In vivo amyloid imaging in cortical superficial siderosis: Author's response to Linn J.'s rapid response letter

Rik Vandenberghe, Director memory clinic,
August 26, 2010

We thank J. Linn for her interest in our paper.

Following acceptance of the final version of our in vivo amyloid imaging paper in December 2009 (1), 2 subsequent papers (2,3) were published that used a different methodology and design but were in full accordance with our findings. In our paper, we report the clinical history, CT, MR and in vivo amyloid imaging in 2 cases with cortical superficial siderosis. Both cases had a positive amyloid scan. The PIB pattern in our two cases with superficial siderosis was closely similar to that typically seen in Alzheimer disease (AD). We conclude that cortical superficial siderosis falls within the spectrum of cerebral amyloid angiopathy (CAA) and Alzheimer disease (AD) and constitutes an occasional complication of cerebral amyloidosis (1). Following acceptance of our paper, a series of 38 pathologically confirmed CAA patients was published (2), including 2 cases who had superficial siderosis on MRI in the absence of microbleeds or macrohemorrhages, similarly to our case 1 (Fig 1B). On that basis, Linn et al. proposed in April 2010 to modify the criteria for CAA and include superficial siderosis as one of the imaging criteria. If we apply the modified criteria, our case 1 fulfills the modified Boston criteria of possible CAA. As mentioned in the discussion (1), case 2 fulfills the criteria of probable CAA according to the Boston criteria and also according to the modified criteria (2010). In a third paper, Kumar et al. (2010) published a consecutive series of 13 cases of atraumatic localized convexal subarachnoid hemorrhage above 60 years of age (along with 16 younger cases who are not directly relevant to the current discussion) (3). In 5-7 cases, the clinical history was remarkably similar to that observed in our 2 cases, with stereotyped paroxysmal episodes of focal neurological loss, sometimes with a migratory pattern. The CT image of intrasulcal hemorrhage also closely resembled that shown in Fig 1A and C (1). On the basis of the MRI findings (superficial siderosis, cortical microbleeds or macrohemorrhage), Kumar et al. propose that convexal subarachnoid hemorrhages in patients above 60 years of age, may be caused by cerebral amyloid angiopathy. Taken together, these 3 papers provide novel and converging evidence that, clinically, cerebral amyloid angiopathy should be considered as a cause in patients above the age of 60 years with stereotyped episodes of focal neurological loss and cognitive decline and superficial siderosis on MRI, even in the absence of other MRI abnormalities, in particular if the distribution of the siderosis is mainly supratentorial.

1. Dhollander I. et al., In vivo amyloid imaging in cortical superficial siderosis. J Neurol Neurosurg Psychiatry 2010 doi 10.1136/jnnp.2009.194480

2. Linn J. et al., Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy. Neurology 2010; 74; 1346-1350

3. Kumar S. et al., Atraumatic convexal subarachnoid hemorrhage: clinical presentation, imaging patterns, and etiologies. Neurology 2010; 74; 893- 899

Conflict of Interest:

PI of a GE Healthcare sponsored phase I and phase II study, as well as of therapeutic phase II and phase III trials sponsored by EliLilly, Medivation, Novartis and Pfizer.

Conflict of Interest

None declared