Original Paper Received: March 27, 2014 Accepted: April 22, 2014 Published online: July 23, 2014
Cerebrovasc Dis 2014;37:431–437 DOI: 10.1159/000363129
Incidence of Cardioembolic Stroke Including Paradoxical Brain Embolism in Patients with Acute Ischemic Stroke before and after the Great East Japan Earthquake Ryo Itabashi a, b Eisuke Furui a Shoichiro Sato a Yukako Yazawa a Kenta Kawata a Etsuro Mori b
a
Department of Stroke Neurology, Kohnan Hospital, and b Department of Behavioral Neurology and Cognitive Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Japan
Key Words Acute stroke · Cardiac embolism · Deep vein thrombosis · Paradoxical embolism · Great East Japan Earthquake
Abstract Background: The incidence of heart disease or deep vein thrombosis (DVT) reportedly increased after the Great East Japan Earthquake. We hypothesized that the incidence of cardioembolic stroke (CES) including paradoxical brain embolism (PBE) among patients with acute stroke would increase after the earthquake due to cessation of antithrombotic therapy or the increase in heart disease and DVT associated with the evacuation. The aim of this study is to evaluate the changes in the prevalence of DVT and the incidence of CES including PBE in acute ischemic stroke before and after the earthquake. Methods: We retrospectively studied 1,044 consecutive ischemic stroke patients (73.1 ± 12.5 years old, male 61.5%) who were admitted to a comprehensive stroke center (from January 2010 through March 2012) located in the earthquake disaster area within 7 days after stroke onset. The prevalence of DVT and the incidence of CES including PBE were compared before and after the earthquake of 11 March 2011. Results: The median of the initial
© 2014 S. Karger AG, Basel 1015–9770/14/0376–0431$39.50/0 E-Mail [email protected] www.karger.com/ced
National Institutes of Health Stroke Scale (NIHSS) scores was 4 (interquartile range: 1–8). Two hundred and eighty-two patients (27.0% of those surveyed) were diagnosed with CES. After adjustment for sex, age, NIHSS score, and patient’s residential address, the proportion of CES patients was significantly increased after the earthquake (odds ratio, OR 1.61, 95% confidence interval, 95% CI: 1.20–2.17). Eighty-nine patients (8.5% of those surveyed) had DVT. Compared with 2010 findings, the prevalence of DVT was significantly increased in the fourth quarter of 2011 and the first quarter of 2012 (OR 1.85, 95% CI: 1.05–3.24). Nineteen (1.8% of those surveyed) were diagnosed with PBE. The proportion of PBE patients was also significantly increased in the second half of 2011 (OR 3.69, 95% CI: 1.28–12.1). Conclusions: The incidence of CES was significantly increased after the earthquake, compared with the period before the earthquake. We encountered more PBE in the period from 3 to 9 months after the earthquake and found more DVT in the acute ischemic stroke patients in the period from 6 through 12 months after the earthquake. In these types of disasters, we have to ensure the distribution of drugs, including antithrombotics, and support the prevention of DVT in the refugees. © 2014 S. Karger AG, Basel
Ryo Itabashi, MD Department of Stroke Neurology, Kohnan Hospital 4-20-1 Nagamachi-minami, Taihaku-ku Sendai 982-8523 (Japan) E-Mail ritabash @ kohnan-sendai.or.jp
Introduction
The Great East Japan Earthquake and Tsunami of 11 March 2011 was one of the largest earthquakes ever recorded in Japan. The earthquake caused huge damage and forced many people to be evacuated to shelter, such as public halls, gymnasiums, and schools in the disaster areas. Furthermore, an insufficiency of medical supply including antithrombotics occurred in the coastal area because of distribution failure, especially to these refugees. In the Prefecture of Miyagi, close to the epicenter of the earthquake and where the damage was greatest (fig. 1a), it was reported that the incidence of heart disease, including heart failure and acute coronary syndrome, increased soon after the earthquake occurred [1]. Some physicians reported a high incidence of deep vein thrombosis (DVT) in the refugees around the northeast coast [2, 3]. They hypothesized that DVT in refugees would be caused by tsunami-related lower limb injury, reduced frequency of urination, inactivity, or dehydration. Paradoxical brain embolism (PBE) generally refers to a venous clot, such as DVT, that passes through a rightto-left shunt and produces an ischemic stroke. PBE has been considered a rare cause of stroke, especially in juvenile patients [4, 5]. It has been reported that the incidence of PBE is 1.8–12.8% among stroke patients [6]. From recent studies, however, PBE might