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Background and ObjectivesSuperficial siderosis, bibrachial amyotrophy, and spinal cord herniation are unusual but serious long-term sequelae of persistent spontaneous spinal CSF leaks in patients with spontaneous intracranial hypotension (SIH), particularly ventral spinal CSF leaks. However, the risk of developing such sequelae has not been established in this population. We undertook this study to determine the risk of these serious complications of persistent ventral spinal CSF leaks.MethodsThis cohort study was conducted using data from a prospectively maintained database of patients who meet the modified International Classification of Headache Disorders, 3rd edition criteria for SIH. The patient population consisted of a consecutive group of patients with SIH and persistent ventral spinal CSF leaks who were first seen within 1 year of onset of SIH symptoms and who had at least 1 year of follow-up.ResultsAmong 51 patients with SIH and a persistent ventral spinal CSF leak, superficial siderosis developed in 6 patients and bibrachial amyotrophy in 2 patients during 280 patient-years of follow-up. The probability of these complications increased from 0% at 48 months to 4.5% (95% confidence interval [CI] 1.0%–28.0%) at 56 months, 10.5% (95% CI 3.0%–36.4%) at 96 months, 32.7% (95% CI 15.0%–62.8%) at 144 months, and 57.9% (95% CI 30.2%–87.6%) at 192 months. None of the patients developed spinal cord herniation.DiscussionAmong patients with SIH and a persistent ventral spinal CSF leak, the risk of developing serious long-term sequelae is considerable. This study shows that early treatment of a ventral spinal CSF leak offers a unique opportunity to prevent neurologic disability from superficial siderosis and bibrachial amyotrophy.

Superficial siderosis refers to hemosiderin deposition along the pial surface of the brain and spinal cord. It results from chronic and repetitive low-grade bleeding into the subarachnoid space. Dural tears are a common cause of superficial siderosis. Although such tears typically occur in the spine, dural tears can also occur in the posterior fossa. In many cases, posterior fossa dural tears are iatrogenic, and patients may present with neuroimaging evidence of postoperative pseudomeningoceles. We present a case of superficial siderosis caused by a persistent posterior fossa dural leak. The patient presented with superficial siderosis 30 years after a Chiari I malformation repair. A pinhole-sized dural tear was identified preoperatively using computed tomography cisternography. The dural defect was successfully repaired. An additional small tear that was not seen on imaging was also identified at surgery and successfully repaired.

Hepatic splenosis, a rare entity, is the ectopic implantation of splenic tissue into the hepatic parenchyma, most often incidentally seen in patients with a history of splenic trauma and splenectomy. We present a unique case of hepatic splenosis in a patient with hemosiderosis and splenectomy following the incidental finding of hepatic masses on pretransplant imaging. Final diagnosis was made based on cross-sectional imaging characteristics matching that of the left upper quadrant splenules alone. We discuss common characteristics of hepatic splenosis on multiple modalities, the effect of iron deposition on the imaging characteristics of hepatic and splenic tissue and how that impacts the differential and diagnosis. This case highlights the unique imaging characteristics hepatic splenosis can have particularly in the setting of hemosiderosis. Hepatic splenosis imaging diagnosis has a significant advantage over tissue diagnosis in terms of decreased risk, time and cost.

Background: Thalassemia major anemia patients require repeated blood transfusions, which improves their survival and quality of life, however it leads to iron overload and cellular damage. Serum ferritin and liver biopsy were used classically to measure iron overload and to monitor patient response to chelation therapy. Magnetic resonance imaging (MRI T2*) has proven to be a non-invasive, effective technique in detecting and quantifying myocardial and hepatic iron overload and in adjustment of iron chelation therapy.Aim of Work: To assess myocardial siderosis among our patients using MRI T2* technique and to correlate it with hepatic iron load and left ventricular ejection fraction (LVEF).Patients and methods: Our study included 42 cases of regularly transfused patients. Hepatic and myocardial iron overload were measured by multi-breath-hold MRI T2* technique and a cine view sequence was used to assess left ventricular function (EF).Results: Myocardial and hepatic iron overload were inter-correlated to each other and correlated to left ventricular function (LVEF). There was insignificant correlation between cardiac and hepatic T2* value results (k = 0.014, P > 0.05). However, there was a progressive and significant decline in left ventricular ejection fraction (r = 0·61, P < 0·001) in patients with low cardiac T2* values (T2* < 20 ms).Conclusion: MRI T2* technique is a precise, reproducible, and non-invasive technique for measuring tissue iron concentration and sparing the patients from an invasive biopsy technique. It also benefits in early detection of cardiac dysfunction and provides a follow up tool helping in chelation therapy adjustment.

Objectives We want to report the clinical and radiological features of our cohort of patients diagnosed with cerebral amyloid angiopathy-related inflammation (CAA-RI) according to the Boston Criteria and additionally to disclose some atypical clinical characteristics observed in some of them to provide more knowledge about this novel entity. Methods We describe 5 patients with probable CAA-RI according to a validation study of proposed criteria for the diagnosis of CAA-RI at University Hospital Josep Trueta of Girona. We consider some clinical characteristics which include the response to immunotherapy, CSF findings, and MRI features. The patient’s neurologic outcomes were assessed using the modified Rankin Scale (mRS). Results We collected 5 patients admitted for probable CAA-RI. Most were women and the median age was 72 years. The median mRS score at the onset of disease was 1. Parietal lobes were most affected clinically as well as radiologically. Two patients had intracranial hemorrhage. Decreased levels of CSF amyloid beta 42 and 40 protein were observed. Corticosteroids were used in four patients and a remarkable improvement was observed in all of them. Conclusions CAA-RI is a condition that predominantly affects parietal lobes according to our case series and this involvement seems to be directly related to a greater burden of microbleeds, cortical siderosis, WMH, and lobar hemorrhages on these lobes. Decreased levels of CSF amyloid beta protein plus increased total tau protein should be considered as part of the diagnostic criteria of CAA-RI. We recommend corticosteroids using, as they have been demonstrated to be very effective in managing CAA-RI.

