1-s2.0-S1525505013004186 TUGAS INDAH-main

8/16/2019 1-s2.0-S1525505013004186 TUGAS INDAH-main

1/5

Risks of subsequent epilepsy among patients with hypertensiveencephalopathy: A nationwide population-based study

Tzu-Tsao Chung a,1, Chi-Yu Lin b,1, Wen-Y en Huang c,d, Cheng-Li Lin e,f ,Fung-Chang Sung g,h,i, j, Chia-Hung Kao d,e,⁎a Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwanb Department of Neurology, Changhua Christian Hospital, Changhua, Taiwanc Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwand Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwane Management Of ce for Health Data, China Medical University Hospital, Taichung, Taiwanf Department of Public Health, China Medical University, Taichung, Taiwang

Graduate Institute of Clinical Medicine Science, College of Medicine, China Medical University, Taichung, Taiwanh School of Medicine, College of Medicine, China Medical University, Taichung, Taiwani Department of Nuclear Medicine, China Medical University Hospital, Taichung, Taiwan j PET Center, China Medical University Hospital, Taichung, Taiwan

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

Article history:

Received 15 May 2013

Revised 10 August 2013

Accepted 12 August 2013

Available online 30 September 2013

Keywords:

Hypertensive encephalopathy

Epilepsy

Seizure

Reversible posterior leukoencephalopathy

syndrome

Risk factors

Background: To determine whether the diagnosis of hypertensive encephalopathy (HE) is linked to an increased

risk of subsequent epilepsy by using a nationwide population-based retrospective study.

Methods: Our study featured a study cohort and a comparison cohort. The study cohort consisted of all patients

with newly diagnosed HE between 1997 and 2010, compiled from universal insurance claims data on patients

with hypertension taken from the National Health Insurance Research Database. The comparison cohort

comprised the remaining hypertensive patients without encephalopathy. The follow-up period was terminated

followingthe development of epilepsy,death, withdrawalfrom theNational HealthInsurance system, or theend

of 2010. We determined the cumulative incidences and hazard ratios (HRs) of epilepsy development.

Results: The incidence of subsequent epilepsy was 2.25-fold higher in the patients with HE than in comparisons(4.17 vs. 1.85 per 1000 person-years), with an adjusted HR of 2.06 (95% CI = 1.66–2.56) in the multivariable

Cox proportional-hazards regression analysis. The incidence of epilepsy was higher in men, younger patients

with HE, and those with brain disorders.

Conclusions: We found that, in Taiwan, patients with HE are at an increased risk of subsequent epilepsy. Physi-

cians should be aware of HE's link to epilepsy when assessing patients with HE.

© 2013 Elsevier Inc. All rights reserved.

1. Introduction

In 1928, Oppenheimer et al. rst introduced the term “hypertensive

encephalopathy” (HE) to describe acute episodes of several cerebral

phenomena correlated with hypertension [1]. It is now known as an

acute organic brain syndrome characterized by unspecic neurological

symptoms such as headache, visual disturbance, altered mental status,

and seizure [2]. The term “reversible posterior leukoencephalopathy

syndrome” has also been used because the most common abnormality

associated with the syndrome in computed tomography and magnetic

resonance images is edema involving white matter in the parieto-

occipital areas [2–4]. It is suggested that extreme elevation of systemic

blood pressure causes the breakdown of the autoregulatory capability

of the brain vasculature, resulting in associated neurological syndromes

[4]. Although HE is usually reversible, failure to promptly treat the

dramatic rise in blood pressure may lead to fatal consequences. It is an

emergent syndrome that requires correct identication and early man-

agement. Theexactincidenceof HE is unknown. However, hypertensive

crises represent more than one-fourth of all medical emergencies and

can result in acute end-organ injuries such as cerebral infarction, acute

myocardial infarction, heart failure, acute renal failure, and HE [5].

Epilepsy is commonly concomitant with acute episodes of HE, most

likely because of the irritation caused by transudate in the interstitium.

However, the probability and frequency of epilepsy in the durable

follow-up of patients with a history of acute episodes of HE remain

unclear. The understanding of this issue may provide information valu-

able to follow-up strategies for patients with HE.

Epilepsy & Behavior 29 (2013) 374–378

⁎ Corresponding author at: Graduate Institute of Clinical Medicine Science and School of

Medicine, China Medical University, 2 Yuh-Der Road Taichung 404, Taiwan. Fax: +886 4

2233 6174.

