Search

Iron is essential for functioning of cells and of the body as a whole. Perls staining allows the histopathological identification of iron deposits. By classifying hepatic siderosis as parenchymal, mesenchymal or mixed, it may guide the search for its etiology. HFE1 hemochromatosis is the most common siderosis. Its diagnosis is currently based on genetic analysis. Its expressivity being variable and its penetrance incomplete, the demonstration of hepatic siderosis may represent a mode of discovery., (Copyright © 2024. Published by Elsevier Masson SAS.)

The figure shows tissue samples taken from three previous cases, revealing the cause of hemosiderin deposition in the central nervous system because of superficial siderosis., (© 2024 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.)

Abstract: Chronically transfused patients with sickle cell disease typically do not exhibit iron-mediated extrahepatic toxicity. However, we demonstrate that the pituitary gland is vulnerable to iron deposition, and it occurs regardless of other extrahepatic involvement. Severe pituitary siderosis is associated with early organ dysfunction., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Background: In pediatric transfusion-dependent thalassemia (TDT) patients, we evaluated the prevalence, pattern, and clinical associations of pancreatic siderosis and the changes in pancreatic iron levels and their association with baseline and changes in total body iron balance., Procedure: We considered 86 pediatric TDT patients consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Iron overload (IO) was quantified by R2* magnetic resonance imaging (MRI)., Results: Sixty-three (73%) patients had pancreatic IO (R2* > 38 Hz). Global pancreas R2* values were significantly correlated with mean serum ferritin levels, MRI liver iron concentration (LIC) values, and global heart R2* values. Global pancreas R2* values were significantly higher in patients with altered versus normal glucose metabolism. Thirty-one patients also performed the follow-up MRI at 18 ± 3 months. Higher pancreatic R2* values were detected at the follow-up, but the difference versus the baseline MRI was not significant. The 20% of patients with baseline pancreatic IO showed no pancreatic IO at the follow-up. The 46% of patients without baseline pancreatic IO developed pancreatic siderosis. The changes in global pancreas R2* between the two MRIs were not correlated with baseline serum ferritin levels, baseline, final, and changes in MRI LIC values, or baseline pancreatic iron levels., Conclusions: In children with TDT, pancreatic siderosis is a frequent finding associated with hepatic siderosis and represents a risk factor for myocardial siderosis and alterations of glucose metabolism. Iron removal from the pancreas is exceptionally challenging and independent from hepatic iron status., (© 2024 Wiley Periodicals LLC.)

Objectives: Statins have been associated with an increased risk of spontaneous intracerebral hemorrhage (ICH), but without dedicated study in cerebral amyloid angiopathy (CAA). We aimed to evaluate the association between previous statin treatment and radiological hemorrhagic lesions in a CAA population during a first lobar ICH event., Materials and Methods: We retrospectively included all patients meeting the modified Boston criteria for probable CAA and admitted for a first lobar ICH between 2010 and 2021 at Rouen University Hospital. Patients were classified as having previous statin treatment or not. We compared the ICH volume, the number of associated cerebral microbleeds (CMBs), and cortical superficial siderosis (CSS) according to previous statin treatment or not. We also compared functional outcomes and ICH recurrence during the follow-up period between the two groups., Results: We included 99 patients, 27 of whom had statin treatment prior to their ICH. The ICH volume and the number of CMBs did not differ between groups. Disseminated CSS was initially more frequent in the statin group (88% versus 57%; P=0.019), but this was no longer significant after adjustment for antiplatelet treatment (P=0.13). The long-term outcome was similar between the two groups with no increased risk of ICH recurrence in the statin-treated group (29.63% versus 23.61%, P=0.54)., Conclusions: Previous statin treatment was not associated with more severe hemorrhagic lesions in CAA in terms of ICH volume or number of microbleeds, but a trend for increased disseminated CSS was highlighted, which will require further larger studies., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Three histologic patterns of gastric siderosis (GS) are described: pattern A (predominantly in lamina propria stromal cells-gastric lamina propria siderosis [GLPS]), pattern B (mostly extracellular crystalline iron) and pattern C (predominantly in glandular epithelium-gastric glandular siderosis [GGS]). This study aimed to analyze the association of GGS with clinicopathologic features using 3 cohorts. Cohort #1 consisted of 76 gastric siderosis cases. Upon classifying the cases into 3 groups by percentage of glandular involvement (negative, 1% to 5%, ≥5% GGS), the degree of GGS was positively associated with serum ferritin levels ( P =0.002), transferrin saturation ( P =0.003), and history of blood transfusion ( P =0.009). After excluding cases with coarse extracellular crystalline iron, cohort #1 was reclassified into 3 groups by degree of GLPS (no, rare [discernible at ×20 or ×40], overt [readily visible at low power]). The degree of GLPS was positively correlated with oral iron pill use ( P =0.01), but not serum ferritin levels or transferrin saturation. Cohort #2 contained 31 gastric samples from patients with hereditary hemochromatosis, most received phlebotomy treatment. GGS was identified in 2 (6.4%) patients; both had high ferritin levels. Cohort #3 included 38 gastric samples from patients with cirrhosis. Three (8%) cases showed GGS; serum ferritin level was available for 1 case and was elevated. These results indicate that GGS is associated with systemic iron overload, while GLPS is correlated with oral iron pill use. The identification of GGS, especially when it's ≥5%, should trigger further workup for potential systemic iron overload and underlying etiologies., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Superficial siderosis of the central nervous system is produced by the deposit of hemosiderin within the subpial layers of the central nervous system and central parts of the cranial nerves, leading to progressive degeneration. We report a 55-year-old male who consulted for hearing loss and long-standing progressive decrease in visual acuity, associated with sudden onset of left hemiparesis. A brain CAT scan showed subacute ischemic lesions in the territory of the right posterior cerebral artery (thalamus and right subcortical temporal regions), old ischemic lesions in the right subcortical occipital regions and cerebellar atrophy. A magnetic resonance confirmed the lesions and the presence of superficial diffuse siderosis. A cerebrospinal fluid analysis showed slight xanthochromia, 26 leukocytes/mm3, glucose 51 mg/dL and proteins 1.23 g/L. He was managed with aspirin in low doses and statins. His motor function improved and was discharged two weeks after admission.