Immunoglobulin G4 (IgG4) -related disease (IgG4-RD) is a recently characterized entity in which lymphocytes and plasma cells infiltrate various anatomical sites. IgG4-hepatopathy, which is the manifestation of IgG4-RD, is a broader term covering various patterns of liver injury. The clinical course including the malignant potential of IgG4-RD remains unclear. Here we report the first case of secondary hemochromatosis and hepatocellular carcinoma (HCC) developed from IgG4-hepatopathy. A 67-year-old man was admitted to our hospital due to deteriorated glucose tolerance. Blood test results showed hypergammaglobulinemia, especially IgG4. He was readmitted 2 months later with dyspnea due to lung disease and pleural effusion, with elevated transaminase levels. He underwent liver and lung biopsies and was diagnosed with IgG4-RD, and received steroid therapy, which improved his serum IgG4 levels and imaging abnormalities. A follow-up computed tomography (CT) scan conducted 38 months later demonstrated a 50-mm-diameter tumor segments 7 and 8 of the liver. The resected specimen revealed HCC and abundant siderosis in the background liver, leading to a diagnosis of hemochromatosis. IgG4-positive cells were scarce, probably due to corticosteroid therapy. In the present case, IgG4-RD was well controlled with prednisolone (PSL) and immunosuppressive agent, and chronic hepatitis was not so severe, even though the patient subsequently developed HCC. However, extensive siderosis consistent with hemochromatosis was unexpectedly noted. It is suggested that secondary hemochromatosis and HCC developed during IgG4-RD with hepatopathy. Here we report the present case because it contributes to our understanding of IgG4-RD.

Sporadic cerebral amyloid angiopathy (CAA) is a common age-related cerebral small vessel disease characterized by progressive s-amyloid deposition in the walls of small cortical arteries, arterioles, and capillaries in the cerebral cortex and overlying leptomeninges. CAA-related transient focal neurological episodes (CAA-TFNEs) represent a challenging clinical feature interesting from a pathophysiological point of view. Here we present two cases of CAA-TFNEs in which we performed functional imaging with perfusion-weighted imaging MR and brain 18 F-FDG PET. In both cases, we found a topographic relationship between the involved cortical areas and the clinical expression of CAA-TFNEs. Cortical superficial siderosis in the first case and a convexity subarachnoid hemorrhage in the second case were found in the contralateral rolandic area corresponding to the clinical symptoms. The same areas showed a reduction of rCBV and rCBF on perfusion-weighted MR and were also associated in one case with hypometabolism on 18 F-FDG PET. These new findings strengthen the hypothesis that CAA involves the superficial leptomeningeal arteries but also the short penetrating arterioles reaching different depths in the cortex generating hypoperfusion and altered vascular reactivity and consequently reduced neuronal activity. Understanding CAA-TFNEs is pivotal because they carry a very high risk of subsequent lobar intracerebral hemorrhage but are frequently misdiagnosed as TIAs and treated with antithrombotics enhancing the bleeding risk associated with CAA.

Neonatal hemochromatosis is a rare condition that causes neonatal liver failure, frequently resulting in fetal loss or neonatal death. It is thought that most cases of neonatal hemochromatosis are caused by gestational alloimmune liver disease (GALD), with neonatal hemochromatosis being a phenotype of GALD rather than a disease process. Extrahepatic siderosis in the pancreas, myocardium, thyroid and minor salivary gland is a characteristic feature of neonatal hemochromatosis. There is also sparing of the reticuloendothelial system with no iron deposition in the spleen. Hepatic and extrahepatic siderosis seen in neonatal hemochromatosis is from iron dysregulation secondary to liver damage rather than iron deposition causing the liver damage. The presence of extrahepatic siderosis in the pancreas and thyroid is diagnostic of neonatal hemochromatosis and can be detected noninvasively by multi-echo gradient recalled echo (GRE) T2*-weighted sequence of MRI within hours of birth. This helps to expedite the treatment in the form of intravenous immunoglobulin and exchange transfusion, which improves the survival in these babies. The finding of hepatic siderosis is nonspecific and does not help in the diagnosis of neonatal hemochromatosis because it is seen with other causes of advanced liver disease.

Our aim was to evaluate the detectability of cortical superficial siderosis (cSS) by 3D FLAIR and 3D DIR images in comparison with the SWI images in patients with cognitive dysfunction. We studied 246 patients with cognitive dysfunction (144 women, 102 men; mean age: 75.5 ± 7.53 years) who visited a memory clinic at our hospital and underwent MR examinations at 3 T. Specifically, 16 patients with Alzheimer disease (AD) (n = 11) and AD with cerebrovascular disease (n = 5) manifested cSS based on SWI. Each set of MR images (3D FLAIR and 3D DIR) was reviewed by two reviewers separately for the detection of sulcal hyperintensity that suggested cSS. SWI detected a greater number of cSS sulci than 3D DIR and 3D FLAIR. The sensitivity and specificity for the detection of sulcal hyperintensity were the same between 3D FLAIR and 3D DIR (87.5%/100%). However, 3D DIR detected a greater number of cSS sulci than 3D FLAIR (p = .005). Our study showed that 3D DIR and 3D FLAIR can detect sulcal hyperintensity related to cSS although they are less sensitive to cSS lesions than SWI. • 3D FLAIR and 3D DIR can show sulcal signal abnormalities related to cSS in patients with cognitive dysfunction. • 3D FLAIR and 3D DIR detect sulcal hyperintensity of cSS, although they are less sensitive to cSS than SWI. • Signal alterations due to cSS are more detectable in 3D DIR than in 3D FLAIR.