E-mail address: [email protected] (C.-H. Kao).1 Tzu-Tsao Chung and Chi-Yu Lin contributed equally to this work.

1525-5050/$ – see front matter © 2013 Elsevier Inc. All rights reserved.

http://dx.doi.org/10.1016/j.yebeh.2013.08.013

Contents lists available at ScienceDirect

Epilepsy & Behavior

j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / y e b e h

http://-/?-http://-/?-http://-/?-http://dx.doi.org/10.1016/j.yebeh.2013.08.013http://dx.doi.org/10.1016/j.yebeh.2013.08.013http://dx.doi.org/10.1016/j.yebeh.2013.08.013mailto:[email protected]://dx.doi.org/10.1016/j.yebeh.2013.08.013http://www.sciencedirect.com/science/journal/15255050http://crossmark.crossref.org/dialog/?doi=10.1016/j.yebeh.2013.08.013&domain=pdfhttp://www.sciencedirect.com/science/journal/15255050http://localhost/var/www/apps/conversion/tmp/scratch_5/Unlabelled%20imagehttp://dx.doi.org/10.1016/j.yebeh.2013.08.013http://localhost/var/www/apps/conversion/tmp/scratch_5/Unlabelled%20imagemailto:[email protected]://dx.doi.org/10.1016/j.yebeh.2013.08.013http://-/?-http://-/?-


2/5

In this study, we investigated whether the diagnosis of HE is linked

to an increased risk of developing subsequent epilepsy by using the

Taiwanese National Health Insurance Research Database (NHIRD). The

database is available to researchers in Taiwan and has been extensively

used in epidemiologic studies [6]. The wide coverage of this large,

nationwide database allowed us to examine the relationship between

HE and the subsequent development of epilepsy.

2. Materials and methods

2.1. Data sources

This retrospective study used data retrieved from several claimsles

of the NHIRD, managed by Taiwan's National Health Insurance Research

Institute (NHRI) at the Department of Health. The universal National

Health Insurance (NHI) program was implemented in March 1995

in Taiwan and covered approximately 99% of the total 23.74-million

residents in 2009. This study analyzed the nationwide population-

based database released by the NHRI from 1996 to 2010 for academic

and administrative use. The NHI database includes information on the

basic patient demographic status, medical institutions, details of inpa-

tient orders, ambulatory care, expenditures for care, and physicians

providing services. To protect patient privacy, all patient-level informa-

tion can be retrieved and linked only through scrambled personal iden-

tication. This study was approved by theEthics Review Board of China

Medical University (CMU-REC-101-012).

2.2. Study patients

We identied patients with a diagnosis of hypertension (ICD-9-CM

codes 401–405) from claims data for inpatients for 1997–2010. Patients

aged 20 years and older with newly diagnosed HE (ICD-9-CM code

437.2) were selected for the study cohort. The inpatient diagnosis date

was denedas the index date. Thecomparison cohort wasrandomly se-

lectedfrom therest of the hypertensive patients without a history of HE.

For each patient in the study cohort, 4 comparisons were randomly se-

lected, frequency-matched by sex, age (every 5-year span),and theyear

of the index date. Patients with any record of epilepsy and/or stroke(ICD-9-CM codes 430–438) before the index date were excluded. In

order to exclude acute provoked seizure, we set a lag time of 1 week

to exclude those who had seizures in the rst week after the diagnosis

of HE. Thus, 5 patients were excluded: 3 in the study cohort and 2 in

the comparison cohort.

2.3. Outcome measures

Both cohorts were followed from the index date to the date the pa-

tients received the diagnosis of epilepsy (ICD-9-CM code 345) or until

the patients were censored because of lack of follow-up, death, with-

drawal from the NHI system, or the end of 2010. Because epilepsy was

an emergent and critical condition clinically, we believed that physi-

cians made the diagnosis with caution. We supposed that one codingof345 was enoughto dene the epilepsy. The comorbidities considered

in this study included head injury (ICD-9-CM codes 850–854, 959.01),

meningitis (ICD-9-CM codes 0130, 0360,0470, 0471, 0478, 0479, 0490,

0491, 0530, 0721, 0942, 1142, 320, 321, 322, 00321, 05472, 09042,

09181, 09882, 10081, 11283, 11501, 11591), encephalitis (ICD-9-CM

codes 0136, 0361, 0462, 0520, 0550, 0722, 1390, V050, 062, 063, 064,

323, 09041, 09481), multiple sclerosis (ICD-9-CM code 340), and alco-

holism (ICD-9-CM codes 303, 305.00, 305.01, 305.02, 305.03, V11.3).

