Epilepsy & Behavior 28 (2013) 391–394

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Epilepsy & Behavior

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Obesity in adults with epilepsy

Jaromir Janousek, Arkady Barber, Lenka Goldman, Pavel Klein ⁎
Epilepsy, Mid-Atlantic Epilepsy and Sleep Center, Bethesda, MD 20817, USA

a r t i c l e i n f o a b s t r a c t

Article history: Sixty-eight percent of the US adult population is overweight, and 35% is obese. The rate of obesity in patients with
Received 11 January 2013 epilepsy is unknown. Its determination was the goal of the present study. Weight and height were measured, and
Revised 9 April 2013 body mass index (BMI) was calculated in all newly evaluated patients with epilepsy at a single epilepsy center
Accepted 10 May 2013
between 2003 and 2009. Five hundred fifty-four patients aged ≥16–87 years were included (62.7% were
Available online 14 July 2013
women, 12.6% with primary generalized epilepsy, and 86.4% with localization-related epilepsy). Three hundred
Keywords:
six (55.2%) patients were overweight or obese (BMI > 25 kg/m2) (95% confidence interval [CI]: 51.1%–59.3%),
Epilepsy 173 (31.2%) were obese (BMI > 30 kg/m2) (95% CI: 27.5%–35.2%), and 24 (4.3%) were morbidly obese
Seizures (BMI > 40 kg/m2). Overweight/obesity combined was more common in men (65.4% [95% CI: 58.8%–71.5%])
Obesity than in women (49% women [95% CI: 43.3%–54.3%]) (p ≤ 0.001). The rate of overweight/obesity combined
Antiepileptic drugs trended to be greater in blacks (67.9%) than in whites (51.9%). Obesity alone was more common in blacks
(46.4%) than in whites (29.4%), with too few Hispanics and Asians to allow a comparison. Overweight/obesity
and obesity rates were higher in patients with refractory than nonrefractory epilepsy (60.4% vs. 49.2% over-
weight, 36.9% vs.24.6% obesity). Obesity was more common in patients treated with polytherapy than those
treated with monotherapy (37.7% vs. 25%). There were no associations between obesity and other disease char-
acteristics such as epilepsy type, duration, or etiology. Obesity is common in patients with epilepsy, similar to the
general population.
© 2013 Elsevier Inc. All rights reserved.

1. Introduction All consecutively newly evaluated patients with epilepsy at a

Sixty-eight percent of the US adult population is overweight, defined
as a body mass index (BMI) of >25 kg/m2, including 35.7% of US adults
who are obese (with a BMI of >30 kg/m2) [1,2]. Patients with epilepsy
may have a greater risk for obesity than the general population because
they are often sedentary and may be treated with weight gain-causing
medications such as valproate (VPA) and pregabalin (PG) and because
epilepsy could potentially affect hypothalamic neuroendocrine control
of energy homeostasis, akin to its effect on reproductive endocrine func-
tion [3,4]. While a number of surveys have estimated the prevalence
of obesity in patients using self-reported epilepsy and self-reported
weight and height information [5–9], the frequency of obesity in epilep-
sy has not been systematically studied in patients with verified epilepsy
and BMI [10]. The goal of the present study was to determine the fre-
quency of obesity in a patient population with epilepsy.
2. Methods
The study was approved by the institutional review board of Holy
Cross Hospital, Silver Spring, MD. The study was performed in accor-
dance with the ethical standards of the 1964 Declaration of Helsinki.
⁎ Corresponding author at: Mid-Atlantic Epilepsy and Sleep Center, 6410 Rockledge
Drive, Suite 410, Bethesda, MD 20817, USA. Fax: +1 301 530 0046.
E-mail address: kleinp@epilepsydc.com (P. Klein).
single epilepsy center between 9/2003 and 5/2009 had weight and
height measured and body mass index (BMI) calculated as part of a
routine physical examination. Weight and height were measured
using standardized techniques and equipment. Body mass index was
calculated as weight in kilograms divided by height in meters squared,
rounded to the nearest decimal. Epilepsy evaluation included EEG and,
where normal, long-term EEG monitoring and MRI. Epilepsy and sei-
zure types were classified according to the International League
Against Epilepsy guidelines [11]. Patients with nonepileptic seizures,
ketogenic diet treatment within 2 years of evaluation, a history of bar-
iatric surgery, and pregnancy were excluded. (Patients treated with
ketogenic diet were excluded because the diet can cause significant
weight loss; patients with history of bariatric surgery were excluded
because their surgery indicates a history of obesity which may not
be reflected in the current BMI.) Overweight was defined as a BMI
>25–30 kg/m2, obesity as a BMI ≥30 kg/m2, and morbid obesity
(grade 3 obesity) as a BMI ≥ 40 kg/m2 [1]. Seizure refractoriness was
defined as persistence of ≥ 1 seizure per 6 months in spite of past or
present treatment with ≥3 AEDs. Statistical analysis included χ2 or
Fisher's exact test and multivariate logistic regression analysis. Be-
cause of the multiple comparisons made, significance was set conserva-
tively at p ≤ 0.01. Logistic regression analysis used BMI as the
dependent variable and age, gender, ethnicity, epilepsy duration, etiol-
ogy, epilepsy refractoriness, and AED mono- vs. polytherapy status as
the predictor variables.

