Intervent Neurol 2014;3:56–66 DOI: 10.1159/000369481 Published online: December 9, 2014
© 2014 S. Karger AG, Basel 1664–9737/14/0031–0056$39.50/0 www.karger.com/ine
Original Paper
Aggressive Medical Care in Young Chinese Patients with Ischemic Stroke of Undetermined Etiology: A Retrospective Study Ling Liu
Fang Yang
Min Li
Huajuan Hou
Qin Yin
Renliang Zhang
Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, PR China
Key Words Medical care · Undetermined etiology · Young stroke patients Abstract Objectives: This study aimed to investigate the clinical and angiographic characteristics of ischemic stroke of undetermined etiology in young Chinese adults and to observe the effects of medication on their long-term outcomes. Methods: A total of 179 consecutive young patients with ischemic stroke of undetermined etiology were retrospectively analyzed for clinical and angiographic characteristics, laboratory tests, the choice of drug treatment, and followup outcomes. Any predictive power for recurrent stroke and new lesions or aggravated stenosis was analyzed. Results: 170 patients were clinically followed up for a median of 25 months (range, 4–92), and 65 patients with 114 lesions had angiographic follow-up for a median of 7 months. A total of 53 patients were enrolled in a routine medical management (RMM) group, and 117 were treated with corticosteroids plus RMM (aggressive medical management, AMM). Kaplan-Meier survival analysis revealed that differences in the 2-year cumulative stroke-free rate and in the 18-month cumulative worsening and/or new lesion-free rate between the RMM and AMM groups were significant (p < 0.05). Multivariate and Cox regression analyses revealed that the choice of drug therapy and erythrocyte sedimentation rate were associated with recurrent stroke, that AMM was independently associated with a decreased risk of worsening lesion, and that worsening lesion was the only independent predictor of recurrent
L.L., F.Y., M.L., and H.H. contributed equally to this work. Dr. Renliang Zhang, MD, PhD Department of Neurology Jinling Hospital, Nanjing University School of Medicine 305# East Zhongshan Road, Nanjing, Jiangsu 210002 (PR China) E-Mail zhangrenliang @ gmail.com
57
Intervent Neurol 2014;3:56–66 DOI: 10.1159/000369481
© 2014 S. Karger AG, Basel www.karger.com/ine
Liu et al.: Aggressive Medical Care in Young Chinese Patients with Ischemic Stroke of Undetermined Etiology: A Retrospective Study
stroke. Conclusion: Compared with RMM, AMM is more efficacious in the prevention of secondary ischemic stroke and progressive arterial lesions among young adults with ischemic stroke of undetermined etiology. © 2014 S. Karger AG, Basel
Introduction
Ischemic strokes occurring in patients aged 1.3 billion and an uneven development of regional economies. Until now, published studies on young adults suffering from stroke mainly focused on its clinical subtypes, the distribution of stroke etiologies, prognosis, and associated cerebrovascular disease risk factors [7] and rarely referred to its medication and angiographic characteristics. In the present study, we attempted to retrospectively review the incidence of ischemic stroke of undetermined etiology among young Chinese patients (aged 18–45 years) as well as their clinical and angiographic characteristics. Meanwhile, we compared the efficacy of aggressive (AMM) and routine medical management (RMM) in clinical and angiographic outcomes. Materials and Methods Patients This study was approved by the ethics committee of our institution, and written informed consent was obtained from all patients and their families. The Nanjing Stroke Registry Program (NSRP) [8] is a program conducted in mainland China, which contains a variety of information including demographic, clinical, and imaging data as well as laboratory tests. Ischemic stroke patients aged 15 mg/l) IgM IgA IgG ASO (>20 IU/ml) Qualifying events TIA Ischemic stroke