Introduction: Although hyperferritinemia may reflect the inflammatory status of patients with non-alcoholic fatty liver disease (NAFLD), approximately 33% of hyperferritinemia cases reflect real hepatic iron overload., Aim: To evaluate a non-invasive method for assessing mild iron overload in patients with NAFLD using 3T magnetic resonance imaging (MRI) relaxometry, serum hepcidin, and the expression of ferritin subunits., Methods: This cross-sectional study assessed patients with biopsy-proven NAFLD. MRI relaxometry was performed using a 3T scanner in all patients, and the results were compared with iron content determined by liver biopsy. Ferritin, hepcidin, and ferritin subunits were assessed and classified according to ferritin levels and to siderosis identified by liver biopsy., Results: A total of 67 patients with NAFLD were included in the study. MRI revealed mild iron overload in all patients (sensitivity, 73.5%; specificity, 70%). For mild (grade 1) siderosis, the transverse relaxation rate (R 2 *) threshold was 58.9 s -1 and the mean value was 72.5 s -1 (SD, 33.9), while for grades 2/3 it was 88.2 s -1 (SD, 31.9) (p < 0.001). The hepcidin threshold for siderosis was > 30.2 ng/mL (sensitivity, 87%; specificity, 82%). Ferritin H and ferritin L subunits were expressed similarly in patients with NAFLD, regardless of siderosis. There were no significant differences in laboratory test results between the groups, including glucose parameters and liver function tests., Conclusions: MRI relaxometry and serum hepcidin accurately assessed mild iron overload in patients with dysmetabolic iron overload syndrome., Competing Interests: Conflicts of interest The authors declare that they have no conflicts of interest., (Copyright © 2022 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Pulmonary siderosis or welder's lung is an occupational lung disease that is usually observed after chronic exposure to iron dust., Observation: A 55-years-old welder visited hospital with dyspnea linked to occupational exposure. Pulmonary function studies revealed lung function abnormalities with decerase of FEV1 and TPC. Based on the chest Tomography CT results, he was diagnosed with obliterans bronchiolitis. A chest biopsy was performed and the specimen is for a pulmonary siderosis aspect., Discussion: This case of pulmonary siderosis is an unusual one by symptoms, CT images and short latency of exposure. An intense inhalation of iron particles could explain this case and inflammatory process and it highlights need of histological analysis of chest biopsy., (Copyright © 2022 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Background: Histopathological evidence of cerebral vascular amyloid β accumulation is the gold standard to diagnose cerebral amyloid angiopathy (CAA). Neuroimaging findings obtained with CT and MRI can suggest the presence of CAA when histopathology is lacking. We explored the role of amyloid PET in patients with lobar intracerebral hemorrhage (ICH) as this may provide molecular evidence for CAA as well., Methods: In this retrospective, monocenter analysis, we included consecutive patients with non-traumatic lobar ICH who had undergone amyloid PET. We categorized patients according to amyloid PET status and compared demographics and neuroimaging findings. We calculated sensitivity and specificity of the simplified Edinburgh criteria and amyloid PET with probable modified Boston criteria as reference standard, as well as sensitivity and specificity of the simplified Edinburgh and modified Boston criteria with amyloid PET status as molecular marker for presence or absence of CAA., Results: We included 38 patients of whom 24 (63%) were amyloid PET positive. Amyloid PET positive patients were older at presentation (p = 0.004). We observed no difference in prevalence of subarachnoid hemorrhages, fingerlike projections or microbleeds between both groups, but cortical superficial siderosis (p = 0.003) was more frequent in the amyloid PET positive group. In 5 out of 38 patients (13%), the modified Boston criteria were not fulfilled due to young age or concomitant vitamin K antagonist use with INR > 3.0. With the modified Boston criteria as reference standard, there was no difference in sensitivity nor specificity between the simplified Edinburgh criteria and amyloid PET status. With amyloid PET status as reference standard, there was also no difference in sensitivity nor specificity between the simplified Edinburgh and modified Boston criteria., Conclusions: Amyloid PET was positive in 63% of lobar ICH patients. Under certain circumstances, patients might not be diagnosed with probable CAA according to the modified Boston criteria and in these cases, amyloid PET may be useful. Accuracy to predict CAA based on amyloid PET status did not differ between the simplified Edinburgh and modified Boston criteria., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Kumar defined duropathies as disorders with dural defects-related cerebrospinal fluid leaks, particularly of spinal anterior dura mater, Superficial (hemo) siderosis (SS) and multisegemental amyotrophy (MSAM) were included in duropathies. Dural defects of SS had two types; one was incomplete closure of the dura in the spinal and cranial operations, the other was a spontaneous defect in the spinal anterior dura mater. In a majority of SS patients, spontaneous dural defects were detected at the levels of C7/Th1 to Th2/Th3 on axial FIESTA (fast imaging employing steady state acquisition) images. Similarly, dural defects in our 6 cases with MSAM were showed at C7/Th1 to Th2/Th3. Axial FIESTA images were crucial on MR imaging. T 2 weighted images demonstrated abnormal hyperintense lesions in both anterior horns at the level of C3 spinal cord in all of 7 patients with MSAM. A dural defect in one case was not found.

