1	ASNR 2006 eSE: “Superficial Siderosis of the CNS: Etiologic & Imaging Findings” Besada,C.(1)· Scalise,G.(1)· Funes,J.(1)· Yacovino,D.(1)· Santa Cruz,D(1)· Romero,C.(2)· Taratuto,A.(2)· Ameriso,S.(2)· Meli,F.(2) Hospital Francés, (2) FLENI Buenos Aires, ARGENTINA.
2	Purpose To demonstrate the importance of gradient echo (GRE) sequences in the diagnosis of superficial siderosis (SS). To include amyloid angiopathy (AA) into the possible etiologies of chronic repeated subarachnoideal bleeding leading to this infrequent entity, which has not been emphasized.
3	Methods We have evaluated 7 cases with signs of SS in MRI. In all of them we included gradient-echo sequences in the exam, making the images much more conspicuous. We also compare classical sequences: T1, T2 and FLAIR with GRE sequences. Some cases have also gone through other imaging studies, particularly to exclude vascular anomalies and tumors of the brain and spinal cord.
4	Definition Superficial Siderosis is a pathological condition characterized by abnormal deposition of hemosiderin in the leptomeninges and in the subpial layers of the brain and spinal cord. It has an insidious and progressive clinical course. MRI confirms the presence of deposits of hemosiderin in the leptomeninges and subpial space.
5	Definition The disorder has been identified in patients of all ages. Men affected more often than women at a ratio of 3:1 (our seven cases are males) Prevalence: 5th decade. There is no evidence of developement of SS until after approximately 6 months of repeated bleeding.
6	History The superficial siderosis of the CNS is an infrequent entity. The first description was made by Hamill in 1908. Many isolated cases are increasingly published till then. Almost 190 cases have been reported till november 2004. It is a distinct entity from systemic hemochromatosis.
7	Clinical Findings Sensorineural hearing loss, Cerebellar ataxia Mielopathy
8	Findings in MRI MR findings are pathognomonic. T2-weighted and particularly gradient-echo sequences reveal characteristic hypointensity along the pial surface of the brain, spinal cord and/or ependyma of the ventricles.
9	Imaging Findings Issues MRI confirms the presence of deposits of hemosiderin in the leptomeninges and subpial space in clinically suspected patients. With the widespread use of MRI and particularly GRE sequences, an increasing number of less severe cases without the clinical triad, asyntomatic/underdiagnosed or missdiagnosed cases are being discovered. (case Nº 7) The extent and distribution of siderosis does not correlate strictly with the clinical severity.
10	Pathogenesis It has been suggested that high iron and ferritin levels in CSF have a central role in the pathogenesis of SS. The eight cranial nerve and the cerebellar cortex are specially vulnerable, leading to the clinical signs of ataxia and hearing loss. Cerebellum´s affection is supposed to be related to its unique ability to biosynthesize ferritin in response to increased iron/heme concentrations and VIII compromise is thought to be due to his long cisternal traject. Other authors use the concept of recirculation of the CSF through the ventricular system, to explain the findings of SS.
11	Etiologies: chronic bleeding Idiopathic Vascular anomalies: MAV, aneurysm, cavernous malformation (brain and spinal) Brain or spinal tumors Postsurgical Posttraumatic Anticoagulant therapy Amyloid Angiopathy (even when it is not generally included between the etiologies of SS, there are many cases reporting the relationship between both entities and our series confirm this issue)
12	Treatement The first issue is to exclude and prevent any cause of rebleeding. In patients without a bleeding source, several treatements have been proposed: iron chelation, CSF shunting and heme oxygenase inhibitors. These therapies may arrest the progression of the disease, but their efficacy is disputed.
13	Our cases
14	"Patient M 43y" Patient M 43y, with headaches of 10 days of evolution. SS was incidentally discovered in his first MR exam. He went through all imaging studies to exclude vascular anomalies and tumors of the neuroaxis, that were negative. We concluded this is a presymtomatic stage of a primary or idiopathic form of SS. Look at the images !!!
15
16
17	"Patient M 61y" Patient M 61y, with the classic clinical triad. He had a previous brain and cervical spine MRI without GRE sequences. In that study the SS was subtle and underviewed by the neuroradiologist. We repeated the exam adding the GRE sequences and we clearly show the leptomeningeal hipointensity. He went through all imaging studies to exclude vascular anomalies and tumors of the brain and spinal cord, that were negative. We concluded this is a primary or idiopathic form of SS. Look at the images !!!
18
19
20
21	"Patient M 60y with antecedents..." Patient M 60y with antecedents of an aneurysm of the right Sylvian artery, discovered 2 years ago after an episode of SAH. He underwent surgery and one year after, we discovered signs of SS in the follow up MRI. We concluded this is a secondary form of SS, caused by a subarachnoideal bleeding of an aneurysm. Look at the images !!!
22
23	"Patient M59y with antecedents of..." Patient M59y with antecedents of a left temporal hematoma. He presented with a subacute left frontal hematoma. Digital angiography was normal and brain biopsy was positive for Amyloid Angiopathy. We concluded this is a secondary form of SS, related to repeated subarachnoideal and parenchymal bleeding, due to AA. Look at the images !!!
