Introduction: Poststroke sleep disturbances are common and can affect stroke outcomes, but the clinical studies mainly focus on breathing-related sleep disorders, while the bidirectional impact of circadian rhythm dysfunction in ischemic stroke remains unknown. This study observed the characteristics of melatonin secretion in acute ischemic stroke patients and evaluated whether melatonin rhythm impacts the prognosis after stroke by assessing the neurological function, cognition, emotion, and quality of life 3 months after stroke. Methods: Acute ischemic stroke patients were selected from the Department of Neurology Inpatients of the Second Hospital affiliated with Soochow University from October 2019 to July 2021. Healthy control subjects were recruited at the same time. Demographic and clinical data were collected, and relevant scale scores (including neurological function, cognition, emotion, and sleep) were assessed within 2 weeks of onset and followed up 3 months later. All participants collected salivary melatonin samples on the 4th day of hospitalization and dim light melatonin onset (DLMO) was calculated according to melatonin concentration. Stroke patients were then divided into three groups based on their DLMO values. Results: A total of 74 stroke patients and 33 control subjects were included in this analysis. Compared with healthy controls, stroke patients exhibited a delayed melatonin rhythm during the acute phase of stroke (21:36 vs. 20:38, p = 0.004). Stroke patients were then divided into three groups, namely normal (n = 36), delayed (n = 28), or advanced DLMO (n = 10), based on their DLMO values. A χ2 test showed that there were significant differences in the rate of poor prognosis (p = 0.011) and depression tendency (p = 0.028) among the three groups. A further pairwise comparison revealed that stroke patients with delayed DLMO were more likely to experience poor short-term outcomes than normal DLMO group (p = 0.003). The average melatonin concentration of stroke patients at 5 time points was significantly lower than that of the control group (3.145 vs. 7.065 pg/mL, p < 0.001). Accordingly, we split stroke patients into three groups, namely low melatonin level (n = 14), normal melatonin level (n = 54), or high melatonin level (n = 6). Unfortunately, there were no great differences in the clinical characteristics, cognition, emotion, sleep quality, and short-term outcome among groups. Conclusions: This is a preliminary study, and our results indicate that changes in melatonin secretion phase of stroke patients may have effect on their short-term prognosis.

1.
Mukherjee
D
,
Patil
CG
.
Epidemiology and the global burden of stroke
.
World Neurosurg
.
2011
76
6 Suppl
S85
90
.
2.
Feigin
VL
,
Forouzanfar
MH
,
Krishnamurthi
R
,
Mensah
GA
,
Connor
M
,
Bennett
DA
.
Global and regional burden of stroke during 1990-2010: findings from the global burden of disease study 2010
.
Lancet
.
2014
;
383
(
9913
):
245
54
.
3.
Palma
JA
,
Urrestarazu
E
,
Iriarte
J
.
Sleep loss as risk factor for neurologic disorders: a review
.
Sleep Med
.
2013
;
14
(
3
):
229
36
.
4.
Fu
X
,
You
SJ
,
Li
J
,
Liu
CF
.
Sleep disorders and acute stroke: profile and research opportunities
.
Chin Med J
.
2021
;
134
(
6
):
631
3
.
5.
Gottlieb
E
,
Landau
E
,
Baxter
H
,
Werden
E
,
Howard
ME
,
Brodtmann
A
.
The bidirectional impact of sleep and circadian rhythm dysfunction in human ischaemic stroke: a systematic review
.
Sleep Med Rev
.
2019
;
45
:
54
69
.
6.
Panda
S
,
Hogenesch
JB
,
Kay
SA
.
Circadian rhythms from flies to human
.
Nature
.
2002
;
417
(
6886
):
329
35
.
7.
Reppert
SM
,
Weaver
DR
.
Coordination of circadian timing in mammals
.
Nature
.
2002
;
418
(
6901
):
935
41
.
8.
Pandi-Perumal
SR
,
Smits
M
,
Spence
W
,
Srinivasan
V
,
Cardinali
DP
,
Lowe
AD
.
Dim Light Melatonin Onset (DLMO): a tool for the analysis of circadian phase in human sleep and chronobiological disorders
.
