Epidemiology of Epilepsy: From Epilepsy to Epilepsy Plus. December, 2011

Transcription

1 Epidemiology of Epilepsy: From Epilepsy to Epilepsy Plus December, 2011 Dale C. Hesdorffer, PhD, GH Sergievsky Center, Columbia University American Epilepsy Society Annual Meeting

2 Disclosure No Commercial Interests to disclose American Epilepsy Society Annual Meeting

3 Learning Objectives Understand how epilepsy epidemiology has evolved over the last 75 years for: Prevalence and Incidence Comorbidities Mortality Directions for the future American Epilepsy Society Annual Meeting

4 Natural History of Disease Comorbidity Risk factors Incidence Prevalence Prognosis Subclinical Phase Clinical Phase Biologic onset Signs and symptoms Medical care Diagnosis Treatment of disease of disease sought Death Seizures Epilepsy AED 4

5 Early incidence and prevalence studies of epilepsy Definitions of epilepsy for incidence: Any single seizure or two seizures, including acute symptomatic (Kurland, 1959; Crombie, 1960) Epilepsy was not defined as two or more unprovoked seizures until Hauser et al 1973 Prevalence: Early studies included cases from referral centers 5

6 Prevalence of epilepsy Rochester 1955 Iceland 1960 Niigata City Japan 1961 Oslo,Norway Mariana Islands, 1962 Northern Israel Semokewe reserve, Africa South Africa, 1959 Ethiopia GP survey WWI US draft WW II draft Prevalence per 1,000 Kurland, 1959; Gudmundsson, 1966; Sato, 1964; Krohn, 1961; Lessell, 1962; Wajsbort, 1967; Levy, 1964; Pond, 1960; Bird, 1962; Giel, 1970; Davenport, 1923; Edwards,

7 Prevalence of epilepsy Rochester 1955 Iceland 1960 Niigata City Japan 1961 Oslo,Norway Mariana Islands, 1962 Northern Israel Semokewe reserve, Africa South Africa, 1959 Ethiopia GP survey WWI US draft WW II draft Early study Prevalence per 1,000 Early study Kurland, 1959; Gudmundsson, 1966; Sato, 1964; Krohn, 1961; Lessell, 1962; Wajsbort, 1967; Levy, 1964; Pond, 1960; Bird, 1962; Giel, 1970; Davenport, 1923; Edwards,

8 Prevalence of epilepsy in recent door-to-door surveys Place Age adjusted Prevalence Study New York 5.0 Kelvin, 2007 Honduras 16.0 Medina, 2005 Argentina 3.7 Melcon, 2007 Italy 3.3 Rocca, 2001 Turkey 7.0 Onal, 2002 China 4.4 Li, 1985 India 4.4 Radhakrishna, 2000 Saudi Arabia 5.1 Al Rejeh, 2001 Zambia 13.2 Birbeck, 2004 Tanzania 6.8 Dent,

9 Prevalence of epilepsy in adults: Recent record-based studies Place Age adjusted Prevalence Study Rochester 7.1 Hauser, 1994 Spain 4.1 Luengo, 2001 Iceland 4.3 Olafsson, 1999 Aeolian Islands 3.0 Gallitto, 2005 Croatia 4.8 Beilen, 2007 Thailand 7.1 Asawavichienjinda,

10 Estimated number with prevalent epilepsy worldwide Range of prevalence: 3.0/1,000 to 16/1,000 Estimated world population: 6,991,318,084 Number of people with prevalent epilepsy: 20,973,954 to 111,861,089 10

11 First published studies of seizure incidence Incidence per 100, (Crombie 1960) (Kurland 1959) Years 11

12 Incidence of epilepsy per 100,000 Resource poor countries Developed countries Tanzania Ethiopia Chile Iceland Stockholm Rochester Northern Manhattan Rwiza et al, 1992; Tekle_Haimanot et al, 1997; Lavados et al, 1991; Olafsson et al, ; Adelöw, et al 2009; 12 Hauser et al, 1993; Benn et al, 2008

13 Meta-analyses of incidence rates Median incidence rate per 100,000/year High income: 45.0 (IQR ) Middle and low income: 81.7 (IQR ) Ngugi et al, 2011 Median incidence rate 50/100,000 Kotsopoulos et al,

14 Incidence 75 years ago and now Commonalities Men > women Highest in the young and older adults More than 50% have unknown, genetic or presumed genetic etiology 14

15 Temporal changes in epilepsy incidence in adults Adults under age 65: A decreased incidence 18% in Finland from Older adults: An increased incidence 100% in older adults in Rochester when decade was compared to the earlier decades 81% in Finland from 1986 to 2008 Hauser, 1993; Sillanpaa,

16 Temporal changes in epilepsy incidence A decreased incidence in children 40% in children in Rochester when decade was compared to the earlier decades 60% among children in British GP practices, % in Sweden from 1975 to % in Finland from Hauser, 1993; Cockerell, 1995; Heijbel 1975; Blom, 1978; Sillanpaa,

17 Estimated number with new onset epilepsy yearly world-wide Range of incidence: 33.5/100,000 to 113/100,000 Estimated world population: 6,991,318,084 New cases of epilepsy per year: 2,342,091 to 7,900,189 per year 17

18 Epilepsy risk factors Stroke Traumatic brain injury CNS infections Prenatal insult Intellectual disability Cerebral palsy Autism* Dementia Neoplasm Cystercercosis 18

