Accepted Manuscript Title: Sleep disorders and circadian rhythm in epilepsy revisited: a prospective controlled study Author: Iris Unterberger, David Gabelia, Manuela Prieschl, Kevin Chea, Matthias Hofer, Birgit Högl, Gerhard Luef, Birgit Frauscher PII: DOI: Reference:
S1389-9457(14)00498-5 http://dx.doi.org/doi: 10.1016/j.sleep.2014.09.021 SLEEP 2621
To appear in:
Sleep Medicine
Received date: Revised date: Accepted date:
5-8-2014 23-9-2014 24-9-2014
Please cite this article as: Iris Unterberger, David Gabelia, Manuela Prieschl, Kevin Chea, Matthias Hofer, Birgit Högl, Gerhard Luef, Birgit Frauscher, Sleep disorders and circadian rhythm in epilepsy revisited: a prospective controlled study, Sleep Medicine (2014), http://dx.doi.org/doi: 10.1016/j.sleep.2014.09.021. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Sleep disorders and circadian rhythm in epilepsy revisited: a prospective controlled study Iris Unterbergera, David Gabeliaa, Manuela Prieschla, Kevin Cheaa, Matthias Hofera, Birgit Högla, Gerhard Luefa, Birgit Frauschera,*
a
Department of Neurology, Innsbruck Medical University, Anichstrasse 35, A-6020
Innsbruck, Austria
*Corresponding author. Department of Neurology, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria. Tel.: +43 512 504-2811; fax: +43 512 504-23840. E-mail address: [email protected] (Birgit Frauscher, MD) Highlights
A sleep questionnaire study of 200 non-comorbid people with epilepsy, and 100 controls.
Acute effects of seizures on sleep-wake rhythm are frequent in epilepsy.
Chronic sleep disturbance is not more common in well-controlled epilepsy.
Page 1 of 30
Unterberger I et al. Sleep disorders & circadian rhythm in epilepsy Comorbidity and seizure frequency contribute to disturbed sleep in epilepsy.
2
Page 2 of 30
Unterberger I et al. Sleep disorders & circadian rhythm in epilepsy
Abstract Objective: Sleep disturbance is reported to be frequent in epilepsy. The role of comorbidity, which is frequently accompanied by sleep disturbance, has not been investigated. The present study assessed sleep disorders and circadian rhythm in people with epilepsy, in whom, relevant comorbidity was carefully excluded. Methods: Two hundred people with epilepsy (100 generalized, 100 partial), without relevant psychiatric, neurological or internal comorbidity, were compared to 100 matched controls. The questionnaire contained specifically tailored questions to address the association between epilepsy and sleep disturbance, and validated questionnaires aimed at sleep quality, excessive daytime sleepiness (EDS), circadian
Comment [JM1]: Do you mean validated questions?
rhythm, sleep disorders, and quality of life. Results: Forty-one percent of the participants reported on the acute effects of present or past seizures on sleep-wake rhythm, whereas chronic effects were not evident. Participants and controls did not differ in the rates of chronic sleep disturbance, EDS and presence of sleep disorders (all ps n.s.). Apart from earlier
Comment [JM2]: Please write this in full
sleep times on workdays (p=0.001) in those with epilepsy, circadian variables were similarly distributed. Epilepsy was well controlled, with 75.9% being seizure free for ≥1 year. Longer durations of epilepsy showed a negative correlation with sleep quality (rho=0.256, p1 per week, %
75.9 81.8 13.6 2.5 2
Comment [JM23]: Do you mean minus 5?