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392 J. Janousek et al. / Epilepsy & Behavior 28 (2013) 391–394

3. Results
Five hundred ninety-seven patients with epilepsy were evaluated.
Twenty-two patients who were children b16 years old were excluded.
Data were missing for weight, height, or both in 21 patients, leaving 554
patients for analysis (age range: 16–87). Three hundred forty-three
(61.9%) patients were female (Table 1). Seventy-three (13.2%) patients
had primary generalized epilepsy (PGE), 477 (86.1%) had localization-
related epilepsy (LRE), and 4 (0.7%) had Lennox–Gastaut syndrome
(n = 3) or indeterminate epilepsy. Of the patients, 53.8% had refractory
epilepsy. The mean duration of epilepsy was 15.1 years (SD: 13.5;
median: 12.1 years). Of the patients, 45.5% were on antiepileptic drug
(AED) monotherapy, 49.3% were on polytherapy, and 5.2% were on no
AEDs.
Antiepileptic drugs used at the time of evaluation in monotherapy
and mono/polytherapy combined were levetiracetam (LEV, n = 76
monotherapy/196 polytherapy), lamotrigine (LMT, n = 32/108), car-
bamazepine (CBZ, n = 26/84), phenytoin (PHT, n = 37/83), valproate
(VPA, n = 26/82), topiramate (TPM, n = 12/69), oxcarbazepine (OX,
n = 14/60), phenobarbital or primidone (n = 0/30), pregabalin (PG,

Table 1
Effects of gender, epilepsy type, refractoriness, duration, and comorbid depression on obesity in patients with epilepsy (figures in parentheses are percentages, followed by 95%
confidence intervals, all rounded to the nearest decimal). The BMI ≥ 30 category includes patients with a BMI ≥40. Because of the small size, the 95% CIs of groups with n ≤ 5
may not be reliable estimates.

N BMI ≤ 25 (%) BMI > 25 BMI ≥ 30 (%) BMI ≥ 40 (%)

(95% CI) (95% CI)

