rational perspective for discussing mortality risks, especially with new patients. Type of epilepsy and presentation strongly determine the mortality risk High Risk: Encephalopathic Epilepsies (West, Dravet, LGS, etc): Most mortality is not epilepsy related, Seizures add substantially to the burden Moderate Risk: Nonsyndromic Epilepsies (most like adult epilepsy) Risk depends on presentation: complicated or not Seizure related mortality occurs (~in adults?) Transition to adulthood and to assuming responsibility for self and care are a priority Low Risk: BECTS, CAE JAE JME other GGE No measurably increased risk of mortality from seizures Not measurable absent Reassuring especially if seizures resolved, but never cavalier! Forensic/SUDC Statistics Berg et al. Pediatrics, 213 4

6 215 AES Annual Meeting pameaesnet.org 216 PAME CONFERENCE JUNE ALEXANDRIA, VA 5

7 215 AES Annual Meeting Disclosure SUDEP in Children: Compare & Contrast with Adult Literature None Sanjeev V. Kothare, MD, FAAN Professor Of Neurology & Pediatrics Director, Pediatric Sleep Program NYU Langone Medical Center & School of Medicine JUNE 216 Learning Objectives Following participation in this activity, learners should be able to: Be knowledgeable on cardiorespiratory abnormalities observed during seizures in children. Be aware of the differences in these abnormalities in adults as compared to children. Be aware of differing epidemiology and possible mechanisms to explain SUDEP in children as compared to SUDEP in adults. Some Basic Facts Concerning SUDEP The Epilepsy usually begins before age 16 years. There must be a high seizure burden. Long standing chronic refractory epilepsy (usually 2 years duration). Type of epilepsy: tonic, secondary generalized, prolonged, in prone position in sleep. Must continue to have refractory seizures at the time of occurrence of SUDEP. 1

8 215 AES Annual Meeting Summary 11 seizures in 26 children were recorded (average age 3.9 years). Ictal central apnea was more prevalent in patients with younger age, temporal lobe, left sided, symptomatic generalized, longer duration seizures, with desaturation, ictal bradycardia, and more antiepileptic drugs. Ictal bradypnea was more prevalent in left sided, symptomatic generalized seizures, and with brain MRI lesions. Ictal tachypnea was more prevalent in older age, female gender, right sided seizures, fewer AEDs, and less prevalent in symptomatic generalized seizures. Ictal bradycardia was more prevalent in male patients, with longer duration seizures, desaturation, and more AEDs. Desaturations were more prevalent in longer duration seizures, with ictal apnea, ictal bradycardia, and with more AEDs. Summary 11 seizures in 26 children and 55 seizures in 22 adults were recorded. Ictal central apnea and bradycardia occurred more often in children than in adults. Ictal tachycardia occurred more often in adults than in children. Frequency of postictal generalized EEG suppression (PGES) of longer duration occurred more often in adults than in children. There may be an age related effect on cardiorespiratory and EEG abnormalities associated with seizures, with higher rates of apnea and bradycardia in children and a much higher prevalence of PGES of longer duration in adults. This may indicate why, despite lower rates of cardiopulmonary dysfunction, adults die more frequently from SUDEP than children. Multiple Mechanism to Explain SIDS Similar Models to Explain SUDEP Prematurity, VLBW 1 4 months, prone Seizure Burden Vulnerable Age, State, Environment. Co sleeping, passive smoke, overheating Genetic Predisposition 2

9 215 AES Annual Meeting Can SUDEP Occur in Pediatrics? Can SUDEP Occur in Pediatrics? Yes, but much less common. Why: possible hypothesis Autonomic shutdown occurs less frequently, with lesser frequency & duration of PGES: time bound phenomenon wherein a critical duration of epilepsy invokes this phenomenon. Central apneas and hypoventilation is better tolerated. More cardiopulmonary reserve. More supervision and hence more intervention. When is it likely to occur? In certain genetic syndromes: Dravet syndrome. 15q isodicentric duplication syndrome. Ring chromosome 2 syndrome. Long QT interval syndromes (KCNQ1, KCNH2, SCN5A). Serotoninergic and purinergic (adenosine) genetic mechanisms. Impact on Clinical Care and Practice Very little data available on pediatric SUDEP. Multi centric longitudinal studies are needed. More data needs to be available from SUDC sites. pameaesnet.org 216 PAME CONFERENCE JUNE ALEXANDRIA, VA 3

10 215 AES Annual Meeting Disclosure Lessons Learned From Sudden Unexplained Death In Childhood: Research and Advocacy The SUDC Foundation Executive Director Laura Crandall, MA NYU Langone Medical Center JUNE 216 Learning Objectives SUDC is currently defined as History of SUDC and Febrile Seizures Advocacy Efforts in SUDC Research Networking with Medical Examiners & Coroners Promoting Death Investigation and Autopsy Standards Legislative Advocacy U.S. Federal Efforts Working with your Medicolegal Death Investigation System the sudden death of a child older than one year of age which remains unexplained after a thorough case investigation, including review of the clinical history and circumstances of death, and performance of a complete autopsy with appropriate ancillary testing. Krous et al., Ped Dev Path 25 SUDCRRC May 216 Background No definition until 25 Incidence of SUDC among children 1 18 years of age ~344 deaths/year 22 (~6%) of the deaths among children ages 1 4 yrs Limited awareness and research greatly impact our understanding Lack of ICD code impairs ability to track In contrast to Sudden Infant Death Syndrome (SIDS), where genetic discoveries and extensive risk reduction public awareness programs have decreased rates by 5% over the past two decades, very little progress has been made towards understanding the pathogenesis of SUDC and rates of SUDC have doubled during this period. R99*= 223 toddler deaths R99*= 152 infants R99*= 375 R99= Undetermined * R99 is defined in ICD as Ill defined and unknown cause of mortality and is currently our only measure for assessing SUDC. If included in leading causes of death chart SUDC in toddlers would rank 5th and among older teens thru 24 years of age 6th. SUDCRRC May 216 1