CAE, childhood absence epilepsy; FLE, frontal lobe epilepsy; GMA, generalized epilepsy with GM on awakening seizures; JAE, juvenile absence epilepsy; JME, 25
Page 25 of 30
Unterberger I et al. Sleep disorders & circadian rhythm in epilepsy juvenile myoclonic epilepsy; OLE, occipital lobe epilepsy; TLE, temporal lobe epilepsy
26
Page 26 of 30
Unterberger I et al. Sleep disorders & circadian rhythm in epilepsy Table 3. Circadian rhythmicity in participants with epilepsy and controls
Circadian variables
Participants with epilepsy
Controls
pValue
(100)
Generalized epilepsy
Focal epilepsy
(100)
(100)
22:40
22:33
(20:06-01:15)
(20:30-03:00)
02:35
02:30
(00:48-06:15)
(23:15-06:30)
06:25
06:00
(04:00-12:00)
(02:00-10:30)
7.5
7.7
(5.3-11.5)
(4.8-10.8)
23:31
23:20
(20:35-03:10)
(21:15-03:00)
03:56
03:38
(01:18-08:20)
(01:35-07:47)
08:00
07:30
(05:00-13:30)
(04:30-13:00)
8.8
8.3
(5.3-12.9)
(4.8-11.8)
1.2
1.0
(0.0-5.6)
(0.0-4.1)
1.4
0.7
(0.0-6.4)
(0.0-6.7)
pvalue
(200)
Sleep onset on workdays Midsleep on workdays Sleep end on workdays Sleep duration on workdays, h Sleep onset on non-workdays Midsleep on nonworkdays Sleep end on nonworkdays Sleep duration on non-workdays, h Social jetlag, h
Accumulated sleep deprivation, h
22:35
23:10
(20:06-03:00)
(21:00-04:01)
02:30
02:45
(23:15-06:30)
(00:45-08:06)
06:15
06:15
(02:00-12:00)
(04:00-12:00)
7.6
7.5
(4.8-11.5)
(4.5-10.4)
23:30
00:05
(20:00-3:10)
(21:00-04:25)
03:45
04:10
(23:30-08:20)
(01:00-08:43)
08:00
08:00
(04:30-13:30)
(05:00-13:00)
8.6
8.4
(4.8-12.9)
(4.8-13.5)
1.1
1.0
(0.0-5.6)
(0.0-5.6)
1.1
1.1
(0.0-6.9)
(0.0-7.6)
0.001*
0.022
0.341
0.314
0.008
0.103
0.457
0.235
0.956
0.892
0.213
0.108
0.178
0.777
0.810
0.233
0.046
0.012
0.432
0.121
27
Page 27 of 30
Unterberger I et al. Sleep disorders & circadian rhythm in epilepsy Data are present as median (range). *Significant p-values withstanding correction for Bonferroni.
28
Page 28 of 30
Unterberger I et al. Sleep disorders & circadian rhythm in epilepsy
Table 4. Analysis of participants with epilepsy, with and without excessive daytime sleepiness Participants with epilepsy and EDS
Participants with epilepsy without EDS
(n=16)
(n=184)
BMI
24.4 (20.0-32.0)
23.5 (16.0-49.0)
0.476
Age
35 (23-62)
35 (18-74)
0.376
62.5
47.0
0.234
19 (3-51)
17 (0-59)
0.396
69.0
48.1
0.113
Variables
p-value
General variables
Sex, men %
Comment [JM24]: Please write in full or list in footnotes
Epilepsy-specific variables Epilepsy onset, age Epilepsy type, focal % Seizure rate
0.017
0 seizures/6 months, %
56.3
83.1
S1389-9457(14)00498-5 http://dx.doi.org/doi: 10.1016/j.sleep.2014.09.021 SLEEP 2621
To appear in:
Sleep Medicine
Received date: Revised date: Accepted date:
5-8-2014 23-9-2014 24-9-2014
Please cite this article as: Iris Unterberger, David Gabelia, Manuela Prieschl, Kevin Chea, Matthias Hofer, Birgit Högl, Gerhard Luef, Birgit Frauscher, Sleep disorders and circadian rhythm in epilepsy revisited: a prospective controlled study, Sleep Medicine (2014), http://dx.doi.org/doi: 10.1016/j.sleep.2014.09.021. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Sleep disorders and circadian rhythm in epilepsy revisited: a prospective controlled study Iris Unterbergera, David Gabeliaa, Manuela Prieschla, Kevin Cheaa, Matthias Hofera, Birgit Högla, Gerhard Luefa, Birgit Frauschera,*
a
Department of Neurology, Innsbruck Medical University, Anichstrasse 35, A-6020
Innsbruck, Austria
*Corresponding author. Department of Neurology, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria. Tel.: +43 512 504-2811; fax: +43 512 504-23840. E-mail address: [email protected] (Birgit Frauscher, MD) Highlights
A sleep questionnaire study of 200 non-comorbid people with epilepsy, and 100 controls.
Acute effects of seizures on sleep-wake rhythm are frequent in epilepsy.
Chronic sleep disturbance is not more common in well-controlled epilepsy.
Page 1 of 30
Unterberger I et al. Sleep disorders & circadian rhythm in epilepsy Comorbidity and seizure frequency contribute to disturbed sleep in epilepsy.