be a common cause of cryptogenic stroke unrelated to patient’s age [7]. We thus hypothesized that the incidence of cardioembolic stroke (CES) including PBE among patients with acute stroke would increase after the Great East Japan Earthquake due to cessation of antithrombotic therapy or the increase in heart disease and DVT associated with the evacuation. The association between the disaster and detailed stroke subtypes has not been determined to date. The aim of this study is to evaluate the changes in the prevalence of DVT and the incidence of CES including PBE in acute ischemic stroke before and after the earthquake. Methods Study Population The subjects of the present study were 1,044 consecutive patients (73.1 ± 12.5 years old, male 61.5%) with acute ischemic stroke who were admitted to Kohnan Hospital (Sendai, Miyagi, Japan) within 7 days after stroke onset, between January 2010 and March 2012. Kohnan Hospital is the comprehensive stroke center in the Prefecture of Miyagi. Because of the inland location in the Prefecture of Miyagi (fig. 1b), the damage to our hospital from the earthquake
432
Cerebrovasc Dis 2014;37:431–437 DOI: 10.1159/000363129
and tsunami was minimal. Therefore, we could continue routine examinations during the catastrophe, including ultrasonography to evaluate the embolic source in cryptogenic stroke. The clinical and investigative data thus prospectively collected in a standardized fashion were entered into the Kohnan Hospital Stroke Registry. All patients with acute stroke admitted to our institute during this period were examined by neurologists, neurosurgeons, or both, and were screened by routine laboratory tests, as well as computerized tomography (CT) or magnetic resonance imaging (MRI). Ischemic stroke was diagnosed by stroke neurologists (board-certified neurologists specializing in the care of stroke patients) based on clinical and brain imaging findings. Patients with unknown cause of stroke were evaluated with multimodal examinations, including 24-hour monitoring of electrocardiograms, transcranial Doppler, transesophageal echocardiography, and ultrasonography of the lower extremities when not contraindicated. Neurological deficits were evaluated using the National Institutes of Health Stroke Scale (NIHSS) score upon admission [8]. Etiological Diagnosis The criteria for the indication of ultrasonography of the lower extremities to evaluate DVT were follows: (a) unknown cause of stroke in spite of initial evaluation (including electrocardiogram and brain imaging upon admission); (b) elevated serum levels of D-dimer or a degradation product of fibrin in patients with acute stroke. The diagnosis of CES was made when all of the following criteria [8, 9] were present: (1) concurrent cardiac source for an embolus, such as atrial fibrillation (AF), segmental wall akinesis, cardiomyopathy, or right-to-left shunt with DVT or pulmonary thromboembolism, and (2) no arterial stenosis of greater than 50% proximal to the lesions. Among patients with CES, the diagnosis of PBE was made when all following criteria [10] were present: (1) brain infarction demonstrated by CT or MRI; (2) right-to-left shunt; (3) deep venous thrombus or pulmonary thromboembolism; (4) neurological features of brain embolism, such as cortical infarction demonstrated by CT or MRI, and angiographic findings of intraluminal filling defect or reopening of previously occluded arteries, and (5) absence of other sources of embolism, such as heart disease, complicated atherosclerotic plaque at the aortic arch, or arterial stenotic lesion proximal to the lesion. Analysis The prevalence of DVT and AF, and the incidence of CES including PBE were compared between before and after the earthquake of 11 March 2011. The Student t test, χ2 test, and KruskalWallis test were used as appropriate. To identify the impact of the earthquake, multivariate logistic regression analyses were applied. All models were adjusted for age, sex, initial NIHSS score, and patient’s residential address (living in the municipalities along the coast or not). The definition of municipalities along the coast was based on a previous study [1]. We included two time variables in the regression models: (1) a two-categorical time variable categorized into time periods before and after the earthquake of 11 March 2011, and (2) 3-month periods from January 2010 to March 2012, with the first four quarters combined to a year period being the reference category. Statistical analyses were done with the JMP (SAS Institute Inc., Cary, N.C., USA) statistical software package. A value of p < 0.05 (two-sided) was considered to indicate a significant difference.