24
25	"Patient M85y" Patient M85y. Follow up of bilateral SAH. MR showed a chronic parenchymal hematoma (asyntomatic) and signs of SS. Digital angiography was negative. We concluded this is a secondary form of SS, related to repeated subarachnoideal and parenchymal bleeding, probably due to AA. (it is not confirmed because the family refused the brain biopsy) Look at the images !!!
26
27	"Patient M84y" Patient M84y. MR showed two chronic parenchymal hematomas (both asyntomatic) and signs of diffuse SS. We also made a Magnetic Resonance Angiography (MRA) that was normal. Digital angiography was refused by the family. We concluded this is a secondary form of SS, related to repeated subarachnoideal and parenchymal bleeding, probably due to AA. (it is not confirmed because the family also refused the brain biopsy) Look at the images !!!
28
29
30
31	"Patient M59y without previous..." Patient M59y without previous antecedents. He debutated with an aphasia. MR showed a left frontal subacute hematoma, an old occipital one (that had been asyntomatic) and signs of diffuse SS. We also made an MRA (Magnetic Resonance Angiography) that was normal. Brain biopsy was performed and it was diagnosed as Amyloid angiopathy. We concluded this is a secondary form of SS, related to repeated subarachnoideal and parenchymal bleeding, due to AA. Look at the images !!!
32
33
34	Summary of findings in our cases In 4 cases we found associated intraparenchymal hematomas (most of them asyntomatic). These patients were old aged, suggesting the diagnosis of amyloid angiopathy. (excepting case 4 and 7: 59 years old). These two cases (Nº 4 and 7) were confirmed by brain biopsy. In 2 cases, the deposition of hemosiderin in the leptomeninges was characteristic of the idiopathic form of SS, affecting mainly the posterior fossa. Vascular anomalies and tumors were excluded. One of these patients was asyntomatic and the other was clinically and imaging underdiagnosed without GRE sequences.
35	Summary of findings in our cases None of our patients showed anomalies in the angiographic studies, excepting the one with the aneurysm of the Sylvian artery (case Nº3) The first case is in a presymtomatic stage, discovered incidentally by MR. All our patients were males.
36
37	Conclusion We highlight the role of the GRE sequences in the depiction of SS by MRI. We propose to include amyloid angiopathy between the possible etiologies of this condition, specially when it is associated to intraparenchymal hematomas in elderly people.
38	Bibliography 1-J of the Neurological science, III (1992) pag 20-25. SS of the CNS: report 3 cases and review 2-Ann Neurol 1993,34:646-653. The pathogenesis of SS of the CNS 3-J of neuroscience research 1994,37:461-465. Isoforms of ferritin have a specific cellular distribution in the brain 4-Movement Desorders 1994,vol 9,n 5:559-562 Hemosiderosis of the CNS 5-Brain 1995,118:1051-1066. SS of the CNS 6-Neurology 1995,45:1000-1002. Recurrent SHA due to endometriosis 7-Medical Hypotheses 1996,47:261-264. SS of the brain: roles for CFC, iron and the hidroxil radical 8-Clinical Imaging 1997,21:241-245. SS of the CNS.Its MRI manifestations 9-Neuroradiology 1998,40:312-314. Secundary SS of the CNS in a patient. 10-AJNR 1999,20:1245-1248. SS of the CNS associated whit multiple cavernous malformations 11-J of Clinical Neuroscience 1999,5:532-535. SS of the CNS decondary to a thalamic hamartoma 12-Ital J Neurol Sci 1999,20:247-249. SS of the CNS and anticoagulant therapy: a case report 13-J Neurol 1999,246:980-981. SS of the CNS as a rare differential diagnosis of Chronic back pain 14-J Neurol 2001,248:63-64. Polyradiculopathy in the course of SS of the CNS 15-J Neurol 2001,248:1099-1100. Polyradiculopathy in the course of SS of the CNS 16-The Lancet Neurology 2002,1:326. SS 20 years after brain tumor 17-J of Stroke and Cerebrovasc dis 2002,11:288-289. SS of the CNS in a patient whit chronic SH missdiagnosed as MS 18-J Neurol Neurosurg Psychiatry 2002,72:274-280. SS associated whit anterior horn cell dysfunction 19-Thombosis Research III 2003,pag 193-196. Continuation of oral ACO despite SS 20-J Neurol Neurosurg Psychiatry 2003,74:1326-1328. SS of the CNS many years after neurosurgical procedures 21-Otology & Neurotology 2003,24:90-95. SS of the meninges and its otolaringologic connection: 5 patients 22-Otology & Neurotology 2003,24:738-742. Longitudinal analysis of hearing loss in a case of hs of CNS 23-J Neurol Neurosurg Psychiatry 2004,75:1463-1466. Familial leptomeningeal amyloidosis whit a trasthyretin 24-J Neurol Neurosurg Psychiatry 2004,75:188-190. The importance of suspecting SS of the CNS in clinical practice 25-Neurology 2004,62:1022-1023. Effects of shunting in Cfs in SS of the CNS. 26-Otology & Neurotology 2004,25:193-194. SS of the CNS 27-Pediatr Neurol 2005,32:346-349. CNS siderosis and Dandy Walker variant after neonatal thrombocytopenia 28-Clinical Neurology and Neurosurgery 2005. SS of the CNS: report of 3 cases and review of the literature 29-Diagnostico 2005,vol XIV n°148:198-200. Siderosis del SNC.Presentación típica en secuencias RM GRE