Etiology, 3-Month Functional Outcome and Recurrent Events in Non-Traumatic Intracerebral Hemorrhage

doi:10.5853/jos.2021.01823

. 2022 May;24(2):266-277.

doi: 10.5853/jos.2021.01823. Epub 2022 May 31.

Etiology, 3-Month Functional Outcome and Recurrent Events in Non-Traumatic Intracerebral Hemorrhage

Martina B Goeldlin^{1

2}, Achim Mueller³, Bernhard M Siepen^{1

2}, Madlaine Mueller¹, Davide Strambo⁴, Patrik Michel⁴, Michael Schaerer⁵, Carlo W Cereda⁶, Giovanni Bianco⁶, Florian Lindheimer⁷, Christian Berger⁷, Friedrich Medlin⁸, Roland Backhaus⁹, Nils Peters⁹, Susanne Renaud¹⁰, Loraine Fisch¹¹, Julien Niederhaeuser¹¹, Emmanuel Carrera¹², Elisabeth Dirren¹², Christophe Bonvin¹³, Rolf Sturzenegger¹⁴, Timo Kahles¹⁵, Krassen Nedeltchev¹⁵, Georg Kaegi¹⁶, Jochen Vehoff¹⁶, Biljana Rodic¹⁷, Manuel Bolognese¹⁸, Ludwig Schelosky¹⁹, Stephan Salmen^{1

20}, Marie-Luise Mono²¹, Alexandros A Polymeris²², Stefan T Engelter^{22

23}, Philippe Lyrer²², Susanne Wegener³, Andreas R Luft^{3

24}, Werner Z'Graggen^{1

25}, David Bervini²⁵, Bastian Volbers^{1

26}, Tomas Dobrocky²⁷, Johannes Kaesmacher^{2

27

28}, Pasquale Mordasini²⁷, Thomas R Meinel^{1

2}, Marcel Arnold¹, Javier Fandino²⁹, Leo H Bonati²², Urs Fischer²², David J Seiffge¹; SSR Investigators

Affiliations

¹ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
² Graduate School of Health Sciences, University of Bern, Bern, Switzerland.
³ Department of Neurology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
⁴ Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
⁵ Department of Neurology, Buergerspital Solothurn, Solothurn, Switzerland.
⁶ Stroke Center EOC, Neurocenter of Southern Switzerland, Lugano, Switzerland.
⁷ Stroke Unit, Department of Internal Medicine, Hospital of Grabs, Grabs, Switzerland.
⁸ Stroke Unit and Division of Neurology, Department of Internal Medicine, HFR Fribourg-Cantonal Hospital, Villars-sur-Glâne, Switzerland.
⁹ Stroke Center Hirslanden, Klinik Hirslanden Zurich, Zurich, Switzerland.
¹⁰ Division of Neurology, Pourtalès Hospital, Neuchatel, Switzerland.
¹¹ Stroke Unit, GHOL, Hospital Nyon, Nyon, Switzerland.
¹² Stroke Research Group, Department of Clinical Neurosciences, Geneva University Hospital, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
¹³ Service of Neurology, Valais Hospital, Sion, Switzerland.
¹⁴ Department of Internal Medicine, Hospital Graubünden, Chur, Switzerland.
¹⁵ Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland.
¹⁶ Department of Neurology, Cantonal Hospital, St. Gallen, Switzerland.
¹⁷ Stroke Unit, Department of Neurology, Cantonal Hospital Winterthur (KSW), Winterthur, Switzerland.
¹⁸ Neurology Department, Lucerne Cantonal Hospital (LUKS), Luzern, Switzerland.
¹⁹ Division of Neurology, Kantonsspital Münsterlingen, Munsterlingen, Switzerland.
²⁰ Stroke Unit, Department of Neurology, Hospital Biel, Biel, Switzerland.
²¹ Stadtspitäler Triemli und Waid, Zurich, Switzerland.
²² Department of Neurology and Stroke Center, University Hospital Basel, University of Basel, Basel, Switzerland.
²³ Neurology and Neurorehabilitation, University Department of Geriatric Medicine FELIX PLATTER, University of Basel, Basel, Switzerland.
²⁴ Cereneo Center for Neurology and Rehabilitation, Vitznau, Switzerland.
²⁵ Department of Neurosurgery, Inselspital, Bern University Hospital, Bern, Switzerland.
²⁶ Department of Neurology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg (FAU), Erlangen, Germany.
²⁷ University Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
²⁸ University Institute of Diagnostic, Interventional and Paediatric Radiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
²⁹ Department of Neurosurgery, Cantonal Hospital Aarau, Aarau, Switzerland.

