Original Paper Eur Neurol 2016;76:295–301 DOI: 10.1159/000452659
Received: September 8, 2016 Accepted: October 14, 2016 Published online: November 3, 2016
Etiologic and Clinical Characterization of Patients with Recurrent Spontaneous Intracerebral Hemorrhage Marc E. Wolf Angelika Alonso Anne D. Ebert Kristina Szabo Anastasios Chatzikonstantinou Department of Neurology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
Abstract Background: The impact of recurrent stroke has been extensively addressed with regard to ischemic stroke, revealing potentially different etiologies of recurrent events in the individual patient. In contrast, data on recurrent intracerebral hemorrhage (ICH) are scarce, especially considering etiologic characterization. We aimed to determine the etiology of recurrent ICH at each event to identify potential etiologic changes. Patients and Methods: We analyzed the data of patients admitted to our stroke unit with recurrent ICH between 1998 and 2014 with regard to clinical characteristics and etiology. Results: Thirty-three patients (2.6%) with recurrent ICH were identified. Mean age (mean ± SD) at the initial event was 69 ± 9 and 72 ± 9 years at recurrence. Median interval between events was 18 months. Mean National Institutes of Health Stroke Scale (first/second event) was 4/9 at admission and 2/8 at discharge. Over 30% of patients developed symptomatic epilepsy. Etiologic distribution was (first/second event) the following: probable cerebral amyloid angiopathy (CAA) (12/20), possible CAA (3/0), hypertensive (5/4), anticoagulation (4/3), vascular
© 2016 S. Karger AG, Basel 0014–3022/16/0766–0295$39.50/0 E-Mail [email protected] www.karger.com/ene
malformation (2/4), ischemia with secondary hemorrhage (4/0), vasculitis (0/1), undetermined (4/0). Conclusions: Recurrent ICH is rare, CAA being its most common etiology. Etiology of ICH may differ between the first/second event in about 10%. The findings indicate the need of a complete and distinct work-up including MRI in every instance of ICH recurrence. © 2016 S. Karger AG, Basel
Background
The impact of recurrent stroke has been extensively addressed in several studies with regard to ischemic stroke, revealing potentially different etiologies of recurrent events in the individual patient [1, 2]. Intracerebral hemorrhage (ICH) accounts for about 10–15% of acute stroke [3]. However, data on recurrent ICH is scarce. In a recent systematic review and meta-analysis, the annual rate of ICH recurrence has been assessed with about 2% and the risk of recurrent ICH by 1 year was between 1.8 and 7.4% [4]. Current studies indicated that the proportion of lobar hemorrhage as a manifestation of cerebral amyloid angiopathy (CAA) has continuously grown during the last 2 decades [5]. The risk of recurrence was estimated higher after lobar ICH compared to subcortical hyMarc E. Wolf Department of Neurology Universitätsmedizin Mannheim Theodor-Kutzer-Ufer 1-3, DE–68167 Mannheim (Germany) E-Mail wolf @ neuro.ma.uni-heidelberg.de
Downloaded by: UCL 144.82.108.120 - 11/3/2016 5:15:25 PM
Key Words Intracerebral hemorrhage · Recurrence · Etiology · Cerebral amyloid angiopathy
Patients and Methods Patients We retrospectively analyzed the data of our stroke database between 1998 and 2014 for patients admitted to our stroke unit with spontaneous ICH and recurrent spontaneous ICH. The local ethics committee approved the use of this data for the purpose of the study. Diagnosis of ICH was established by a stroke neurologist after clinical examination and initial brain imaging. Patients with recurrent ICH were further characterized with regard to clinical presentation, previous history and medication, cardiovascular risk factors and clinical outcome (National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scal (mRS)) at admission and discharge. The etiology of ICH was definitively established after comprehensive stroke work-up and assigned to one of the following categories: probable/possible CAA, arterial hypertension (HT), anticoagulation, vascular malformation, secondary hemorrhage of ischemic lesion, vasculitis or undetermined. The diagnosis of CAA was established and refined according to the Boston criteria [8]. Hematoma volumes were calculated using initial CT images according to the ABC/2 formula [9]. The method was adapted to MRI evaluation in cases where no CT had been performed. Statistical Analysis Patients with CAA were compared to patients with other etiologies (‘no CAA’) (based on final diagnosis at the second event) regarding baseline characteristics and outcome parameters. To compare dichotomous or nominal data, we used the chi-square test (in case of cell counts 40-year-old patient with severe HT and consecutive recurrent hypertensive subcortical ICH.