All 554 248 (44.8) 306 (55.2) (51.1–59.3) 173 (31.2) (27.5–35.2) 24 (4.3)
Men 211 (38.1) 73 (34.6) 138 (65.4) (58.8–71.5) 64 (30.3) (24.5–36.9) 7 (3.3)
Women 343 (61.9) 175 (51) 168 (49) (43.3–54.3) 109 (31.8) (27.1–36.9) 17 (5)
pa b0.001 NS NS
Race
White 378 182 (48.1) 196 (51.9) (46.8–56.8) 111 (29.4) (25.0–34.2) 14 (3.7)
Black 112 36 (32.1) 76 (67.9) (58.7–75.8) 52 (46.4) (37.5–55.6) 9 (8)
Hispanic 33 15 (45.4) 18 (54.6) (38.0–70.2) 8 (24.4) (12.6–41.3) 1 (3)
Asian 25 14 (56) 11 (44) (26.7–63.0) 1 (4) (0.1–21.1) 0
Other/unknownb 6 1 5 1 0
pa 0.02 b0.001 NS
Age
16–≤30 years 151 92 (60.9) 59 (39.1) (31.7–47.0) 26 (17.2) (12–24.1) 5 (3.3)
31–≤60 years 324 127 (39.2) 197 (60.9) (55.4–66.0) 128 (39.5) (34.3–44.9) 19 (5.9)
>61 years 79 29 (36.7) 50 (63.3) (52.3–73.1) 19 (24.1) (15.9–38.3) 0
pa b0.001 b0.001 0.055
Epilepsy type
LRE 477 (86.1) 211 (44.2) 266 (55.8) (51.3–60.2) 146 (30.6) (26.6–34.9) 21 (4.4)
PGE 73 (13.2) 34 (46.6) 39 (53.4) (42.1–64.4) 27 (37) (26.8–45.5) 3 (4.1)
LGS/otherb 4 3 1 0 0
pa NS NS NS
Epilepsy duration
b1 year 88 35 (39.8) 53 (60.2) (49.8–69.8) 31 (35.2) (26.0–45.7) 5 (5.7)
1–5 years 78 32 (41) 46 (59) (47.9–69.2) 30 (38.5) (28.4–49.6) 4 (5.1)
>5 years 388 181 (46.6) 207 (53.4) (48.4–58.3) 112 (28.9) (24.6–33.6) 15 (4.7)
>10 yearsc 284 126 (44.4) 158 (55.6) (49.8–61.3) 76 (26.8) (21.9–32.2) 9 (3.2)
pa NS NS NS
Refractorinessd
Nonrefractory 256 (46.2) 130 (50.8) 126 (49.2) (43.2–55.3) 63 (24.6) (19.7–30.3) 8 (3.1)
Refractory 298 (53.8) 118 (39.6) 180 (60.4) (54.8–65.8) 110 (36.9) (31.6–42.5) 16 (5.4)
pa 0.01 0.002 NS
Seizure frequency
Seizure free > 12 m 178 (32.1) 84 (47.2) 94 (52.8) (45.5–60.1) 45 (25.3) (19.4–32.2) 6 (3.4)
≥1/6–12 months 78 (14.1) 46 (59) 32 (41) (30.8–52.1) 18 (23.1) (15–33.6) 2 (2.6)
≥1/1–6 months 84 (15.2) 27 (32.1) 57 (67.9) (57.3–76.9) 31 (36.9) (27.4–47.6) 6 (7.1)
≥1/month 214 (38.6) 91 (42.5) 123 (57.5) (50.8–63.9) 79 (36.9) (30.7–43.6) 10 (4.7)
≥1/week 109 44 (40.4) 65 (59.6) (50.3–68.4) 42 (38.5) (29.9–47.9) 6 (5.5)
pa 0.009 0.02 NS
Etiology
PGE 73 34 (46.6) 39 (53.4) (42.1–64.4) 27 (37) (26.8–48.5) 3 (4.1)
Cryptogenic 202 81 (40.1) 121 (59.9) (53.0–66.4) 66 (32.7) (26.6–39.4) 10 (5)
PTE 79 29 (36.7) 50 (63.3) (52.3–73.1) 26 (32.9) (23.5–43.9) 3 (3.8)
Vascular 76 37 (48.7) 39 (51.3) (40.3–62.2) 23 (30.3) (21.1–41.4) 3 (3.9)
Static encephalopathy 50 28 (56) 22 (44) (31.2–57.7) 14 (28) (17.4–41.8) 3 (6)
Neoplasm 35 17 (48.6) 18 (51.4) (35.6–67.01) 5 (14.3) (5.8–29.9) 0
Infection 29 16 (55.2) 13 (44.8) (28.4–62.4) 9 (31) (14.0–55.1) 1 (3.4)
Othersb 10 6 (60) 4 (40) 3 (30) 1 (10)
pa NS NS NS
Comorbidity
Depression 191 82 (42.9) 109 (57.1) (50.0–63.9) 61 (31.9) (25.7–38.9) 11 (5.8)
pa NS NS NS
a
Statistically significant difference using Fisher's exact test or χ2.
b
Other/unknown category is not included in statistical calculations.
c
Epilepsy duration >10 years includes patients with epilepsy duration of >5 years.
d
Refractory seizures are defined as ≥1 seizure/≥6 months.