Objective We aimed to characterize cortical superficial siderosis, its determinants and sequel, in community-dwelling older adults. Methods The sample consisted of Framingham ( n = 1724; 2000–2009) and Rotterdam ( n = 4325; 2005–2013) study participants who underwent brain MRI. In pooled individual-level analysis, we compared baseline characteristics in patients with cortical superficial siderosis to two reference groups: (i) persons without hemorrhagic MRI markers of cerebral amyloid angiopathy (no cortical superficial siderosis and no microbleeds) and (ii) those with presumed cerebral amyloid angiopathy based on the presence of strictly lobar microbleeds but without cortical superficial siderosis. Results Among a total of 6049 participants, 4846 did not have any microbleeds or cortical superficial siderosis (80%), 401 had deep/mixed microbleeds (6.6%), 776 had strictly lobar microbleeds without cortical superficial siderosis (12.8%) and 26 had cortical superficial siderosis with/without microbleeds (0.43%). In comparison to participants without microbleeds or cortical superficial siderosis and to those with strictly lobar microbleeds but without cortical superficial siderosis, participants with cortical superficial siderosis were older (OR 1.09 per year, 95% CI 1.05, 1.14; p 999.99; p = 0.006). During a mean follow-up of 5.6 years, 42.4% participants with cortical superficial siderosis had a stroke (five intracerebral hemorrhage, two ischemic strokes and four undetermined strokes), 19.2% had transient neurological deficits and 3.8% developed incident dementia. Conclusion Our study adds supporting evidence to the association between cortical superficial siderosis and cerebral amyloid angiopathy within the general population. Community-dwelling persons with cortical superficial siderosis may be at high risk for intracerebral hemorrhage and future neurological events.

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. T2 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.

Background and purpose Superficial siderosis of the central nervous system is a sporadic finding in magnetic resonance imaging, resulting from recurrent bleedings into the subarachnoid space. This study aimed to determine the frequency of spinal dural cerebrospinal fluid (CSF) leaks amongst patients with a symmetric infratentorial siderosis pattern. Methods In all, 97,733 magnetic resonance images performed between 2007 and 2018 in our neurocenter were screened by a keyword search for "hemosiderosis" and "superficial siderosis." Siderosis patterns on brain imaging were classified according to a previously published algorithm. Potential causative intracranial bleeding events were also assessed. Patients with a symmetric infratentorial siderosis pattern but without causative intracranial bleeding events in history were prospectively evaluated for spinal pathologies. Results Forty-two patients with isolated supratentorial siderosis, 30 with symmetric infratentorial siderosis and 21 with limited (non-symmetric) infratentorial siderosis were identified. Amyloid angiopathy and subarachnoid hemorrhage were causes for isolated supratentorial siderosis. In all four patients with a symmetric infratentorial siderosis pattern but without a causative intracranial bleeding event in history, spinal dural abnormalities were detected. Dural leaks were searched for in patients with symmetric infratentorial siderosis and a history of intracranial bleeding event without known bleeding etiology, considering that spinal dural CSF leaks themselves may also cause intracranial hemorrhage, for example by inducing venous thrombosis due to low CSF pressure. Thereby, one additional spinal dural leak was detected. Conclusions Persisting spinal dural CSF leaks can frequently be identified in patients with a symmetric infratentorial siderosis pattern. Diagnostic workup in these cases should include magnetic resonance imaging of the whole spine.

Background and Purpose: We aimed to determine whether lobar cerebellar microbleeds or concomitant lobar cerebellar and deep microbleeds, in the presence of lobar cerebral microbleeds, attribute to underlying advanced cerebral amyloid angiopathy pathology or hypertensive arteriopathy. Methods: We categorized 71 patients with suspected cerebral amyloid angiopathy markers (regardless of the presence of deep and cerebellar microbleeds) into 4 groups according to microbleed distribution: L (strictly lobar cerebral, n=33), L/LCbll (strictly lobar cerebral and strictly lobar cerebellar microbleeds, n=13), L/Cbll/D (lobar, cerebellar, and deep microbleeds, n=17), and L/D (lobar and deep, n=8). We additionally categorized patients with cerebellar microbleeds into 2 groups according to dentate nucleus involvement: strictly lobar cerebellar (n=16) and dentate (n=14). We then compared clinical characteristics, Aβ (amyloid-β) positivity on PET (positron emission tomography), magnetic resonance imaging cerebral amyloid angiopathy markers, and cerebral small vessel disease burden among groups. Results: The frequency of Aβ positivity was higher in the L and L/LCbll groups (81.8% and 84.6%) than in the L/Cbll/D and L/D groups (37.5% and 29.4%; P P =0.001). The L/LCbll group had more lobar cerebral microbleeds than the L group (93.2±121.8 versus 38.0±40.8, P =0.047). The lobar cerebellar group had a higher Aβ positivity (75% versus 28.6%, P =0.011) and lower lacune number (2.3±3.7 versus 8.6±1.2, P =0.041) than the dentate group. Conclusions: Strictly lobar cerebral and cerebellar microbleeds are related to cerebral amyloid angiopathy, whereas any combination of concurrent lobar and deep microbleeds suggest hypertensive angiopathy regardless of cerebral or cerebellar compartments.

