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original article

Long-Term Mortality in Childhood-Onset

Epilepsy
Matti Sillanp, M.D., Ph.D., and Shlomo Shinnar, M.D., Ph.D.

A BS T R AC T
Background
From the Departments of Pediatric Neurology and Public Health, University of
Turku and Turku University Hospital
both in Turku, Finland (M.S.); and the
Departments of Neurology, Pediatrics,
and Epidemiology and Population Health
and the Comprehensive Epilepsy Management Center, Montefiore Medical Center,
Albert Einstein College of Medicine, Bronx,
NY (S.S.). Address reprint requests to Dr.
Shinnar at the Comprehensive Epilepsy
Management Center, Montefiore Medical
Center, 111 E. 210th St., Bronx, NY 10467,
or at sshinnar@montefiore.org.
N Engl J Med 2010;363:2522-9.
Copyright 2010 Massachusetts Medical Society.

There are few studies on long-term mortality in prospectively followed, well-characterized cohorts of children with epilepsy. We report on long-term mortality in a
Finnish cohort of subjects with a diagnosis of epilepsy in childhood.
Methods

We assessed seizure outcomes and mortality in a population-based cohort of 245

children with a diagnosis of epilepsy in 1964; this cohort was prospectively followed
for 40 years. Rates of sudden, unexplained death were estimated. The very high
autopsy rate in the cohort allowed for a specific diagnosis in almost all subjects.
Results

Sixty subjects died (24%); this rate is three times as high as the expected age- and
sex-adjusted mortality in the general population. The subjects who died included 51
of 107 subjects (48%) who were not in 5-year terminal remission (i.e., 5 years
seizure-free at the time of death or last follow-up). A remote symptomatic cause of
epilepsy (i.e., a major neurologic impairment or insult) was also associated with an
increased risk of death as compared with an idiopathic or cryptogenic cause (37% vs.
12%, P<0.001). Of the 60 deaths, 33 (55%) were related to epilepsy, including sudden,
unexplained death in 18 subjects (30%), definite or probable seizure in 9 (15%),
and accidental drowning in 6 (10%). The deaths that were not related to epilepsy
occurred primarily in subjects with remote symptomatic epilepsy. The cumulative
risk of sudden, unexplained death was 7% at 40 years overall and 12% in an analysis that was limited to subjects who were not in long-term remission and not receiving
medication. Among subjects with idiopathic or cryptogenic epilepsy, there were no
sudden, unexplained deaths in subjects younger than 14 years of age.
Conclusions

Childhood-onset epilepsy was associated with a substantial risk of epilepsy-related

death, including sudden, unexplained death. The risk was especially high among children who were not in remission. (Funded by the Finnish Epilepsy Research Foundation.)

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Mortality in Childhood-Onset Epilepsy

ew studies have evaluated long-term

mortality in well-characterized cohorts of
children with epilepsy. With a few notable
exceptions,1-3 studies involving adults are usually
retrospective.4-11 In pediatric series, the followup is generally 5 to 10 years.12-18 In all series, autopsy confirmation of an absence of other causes
of death, which is necessary to confirm sudden,
unexplained death in persons with epilepsy,19 is
rare. We present mortality data from a cohort of
245 subjects with childhood-onset epilepsy who
were followed for 40 years. Rates of autopsy in
this cohort were high.

Me thods
Subjects and Study Design

The study population included all children younger than 16 years of age who were living in the
catchment area of Turku University Hospital,
Turku, Finland, at the end of 1964 and who had
epilepsy, which was defined as at least two unprovoked seizures. The subjects were identified
from the files of Turku University Hospital, other
hospitals and institutions in southern Finland, and
private surgeons and from Finlands National
Health Service registry, which covers the entire
population of that country. Of the 245 patients
identified, the majority (223 patients) were seen
in Turku University Hospital. In the 1960s, all
pediatric patients who had one or more epileptic
seizures were referred for inpatient hospital evaluation. The study population has been described
previously.20-22
The 245 subjects included 150 subjects with
incident cases of epilepsy (61%) whose initial visit
for the evaluation of new-onset seizures occurred
between 1961 and 1964. The remaining 95 subjects with prevalent cases of epilepsy (39%) were
seen before 1961, but they were seen again during the 19611964 study period for active epilepsy
(at least one epileptic seizure during the preceding 3 years and a prior diagnosis of epilepsy). Excluded were children who had febrile seizures only
or other acute symptomatic seizures and children
with a single unprovoked seizure. Also excluded
were children with an onset of epilepsy before
1961 who were either in remission or who died
before 1961.
A follow-up examination was performed every
fifth year up to 2002. Data on deaths were obtained from continuous follow-up of the patients

in the intervals between the 5-year examinations.