37.6 ± 6.2 34 (74.9)
37.0 ± 6.4 85 (75.6)
38.5 ± 5.4 49 (75.4)
24 (0 – 92) 31.5 ± 24.2
24 (0 – 85) 31.5 ± 24.5
24 (6 – 92) 31.4 ± 23.8
34 (19.0) 30 (16.3) 41 (22.9) 14 (7.8) 19 (10.6) 38 (21.2) 24 (13.4)
23 (20.2) 18 (15.8) 24 (21.1) 7 (6.1) 11 (9.6) 23 (20.2) 16 (14.0)
11 (16.9) 12 (18.5) 17 (26.2) 7 (10.8) 8 (12.3) 15 (23.1) 8 (12.3)
40 (22.3) 139 (77.7)
28 (24.6) 86 (75.4)
12 (18.5) 53 (81.5)
84 (46.9) 162
84 (73.7) 48
0 (100) 114
113 47 (29.0) 17 (10.5) 45 (27.8) 4 (2.5) 49 4 (2.5) 5 (3.1) 40 (24.7) 78.37 ± 12.07
14 (29.2) 4 (8.3) 11 (22.9) 2 (4.2) 46 2 (4.2) 2 (4.2) 13 (27.1) 79.09 ± 12.07
33 (28.9) 13 (11.4) 34 (29.8) 2 (1.8) 2 (1.8) 3 (2.6) 27 (23.7) 76.67 ± 12.00
55 (30.7) 124 (69.3)
38 (33.3) 76 (66.7)
17 (26.2) 48 (73.8)
No stenosis Lesions, n Lesion location Anterior circulation Extracranial ICA Intracranial ICA Middle cerebral artery Anterior cerebral artery Posterior circulation Posterior cerebral artery Basilar artery Vertebral artery Mean degree of stenosis, ± SDa Treatment RMM AMM
Data are expressed as numbers with percentages in parentheses unless otherwise indicated. a The degree of stenosis was determined by the WASID method.
Results
Baseline Characteristics Between March 2005 and March 2012, data of 458 consecutive young patients with ischemic stroke (aged 18–45 years) were extracted from the NSRP, and 179 (39.1%) of them were diagnosed with ischemia of undetermined etiology. The baseline patient characteristics are presented in table 1. The mean age of all participants was 37.6 ± 6.2 years, and 134 (74.9%) of the patients were males. The qualifying events before enrolment were cerebral infarction (77.7%) and TIA (22.3%). A total of 55 (30.7%) patients were assigned to the RMM group and 124 (69.3%) to the AMM group. Blood examination was normal in the majority of the patients; only some had increased serum levels of IgG (20.2%), IgM (7.3%), and IgA (10.1%), ESR (18.4%), CRP (22.9%), and ASO (12.8%), or decreased C3 levels (15.6%). A total of 84 (46.9%) patients had no DSA-
60
Intervent Neurol 2014;3:56–66 DOI: 10.1159/000369481
© 2014 S. Karger AG, Basel www.karger.com/ine
Liu et al.: Aggressive Medical Care in Young Chinese Patients with Ischemic Stroke of Undetermined Etiology: A Retrospective Study
Table 2. Clinical and angiographic outcomes during follow-up End points
Clinical follow-up, months Median (range)
RMM (n = 53)
22 (4 – 85)
AMM (n = 117)
31 (6 – 92)
HR unadjusted
p
–6.61345 ± 3.90507 (–14.32279 – 1.09589)a
0.092
–1.93162 ± 0.98747 (–0.1783 – 3.88107)a
0.052
adjusted
p
28.6 ± 22.7
35.2 ± 24.0
Mean age ± SD, years
39.0 ± 5.5
37.1 ± 6.2
Clinical outcomes Recurrence
10 (18.9)
2 (1.7)
0.082 (0.018 – 0.375)
0.001
0.04 (0.008 – 0.211)
0.000
Angiographic outcomes Progression Improvement No change New lesion
43 9 (20.9) 10 (23.3) 17 (39.5) 7 (16.3)
71 4 (5.6) 44 (62.0) 22 (31.0) 1 (1.4)
0.211 (0.077 – 0.578)
0.002
0.160 (0.053 – 0.485)
0.001
DSA follow-up time, months Median (range)
8.0 (4.5 – 20)
–0.31952 ± 0.580994 (–0.83164 to 1.47068)a
0.583
Mean ± SD
8.2 ± 3.4
Mean ± SD
7 (4 – 18) 7.9 ± 2.8
Values are presented as numbers with percentages in parentheses unless otherwise indicated. Recurrence: cerebral infarction or TIA. Adjusted: adjusted by all the variables presented in table 1 using Cox proportional hazard analyses. a t value = mean ± SE with 95% CI in parentheses.