b
Etiology of Recurrent ICH CAA is increasingly recognized as a major cause of recurrent ICH [5–7]. This could be confirmed in our study. However, different etiologies should not be neglected, since cortical ICH might be due to vascular malformations or vasculitis, as shown in the present study. Those etiologies require specific treatment options crucial for the further outcome of the patient. Over 10% of the patients had a typical subcortical hypertensive ICH, which might have been prevented by intensified antihypertensive treatment. This finding stresses the importance of optimized secondary prophylaxis and supports previous findings [10]. The phenotype of simultaneous multiple ICHs was not restrict-
ed to a specific etiology in our study, which supports other previous data [11, 12]. The etiology of ICH changed in 24% of the patients between the first and second event. However, when excluding the 4 patients who initially had an undetermined etiology, the value is lower (about 12%). This seems to roughly confirm previous results showing about 18% of patients with different pathophysiology in recurrent ICH in a population of 185 patients [13]. It underlines again the need of a complete and distinct work-up of patients with ICH. An overhasty classification either as hypertensive or CAA-associated ICH based on CT or on the etiology of a previous ICH should be avoided.
Etiology of Recurrent ICH
Eur Neurol 2016;76:295–301 DOI: 10.1159/000452659
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a
Etiologic classification can have a great impact on strategies for secondary prevention of ICH, such as controlling the blood pressure in hypertensive patients or avoiding anticoagulation in CAA patients. Secondary prophylaxis of ICH is rather difficult, since patients are not only at risk to suffer recurrent ICH but also might develop ischemic stroke on follow-up, which was the case in 34 patients with initial ICH identified during the study period. The patients of our study had a classical cardiovascular risk profile, supporting this issue of an elevated risk for further cerebrovascular events.
The Role of MRI In patients with atypical cortical bleedings, MRI with T2* sequences was helpful to establish the diagnosis of CAA, thus reducing the proportion of undetermined etiologies (fig. 2). Diffusion-weighted imaging was crucial to identify concomitant ischemic lesions, helping to confirm suspected cases of secondary hemorrhage and therefore fundamentally changing the long-term treatment options in these patients. MRI is therefore very helpful to establish and refine the etiology of ICH and should therefore be used routinely in these cases.
Risk of Recurrence According to ICH Localization In a recent observational study, 1,145 consecutive patients with ICH, who survived at least 90 days, were followed in view of recurrent events and blood pressure control. The rate of recurrence war higher in lobar ICH compared to non-lobar localization. Inadequate blood pressure control was associated with higher risk of ICH recurrence independent of the localization [14]. In another series of 24 patients with recurrent ICH, HT was considered as the etiology in the majority of the cases; however, the most common imaging features were lobar bleedings potentially suggestive of CAA, which was not formally diagnosed in the absence of bioptic results [15]. Overall, lobar ICH seems to be more prone to recurrence [6, 7]. The high number of lobar ICH compared to subcortical ICH in our study seems to confirm this tendency, but the study was not specifically designed to evaluate such prognostic trends. The occurrence of recurrent stroke with about 50% of hemorrhagic and 50% of ischemic origin confirms recent findings [4]. The risk of recurrent stroke was investigated in a multicenter series containing 496 patients with spontaneous ICH followed for 2 years. Risk of recurrent ICH remained high beyond the first year in lobar ICH, while in subcortical ICH it decreased after the first year. However, in both groups, the risk of a recurrent event of ischemic origin was higher than for ICH [16]. In our series, 12 out of 33 recurrent events occurred within the first 12 months, but most had a cortical localization and several subcortical ICHs occurred after a period of over 12 months. This indicates the need for long-term care on risk factors that should not be limited to the subacute phase after stroke. This seems even more important since the long-term compliance needs to be improved as reflected by the results of our study with 32 patients having a diagnosis of HT but only 23 being on an antihypertensive treatment at the recurrent event.
