Risk of intracranial haemorrhage and ischaemic stroke after convexity subarachnoid haemorrhage in cerebral amyloid angiopathy: international individual patient data pooled analysis

Isabel Charlotte Hostettler¹, Duncan Wilson¹, Catherine Arnold Fiebelkorn², Diane Aum³, Sebastián Francisco Ameriso⁴, Federico Eberbach⁴, Markus Beitzke⁵, Timothy Kleinig⁶, Thanh Phan^{7

8}, Sarah Marchina⁹, Romain Schneckenburger¹⁰, Maria Carmona-Iragui¹¹, Andreas Charidimou¹², Isabelle Mourand¹³, Sara Parreira¹⁴, Gareth Ambler¹⁵, Hans Rolf Jäger¹⁶, Shaloo Singhal^{7

8}, John Ly^{7

8}, Henry Ma^{7

8}, Emmanuel Touzé¹⁷, Ruth Geraldes^{18

19}, Ana Catarina Fonseca¹⁴, Teresa Melo¹⁴, Pierre Labauge¹³, Pierre-Henry Lefèvre²⁰, Anand Viswanathan¹², Steven Mark Greenberg¹², Juan Fortea¹¹, Marion Apoil¹⁰, Marion Boulanger^{10

17}, Fausto Viader¹⁰, Sandeep Kumar⁹, Velandai Srikanth^{7

8}, Ashan Khurram⁶, Franz Fazekas⁵, Veronica Bruno⁴, Gregory Joseph Zipfel³, Daniel Refai²¹, Alejandro Rabinstein², Jonathan Graff-Radford², David John Werring²²

Affiliations

¹ Stroke Research Centre, University College London, National Hospital of Neurology and Neurosurgery, Institute of Neurology, Queen Square, London, WC1N, UK.
² Department of Neurology, Mayo Clinic, Rochester, MN, USA.
³ Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, USA.
⁴ Institute for Neurological Research, Fleni, Buenos Aires, Argentina.
⁵ Department of Neurology, Medical University of Graz, Graz, Austria.
⁶ Department of Neurology, Royal Adelaide Hospital, Adelaide, Australia.
⁷ Department of Neurology, Monash Health and Stroke and Ageing Research Group, Melbourne, Australia.
⁸ Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia.
⁹ Department of Neurology, Stroke Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
¹⁰ Department of Neurology, CHU Caen Normandie, Caen, France.
¹¹ Memory Unit, Department of Neurology, Hospital de la Santa Creu I Sant Pau, Institut Investigació Biomèdica Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
¹² J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
¹³ Department of Neurology, CHU de Montpellier, Hôpital Gui-de-Chauliac, Montpellier, France.
¹⁴ Stroke Unit, Department of Neuroscience, Hospital de Santa Maria, University of Lisbon, Lisbon, Portugal.
¹⁵ Department of Statistical Science, UCL, London, WC1E 6BT, UK.
¹⁶ Neuroradiological Academic Unit, Department of Brain Repair & Rehabilitation, University College London, Institute of Neurology, London, UK.
¹⁷ Normandy University, UNICAEN, INSERM U1237, Caen, France.
¹⁸ Nuffield Department of Clinical Neurosciences, Oxford University Hospitals, Oxford, UK.
¹⁹ Neurology department, Frimley Health Foundation Trust, Camberley, UK.
²⁰ Department of Neuroradiology, CHU de Montpellier, Hôpital Gui-de-Chauliac, Montpellier, France.
²¹ Department of Neurosurgery, Emory University, Atlanta, GA, USA.
²² Stroke Research Centre, University College London, National Hospital of Neurology and Neurosurgery, Institute of Neurology, Queen Square, London, WC1N, UK. d.werring@ucl.ac.uk.

PMID: 34272978
PMCID: PMC8857171
DOI: 10.1007/s00415-021-10706-3

Risk of intracranial haemorrhage and ischaemic stroke after convexity subarachnoid haemorrhage in cerebral amyloid angiopathy: international individual patient data pooled analysis

Isabel Charlotte Hostettler et al. J Neurol. 2022 Mar.

. 2022 Mar;269(3):1427-1438.

doi: 10.1007/s00415-021-10706-3. Epub 2021 Jul 17.

Authors

Affiliations

¹ Stroke Research Centre, University College London, National Hospital of Neurology and Neurosurgery, Institute of Neurology, Queen Square, London, WC1N, UK.
² Department of Neurology, Mayo Clinic, Rochester, MN, USA.
³ Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, USA.
⁴ Institute for Neurological Research, Fleni, Buenos Aires, Argentina.
⁵ Department of Neurology, Medical University of Graz, Graz, Austria.
⁶ Department of Neurology, Royal Adelaide Hospital, Adelaide, Australia.
⁷ Department of Neurology, Monash Health and Stroke and Ageing Research Group, Melbourne, Australia.
⁸ Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia.
⁹ Department of Neurology, Stroke Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
¹⁰ Department of Neurology, CHU Caen Normandie, Caen, France.
¹¹ Memory Unit, Department of Neurology, Hospital de la Santa Creu I Sant Pau, Institut Investigació Biomèdica Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
¹² J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
¹³ Department of Neurology, CHU de Montpellier, Hôpital Gui-de-Chauliac, Montpellier, France.
¹⁴ Stroke Unit, Department of Neuroscience, Hospital de Santa Maria, University of Lisbon, Lisbon, Portugal.
¹⁵ Department of Statistical Science, UCL, London, WC1E 6BT, UK.
¹⁶ Neuroradiological Academic Unit, Department of Brain Repair & Rehabilitation, University College London, Institute of Neurology, London, UK.
¹⁷ Normandy University, UNICAEN, INSERM U1237, Caen, France.
¹⁸ Nuffield Department of Clinical Neurosciences, Oxford University Hospitals, Oxford, UK.
¹⁹ Neurology department, Frimley Health Foundation Trust, Camberley, UK.
²⁰ Department of Neuroradiology, CHU de Montpellier, Hôpital Gui-de-Chauliac, Montpellier, France.
²¹ Department of Neurosurgery, Emory University, Atlanta, GA, USA.
²² Stroke Research Centre, University College London, National Hospital of Neurology and Neurosurgery, Institute of Neurology, Queen Square, London, WC1N, UK. d.werring@ucl.ac.uk.