11 215 AES Annual Meeting Leading causes of death age 1 4: US 214 (CDC Vital Statistics) Diagnoses of Exclusion 1,2 1, 8 Motor vehicle Death Scene Investigation Negative 6 4 Drowning Autopsy Unremarkable 2 Other unintentional Unintentional Injury Congenital anomolies Homicide Malignant neoplasms R99 Ill defined conditions Clinical History Negative (Blair, P. as cited in Sidebotham & Fleming, 27 p.41) SUDCRRC May 216 We just don t know SUDC Funding & Research FUNDING BY Deaths SIDS 1563/yr $>5 Million last 2 years SUDEP > 275/yr <$75 million last 2 years SUDC 388/yr $<1 million last 2 years Bike accidents (1 19 years): 97/year Fires and burns (1 14 years): 281/year Motor vehicle accidents (1 14) 1,83/year RESEARCH (PubMed) SIDS 1,829 SUDC <2 Bicycle accidents children 616 Motor vehicle accidents children 8,372 SUDCRRC May 216 Barriers to SUDC Research Lack of Awareness MDI and Law Enforcement Investigations Lack autopsy standards Retention of Brain not common Retention of viable specimen for genetics not universal Variations in MDI policies re: retention and release Variability/Lack of criteria for COD Difficulty in admitting I don t know Real Incidence of SUDC is unknown Limited resources of MDI offices Families living with great uncertainty and inconsistent treatment! SUDCRRC May 216 LC7 Sudden Unexplained Death in Childhood (SUDC) Krous HF, et al. Ped Dev Pathol, 25; Hesdorffer et al, Epilepsia 215 Sudden death of a child >12 mos; unexplained after a thorough autopsy & case investigation. Category of deaths that elude us 123 Case Referrals to SUDC Foundation (211 14) Predominantly males, ages 1 3 yo Febrile seizures up 32% of cases Possible SUDEP like mechanism Most born at term and as singletons Most found prone, often with face down Minor pathologic findings common, but do not explain death SUDCRRC May 216 SUDCRRC May 216 Review the child s death, medical and family history by FP panel for cause of death Neuroimaging/ neuropathology consultations Genetic analysis (whole exome sequencing) on SUDC child, biological parents and symptomatic relatives Study the risks that lead to SUDC Provide families with study report Identify at risk individuals to establish prevention strategies 2

12 Slide 11 LC7 first bullet- change to equal or greater than 12 months. (SIDS is less than 12 months, so SUDC covers deaths on the first birthday. Laura Crandall, 12/13/215

13 215 AES Annual Meeting Advocacy Do Your Homework First What are the problems you are trying to address? Why do they exist? What are your goals? Needs Assessment Do you know the solution? Are Laws the answer? Health Policy? Is it purely a funding issue? Awareness? Research Efforts What are the policies of ME/C offices around Child Death investigations? What are the experiences of families? Rudd R, Capizzi Marain L, Crandall L To Hold or Not to Hold: Medicolegal Death Investigation Practices During Unexpected Child Death Investigations and the Experiences of Next of Kin. Am J Forensic Med Pathol. 214 Jun;35(2):132 9 A commentary on lack of protocols affecting mourning rituals. Are practices backed by science? Baker AM, Crandall L. To Hold Or Not To Hold. Forensic Sci Med Pathol. 29 (Dec; 5(4): Epub 29 Nov 13. Federal Efforts 29 NAS Report: Strengthening Forensic Science in the United States: A Path Forward National Commission on Forensic Science (by DOJ) Organization of Scientific Area Committees (by NIST and DOJ) Sudden Unexpected Death Data Enhancement And Awareness Act (passed into law ) Sudden Death In the Young Registry (NIH and CDC) SUID Case Registry (CDC) SUDC s Work with Medical Examiners Coroners National Association of Medical Examiners (NAME) Member Annual Exhibitor Genetic Specimen Standard International Association of Coroners & Medical Examiners Involvement on SAB Offering Resources from the SUDC Foundation Help For Families Brochure NAME Interim Scientific Program February 23, Attendees 29 Countries Working WITH Your Medicolegal Death Investigation System UUUggh! The Unexpected, Unexplained and Often Undetermined What are your goals? What are the barriers? Why do the barriers exist? What is the history behind them? Get to Know your Medical Examiner/Coroner BEFORE you need them! 3

14 215 AES Annual Meeting Recognize You are all the same page Scope of Work Statutory Authority Department they reside Limited resources personnel, time, $ Their mandate Varying systems with varying viewpoints on role in public health Impact on Clinical Care and Practice Communication with Medical Examiners Make Connections Now How can you help them? What can you offer them? How can you work together? Partnering with Advocacy Groups Strategic Plans: Health Policy, Legislative and/or ME/C Offices Coordination of Family and Medical Professional Efforts pameaesnet.org 216 PAME CONFERENCE JUNE ALEXANDRIA, VA 4