Outcome We found a better outcome for patients with CAA compared to other etiologies, which is in line with previous reports about better prognosis of lobar hemorrhage compared to hypertensive ICH [17]. The better prognosis might be one explanation for higher recurrence rates, since hypertensive ICH more often leads to early mortality [4]. Occurrence of epilepsy in about 30% was marginally higher than the previously reported 14–25% [18, 19]. Probably due to the small number of patients, its association with CAA showed only a trend toward but did not reach statistical significance; anyhow, all patients who developed epilepsy had at least 1 lobar ICH [19].
Eur Neurol 2016;76:295–301 DOI: 10.1159/000452659
Disclosure Statement The authors have no conflicts of interest to disclose.
Wolf/Alonso/Ebert/Szabo/ Chatzikonstantinou
Downloaded by: UCL 144.82.108.120 - 11/3/2016 5:15:25 PM
300
Limitations Due to the rarity of recurrent ICH, the number of patients in this single-center study remains low, although the analyzed period was quite long with over 15 years. During this period of time, MRI has become the standard imaging procedure in atypical ICH in larger stroke centers – but was not yet used that often at the beginning of the study. This might have influenced the diagnostic interpretation of possible or probable CAA in earlier patients. We might also have missed some further events of either hemorrhagic, ischemic or ictal origin, meaning that recurrent events could be eventually slightly higher than reported. In summary, CAA is the most common etiology of recurrent ICH; however, a distinct work-up including MRI is useful at each distinct event, since the etiology of ICH might change in about 10% between the events. This change of etiologic classification has a potential impact on secondary prophylaxis and therefore underlines the need of a rigorous work-up.
References
Etiology of Recurrent ICH
6 Passero S, Burgalassi L, D’Andrea P, Battistini N: Recurrence of bleeding in patients with primary intracerebral hemorrhage. Stroke 1995;26:1189–1192. 7 Yen CC, Lo YK, Li JY, Lin YT, Lin CH, Gau YY: Recurrent primary intracerebral hemorrhage: a hospital based study. Acta Neurol Taiwan 2007;16:74–80. 8 Vonsattel JP, Myers RH, Hedley-Whyte ET, Ropper AH, Bird ED, Richardson EP Jr: Cerebral amyloid angiopathy without and with cerebral hemorrhages: a comparative histological study. Ann Neurol 1991; 30: 637– 649. 9 Kothari RU, Brott T, Broderick JP, et al: The ABCs of measuring intracerebral hemorrhage volumes. Stroke 1996;27:1304–1305. 10 Misra UK, Kalita J, Somarajan BI: Recurrent intracerebral hemorrhage in patients with hypertension is associated with APOE gene polymorphism: a preliminary study. J Stroke Cerebrovasc Dis 2013;22:758–763. 11 Chen Y, Henon H, Bombois S, Pasquier F, Cordonnier C: Multiple simultaneous spontaneous intracerebral hemorrhages: a rare entity. Cerebrovasc Dis 2016;41:74–79. 12 Takeuchi S, Takasato Y, Masaoka H, Hayakawa T, Yatsushige H, Sugawara T: Simultane-
13
14
15 16
17
18 19
Eur Neurol 2016;76:295–301 DOI: 10.1159/000452659
ous multiple hypertensive intracranial hemorrhages. J Clin Neurosci 2011;18:1215–1218. Yeh SJ, Tang SC, Tsai LK, Jeng JS: Pathogenetical subtypes of recurrent intracerebral hemorrhage: designations by SMASH-U classification system. Stroke 2014;45:2636–2642. Biffi A, Anderson CD, Battey TW, et al: Association between blood pressure control and risk of recurrent intracerebral hemorrhage. JAMA 2015;314:904–912. Neau JP, Ingrand P, Couderq C, et al: Recurrent intracerebral hemorrhage. Neurology 1997;49:106–113. Weimar C, Benemann J, Terborg C, et al: Recurrent stroke after lobar and deep intracerebral hemorrhage: a hospital-based cohort study. Cerebrovasc Dis 2011;32:283–288. Samarasekera N, Fonville A, Lerpiniere C, et al: Influence of intracerebral hemorrhage location on incidence, characteristics, and outcome: population-based study. Stroke 2015;46:361–368. Bladin CF, Alexandrov AV, Bellavance A, et al: Seizures after stroke: a prospective multicenter study. Arch Neurol 2000;57:1617–1622. Faught E, Peters D, Bartolucci A, Moore L, Miller PC: Seizures after primary intracerebral hemorrhage. Neurology 1989;39:1089–1093.
