Acute convexity subarachnoid haemorrhage and cortical superficial siderosis in probable cerebral amyloid angiopathy without lobar haemorrhage

Abstract

Introduction: Acute non-traumatic convexity subarachnoid haemorrhage (cSAH) is increasingly recognised in cerebral amyloid angiopathy (CAA). We investigated: (a) the overlap between acute cSAH and cortical superficial siderosis-a new CAA haemorrhagic imaging signature and (b) whether acute cSAH presents with particular clinical symptoms in patients with probable CAA without lobar intracerebral haemorrhage.

Methods: MRI scans of 130 consecutive patients meeting modified Boston criteria for probable CAA were analysed for cortical superficial siderosis (focal, ≤3 sulci; disseminated, ≥4 sulci), and key small vessel disease markers. We compared clinical, imaging and cortical superficial siderosis topographical mapping data between subjects with versus without acute cSAH, using multivariable logistic regression.

Results: We included 33 patients with probable CAA presenting with acute cSAH and 97 without cSAH at presentation. Patients with acute cSAH were more commonly presenting with transient focal neurological episodes (76% vs 34%; p<0.0001) compared with patients with CAA without cSAH. Patients with acute cSAH were also more often clinically presenting with transient focal neurological episodes compared with cortical superficial siderosis-positive, but cSAH-negative subjects with CAA (76% vs 30%; p<0.0001). Cortical superficial siderosis prevalence (but no other CAA severity markers) was higher among patients with cSAH versus those without, especially disseminated cortical superficial siderosis (49% vs 19%; p<0.0001). In multivariable logistic regression, cortical superficial siderosis burden (OR 5.53; 95% CI 2.82 to 10.8, p<0.0001) and transient focal neurological episodes (OR 11.7; 95% CI 2.70 to 50.6, p=0.001) were independently associated with acute cSAH.

Conclusions: This probable CAA cohort provides additional evidence for distinct disease phenotypes, determined by the presence of cSAH and cortical superficial siderosis.

Figure 1.

Cortical superficial siderosis (cSS) topographical mapping pipeline and methodology.

Figure 2.

Flow-chart of patient selection.

Figure 3.

Representative patients with and without cSAH. 1.5 Tesla axial brain MRI sequences (A) FLAIR (left) sequence and SWI (right) axial sections in an 82-year old male evaluated for rapidly progressing right sided tingling resolved in 15 minutes after onset. No relevant medical history. Imaging demonstrates acute subarachnoid blood in the central sulcus (white arrowheads) and bilateral disseminated foci of cortical superficial siderosis (white rectangles). (B) SWI axial sequence in a 75-year old female with repeated stereotyped episodes of dizziness and left sided hand tingling. Imaging demonstrates chronic focal cortical superficial siderosis affecting the right central sulcus (white rectangle) as well as strictly lobar cerebral microbleeds (black arrowheads).

Figure 4.

Averaged surface heat maps showcasing the whole brain distribution and frequency of cortical superfical siderosis sites in the two patient study groups: (a) probable CAA patients without acute cSAH (i.e. cSAH negative group, top panel); and (b) probable CAA patients presenting with acute cSAH (cSAH positive group, lower panel). The areas in the circle include the pre-central and central sulcus for illustration purposes. Compared to patients without acute cSAH (top panel), the patient group with acute cSAH in the lower panel demonstrates more extensive involvement by cSS – more brain areas are affected with higher degree of cSS per region. This is especially evident in the pre-central and central sulcus (circled areas), in which multiple cSS sites are covering the whole sulci. These eloquent areas are particular symptomatogenic and the occurrence of cSS (or cSAH in the acute stange) might underpin transient focal neurological episodes often seen in CAA patients (“amyloid spells”). The color scale bar indicates the degree of cSS involvement in different brain areas in our cohort.