2.4. Statistical analysis

The sociodemographic distribution and prevalence of comorbidities

were compared between the study and comparison cohorts and exam-

ined using theχ 2

test.The sex-, age-, and comorbidity-specic incidence

densities of epilepsy were measured and compared for both cohorts.

Poisson regression was used to estimate an incidence rate ratio (IRR)

and a 95% condence interval between the study cohort and the

comparison cohort. Multivariate Cox proportional-hazards regression

analysis was used to estimate the risk of epilepsy in association

with HE, controlling for sociodemographic factors and comorbidities.

The follow-up years were partitioned into 4 segments (≤3 years,

3–6 years, 6–9 years, and N 9 years) to observe the change in epilepsy

hazard. The cumulative incidence of epilepsy for both the studyand the comparison cohorts was calculated using the Kaplan–Meier

method, and the difference was tested using the log-rank test. The

analyses were performed using the SAS statistical package (version

9.2; SAS Institute Inc., Cary, NC, USA), and the Kaplan–Meier survival

curve was plotted using R software (R Foundation for Statistical

Computing, Vienna, Austria). The statistical signicance was accepted

at an α-value of 0.05.

3. Results

Among patientswith hypertensionbut freefrom stroke,we identied

5766 patients with HE for the study cohort and selected 23,074 patients

for the comparison cohort. Patients in both cohorts were predominantly

female and over 65 years of age. Comorbidities were more prevalent

in the study cohort than in the comparison cohort, particularly for head

injury, meningitis, encephalitis, and alcoholism (Table 1).

The incidence of epilepsy in the study cohort was 2.26-fold greater

than that in the comparison cohort (4.17 vs. 1.85 per 1000 person-

years), with an adjusted HR of 2.06 (95% CI: 1.66–2.56) (Table 2). Men

were at higher risk than women to have epilepsy in both cohorts. The

HE to non-HE adjusted HR was also higher for males than for females

(2.27 vs. 1.84). Age-specic data showed that epilepsy incidence was

the highest in patients with HE 20–39 years of age, although there

were more cases of epilepsy in the older groups. The study cohort to

comparison cohort relative risk of epilepsy was the highest for those

aged 40–64 years old, with an adjusted HR of 2.59 (p b 0.001).

Table 2 also shows that epilepsy incidence increased for those with co-

morbidity, with the highest incidence for those with meningitis,

followed by those with encephalitis, alcoholism, and head injury.Theincidence of epilepsy wasconsistently higherin thestudy cohort

with HE than in the comparison cohort during the follow-up period

(Table 3). The incidence of epilepsy was the highest during the initial

3 years after HE diagnosis with an adjusted HR of 3.03 compared with

the corresponding comparisons. The cumulative incidence curve for

Table 1

Demographic characteristics and comorbidity in patients with and without hypertensive

encephalopathy.

Variable Hypertensive encephalopathy p-Valuea

No Yes

N = 23,074 N = 5766

n (%) n (%)

Sex

Female 13,210 (57.3) 3303 (57.3) 0.99

Male 9864 (42.8) 2463 (42.7)

Age, median (IQR) 69.5 (59.1–77.0) 69.5 (59.1–76.9) 0.84b

Stratied age

20–39 648 (2.81) 161 (2.79) 0.99

40–64 8024 (34.8) 2004 (34.8)

65+ 14,402 (62.4) 3601 (62.4)

Comorbidity

Head injury 2541 (11.0) 1190 (20.6) b0.0001

Meningitis 103 (0.45) 49 (0.85) 0.0002

Encephalitis 48 (0.21) 22 (0.38) 0.02

Multiple sclerosis 8 (0.03) 2 (0.03) 0.30

Alcoholism 232 (1.01) 84 (1.46) 0.003

a Chi-square test.b

Mann–

Whitney U test.

375T.-T. Chung et al. / Epilepsy & Behavior 29 (2013) 374– 378


3/5

epilepsy showed that the study cohort had a signicantly higher risk of

epilepsy than the comparison cohort (log-rank test b 0.0001) (Fig. 1).