PMID: 34272978
PMCID: PMC8857171
DOI: 10.1007/s00415-021-10706-3

Abstract

Objective: To investigate the frequency, time-course and predictors of intracerebral haemorrhage (ICH), recurrent convexity subarachnoid haemorrhage (cSAH), and ischemic stroke after cSAH associated with cerebral amyloid angiopathy (CAA).

Methods: We performed a systematic review and international individual patient-data pooled analysis in patients with cSAH associated with probable or possible CAA diagnosed on baseline MRI using the modified Boston criteria. We used Cox proportional hazards models with a frailty term to account for between-cohort differences.

Results: We included 190 patients (mean age 74.5 years; 45.3% female) from 13 centers with 385 patient-years of follow-up (median 1.4 years). The risks of each outcome (per patient-year) were: ICH 13.2% (95% CI 9.9-17.4); recurrent cSAH 11.1% (95% CI 7.9-15.2); combined ICH, cSAH, or both 21.4% (95% CI 16.7-26.9), ischemic stroke 5.1% (95% CI 3.1-8) and death 8.3% (95% CI 5.6-11.8). In multivariable models, there is evidence that patients with probable CAA (compared to possible CAA) had a higher risk of ICH (HR 8.45, 95% CI 1.13-75.5, p = 0.02) and cSAH (HR 3.66, 95% CI 0.84-15.9, p = 0.08) but not ischemic stroke (HR 0.56, 95% CI 0.17-1.82, p = 0.33) or mortality (HR 0.54, 95% CI 0.16-1.78, p = 0.31).

Conclusions: Patients with cSAH associated with probable or possible CAA have high risk of future ICH and recurrent cSAH. Convexity SAH associated with probable (vs possible) CAA is associated with increased risk of ICH, and cSAH but not ischemic stroke. Our data provide precise risk estimates for key vascular events after cSAH associated with CAA which can inform management decisions.

Keywords: Cerebral amyloid angiopathy; Intracerebral haemorrhage; Ischemic stroke; Non-traumatic convexity/convexal/cortical subarachnoid haemorrhage; Stroke.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

**Fig. 1**
Kaplan Maier survival estimates for all outcome events in the whole cohort

**Fig. 2**
Kaplan Maier survival estimates based on outcome and probable CAA status: A ICH; B recurrent cSAH; C ischemic stroke; and D death

See this image and copyright information in PMC

References

1. Beitzke M, Gattringer T, Enzinger C, Wagner G, Niederkorn K, Fazekas F. Clinical presentation, etiology, and long-term prognosis in patients with nontraumatic convexal subarachnoid haemorrhage. Stroke; J Cereb Circ. 2011;42(11):3055–3060. doi: 10.1161/STROKEAHA.111.621847. - DOI - PubMed
1. Hostettler IC, Werring DJ. Acute convexity subarachnoid haemorrhage: what the neurosurgeon needs to know. World Neurosurg. 2018 doi: 10.1016/j.wneu.2018.12.062. - DOI - PubMed
1. Ni J, Auriel E, Jindal J, Ayres A, Schwab KM, Martinez-Ramirez S, Gurol EM, Greenberg SM, Viswanathan A. The characteristics of superficial siderosis and convexity subarachnoid haemorrhage and clinical relevance in suspected cerebral amyloid angiopathy. Cerebrovasc Dis. 2015;39(5–6):278–286. doi: 10.1159/000381223. - DOI - PMC - PubMed
1. Kumar S, Goddeau RP, Jr, Selim MH, Thomas A, Schlaug G, Alhazzani A, Searls DE, Caplan LR. Atraumatic convexal subarachnoid haemorrhage: clinical presentation, imaging patterns, and etiologies. Neurology. 2010;74(11):893–899. doi: 10.1212/WNL.0b013e3181d55efa. - DOI - PMC - PubMed
1. Stanton JED, Chandratheva A, Wilson D, Hostettler IC, Islam S, Werring DJ. Clinical features distinguish cerebral amyloid angiopathy-associated convexity subarachnoid haemorrhage from suspected TIA. J Neurol. 2020;267(1):133–137. doi: 10.1007/s00415-019-09558-9. - DOI - PMC - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
Medical
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Risk of intracranial haemorrhage and ischaemic stroke after convexity subarachnoid haemorrhage in cerebral amyloid angiopathy: international individual patient data pooled analysis

Affiliations

Risk of intracranial haemorrhage and ischaemic stroke after convexity subarachnoid haemorrhage in cerebral amyloid angiopathy: international individual patient data pooled analysis

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Medical