Letter

H.X. Bai
Department of Radiology
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania

H. Zhou
Department of Neurology
Xiangya Hospital, Central South University
Hunan, China

X. Tan, X. Huang and L. Yang
Department of Neurology
The Second Xiangya Hospital, Central South University
Hunan, China

We read with great interest a recent article by Inoue et al¹ on the diagnostic significance of cortical superficial siderosis (cSS) for Alzheimer disease in patients with cognitive impairment. The article focused on presymptomatic cases of cSS diagnosed by MR imaging.

The major finding of the article was that cSS was associated with a lobar location of microbleeds (MBs) and may be an initial radiologic finding of cerebral amyloid angiopathy (CAA) in patients with cognitive impairment. Lobar location includes both the cortical gray matter and the subcortical white matter. The imaging manifestations of hemosiderin deposition from cSS and MBs from CAA can be indistinguishable on gradient-echo T2-weighted images,² especially when MBs are seen on the surface of the cerebral cortex. There is even a suggestion that CAA can be an underlying cause of cSS.³ In the current study, there was 72% correspondence between the location of cSS and that of MBs. The definition of cSS was only based on the shape of the signal abnormality on SWI (ie, linear). Because there are currently no widely recognized criteria to distinguish hemosiderin deposition from MBs on imaging, it may be helpful to show interobserver variability in the assignment of individual lesions to ensure agreement on the nature of the hypointensity seen on T2-weighted MR imaging.

Although its detection has increased with the advances in MR imaging technology, cSS is still a rare disease.⁴ The most accepted hypothesis for its etiology has been chronic iron deposition in neuronal tissues associated with CSF.⁵ Chronic bleeding into the subarachnoid space of the brain releases erythrocytes into the CSF. The chronic bleeding source can be a result of past brain surgery or CNS trauma.⁵ Less common bleeding sources include CSF cavity lesions, tumors, vascular malformations, and so forth.⁴ The authors stated that cSS related to previous symptomatic subarachnoid hemorrhage, traumatic subdural hematoma, or intracranial surgery was not included, but they did not provide information on the number of patients excluded. According to the literature, the source of bleeding was never found in as many as half of all described cases.⁴ Even for the 12 patients included in the analysis, it is possible that they still had an occult source of bleeding. Consequently, the relationship between cSS and CAA may be either overestimated or underestimated in the studied cohort, depending on how many patients were excluded due to a known bleeding source.

In conclusion, the pathogenesis of cSS from CAA is still an unproven hypothesis. An unidentified bleeding source may account for cSS in the studied cohort instead of CAA.

References

1. Inoue Y, Nakajima M, Uetani H, et al. Diagnostic significance of cortical superficial siderosis for Alzheimer disease in patients with cognitive impairment. AJNR Am J Neuroradiol 2015 Oct 8. [Epub ahead of print]
2. Kumar N. Neuroimaging in superficial siderosis: an in-depth look. AJNR Am J Neuroradiol 2010;31:5–14
3. Linn J, Herms J, Dichgans M, et al. Subarachnoid hemosiderosis and superficial cortical hemosiderosis in cerebral amyloid angiopathy. AJNR Am J Neuroradiol 2008;29:184–86
4. Fearnley JM, Stevens JM, Rudge P. Superficial siderosis of the central nervous system. Brain 1995;118:1051–66
5. Kumar N. Superficial siderosis: associations and therapeutic implications. Arch Neurol 2007;64:491–96

Reply

Y. Inoue and M. Nakajima
Department of Neurology

T. Hirai
Department of Diagnostic Radiology

Y. Ando
Department of Neurology
Graduate School of Medical Sciences
Kumamoto University
Kumamoto, Japan

We sincerely thank Harrison X. Bai and colleagues for their interest and comments regarding our recent article, in which we demonstrated the diagnostic significance of cortical superficial siderosis (cSS) for Alzheimer disease in patients with cognitive impairment.¹

Regarding the methodologic issues of the present study that their letter raises, the diagnosis of cSS seen on susceptibility-weighted imaging was based on collegial discussion with experienced neuroradiologists, and no data are available for interobserver variability. We defined cSS as linear hypointensities on the surface of the cerebral gyri on SWI. The appearance of cSS on SWI was obvious in this study; fortunately, we had no difficulty in distinguishing cSS from lobar cerebral microbleeds (MBs). 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.

We agree with their statement that elucidating the pathogenesis of cSS from cerebral amyloid angiopathy (CAA) warrants further analysis. However, imaging-histopathologic correlations shown in cases with CAA might indicate that recurrent blood leakage of meningeal vessels leads to the propagation of cSS.³ To confirm the progression of CAA-related cSS, prospective studies are needed that recruit patients with CAA based on the Boston criteria.⁴

References

1. Inoue Y, Nakajima M, Uetani H, et al. Diagnostic significance of cortical superficial siderosis for Alzheimer disease in patients with cognitive impairment. AJNR Am J Neuroradiol 2015 Oct 8. [Epub ahead of print]
2. Charidimou A, Linn J, Vernooij MW, et al. Cortical superficial siderosis: detection and clinical significance in cerebral amyloid angiopathy and related conditions. Brain 2015;138:2126–39
3. Beitzke M, Enzinger C, Wünsch G, et al. Contribution of convexal subarachnoid hemorrhage to disease progression in cerebral amyloid angiopathy. Stroke 2015;46:1533–40
4. Knudsen KA, Rosand J, Karluk D, et al. Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston criteria. Neurology 2001;56:537–39

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