PMID: 35677981
PMCID: PMC9194537
DOI: 10.5853/jos.2021.01823

Etiology, 3-Month Functional Outcome and Recurrent Events in Non-Traumatic Intracerebral Hemorrhage

Martina B Goeldlin et al. J Stroke. 2022 May.

. 2022 May;24(2):266-277.

doi: 10.5853/jos.2021.01823. Epub 2022 May 31.

Authors

Affiliations

¹ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
² Graduate School of Health Sciences, University of Bern, Bern, Switzerland.
³ Department of Neurology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
⁴ Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
⁵ Department of Neurology, Buergerspital Solothurn, Solothurn, Switzerland.
⁶ Stroke Center EOC, Neurocenter of Southern Switzerland, Lugano, Switzerland.
⁷ Stroke Unit, Department of Internal Medicine, Hospital of Grabs, Grabs, Switzerland.
⁸ Stroke Unit and Division of Neurology, Department of Internal Medicine, HFR Fribourg-Cantonal Hospital, Villars-sur-Glâne, Switzerland.
⁹ Stroke Center Hirslanden, Klinik Hirslanden Zurich, Zurich, Switzerland.
¹⁰ Division of Neurology, Pourtalès Hospital, Neuchatel, Switzerland.
¹¹ Stroke Unit, GHOL, Hospital Nyon, Nyon, Switzerland.
¹² Stroke Research Group, Department of Clinical Neurosciences, Geneva University Hospital, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
¹³ Service of Neurology, Valais Hospital, Sion, Switzerland.
¹⁴ Department of Internal Medicine, Hospital Graubünden, Chur, Switzerland.
¹⁵ Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland.
¹⁶ Department of Neurology, Cantonal Hospital, St. Gallen, Switzerland.
¹⁷ Stroke Unit, Department of Neurology, Cantonal Hospital Winterthur (KSW), Winterthur, Switzerland.
¹⁸ Neurology Department, Lucerne Cantonal Hospital (LUKS), Luzern, Switzerland.
¹⁹ Division of Neurology, Kantonsspital Münsterlingen, Munsterlingen, Switzerland.
²⁰ Stroke Unit, Department of Neurology, Hospital Biel, Biel, Switzerland.
²¹ Stadtspitäler Triemli und Waid, Zurich, Switzerland.
²² Department of Neurology and Stroke Center, University Hospital Basel, University of Basel, Basel, Switzerland.
²³ Neurology and Neurorehabilitation, University Department of Geriatric Medicine FELIX PLATTER, University of Basel, Basel, Switzerland.
²⁴ Cereneo Center for Neurology and Rehabilitation, Vitznau, Switzerland.
²⁵ Department of Neurosurgery, Inselspital, Bern University Hospital, Bern, Switzerland.
²⁶ Department of Neurology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg (FAU), Erlangen, Germany.
²⁷ University Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
²⁸ University Institute of Diagnostic, Interventional and Paediatric Radiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
²⁹ Department of Neurosurgery, Cantonal Hospital Aarau, Aarau, Switzerland.

PMID: 35677981
PMCID: PMC9194537
DOI: 10.5853/jos.2021.01823

Abstract

Background and purpose: Knowledge about different etiologies of non-traumatic intracerebral hemorrhage (ICH) and their outcomes is scarce.

Methods: We assessed prevalence of pre-specified ICH etiologies and their association with outcomes in consecutive ICH patients enrolled in the prospective Swiss Stroke Registry (2014 to 2019).

Results: We included 2,650 patients (mean±standard deviation age 72±14 years, 46.5% female, median National Institutes of Health Stroke Scale 8 [interquartile range, 3 to 15]). Etiology was as follows: hypertension, 1,238 (46.7%); unknown, 566 (21.4%); antithrombotic therapy, 227 (8.6%); cerebral amyloid angiopathy (CAA), 217 (8.2%); macrovascular cause, 128 (4.8%); other determined etiology, 274 patients (10.3%). At 3 months, 880 patients (33.2%) were functionally independent and 664 had died (25.1%). ICH due to hypertension had a higher odds of functional independence (adjusted odds ratio [aOR], 1.33; 95% confidence interval [CI], 1.00 to 1.77; P=0.05) and lower mortality (aOR, 0.64; 95% CI, 0.47 to 0.86; P=0.003). ICH due to antithrombotic therapy had higher mortality (aOR, 1.62; 95% CI, 1.01 to 2.61; P=0.045). Within 3 months, 4.2% of patients had cerebrovascular events. The rate of ischemic stroke was higher than that of recurrent ICH in all etiologies but CAA and unknown etiology. CAA had high odds of recurrent ICH (aOR, 3.38; 95% CI, 1.48 to 7.69; P=0.004) while the odds was lower in ICH due to hypertension (aOR, 0.42; 95% CI, 0.19 to 0.93; P=0.031).