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 J. Janousek et al. / Epilepsy & Behavior 28 (2013) 391–394 393

60 55.2 Obesity was most common in the middle aged patients (17.2% vs.
50 44.8 39.5% and 24.1%, p ≤ 0.001).
% of patients

40 31.2 <25
3.4. Insurance/employment demographics
30 >25
Nine percent of the patients had no insurance, 22% were on Medicaid
20 >30
4.3
or similar assistance programs, 30% were on Medicare (because of either
10 >40 age or long-term disability), and 39% had private insurance. Among pa-
0
tients out of school or college who were not of retirement age, 27.8%
BMI were unemployed (including patients with static encephalopathy).

Fig. 1. Prevalence of overweight and obesity in patients with epilepsy. 3.5. Disease characteristics

There was no statistically significant difference in rates of over-

n = 3/29), zonisamide (ZN, n = 2/18), gabapentin (GP, n = 5/25),
and clonazepam, felbamate, tiagabine, ethosuximide, and others (all
combined, n = 4/19).
Three hundred six (55.2%) patients were overweight or obese, 173
(31.2%) were obese, and 24 (4.3%) were morbidly obese (Fig. 1).
3.1. Gender
weight or obesity by epilepsy type (PGE vs. LRE), duration, or etiology,
although obesity rate trended lower in patients with neoplastic etiology
(14.3%, including benign and nonbenign neoplasm) than with other
etiologies. Both overweight and obesity were more frequent in patients
with refractory epilepsy than those with nonrefractory epilepsy (60.4%
vs. 49.2% overweight and 36.9% vs. 24.6% obesity, p = 0.011 and 0.002,
respectively).

More men than women were overweight/obese combined (65.4%
men vs. 49% women, p ≤ 0.001), but there was no significant differ-
ence between genders in the rate of obesity: 30.3% men vs. 31.8%
women.
3.2. Race
Overweight/obesity combined trended to be greater in blacks
(67.9%) than in whites (51.9%), Hispanics (54.6%), and Asians (44%)
(p = 0.02). Obesity was greater in blacks (46.4%) than in whites
(29.4%, p = 0.001 for the black/white two-group comparison and
p ≤ 0.001 for the comparison of all four racial groups). For both over-
weight/obesity and obesity alone, the number of Hispanics and Asians
was too small to allow a meaningful comparison.
3.3. Age
The rate of overweight/obesity combined was less in the young pa-
tients (16–30 years) than in the middle aged (31–60 years) and the el-
derly (>61 years): 39.1%, 60.9%, and 63.3%, respectively (p ≤ 0.001).
3.6. Antiepileptic drugs (Table 2)
Monotherapy-treated and untreated patients had lower rates of
obesity than polytherapy-treated patients (25% and 24.1% vs. 37.7%,
p = 0.005). Because of low numbers of monotherapy-treated patients
with some AEDs, we grouped together two medications with recog-
nized weight-gaining potential, PG and GB, and two medications with
weight-losing potential, TPM and ZN. Among monotherapies, the low-
est rates of overweight/obesity combined were in levetiracetam- and
valproate-treated patients (LEV: 40.8%, VPA: 42.3%, CBZ/OXC: 57.5%,
LMT: 59.4%, PHT: 73%, PG/GB: 82.5%, and TPM/ZN: 85.7%, p = 0.005).
Obesity was higher in the TPM/ZN-treated patients (78.6%) than in
other monotherapies (range: 12.5%–27%, p ≤ 0.002). Differences in
obesity rates among other monotherapies did not reach statistical
significance.
4. Discussion
The study shows that overweight/obesity is common in patients
with epilepsy. To our knowledge, this is the first large-scale study of

Table 2
Associations of treatment on obesity in patients with epilepsy (figures in parentheses are percentages, followed by 95% confidence intervals, all rounded to the nearest decimal).
The BMI ≥ 30 category includes patients with a BMI ≥40. Because of the small size, 95% CIs of groups with n ≤ 5 may not be reliable estimates.