Itabashi/Furui/Sato/Yazawa/Kawata/Mori
a
b Miyagi
Kohan hospital The epicenter
200 km
160
40
140
35
120
30
4.5
12
4.0
10 8 6 4 2
I 2012
IV 2011
III 2011
II 2011
I 2011
IV 2010
14
IV 2010
b
III 2010
I 2012
IV 2011
III 2011
II 2011
I 2011
IV 2010
III 2010
II 2010
0 I 2010
5
0
PBE incidence (%)
3.5 3.0 2.5 2.0 1.5 1.0 0.5 I 2012
IV 2011
III 2011
d
II 2011
I 2012
IV 2011
III 2011
II 2011
I 2011
IV 2010
III 2010
II 2010
I 2010
0 I 2011
DVT prevalence (%)
10
20
0
c
15
III 2010
40
20
II 2010
60
20 km
25
II 2010
80
I 2010
100
Miyagi prefecture
I 2010
CES incidence (%)
Patients (n)
tween the epicenter of the earthquake and the Prefecture of Miyagi. b The location of Kohnan Hospital in the Prefecture of Miyagi.
a
Kohan hospital
Tokyo
Fig. 1. a The positional relationship be-
Fig. 2. Arrowheads indicate the Great Japan Earthquake and Tsunami of 11 March 2011. a The number of patients with acute ischemic stroke. b The incidence of CES. c The prevalence of DVT in patients with acute stroke. d The incidence of PBE.
The median initial NIHSS score was 4 (interquartile range: 1–8). The number of patients with acute ischemic stroke who were admitted to our institute increased after
the earthquake, followed by a decrease after the second quarter of 2011 (fig. 2a). Two hundred and eighty-two patients (27.0% of those surveyed) were diagnosed with CES. The proportion of CES patients increased after the first quarter of 2011
Cardioembolic Stroke before and after the Great East Japan Earthquake
Cerebrovasc Dis 2014;37:431–437 DOI: 10.1159/000363129
Results
433
Table 1. Analysis of the incidence of CES
Model 1
Cerebrovasc Dis 2014;37:431–437 DOI: 10.1159/000363129
Incidence of Cardioembolic Stroke Including Paradoxical Brain Embolism in Patients with Acute Ischemic Stroke before and after the Great East Japan Earthquake Ryo Itabashi a, b Eisuke Furui a Shoichiro Sato a Yukako Yazawa a Kenta Kawata a Etsuro Mori b
a
Department of Stroke Neurology, Kohnan Hospital, and b Department of Behavioral Neurology and Cognitive Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Japan
Key Words Acute stroke · Cardiac embolism · Deep vein thrombosis · Paradoxical embolism · Great East Japan Earthquake
Abstract Background: The incidence of heart disease or deep vein thrombosis (DVT) reportedly increased after the Great East Japan Earthquake. We hypothesized that the incidence of cardioembolic stroke (CES) including paradoxical brain embolism (PBE) among patients with acute stroke would increase after the earthquake due to cessation of antithrombotic therapy or the increase in heart disease and DVT associated with the evacuation. The aim of this study is to evaluate the changes in the prevalence of DVT and the incidence of CES including PBE in acute ischemic stroke before and after the earthquake. Methods: We retrospectively studied 1,044 consecutive ischemic stroke patients (73.1 ± 12.5 years old, male 61.5%) who were admitted to a comprehensive stroke center (from January 2010 through March 2012) located in the earthquake disaster area within 7 days after stroke onset. The prevalence of DVT and the incidence of CES including PBE were compared before and after the earthquake of 11 March 2011. Results: The median of the initial
© 2014 S. Karger AG, Basel 1015–9770/14/0376–0431$39.50/0 E-Mail [email protected] www.karger.com/ced
National Institutes of Health Stroke Scale (NIHSS) scores was 4 (interquartile range: 1–8). Two hundred and eighty-two patients (27.0% of those surveyed) were diagnosed with CES. After adjustment for sex, age, NIHSS score, and patient’s residential address, the proportion of CES patients was significantly increased after the earthquake (odds ratio, OR 1.61, 95% confidence interval, 95% CI: 1.20–2.17). Eighty-nine patients (8.5% of those surveyed) had DVT. Compared with 2010 findings, the prevalence of DVT was significantly increased in the fourth quarter of 2011 and the first quarter of 2012 (OR 1.85, 95% CI: 1.05–3.24). Nineteen (1.8% of those surveyed) were diagnosed with PBE. The proportion of PBE patients was also significantly increased in the second half of 2011 (OR 3.69, 95% CI: 1.28–12.1). Conclusions: The incidence of CES was significantly increased after the earthquake, compared with the period before the earthquake. We encountered more PBE in the period from 3 to 9 months after the earthquake and found more DVT in the acute ischemic stroke patients in the period from 6 through 12 months after the earthquake. In these types of disasters, we have to ensure the distribution of drugs, including antithrombotics, and support the prevention of DVT in the refugees. © 2014 S. Karger AG, Basel