Detailed information collected about this subgroup included the date and time of death, the
immediate cause of death, the underlying cause
of death, and autopsy data, when available. Written informed consent obtained from all subjects
or their caregivers permitted access to the hospital files in order to abstract data on the last stages
of the disease before death. To ensure full coverage of all deaths, we also sent a list of the names
of all 245 subjects (and their unique identification
numbers), except those known to be dead, to the
Finnish National Death Register every 5 years and
requested a list of deaths and copies of the death
certificates. Five subjects migrated out of Finland
and were last known to be alive 10, 19, 25, 32,
and 36 years after the onset of epilepsy. Complete
data until death or January 1, 2003, were available for all the remaining subjects. The median
duration of follow-up to the last follow-up contact
or death was 40.0 years (range, 2 to 53) among all
245 subjects and 39.5 years (range, 2 to 42) among
the 150 subjects with incident cases of epilepsy.
The joint ethics review committee of the University of Turku Medical School and University Hospital of Turku approved the study design.
Data on autopsies performed for clinical or
forensic reasons, or both, were available for this
study. The autopsy rate was 70% (42 of 60 deaths)
for all deaths in the cohort and 80% (24 of 30
deaths) for incident cases. Full autopsies of all organs were performed, although in a few subjects,
a less detailed forensic autopsy was performed.
The results of toxicologic screening were obtained
in all subjects. Of the six subjects with incident
cases of epilepsy who were not examined at autopsy, two had malignant, aggressive carcinoma
and permission for an autopsy was not given by
the subjects relatives; two had severe cognitive
impairment, were completely bedridden, and died
of pneumonia; one had progressive muscular dystrophy with pneumonia; and one, who had moderate cognitive impairment, died after an epileptic seizure.
Definitions

Epileptic syndromes, epilepsies, epileptic seizures,

and the causes of seizures were defined according to the guidelines for epidemiologic research
of the International League Against Epilepsy.23-25
Subjects with remote symptomatic epilepsy had
either a major neurologic impairment (e.g., cog-

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Table 1. Mortality among Subjects with Childhood-Onset Epilepsy.*

Variable
Total deaths no.

All Subjects
(N=245)

Subjects with Idiopathic or

Cryptogenic Epilepsy
(N=122)

Subjects with Epilepsy Due to

Remote Symptomatic Causes
(N=123)

60

15

45

Age at death yr
Median

23

26

21

Range

150

1150

149

8692

4638

4054

All

6.90 (5.38.9)

3.23 (1.95.4)

11.10 (8.314.9)

Men

7.33 (5.210.2)

2.69 (1.26.0)

11.63 (8.016.8)

Women

6.41 (4.49.4)

3.74 (1.97.2)

10.33 (6.416.6)

51/60 (85)

11/15 (73)

40/45 (89)

No. of person-yr
No. of deaths/1000 person-yr (95% CI)

Remission status at time of death

Not in remission no./total no. of deaths (%)
In remission no./total no. of deaths (%)

9/60 (15)

4/15 (27)

5/45 (11)

Receiving medication no.

Not receiving medication no.

* CI denotes confidence interval.

A remote symptomatic cause of epilepsy indicates epilepsy associated with a major neurologic abnormality or insult.
A total of 107 subjects in the study cohort were not in 5-year terminal remission, and 138 were in 5-year terminal remission; of the 138 subjects in 5-year terminal remission, 35 were receiving medication and 103 were not.

nitive impairment, clinically significant developmental delay [developmental quotient <70 in children younger than 7 years of age], cerebral palsy,
or autism) or a history of a major neurologic insult (e.g., head trauma, stroke, or meningitis). The
remaining subjects were determined to have cryptogenic or idiopathic epilepsy. The classification
of epilepsy was made in all subjects, and the detailed seizure types and epilepsy syndromes in this
cohort have been reported previously.22 These classifications were determined before the new classifications of epilepsy syndromes26 and are used
here for consistency with previous studies.
Sudden, unexpected death in a person with
epilepsy was defined, in accordance with the definition by Annegers,19 as sudden death with no
evidence of a seizure and no other identified cause
of death, with confirmation of these findings by
autopsy. In almost all cases of sudden, unexplained death in a person with epilepsy, pulmonary edema was detected on autopsy. We also examined the rates of sudden, unexplained death
among persons with epilepsy in accordance with
the alternative definition by Nashef,27 which
includes deaths for which there is evidence of
probable or definite seizures, although it excludes
deaths in persons with known status epilepticus.
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Statistical Analysis