ObjectivesCardiac T2* MRI (T2*CMR), for accurate estimation of myocardial siderosis, was introduced as part of a QI collaborative to optimise chelation therapy in order to improve cardiac morbidity in transfusion dependent thalassaemia (TDT) patients. We report the impact of this QI initiative from two thalassaemia centres from this collaborative.Design and settingA key driver based quality initiative was implemented to improve chelation in TDT patients registered at these two centres in Karachi, Pakistan. Protocol optimisation and compliance to treatment through training, communication and feedback were used as the drivers for QI intervention. Preintervention variables (demographics, chelation history, T2*CMR, echocardiography and holters) were collected from January 2015 to December 2016) and compared with variables in the post implementation phase (January to December 2019). A standardised adverse event severity for chelators and its management was devised for safe drug therapy as well as ensuring compliance to the regimen. Preintervention and postintervention variables were compared using non-parametric test. P valueResults100 patients with TDT, median age 17 (9–34) years, were included. An increase or stabilisation of T2*CMR was documented in 82% patients in the postintervention phase especially in patients with severe myocardial iron overload (5.5 vs 5.3 ms, p ConclusionThis QI initiative improved the chelation therapy leading to improved cardiac status in TDT patients at the participating centres.

Purpose The purpose of this paper is to provide a meaningful literature review about the epidemiology, pathogenesis, clinical signs, imaging and treatment of ocular siderosis (OS). Methods A computerized search from inception up to March 2020 of the online electronic database PubMed was performed using the following search strings: “ocular siderosis” and “siderosis bulbi”. The reference list in each article was analysed for additional relevant publications. Results OS is an uncommon cause of visual loss due to a retained ferrous intraocular foreign body (IOFB). It may develop from 18 days to years after a penetrating trauma that usually occurs during hammering. On average, patients are 22–25 years old, and the vast majority are male. The most common cause of OS development is delayed presentation by the patient or missed diagnosis of IOFB after trauma. The pathophysiology is not fully understood; nevertheless, iron deposition causes hydroxyl radical formation, which damages photoreceptors and retinal pigment epithelium. Moreover, iron damages retinal vessels with consequent inner retinal layers degeneration. The most frequent signs are iris heterochromia, pupillary mydriasis, cataract development and retinal arteriolar narrowing with pigmentary retinal degeneration. Electroretinogram signs, in particular, b-wave amplitude reduction, arise earlier than clinical signs. Orbital CT scans and ultrasonography play an essential role in detecting IOFBs. Treatment depends on the IOFB location and OS development. However, it is crucial to remove the IOFB after OS development because visual acuity and clinical signs may improve. Anterior segment IOFBs can be dislodged using an intraocular magnet (IOM) or forceps through limbal paracentesis. In contrast, posterior segment IOFBs require a pars plana vitrectomy and IOM or forceps to be removed through an enlarged sclerotomy or the limbus. Conclusion Recommending the usage of protective glasses and spreading knowledge about OS may further benefit patient care.

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

Purpose Α customized approach to determine R2* relaxation rate for hepatic iron concentration (HIC) estimation is presented, and is evaluated in the context of concurrent liver fat infiltration. Methods The proposed method employs a customized acquisition protocol, featuring a 16-echo, gradient-echo sequence, and a bi-exponential least squares fitting that considers baseline noise and uses a cosine function to correct for fat-induced signal oscillation. 193 patients with wide-ranging HIC and liver fat fraction (FF) were imaged at 1.5 T. In severely iron-overload patients, a four-echo train technique was applied to enforce all 16 echoes in the 1.2–4.0 ms range. Acquired data were compared to corresponding results obtained with the IDEAL IQ method. Results Techniques employed to counter the rapid signal decay in iron-overloaded liver, such as the offset and the truncation methods, have to be combined with the appropriate calibration curve to provide reliable HIC estimation. When high grade steatosis and siderosis co-exist, fat-suppression may downgrade siderosis. A high correlation was observed between data obtained with the proposed technique and the IDEAL IQ method, except from the high R2* region. However, systematic differences were detected. In the concurrent presence of high FF and non-severe iron overload, it is postulated that the bi-exponential model may attribute patient siderosis grading more accurately than IDEAL IQ, while simultaneously providing reliable FF estimation. Conclusions The proposed approach is widely available and seems capable of providing reliable R2* measurements regardless of liver steatosis grading, whilst it succeeds in averting significant R2* underestimation in severely iron-overloaded liver.

Background The key imaging features of cerebral amyloid angiopathy (CAA) are lobar, cortical, or cortico-subcortical microbleeds, macrohaemorrhages and cortical superficial siderosis (cSS). In contrast, hypertensive angiopathy is characterized by (micro) haemorrhages in the basal ganglia, thalami, periventricular white matter or the brain stem. Another distinct form of haemorrhagic microangiopathy is mixed cerebral microbleeds (mixed CMB) with features of both CAA and hypertensive angiopathy. The distinction between the two entities (CAA and mixed CMB) is clinically relevant because the risk of haemorrhage and stroke should be well balanced if oral anticoagulation is indicated in CAA patients. We aimed to comprehensively compare these two entities. Methods Patients with probable CAA according to the modified Boston criteria and mixed CMB without macrohaemorrhage were retrospectively identified from our database. Comprehensive comparison regarding clinical and radiological parameters was performed between the two cohorts. Results Patients with CAA were older (78 ± 8 vs. 74 ± 9 years, p = 0.036) and had a higher prevalence of cSS (19% vs. 4%, p = 0.027) but a lower prevalence of lacunes (73% vs. 50%, p = 0.018) and deep lacunes (23% vs. 51%, p = 0.0003) compared to patients with mixed CMB. Logistic regression revealed an association between the presence of deep lacunes and mixed CMB. The other collected parameters did not reveal a significant difference between the two groups. Conclusions CAA and mixed CMB demonstrate radiological differences in the absence of macrohaemorrhages. However, more clinically available biomarkers are needed to elucidate the contribution of CAA and hypertensive angiopathy in mixed CMB patients.