301
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1 Wolf ME, Sauer T, Hennerici MG, Chatzikonstantinou A: Characterization of patients with recurrent ischaemic stroke using the ASCO classification. Eur J Neurol 2013; 20: 812–817. 2 Hillen T, Coshall C, Tilling K, Rudd AG, McGovern R, Wolfe CD: Cause of stroke recurrence is multifactorial: patterns, risk factors, and outcomes of stroke recurrence in the south London stroke register. Stroke 2003;34: 1457–1463. 3 van Asch CJ, Luitse MJ, Rinkel GJ, van der Tweel I, Algra A, Klijn CJ: Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. Lancet Neurol 2010; 9: 167– 176. 4 Poon MT, Fonville AF, Al-Shahi Salman R: Long-term prognosis after intracerebral haemorrhage: systematic review and metaanalysis. J Neurol Neurosurg Psychiatry 2014; 85:660–667. 5 Bejot Y, Cordonnier C, Durier J, Aboa-Eboule C, Rouaud O, Giroud M: Intracerebral haemorrhage profiles are changing: results from the Dijon population-based study. Brain 2013;136(pt 2):658–664.
Received: September 8, 2016 Accepted: October 14, 2016 Published online: November 3, 2016
Etiologic and Clinical Characterization of Patients with Recurrent Spontaneous Intracerebral Hemorrhage Marc E. Wolf Angelika Alonso Anne D. Ebert Kristina Szabo Anastasios Chatzikonstantinou Department of Neurology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
Abstract Background: The impact of recurrent stroke has been extensively addressed with regard to ischemic stroke, revealing potentially different etiologies of recurrent events in the individual patient. In contrast, data on recurrent intracerebral hemorrhage (ICH) are scarce, especially considering etiologic characterization. We aimed to determine the etiology of recurrent ICH at each event to identify potential etiologic changes. Patients and Methods: We analyzed the data of patients admitted to our stroke unit with recurrent ICH between 1998 and 2014 with regard to clinical characteristics and etiology. Results: Thirty-three patients (2.6%) with recurrent ICH were identified. Mean age (mean ± SD) at the initial event was 69 ± 9 and 72 ± 9 years at recurrence. Median interval between events was 18 months. Mean National Institutes of Health Stroke Scale (first/second event) was 4/9 at admission and 2/8 at discharge. Over 30% of patients developed symptomatic epilepsy. Etiologic distribution was (first/second event) the following: probable cerebral amyloid angiopathy (CAA) (12/20), possible CAA (3/0), hypertensive (5/4), anticoagulation (4/3), vascular
© 2016 S. Karger AG, Basel 0014–3022/16/0766–0295$39.50/0 E-Mail [email protected] www.karger.com/ene
malformation (2/4), ischemia with secondary hemorrhage (4/0), vasculitis (0/1), undetermined (4/0). Conclusions: Recurrent ICH is rare, CAA being its most common etiology. Etiology of ICH may differ between the first/second event in about 10%. The findings indicate the need of a complete and distinct work-up including MRI in every instance of ICH recurrence. © 2016 S. Karger AG, Basel
Background
The impact of recurrent stroke has been extensively addressed in several studies with regard to ischemic stroke, revealing potentially different etiologies of recurrent events in the individual patient [1, 2]. Intracerebral hemorrhage (ICH) accounts for about 10–15% of acute stroke [3]. However, data on recurrent ICH is scarce. In a recent systematic review and meta-analysis, the annual rate of ICH recurrence has been assessed with about 2% and the risk of recurrent ICH by 1 year was between 1.8 and 7.4% [4]. Current studies indicated that the proportion of lobar hemorrhage as a manifestation of cerebral amyloid angiopathy (CAA) has continuously grown during the last 2 decades [5]. The risk of recurrence was estimated higher after lobar ICH compared to subcortical hyMarc E. Wolf Department of Neurology Universitätsmedizin Mannheim Theodor-Kutzer-Ufer 1-3, DE–68167 Mannheim (Germany) E-Mail wolf @ neuro.ma.uni-heidelberg.de
