Cortical Superficial Siderosis and Risk of Recurrent Intracerebral Hemorrhage in Cerebral Amyloid Angiopathy. (CORELIA)

COrtical Superficial Siderosis and REcurrent Lobar Intracerebral Hemorrhage in Cerebral Amyloid Angiopathy.

Cerebral amyloid angiopathy (CAA) is a major cause of lobar intracerebral hemorrhage (ICH) in the elderly with high risk of recurrence.

The investigators aim to determine the relationship between cortical superficial siderosis (cSS), a MRI hemorrhagic marker of CAA and the risk of symptomatic ICH recurrence in a multicentric prospective cohort of patients with acute lobar ICH related to CAA. The investigators hypothesize that patients with cSS have an increased risk of recurrent symptomatic ICH relative to those without cSS.

Study Overview

• Status: Active, not recruiting
• Conditions: Cerebral Amyloid Angiopathy
• Intervention / Treatment: Other: neurological, neuropsychological and MRI evaluation

Detailed Description

Patients with acute lobar ICH fulfilling the Boston criteria for probable or possible CAA will be enrolled within 30 days after ICH onset. Brain MRI performed at baseline will be analyzed blinded to clinical data. Patients with presence of cSS will be compared with those without cSS.

During a systematic follow-up of 24 months, patients will undergo neurological, neuropsychological and MRI evaluation. The investigators will compare the rate of recurrent symptomatic ICH at 24 months in patients with vs. without cSS.

• Study Type: Interventional
• Enrollment (Actual): 170
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bordeaux, France
    • Pellegrin Hospital
  • Montpellier, France
    • Gui de Chauliac Hospital
  • Paris, France
    • Lariboisiere Hospital
  • Toulouse cedex 9, France, 31059
    • CHU Purpan. Hôpital Pierre-Paul Riquet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Lobar ICH within 30 days after onset
• Available brain MRI sequences of adequate quality including fluid-attenuated inversion recovery (FLAIR) and T2*-weighted gradient-recalled echo (T2*-GRE) sequences.
• Modified Boston criteria for probable or possible CAA
• Age ≥ 55 years
• Written consent

Exclusion Criteria:

• Secondary brain hemorrhage : vascular malformation (arteriovenous malformation, aneurysm, cavernous); cerebral veinous thrombosis; brain tumor; coagulopathy; vasculitis; hemorrhagic infarction,
• Infratentorial siderosis
• Contraindications to MRI
• Neurosurgical intervention before inclusion,
• Progressive neoplasm
• Patient without affiliation to the french social security
• Patient under guardianship

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Patients with cortical superficial siderosis.; During a systematic follow-up of 24 months, patients will undergo neurological, neuropsychological and MRI evaluation	Other: neurological, neuropsychological and MRI evaluation; neurological, neuropsychological and MRI evaluation
Other: Patients without cortical superficial siderosis; During a systematic follow-up of 24 months, patients will undergo neurological, neuropsychological and MRI evaluation	Other: neurological, neuropsychological and MRI evaluation; neurological, neuropsychological and MRI evaluation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrent symptomatic intracerebral hemorrhage at 24 months	Recurrent symptomatic intracerebral haemorrhage is defined as a further intracerebral hemorrhage documented by CT scan or MRI, associated with new neurologic symptoms	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrent symptomatic ICH at 12 months	Recurrent symptomatic intracerebral haemorrhage is defined as a further intracerebral hemorrhage documented by CT scan or MRI, associated with new neurologic symptoms.	12 months
Transient Focal Neurological Episodes (TFNE) at 12 and 24 months	TFNE was defined as transient (≤24 hours), with fully resolving, focal neurological symptoms that had no known alternative explanation other than CAA (e.g., structural brain lesion, atrial fibrillation, extracranial, or intracranial stenosis)	12 and 24 months
mortality or dependance at 12 and 24 months	Mortality and dependence defined by a modified Rankin scale >2	12 and 24 months
Cognitive decline at 12 and 24 months	moderate or severe vascular cognitive disorders (VCD) according to the VASCOG criteria.	12 and 24 months
New MRI hemorrhagic lesion at 12 months	Presence of new symptomatic or asymptomatic hemorrhagic lesion (ICH, microbleeds, convexity subarachnoid hemorrhage) on follow-up MRI at 12 months	12 months
Extent of cortical superficial siderosis at 12 months	Extent of cSS is assessed on follow up MRI at 12 months according to the current guidelines: 0: no cSS; 1: focal cSS (restricted to ≤3 sulci); 2: disseminated cSS (≥4 sulci).	12 months
frequency of APOE ε2 and ε4 allele	frequency of both ε2 and ε4 allele on Apolipoprotein E (APOE) genotype at baseline	baseline

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Nicolas RAPOSO, MD, University Hospital, Toulouse; Principal Investigator: Lionel CALVIERE, University Hospital, Toulouse

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2018
• Primary Completion (Actual): February 28, 2023
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: March 7, 2018
• First Submitted That Met QC Criteria: March 7, 2018
• First Posted (Actual): March 14, 2018

Study Record Updates

• Last Update Posted (Actual): July 28, 2023
• Last Update Submitted That Met QC Criteria: July 27, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: intracerebral hemorrhage; Magnetic Resonance Imaging; cerebral amyloid angiopathy; cortical superficial siderosis
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Lung Diseases; Genetic Diseases, Inborn; Occupational Diseases; Proteostasis Deficiencies; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Pneumoconiosis; Lung Diseases, Interstitial; Lung Injury; Brain Diseases, Metabolic, Inborn; Cerebral Arterial Diseases; Intracranial Arterial Diseases; Intracranial Hemorrhages; Cerebral Small Vessel Diseases; Amyloidosis, Familial; Hemorrhage; Amyloidosis; Cerebral Hemorrhage; Cerebral Amyloid Angiopathy; Cerebral Amyloid Angiopathy, Familial; Siderosis
• Other Study ID Numbers: RC31/16/8919; 2017-A01524-49 (Other Identifier: ID-RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No