verified intra- or extracranial artery stenosis (degree of stenosis
© 2014 S. Karger AG, Basel 1664–9737/14/0031–0056$39.50/0 www.karger.com/ine
Original Paper
Aggressive Medical Care in Young Chinese Patients with Ischemic Stroke of Undetermined Etiology: A Retrospective Study Ling Liu
Fang Yang
Min Li
Huajuan Hou
Qin Yin
Renliang Zhang
Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, PR China
Key Words Medical care · Undetermined etiology · Young stroke patients Abstract Objectives: This study aimed to investigate the clinical and angiographic characteristics of ischemic stroke of undetermined etiology in young Chinese adults and to observe the effects of medication on their long-term outcomes. Methods: A total of 179 consecutive young patients with ischemic stroke of undetermined etiology were retrospectively analyzed for clinical and angiographic characteristics, laboratory tests, the choice of drug treatment, and followup outcomes. Any predictive power for recurrent stroke and new lesions or aggravated stenosis was analyzed. Results: 170 patients were clinically followed up for a median of 25 months (range, 4–92), and 65 patients with 114 lesions had angiographic follow-up for a median of 7 months. A total of 53 patients were enrolled in a routine medical management (RMM) group, and 117 were treated with corticosteroids plus RMM (aggressive medical management, AMM). Kaplan-Meier survival analysis revealed that differences in the 2-year cumulative stroke-free rate and in the 18-month cumulative worsening and/or new lesion-free rate between the RMM and AMM groups were significant (p < 0.05). Multivariate and Cox regression analyses revealed that the choice of drug therapy and erythrocyte sedimentation rate were associated with recurrent stroke, that AMM was independently associated with a decreased risk of worsening lesion, and that worsening lesion was the only independent predictor of recurrent
L.L., F.Y., M.L., and H.H. contributed equally to this work. Dr. Renliang Zhang, MD, PhD Department of Neurology Jinling Hospital, Nanjing University School of Medicine 305# East Zhongshan Road, Nanjing, Jiangsu 210002 (PR China) E-Mail zhangrenliang @ gmail.com
57
Intervent Neurol 2014;3:56–66 DOI: 10.1159/000369481
© 2014 S. Karger AG, Basel www.karger.com/ine
Liu et al.: Aggressive Medical Care in Young Chinese Patients with Ischemic Stroke of Undetermined Etiology: A Retrospective Study
stroke. Conclusion: Compared with RMM, AMM is more efficacious in the prevention of secondary ischemic stroke and progressive arterial lesions among young adults with ischemic stroke of undetermined etiology. © 2014 S. Karger AG, Basel
Introduction
Ischemic strokes occurring in patients aged 1.3 billion and an uneven development of regional economies. Until now, published studies on young adults suffering from stroke mainly focused on its clinical subtypes, the distribution of stroke etiologies, prognosis, and associated cerebrovascular disease risk factors [7] and rarely referred to its medication and angiographic characteristics. In the present study, we attempted to retrospectively review the incidence of ischemic stroke of undetermined etiology among young Chinese patients (aged 18–45 years) as well as their clinical and angiographic characteristics. Meanwhile, we compared the efficacy of aggressive (AMM) and routine medical management (RMM) in clinical and angiographic outcomes. Materials and Methods Patients This study was approved by the ethics committee of our institution, and written informed consent was obtained from all patients and their families. The Nanjing Stroke Registry Program (NSRP) [8] is a program conducted in mainland China, which contains a variety of information including demographic, clinical, and imaging data as well as laboratory tests. Ischemic stroke patients aged 15 mg/l) IgM IgA IgG ASO (>20 IU/ml) Qualifying events TIA Ischemic stroke