Downloaded by: UCL 144.82.108.120 - 11/3/2016 5:15:25 PM
Key Words Intracerebral hemorrhage · Recurrence · Etiology · Cerebral amyloid angiopathy
Patients and Methods Patients We retrospectively analyzed the data of our stroke database between 1998 and 2014 for patients admitted to our stroke unit with spontaneous ICH and recurrent spontaneous ICH. The local ethics committee approved the use of this data for the purpose of the study. Diagnosis of ICH was established by a stroke neurologist after clinical examination and initial brain imaging. Patients with recurrent ICH were further characterized with regard to clinical presentation, previous history and medication, cardiovascular risk factors and clinical outcome (National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scal (mRS)) at admission and discharge. The etiology of ICH was definitively established after comprehensive stroke work-up and assigned to one of the following categories: probable/possible CAA, arterial hypertension (HT), anticoagulation, vascular malformation, secondary hemorrhage of ischemic lesion, vasculitis or undetermined. The diagnosis of CAA was established and refined according to the Boston criteria [8]. Hematoma volumes were calculated using initial CT images according to the ABC/2 formula [9]. The method was adapted to MRI evaluation in cases where no CT had been performed. Statistical Analysis Patients with CAA were compared to patients with other etiologies (‘no CAA’) (based on final diagnosis at the second event) regarding baseline characteristics and outcome parameters. To compare dichotomous or nominal data, we used the chi-square test (in case of cell counts 40-year-old patient with severe HT and consecutive recurrent hypertensive subcortical ICH.
b
Etiology of Recurrent ICH CAA is increasingly recognized as a major cause of recurrent ICH [5–7]. This could be confirmed in our study. However, different etiologies should not be neglected, since cortical ICH might be due to vascular malformations or vasculitis, as shown in the present study. Those etiologies require specific treatment options crucial for the further outcome of the patient. Over 10% of the patients had a typical subcortical hypertensive ICH, which might have been prevented by intensified antihypertensive treatment. This finding stresses the importance of optimized secondary prophylaxis and supports previous findings [10]. The phenotype of simultaneous multiple ICHs was not restrict-
ed to a specific etiology in our study, which supports other previous data [11, 12]. The etiology of ICH changed in 24% of the patients between the first and second event. However, when excluding the 4 patients who initially had an undetermined etiology, the value is lower (about 12%). This seems to roughly confirm previous results showing about 18% of patients with different pathophysiology in recurrent ICH in a population of 185 patients [13]. It underlines again the need of a complete and distinct work-up of patients with ICH. An overhasty classification either as hypertensive or CAA-associated ICH based on CT or on the etiology of a previous ICH should be avoided.
Etiology of Recurrent ICH
Eur Neurol 2016;76:295–301 DOI: 10.1159/000452659
299
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a
Etiologic classification can have a great impact on strategies for secondary prevention of ICH, such as controlling the blood pressure in hypertensive patients or avoiding anticoagulation in CAA patients. Secondary prophylaxis of ICH is rather difficult, since patients are not only at risk to suffer recurrent ICH but also might develop ischemic stroke on follow-up, which was the case in 34 patients with initial ICH identified during the study period. The patients of our study had a classical cardiovascular risk profile, supporting this issue of an elevated risk for further cerebrovascular events.