Cortical superficial siderosis is an established haemorrhagic neuroimaging marker of cerebral amyloid angiopathy. In fact, cortical superficial siderosis is emerging as a strong independent risk factor for future lobar intracerebral haemorrhage. However, the underlying neuropathological correlates and pathophysiological mechanisms of cortical superficial siderosis remain elusive. Here we use an in vivo MRI, ex vivo MRI, histopathology approach to assess the neuropathological correlates and vascular pathology underlying cortical superficial siderosis. Fourteen autopsy cases with cerebral amyloid angiopathy (mean age at death 73 years, nine males) and three controls (mean age at death 91 years, one male) were included in the study. Intact formalin-fixed cerebral hemispheres were scanned on a 3 T MRI scanner. Cortical superficial siderosis was assessed on ex vivo gradient echo and turbo spin echo MRI sequences and compared to findings on available in vivo MRI. Subsequently, 11 representative areas in four cases with available in vivo MRI scans were sampled for histopathological verification of MRI-defined cortical superficial siderosis. In addition, samples were taken from predefined standard areas of the brain, blinded to MRI findings. Serial sections were stained for haematoxylin and eosin and Perls' Prussian blue, and immunohistochemistry was performed against amyloid-β and GFAP. Cortical superficial siderosis was present on ex vivo MRI in 8/14 cases (57%) and 0/3 controls (P = 0.072). Histopathologically, cortical superficial siderosis corresponded to iron-positive haemosiderin deposits in the subarachnoid space and superficial cortical layers, indicative of chronic bleeding events originating from the leptomeningeal vessels. Increased severity of cortical superficial siderosis was associated with upregulation of reactive astrocytes. Next, cortical superficial siderosis was assessed on a total of 65 Perls'-stained sections from MRI-targeted and untargeted sampling combined in cerebral amyloid angiopathy cases. Moderate-to-severe cortical superficial siderosis was associated with concentric splitting of the vessel wall (an advanced form of cerebral amyloid angiopathy-related vascular damage) in leptomeningeal vessels (P < 0.0001), but reduced cerebral amyloid angiopathy severity in cortical vessels (P = 0.048). In terms of secondary tissue injury, moderate-to-severe cortical superficial siderosis was associated with the presence of microinfarcts (P = 0.025), though not microbleeds (P = 0.973). Collectively, these data suggest that cortical superficial siderosis on MRI corresponds to iron-positive deposits in the superficial cortical layers, representing the chronic manifestation of bleeding episodes from leptomeningeal vessels. Cortical superficial siderosis appears to be the result of predominantly advanced cerebral amyloid angiopathy of the leptomeningeal vessels and may trigger secondary ischaemic injury in affected areas., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Autopsy reports of 78 stillbirths and early infant deaths (up to age 8 weeks) were reviewed to investigate the prevalence of extrahepatic nonreticuloendothelial siderosis (EHNRS) in the context of neonatal liver failure. Of these, 10 liveborns (12.8%), M:F 3:2, with mean gestational age 37.6 weeks (range: 35-39) and mean age at the time of demise 19.1 days (range: 7-42), showed significant liver injury: infection (n = 7, viral > fungal), congenital malformations (n = 2), and ischemia (n = 1). None had maternal history of gestational alloimmune liver disease (GALD) or previous fetal/neonatal death due to liver failure. Seven of 10 cases (70%) showed EHNRS: pancreas (n = 6), kidneys (n = 4), thyroid and adrenal glands (n = 3), and bronchial glands and heart (n = 2). Iron deposition was most frequent in the pancreas (60%), most diffuse in the kidneys, and seen in at least 2 organs, with pancreas and kidney being the most frequent combination. Hepatic C5b-9 expression was variable (1+ to 4+) except 1 case (100% necrosis). The duration of illness and the mean age at the time of demise tended to be higher in those with EHNRS. In summary, hepatic and EHNRS, with or without C5b-9 expression, are not specific for GALD. Other causes of liver failure should be investigated as clinically and pathologically appropriate.

Objective: To report 2 cases of superficial siderosis of central nervous system (SS-CNS) and a review of the literature. Methods: We have analyzed the clinical data and relevant features of two patients with SS-CNS who were presented with ataxia and slurred speech. Both patients undertook blood tests, lumbar puncture, head CT (computer tomography) scans, and brain and spinal cord magnetic resonance (MR) scans. In addition, the first patient also undewent enhanced susceptibility-weighted angiography (ESWAN) and the second patient undertook susceptibility weighted imaging (SWI) scan. We searched PubMed with the keywords superficial siderosis and superficial siderosis of central nervous system, and selected publications that seemed appropriate. Results: A neurological examination revealed bilateral sensorineural hearing impairment in both the patients. Their past history was not significant to identify hemorrhage. Brain MR scans demonstrated typical hypointensity rimming at the brain surface on T2 weighted images. The patients were diagnosed with SS-CNS. Conclusion: SS-CNS should be highly suspected in patients with progressive sensorineural hearing loss, ataxia, and signs of pyramidal tracts, and MR scans of brain and whole spinal cord should be undertaken to confirm the diagnosis. Advanced MRI techniques such as SWI and ESWAN are helpful in making the diagnosis of SS-CNS. The cause of hemorrhage is not identified in most cases.

Superficial siderosis (SS) is a rare, neurodegenerative disease that results from toxic accumulation of hemosiderin on the surface of the brain and spinal cord. The Japanese guidelines for diagnosis and classification of SS have been classified into three categories, according to the distribution of iron deposition and the clinical symptoms, as follows: "classical" type, "localized" type and "atypical" type. In "classical" type SS, patients typically present with slowly progressive and irreversible cerebellar ataxia, sensorineural hearing loss, and/or myelopathy, due to involvement of the acoustic nerve, cerebellum, and spinal cord. T2-weighted imaging (WI) or T2 * WI demonstrates characteristic linear low intensity signals along the surface of the brain and spinal cord. However, the natural history and clinical evolution of SS are poorly understood. Furthermore identification and resolution of the bleeding source do not elicit prompt clinical recovery or radiological reversal of SS in most cases. Pharmacological treatments for SS primarily include strategies that produce iron chelation. For example, deferiprone is the only treatment that crosses the blood-brain barrier and binds hemosiderin in the central nervous system.

Cortical superficial siderosis (cSS) is a pathologic and radiologic diagnosis of hemosiderin deposition in subpial brain layers. However, cSS has not been fully studied in patients with acute stroke. Here, we investigated the prevalence of cSS in patients with acute stroke and analyzed the relationship between cSS and different clinical and neuroimaging characteristics. From September 2014 through June 2016, consecutive patients with acute stroke who were admitted to our department were retrospectively investigated. We analyzed the prevalence of cSS and the associations between cSS and risk factors, the topographic distribution of cerebral microbleeds (CMBs), and the severity of white matter lesions (WMLs). In total, 739 patients (589 patients with ischemic stroke/transient ischemic stroke [IS/TIA] and 150 with intracerebral hemorrhage [ICH]; mean age, 71.4 years) were enrolled. We identified cSS in six (1.0%) patients with IS/TIA and seven (4.7%) patients with ICH. The presence of cSS was associated with ICH (P < 0.0001), WMLs (P = 0.0105), and lobar and non-lobar CMBs (both P < 0.0001); no associations between cSS and age, sex, cardiovascular risk factors, IS subtype classification, or antiplatelet and anticoagulant therapy were found. In a multivariable logistic regression analysis, high numbers of lobar CMBs (≥ 2; odds ratio, 11.03; 95% confidence interval, 2.03-205.40; P = 0.0029) were independently associated with cSS. Furthermore, cSS was often located near lobar CMBs. Our results suggest that cSS is prevalent in ICH and is independently associated with lobar CMBs; however, no associations between cSS and other risk factors or comorbidities were observed.