4. Discussion

To the best of ourknowledge, this study is the rst attempt to inves-

tigate the risk of epilepsy among patients with HE after adjusting for

patient comorbid medical disorders by using a nationwide population-

based data set. Our study shows that the likelihood of epilepsy develop-

ment is 2.06-fold greater among patients with HE than among hyper-

tensive patients without encephalopathy. Furthermore, we found that

patients with HE with comorbidities of head injury, meningitis, and

alcoholism were at an additionally higher risk of epilepsy than those

without the comorbidities.

The overall demographic-specic incidence of epilepsy after strati-

ed analyses of sex and age is signicantly higher in the cohort with

HE than in the comparison cohort. We found that the relative risk of

epilepsy was higher in men than in women (adjusted HR = 2.27 vs.

1.84), concurring with well-established databases of sex comparisons

in epilepsy [7].

Moreover, the relative incidence of epilepsy is still higher in the

long-term follow-up, further conrming that the risk of epilepsy in

patients with HE is “truly” increased. Furthermore, approximately half

of epilepsy diagnoses occurred within the initial 3 years after the rst

Table 2

Incidence of epilepsy by sex, age, and comorbidity and Cox model-measured hazards between patients with and without hypertensive encephalopathy.


No Yes

Variables Event PY Ratea Event PY Ratea IRR b (95% CI) Adjusted HR (95% CI)

Allc 288 155,664 1.85 119 28,513 4.17 2.26 (2.08, 2.44)⁎⁎⁎ 2.06 (1.66, 2.56)⁎⁎⁎

Sexd

Female 145 89,951 1.61 53 16,939 3.13 1.94 (1.74, 2.17)⁎⁎⁎ 1.84 (1.34, 2.53)⁎⁎⁎

Male 143 65,713 2.18 66 11,574 5.70 2.61 (2.33, 2.94)⁎⁎⁎

2.27 (1.69, 3.07)⁎⁎⁎

Stratied agee

20–39 13 4526 2.87 5 920 5.43 1.89 (1.21, 2.96)⁎⁎ 1.58 (0.54, 4.61)

40–64 80 63,902 1.25 45 12,049 3.73 2.98 (2.62, 3.40)⁎⁎⁎ 2.59 (1.78, 3.76)⁎⁎⁎

65+ 195 87,236 2.24 69 15,545 4.44 1.99 (1.79, 2.20)⁎⁎⁎ 1.83 (1.38, 2.42)⁎⁎⁎

Comorbidity

Head injuryf

No 212 137,599 1.54 87 22,414 3.88 2.52 (2.31, 2.75)⁎⁎⁎ 2.55 (1.98, 3.27)⁎⁎⁎

Yes 76 18,065 4.21 32 6100 5.25 1.25 (1.02, 1.53)⁎ 1.23 (0.81, 1.87)

Meningitisg

No 281 155,051 1.81 113 28,285 4.00 2.20 (2.03, 2.39)⁎⁎⁎ 2.06 (1.65, 2.57)⁎⁎⁎

Yes 7 613 11.4 6 228 26.3 2.30 (1.07, 4.97)⁎ 2.00 (0.59, 6.80)

Encephalitish

No 286 155,309 1.84 118 28,437 4.15 2.25 (2.08, 2.44)⁎⁎⁎ 2.05 (1.64, 2.55)⁎⁎⁎

Yes 2 356 5.62 1 76 13.2 2.33 (0.57, 9.51) 2.21 (0.14, 34.7)

Multiple sclerosisi

No 288 155,597 1.85 119 28,511 4.17 2.26 (2.08, 2.44)⁎⁎⁎ 2.06 (1.66, 2.56)⁎⁎⁎

Yes 0 67 0.00 0 2.74 0.00 – –

Alcoholism j

No 279 154,099 1.81 116 28,039 4.14 2.29 (2.11, 2.48)⁎⁎⁎ 2.10 (1.68, 2.62)⁎⁎⁎

Yes 9 1566 5.75 3 474 6.33 1.10 (0.56, 2.18) 1.06 (0.28, 4.00)

