Superficial Siderosis in Patients With Suspected Cerebral Amyloid Angiopathy (SuSPect-CAA)

Observational Study on the Prognostic Relevance of Supratentorial Superficial Siderosis in Patients With Suspected Cerebral Amyloid Angiopathy

Aim of the SuSPect-CAA study is to prospectively evaluate the prognostic significance of cortical superficial siderosis in patients with suspected cerebral amyloid angiopathy with a primary focus on future stroke and mortality.

Study Overview

• Status: Unknown
• Conditions: Ischemic Stroke; Cerebral Amyloid Angiopathy; Intracerebral Hemorrhage

Detailed Description

Non-traumatic cortical superficial siderosis (cSS) is a common finding in patients with cerebral amyloid angiopathy (CAA) and can be its sole imaging sign. The clinical features and course as well as the prognostic significance of cSS in CAA patients remain unclear. In a retrospective study we have previously shown that cSS might be an important predictor or warning sign for future intracranial hemorrhage. However, prospective data are missing.

The Superficial Siderosis in Patients with suspected Cerebral Amyloid Angiopathy (SuSPect-CAA) study is designed as a prospective observational multi-centre cohort study. Primary objective of the study is to evaluate if cSS is a predictor for future stroke and mortality (primary endpoint: combined rate of stroke and death after 36 months). Secondary objectives of the study include 1) to evaluate if cSS represents a marker of future intracranial haemorrhage, especially at the site of initial siderosis, 2) to describe the clinical presentation and course of cSS, 3) to assess to associated imaging findings, 4) to determine the differential diagnoses of cSS.

All subjects presenting to the respective neurological centers (out- or inpatient treatment with neuroimaging) will be screened. The study population will consist of two patient groups: 1) Patients meeting the modified Boston criteria for probable or possible CAA, i. e. patients with SS +/- lobar intracerebral hemorrhage or microbleeds in cortico-subcortical localization and absence of other cause of hemorrhage than CAA will be assigned to the study group. 2) Patients meeting the classic Boston criteria for possible or probable CAA but without any SS will be assigned to the control group. A total of 100 patients per group will be enrolled. Baseline and follow-up assessment at 6, 12, 24, and 36 months will be performed by visits in the respective neurological outpatient clinic including a structured interview and neurological exam, neuropsychological tests, EEG and MRI.

• Study Type: Observational
• Enrollment (Actual): 302

Contacts and Locations

Study Locations

• Germany
  • Munich, Germany, 81377
    • Ludwig-Maximilians-University

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

hospital based

Description

Inclusion Criteria (study group):

• Fulfillment of the modified Boston criteria for CAA-related hemorrhage with evidence of supratentorial superficial siderosis on MRI
• MR-/CT-/digital subtraction (DS) -angiography without evidence of cerebral aneurysm, arterio-venous malformation (AVM) , AV-fistula or other pathology of relevance (e.g. tumor, hemorrhagic infarction)
• A maximum of two lobar or cerebellar intracranial hemorrhages (ICH) (old or acute)
• Written informed consent by patient or guardian prior to study participation
• Willingness to participate in follow-up

Inclusion Criteria (control group):

• Fulfillment of the classic Boston criteria for CAA-related hemorrhage
• Absence of superficial siderosis on MRI
• A maximum of two lobar or cerebellar ICHs (old or acute)
• MR-/CT-/DS -angiography without evidence of cerebral aneurysm, AVM, AV-fistula or other pathology of relevance (e.g. tumor, hemorrhagic infarction)
• Written informed consent by patient or guardian prior to study participation
• Willingness to participate in follow-up

Exclusion Criteria (both groups):

• Severe medical condition with expected life expectancy <3 years
• More than two lobar or cerebellar ICH (old or acute)
• any intracerebral hemorrhage in the deep grey matter (basal ganglia or thalami) or in the brain stem
• History of head trauma resulting in loss of consciousness or radiologically visible traumatic brain injury (contusions, diffuse axonal damage) in the last 5 years prior to inclusion
• Cerebral aneurysm or history of aneurysmal subarachnoid hemorrhage
• Infratentorial siderosis
• Infratentorial subarachnoid hemorrhage

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Study Group; Patients with cortical superficial siderosis and possible or probable cerebral amyloid angiopathy meeting the modified Boston criteria.
Control Group; Patients with possible or probable cerebral amyloid angiopathy meeting the classic Boston criteria but without any cortical superficial siderosis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Combined rate of stroke and death	All cause mortality and stroke (WHO-definition)	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of intracranial hemorrhage	Rate of any intracranial hemorrhage as assessed by cerebral imaging	6, 12, 24, 36 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical presentation and course of superficial siderosis	A detailed analysis on the clinical presentation and course of superficial siderosis will be performed (detailed questionnaire, comprehensive neurological examinations, disability scales, neuropsychological tests)	0, 6, 12, 24, 36 months
Imaging findings associated with superficial siderosis	Localization, extent and progression of superficial siderosis will be assessed on MR-imaging. In addition, the prevalence, incidence, localization, number or extent of cerebral microbleeds, white matter disease, and acute ischemic lesions will be determined using follow-up MRI.	0, 6, 12, 24, 36 months
Differential causes of superficial siderosis	At the time of patient screening and follow-up we will systematically evaluate the underlying causes of superficial siderosis and potential differential diagnoses based on the available clinical, laboratory and imaging data, as well as published diagnostic criteria.	0, 6, 12, 24, 36 months

Collaborators and Investigators

• Sponsor: Ludwig-Maximilians - University of Munich
• Investigators: Principal Investigator: Frank Wollenweber, MD, Institute for Stroke and Dementia Research, Ludwig-Maximilans-University; Principal Investigator: Jennifer Linn, MD, Department of Neuroradiology, Carl Carus University Dresden; Principal Investigator: Christian Opherk, MD, Institute for Stroke and Dementia Research, Ludwig-Maximilans-University; Study Director: Martin Dichgans, MD, Institute for Stroke and Dementia Research, Ludwig-Maximilians-University

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): May 1, 2019

Study Registration Dates

• First Submitted: May 15, 2013
• First Submitted That Met QC Criteria: May 15, 2013
• First Posted (Estimate): May 17, 2013

Study Record Updates

• Last Update Posted (Actual): August 11, 2017
• Last Update Submitted That Met QC Criteria: August 9, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: intracerebral hemorrhage; cerebral amyloid angiopathy; supratentorial 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; Stroke; Brain Diseases, Metabolic, Inborn; Cerebral Arterial Diseases; Intracranial Arterial Diseases; Intracranial Hemorrhages; Cerebral Small Vessel Diseases; Amyloidosis, Familial; Ischemic Stroke; Hemorrhage; Amyloidosis; Cerebral Hemorrhage; Cerebral Amyloid Angiopathy; Cerebral Amyloid Angiopathy, Familial; Siderosis
• Other Study ID Numbers: SuSPect-CAA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided