Cerebral Superficial Siderosis : Etiology, Neuroradiological Features and Clinical Findings

Abstract

Superficial siderosis (SS) of the central nervous system constitutes linear hemosiderin deposits in the leptomeninges and the superficial layers of the cerebrum and the spinal cord. Infratentorial (i) SS is likely due to recurrent or continuous slight bleeding into the subarachnoid space. It is assumed that spinal dural pathologies often resulting in cerebrospinal fluid (CSF) leakage is the most important etiological group which causes iSS and detailed neuroradiological assessment of the spinal compartment is necessary. Further etiologies are neurosurgical interventions, trauma and arteriovenous malformations. Typical neurological manifestations of this classical type of iSS are slowly progressive sensorineural hearing impairment and cerebellar symptoms, such as ataxia, kinetic tremor, nystagmus and dysarthria. Beside iSS, a different type of SS restricted to the supratentorial compartment can be differentiated, i.e. cortical (c) SS, especially in older people often due to cerebral amyloid angiopathy (CAA). Clinical presentation of cSS includes transient focal neurological episodes or "amyloid spells". In addition, spontaneous and amyloid beta immunotherapy-associated CAA-related inflammation may cause cSS, which is included in the hemorrhagic subgroup of amyloid-related imaging abnormalities (ARIA). Because a definitive diagnosis requires a brain biopsy, knowledge of neuroimaging features and clinical findings in CAA-related inflammation is essential. This review provides neuroradiological hallmarks of the two groups of SS and give an overview of neurological symptoms and differential diagnostic considerations.

Keywords: Amyloid related imaging abnormalities; Cerebral amyloid angiopathy; Cortical; Infratentorial; Superficial siderosis.

Fig. 1

Algorithm of different types of superficial siderosis (SS) and the corresponding assumed etiologies. ARIA—H: amyloid-related imaging abnormalities, hemorrhagic type, AVM arteriovenous malformation, CAA cerebral amyloid angiopathy, CSF cerebrospinal fluid, ICH intracerebral hemorrhage, RCVS reversible cerebral vasoconstriction syndrome, SAH subarachnoid hemorrhage

Fig. 2

Diagnostic value of different MRI sequences in the detection of superficial siderosis (SS). A 61-year-old man with SS due to ongoing hemorrhage from a melanoma metastasis in the right frontal cortex. In T2*-GRE (f) and susceptibility-weighted imaging (SWI) (b,g), SS is revealed by dark rims on the surface of affected structures, e.g., the mesencephalon (arrow), with SWI being more sensitive. Minimum intensity projections (mIPs) of SW images (c,h) further enhance the conspicuousness of SS. In addition, filtered phase image of SWI (a) can be used to distinguish paramagnetic (hemorrhage/iron, dark here) from diamagnetic substances (calcification, bright here), as they have opposite signal intensities. In general, susceptibility effects are more pronounced on images acquired at 3 T (f–j) than on images acquired at 1.5 T (a–e). Whereas at 3 T a hypointense rim around the mesencephalon is seen in T2WI and fluid attenuated inversion recovery (FLAIR) images (i,j, arrow), SS is almost undetectable at 1.5 T in T2WI and FLAIR (d,e, arrow). a–e 1.5 T (Achieva dStream, Philips); a–c SWI, TR/α 52 ms/20°, 4 echoes TE1 = 12 ms, ∆TE = 11 ms; d T2, TR/TE/α = 5762 ms/110 ms/90°; e FLAIR, TR/TE/TI/α = 11000 ms/140 ms/2800 ms/90°; f–j 3 T (Skyra fit, Siemens); f T₂*-GRE, TR/TE/α = 631 ms/20 ms/20°; g, h SWI, TR/TE/α = 27 ms/20 ms/15°; i T2, TR/TE/α = 4980 ms/92 ms/150°, j FLAIR: TR/TE/TI/α = 8500 ms/81 ms/2440 ms/150°. TR repetition time, TE echo time, TI inversion time, α flip angle

Fig. 3

Classical infratentorial superficial siderosis (iSS) in a 77-year-old woman with progressive hearing loss, gait ataxia, visual disturbances and optical hallucinations over 6 months. Axial T2*-GRE (a–f) showing SS of the upper cervical spinal cord (a, arrow), the VIII cranial nerve but sparing the VII cranial nerve (b: arrowhead, arrow), the cerebellum and mesencephalon (c,d: arrow), the medial Sylvian fissure (e, arrow) and of the medial occipital lobes (f, arrow)

Fig. 4

A 73-year-old woman suffering from recurrent severe headache attacks due to ventral dural defect at the level of the second thoracic vertebra with spontaneous intracranial hypotension and recurrent subarachnoid bleeding over more than 10 years. Axial susceptibility-weighted imaging (SWI) (a,b) and axial T2-weighted images (WI) (c,d; arrow) showing extensive superficial siderosis (SS) especially infratentorial; e, f CT disclosing slight hyperdense pontine and mesencephalic surface (arrow). Cerebrospinal fluid (CSF) analysis demonstrating auburn liquor (g); h xanthochrome supernatant and sedimentation of erythrocytes after centrifugation (h, arrow). i,j (SWI sag.) Extensive spinal SS (arrows) and ventral epidural fluid collection at the upper thoracic level (arrowheads)