Background: In patient with cerebral amyloid angiopathy (CAA) presenting with lobar hemorrhage (LH), magnetic resonance imaging (MRI) white matter hyperintensities (WMH) tend to be predominant in posterior regions with the "multiple subcortical spots" WMH pattern as the most frequent topographical WMH pattern. Our aim was to analyze WMH severity and topographical distribution in patients with cortical superficial siderosis (CSS)., Methods: We retrospectively analyzed MRIs from consecutive symptomatic isolated (i.e., without LH) CSS and LH-CAA (with or without associated CSS) patients. We analyzed baseline clinical characteristics including age, history of hypertension, diabetes, hypercholesterolemia, and pre-existing cognitive deficit. The presence of lobar microbleeds (MB) was scored on T2*. FLAIR (fluid-attenuated inversion recovery) WMH severity (using the Fazekas scale) and topographical distribution (using [slightly modified] earlier described WMH patterns) were analyzed and compared between both groups., Results: Twenty CSS and 63 LH-CAA patients were analyzed. Baseline clinical characteristics were similar between both groups, except for hypercholesterolemia less frequently present in the CSS group (P = .026). Lobar MB were significantly less frequently present in the CSS group (P < .01), and CSS was more frequently focal in the CSS group compared with LH-CAA patients with associated CSS (P = .03). Mean Fazekas scale was significantly lower in CSS patients (P = .011). WMH patterns did not differ between both groups, with the multiple subcortical spots pattern as the most frequently observed pattern., Conclusions: Relative severe WMH scores and similar topographical distribution in CSS patients argue for WMH as a CAA-related feature in these patients with isolated CSS, adding level of evidence that isolated CSS could correspond to early manifestations of CAA., (Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Objective: To identify predictors of early lobar intracerebral hemorrhage (ICH) recurrence, defined as a new ICH within 6 months of the index event, in patients with cerebral amyloid angiopathy (CAA)., Methods: Participants were consecutive survivors (age ≥55 years) of spontaneous symptomatic probable or possible CAA-related lobar ICH according to the Boston criteria, drawn from an ongoing single-center cohort study. Neuroimaging markers ascertained in CT or MRI included focal (≤3 sulci) or disseminated (>3 sulci) cortical superficial siderosis (cSS), acute convexity subarachnoid hemorrhage (cSAH), cerebral microbleeds, white matter hyperintensities burden and location, and baseline ICH volume. Participants were followed prospectively for recurrent symptomatic ICH. Cox proportional hazards models were used to identify predictors of early recurrent ICH adjusting for potential confounders., Results: A total of 292 patients were enrolled. Twenty-one patients (7%) had early recurrent ICH. Of these, 24% had disseminated cSS on MRI and 19% had cSAH on CT scan. In univariable analysis, the presence of disseminated cSS, cSAH, and history of previous ICH were predictors of early recurrent ICH (p < 0.05 for all comparisons). After adjusting for age and history of previous ICH, disseminated cSS on MRI and cSAH on CT were independent predictors of early recurrent ICH (hazard ratio [HR] 3.92, 95% confidence interval [CI] 1.38-11.17, p = 0.011, and HR 3.48, 95% CI 1.13-10.73, p = 0.030, respectively)., Conclusions: Disseminated cSS on MRI and cSAH on CT are independent imaging markers of increased risk for early recurrent ICH. These markers may provide additional insights into the mechanisms of ICH recurrence in patients with CAA., (© 2016 American Academy of Neurology.)

Background and Purpose: Transient focal neurological episodes occur in cerebral amyloid angiopathy (CAA) and can mimic transient ischemic attack (TIA). Risk factors and outcomes of minor ischemic stroke or TIA might differ in patients with and without cerebral microbleeds (CMBs), including CAA-consistent lobar CMB., Methods: Baseline magnetic resonance imaging (MRI) was analyzed for CMBs and cortical superficial siderosis in 416 patients in the prospective computed tomography and MRI in the CATCH study (Triage of TIA and Minor Cerebrovascular Events to Identify High Risk Patients). Clinical symptoms, baseline characteristics, recurrence, and 90-day modified Rankin Scale were prospectively collected. MRI white-matter hyperintensity was measured using the Fazekas scale., Results: CMBs were detected in 65 (15.6%) and cortical superficial siderosis in 11 patients (2.6%). Lobar CMBs were present in 49 (11.8%). In multivariable logistic regression adjusted for risk factors and age, subcortical Fazekas score was associated with lobar CMB (odds ratio, 2.07; 95% confidence interval, 1.23-3.48; P=0.006). Forty-two patients (10.1%) had lobar-only CMBs with or without cortical superficial siderosis consistent with modified Boston criteria for possible/probable CAA. The possible/probable CAA pattern was not predictive of recurrent TIA (odds ratio, 0.42; 95% confidence interval, 0.05-3.31; P=0.41), stroke (odds ratio, 1.24; 95% confidence interval, 0.26-5.99; P=0.79), or 90-day modified Rankin Scale score ≥2 (odds ratio, 1.38; 95% confidence interval, 0.62-3.07; P=0.42)., Conclusions: CMBs in TIA and minor stroke are moderately common but do not predict recurrence or 90-day outcome. CAA-related transient focal neurological episodes and TIA have overlapping clinical symptoms, suggesting that MRI may be needed for differentiation., (© 2016 American Heart Association, Inc.)

A 74-year-old female patient, who was diagnosed with neurofibromatosis type 1 (NF1) at the age of 40, was admitted with complaints of flickering vision and gait disturbance for the last 2 years. On admission, neurological examination revealed mild bilateral hearing loss and ataxia in the limb and trunk. Laboratory tests revealed anti-hepatitis C virus (HCV) antibody positivity and elevated HCV RNA by real-time polymerase chain reaction. The cerebrospinal fluid examination revealed a slightly yellowish appearance with elevated total protein levels. Gradient echo T2*-weighted brain magnetic resonance imaging (MRI) demonstrated a rim of hypointense lesions surrounding the surface of the cerebellum, brainstem, frontal and temporal lobes, and thalamus, which was considered as hemosiderin depositions. From these MRI findings, she was diagnosed as having superficial siderosis of the central nervous system. Cerebral angiography revealed an aneurysm-like dilatation at the bifurcation of the right internal carotid-posterior communicating artery. (99m)Tc-ethyl cysteinate dimer single-photon emission computed tomography revealed hypoperfusion in the bilateral frontal and temporal lobes. Pelvic plain X-ray, pelvic computed tomography, and lumbosacral MRI revealed a sacral defect and an anterior sacral polycystic meningocele communicating with the spinal subarachnoid space. The patient's symptoms gradually worsened, and she died of septic shock because of pyelonephritis at the age of 77. An autopsy was performed; on pathological examination, we did not observe any findings associated with rupture of the aneurysm-like dilatation in the bifurcation of the right internal carotid-posterior communicating artery and cerebral amyloid angiopathy. Because duropathies-a new neurological disease concept-have been implicated as a cause of bleeding in the superficial siderosis, the anterior sacral polycystic meningocele, a type of duropathies, was presumed to be the most probable bleeding source of the superficial siderosis in this patient. Bleeding from the meningocele might result from the vulnerability of vessel walls in NF1.

