Cortical superficial siderosis: detection and clinical significance in cerebral amyloid angiopathy and related conditions

Abstract

Cortical superficial siderosis describes a distinct pattern of blood-breakdown product deposition limited to cortical sulci over the convexities of the cerebral hemispheres, sparing the brainstem, cerebellum and spinal cord. Although cortical superficial siderosis has many possible causes, it is emerging as a key feature of cerebral amyloid angiopathy, a common and important age-related cerebral small vessel disorder leading to intracerebral haemorrhage and dementia. In cerebral amyloid angiopathy cohorts, cortical superficial siderosis is associated with characteristic clinical symptoms, including transient focal neurological episodes; preliminary data also suggest an association with a high risk of future intracerebral haemorrhage, with potential implications for antithrombotic treatment decisions. Thus, cortical superficial siderosis is of relevance to neurologists working in neurovascular, memory and epilepsy clinics, and neurovascular emergency services, emphasizing the need for appropriate blood-sensitive magnetic resonance sequences to be routinely acquired in these clinical settings. In this review we focus on recent developments in neuroimaging and detection, aetiology, prevalence, pathophysiology and clinical significance of cortical superficial siderosis, with a particular emphasis on cerebral amyloid angiopathy. We also highlight important areas for future investigation and propose standards for evaluating cortical superficial siderosis in research studies.

Remote Intracerebral Hemorrhage After Intravenous Thrombolysis

“…7 CSS is uncommon (≈1% of acute ischemic stroke) 16 and reflects repeated episodes of hemorrhage into the subarachnoid space from brittle superficial cortical or leptomeningeal CAA-laden vessels, potentially heralding a high risk of future lobar ICH. 17 Sporadic CAA renders small cortical vessels brittle and fragile because of vascular amyloid-β deposition, increasing their vulnerability to bleeding when hemostasis is acutely impaired after IV-r-tPA. 7 The mechanism accounting for vessel rupture after amyloid deposition is not clear, but fibrinoid necrosis and microaneurysm seem likely to be involved.…”

“…Compared with those without MRI, these patients were younger (70.9±12.9 versus 76.2±11.9; P<0.001), the proportion of women was lower (43.4% versus 49.9%; P=0.045), and the 24-hour stroke severity was lower (median NIHSS score, 3 [1][2][3][4][5][6][7] versus 6 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]; P<0.001). Fourteen patients (3.4%) had a rPH, 4 patients (0.9%) had a rPH with a concomitant PH, 26 patients had PH (6.3%), and 365 patients (89.4%) were without any rPH or PH.…”

“…17,24 Finally, most MRI were performed after IV-r-tPA. CSS or CMB could be caused by IV-r-tPA, 17,21 and new ischemic lesions may appear during the first days of hospitalization. Whether or not RSI or CAA markers were present before IV-r-tPA makes our conclusions less reliable.…”

Small vessel disease burden in cerebral amyloid angiopathy without symptomatic hemorrhage

“…32 Being associated with transient focal neurologic episodes and linked to the occurrence of convexity subarachnoid bleeds, 33 the higher prevalence of cSS in patients seen for TFNEs is somewhat expected. 34 Nonetheless, this finding supports the hypothesis that clinical expression of the disease is related to the type of underlying SVD changes on MRI.…”

Reply:

“…Very superficial clusters of multiple MBs can be mistaken for cSS, but these would be distinguished by their irregular appearance. 2 In relation to exclusions, 4 patients with previous symptomatic subarachnoid hemorrhage, 23 patients with traumatic subdural hematoma, and 1 patient with an intracranial operation were excluded according to medical charts. We therefore presented 12 cases with cSS that did not seem to have occult sources of bleeding, as the authors pointed out.…”