Prog Neuropsychopharmacol Biol Psychiatry
.
2007
;
31
(
1
):
1
11
.
9.
Takaesu
Y
,
Inoue
Y
,
Ono
K
,
Murakoshi
A
,
Futenma
K
,
Komada
Y
.
Circadian rhythm sleep-wake disorders as predictors for bipolar disorder in patients with remitted mood disorders
.
J Affect Disord
.
2017
;
220
:
57
61
.
10.
Hida
A
,
Kitamura
S
,
Mishima
K
.
Pathophysiology and pathogenesis of circadian rhythm sleep disorders
.
J Physiol Anthropol
.
2012
;
31
(
1
):
7
.
11.
Atanassova
PA
,
Terzieva
DD
,
Dimitrov
BD
.
Impaired nocturnal melatonin in acute phase of ischaemic stroke: cross-sectional matched case-control analysis
.
J Neuroendocrinol
.
2009
;
21
(
7
):
657
63
.
12.
Yang
Y
,
Jiang
S
,
Dong
Y
,
Fan
C
,
Zhao
L
,
Yang
X
.
Melatonin prevents cell death and mitochondrial dysfunction via a SIRT1-dependent mechanism during ischemic-stroke in mice
.
J Pineal Res
.
2015
;
58
(
1
):
61
70
.
13.
Chen
KH
,
Lin
KC
,
Ko
SF
,
Chiang
JY
,
Guo
J
,
Yip
HK
.
Melatonin against acute ischaemic stroke dependently via suppressing both inflammatory and oxidative stress downstream signallings
.
J Cell Mol Med
.
2020 Sep
24
18
10402
19
.
14.
Horne
JA
,
Ostberg
O
.
A self-assessment questionnaire to determine morningness-eveningness in human circadian rhythms
.
Int J Chronobiol
.
1976
;
4
(
2
):
97
110
.
15.
Rankin
J
.
Cerebral vascular accidents in patients over the age of 60. II. Prognosis
.
Scott Med J
.
1957
;
2
(
5
):
200
15
.
16.
Morin
CM
,
Belleville
G
,
Belanger
L
,
Ivers
H
.
The Insomnia Severity index: psychometric indicators to detect insomnia cases and evaluate treatment response
.
Sleep
.
2011
;
34
(
5
):
601
8
.
17.
Stiasny-Kolster
K
,
Mayer
G
,
Schafer
S
,
Moller
JC
,
Heinzel-Gutenbrunner
M
,
Oertel
WH
.
The REM sleep behavior disorder screening questionnaire--a new diagnostic instrument
.
Mov Disord
.
2007
;
22
(
16
):
2386
93
.
18.
Kwah
LK
,
Diong
J
.
National Institutes of Health Stroke Scale (NIHSS)
.
J Physiother
.
2014
;
60
(
1
):
61
.
19.
Benloucif
S
,
Burgess
HJ
,
Klerman
EB
,
Lewy
AJ
,
Middleton
B
,
Murphy
PJ
.
Measuring melatonin in humans
.
J Clin Sleep Med
.
2008
;
4
(
1
):
66
9
.
20.
Pullman
RE
,
Roepke
SE
,
Duffy
JF
.
Laboratory validation of an in-home method for assessing circadian phase using Dim Light Melatonin Onset (DLMO)
.
Sleep Med
.
2012
;
13
(
6
):
703
6
.
21.
Shulman
KI
,
Herrmann
N
,
Brodaty
H
,
Chiu
H
,
Lawlor
B
,
Ritchie
K
.
IPA survey of brief cognitive screening instruments
.
Int Psychogeriatr
.
2006
;
18
(
2
):
281
94
.
22.
Nasreddine
ZS
,
Phillips
NA
,
Bedirian
V
,
Charbonneau
S
,
Whitehead
V
,
Collin
I
.
The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment
.
J Am Geriatr Soc
.
2005
;
53
(
4
):
695
9
.
23.
Clark
DB
,
Donovan
JE
.
Reliability and validity of the Hamilton anxiety rating scale in an adolescent sample
.
J Am Acad Child Adolesc Psychiatry
.