Objectives: Estimating the prevalence of glutathione S-transferase gene polymorphism (GSTM1) null genotype among patients with beta thalassemia major (β-TM) in relation to myocardial status assessed by tissue Doppler and cardiac siderosis assessed by cardiac magnetic resonance imaging (MRI) T2*., Methods: Hundred patients with β-TM and 100 healthy controls were enrolled. Complete blood count (CBC), mean serum ferritin and GSTM1 genotyping, echocardiography, tissue Doppler, and cardiac MRI T2* were done., Results: Serum ferritin ranged from 1200 to 8000 ng/ml, and mean T2* value was 27.10 ± 11.20 ms. Of patients, 68 (68%) had no cardiac siderosis, while 24 (24%) with mild to moderate, and 8 (8%) with sever cardiac siderosis. T2* values were not correlated with serum ferritin (r = -0.09, P = 0.50). GSTM1 null genotype was prevalent in 46% of patients and 40% of controls (P = 0.69). Patients with null genotype had significantly shorter T2* (P = 0.001), higher left ventricular end-diastolic diameter (P = 0.002), and shorter ejection time (P = 0.005) with no significant relation to serum ferritin (P = 0.122). GSTM1 null genotype was the only predictor for cardiac iron overload (P = 0.002)., Discussion: Serum ferritin concentrations have been shown to correlate poorly with all stages of cardiac dysfunction. Low cardiac MRI T2* values occur in patients with β-TM despite good chelation therapy, suggesting a possible role of genetic factors in cardiac siderosis., Conclusion: GSTM1 null genotype is significantly associated with cardiac iron overload independent of serum ferritin in Egyptian patients with β-TM.

Objective: To investigate the value of susceptibility-weighted imaging (SWI) for characterization of hepatocellular carcinoma (HCC) and dysplastic nodule (DN)., Materials and Methods: Sixty-eight cirrhotic patients with 89 hepatocellular nodules underwent SWI. The radiological features of hepatocellular nodules on SWI were classified into three types: type A (iso- or hypointensity, and background liver siderosis), type B (hyperintensity, and background liver siderosis), or type C (hyperintensity, and no background liver siderosis). Intranodular and background liver iron content was quantified and correlated with SWI pattern. Prussian blue staining was performed to quantify intranodular and background liver iron content., Results: Type A pattern (n = 12) contained 11 (91.7%) DNs and 1 (8.3%) HCC, Type B pattern (n = 66) comprised 1 (1.5%) DN and 65 (98.5%) HCCs (including 12 DN-HCCs and 53 overt HCCs), and type C pattern (n = 11) was exclusively seen in HCCs. The iron scores of DN-HCCs and overt HCCs were significantly lower than those of background livers [(0.091±0.30) VS (2.18±0.87), P = 0.000; (0.11±0.41) VS (2.16±0.97), P = 0.000; respectively]. There was no significant difference between iron scores of DNs and those of background livers [(1.92±0.29) VS (2.17±039), P = 0.191]. For lesion-based and patient-based analysis of HCCs (DN-HCCs and overt HCCs), type B pattern showed a sensitivity, specificity, accuracy, positive predicative value (PPV), and negative predicative value (NPV) of 84.4% and 84.4%, 91.7% and 75%, 85.4% and 83.8%, 98.5% and 98.2%, 47.8% and 23.1%, respectively., Conclusion: SWI can provide valuable information for characterization of HCC and DN based on endogenous iron reduction during hepatocarcinogenesis.

Background: Myocardial black blood (BB) T2* relaxometry at 1.5T provides robust, reproducible and calibrated non-invasive assessment of cardiac iron burden. In vitro data has shown that like T2*, novel native Modified Look-Locker Inversion recovery (MOLLI) T1 shortens with increasing tissue iron. The relative merits of T1 and T2* are largely unexplored. We compared the established 1.5T BB T2* technique against native T1 values at 1.5T and 3T in iron overload patients and in normal volunteers., Methods: A total of 73 subjects (42 male) were recruited, comprising 20 healthy volunteers (controls) and 53 patients (thalassemia major 22, sickle cell disease 9, hereditary hemochromatosis 9, other iron overload conditions 13). Single mid-ventricular short axis slices were acquired for BB T2* at 1.5T and MOLLI T1 quantification at 1.5T and 3T., Results: In healthy volunteers, median T1 was 1014 ms (full range 939-1059 ms) at 1.5T and modestly increased to 1165ms (full range 1056-1224 ms) at 3T. All patients with significant cardiac iron overload (1.5T T2* values <20 ms) had T1 values <939 ms at 1.5T, and <1056 ms at 3T. Associations between T2* and T1 were found to be moderate with y =377 · x(0.282) at 1.5T (R(2) = 0.717), and y =406 · x(0.294) at 3T (R(2) = 0.715). Measures of reproducibility of T1 appeared superior to T2*., Conclusions: T1 mapping at 1.5T and at 3T can identify individuals with significant iron loading as defined by the current gold standard T2* at 1.5T. However, there is significant scatter between results which may reflect measurement error, but it is also possible that T1 interacts with T2*, or is differentially sensitive to aspects of iron chemistry or other biology. Hurdles to clinical implementation of T1 include the lack of calibration against human myocardial iron concentration, no demonstrated relation to cardiac outcomes, and variation in absolute T1 values between scanners, which makes inter-centre comparisons difficult. The relative merits of T1 at 3T versus T2* at 3T require further consideration.

Cortical superficial siderosis describes a distinct pattern of blood-breakdown product deposition limited to cortical sulci over the convexities of the cerebral hemispheres, sparing the brainstem, cerebellum and spinal cord. Although cortical superficial siderosis has many possible causes, it is emerging as a key feature of cerebral amyloid angiopathy, a common and important age-related cerebral small vessel disorder leading to intracerebral haemorrhage and dementia. In cerebral amyloid angiopathy cohorts, cortical superficial siderosis is associated with characteristic clinical symptoms, including transient focal neurological episodes; preliminary data also suggest an association with a high risk of future intracerebral haemorrhage, with potential implications for antithrombotic treatment decisions. Thus, cortical superficial siderosis is of relevance to neurologists working in neurovascular, memory and epilepsy clinics, and neurovascular emergency services, emphasizing the need for appropriate blood-sensitive magnetic resonance sequences to be routinely acquired in these clinical settings. In this review we focus on recent developments in neuroimaging and detection, aetiology, prevalence, pathophysiology and clinical significance of cortical superficial siderosis, with a particular emphasis on cerebral amyloid angiopathy. We also highlight important areas for future investigation and propose standards for evaluating cortical superficial siderosis in research studies., (© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: Ocular siderosis is a rare sight-threatening complication that occurs after a penetrating ocular injury by an iron-containing foreign body. The purposes of this study were to (i) investigate the histopathology, electrophysiology and iron levels/accumulation in ocular siderosis using an animal (Guinea pig) model and (ii) determine the appropriate timing for follow-up foreign body-removal surgery., Materials and Methods: Thirty guinea pigs were divided into five groups (n = 6 animals/group). On day-1, an iron body was inserted into the vitreous of the right eye of all animals; the left eyes were left undisturbed and were used as controls. At the end of each week during the 5-week study period, electroretinography (ERG) was performed on all animals in one of the five groups. Each animal in that group was sacrificed, after which both eyes were enucleated for histopathological and pharmacological evaluation of intraocular iron., Results: Accumulated iron levels of study eyes were significantly higher than those of control eyes (135.13 and 13.55 μg/g, respectively, p < 0.01). In addition, there was a significant decrease in electrophysiological responses of study eyes. During the first week, iron levels were higher in study eyes than control eyes, but neither histological iron accumulation nor decreased electrophysiological responses could be detected. By the end of the second week, increased iron accumulation was observed histologically in intraocular tissues, along with signs of retinal toxicity, as verified by decreased electrophysiological responses., Conclusions: The present study indicates that the 14th day after a penetrating eye injury by an iron-containing intraocular foreign body represents a clinically critical threshold, after which structural damage to and functional alterations in ocular tissues occur.