a Incidence rate per 1000 person-years.b Incidence rate ratio.c Adjusted HR was calculated by Cox proportional hazard regression and adjusted for age, sex, head injury, meningitis, encephalitis, and alcoholism.d Adjusted HR was calculated by Cox proportional hazard regression stratied by sex and adjusted for age, head injury, meningitis, encephalitis, and alcoholism.e Adjusted HR was calculated by Cox proportional hazard regression stratied by age and adjusted for sex, head injury, meningitis, encephalitis, and alcoholism.f Adjusted HR was calculated by Cox proportional hazard regression stratied by head injury and adjusted for age, sex, meningitis, encephalitis, and alcoholism.g Adjusted HR was calculated by Cox proportional hazard regression stratied by meningitis and adjusted for age, sex, head injury, encephalitis, and alcoholism.h Adjusted HR was calculated by Cox proportional hazard regression stratied by encephalitis and adjusted for age, sex, head injury, meningitis, and alcoholism.i Adjusted HR was calculated by Cox proportional hazard regression stratied by multiple sclerosis and adjusted for age, sex, head injury, meningitis, encephalitis, and alcoholism. j Adjusted HR was calculated by Cox proportional hazard regression stratied by alcoholism and adjusted for age, sex, head injury, meningitis, and encephalitis.

⁎ p b 0.05.⁎⁎ p b 0.01.

⁎⁎⁎ p b 0.001.

Table 3

Hazard ratio for epilepsy compared between patients with and without hypertensive encephalopathy by follow-up duration.


Follow-up timea No Yes IRR c (95% CI) Adjusted HR (95% CI)

Event PY Rateb Event PY Rateb

≤3 years 88 61,247 1.44 59 12,699 4.65 3.23 (2.98, 3.51)⁎⁎⁎ 3.03 (2.17, 4.23)⁎⁎⁎

3–6 years 89 46,898 1.90 29 8414 3.45 1.82 (1.63, 2.02)⁎⁎⁎ 1.65 (1.08, 2.52)⁎

6–9 years 72 30,892 2.33 20 4990 4.01 1.72 (1.51, 1.96)⁎⁎⁎ 1.48 (0.90, 2.45)

N9 years 39 16,625 2.35 11 2410 4.56 1.95 (1.63, 2.32)⁎⁎⁎ 1.57 (0.78, 3.17)

a Adjusted HR was calculated by Cox proportional hazard regression stratied by follow-up duration and adjusted for age, sex, head injury, meningitis, encephalitis, and alcoholism.b Incidence rate per 1000 person-years.c Incidence rate ratio.⁎ p b 0.05.

⁎⁎ p b 0.01.⁎⁎⁎

p b

0.001.

376 T.-T. Chung et al. / Epilepsy & Behavior 29 (2013) 374– 378


4/5

episode of HE, with a decreased relative incidence of epilepsy in the

prolonged follow-up. In a recent meta-analysis, the estimated median

incidence of epilepsy was 0.504 per 1000 person-years [8]. However,

the overall incidence of epilepsy in our study was high, with a rate

of 4.17 per 1000 person-years in the cohort with HE and 1.85 per

1000 person-years in the comparison cohort. This is probably because

the participants were relatively older; 62.4% of both cohorts were age

65 or older. However, the age-specic incidence of epilepsy was the

lowest for those aged 40–64, indicating a U-shape association with

age. With the highest incidence of epilepsy, younger patients with HE

deserve greater attention after the diagnosis of HE.

Changes in the degree of hypertension can generate the auto-

regulatory dysfunction of cerebral blood ow [9]. Recent reports assertthat HE occurs in 15%–20% of patients in whom malignanthypertension

was present [10,11]. It is an acute organic brain syndrome resulting

from disrupted autoregulation of cerebral blood ow. An acute pro-

voked seizure is a frequently concomitant with HE [2,12]. There may

be generalized, focal, or focal with secondarily generalized tonic–clonic

convulsions. The pathogenesis of acute provoked seizure following HE

is incompletely understood. It seems to be the irritative effects of the

uid in the brain interstitium related to cytotoxic edema or vasogenic

edema [1,3,13–15]. The cytotoxic edema results from the infarction

caused by thrombosis of arterioles and brinoid necrosis [13–15].

Conversely, vasogenic edema is related to hypertensive cerebrovascular

endothelial dysfunction or disruption of the blood–brain barrier with

increased permeability [3,9,15]. However, the disruption is the most

widely accepted basis for HE [16]. Therefore, to reduce acute provokedseizure, neuroprotection following diagnosis of HE deserves further re-

search. The pathogenesis of later spontaneous unprovoked seizures, the

endpoint of thepresent study, is even less studied and discussed. It may

reect more permanent structural and physiologic changes within the

brain. We found an increased risk of later epilepsy in patients with HE.