1994
;
33
(
3
):
354
60
.
24.
Moberg
PJ
,
Lazarus
LW
,
Mesholam
RI
,
Bilker
W
,
Chuy
IL
,
Neyman
I
.
Comparison of the standard and structured interview guide for the Hamilton Depression Rating Scale in depressed geriatric inpatients
.
Am J Geriatr Psychiatry
.
2001
;
9
(
1
):
35
40
.
25.
Buysse
DJ
,
Reynolds
CF
3rd
,
Monk
TH
,
Berman
SR
,
Kupfer
DJ
.
The Pittsburgh sleep quality index: a new instrument for psychiatric practice and research
.
Psychiatry Res
.
1989
;
28
(
2
):
193
213
.
26.
Takegami
M
,
Hayashino
Y
,
Chin
K
,
Sokejima
S
,
Kadotani
H
,
Akashiba
T
.
Simple four-variable screening tool for identification of patients with sleep-disordered breathing
.
Sleep
.
2009
;
32
(
7
):
939
48
.
27.
Cruz-Cruz
C
,
Martinez-Nunez
JM
,
Perez
ME
,
Kravzov-Jinich
J
,
Rios-Castaneda
C
,
Altagracia-Martinez
M
.
Evaluation of the Stroke-Specific Quality-Of-Life (SSQOL) scale in Mexico: a preliminary approach
.
Value Health Reg Issues
.
2013
;
2
(
3
):
392
7
.
28.
Bittencourt
LR
,
Silva
RS
,
Santos
RF
,
Pires
ML
,
Mello
MT
.
[Excessive daytime sleepiness]
.
Braz J Psychiatry
.
2005
27
Suppl 1
16
21
.
29.
Beloosesky
Y
,
Grinblat
J
,
Laudon
M
,
Grosman
B
,
Streifler
JY
,
Zisapel
N
.
Melatonin rhythms in stroke patients
.
Neurosci Lett
.
2002
;
319
(
2
):
103
6
.
30.
Chen
TY
,
Lee
MY
,
Chen
HY
,
Kuo
YL
,
Lin
SC
,
Wu
TS
.
Melatonin attenuates the postischemic increase in blood-brain barrier permeability and decreases hemorrhagic transformation of tissue-plasminogen activator therapy following ischemic stroke in mice
.
J Pineal Res
.
2006
;
40
(
3
):
242
50
.
31.
Bassetti
CL
,
Hermann
DM
.
Sleep and stroke
.
Handb Clin Neurol
.
2011
;
99
:
1051
72
.
32.
Andrabi
SS
,
Parvez
S
,
Tabassum
H
.
Melatonin and ischemic stroke: mechanistic roles and action
.
Adv Pharmacol Sci
.
2015
;
2015
:
384750
.
33.
Ballard
C
,
Rowan
E
,
Stephens
S
,
Kalaria
R
,
Kenny
RA
.
Prospective follow-up study between 3 and 15 months after stroke: improvements and decline in cognitive function among dementia-free stroke survivors >75 years of age
.
Stroke
.
2003
;
34
(
10
):
2440
4
.
34.
Rafsten
L
,
Danielsson
A
,
Sunnerhagen
KS
.
Anxiety after stroke: a systematic review and meta-analysis
.
J Rehabil Med
.
2018
;
50
(
9
):
769
78
.
35.
Sletten
TL
,
Cappuccio
FP
,
Davidson
AJ
,
Van Cauter
E
,
Rajaratnam
SMW
,
Scheer
FAJL
.
Health consequences of circadian disruption
.
Sleep
.
2020
43
1
zsz194
.
36.
Monteleone
P
,
Maj
M
.
The circadian basis of mood disorders: recent developments and treatment implications
.
Eur Neuropsychopharmacol
.
2008
;
18
(
10
):
701
11
.
37.
Yang
MY
,
Lin
PW
,
Lin
HC
,
Lin
PM
,
Chen
IY
,
Friedman
M
.
Alternations of circadian clock genes expression and oscillation in obstructive sleep apnea
.
J Clin Med
.
2019
;
8
(
10
):
1634
.
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