Superficial siderosis of the CNS is a rare disease characterized by the deposition of hemosiderin in the subpial layers of the CNS as the result of chronic subarachnoid bleeding. The arrest of bleeding is important for preventing the progression of this disease; however, the exact source of bleeding remains unknown in most cases because of a lack of objective surgical data. The authors of this report have described a unique case of superficial siderosis following cervical laminectomy and autograft fusion for the removal of a spinal schwannoma; the bleeding source was verified by intraoperative and histopathological findings. The patient exhibited no obvious neurological deficits, such as hearing loss or cerebellar ataxia, when the superficial siderosis was diagnosed, although there were the social impairments associated with schizophrenia. During repair surgery, the bleeding source was revealed as the bone marrow vasculature of the remaining vertebral arch, and not the fragile vessels at the dural defect or the residual tumor. Chronic bleeding was stopped before the onset of irreversible neurological deficits in this case. Bone marrow exposed to the intrathecal space may represent a chronic bleeding source in patients with superficial siderosis following CNS surgery including laminectomy or craniotomy. The following recommendations have been proposed for superficial siderosis of the CNS from both a preventative and a therapeutic perspective: 1) During CNS surgery, neurosurgeons should make every effort to prevent exposing bone marrow to the intrathecal space to avoid the risk of chronic subarachnoid bleeding. 2) In the case of a large dural defect and pseudomeningocele following CNS surgery, bone marrow around the dural defect should be considered as the bleeding source of superficial siderosis, and such cases should undergo revision surgery before the progression of this disease.

Skin reactions against injected or implanted foreign materials are not rare. Siderosis is a disease characterized by the accumulation of iron in various tissues. Brownish-gray discoloration of the skin can be seen as a side-effect on the injection area after the parenteral iron treatment. Here, we present cutaneous siderosis case developed after multiple intramuscular iron injection on the gluteal region for iron-deficiency anemia. Development of cutaneous siderosis after intramuscular iron injection rarely has been reported in the literature before.

Giant cell interstitial pneumonia (GIP)-like pulmonary alterations as a special form of condensate pneumopathy may result following inhalation of certain types of tobacco smoke which can cause a pitfall diagnosis of sideropneumoconiosis or hard metal lung disease. Exact information regarding the patient occupation and smoking history and especially regarding the origin of the cigarettes helps to clarify the findings.

Objective: To study the radiographycal changes and prognosis of welders' pneumoconiosis patients diagnosed within the last few years., Methods: Occupational hygienics data (including years on welding work, welding materials exposed to and work environment), symptoms, lung function test results and follow-up data of 136 welders' pneumoconiosis patients were collected retrospectively. The follow-up lasted up till June 30, 2014, with follow-up interval being one year. Chest radiographs were read/reviewed together by 3 senior experts experienced in pneumoconiosis diagnosing and shape and size of small opacity, overall profusion, affected lung zones and pneumoconiosis stages were all logged., Results: Of all 136 pneumoconiosis cases, five were of stage II and 131 were stage I, and they had been engaged in welding work for 9.2±6.34 years. All patients were present with slight symptoms including coughing, chest distress and dyspnea, while their lung function remained normal. Small round opacities were found on chest radiographs of 88.9% of the 136 cases. Years of follow-up on 131 cases of stage I Welder's pneumoconiosis showed that irregular small opacities remained fundamentally unchanged, while small round opacities tended to gradually lessen instead of coalescence. Two years after primary diagnosing, the total affected lung zones of follow-up objects were noticed to start lessening, and reduced by 0.02 per patient among the 48 follow-up subjects. Of the 48 cases followed up up to six years after primary diagnosing, the affected lung zone number was reduced by 0.54 per patient while 4 cases (8%) went down to below stage I. As of the 36 patients followed up 10 years after after primary diagnosis, the number of affected lung areas decreased by 1.14, and 22% (8 cases) appeared less than stage I on chest radiograph., Conclusion: It seemed that the so-called welders' pneumoconiosis featuring small round opacities tended to get improved over time, which suggested the diagnosis of siderosis.

Objective: To determine prevalence, topography, and severity of cortical superficial siderosis (SS), a recently recognized manifestation of cerebral amyloid angiopathy, and its possible association with Alzheimer disease (AD) in a memory clinic patient cohort., Methods: We included 809 patients (56% men, aged 66 ± 10 years) from the Amsterdam Dementia Cohort between November 2010 and November 2012 scanned on a 3-tesla MRI system. We analyzed prevalence and topography of cortical SS according to demographic, clinical, and MRI data. Agreement for SS detection between 2 neuroradiologists was calculated by using Cohen κ., Results: Agreement for detection of SS was excellent (unweighted κ of 0.81). In 17 patients (2.1%), cortical SS was found without a known cause. The prevalence of idiopathic SS differed according to diagnostic groups (p < 0.001): nearly 5% (95% confidence interval [CI] 2.8%-8.2%) in patients with AD (n = 168) vs 2% (95% CI 0.7%-6.0%) in patients with mild cognitive impairment (n = 143) and 2.5% (95% CI 0.7%-8.7%) in other types of dementia (n = 80). By contrast, SS was not found in patients with subjective complaints (n = 168) or in those with other disorders (n = 157). Presence of SS was associated with APOE ε4, microbleeds, and white matter hyperintensities (all p < 0.05) independent of diagnosis., Conclusion: The prevalence of cortical SS in a memory clinic setting is higher than reported in the general population but lower than reported in cerebral amyloid angiopathy. The relatively high prevalence of SS in AD suggests that SS is a relevant radiologic manifestation of amyloid pathology in AD. Presence of SS does not seem to predict severity of AD. Further longitudinal research is needed to investigate clinical relevance.

