Association of 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

Association of 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

BMJ Open

INTRODUCTION: Worldwide, 2 million patients aged 18-50 years suffer a stroke each year, and this number is increasing. Knowledge about global distribution of risk factors and aetiologies, and information about prognosis and optimal secondary prevention in young stroke patients are limited. This limits evidence-based treatment and hampers the provision of appropriate information regarding the causes of stroke, risk factors and prognosis of young stroke patients. METHODS AND ANALYSIS: The Global Outcome Assessment Life-long after stroke in young adults (GOAL) initiative aims to perform a global individual patient data meta-analysis with existing data from young stroke cohorts worldwide. All patients aged 18-50 years with ischaemic stroke or intracerebral haemorrhage will be included. Outcomes will be the distribution of stroke aetiology and (vascular) risk factors, functional outcome after stroke, risk of recurrent vascular events and death and finally the use of secondary prevention. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and climate of residence. ETHICS AND DISSEMINATION: Ethical approval for the GOAL study has already been obtained from the Medical Review Ethics Committee region Arnhem-Nijmegen. Additionally and when necessary, approval will also be obtained from national or local institutional review boards in the participating centres. When needed, a standardised data transfer agreement will be provided for participating centres. We plan dissemination of our results in peer-reviewed international scientific journals and through conference presentations. We expect that the results of this unique study will lead to better understanding of worldwide differences in risk factors, causes and outcome of young stroke patients

Global Outcome Assessment Life-long after stroke in young adults initiative-the GOAL initiative : study protocol and rationale of a multicentre retrospective individual patient data meta-analysis

Introduction Worldwide, 2 million patients aged 18-50 years suffer a stroke each year, and this number is increasing. Knowledge about global distribution of risk factors and aetiologies, and information about prognosis and optimal secondary prevention in young stroke patients are limited. This limits evidence-based treatment and hampers the provision of appropriate information regarding the causes of stroke, risk factors and prognosis of young stroke patients. Methods and analysis The Global Outcome Assessment Life-long after stroke in young adults (GOAL) initiative aims to perform a global individual patient data meta-analysis with existing data from young stroke cohorts worldwide. All patients aged 18-50 years with ischaemic stroke or intracerebral haemorrhage will be included. Outcomes will be the distribution of stroke aetiology and (vascular) risk factors, functional outcome after stroke, risk of recurrent vascular events and death and finally the use of secondary prevention. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and climate of residence.Peer reviewe

Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data

Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. Methods: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0–1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0–2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4–6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. Findings: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10–2·03]; p=0·011), with low heterogeneity across studies (I2=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05–1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06–2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4–6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52–1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03–4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22–25·50]; p=0·024). Interpretation: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. Funding: None