Our statistical methods took into account the timedependent nature of the mortality data. The rate
of death was calculated as the number of deaths
divided by the person-years at risk during the
study; direct adjustment for age and sex was performed on the basis of the 2002 Finnish population. The product-limit method was used to calculate the risk of death from the onset of
epilepsy.28,29 Data on subjects were censored at
the time of the last follow-up or on January 1,
2003. Standard errors and 95% confidence intervals were calculated with the use of a modification of the Greenwood formula.29 Univariate and
multivariate analyses were performed with the use
of the Cox proportional-hazards model, and remission status was treated as a time-dependent covariate.29-31 Rates of death according to remission
status were adjusted for the number of personyears at risk during the remission period. Rate
ratios with 95% confidence intervals were calculated with the use of the Cox regression models.
When the cohort with incident epilepsy and the
cohort with prevalent epilepsy were combined, adjustment was made for the left truncation due to
the delayed entry of the cohort with prevalent epilepsy.32 A direct age- and sex-adjusted standard

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Mortality in Childhood-Onset Epilepsy

Table 2. Causes of Death.

All Subjects
(N=245)

Variable
Total deaths no.
Death related to epilepsy no./total
no. of deaths (%)

Subjects with Idiopathic or

Cryptogenic Epilepsy
(N=122)

Subjects with Epilepsy Due to

Remote Symptomatic Causes
(N=123)*

60

15

45

33/60 (55)

9/15 (60)

24/45 (53)

Witnessed seizure no.

Status epilepticus no.

Probable seizure no.

Drowning no.

Sudden, unexplained death no.

Death not related to epilepsy no./
total no. of deaths (%)
Pneumonia no.
Cardiovascular disease no.

18

11

26 (43)

6 (40)

20 (44)

12

12

Suicide no.

Other cause of death no.

Cause of death unknown no.

* A remote symptomatic cause of epilepsy indicates epilepsy associated with a major neurologic abnormality or insult.

mortality ratio was calculated; this was defined

as the ratio of the number of deaths observed in
the study group to the number that would be expected if the age- and sex-specific rates of death
in the study population were the same as those in
the general population of the study area from
1945 through 2002.31,33 The standard mortality
ratio adjusted for age, sex, and time period was
calculated with the use of 5-year periods for 5-year
age groups, and 95% confidence intervals were
determined. The case fatality rate was defined as
the proportion of persons who died during followup. Statistical computations were performed with
the use of SAS software, version 9.1.3 (SAS Institute).

R e sult s
Characteristics of the Study Population

A total of 245 subjects, 150 with incident cases of

epilepsy and 95 with prevalent cases of epilepsy,
were included in the study. The median age at the
onset of epilepsy was 3 years (range, 0 to 14)
among subjects with incident cases of epilepsy
and 2 years (range, 0 to 12) among subjects with
prevalent cases of epilepsy. A total of 122 subjects had idiopathic or cryptogenic epilepsy, and
123 subjects had remote symptomatic epilepsy
(i.e., epilepsy associated with a major neurologic

abnormality or insult). The median duration of epilepsy before achieving 5-year long-term remission
was 17 years (range, 1 to 52) for surviving subjects and 22 years (range, 1 to 50) for those who
died during the follow-up period. At the time of
the last follow-up contact or death, 110 patients
(45%) were in 5-year terminal remission and were
not receiving medication, 28 (11%) were in 5-year
terminal remission and were receiving medication, and 107 (44%) were not in 5-year remission.
Overall Mortality

During the median follow-up period of 40 years,

60 subjects died, for an overall case fatality rate
of 24% and a rate of death of 6.9 per 1000 person-years among all subjects (Table 1). The rates
of death among the subjects with incident cases
of epilepsy (5.3 per 1000 person-years) and those
with prevalent cases (9.6 per 1000 person-years)
did not differ significantly, and the two groups
were therefore combined. Details on incident cases are included in the Supplementary Appendix,
available with the full text of this article at NEJM
.org. The age- and sex-adjusted rates of death were
7.2 per 1000 person-years, with standard mortality ratios of 5.5 (95% confidence interval [CI], 4.6
to 6.6) in incident cases and 6.4 (95% CI, 5.9 to
7.0) in the overall cohort; the latter ratio is an estimate and was not adjusted for the delayed entry

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Cumulative Rate of Death

50

40
Remote symptomatic cause

30

20
Idiopathic or cryptogenic cause

10

10

15

20

25

30

35

40

Years after the Onset of Epilepsy

Figure 1. Cumulative Rate of Death According to Cause of Epilepsy.