This may provide the basis of ongoing research on the pathogenesis

and prevention strategy of later spontaneous unprovoked seizures in

patients with HE.

The timing of the most development of spontaneous unprovoked

seizures after HE is important. We found that most of the seizures hap-

pened in therst3 years even though theincreased incidenceof epilep-

sy was found within 6 years after occurence of HE. This pattern is

similar to that of epilepsy after a traumatic brain injury. Approximately

40% of individuals with epilepsy after head trauma have onset within

6 months, 50% within 1 year, and 80% within 2 years [17,18]. The

more severe the head injury, the longer the patient is at risk for late sei-

zures. This information has implications in the follow-up strategy and

management of patients with HE.

A particular strength of this study is the use of a nationwide

population-based data set that provides a suf cient samplesize and sta-

tistical power to explore the link between HE and epilepsy. In addition,

thepatients in our study displayed a wide range of demographic charac-

teristics, which allowed us to perform strati

ed analyses according tosex, age, and comorbidities. Nevertheless, some insuf ciencies in our

study should be addressed. First, additional theoretically relevant con-

founding variables such as smoking, diabetes, and a family history of

epilepsy could not be included in our analysis because they were not in-

cluded in our data set. Further study is needed to clarify the effects

of these factors. Second, we might not be able to completely exclude

study subject “misclassication”. A patient with HE, with symptoms of

headache, visual disturbance, and altered mental status but no seizure,

might not seek medical advice and may thus be misclassied as having

hypertension only and be included in the comparison cohort. We be-

lieved that this probability was extremely low because few patients

would tolerate acute HE symptoms without medical intervention.

Moreover, our patients could seek medical advice easily because of the

high accessibility of medical services in Taiwan.

5. Conclusion

We found that the risk for epilepsy in Taiwan was approximately

2.24-fold greater among patients who had been previously diagnosed

with HE compared to those who had not and that this association was

entirely independent of age, sex, head injury, meningitis, encephalitis,

alcoholism, and multiple sclerosis. Thus, physicians should be aware

of HE's link to epilepsy when assessing patients with HE. Furthermore,

because approximately half of the epilepsy diagnoses occurred within

3 years from the onset of HE, routine follow-up examinations and con-

trol of blood pressure should be performed for at least 3 years.

Contributors

Conception/design: Tzu-Tsao Chung, Chi-YuLin, and Chia-Hung Kao.

Provision of study material or patients: Wen-Yen Huang, Cheng-Li

Lin, and Fung-Chang Sung.

Collection and/or assembly of data: Cheng-Li Lin and Fung-Chang

Sung.

Data analysis and interpretation: Tzu-Tsao Chung, Chi-Yu Lin,

Wen-Yen Huang, Fung-Chang Sung, and Chia-Hung Kao.

Manuscript writing: All authors.

Final approval of manuscript: All authors.

Conict of interest

All authors state that they have no conicts of interest.

Acknowledgments

The study was supported in part by the study projects (DMR-101-

061 and DMR-100-076) in China Medical University hospital, the

Taiwan Department of Health Clinical Trial and Research Center and

for Excellence (DOH102-TD-B-111-004), and the Taiwan Department

of Health Cancer Research Center for Excellence (DOH102-TD-C-111-

005). The funders had no role in study design, data collection and anal-

ysis, decision to publish, or preparation of the manuscript.

References

[1] Oppenheimer BS, Fishberg AM. Hypertensive encephalopathy. Arch Intern Med

(Chic) 1928;41:264–

78.

Fig. 1. Cumulative incidence of epilepsy compared between cohorts with and without

hypertensive encephalopathy using the Kaplan–

Meier method.

377T.-T. Chung et al. / Epilepsy & Behavior 29 (2013) 374– 378

http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0005http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0005http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0005http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0005http://localhost/var/www/apps/conversion/tmp/scratch_5/image%20of%20Fig.%E0%B1%80http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0005http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0005


5/5

[2] Weingarten KL, Zimmerman RD, Pinto RS, Whelan MA. Computed tomographicchanges of hypertensive encephalopathy. AJNR Am J Neuroradiol 1985;6:395–8.