Background: Management of beta-thalassemia major (TM) requires life-long hemotransfusions leading to iron overload. Iron elimination is enhanced by the use of modern chelators. Aim: To assess the effect of modern chelation therapy by dynamics of serum ferritin concentration and liver MRI T2*. Patients and methods: Forty-six patients with TM (male to female ratio =1:1, mean age 33.2±10.9 years) were prospectively studied between 2011 and 2014. Twenty-one patients (45.7%) were treated with deferasirox, 17 (37%) – with deferiprone, and 8 (17.3%) – with deferiprone in combination with deferoxamine. Ferritin was measured by ELISA. MRI T2* was assessed by Siemens Magnetom Avanto 1.5T. The patients were allocated into 3 groups based on their initial ferritin level and liver MRI T2*. Statistical analysis was performed using SPSS v. 18 for Windows. Data were analysed by descriptive analysis, analysis of variance and correlative analysis, means were compared using t-test and one-way ANOVA. Results: In 2011, 9 (19.5%) patients had normal liver MRI T2*; in 2014 they were 17 (37%). The patients with mild grade liver siderosis were 12 (26%) in 2011, and in 2014 they were 14 (30.4%). In 2011, the patients with moderate liver siderosis were 14 (30.4%), and in 2014 – 12 (26.0%). Eleven patients (23.9%) had severe liver siderosis in 2011 and only two patients (4.0%) were diagnosed with the condition in 2014. Conclusion: A reduction of iron overload was found in all studied groups. This positive effect is attributed to the use of modern chelators and the ease of access to accurate monitoring.

Background Detection of brain-MRI T2/T2* gradient echo images (T2*GRE)-hypointensity can be compatible with iron accumulation and leads to a differential diagnosis work-up including neurodegeneration with brain iron accumulation (NBIA) and Wilson Disease. Idiopathic or secondary brain calcification can be also associated with neurological involvement and brain-MRI T2/T2*GRE-hypointensity. Hereditary hemochromatosis (HH), characterized by systemic iron loading, usually does not involve the CNS, and only sporadic cases of neurological abnormalities or brain-MRI T2/T2*GRE-hypointensity have been reported. Case presentation A 59-year-old man came to our observation after a diagnosis of HH carried out in another hospital 2 years before. First-level genetic test had revealed a homozygous HFE p.Cys282Tyr (C282Y) mutation compatible with the diagnosis of HFE-related HH, thus phlebotomy treatment was started. The patient had a history of metabolic syndrome, type-2 diabetes, autoimmune thyroiditis and severe chondrocalcinosis. Brain-MRI showed the presence of bilateral T2*GRE hypointensities within globus pallidus, substantia nigra, dentate nucleus and left pulvinar that were considered expression of cerebral siderosis. No neurological symptoms or family history of neurological disease were reported. Neurological examination revealed only mild right-sided hypokinetic-rigid syndrome. Vitamin D–PTH axis, measurements of serum ceruloplasmin and copper, and urinary copper were within the normal range. A brain computed tomography (CT) was performed to better characterize the suspected and unexplained brain iron accumulation. On the CT images, the hypointense regions in the brain MRI were hyperdense. DNA sequence analysis of genes associated with primary familial brain calcification and NBIA was negative. Conclusions This report highlights the importance of brain CT-scan in ambiguous cases of suspected cerebral siderosis, and suggests that HH patients with a severe phenotype, and likely associated with chondrocalcinosis, may display also brain calcifications. Further studies are needed to confirm this hypothesis. So far, we can speculate that iron and calcium homeostasis could be reciprocally connected within the basal ganglia.

BACKGROUND Cortical superficial siderosis (cSS) is a hemorrhagic marker of blood-brain barrier disruption detected in brain MRI. Together with cerebral microbleeds (CMB), they are recognized as a small vessel disease marker associated with cerebral amyloid angiopathy. OBJECTIVE This study aims to determine the prevalence and the characteristics of cSS in a memory clinic population. METHODS Cross-sectional retrospective analysis of 613 patients from Geneva University Hospitals memory clinic. All patients underwent standardized brain MRI and neuropsychological assessment with diagnosis confirmed by an expert. The presence of cSS was visually assessed and classified as focal (restricted to 3 sulci) or disseminated within the correspondent topography. CMB were classified according to the Microbleed Anatomical Rating Scale. RESULTS cSS was detected in 26/613 patients (4.2%), classified as disseminated in 5/26 cases (19%). Alzheimer's disease (AD) and AD associated with a significant vascular component were the diagnoses more frequently related to cSS (18/26; 69%). Patients with cSS had an increased prevalence of both hypertension (81% versus 57%; p = 0.015) and WMH burden (p = 0.012). The overall prevalence of cerebral microbleeds (69% versus 32%; p