N BMI ≤ 25 (%) BMI > 25 (%) BMI ≥ 30 (%) BMI ≥ 40 (%)

(95% CI) (95% CI)

All 554 248 (44.8) 306 (55.2) 173 (31.2) 24 (4.3)

Rx: mono/poly
No Rx 29 (5.2) 14 (48.3) 15 (51.7) (34.3–68.6) 7 (24.1) (12–42.4) 0
Mono Rx 252 (45.5) 111 (44) 141 (56) (49.8–62.0) 63 (25) (20–30.1) 6 (2.4)
Poly Rx 273 (49.3) 123 (45.1) 150 (55) (49.0–60.7) 103 (37.7) (30.5–43.6) 18 (6.6)
pa NS 0.005 0.03
Rx: mono Rxb
LEVb 76 45 (59.2) 31 (40.8) (30.4–52) 11 (14.5) (8.1–24.3) 1 (1.3)
VPA 26 15 (57.7) 11 (42.3) (25.5–61.1) 7 (26.9) (13.5–46.3) 0
CBZ or OX 40 17 (42.5) 23 (57.5) (42.2–71.5) 8 (20) (10.2–35) 1 (2.5)
LMT 32 13 (40.6) 19 (59.4) (42.2–74.5) 4 (12.5) (4.4–28.7) 0
PHT 37 10 (27) 27 (73) (56.9–84.8) 10 (27) (15.2–43.1) 1 (2.7)
PG or GB 8 3 (37.5) 5 (82.5) (30.4–86.5) 2 (25) (6.3–59.9) 0
TPM or ZN 14 2 (14.3) 12 (85.7) (58.8–97.2) 11 (78.6) (51.7–93.2) 2 (14.2)
Otherc 19
pa 0.005 b0.001 0.07
a
Statistically significant difference using Fisher's exact test or χ2.
b
AED abbreviations: CBZ = carbamazepine, GB = gabapentin, LEV = levetiracetam, LMT = lamotrigine, OX = oxcarbazepine, PHT = phenytoin, PG = pregabalin, TPM =
topiramate, VP = valproate.
c
The “Other” category is not included in statistical calculations. Other AEDs include clonazepam, ethosuximide, felbamate, phenobarbital, primidone, and tiagabine.