Fig. 5

Classical superficial siderosis (SS) in a 59-year-old man suffering from progressive gait ataxia within 6 months and traumatic nerve root injury C7 and C8 30 years ago. a–d Axial susceptibility-weighted imaging (SWI) showing SS with pial signal loss (arrowheads) especially in the posterior fossa (a,b) and partially supratentorial (c,d: arrowheads). e–j SS also of the spinal cord (e,f: T2*-weighted images [WI] sag.; arrows); enlarged empty nerve root pouches C7 and C8 left (g,h: T2* WI sag. and ax. arrows) with inhomogeneous contrast enhancement (i, post contrast T1 WI ax. arrow); j cerebrospinal fluid (CSF) analysis exhibits silent chronic subarachnoid bleeding with erythrocytes and siderophages (arrow; magnification: 200x)

Fig. 6

A 74-year-old woman suffering from recurrent cortical subarachnoid hemorrhage (cSAH) in cerebral amyloid angiopathy (CAA). a–d First cSAH frontal right (a: CT ax., arrow) with sulcal hyperintense signal changes on fluid attenuated inversion recovery (FLAIR) images (b, arrow) and sulcal signal loss on T2*WI (c,d: arrow); additional cortical superficial siderosis (cSS) left (c,d: arrowhead); e–g second cSAH paramedian frontal left (e: FLAIR ax.; g: T2*WI ax.; arrowhead); note characteristic bilinear track-line appearance of cSS in the chronic stage (f,g: T2*WI, arrow); h–k third cSAH frontodorsal left (h: CT ax., arrow) with signal loss on SWI (i–k, arrow) and progressive cSS bilaterally

Fig. 7

A 72-year-old man with beginning dementia suffering from temporary hemiparesis right and aphasia due to cerebral amyloid angiopathy (CAA). Acute cortical subarachnoid hemorrhage (cSAH); b fluid attenuated inversion recovery [FLAIR ax.; c susceptibility-weighted imaging (SWI) ax.; d diffusion-weighted imaging (DWI) ax., b = 1000 s/mm², arrow. Enlarged perivascular spaces (PVS) (a,e: T2WI ax.; arrow), focal small gliosis (b,f: FLAIR ax.; arrowhead), multiple microbleeds (MB) and cortical superficial siderosis (cSS) (c,g: SWI ax.) beside residual atypical intracerebral bleeding frontal left (c,g: arrowhead)

Fig. 8

Cortical vein thrombosis as a possible mimic of cortical superficial siderosis (cSS) in a 27-year-old woman with right-sided headache and sensory Jacksonian seizures. MRI demonstrating cortical hyperintense lesion postcentral parietal right (a: T2 WI ax.; b fluid attenuated inversion recovery [FLAIR] images ax.; arrow), signal loss and “blooming” of the central vein (c, T2*WI ax.; arrow) without cSS, circumscribed peripheral contrast enhancement (d,e T1 WI ax., post contrast T1 WI ax.; arrow) and restricted diffusion of the thrombus (f, diffusion-weighted imaging [DWI] ax., b = 1000 s/mm², arrow)

Fig. 9

CAA related inflammation (CAA-ri) in a 61-year-old man suffering from subacute psychosyndrome with disturbance of consciousness and executive disorders. a–d bifrontal left dominant hyperintense lesions with sulcal effusions (a,b: fluid attenuated inversion recovery [FLAIR] images ax.; arrows), accentuated microbleeds (MB) (c, susceptibility-weighted imaging [SWI] ax.; arrows) and hypointense signal conversion on postcontrast (pc) T1 WI (d, arrows) with enhancement; e–h follow-up MRI 13 months later after 3 bouts of high-dose methylprednisolone infusions, neurological examination was unremarkable. Completely resolved lesions frontal (e,f), unchanged cortical and subcortical MB (c,g; arrowheads)

Fig. 10

Amyloid related imaging abnormalities (ARIA). a–e fluid attenuated inversion recovery [FLAIR] images ax. showing encephalopathic type of ARIA (ARIA—E) in a 54-year-old man treated with aducanumab, weeks 14 (a), 30 (b), 34 (c), 38 (d) 40 (e) after treatment initiation; sulcal effusions (b–d, arrowhead) and additional hyperintense lesion in the occipital lobe (b–d, arrow), which completely resolved at week 40. T2* WI ax. (f–i) and FLAIR ax. (j,k) demonstrating hemorrhagic type of ARIA (ARIA-H) and ARIA‑E in a 68-year-old woman treated with aducanumab at baseline (f), weeks 14 (g), 18 (h,j), 20 (i) and 94 (k)