Background and Purpose: Although evidence accumulates that the cerebellum is involved in cerebral amyloid angiopathy (CAA), cerebellar superficial siderosis is not considered to be a disease marker. The objective of this study is to investigate cerebellar superficial siderosis frequency and its relation to hemorrhagic magnetic resonance imaging markers in patients with sporadic and Dutch-type hereditary CAA and patients with deep perforating arteriopathy–related intracerebral hemorrhage. Methods: We recruited patients from 3 prospective 3 Tesla magnetic resonance imaging studies and scored siderosis and hemorrhages. Cerebellar siderosis was identified as hypointense linear signal loss (black) on susceptibility-weighted or T2*-weighted magnetic resonance imaging which follows at least one folia of the cerebellar cortex (including the vermis). Results: We included 50 subjects with Dutch-type hereditary CAA, (mean age 50 years), 45 with sporadic CAA (mean age 72 years), and 43 patients with deep perforating arteriopathy–related intracerebral hemorrhage (mean age 54 years). Cerebellar superficial siderosis was present in 5 out of 50 (10% [95% CI, 2–18]) patients with Dutch-type hereditary CAA, 4/45 (9% [95% CI, 1–17]) patients with sporadic CAA, and 0 out of 43 (0% [95% CI, 0–8]) patients with deep perforating arteriopathy–related intracerebral hemorrhage. Patients with cerebellar superficial siderosis had more supratentorial lobar (median number 9 versus 2, relative risk, 2.9 [95% CI, 2.5–3.4]) and superficial cerebellar macrobleeds (median number 2 versus 0, relative risk, 20.3 [95% CI, 8.6–47.6]) compared with patients without the marker. The frequency of cortical superficial siderosis and superficial cerebellar microbleeds was comparable. Conclusions: We conclude that cerebellar superficial siderosis might be a novel marker for CAA.

In thalassemia major, pancreatic iron was demonstrated as a powerful predictor not only for the alterations of glucose metabolism but also for cardiac iron, fibrosis, and complications, supporting a profound link between pancreatic iron and heart disease. We determined for the first time the prevalence of pancreatic iron overload (IO) in thalassemia intermedia (TI) and systematically explored the link between pancreas T2* values and glucose metabolism and cardiac outcomes. We considered 221 beta-TI patients (53.2% females, 42.95 ± 13.74 years) consecutively enrolled in the Extension–Myocardial Iron Overload in Thalassemia project. Magnetic Resonance Imaging was used to quantify IO (T2* technique) and biventricular function and to detect replacement myocardial fibrosis. The glucose metabolism was assessed by the oral glucose tolerance test (OGTT). Pancreatic IO was more frequent in regularly transfused (N = 145) than in nontransfused patients (67.6% vs. 31.6%; p < 0.0001). In the regular transfused group, splenectomy and hepatitis C virus infection were both associated with high pancreatic siderosis. Patients with normal glucose metabolism showed significantly higher global pancreas T2* values than patients with altered OGTT. A pancreas T2* < 17.9 ms predicted an abnormal OGTT. A normal pancreas T2* value showed a 100% negative predictive value for cardiac iron. Pancreas T2* values were not associated to biventricular function, replacement myocardial fibrosis, or cardiac complications. Our findings suggest that in the presence of pancreatic IO, it would be prudent to initiate or intensify iron chelation therapy to prospectively prevent both disturbances of glucose metabolism and cardiac iron accumulation.

Duodenal pseudomelanosis (also known as pseudomelanosis duodeni) is a rare endoscopic incidental finding defined by a pigmentation limited to the apex of the intestinal villi, which requires histological confirmation. While its exact pathogenesis is still poorly understood, it appears free from clinical consequences. This condition is believed to be associated with oral iron intake, antihypertensive drugs containing a sulfur moiety (i.e., hydralazine, furosemide), and several chronic diseases (i.e., hypertension, end-stage renal disease, diabetes). However, the exact prevalence of these treatments and comorbidities among patients with duodenal pseudomelanosis is not clearly defined. Several case reports and case series about duodenal pseudomelanosis have been published in recent years. In this review, we aimed to clearly define its endoscopic and microscopic presentation; its epidemiology, associated comorbidities, and drugs; the most useful special histochemical techniques used to classify the nature of the pigmentation; and the most relevant differential diagnoses. In addition, by considering our findings, we also formulated a number of hypotheses about its pathogenesis.

Background and Purpose: Intracerebral hemorrhage (ICH) is an acute manifestation of cerebral small vessel disease (CSVD), usually cerebral amyloid angiopathy or hypertensive arteriopathy. CSVD-related imaging findings are associated with increased depression incidence in the general population. Neuroimaging may, therefore, provide insight on depression risk among ICH survivors. We sought to determine whether CSVD CT and magnetic resonance imaging markers are associated with depression risk (before and after ICH), depression remission, and effectiveness of antidepressant treatment. Methods: We analyzed data from the single-center longitudinal ICH study conducted at Massachusetts General Hospital. Participants underwent CT and magnetic resonance imaging imaging and were followed longitudinally. We extracted information for neuroimaging markers of CSVD subtype and severity. Outcomes of interest included pre-ICH depression, new-onset depression after ICH, resolution of depressive symptoms, and response to antidepressant treatment. Results: We followed 612 ICH survivors for a median of 47.2 months. Multiple CSVD-related markers were associated with depression risk. Survivors of cerebral amyloid angiopathy-related lobar ICH were more likely to be diagnosed with depression before ICH (odds ratio, 1.68 [95% CI, 1.14–2.48]) and after ICH (sub-hazard ratio, 1.52 [95% CI, 1.12–2.07]), less likely to achieve remission of depressive symptoms (sub-hazard ratio, 0.69 [95% CI, 0.51–0.94]), and to benefit from antidepressant therapy ( P =0.041). Cerebral amyloid angiopathy disease burden on magnetic resonance imaging was associated with depression incidence and treatment resistance (interaction P =0.037), whereas hypertensive arteriopathy disease burden was only associated with depression incidence after ICH. Conclusions: CSVD severity is associated with depression diagnosis, both before and after ICH. Cerebral amyloid angiopathy-related ICH survivors are more likely to experience depression (both before and after ICH) than patients diagnosed with hypertensive arteriopathy-related ICH, and more likely to report persistent depressive symptoms and display resistance to antidepressant treatment.