[3] Schwartz RB, Jones KM, Kalina P, Bajakian RL, Mantello MT, Garada B, et al. Hyper-tensive encephalopathy: ndings on CT, MR imaging, and SPECT imaging in 14cases. AJR Am J Roentgenol 1992;159:379–83.

[4] Hinchey J, ChavesC, Appignani B, Breen J, PaoL, Wang A, et al. A reversibleposteriorleukoencephalopathy syndrome. N Engl J Med 1996;334:494–500.

[5] Papadopoulos DP, Mourouzis I, Thomopoulos C, Makris T, Papademetriou V. Hyper-tension crisis. Blood Press 2010;19:328–36.

[6] Chen YC, Wu JC, Chen TJ, Wetter T. Reduced access to database. A publicly availabledatabase accelerates academic production. BMJ 2011;342:d637.

[7] McHugh JC, Delanty N. Epidemiology and classication of epilepsy: gender compar-isons. Int Rev Neurobiol 2008;83:11–26.[8] Ngugi AK,Kariuki SM,Bottomley C, KleinschmidtI, SanderJW, NewtonCR. Incidence

of epilepsy: a systematic review and meta-analysis. Neurology 2011;77:1005–12.[9] Vaughan CJ, Delanty N. Hypertensive emergencies. Lancet 2000;356:411–7.

[10] Amraoui F, van Montfrans GA, van den Born BJ. Value of retinal examination inhypertensive encephalopathy. J Hum Hypertens 2010;24:274–9.

[11] Zampaglione B, Pascale C, Marchisio M, Cavallo-Perin P. Hypertensive urgen-cies and emergencies. Prevalence and clinical presentation. Hypertension1996;27:144–7.

[12] Delanty N, VaughanCJ, FrenchJA. Medicalcauses of seizures.Lancet1998;352:383–90.[13] Weingarten K, Barbut D, Filippi C, ZimmermanRD. Acute hypertensive encephalopa-

thy: ndings on spin-echo and gradient-echo MR imaging. AJR Am J Roentgenol1994;162:665–70.

[14] Chester EM, Agamanolis DP, Banker BQ, Victor M. Hypertensive encephalopathy: aclinicopathologic study of 20 cases. Neurology 1978;28:928–39.

[15] Schaefer PW, Buonanno FS, Gonzalez RG, Schwamm LH. Diffusion-weighted imagingdiscriminates between cytotoxic and vasogenic edema in a patient with eclampsia.

Stroke 1997;28:1082–

5.[16] Bhagavati S, Chum F, Choi J. Hypertensive encephalopathy presenting with isolatedbrain stem and cerebellar edema. J Neuroimaging 2008;18:454–6.

[17] Annegers JF, Grabow JD, Groover RV, Laws Jr ER, Elveback LR, Kurland LT. Seizuresafter head trauma: a population study. Neurology 1980;30:683–9.

[18] Annegers JF, Hauser WA, Coan SP, Rocca WA. A population-based study of seizuresafter traumatic brain injuries. N Engl J Med 1998;338:20–4.

378 T.-T. Chung et al. / Epilepsy & Behavior 29 (2013) 374– 378
http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0010http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0010http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0010http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0010http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0015http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0015http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0015http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0015http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0015http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0015http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0015http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0020http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0020http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0020http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0020http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0025http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0025http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0025http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0025http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0090http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0090http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0030http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0030http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0030http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0030http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0030http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0030http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0085http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0085http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0085http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0085http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0035http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0035http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0035http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0040http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0040http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0040http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0040http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0045http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0045http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0045http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0045http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0045http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0050http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0050http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0050http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0055http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0055http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0055http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0055http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0055http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0055http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0055http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0060http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0060http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0060http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0060http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0065http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0065http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0065http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0065http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0065http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0070http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0070http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0070http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0070http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0075http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0075http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0075http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0075http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0080http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0080http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0080http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0080http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0080http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0080http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0075http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0075http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0070http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0070http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0065http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0065http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0065http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0060http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0060http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0055http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0055http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0055http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0050http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0045http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0045http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0045http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0040http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0040http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0035http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0085http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0085http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0030http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0030http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0090http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0090http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0025http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0025http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0020http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0020http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0015http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0015http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0015http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0010http://refhub.elsevier.com/S1525-5050(13)00418-6/rf0010

1-s2.0-S1525505013004186 TUGAS INDAH-main

Documents

Transcript of 1-s2.0-S1525505013004186 TUGAS INDAH-main