A remote symptomatic cause indicates epilepsy that is associated with a
major neurologic abnormality or insult.

of subjects with prevalent cases of epilepsy. The

causes of death and their relationship to remission status and cause of epilepsy are summarized
in Tables 1 and 2. The highest rate of death occurred among subjects who were not in 5-year terminal remission; only 4 deaths occurred in the 103
subjects in 5-year terminal remission who were
not receiving medication at the time of death or
the last follow-up contact (1.5 deaths per 1000
person-years), as compared with 5 deaths in 35
subjects in 5-year remission who were receiving
medication (11.8 per 1000 person-years) and 51
deaths in the 107 subjects who were not in 5-year
remission (15.9 per 1000 person-years) (P<0.001).
As expected, the rates of death were significantly
higher among subjects with epilepsy due to remote
symptomatic causes (11.1 deaths per 1000 personyears) than among subjects with cryptogenic epilepsy (2.9 per 1000 person-years) and those with
idiopathic epilepsy (3.5 per 1000 person-years)
(P<0.001) (Fig. 1 and Table 1). More than three
quarters of the deaths occurred in subjects who
were not in 5-year terminal remission and in the
groups with epilepsy due to remote symptomatic
causes; these included 21 of the 26 deaths not
directly related to epilepsy and 24 of the 33 deaths
related to epilepsy. The difference in the rates of
death between subjects with epilepsy due to remote symptomatic causes and subjects with idiopathic or cryptogenic epilepsy was significant (11.1
deaths per 1000 person-years vs. 3.2 per 1000 person-years, P<0.001).
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Deaths in childhood occurred primarily in the

group of subjects with epilepsy due to remote
symptomatic causes and were most often related
not to epilepsy but to the underlying disease (Ta
ble 1). Deaths due to epilepsy-related causes in
subjects with cryptogenic or idiopathic epilepsy
occurred primarily in adolescence and adulthood.
The risk factors for both overall death and epilepsy-related death are summarized in Table 3. Univariate analysis showed that the hazard ratio for
death was significantly increased among subjects
who were not in 5-year terminal remission, those
with a remote symptomatic cause of epilepsy, and
those with a history of status epilepticus. Within
the group of patients with remote symptomatic
epilepsy, severe cognitive impairment was associated with an increased mortality (rate ratio, 4.1;
95% CI, 2.0 to 8.3; P<0.001). On multivariable
analysis, only 5-year terminal remission was significantly associated with the hazard ratio for
death. The other variables have previously been
shown to be associated with a lack of remission.20-22 Other factors, such as the type of epilepsy (localization-related epilepsy, temporallobe epilepsy, or another type of epilepsy) or cerebral palsy, did not influence the risk of death in
the group of subjects with remote symptomatic
epilepsy.
Causes of Death

The causes of death are listed in Table 2. Among

the 60 patients who died, the cause of death was
not directly related to the seizure disorder but
instead was related to the underlying neurologic
problem or to another disease in 26 patients (43%)
and was related to the epilepsy in 33 patients
(55%); the latter group included sudden, unexplained death in epilepsy in 18 patients (30%),
probable or definite seizure in 9 (15%), and accidental drowning in 6 (10%). With the use of the
alternative classification of sudden, unexplained
death in epilepsy,27 which includes possible or
definite seizures as long as the seizures were not
status epilepticus, 38% of the deaths were due to
sudden, unexplained death in epilepsy, 7% were
due to status epilepticus, and 10% were due to
accidental drowning.
Sudden, Unexplained Death and EpilepsyRelated Deaths

There were 18 cases of sudden, unexplained

death,19 including 15 cases that were confirmed
by autopsy. Seven of the subjects with sudden,

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Mortality in Childhood-Onset Epilepsy

Table 3. Predictors of Death.*

Risk Factor

Univariate Analysis
Hazard Ratio
(95% CI)

Absence of 5-yr terminal remission

Multivariate Analysis

P Value

Hazard Ratio
(95% CI)