Pulmonary siderosis is a rare occupational lung disease. Traditionally, it has been considered a "benign pneumoconiosis" because of the absence of associated clinical symptoms or pulmonary fibrosis. However, few authors have reported the evidence of pulmonary symptoms with lung fibrosis on high-resolution computed tomography and lung biopsy. Symptomatic pulmonary siderosis in scissors/knife sharpening worker has not been described in past literature. We report a case of biopsy proven symptomatic pulmonary siderosis in scissors/knife sharpening worker, who was unnecessarily treated with antitubercular therapy for 3 months.

Beta-thalassemias are a group of inherited, autosomal recessive diseases, characterized by reduced or absent synthesis of beta-globin chains of the hemoglobin tetramer, resulting in variable phenotypes, ranging from clinically asymptomatic individuals to severe anemia. Three main forms have been described: heterozygotes, homozygotes β+, and homozygotes β°. Beta-thalassemia major (β-TM), the most serious form, is characterized by an absent synthesis of globin chains that are essential for hemoglobin formation, causing chronic hemolytic anemia. Cardiac complications represent a leading cause of mortality in β-TM patients, although an important and progressive increase of life expectancy has been demonstrated after the introduction of chelating therapies. Iron overload is the primary factor of cardiac damage resulting in thalassemic cardiomyopathy, in which diastolic dysfunction usually happens before systolic impairment and overt heart failure (HF). Although iron-induced cardiomyopathy is slowly progressive and it usually takes several decades for clinical and laboratory features of cardiac dysfunction to manifest, arrhythmias or sudden death may be present without signs of cardiac disease and only if myocardial siderosis is present. Careful analysis of electrocardiograms and other diagnostic tools may help in early identification of high-risk β-TM patients for arrhythmias and sudden cardiac death.

Cerebral amyloid angiopathy (CAA) might disturb the sensitive mechanism of cerebral pressure autoregulation. This study examines whether dynamic cerebral autoregulation (CA) is impaired in the posterior or anterior circulation of CAA patients. Fifteen patients with known CAA on magnetic resonance imaging (MRI) and 14 age-matched controls were examined with transcranial Doppler. Dynamic CA was assessed in the middle (MCA) and posterior cerebral artery (PCA) via transfer function phase and gain during respiratory-induced 0.1 Hz oscillations of arterial pressure. Within the patient group, 4 patients showed additional microbleeds in the basal ganglia on the MRI performed within the study (pure CAA vs mixed microbleeds). PCA phase was significantly lower in patients compared with controls (p = 0.018), particularly in patients with pure CAA (p = 0.0034). MCA values showed a similar but non-significant trend towards lower phase in patients with pure CAA. Poorer phase was associated with a higher number of microbleeds on MRI (MCA r = −0.57, p = 0.027; PCA r = −0.52, p = 0.098) and superficial cortical siderosis (PCA: p = 0.0025). In conclusion, dynamic cerebral autoregulation is impaired in patients with CAA. The degree of impairment is associated with the extent of cerebral microbleeds.

Patient: Male, 77 Final Diagnosis: Cerebral amyloid angiopathy Symptoms: Aphasia • hemiparesis Medication: — Clinical Procedure: Hematoma evacuation Specialty: Neurosurgery Objective: Unusual clinical course Background: Cerebral amyloid angiopathy (CAA) results from progressive deposition of amyloid-β in the walls of cortical and leptomeningeal vessels, leading to CAA-associated intracerebral hemorrhage (ICH). Hematoma expansion is a common early complication of spontaneous ICH, and is a strong independent predictor of poor outcome. However, there are limited reports of hematoma expansion related to CAA-associated ICH. Herein, we describe a novel case of hematoma expansion with a fluid-blood level in the cystic cavity of CAA-associated ICH. Case report: A 76-year-old male was initially diagnosed with probable CAA according to the modified Boston criteria, and presented with lobar ICH in the left frontal lobe 4 months later. Admission computed tomography scans showed an ICH including a high-density hematoma within a cystic cavity, revealing a clearly lower-density fluid component. Serial computed tomography scans showed no evidence of an expansion of the high-density clot, but obvious expansion of the fluid component containing a fluid-blood level. We recognized a bleeding site with no enhancement on preoperative magnetic resonance imaging. Left frontal craniotomy revealed a liquefied hematoma, which was removed by suction. We subsequently evacuated the blood clot extending into the left frontal sulcus, and confirmed and cauterized the bleeding site, leading to successful hemostasis. Conclusions: We report a CAA-associated ICH case showing hematoma expansion with a fluid-blood level. Intraparenchymal fluid-blood level suggests extravasation of blood into pre-existing cystic cavities because of hematoma lique-faction. Thus, fluid-blood levels are an important finding of hematoma expansion in acute CAA-associated ICH, and early treatment should be considered.

