Estimating risk for developing epilepsy
A population-based study in Rochester, Minnesota
D.C. Hesdorffer, PhD
G. Logroscino, MD
E.K.T. Benn, MPH
G. Cascino, MD
W.A. Hauser, MD
Objectives: Previous studies that have assessed the risk of developing epilepsy have failed to
account for the competing risk of death, significant in the elderly where epilepsy incidence
is highest. We report the lifetime risk for epilepsy, accounting for the competing risk of
Methods: Lifetime risk and cumulative incidence of epilepsy were examined among Rochester,
MN, residents between 1960 and 1979. Age-, gender-, and calendar year–specific deaths
were obtained for Rochester, MN. Lifetime risk was calculated as the conditional probability
of developing epilepsy by a specific age for a person reaching that age who had not yet
developed epilepsy. Lifetime risk and cumulative incidence were compared for age and time
Results: We identified 412 individuals with incident epilepsy diagnosed between January 1,
1960, and December 31, 1979. Lifetime risk was 1.6% to age 50 and 3.0% to age 80; cumula-
tive incidence was 1.7% to age 50 and 3.4% to age 80. Similar differences were seen across
epilepsy etiologies. Lifetime risk through 87 years of age increased over time from 3.5% in
1960–1969 to 4.2% in 1970–1979.
Conclusions: One in 26 people will develop epilepsy during their lifetime. Lifetime risk provides an
estimate of an individual’s risk for epilepsy over his or her remaining lifetime, translates into the
number of people who are expected to develop epilepsy, and assists health care planners as they
estimate service needs for epilepsy. Neurology®2011;76:23–27
LR ? lifetime risk.
Epilepsy is the fourth most common neurologic disorder with an average annual incidence of
about 55 per 100,000 population in the United States1and in Europe. The incidence curve is
j-shaped with high incidence rates in infants under 1 year of age (100/100,000), falling by age
20, and remaining low (20/100,000) until age 60, when it begins a dramatic climb, reaching
175/100,000 by age 80.
The long-term risk for developing epilepsy is measured as the lifetime risk (LR), which is the
probability that a person will develop epilepsy over his or her remaining lifetime.2Because it
considers the impact of the competing risk of dying, the LR is important for diseases like
epilepsy, where the incidence increases dramatically in older ages. Useful to clinicians, it de-
scribes the risk of developing epilepsy in individuals from their current age through their
remaining lifetime. LR is also useful for public health planning purposes because it forecasts the
burden of epilepsy in the community.
LR has been measured for other diseases with high incidence in the elderly, including stroke
and Alzheimer disease,3but LR for epilepsy has not been assessed. This is relevant because the
From the Departments of Neurology, Epidemiology, and Biostatistics (D.C.H., E.K.T.B., N.K., W.A.H.), Gertrude H. Sergievsky Center, Mailman
School of Public Health at Columbia University, New York, NY; Department of Neurology (G.L.), University of Bari, Bari, Italy; and Departments of
Neurology and Health Sciences Research (G.C., W.A.H.), Mayo Clinic and Mayo Foundation, Rochester, MN. N.K. was a high school intern at
Columbia University during her work on this manuscript. She is now a student at Boston University.
Study funding: Supported in part by grants from NINDS (5-P50-NS-16308) to the University of Minnesota and NIH (MO1RR00645) to Columbia
Disclosure: Author disclosures are provided at the end of the article.
Address correspondence and
reprint requests to Dr. D.C.
Hesdorffer, G.H. Sergievsky
Center, 630 West 168th Street,
P&S Unit 16, New York, NY
Copyright © 2010 by AAN Enterprises, Inc.
incidence of epilepsy increases dramatically
beginning at age 60 years and the elderly are
the fastest growing segment of the general
population in developed countries. We
present estimates of the LR for epilepsy in a
population-based study from Rochester, MN,
during the period 1960 through 1979.
