The characteristics of superficial siderosis and convexity subarachnoid hemorrhage and clinical relevance in suspected cerebral amyloid angiopathy

Abstract

Background and aims: Systematic studies of superficial siderosis (SS) and convexity subarachnoid hemorrhage (cSAH) in patients with suspected cerebral amyloid angiopathy (CAA) without lobar intracerebral hemorrhage (ICH) are lacking. We sought to determine the potential anatomic correlation between SS/cSAH and transient focal neurological episodes (TFNE) and whether SS/cSAH is predictor of future cerebral hemorrhagic events in these patients.

Methods: We enrolled 90 consecutive patients with suspected CAA (due to the presence of strictly lobar microbleeds (CMBs) and/or SS/cSAH) but without the history of symptomatic lobar ICH who underwent brain MRI including T2*-weighted, diffusion-weighted imaging and fluid-attenuated inversion recovery sequences from an ongoing single center CAA cohort from 1998 to 2012. Evaluation of SS, cSAH and CMBs was performed. Medical records and follow-up information were obtained from prospective databases and medical charts. TFNE was defined according to published criteria and electroencephalogram reports were reviewed.

Results: Forty-one patients (46%) presented with SS and/or cSAH. The prevalence of TFNE was significantly higher in those with SS/cSAH (61 vs. 10%; p < 0.001) and anatomically correlated with the location of cSAH, but not SS. The majority of TFNE in patients with SS/cSAH presented with spreading sensory symptoms. Intermittent focal slowing on electroencephalogram was present in the same area as SS/cSAH in 6 patients, but no epileptiform activity was found in any patients. Among those with available clinical follow-up (76/90 patients, 84%), ten patients with SS/cSAH (29%, median time from the scan for all patients with SS/cSAH: 21 months) had a symptomatic cerebral bleeding event on follow up (average time to events: 34 months) compared with only 1 event (2.4%, 25 months from the scan) in patients without SS/​cSAH (time to event: 25 months) (p = 0.001). The location of hemorrhages on follow-up scan was not in the same location of previously noted SS/cSAH in 9 of 10 patients. Follow-up imaging was obtained in 9 of 17 patients with cSAH and showed evidence of SS in the same location as initial cSAH in all these 9 cases.

Conclusions: SS/cSAH is common in patients with suspected CAA without lobar intracerebral hemorrhage and may have a significantly higher risk of future cerebral bleeding events, regardless of the severity of the baseline CMB burden. The findings further highlight a precise anatomical correlation between TFNE and cSAH, but not SS. Distinct from transient ischemic attack or seizure, the majority of TFNE caused by SS/cSAH appear to present with spreading sensory symptoms.

Figure 1. An example of “clinically silent” SS

A 72-year-old man presents with transient spreading sensory loss starting in the left thumb and spreading to the fingers. Flair shows hyperintensity in right central sulcus (A, arrows). GRE demonstrates multiple hypointensities in the same hemisphere beyond the central sulcus (B, arrow heads for SS and arrows for cSAH). No DWI positive lesion is found (C).

Figure 2. An example of recurrent cSAH

A 75-year-old woman presented with transient left upper extremity tingling and slurred speech for 20–30 min and right headache before episode. MRI at the same day shows hyperintensity suggesting cSAH within right central sulcus on FLAIR (A1, arrows), single line hypointensity on GRE (A2, arrow) and no positive lesion on DWI (A3). CT shows subtle hyperintensity at same area (A4, arrow). Three weeks later, the patient has a recurrent episode with transient right 4th and fifth finger tingling and slurred speech lasting for 2–3 minutes. MRI within 24 hours shows hyperintensity in left central sulcus on FLAIR (B1, arrows), subtle hypointensity on GRE (B2, arrow) and no DWI positive lesion at the same time (B3). MRV demonstrates no venous sinus thrombosis (B4).

Figure 3. SS is a continuum from acute, focal linear cSAH and SS/cSAH independently predicts symptomatic intracerebral bleeding event

A 77-year-old woman presented with transient left hand numbness (panel A and B). Both CT (A1, arrows) and FLAIR (A2, arrow) within 2 days demonstrate hyperintensity in right central sulcus and post-central sulcus. Slight elevated DWI signal (A3, arrows) is noted along the right central sulcus associated with areas of cSAH. GRE shows hypointensities at the same areas (B1, arrow). Two-month follow-up GRE shows chronic SS in the same area (B2, arrow). The patient had a left frontal ICH after 40 months (B3, arrow).