P Value

5.3 (2.611.0)

<0.001

4.7 (1.514.9)

0.007

Remote symptomatic cause of epilepsy

3.4 (1.96.1)

<0.001

1.5 (0.73.6)

0.31

Prior status epilepticus

1.9 (1.23.2)

0.01

1.5 (0.73.0)

0.28

Age at onset <2 yr

1.4 (0.82.3)

0.20

1.7 (0.83.5)

0.13

Absence of 5-yr terminal remission

6.4 (2.218.8)

<0.001

4.7 (1.514.9)

0.007

Remote symptomatic cause of epilepsy

3.1 (1.46.7)

0.004

1.5 (0.73.6)

0.31

Prior status epilepticus

2.1 (1.14.2)

0.03

1.5 (0.73.0)

0.28

Age at onset <2 yr

1.9 (0.963.8)

0.06

1.7 (0.83.5)

0.13

Absence of 5-yr terminal remission

5.2 (1.418.5)

0.01

5.0 (1.220.1)

0.02

Prior status epilepticus

2.8 (1.17.0)

0.03

2.6 (0.97.5)

0.07

Age at onset <2 yr

2.1 (0.85.5)

0.11

1.9 (0.75.2)

0.20

Remote symptomatic cause of epilepsy

1.9 (0.74.8)

0.20

0.8 (0.32.4)

0.72

Localization-related epilepsy

0.8 (0.32.0)

0.60

0.5 (0.21.5)

0.21

All deaths

Epilepsy-related deaths

Sudden, unexplained deaths

* A Cox proportional-hazards model was used to assess the risk of death associated with an absence of 5-year terminal
remission, with remission status treated as a time-dependent covariate. A remote symptomatic cause of epilepsy indicates epilepsy associated with a major neurologic abnormality or insult. CI denotes confidence interval.

unexplained death had idiopathic or cryptogenic

epilepsy, and 11 had epilepsy due to remote symptomatic causes. The median age at death among
the subjects with sudden, unexplained death was
25 years (range, 4 to 49) overall, 27 years (range,
13 to 48) among subjects with idiopathic or cryptogenic epilepsy, and 23 years (range, 4 to 49)
among those with epilepsy due to remote symptomatic causes. Although there were two cases of
probable sudden, unexplained death among children 6 and 8 years of age with remote symptomatic epilepsy, all cases of sudden, unexplained
death in the group with cryptogenic or idiopathic epilepsy occurred in adolescents and adults
(Table 3). With the use of the alternative definition of sudden, unexplained death in epilepsy,27
there were 23 cases, 17 of which were confirmed
by autopsy.
Over the 40-year follow-up period, the risk of
sudden, unexplained death among subjects with
epilepsy was 7% (95% CI, 5 to 12) among all
subjects and 12% (95% CI, 8 to 20) among those
who were not in 5-year terminal remission and
who were not receiving medication (Fig. 2). Among
subjects with idiopathic or cryptogenic epilepsy,

the risk of sudden, unexplained death19 was 5%

(95% CI, 2 to 11) overall, and the risk was 15%
(95% CI, 7 to 31) among subjects who were not
in 5-year terminal remission and no longer receiving medication. On univariate analysis, the absence of terminal remission and a history of status epilepticus, but not a remote symptomatic
cause or a localization-related epilepsy syndrome,
were associated with an increased risk of sudden,
unexplained death among subjects with epilepsy
(Table 3). On multivariate analysis, only the absence of 5-year terminal remission was significantly associated with sudden, unexplained death.
The hazard ratios for all epilepsy-related deaths
are shown in Table 3. Not surprisingly, these
ratios are similar to those of sudden, unexplained
death among subjects with epilepsy. According
to the alternative Nashef criteria,27 most of the
epilepsy-related deaths would qualify as sudden,
unexplained death in subjects with epilepsy.