37.6 ± 6.2 34 (74.9)
37.0 ± 6.4 85 (75.6)
38.5 ± 5.4 49 (75.4)
24 (0 – 92) 31.5 ± 24.2
24 (0 – 85) 31.5 ± 24.5
24 (6 – 92) 31.4 ± 23.8
34 (19.0) 30 (16.3) 41 (22.9) 14 (7.8) 19 (10.6) 38 (21.2) 24 (13.4)
23 (20.2) 18 (15.8) 24 (21.1) 7 (6.1) 11 (9.6) 23 (20.2) 16 (14.0)
11 (16.9) 12 (18.5) 17 (26.2) 7 (10.8) 8 (12.3) 15 (23.1) 8 (12.3)
40 (22.3) 139 (77.7)
28 (24.6) 86 (75.4)
12 (18.5) 53 (81.5)
84 (46.9) 162
84 (73.7) 48
0 (100) 114
113 47 (29.0) 17 (10.5) 45 (27.8) 4 (2.5) 49 4 (2.5) 5 (3.1) 40 (24.7) 78.37 ± 12.07
14 (29.2) 4 (8.3) 11 (22.9) 2 (4.2) 46 2 (4.2) 2 (4.2) 13 (27.1) 79.09 ± 12.07
33 (28.9) 13 (11.4) 34 (29.8) 2 (1.8) 2 (1.8) 3 (2.6) 27 (23.7) 76.67 ± 12.00
55 (30.7) 124 (69.3)
38 (33.3) 76 (66.7)
17 (26.2) 48 (73.8)
No stenosis Lesions, n Lesion location Anterior circulation Extracranial ICA Intracranial ICA Middle cerebral artery Anterior cerebral artery Posterior circulation Posterior cerebral artery Basilar artery Vertebral artery Mean degree of stenosis, ± SDa Treatment RMM AMM
Data are expressed as numbers with percentages in parentheses unless otherwise indicated. a The degree of stenosis was determined by the WASID method.
Results
Baseline Characteristics Between March 2005 and March 2012, data of 458 consecutive young patients with ischemic stroke (aged 18–45 years) were extracted from the NSRP, and 179 (39.1%) of them were diagnosed with ischemia of undetermined etiology. The baseline patient characteristics are presented in table 1. The mean age of all participants was 37.6 ± 6.2 years, and 134 (74.9%) of the patients were males. The qualifying events before enrolment were cerebral infarction (77.7%) and TIA (22.3%). A total of 55 (30.7%) patients were assigned to the RMM group and 124 (69.3%) to the AMM group. Blood examination was normal in the majority of the patients; only some had increased serum levels of IgG (20.2%), IgM (7.3%), and IgA (10.1%), ESR (18.4%), CRP (22.9%), and ASO (12.8%), or decreased C3 levels (15.6%). A total of 84 (46.9%) patients had no DSA-
60
Intervent Neurol 2014;3:56–66 DOI: 10.1159/000369481
© 2014 S. Karger AG, Basel www.karger.com/ine
Liu et al.: Aggressive Medical Care in Young Chinese Patients with Ischemic Stroke of Undetermined Etiology: A Retrospective Study
Table 2. Clinical and angiographic outcomes during follow-up End points
Clinical follow-up, months Median (range)
RMM (n = 53)
22 (4 – 85)
AMM (n = 117)
31 (6 – 92)
HR unadjusted
p
–6.61345 ± 3.90507 (–14.32279 – 1.09589)a
0.092
–1.93162 ± 0.98747 (–0.1783 – 3.88107)a
0.052
adjusted
p
28.6 ± 22.7
35.2 ± 24.0
Mean age ± SD, years
39.0 ± 5.5
37.1 ± 6.2
Clinical outcomes Recurrence
10 (18.9)
2 (1.7)
0.082 (0.018 – 0.375)
0.001
0.04 (0.008 – 0.211)
0.000
Angiographic outcomes Progression Improvement No change New lesion
43 9 (20.9) 10 (23.3) 17 (39.5) 7 (16.3)
71 4 (5.6) 44 (62.0) 22 (31.0) 1 (1.4)
0.211 (0.077 – 0.578)
0.002
0.160 (0.053 – 0.485)
0.001
DSA follow-up time, months Median (range)
8.0 (4.5 – 20)
–0.31952 ± 0.580994 (–0.83164 to 1.47068)a
0.583
Mean ± SD
8.2 ± 3.4
Mean ± SD
7 (4 – 18) 7.9 ± 2.8
Values are presented as numbers with percentages in parentheses unless otherwise indicated. Recurrence: cerebral infarction or TIA. Adjusted: adjusted by all the variables presented in table 1 using Cox proportional hazard analyses. a t value = mean ± SE with 95% CI in parentheses.
verified intra- or extracranial artery stenosis (degree of stenosis
