Cortical Superficial Siderosis Evolution

Abstract

Background and Purpose- We investigated cortical superficial siderosis (cSS) progression and its clinical relevance for incident lobar intracerebral hemorrhage (ICH) risk, in probable cerebral amyloid angiopathy presenting with neurological symptoms and without ICH at baseline. Methods- Consecutive patients meeting modified Boston criteria for probable cerebral amyloid angiopathy from a single-center cohort who underwent magnetic resonance imaging (MRI) at baseline and during follow-up were analyzed. cSS progression was assessed by comparison of the baseline and follow-up images. Patients were followed prospectively for incident symptomatic ICH. cSS progression and first-ever ICH risk were investigated in Cox proportional hazard models adjusting for confounders. Results- The cohort included 118 probable cerebral amyloid angiopathy patients: 72 (61%) presented with transient focal neurological episodes and 46 (39%) with cognitive complaints prompting the baseline MRI investigation. Fifty-two patients (44.1%) had cSS at baseline. During a median scan interval of 2.2 years (interquartile range, 1.2-4.4 years) between the baseline (ie, first) MRI and the latest MRI, cSS progression was detected in 33 (28%) patients. In multivariable logistic regression, baseline cSS presence (odds ratio, 4.04; 95% CI, 1.53-10.70; P=0.005), especially disseminated cSS (odds ratio, 9.12; 95% CI, 2.85-29.18; P<0.0001) and appearance of new lobar microbleeds (odds ratio, 4.24; 95% CI, 1.29-13.9; P=0.017) were independent predictors of cSS progression. For patients without an ICH during the interscan interval (n=105) and subsequent follow-up (median postfinal MRI time, 1.34; interquartile range, 0.3-3 years), cSS progression independently predicted increased symptomatic ICH risk (hazard ratio, 3.76; 95% CI, 1.37-10.35; P=0.010). Conclusions- Our results suggest that cSS evolution may be a useful biomarker for assessing disease progression and ICH risk in cerebral amyloid angiopathy patients and a candidate biomarker for clinical studies and trials.

Keywords: cerebral amyloid angiopathy; cerebral hemorrhage; disease progression; magnetic resonance imaging; siderosis.

Figure 1.

(A) Study methods schematic according to the two basic aims: (a) cSS progression prevalence and predictors between baseline and follow-up MRI (i.e. MRI follow-up period); (b) incident first-ever lobar ICH risk during clinical follow-up (i.e. clinical follow-up period) in relation to cSS progression, in stroke-free CAA patients during the MRI follow-up period. (B) Flow chart of patient selection.

Figure 2.

Representative examples of probable CAA patients without ICH at baseline and cSS progression in follow-up MRI. (A) One new focus of cSS (right image) after a follow-up of 2.5 years. (B) A new focus of cSS (after 6 months) in a patient with disseminated cSS at baseline. (C) Three new cSS areas in a patient with a single focus of cSS at baseline (black squares) and progression of cSS in the same area as baseline (white square and lower inset), after 2 years. All images are T2*-GRE MRI at 1.5T.

Figure 3.

Kaplan-Meier estimates of time to symptomatic lobar ICH based on cortical superficial siderosis (cSS) progression.