A 36-year-old man with progressive hearing impairment visited our hospital complaining of a severe headache. A neurological examination revealed bilateral sensorineural hearing impairment, mild ataxia, hyperreflexia and mild cognitive dysfunction. Brain MRI demonstrated hydrocephalus and typical hypointensity rimming the brain surface on T2(*)-weighted images. The patient was diagnosed as having superficial siderosis. Spinal MRI disclosed the presence of a lumbar intradural extramedullary mass. The surgically resected tumor was histologically found to be a cavernous angioma. Superficial siderosis is an important cause of hearing loss. With respect to the detection of disorders underlying this pathological condition, MRI examinations, including those of the brain and whole spinal cord, are recommended.

Recent data suggest an association of serum ferritin (SF) with waiting list (WL) and postliver transplant (LT) outcomes. To assess the predictive capacity of SF on pre- and post-LT outcomes, and to identify whether recipient or donor liver siderosis is associated with post-LT survival; a retrospective analysis of 1079 patients assessed for first LT, 2000-2007 was performed. Iron deposition in the liver tissue was assessed using a semi-quantitative grading system. Median age was 54 (18-82) years and 67% were male. Seventeen per cent had hepatocellular carcinoma (HCC). Median Model for End-stage Liver Disease MELD score was 14 (6-40), ferritin was 174 μg/l (4-4597) with 36.5% had a SF ≥ μg/l. Age (OR = 1.028) and MELD score (OR = 1.158) were independently associated with WL mortality (P < 0.001), whilst SF was not (P = NS). Age (OR = 1.018), HCC (OR = 1.542) and cold ischemia time (CIT) ≥ 10 h (OR = 1.418) were independently associated with post-LT survival (P < 0.05). Explant siderosis grade <2 was seen in 376 (71.7%) patients. Patients with explant siderosis grade ≥ 2 had inferior 12-month post-LT survival (P = 0.030). Presence of graft siderosis (15.8% of patients) was not associated with survival. In conclusion, we found a limited role for SF as a prognostic indicator for pre- or post-transplant survival., (© 2013 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Objective: We investigated the prevalence and clinical-radiologic associations of cortical superficial siderosis (cSS) in patients with probable cerebral amyloid angiopathy (CAA) compared to those with intracerebral hemorrhage (ICH) not attributed to CAA., Methods: We conducted a retrospective multicenter cohort study of 120 patients with probable CAA and 2 comparison groups: 67 patients with either single lobar ICH or mixed (deep and lobar) hemorrhages; and 22 patients with strictly deep hemorrhages. We rated cSS, ICH, white matter changes, and cerebral microbleeds., Results: cSS was detected in 48 of 120 (40%; 95% confidence interval [CI]: 31.2%-49.3%) patients with probable CAA, 10 of 67 (14.9%; 95% CI: 7.4%-25.7%) with single lobar ICH or mixed hemorrhages, and 1 of 22 (4.6%; 95% CI: 0.1%-22.8%) patients with strictly deep hemorrhages (p < 0.001 for trend). Disseminated cSS was present in 29 of 120 (24%; 95% CI: 16.8%-32.8%) patients with probable CAA, but none of the other patients with ICH (p < 0.001). In probable CAA, age (odds ratio [OR]: 1.09; 95% CI: 1.03-1.15; p = 0.002), chronic lobar ICH (OR: 3.94; 95% CI: 1.54-10.08; p = 0.004), and a history of transient focal neurologic episodes (OR: 11.08; 95% CI: 3.49-35.19; p < 0.001) were independently associated with cSS. However, cSS occurred in 17 of 48 patients with probable CAA (35.4%; 95% CI: 22.2%-50.5%) without chronic lobar ICH., Conclusions: cSS (particularly if disseminated) is a common and characteristic feature of CAA. Chronic lobar ICH is an independent risk factor for cSS, but the causal direction and mechanism of association are uncertain. Hemorrhage into the subarachnoid space, independent of previous (chronic) lobar ICH, must also contribute to cSS in CAA. Transient focal neurologic episodes are the strongest clinical marker of cSS.

Superficial siderosis (SS) is a rare condition in which hemosiderin is deposited on the pial surface of the brain and/or spinal cord. Hemosiderin deposition is the consequence of recurrent or persistent hemorrhage in the subarachnoid space. There are two types of SS. In "classical"-type SS, hypointense MRI signals are observed in the brainstem and cerebellum with diffuse and symmetrical margins. Causes of hemorrhage in the "classical" type include tumor, vascular abnormality, injury, and dural defect. The source of hemorrhage is not apparent in approximately 50% of patients despite extensive examination. In "localized"-type SS, hypointense MRI signals are localized in the cerebral cortex. The most common causes of hemorrhage in the "localized" type are cerebral amyloid angiopathy and/or Alzheimer's disease. Patients with SS usually present with slowly progressive and irreversible cerebellar ataxia, sensorineural hearing loss, and/or myelopathy due to involvement of the acoustic nerve, cerebellum, and spinal cord. T2-weighted imaging (WI) or T2* WI demonstrates characteristic linear low-intensity signals along the surface of the brain and spinal cord. Treatment of SS involves identification and surgical correction of the bleeding source. Deferiprone, which is a lipid-soluble iron chelator that can penetrate the blood-brain barrier, is reportedly effective at improving the clinical symptoms and deposition of hemosiderin. It is thus a hopeful treatment option for SS.

Objective: To identify auditory pathology resulting from superficial siderosis of the central nervous system (SSCN), auditory site of lesion, and a clinical profile for differential diagnosis and development of recommendations., Study Design: Prospective study., Setting: Academic clinical center., Patients: Ten participants with SSCN (the largest prospective evaluation of audiologic status reported to date)., Intervention(s): Demographics, clinical characteristics and history, audiometric evaluation, and Tinnitus Handicap Inventory (THI)., Main Outcome Measure(s): Type and degree of hearing loss, relationship to clinical course of SSCN, and expected results based on age and sex., Results: Sensorineural hearing loss (SNHL) is the most common symptom in SSCN (100%). Tinnitus (100%), imbalance (80%), and gait disorder (80%) were also frequently reported. Hearing loss is typically bilateral, asymmetric, progressive, sloping, and exceeds expected hearing loss related to age and sex. Hearing loss may be cochlear and/or retrocochlear in origin. Decreased word recognition is possible, and traditional amplification may offer limited benefit., Conclusion: We observed significant audiometric findings in all participants. SSCN variably and pathologically targets the auditory system without regard for duration of disorder. A long asymptomatic phase and lack of predictive relationship between duration and severity of hearing loss makes suspicion of SSCN based solely on audiometric battery difficult; however, asymmetric hearing loss exceeding expectations, particularly with history of head trauma or previous neurosurgical procedure, should raise a red flag and trigger further medical evaluation including MRI. Diagnosis of SSCN may alter expectations for audiologic prognosis and is a critical component for comprehensive management of SSCN patients.