Ryo Itabashi, MD Department of Stroke Neurology, Kohnan Hospital 4-20-1 Nagamachi-minami, Taihaku-ku Sendai 982-8523 (Japan) E-Mail ritabash @ kohnan-sendai.or.jp
Introduction
The Great East Japan Earthquake and Tsunami of 11 March 2011 was one of the largest earthquakes ever recorded in Japan. The earthquake caused huge damage and forced many people to be evacuated to shelter, such as public halls, gymnasiums, and schools in the disaster areas. Furthermore, an insufficiency of medical supply including antithrombotics occurred in the coastal area because of distribution failure, especially to these refugees. In the Prefecture of Miyagi, close to the epicenter of the earthquake and where the damage was greatest (fig. 1a), it was reported that the incidence of heart disease, including heart failure and acute coronary syndrome, increased soon after the earthquake occurred [1]. Some physicians reported a high incidence of deep vein thrombosis (DVT) in the refugees around the northeast coast [2, 3]. They hypothesized that DVT in refugees would be caused by tsunami-related lower limb injury, reduced frequency of urination, inactivity, or dehydration. Paradoxical brain embolism (PBE) generally refers to a venous clot, such as DVT, that passes through a rightto-left shunt and produces an ischemic stroke. PBE has been considered a rare cause of stroke, especially in juvenile patients [4, 5]. It has been reported that the incidence of PBE is 1.8–12.8% among stroke patients [6]. From recent studies, however, PBE might be a common cause of cryptogenic stroke unrelated to patient’s age [7]. We thus hypothesized that the incidence of cardioembolic stroke (CES) including PBE among patients with acute stroke would increase after the Great East Japan Earthquake due to cessation of antithrombotic therapy or the increase in heart disease and DVT associated with the evacuation. The association between the disaster and detailed stroke subtypes has not been determined to date. The aim of this study is to evaluate the changes in the prevalence of DVT and the incidence of CES including PBE in acute ischemic stroke before and after the earthquake. Methods Study Population The subjects of the present study were 1,044 consecutive patients (73.1 ± 12.5 years old, male 61.5%) with acute ischemic stroke who were admitted to Kohnan Hospital (Sendai, Miyagi, Japan) within 7 days after stroke onset, between January 2010 and March 2012. Kohnan Hospital is the comprehensive stroke center in the Prefecture of Miyagi. Because of the inland location in the Prefecture of Miyagi (fig. 1b), the damage to our hospital from the earthquake
432
Cerebrovasc Dis 2014;37:431–437 DOI: 10.1159/000363129
and tsunami was minimal. Therefore, we could continue routine examinations during the catastrophe, including ultrasonography to evaluate the embolic source in cryptogenic stroke. The clinical and investigative data thus prospectively collected in a standardized fashion were entered into the Kohnan Hospital Stroke Registry. All patients with acute stroke admitted to our institute during this period were examined by neurologists, neurosurgeons, or both, and were screened by routine laboratory tests, as well as computerized tomography (CT) or magnetic resonance imaging (MRI). Ischemic stroke was diagnosed by stroke neurologists (board-certified neurologists specializing in the care of stroke patients) based on clinical and brain imaging findings. Patients with unknown cause of stroke were evaluated with multimodal examinations, including 24-hour monitoring of electrocardiograms, transcranial Doppler, transesophageal echocardiography, and ultrasonography