Association of the Presence and Pattern of MRI Markers of Cerebral Small Vessel Disease With Recurrent Intracerebral Hemorrhage

BACKGROUND Assessing the risk of recurrent intracerebral hemorrhage (ICH) is of high clinical importance. MRI-based cerebral small vessel disease (SVD) markers may help establish ICH etiological subtypes (including cryptogenic ICH) relevant for recurrence risk. METHODS We investigated the risk of recurrent ICH in a large cohort of consecutive ICH survivors with available MRI at baseline. Patients with macrovascular, structural or other identified secondary causes (other than SVD) were excluded. Based on MRI findings, ICH etiology was defined as probable cerebral amyloid angiopathy (CAA) according to the Boston 2.0 criteria, arteriolosclerosis (non-lobar ICH and additional markers of arteriolosclerosis, absent lobar hemorrhagic lesions), mixed SVD (mixed deep and lobar hemorrhagic changes) or cryptogenic (no MRI markers of SVD). Recurrent ICH was determined using electronic health records and confirmed by neuroimaging. Data from an independent multi-center cohort (CROMIS-2 ICH) was used to confirm core findings. RESULTS Of 443 patients with ICH (mean age 67±13 years, 41% female), ICH etiology was mixed SVD in 36.7%, arteriolosclerosis in 23.6%, CAA in 23.0%, and cryptogenic in 16.7%. During a median follow-up period of 5.7 years (IQR 2.9-10.0, 2682 patient-years), recurrent ICH were found in 59 individual patients (13.3%). The highest recurrence rate per 100 person-years was detected in patients with CAA (8.5, 95% CI 6.1-11.7), followed by mixed SVD (1.8, 95% CI 1.1-2.9) and arteriolosclerosis (0.6, 95% CI 0.3-1.5). No recurrent ICH occurred in patients with cryptogenic ICH during 510 person-years follow-up (97.5% CI, 0-0.7); this finding was confirmed in an independent cohort (CROMIS-2 ICH, n=216), in which there was also no recurrence in patients with cryptogenic ICH. In patients with CAA, cortical superficial siderosis was the imaging feature strongest related with ICH recurrence (hazard ratio 5.7, 95% CI 2.4-13.6). CONCLUSIONS MRI-based etiological subtypes are helpful in determining the recurrence risk of ICH; while the highest recurrence risk was found in CAA, recurrence risk was low for arteriolosclerosis, and negligible for cryptogenic ICH.

[1]  J. Schneider,et al.  The Boston criteria version 2.0 for cerebral amyloid angiopathy: a multicentre, retrospective, MRI–neuropathology diagnostic accuracy study , 2022, The Lancet Neurology.

[2]  A. Luft,et al.  Etiology, 3-Month Functional Outcome and Recurrent Events in Non-Traumatic Intracerebral Hemorrhage , 2022, Journal of stroke.

[3]  K. Rothman,et al.  Risks of Stroke Recurrence and Mortality After First and Recurrent Strokes in Denmark , 2021, Neurology.

[4]  D. Werring,et al.  Small vessel disease burden and intracerebral haemorrhage in patients taking oral anticoagulants , 2021, Journal of Neurology, Neurosurgery, and Psychiatry.

[5]  Sung-Chun Tang,et al.  Long-Term Vascular Outcomes in Patients With Mixed Location Intracerebral Hemorrhage and Microbleeds , 2020, Neurology.

[6]  D. Werring,et al.  Intracerebral hemorrhage: an update on diagnosis and treatment , 2019, Expert review of neurotherapeutics.

[7]  S. Greenberg,et al.  Cortical superficial siderosis and recurrent intracerebral hemorrhage risk in cerebral amyloid angiopathy: Large prospective cohort and preliminary meta-analysis , 2019, International journal of stroke : official journal of the International Stroke Society.

[8]  Eric E. Smith,et al.  Brain hemorrhage recurrence, small vessel disease type, and cerebral microbleeds , 2017, Neurology.

[9]  D. Werring,et al.  The Cerebral Haemorrhage Anatomical RaTing inStrument (CHARTS): Development and assessment of reliability , 2017, Journal of the Neurological Sciences.

[10]  S. Greenberg,et al.  Association Between Blood Pressure Control and Risk of Recurrent Intracerebral Hemorrhage. , 2015, JAMA.

[11]  D. Werring,et al.  The Clinical Relevance of Microbleeds in Stroke study (CROMIS-2): rationale, design, and methods , 2015, International journal of stroke : official journal of the International Stroke Society.

[12]  Michael Tin Chung Poon,et al.  Long-term prognosis after intracerebral haemorrhage: systematic review and meta-analysis , 2013, Journal of Neurology, Neurosurgery & Psychiatry.

[13]  J. Baron,et al.  Cortical superficial siderosis and intracerebral hemorrhage risk in cerebral amyloid angiopathy , 2013, Neurology.

[14]  Nick C Fox,et al.  Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration , 2013, The Lancet Neurology.

[15]  S. Juvela,et al.  Predictors for Recurrent Primary Intracerebral Hemorrhage: A Retrospective Population-based Study , 2013, Stroke.

[16]  S. Greenberg,et al.  Prevalence of Superficial Siderosis in Patients with Cerebral Amyloid Angiopathy , 2010, Neurology.

[17]  D. Werring,et al.  The Microbleed Anatomical Rating Scale (MARS) , 2009, Neurology.

[18]  S. Avikainen,et al.  Long term survival after primary intracerebral haemorrhage: a retrospective population based study , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[19]  A. Alavi,et al.  MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. , 1987, AJR. American journal of roentgenology.

[20]  A. Alexandrov,et al.  Prevalence, Characteristics and Outcomes of Undetermined Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis , 2021 .