2
Page 2 of 30
Unterberger I et al. Sleep disorders & circadian rhythm in epilepsy
Abstract Objective: Sleep disturbance is reported to be frequent in epilepsy. The role of comorbidity, which is frequently accompanied by sleep disturbance, has not been investigated. The present study assessed sleep disorders and circadian rhythm in people with epilepsy, in whom, relevant comorbidity was carefully excluded. Methods: Two hundred people with epilepsy (100 generalized, 100 partial), without relevant psychiatric, neurological or internal comorbidity, were compared to 100 matched controls. The questionnaire contained specifically tailored questions to address the association between epilepsy and sleep disturbance, and validated questionnaires aimed at sleep quality, excessive daytime sleepiness (EDS), circadian
Comment [JM1]: Do you mean validated questions?
rhythm, sleep disorders, and quality of life. Results: Forty-one percent of the participants reported on the acute effects of present or past seizures on sleep-wake rhythm, whereas chronic effects were not evident. Participants and controls did not differ in the rates of chronic sleep disturbance, EDS and presence of sleep disorders (all ps n.s.). Apart from earlier
Comment [JM2]: Please write this in full
sleep times on workdays (p=0.001) in those with epilepsy, circadian variables were similarly distributed. Epilepsy was well controlled, with 75.9% being seizure free for ≥1 year. Longer durations of epilepsy showed a negative correlation with sleep quality (rho=0.256, p1 per week, %
75.9 81.8 13.6 2.5 2
Comment [JM23]: Do you mean minus 5?
CAE, childhood absence epilepsy; FLE, frontal lobe epilepsy; GMA, generalized epilepsy with GM on awakening seizures; JAE, juvenile absence epilepsy; JME, 25
Page 25 of 30
Unterberger I et al. Sleep disorders & circadian rhythm in epilepsy juvenile myoclonic epilepsy; OLE, occipital lobe epilepsy; TLE, temporal lobe epilepsy
26
Page 26 of 30
Unterberger I et al. Sleep disorders & circadian rhythm in epilepsy Table 3. Circadian rhythmicity in participants with epilepsy and controls
Circadian variables
Participants with epilepsy
Controls
pValue
(100)
Generalized epilepsy
Focal epilepsy
(100)
(100)
22:40
22:33
(20:06-01:15)
(20:30-03:00)
02:35
02:30
(00:48-06:15)
(23:15-06:30)
06:25
06:00
(04:00-12:00)
(02:00-10:30)
7.5
7.7
(5.3-11.5)
(4.8-10.8)
23:31
23:20
(20:35-03:10)
(21:15-03:00)
03:56
03:38
(01:18-08:20)
(01:35-07:47)
08:00
07:30
(05:00-13:30)
(04:30-13:00)
8.8
8.3
(5.3-12.9)
(4.8-11.8)
1.2
1.0
(0.0-5.6)
(0.0-4.1)
1.4
0.7
(0.0-6.4)
(0.0-6.7)
pvalue
(200)
Sleep onset on workdays Midsleep on workdays Sleep end on workdays Sleep duration on workdays, h Sleep onset on non-workdays Midsleep on nonworkdays Sleep end on nonworkdays Sleep duration on non-workdays, h Social jetlag, h
Accumulated sleep deprivation, h
22:35
23:10
(20:06-03:00)
(21:00-04:01)
02:30
02:45
(23:15-06:30)
(00:45-08:06)
06:15
06:15
(02:00-12:00)
(04:00-12:00)
7.6
7.5
(4.8-11.5)
(4.5-10.4)
23:30
00:05
(20:00-3:10)
(21:00-04:25)
03:45
04:10
(23:30-08:20)
(01:00-08:43)
08:00
08:00
(04:30-13:30)
(05:00-13:00)
8.6
8.4
(4.8-12.9)
(4.8-13.5)
1.1
1.0
(0.0-5.6)
(0.0-5.6)
1.1
1.1
(0.0-6.9)
(0.0-7.6)
0.001*
0.022
0.341
0.314
0.008
0.103
0.457
0.235
0.956
0.892
0.213
0.108
0.178
0.777
0.810
0.233
0.046
0.012
0.432
0.121
27
Page 27 of 30
Unterberger I et al. Sleep disorders & circadian rhythm in epilepsy Data are present as median (range). *Significant p-values withstanding correction for Bonferroni.
28
Page 28 of 30
Unterberger I et al. Sleep disorders & circadian rhythm in epilepsy
Table 4. Analysis of participants with epilepsy, with and without excessive daytime sleepiness Participants with epilepsy and EDS
Participants with epilepsy without EDS
(n=16)
(n=184)
BMI
24.4 (20.0-32.0)
23.5 (16.0-49.0)
0.476
Age
35 (23-62)
35 (18-74)
0.376
62.5
47.0
0.234
19 (3-51)
17 (0-59)
0.396
69.0
48.1
0.113
Variables
p-value
General variables
Sex, men %
Comment [JM24]: Please write in full or list in footnotes
Epilepsy-specific variables Epilepsy onset, age Epilepsy type, focal % Seizure rate
0.017
0 seizures/6 months, %
56.3
83.1