of the lower extremities when not contraindicated. Neurological deficits were evaluated using the National Institutes of Health Stroke Scale (NIHSS) score upon admission [8]. Etiological Diagnosis The criteria for the indication of ultrasonography of the lower extremities to evaluate DVT were follows: (a) unknown cause of stroke in spite of initial evaluation (including electrocardiogram and brain imaging upon admission); (b) elevated serum levels of D-dimer or a degradation product of fibrin in patients with acute stroke. The diagnosis of CES was made when all of the following criteria [8, 9] were present: (1) concurrent cardiac source for an embolus, such as atrial fibrillation (AF), segmental wall akinesis, cardiomyopathy, or right-to-left shunt with DVT or pulmonary thromboembolism, and (2) no arterial stenosis of greater than 50% proximal to the lesions. Among patients with CES, the diagnosis of PBE was made when all following criteria [10] were present: (1) brain infarction demonstrated by CT or MRI; (2) right-to-left shunt; (3) deep venous thrombus or pulmonary thromboembolism; (4) neurological features of brain embolism, such as cortical infarction demonstrated by CT or MRI, and angiographic findings of intraluminal filling defect or reopening of previously occluded arteries, and (5) absence of other sources of embolism, such as heart disease, complicated atherosclerotic plaque at the aortic arch, or arterial stenotic lesion proximal to the lesion. Analysis The prevalence of DVT and AF, and the incidence of CES including PBE were compared between before and after the earthquake of 11 March 2011. The Student t test, χ2 test, and KruskalWallis test were used as appropriate. To identify the impact of the earthquake, multivariate logistic regression analyses were applied. All models were adjusted for age, sex, initial NIHSS score, and patient’s residential address (living in the municipalities along the coast or not). The definition of municipalities along the coast was based on a previous study [1]. We included two time variables in the regression models: (1) a two-categorical time variable categorized into time periods before and after the earthquake of 11 March 2011, and (2) 3-month periods from January 2010 to March 2012, with the first four quarters combined to a year period being the reference category. Statistical analyses were done with the JMP (SAS Institute Inc., Cary, N.C., USA) statistical software package. A value of p < 0.05 (two-sided) was considered to indicate a significant difference.
Itabashi/Furui/Sato/Yazawa/Kawata/Mori
a
b Miyagi
Kohan hospital The epicenter
200 km
160
40
140
35
120
30
4.5
12
4.0
10 8 6 4 2
I 2012
IV 2011
III 2011
II 2011
I 2011
IV 2010
14
IV 2010
b
III 2010
I 2012
IV 2011
III 2011
II 2011
I 2011
IV 2010
III 2010
II 2010
0 I 2010
5
0
PBE incidence (%)
3.5 3.0 2.5 2.0 1.5 1.0 0.5 I 2012
IV 2011
III 2011
d
II 2011
I 2012
IV 2011
III 2011
II 2011
I 2011
IV 2010
III 2010
II 2010
I 2010
0 I 2011
DVT prevalence (%)
10
20
0
c
15
III 2010
40
20
II 2010
60
20 km
25
II 2010
80
I 2010
100
Miyagi prefecture
I 2010
CES incidence (%)
Patients (n)
tween the epicenter of the earthquake and the Prefecture of Miyagi. b The location of Kohnan Hospital in the Prefecture of Miyagi.
a
Kohan hospital
Tokyo
Fig. 1. a The positional relationship be-
Fig. 2. Arrowheads indicate the Great Japan Earthquake and Tsunami of 11 March 2011. a The number of patients with acute ischemic stroke. b The incidence of CES. c The prevalence of DVT in patients with acute stroke. d The incidence of PBE.
The median initial NIHSS score was 4 (interquartile range: 1–8). The number of patients with acute ischemic stroke who were admitted to our institute increased after
the earthquake, followed by a decrease after the second quarter of 2011 (fig. 2a). Two hundred and eighty-two patients (27.0% of those surveyed) were diagnosed with CES. The proportion of CES patients increased after the first quarter of 2011
Cardioembolic Stroke before and after the Great East Japan Earthquake
Cerebrovasc Dis 2014;37:431–437 DOI: 10.1159/000363129
Results
433
Table 1. Analysis of the incidence of CES
Model 1