Context: As demand for organs to treat end-stage liver disease increases, donor livers once deemed only marginally suitable for donation are being considered for transplantation. Pathologists are increasingly being asked to evaluate these livers for acceptability. This article provides guidelines for frozen section evaluation of livers for transplantation., Objective: This article concentrates on the histopathologic features of transplant suitability with appropriate clinicopathologic correlation for the practicing pathologist. Recommendations for proper handling and sampling of tissue are discussed. Relative and absolute contraindications as well as artifacts and benign conditions are emphasized., Data Sources: Sources include a compilation of the authors' experiences in academic and community liver transplantation centers. In addition, relevant medical literature was reviewed, as well as Web sites specializing in organ transplantation, such as Transplant Pathology Internet Services and the Organ Procurement and Transplantation Network., Conclusions: Malignancy and extensive necrosis in the liver are absolute contraindications to transplantation. Evaluation of macrosteatosis, fibrosis, hepatitis, and necrosis depends on the severity of disease and correlation with the clinical situation. Donor age of greater than 60 years does not preclude transplantation. Artifacts and benign conditions need to be understood to prevent wastage of precious organs and to ensure that an appropriate organ is provided for the recipient.

Cataract formation may be an indicator of early siderosis and has been associated with intralenticular foreign bodies. We report a unique case of histopathologically proven lens siderosis in a young man with a preceding history of trauma but no signs of retained intraocular foreign body. He presented with a total white cataract with brownish deposits on anterior capsule and underwent cataract surgery for same followed by histopathological staining of anterior capsule for iron deposits. This case illustrates the importance of close monitoring of patients with history of trauma or previous penetrating injury to the eye, albeit no intraocular foreign body, as they might develop ocular siderosis at a later stage.

Background: Superficial siderosis (SS) is a rare finding on T2*-weighted magnetic resonance imaging (MRI), regarded as a radiological marker of cerebral amyloid angiopathy (CAA). The present study investigates with 7.0-tesla MRI the prevalence of SS and its underlying pathological substrate in a consecutive series of post-mortem brains of elderly patients with various neurodegenerative and cerebrovascular lesions., Materials and Methods: The prevalence of SS and associated lesions was screened using 7.0-tesla MRI and their neuropathological correlates in 120 post-mortem brains of patients with various neurodegenerative and cerebrovascular diseases., Results: Eighty-three separate zones of SS were detected in 45 brains (37.5%), including 25 areas of disseminated SS (dSS) and 58 areas of focal SS (fSS), restricted to less than 3 sulci. dSS was spatially related to sequels of 14 lobar haematomas and 11 cerebral infarcts, while fSS was connected to 19 microbleeds and 39 micro-infarcts (p < 0.001). Comparison of the 15 CAA to the 30 non-CAA brains showed that dSS was due to an old lobar haematoma in 53% of the former group compared to 3% of the latter group (p = 0.003). fSS was due to a microbleed in 7% of the CAA brains and to 40% of the non-CAA brains (p = 0.03)., Conclusions: SS is associated with both haemorrhagic and ischaemic underlying lesions. It is frequently observed on T2*-weighted 7.0-tesla MRI, and two types of SS may be described. Clinicians should keep in mind that SS may be found in other settings than CAA.

Neonatal hemochromatosis is a rare disease that causes fetal loss and neonatal death in the 1st weeks of life and is one of the most common causes of liver failure in the neonate. The diagnosis is mostly made retrospectively, based on histopathologic features of severe liver fibrosis associated with hepatic and extrahepatic siderosis. Several etiologies may underlie this phenotype, including a recently hypothesized gestational alloimmune disease. Fifty-one cases of liver failure with intrahepatic siderosis in fetuses and neonates were analyzed retrospectively. Maternal and infant data were collected from hospitalization and autopsy reports. All available slides were reviewed independently by 3 pathologists. Immunologic studies were performed on maternal sera collected immediately after delivery. The diagnosis of neonatal haemochromatosis was retained in 33 cases, including 1 case with Down syndrome and 1 case with myofibromas. Liver siderosis was inversely proportional to fibrosis progression. In fetuses, iron storage was more frequent in the thyroid than in the pancreas. Perls staining in labial salivary glands was positive in 1 of 5 cases. Abnormal low signal intensity by magnetic resonance imaging was detected in the pancreas in 2 of 7 cases. Renal tubular dysgenesis was observed in 7 of 23 autopsy cases. Chronic villitis was seen in 7 of 15 placentas. Half of the mothers presented with an autoimmune background and/or autoantibodies in their sera. Our work highlights the importance of autopsy in cases of neonatal hemochromatosis and marshals additional data in support of the hypothesis that neonatal hemochromatosis could reflect maternal immune system dysregulation.

Objective: The purpose of this study was to assess the effect of hepatic iron deposition on apparent diffusion coefficient (ADC) values measured with single-shot echo-planar imaging (EPI) diffusion-weighted MRI (DWI) in patients with liver cirrhosis and in vitro., Materials and Methods: Fifty-two patients with liver cirrhosis who underwent breath-hold single-shot EPI DWI at 1.5 T before liver transplantation were retrospectively assessed. Estimated signal-to-noise ratio (SNRest) and ADC were measured in the right hepatic lobe (for b values of 50 and 500 s/mm2). SNRest and ADC were compared between patients stratified by pathologic iron grade using the Mann-Whitney test. Hepatic ADC values were correlated to T2* values using the Spearman correlation test in a subset of patients. In addition, a phantom consisting of solutions of varying iron concentrations was imaged with single-shot EPI DWI and T2* imaging, and iron concentration was correlated with ADC and T2*., Results: In phantoms, there was a decrease in ADC and T2* with increasing iron concentration (r=-0.95 and -0.92, respectively; p<0.05). Patients with hepatic siderosis had significantly lower SNRest and ADC compared with patients without siderosis (p<0.0001). SNRest at b=50 s/mm2 and b=500 s/mm2 and ADC had a significant negative correlation with pathologic iron grade (r=-0.67 to 0.77, p<0.0001). There was a significant correlation between liver T2* and ADC (r=0.83, p<0.0001)., Conclusion: Hepatic siderosis lowers liver ADC and should be taken into account when using ADC for diagnosing liver cirrhosis.