Conclusions: Although hypertension is the leading etiology of ICH, other etiologies are frequent. One-third of ICH patients are functionally independent at 3 months. Except for patients with presumed CAA, the risk of ischemic stroke within 3 months of ICH was higher than the risk of recurrent hemorrhage.

Keywords: Cerebral hemorrhage; Etiology; Ischemic stroke; Outcome.

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Figures

**Figure 1.**
Mechanistic classification of intracerebral hemorrhage (ICH) etiology: comparison of the original and adapted SMASH-U (structural lesion > systemic disease > medication > amyloid angiopathy > hypertension > unknown) classifications. CAA, cerebral amyloid angiopathy; INR, international normalized ratio.

**Figure 2.**
Frequency of intracerebral hemorrhage etiologies. CAA, cerebral amyloid angiopathy.

**Figure 3.**
Distribution of (A) age, (B) National Institutes of Health Stroke Scale (NIHSS), (C) systolic blood pressure, and (D) time from onset to admission among different intracerebral hemorrhage etiologies. CAA, cerebral amyloid angiopathy. *Clinical findings differed according to the underlying etiology.

**Figure 4.**
Functional outcomes at 3 months according to intracerebral hemorrhage (ICH) etiology. CAA, cerebral amyloid angiopathy; mRS, modified Rankin Scale.

**Figure 5.**
All cerebrovascular events, Ischemic stroke and recurrent intracerebral hemorrhage (ICH) at 3 months according to ICH etiology. CAA, cerebral amyloid angiopathy.

See this image and copyright information in PMC

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[1] Cordonnier C, Demchuk A, Ziai W, Anderson CS. Intracerebral haemorrhage: current approaches to acute management. Lancet. 2018;392:1257–1268. - PubMed

[2] Cordonnier C, Demchuk A, Ziai W, Anderson CS. Intracerebral haemorrhage: current approaches to acute management. Lancet. 2018;392:1257–1268. - PubMed

[3] Hostettler IC, Seiffge DJ, Werring DJ. Intracerebral hemorrhage: an update on diagnosis and treatment. Expert Rev Neurother. 2019;19:679–694. - PubMed

[4] Hostettler IC, Seiffge DJ, Werring DJ. Intracerebral hemorrhage: an update on diagnosis and treatment. Expert Rev Neurother. 2019;19:679–694. - PubMed

[5] Shoamanesh A, Patrice Lindsay M, Castellucci LA, Cayley A, Crowther M, de Wit K, et al. Canadian stroke best practice recommendations: management of spontaneous intracerebral hemorrhage, 7th edition update 2020. Int J Stroke. 2021;16:321–341. - PubMed

[6] Shoamanesh A, Patrice Lindsay M, Castellucci LA, Cayley A, Crowther M, de Wit K, et al. Canadian stroke best practice recommendations: management of spontaneous intracerebral hemorrhage, 7th edition update 2020. Int J Stroke. 2021;16:321–341. - PubMed

[7] Steiner T, Al-Shahi Salman R, Beer R, Christensen H, Cordonnier C, Csiba L, et al. European Stroke Organisation (ESO) guidelines for the management of spontaneous intracerebral hemorrhage. Int J Stroke. 2014;9:840–855. - PubMed

[8] Steiner T, Al-Shahi Salman R, Beer R, Christensen H, Cordonnier C, Csiba L, et al. European Stroke Organisation (ESO) guidelines for the management of spontaneous intracerebral hemorrhage. Int J Stroke. 2014;9:840–855. - PubMed

[9] Adams HP, Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. Classification of subtype of acute ischemic stroke: definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993;24:35–41. - PubMed

[10] Adams HP, Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. Classification of subtype of acute ischemic stroke: definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993;24:35–41. - PubMed

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Etiology, 3-Month Functional Outcome and Recurrent Events in Non-Traumatic Intracerebral Hemorrhage

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Etiology, 3-Month Functional Outcome and Recurrent Events in Non-Traumatic Intracerebral Hemorrhage

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