METHODS Previous studies in Rochester, MN, have as-
sessed the incidence of seizure disorders from 1935 to 1984.1
Our case group is restricted to the subjects who developed
epilepsy between 1960 and 1979. Epilepsy was defined as 2 or
more unprovoked seizures and unprovoked seizures as a sei-
zure without an identified proximate precipitant. Incident ep-
ilepsy was ascertained through the records-linkage system of
the Rochester Epidemiologic Project, which links all medical
records from medical facilities in Southeastern Minnesota
and includes inpatient, outpatient, emergency room, doctor’s
private office, and home visits. We reviewed the medical
records of all residents with a diagnosis of seizure, convulsion,
epilepsy, or conditions known to be related to seizures.
Factors measured. The age at epilepsy diagnosis was used in
calculating cumulative incidence and LR. Separate analysis
considered epilepsy diagnosis at age ?60 years, using 5-year
age groups. Epilepsy etiology was categorized as progressive
symptomatic, remote symptomatic, or idiopathic/cryptoge-
nic.4Deaths in the general population of Rochester, MN,
were obtained by age, gender, and calendar year5-8to
The study was approved by the IRB at Columbia University.
Data were collected by chart abstraction and consent was not
obtained from subjects.
Statistical analysis. We defined Rj as the total population at
risk at any given age j.
Cumulative incidence. We let ejequal the total number of
cases in the study period at each age j. hjestimates the hazard,
which is the probability that a person of age j will develop epi-
lepsy in the next instant of time.9We calculated hjby dividing
ej/Rj. The survival probability (Sj) at each age j was calculated,
using the following:
Sj? exp??1 ? ??hj??
where j ? 1, …, 97.
For example, to determine the cumulative hazard until
age 5, hjwas summated from the age of 0 until 5 with the
negative result of the summation exponentiated (note: Sj? 1
when j ? 0). Next, the hazard (hj) was multiplied by the
survival probability at age j ? 1 (fj? hj[Sj?1]), representing
the age-specific incidence at age j. Finally, cumulative inci-
dence was calculated as the summation of the age-specific
incidences from age 0 to age j (Fj? ?fj).
The cumulative incidence of epilepsy does not reflect the
competing risk of death prominent in the elderly where epi-
lepsy incidence is most increased. Instead, deaths are consid-
ered to be equivalent to withdrawals with the same assumed
but unassessed future risk of epilepsy as subjects who are cen-
Remaining lifetime risk. Unlike cumulative incidence, the
LR adjusts for the competing risk of death by considering deaths
and incident epilepsy as events. That is, people who die are con-
sidered to have zero risk for developing epilepsy. To calculate
LR, the variable hj* represented the adjusted hazard, computed
as the deaths plus cases (ej*) divided by Rj(hj* ? ej*/Rj). The
adjusted hazard was used to calculate the adjusted survival prob-
ability, Uj* (Uj* ? exp[?1* ?(hj*)]). The variable fj* was
calculated by multiplying the original hazard (hj) by Uj*?1, the
age-specific incidence adjusted for the competing risk of death
(fj* ? hj[Uj*?1]). This permitted calculation of LR, a summa-
tion of the age-specific incidences from age 0 to age j adjusted for
the competing risk of death (Fj* ? ?fj*).
RESULTS Incident epilepsy was diagnosed in 412
individuals between January 1, 1960, and Decem-
ber 31, 1979; 60.2% had partial seizures. Median
age was 25.9 years with 26.9% ?60 years at diag-
nosis and 49.3% were female. The number of cases
increased between 1960 and 1969 and 1970–
1979, representing a trajectory of growth and
aging of the population. There were 465,698
person-years of exposure in 1960–1969 and
556,316 in 1970–1979 with a total of 3,885
deaths, 1,737 in 1960–1969, and 2,148 in 1970–
1979. In 1970, life expectancy was 69.4 years for
men and 76.8 years for women in Minnesota.10
Cumulative incidence and lifetime risk for epilepsy.
The cumulative incidence was 0.9% to age 20,
1.7% to age 50, and 3.4% to age 80 (figure 1A).