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394 J. Janousek et al. / Epilepsy & Behavior 28 (2013) 391–394
the rate of obesity in patients with verified epilepsy and BMI in clini-
cal encounters.
Several studies have sought to determine obesity in individuals with
epilepsy. However, they have all used surveys, with telephone surveys
used for the most part [5–9]. In a telephone survey of adults in California
done as part of the California Health Interview Survey (CHIS) to deter-
mine the prevalence of epilepsy and health-related quality of life
among adults with epilepsy, 34.2% of individuals with self-reported epi-
lepsy reported being overweight, and 23.9% reported obesity, compared
with 35.2% overweight and 20.4% obesity in the individuals without ep-
ilepsy [5]. In a similar study done by some of the same authors in 19
other states in the USA, 32.2% of adults with self-reported active epilepsy
and 31.9% of those with inactive epilepsy were classified as obese, com-
pared with 23.3% of adults without epilepsy. Fewer adults with active ep-
ilepsy (60.7%) reported any exercise compared with adults without
epilepsy (75.4%) [6]. In a nationwide study of the 2002 National Health
Interview Survey (NHIS), conducted by the Centers for Disease Control
and Prevention with interviews administered in person, persons with
self-reported seizures were no more likely to be obese/overweight
than persons without seizures [7]. The adjusted odds ratio for over-
weight/obesity between persons with epilepsy and those without it
was 1.0. Most recently, in a Canadian national population-based survey
of health status and health-related behaviors of Canadian adolescents
and adults, obesity was more likely in the population with epilepsy
(19.1%) than in the general population (15.4%) [9].
These studies are limited by the fact that the data are based on
self-reports. The diagnosis of epilepsy is not validated and weight/height
data were not verified by physical examination. Because of the self-
reported nature of the diagnosis of epilepsy, it is possible that individ-
uals with nonepileptic seizures and without epilepsy were included.
All studies excluded institutionalized individuals who may make up a
significant proportion of patients with refractory epilepsy. Responder
rates to the surveys ranged from 33.5% [5] to 85% [9]. The prevalence
of obesity in the recently published Canadian survey is much lower for
the general population than the prevalence of documented obesity in
the US population [1,2]. For these reasons, conclusions drawn from the
survey studies about the prevalence of obesity in the epilepsy popula-
tion should be accepted with caution.
One previous study reported measured BMI in patients with epilepsy.
In a study in Germany in the 1990s, the BMI of 35 adults with epilepsy
was compared to the BMI of 36 unmatched controls. Patients with epi-
lepsy had an average BMI of 25.1 kg/m2 compared with 22.9 kg/m2 for
the control group [12]. Fifty-one percent of patients had BMI in the nor-
mal range (defined at that time in Germany as b24 kg/m2 for males and
b23 kg/m2 for females).
Limitations of our study include the absence of a direct comparison
with a control population, a greater proportion of females than males,
a small number of Hispanics, and the limitation of AED analysis to cur-
rent AED use (not past AED exposure) without dose–weight analysis.
The greater number of women is due to the fact that our center spe-
cializes in the evaluation of women with epilepsy. The absence of a
significant gender difference in overweight/obesity rates in the study
makes that bias probably unimportant. The small number of Hispanics
is due to the location of the practice in an area with underrepresenta-
tion of Hispanics.
We hypothesized that for social, neuroendocrinological, and phar-
macological reasons, the rates of overweight/obesity may be higher in
patients with epilepsy than in the general population. Our results do
not support this hypothesis. In fact, the 55.2% rate of overweight/obesity
(95% CI: 51.1%–59.3%) is lower than the rate of 68% in the general
population, based on the National Health and Nutrition Examination
Surveys (NHANES; 95% CI: 65.3%–69.8%) [1,2]. (In the NHANES surveys,
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the sampled individuals are both interviewed and examined, and their
BMIs are measured, unlike in the above-discussed studies.) Reasons
for these lower rates could include difference in age of the population
groups, difference in sample size, and effects of disease and its treat-
ment on weight. We included patients under 20 who have lower rates
of obesity than adults (17.1% among 12- to 19-year-olds in the general
population) [1], whereas the NHANES population includes only adults
aged 20+ years. Our sample size was smaller than the NHANES sample
size: 554 vs. 5555 [1]. An overrepresentation of one section of the pop-
ulation, e.g., those with lower weight, is more likely to happen with a
smaller sample size.
As in the general population, the rate of combined overweight/
obesity in patients with epilepsy is higher in men than in women:
65.4% vs. 49% in the population with epilepsy compared with 72.3% vs.
64.1% in the general population, while the rates of obesity are similar
for both genders — 30.3% men/31.8% women in the population with ep-
ilepsy compared with 35.5% men/35.8% women in the general popula-
tion [1,2].
Disease characteristics such as epilepsy type (PGE vs. LRE), duration,
and comorbid depression do not appear to affect obesity. However, re-
fractoriness to treatment was associated with higher rates of both over-
weight and obesity, and obesity was more common in patients treated
with polytherapy than those treated with monotherapy.
Paradoxically, patients treated with VPA, known to cause weight
gain, had low rates of overweight and obesity, while patients treated
with TPM, known to cause weight loss, had high rates. This may be
due to the selective use of these AEDs to treat the comorbidity of obesi-
ty. Topiramate is often used to treat patients with epilepsy and obesity,
while VPA is avoided in such patients.
In summary, the frequency of overweight/obesity in patients with
epilepsy is high, although not higher than in the general population.
Obesity is more common in patients with refractory epilepsy and in pa-
tients treated with polytherapy.
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