The Role of MRI In patients with atypical cortical bleedings, MRI with T2* sequences was helpful to establish the diagnosis of CAA, thus reducing the proportion of undetermined etiologies (fig. 2). Diffusion-weighted imaging was crucial to identify concomitant ischemic lesions, helping to confirm suspected cases of secondary hemorrhage and therefore fundamentally changing the long-term treatment options in these patients. MRI is therefore very helpful to establish and refine the etiology of ICH and should therefore be used routinely in these cases.
Risk of Recurrence According to ICH Localization In a recent observational study, 1,145 consecutive patients with ICH, who survived at least 90 days, were followed in view of recurrent events and blood pressure control. The rate of recurrence war higher in lobar ICH compared to non-lobar localization. Inadequate blood pressure control was associated with higher risk of ICH recurrence independent of the localization [14]. In another series of 24 patients with recurrent ICH, HT was considered as the etiology in the majority of the cases; however, the most common imaging features were lobar bleedings potentially suggestive of CAA, which was not formally diagnosed in the absence of bioptic results [15]. Overall, lobar ICH seems to be more prone to recurrence [6, 7]. The high number of lobar ICH compared to subcortical ICH in our study seems to confirm this tendency, but the study was not specifically designed to evaluate such prognostic trends. The occurrence of recurrent stroke with about 50% of hemorrhagic and 50% of ischemic origin confirms recent findings [4]. The risk of recurrent stroke was investigated in a multicenter series containing 496 patients with spontaneous ICH followed for 2 years. Risk of recurrent ICH remained high beyond the first year in lobar ICH, while in subcortical ICH it decreased after the first year. However, in both groups, the risk of a recurrent event of ischemic origin was higher than for ICH [16]. In our series, 12 out of 33 recurrent events occurred within the first 12 months, but most had a cortical localization and several subcortical ICHs occurred after a period of over 12 months. This indicates the need for long-term care on risk factors that should not be limited to the subacute phase after stroke. This seems even more important since the long-term compliance needs to be improved as reflected by the results of our study with 32 patients having a diagnosis of HT but only 23 being on an antihypertensive treatment at the recurrent event.
Outcome We found a better outcome for patients with CAA compared to other etiologies, which is in line with previous reports about better prognosis of lobar hemorrhage compared to hypertensive ICH [17]. The better prognosis might be one explanation for higher recurrence rates, since hypertensive ICH more often leads to early mortality [4]. Occurrence of epilepsy in about 30% was marginally higher than the previously reported 14–25% [18, 19]. Probably due to the small number of patients, its association with CAA showed only a trend toward but did not reach statistical significance; anyhow, all patients who developed epilepsy had at least 1 lobar ICH [19].
Eur Neurol 2016;76:295–301 DOI: 10.1159/000452659
Disclosure Statement The authors have no conflicts of interest to disclose.
Wolf/Alonso/Ebert/Szabo/ Chatzikonstantinou
Downloaded by: UCL 144.82.108.120 - 11/3/2016 5:15:25 PM
300
Limitations Due to the rarity of recurrent ICH, the number of patients in this single-center study remains low, although the analyzed period was quite long with over 15 years. During this period of time, MRI has become the standard imaging procedure in atypical ICH in larger stroke centers – but was not yet used that often at the beginning of the study. This might have influenced the diagnostic interpretation of possible or probable CAA in earlier patients. We might also have missed some further events of either hemorrhagic, ischemic or ictal origin, meaning that recurrent events could be eventually slightly higher than reported. In summary, CAA is the most common etiology of recurrent ICH; however, a distinct work-up including MRI is useful at each distinct event, since the etiology of ICH might change in about 10% between the events. This change of etiologic classification has a potential impact on secondary prophylaxis and therefore underlines the need of a rigorous work-up.