The LR was 0.9% to age 20, 1.6% to age 50, and
3.0% to age 80. The curves begin to noticeably
diverge at age 70 years when mortality begins to
increase, demonstrating that cumulative incidence
overestimates LR when the competing risk of mor-
tality becomes large. Relative to LR, cumulative
incidence was 6.6% higher at age 70–74 and
17.8% higher at age 80–84. These trends were
observed for men and for women (figure 1, B and
C) and by epilepsy etiology, with the greatest dif-
ference observed for progressive symptomatic epi-
lepsy where incidence increases most dramatically
in the elderly (table e-1 and figures e-1, e-2,
and e-3 on the Neurology®Web site at www.
Remaining lifetime risk by age. Remaining LR sets
the risk at 0 for the beginning age or age group,
whereas LR considers the risk from age 0 onward. To
highlight the impact of increasing mortality on dif-
ferences between cumulative incidence and remain-
ing LR for epilepsy, we examined these measures in
the elderly overall and by gender by 5-year age
groups (table 1). With increasing mortality from age
70–74 years onward, remaining LR becomes lower
than cumulative incidence.
We also examined the remaining LR over a 40-
year period, beginning at different ages (table 2).
For a 20-year-old without epilepsy, the LR for ep-
ilepsy is 0.23% over the next 5 years, 0.6%
Neurology 76January 4, 2011
over the next 10 years, and 1.06% over the next 40
years or until age 60 years. In contrast, for a 50-
year-old without epilepsy, the LR for epilepsy is
0.15% over the next 5 years, 0.71% over the next
20 years, and 2.58% over the next 40 years or until
age 90 years.
Time trends in the lifetime risk. The LR of epilepsy
was 3.5% through 97 years of age during 1960–
1969 vs 4.2% during 1970–1979.
Number developing epilepsy. Applying age- and
gender-specific LR estimates to the July 2007 US
population (301,139,947) 11,744,457 individuals
(3.9%) will ultimately develop epilepsy in their
DISCUSSION Based upon the LR calculations in
this population-based study, 1 in 26 people will
develop epilepsy during their lifetime. Men have a
higher risk of developing epilepsy (1 of every 21
males) than women (1 of every 28 females). This
approach is more accurate than cumulative inci-
dence, and it is better comprehended by most peo-
ple who are accustomed to similar statistics
provided for cancer.
Cumulative incidence has been used in etio-
logic studies of epilepsy and for public health pur-
poses to determine health care needs of a
population. It is useful in children, because mor-
tality is low, and in etiologic studies. However,
cumulative incidence may overestimate the risk for
developing diseases with high incidence in the el-
derly where significant mortality represents a com-
peting risk. This is because the cumulative
incidence assumes that individuals who die before
they can be observed to have the disease are as-
sumed to have developed the disease at the same
rate as those who survive.11In contrast, LR adjusts
for the competing risk of death by setting the risk
for disease after death at 0, and it provides a better
measure of the risk for developing epilepsy given
survival to a specific age, particularly in the elderly
where the risk of death due to other causes is
LR can be used for individual risk prediction with
the usual caveats because it is a measure based upon
population estimates3and not upon factors related to
any one individual (e.g., familial life expectancy, risk
factors). Even with this limitation, LR is informative
about the number who will develop epilepsy, 1 in 26
people in the population, which may be easier to
communicate than the percentage of people who will
develop epilepsy by a given age.
The LR for epilepsy from Rochester, MN, is
likely similar to that for other developed countries
with comparable sociodemographics for the spe-
cific birth cohorts. However, our findings may not
be applicable to other populations with markedly
different death rates due to a low life expectancy,
such as developing countries. Additionally, our
findings will not be applicable to other popula-
tions that may have a greater incidence of epilepsy.
Figure 1Cumulative incidence and lifetime risk for epilepsy overall and in
males and females
(A) Cumulative incidence and lifetime risk of epilepsy in males, 1960–1979. (B) Cumulative
incidence and lifetime risk of epilepsy in females, 1960–1979. (C) Cumulative incidence
and lifetime risk of epilepsy, 1960–1979.
Neurology 76 January 4, 2011
These limitations of the LR are small, however,
since the distribution of different etiologic groups
may also differ in different age groups with very
different expectations of life in these settings. The
LR for specific epilepsy etiologies may be greater
in populations where treatments of stroke, for ex-
ample, have markedly improved survival thereby
increasing the time period in which such individu-
als are at increased risk for developing epilepsy.
