Janica E. Walden, MD UNC Division of Neuroradiology

1. Janica E. Walden, MD UNC Division of Neuroradiology

2. Refers to the widespread rust-brown discoloration of the surface of the CNS, secondary to hemosiderin deposition. • Hemosiderin is deposited in the subpial layers of the brain and spinal cord, along the leptomeninges, and along the subependyma of the ventricles. • Hemosiderin deposition is a result of recurrent and persistent bleeding into the subarachnoid space. • Superficial hemosiderin deposition may be accompanied by reactive gliosis, neuronal loss, and demyelination.

3. Superficial Siderosis: Pathogenesis • Recurrent SAH induces intracellular uptake of iron. • Microglia, superficial astrocytes, and cerebellar Bergmann cells take up subarachnoid blood. • Intracellularly the heme is broken down into free iron • Free iron upregulatesferritin production, which sequesters iron. • Ferritin biosynthesis is then overwhelmed by large iron load, resulting in excess free iron. • Excess free iron may stimulate lipid peroxidation and production of reactive oxygen species, leading to localized tissue necrosis.

4. Superficial Siderosis: Pathogenesis • Microglia and Bergmann glia uniquely sensitive to iron-mediated cell damage • Terminal processes of Bergmann glia that interface with the SAS mediate iron uptake from the CSF, inducing ferritin synthesis in these cells • Ferritin sequesters iron but eventually overloaded • Preferential involvement of CN VIII likely due to its extensive lining with central myelin (supported by siderosis-susceptible microglia). • Also likely due to its course through the prepontine cistern, exposing the nerve to abundance of iron

5. Superficial Siderosis: Pathology • Macroscopically, dark brown discoloration of leptomeninges, superficial CNS parenchyma, and subependymal lining. • Leptomeninges are thickened • Varying degrees of neuronal loss, reactive gliosis, and dymyelination. • Superficial folia of the cerebellum almost always involved with loss of Purkinje cells and Bergmann gliosis. • CN VIII (sometimes CN’s I and II) exhibit dense hemosiderin accumulation. • Sometimes associated with demyelination and atrophy.

6. Superficial Siderosis: Causes • No source in approximately 46% of patients • Vascular abnormalities • AVM’s, aneurysms, fragile capillary regrowth after brain surgery • Neoplasms • Ependymomas, oligodendrogliomas, astrocytomas • Trauma • Cervical nerve root avulsions

7. Superficial Siderosis: Clinical Findings • Progressive, bilateral sensorineural hearing loss (95%) • Ataxia (88%) • Pyramidal signs (76%) • Occasionally, dementia, bladder incontinence, anosmia, anisocoria, and sensory deficits. • Men affected more than women (3:1) • Analysis of CSF intermittently may show xanthochromia, elevated red blood cell count, and elevated iron and ferritin levels.

8. Superficial Siderosis: MR Findings • In the past superficial siderosis was diagnosed almost exclusively at autopsy. • Advent of MRI facilitated in vivo diagnosis, and indicated that SS is more common than previously thought. • T2WI and gradient echo susceptibility imaging demonstrates characteristic hypointensity along the pial surface/subarachnoid space of the brain and spinal cord as well as ependyma of the ventricles • Due to the paramagnetic nature of hemosiderin

10. Superficial Siderosis: MR Findings • Less extensive, partially corresponding hyperintense rim may be seen on T1WI • May be due to presence of blood breakdown products at different stages of evolution • Tissue damage secondary to SS may be detected as atrophy and signal intensity abnormality • Findings are characteristically along the surface of the brain stem and cerebellarvermis • CN’s coated with hemosiderin detected by MR in only 25% of cases • Extent or distribution of siderosis doesn’t necessarily correlate with severity of clinical disease.

11. Superficial siderosis

12. Superficial Siderosis: MR Findings • Extra-arachnoid longitudinally oriented intraspinal fluid collection frequently noted. • Variably referred to as meningoceles, pseudomeningoceles, diverticula, or epidural cyst • Nerve root avulsions common association • Within the spine, spinal cord atrophy common. • Peripheralization or clumping of nerve roots may be seen due to chronic SAH-related arachnoiditis. • Management aimed at eliminating the cause of recurrent SAH either by surgical or endovascular treatment.

13. Superficial Siderosis

14. Normal leptomeningeal melanin • Variable thick hypointense rim on ventral surface of medulla on T2WI, skin pigmentation • MR sequence artifacts • Meningioangiomatosis • Rare benign lesion characterized by leptomeningeal calcification and cortical meningovascular proliferation • Coexistent NF in 50% • Neurocutaneousmelanosis • Rare congenital phakomatosis • Normal or abnormal brain surface venous structures

15. Hsu Wendy C, Loevner Laurie A, Forman Mark S, Thaler Erica R. Superficial Siderosis of the CNS Associated with Multiple Cavernous Malformations. AJNR 1999; 20: 1245-1248. • Khalatbari Kimia. Case 141: Superficial Siderosis. Radiology • Kumar N. Neuroimaging in Superficial Siderosis: An In-Depth Look. AJNR 2010; 31: 5-14. • Nanda et al. Superficial siderosis-mechanism of disease: an alternative hypothesis. Annals of Clinical Biochemistry 2010; 47: 275-278.