References
Etiology of Recurrent ICH
6 Passero S, Burgalassi L, D’Andrea P, Battistini N: Recurrence of bleeding in patients with primary intracerebral hemorrhage. Stroke 1995;26:1189–1192. 7 Yen CC, Lo YK, Li JY, Lin YT, Lin CH, Gau YY: Recurrent primary intracerebral hemorrhage: a hospital based study. Acta Neurol Taiwan 2007;16:74–80. 8 Vonsattel JP, Myers RH, Hedley-Whyte ET, Ropper AH, Bird ED, Richardson EP Jr: Cerebral amyloid angiopathy without and with cerebral hemorrhages: a comparative histological study. Ann Neurol 1991; 30: 637– 649. 9 Kothari RU, Brott T, Broderick JP, et al: The ABCs of measuring intracerebral hemorrhage volumes. Stroke 1996;27:1304–1305. 10 Misra UK, Kalita J, Somarajan BI: Recurrent intracerebral hemorrhage in patients with hypertension is associated with APOE gene polymorphism: a preliminary study. J Stroke Cerebrovasc Dis 2013;22:758–763. 11 Chen Y, Henon H, Bombois S, Pasquier F, Cordonnier C: Multiple simultaneous spontaneous intracerebral hemorrhages: a rare entity. Cerebrovasc Dis 2016;41:74–79. 12 Takeuchi S, Takasato Y, Masaoka H, Hayakawa T, Yatsushige H, Sugawara T: Simultane-
13
14
15 16
17
18 19
Eur Neurol 2016;76:295–301 DOI: 10.1159/000452659
ous multiple hypertensive intracranial hemorrhages. J Clin Neurosci 2011;18:1215–1218. Yeh SJ, Tang SC, Tsai LK, Jeng JS: Pathogenetical subtypes of recurrent intracerebral hemorrhage: designations by SMASH-U classification system. Stroke 2014;45:2636–2642. Biffi A, Anderson CD, Battey TW, et al: Association between blood pressure control and risk of recurrent intracerebral hemorrhage. JAMA 2015;314:904–912. Neau JP, Ingrand P, Couderq C, et al: Recurrent intracerebral hemorrhage. Neurology 1997;49:106–113. Weimar C, Benemann J, Terborg C, et al: Recurrent stroke after lobar and deep intracerebral hemorrhage: a hospital-based cohort study. Cerebrovasc Dis 2011;32:283–288. Samarasekera N, Fonville A, Lerpiniere C, et al: Influence of intracerebral hemorrhage location on incidence, characteristics, and outcome: population-based study. Stroke 2015;46:361–368. Bladin CF, Alexandrov AV, Bellavance A, et al: Seizures after stroke: a prospective multicenter study. Arch Neurol 2000;57:1617–1622. Faught E, Peters D, Bartolucci A, Moore L, Miller PC: Seizures after primary intracerebral hemorrhage. Neurology 1989;39:1089–1093.
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1 Wolf ME, Sauer T, Hennerici MG, Chatzikonstantinou A: Characterization of patients with recurrent ischaemic stroke using the ASCO classification. Eur J Neurol 2013; 20: 812–817. 2 Hillen T, Coshall C, Tilling K, Rudd AG, McGovern R, Wolfe CD: Cause of stroke recurrence is multifactorial: patterns, risk factors, and outcomes of stroke recurrence in the south London stroke register. Stroke 2003;34: 1457–1463. 3 van Asch CJ, Luitse MJ, Rinkel GJ, van der Tweel I, Algra A, Klijn CJ: Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. Lancet Neurol 2010; 9: 167– 176. 4 Poon MT, Fonville AF, Al-Shahi Salman R: Long-term prognosis after intracerebral haemorrhage: systematic review and metaanalysis. J Neurol Neurosurg Psychiatry 2014; 85:660–667. 5 Bejot Y, Cordonnier C, Durier J, Aboa-Eboule C, Rouaud O, Giroud M: Intracerebral haemorrhage profiles are changing: results from the Dijon population-based study. Brain 2013;136(pt 2):658–664.