Our data are drawn from 1960 to 1979. This does
not compromise the validity of the comparison be-
tween cumulative incidence and LR. However, with
the increase in life expectancy, the LR of epilepsy
should be greater than what we report, particularly
for males. Between 1970 and 2005 in the United
States, life expectancy has risen from 67.1 years to
75.2 years for males and from 74.7 years to 80.4
years for females.13
Using the methodology described in this arti-
cle, LR has been assessed for other neurologic
disorders, including stroke,3dementia,3and Par-
kinson disease.14In the elderly, the LR for epilepsy
is 0.31% for a 65- to 69-year-old and 1.6% to age
80 for a 50-year-old. In Framingham, MA, the LR
is 14.3% for first stroke to age 85 for a 55-year-
old and 4.0% for dementia to age 80 for a
Our data suggest that almost 12 million individu-
als in the United States will develop epilepsy in their
lifetime. The impact of this calculation is greatest in
the elderly who have the highest incidence, an im-
portant concern given the aging population. Infor-
mation obtained from the LR has several important
uses. LR provides physicians with an estimate of an
individual’s risk for developing epilepsy over his or
her remaining lifetime, a risk estimate that readily
translates into numbers of people who are expected
to develop epilepsy, and it provides useful informa-
tion for health care planners estimating services
needed for epilepsy.
Dr. Hesdorffer has served on a scientific advisory board for Pfizer Inc.; has
received funding for travel from UCB; serves as an Editor of Epilepsia,
Editor of Epilepsy Research, and as a Contributing Editor of Epilepsy Cur-
rents; and has received research support from the CDC (DP002209 [PI]),
the AUCD (RT01 [Co-I (PI of Columbia subcontract)]), the NIH
(NINDS NS31146 [Co-I (PI of Columbia subcontract)]), NINDS
NS043209 [Co-I (PI of Columbia subcontract)]), and NICHD
HD042823 [Co-I]), and the Maternal and Child Health Bureau
(MC00007 [Co-I]). Dr. Logroscino serves as an Associate Editor for Neu-
roepidemiology; has received speaker honoraria from Lundbeck Inc. and
Novartis; serves on the Special Committee of the Italian Ministry of
Health for Neuromuscular diseases; and receives research support from
the University of Bari. E.K.T. Benn and N. Katri report no disclosures.
Dr. Cascino serves as an Associate Editor for Neurology®and receives
research support from NeuroPace, Inc., and the NIH (R01 NS53998-03
[PI]). Dr. Hauser has served on a scientific advisory board for Lundbeck,
Inc. and Ovation Pharmaceuticals, Inc.; has served as a consultant for
Pfizer Inc. and Intranasal; serves on the editorial boards of Acta Neuro-
logica Scandinavia, Neuroepidemiology, and Epilepsy Research; and has re-
ceived research support from the CDC [AAMC MM-1002-07/07 (PI)]
and from the NIH/NINDS [5 T32 NS07153 (PI), R01 NS020656 (Co-
I), R01 NS036319 (Co-I), and R01 NS043472 (Co-I)] and the Hotch-
kiss Neurological Institute.
Received November 7, 2009. Accepted in final form July 15, 2010.
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Table 1 Cumulative incidence and remaining lifetime risk (RLR) for epilepsy in
the elderly, overall and by sex
incidence (%)RLR (%)
incidence (%) RLR (%)
incidence (%)RLR (%)
0.10 0.10 0.10 0.10 0.100.10
0.310.30 0.24 0.230.420.39
0.65 0.61 0.520.49 0.850.78
1.281.13 0.940.85 1.84 1.60
1.851.57 1.531.30 2.40 2.03
2.73 2.18 2.241.793.75 2.99
3.25 2.51 2.77 2.124.26 3.34
Table 2Remaining lifetime risk (RLR) for epilepsy by age
at 5 y
at 10 y
at 20 y
at 30 y
at 40 y
0.13 0.25 0.480.72 1.11
0.140.24 0.49 0.891.75
Neurology 76 January 4, 2011
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