Prevalence and Natural History of Superficial Siderosis

Abstract

Background and Purpose Superficial siderosis (SS) is characterized by hemosiderin deposition in the superficial layers of the central nervous system and can be seen during post-mortem examination or with iron-sensitive magnetic resonance imaging (MRI) techniques. The distribution of SS may predict the probable underlying etiology. This study aimed to report the prevalence and natural history of superficial siderosis (SS) in a population-based study. Methods Brain MRI scans from the Mayo Clinic Study of Aging, a population-based study of residents 50–89 years of age in Olmsted County, Minnesota, were reviewed. Participants with imaging consistent with SS were identified from 2011 through 2016. An inverse probability weighting approach was used to convert our observed frequencies to population prevalence of SS. Additional data abstracted included amyloid Positron Emission Tomography (PET), Apolipoprotein E (APOE) genotype, coexisting cerebral microbleeds, and extent of SS. Results A total of 1,412 participants had eligible MRI scans. Two participants had infratentorial SS, restricted to the posterior fossa. Thirteen participants had cortical SS (cSS) involving the cerebral convexities (7 focal and 6 disseminated). Only three of the participants with cSS (23%) also had cerebral microbleeds. The population prevalence of SS was 0.21% (95% confidence interval [CI]: 0–0.45) in those 50 to 69 years old and 1.43% (CI 0.53–2.34) in those over 69 years old. APOE ε2 allele was more common in those with SS (57.1% vs 15.0%, p < 0.001). Compared to participants without SS, those with SS were also more likely to have a positive amyloid PET scan (76.9% vs 29.8%, p < 0.001) Conclusions SS may be encountered in the general elderly population. The association with increased amyloid burden and APOE ε2 genotype supports cerebral amyloid angiopathy as the most common mechanism. Longitudinal follow up is needed to evaluate the risk of subsequent hemorrhage in cases of incidentally discovered SS.

A Quarter Century of APOE and Alzheimer’s Disease: Progress to Date and the Path Forward

“…APOE4 carriers tend to have a greater burden of amyloid in vessels, leading to microbleeds, but APOE2 carriers appear to be more prone to such vessels rupturing and causing larger hemorrhages (Biffi et al, 2011;Charidimou et al, 2015;Yu et al, 2015). This increased propensity of APOE2 carriers to hemorrhage from CAA is also supported by a recent paper demonstrating that they are much more likely to show superficial siderosis on MRI scans (Pichler et al, 2017). The importance of beta-amyloid deposits in vessels has been highlighted recently in the replicated finding that APOE4-positive AD patients treated with anti-amyloid antibodies are at increased risk for amyloidrelated imaging abnormalities (ARIAs).…”

Asymptomatic Cerebral Small Vessel Disease: Insights from Population-Based Studies

“…In another population-based study (n=1,412) [143] of individuals aged 50 to 89 (of which a portion had dementia or mild cognitive impairment [144]), using data from the Mayo Clinic Study of Aging, 13 subjects (0.9%) were found to have cSS. Unlike the RS, only about one-fifth of these patients had concurrent CMB, a finding which is consistent with other reports [145].…”

Superficial Siderosis Misdiagnosed As Parkinson’s Disease in a 70-year-old Male Breast Cancer Survivor

“…Possible causes of these bleeds include intracranial tumors, head trauma, arteriovenous malformations, aneurysms, cervical root avulsion, neurosurgical procedures, brachial plexus injury, amyloid angiopathy, and chronic subdural hematomas [6][7][8]. Hemosiderin is most commonly found surrounding the brain stem, cerebellum, and basal cisterns as it pools in the posterior fossa, although superficial cortical deposition can be seen as well [1,5,9]. The diagnostic procedure of choice is T2 and susceptibility-weighted (SW) MRI, which visualizes paramagnetic blood products as hypointense [5,9].…”

“…Superficial siderosis is a rare neurological disease associated with chronic subpial deposition of hemosiderin throughout the brain and spinal cord due to recurrent episodes of subarachnoid hemorrhage [1][2][3][4][5][6][7][8][9]. Disease prevalence within the general population remains unclear, although population-based studies have reported a range of 0.21%-1.43% in patients aged over 55 years, with greater prevalence in those aged over 69 years [2,10]. The disease presents clinically as a triad of bilateral sensorineural hearing loss, ataxia, and myelopathy with pathognomonic findings of hypointensities along the brainstem, cerebellum, and spinal cord identified by multisequence MRI.…”