Discussion
The strength of this study is that it involves a cohort that was prospectively followed for 40 years,

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Cumulative Risk of Death

0.5

0.4

0.3
All epilepsy-related deaths
0.2

0.1
Sudden, unexplained deaths
0.0

10

15

20

25

30

35

40

Years after the Onset of Epilepsy

Figure 2. Cumulative Risk of All Epilepsy-Related Deaths and Sudden,

Unexplained Deaths in Subjects with Epilepsy.
Data shown are for patients at risk (i.e., receiving medication, with or without 5-year terminal remission).

with complete ascertainment of death and a high

rate of autopsy-confirmed causes of death. With
the longer follow-up, the epilepsy-related mortality is substantially higher than that reported in
the original 1998 study (33% vs. 20%).20 Also,
classification of the causes of death with the use
of the autopsy data and the more formal definitions of sudden, unexplained death in subjects
with epilepsy also greatly increase the number of
cases. The reclassification substantially changes
the picture of epilepsy-related mortality in this
cohort. Frequent causes of death in Finland in
persons between birth and 54 years of age in
2002 were accidents (accounting for 24.0 deaths
per 100,000 persons), vascular causes (18.0 per
100,000), suicide (13.3 per 100,000), gynecologic
cancer (4.0 per 100,000), and congenital malformations (1.6 per 100,000).
The increased risk of death associated with
childhood-onset epilepsy that we observed was
substantial and persisted into adulthood. The increased risk was limited to subjects who were not
in terminal remission and those who had another
neurologic disability, particularly severe cognitive
impairment. The most important risk factor for
death from any cause as well as for epilepsyrelated death specifically was the absence of 5-year
terminal remission. By definition, epilepsy-related
deaths occurred exclusively in subjects who were
not in 5-year terminal remission. Univariate analy
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sis showed that the absence of 5-year terminal

remission, a remote symptomatic cause (epilepsy
associated with a major neurologic abnormality
or previous insult), severe cognitive impairment,
and a history of status epilepticus also were significant predictors of death; multivariate analysis showed that only the absence of 5-year terminal remission remained an important predictor.
It is somewhat surprising that other factors
known to be associated with increased mortality
among patients with epilepsy did not emerge as
risk factors. Severe cognitive impairment has been
associated with an increased risk of sudden, unexplained death among subjects with epilepsy,
even after adjustment for seizure frequency in a
group with active epilepsy.3,34 The most likely explanation for an absence of this association in
our cohort is that the more severely affected children in the symptomatic group were also less
likely to have seizure-free remission. Deaths unrelated to seizures occurred primarily in the symptomatic group, and in the group with idiopathic
or cryptogenic epilepsy, such deaths occurred at
a much older age.
We had considerable data on and autopsy confirmation of the majority of epilepsy-related deaths.
Depending on which of the two definitions was
used,10,18 sudden, unexplained death occurred in
up to 9% of the entire cohort. This number, however, included subjects who had been in remission
for many years without receiving medication. The
risk of sudden, unexplained death among subjects with epilepsy who were not in 5-year terminal remission was substantially higher. Given our
40-year follow-up period, it is likely that we have
ascertained most of the cases of sudden, unexplained death that will occur in this cohort, since
the peak age period for sudden, unexplained death
in patients with epilepsy is generally between 20
and 40 years of age,4,33 and after 50 years of age,
it can become difficult to make this classification with certainty. Other studies of childhoodonset epilepsy with shorter periods of follow-up
have shown that among children with idiopathic
or cryptogenic epilepsy, the rate of death is no
different from that in the general population, and
in childhood, mortality is increased only among
subjects with remote symptomatic epilepsy.5-9
However, in studies involving adults with sudden,
unexplained death, the onset of epilepsy in childhood is often a risk factor.34-36 In this study,
there were no cases of sudden, unexplained death

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Mortality in Childhood-Onset Epilepsy

among children younger than 14 years of age who lower among those who become seizure-free after
had idiopathic or cryptogenic epilepsy; however, surgery than among those who do not,35 sugthe risk of sudden, unexplained death and other gesting that the risk is potentially modifiable.
epilepsy-related deaths was relatively high among
adults with active epilepsy.
Supported by a grant from the Finnish Epilepsy Research
Our data alone do not provide support for ag- Foundation.
Disclosure forms provided by the authors are available with
gressive treatment to prevent sudden, unexplained the full text of this article at NEJM.org.
death in patients with epilepsy. However, studies
We thank Hannu Kalimo, M.D., Ph.D., professor of neuropaof epilepsy surgery in adults with medically re- thology, and Pekka Saukko, M.D., Ph.D., professor of forensic
medicine, for collecting the autopsy data; Hans Helenius, M.Sc.,
fractory partial epilepsy have shown that the rates for statistical advice; Olli Kaleva, B.A., for computations; and
of sudden, unexplained death are substantially Dale Hesdorffer, Ph.D., for her constructive suggestions.
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3. Walczak TS, Leppik IE, DAmelio M,
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