19 Epilepsy comorbidities Neurological (i.e., migraine, stroke, TBI) Somatic (i.e., arthritis, diabetes, CHD, asthma, heart defects) Psychiatric (i.e., depression, anxiety, ADHD, bipolar disorder, schizophrenia, and psychosis) 19

20 Psychiatric Disorders in Prevalent Epilepsy: Canadian Community Survey Percent Epilepsy Controls Tellez-Zenteno et al, Epilepsia 2007;48:

21 Depression and suicide attempt as a risk factor for epilepsy Odds ratio ( ( ) ( ) 0.00 MDD only SA only Both Adjusted for: Age, gender, SES, MDD, and cumulative alcohol consumption Hesdorffer et al. Ann Neurol 2006;59:

22 Incident depression before and after incident epilepsy compared to controls: GPRD Hesdorffer et al, AES

23 Depression: Risk for Continued Seizures Glasgow Cohort Study OR 10 Risk for pharmaco-resistant epilepsy Crude Adjusted 2.4 ( ) 2.2 ( ) 2.3 ( ) 1 Hitiris et al Epilepsy Res 2007;75: subjects had > 10 seizures before treatment initiation 23

24 Seizure Outcome After Anterior Temporal Lobectomy: Effect of LT History of Depression Percent with depression history % 74% 79% 60 12% Kanner et al, Neurology

25 Is first degree family history of unprovoked seizure associated with affective disorder in probands with uncomplicated epilepsy? DSM affective disorder Adjusted OR=2.9 (95% CI= ) Hesdorffer et al Epilepsy (in press) 25

26 Premorbid depression and epilepsy Premorbid depression increases the risk for: Developing epilepsy Pharmaco-resistant epilepsy Poor outcome after anterior temporal lobectomy Depression in probands with epilepsy is associated with a first degree family history of epilepsy What is the possible mechanism? 26

27 Premorbid Depression: FDA RCTs of SSRIs and SNRIs Seizure incidence in MDD randomized in regulatory studies in major depression (N=70,465) SSRIs and SNRIs associated with lower seizure incidence relative to placebo Placebo group: 19-fold higher incidence of seizures than expected in the general population Alper et al., Biol Psychiatry,

28 General population Seizure Threshold 28

29 Depression General population Seizure Threshold 29

30 What about our 23 year old woman? Simple FS as a child, partial seizures at age 8 continuing into adolescence. Age 23 presents with depression But why? Did she have a family history of depression? Did she have an underlying pathophysiological predisposition to both depression and epilepsy? Did the psychosocial burden of having epilepsy contribute to her depression? The contributions of genetic, biological or psychosocial mechanisms to incident depression after epilepsy are so far unanswered by the epidemiological research 30

31 The Diseases, and Casualities this year being 1632 Bills of Mortality, John Graunt, London, Number Infants Fever Smallpox Teeth Dropsie Childbed 31 Consumption Aged Stillborn Bloody flux Convulsion

32 Long-term mortality in Epilepsy and in Status Epilepticus SMR (95% CI) Epilepsy Idiopathic Remote Neurodeficit Idiopathic symptomatic Status epilepticus Remote Progressive symptomatic symptomatic Hauser et al, 1993; Logroscino et al,

33 Mortality due to accidents and injuries 1% to 27% of all deaths in epilepsy Risk factors for accidents and injuries in epilepsy: Increased seizure frequency Longer duration of epilepsy >3 adverse events due to AEDs Cockrell et al, 1994; Hauser et al, 1980, Rafnsson et al 2001, Shackleton et al, 1999; Tomson et al,

34 Predictors of all deaths, epilepsy-related death and SUDEP Unadjusted analysis Lack of 5 year terminal remission Remote symptomatic etiology History of status epilepticus Onset < 2 years Adjusted analysis Lack of 5 year terminal remission Sillanpää and Shinnar

35 Non-adherence to AEDs and mortality 4 Adherent Nonadherent Referent 1 0 Adherent Nonadherent Faught et al,

36 SUDEP with adjunctive AEDs versus adjunctive placebo: A meta-analysis of phase III RCTs Deaths Number of trials OR (95% CI) Definite/probable SUDEP ( ) Risk of SUDEP more than 5-fold greater on adjunctive Placebo than on adjunctive AED at efficacious dose Ryvlin et al Lancet Neurology

37 Epidemiology of Epilepsy: From Epilepsy to Epilepsy Plus Past: Epidemiology identified the incidence and prevalence of epilepsy and clarified strong risk factors noticeable to treating clinicians. The seizures of epilepsy were the focus of studies Present: Focus has turned the burden of epilepsy that makes it more than just seizures. 37

38 Future directions Epilepsy surveillance Large longitudinal surveillance studies are needed in representative populations: Epilepsy incidence, prevalence, treatment gap and mortality Populations must be large enough to allow for substudies In children and the elderly By seizure type and common syndromes In medically intractable patients In surgical patients 38

39 Summary and future directions Epilepsy plus The bidirectional relationship exists for: Neurological disorders Somatic disorders Psychiatric disorders Further studies of epilepsy comorbidities may inform development of new epilepsy therapies 39

40 Future directions Mortality in epilepsy Future studies should focus upon: Risk factors for epilepsy-related mortality (SUDEP, fatal injuries, suicide) in order to develop interventions to decrease such mortality 40