Background and Purpose— We investigated cortical superficial siderosis (cSS) progression and its clinical relevance for incident lobar intracerebral hemorrhage (ICH) risk, in probable cerebral amyloid angiopathy presenting with neurological symptoms and without ICH at baseline. Methods— Consecutive patients meeting modified Boston criteria for probable cerebral amyloid angiopathy from a single-center cohort who underwent magnetic resonance imaging (MRI) at baseline and during follow-up were analyzed. cSS progression was assessed by comparison of the baseline and follow-up images. Patients were followed prospectively for incident symptomatic ICH. cSS progression and first-ever ICH risk were investigated in Cox proportional hazard models adjusting for confounders. Results— The cohort included 118 probable cerebral amyloid angiopathy patients: 72 (61%) presented with transient focal neurological episodes and 46 (39%) with cognitive complaints prompting the baseline MRI investigation. Fifty-two patients (44.1%) had cSS at baseline. During a median scan interval of 2.2 years (interquartile range, 1.2–4.4 years) between the baseline (ie, first) MRI and the latest MRI, cSS progression was detected in 33 (28%) patients. In multivariable logistic regression, baseline cSS presence (odds ratio, 4.04; 95% CI, 1.53–10.70; P =0.005), especially disseminated cSS (odds ratio, 9.12; 95% CI, 2.85–29.18; P P =0.017) were independent predictors of cSS progression. For patients without an ICH during the interscan interval (n=105) and subsequent follow-up (median postfinal MRI time, 1.34; interquartile range, 0.3–3 years), cSS progression independently predicted increased symptomatic ICH risk (hazard ratio, 3.76; 95% CI, 1.37–10.35; P =0.010). Conclusions— Our results suggest that cSS evolution may be a useful biomarker for assessing disease progression and ICH risk in cerebral amyloid angiopathy patients and a candidate biomarker for clinical studies and trials.

Background Superficial siderosis (SS) associated with craniopharyngioma is an extremely rare occurrence. To our knowledge, only 3 cases have been reported in literature. Two of the cases occurred following resection of the tumor. Similar to the present case, 1 of the cases was discovered before surgical intervention, “pure tumor-related” SS. The clinical presentation, diagnosis, management, and outcome are discussed in this article. Case Description A 50-year-old man presented with an 11-month history of left-sided tinnitus, hearing impairment, and a 2-month history of visual disturbance. Cerebellar ataxia and gait disturbance were found on examination. Brain magnetic resonance imaging findings were consistent with SS. Cerebrospinal fluid (CSF) analysis before surgery revealed xanthochromia confirming an existing chronic sustainable subarachnoid hemorrhage. He underwent a tumor resection in endoscopic endonasal approach followed by stereotactic radiosurgery. On follow-up, the visual symptoms resulting from craniopharyngioma subsided, whereas hearing impairment, cerebellar ataxia, and gait disturbance associated with SS did not progress but were unchanged despite subsequent evidence of watery-clear CSF. Conclusions In the present case, SS could be associated with craniopharyngioma on the basis of CSF findings and clinical symptoms. Detection and early treatment aimed at eliminating the bleeding source offer the best chance of halting the disease process.

The aim of this study was to evaluate the vitamin D-PTH axis in thalassemia major (TM) in relation to hepatic siderosis liver iron content.In this case-controlled observational study, vitamin D-PTH axis was studied in 158 TM and 84 age and ethnicity-matched healthy nonthalassemic controls attending University College Hospital, London. Patients were classified as 25-hydroxy vitamin D (25-OHD) insufficient and sufficient if the value was less than or greater than 50 nmol/L, respectively. 25-OHD data were evaluated in relation to markers of iron load in TM.In TM, 25-OHD insufficiency was 8-fold higher than the control group (odds ratio [OR], 8.1; 95% confidence interval [CI], 4.3-15.0; P0.001). Similarly, serum PTH (P0.001), calcium (P0.001), and phosphate levels (P0.05) were also significantly lower in TM compared with the controls. In TM, serum ferritin of2500 μg/L (OR, 5.3; 95% CI, 2.3-12.3; P0.01), liver iron of7 mg/g dry weight (OR, 8.8; 95% CI, 3.5-10.3; P0.001), and serum alanine aminotransferase of50 IU/L (OR, 9.7; 95% CI, 4.0-23.5; P0.001) were independent risk factors for low 25-OHD levels.Our results suggest that TM had a 8-fold higher risk of 25-OHD insufficiency compared with the controls. This was likely to be associated with hepatic hemosiderosis.

Background: Thalassemia patients have diabetes mellitus subaltern to hemosiderosis.Aim of Study: To asses iron overload in pancreas of pediatrics beta-thalassemia major patients by T2*-Gradient-echo Magnetic Resonance Imaging (MRI) and to study corre-lation of results of data of MRI with affection with diabetes, serum ferritin level, hepatic hemosiderosis, and spleen removal.Methods: 20 (3-thalassemia major patients with regular blood transfusion (11 males and 9 females) follow-up at the Hematology Clinic, Children's Hospital, Tanta University.Results: Striking reduction in hepatic and pancreatic Signal Intensity Ratio (SIR) was appeared in thalassemic patients contrasted with controls (p

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.

Purpose: High-resolution vessel wall magnetic resonance imaging (VW-MRI) could provide a way to identify high risk arteriovenous malformation (AVM) features. We present the first pilot study of clinically unruptured AVMs evaluated by high-resolution VW-MRI.Methods: A retrospective review of clinically unruptured AVMs with VW-MRI between January 1, 2016 and December 31, 2018 was performed documenting the presence or absence of vessel wall “hyperintensity,” or enhancement, within the nidus as well as perivascular enhancement and evidence of old hemorrhage (EOOH). The extent of nidal vessel wall “hyperintensity” was approximated into five groups: 0, 1–25, 26–50, 51–75, and 76–100%.Results: Of the nine cases, eight demonstrated at least some degree of vessel wall nidus “hyperintensity.” Of those eight cases, four demonstrated greater than 50% of the nidus with hyperintensity at the vessel wall, and three cases had perivascular enhancement adjacent to nidal vessels. Although none of the subjects had prior clinical hemorrhage/AVM rupture, of the six patients with available susceptibility weighted imaging to assess for remote hemorrhage, only two had subtle siderosis to suggest prior sub-clinical bleeds.Conclusion: Vessel wall “enhancement” occurs in AVMs with no prior clinical rupture. Additional studies are needed to further investigate the implication of these findings.

Background Deferoxamine retinopathy is the informally designated term used to describe a characteristic pattern of outer retinal degeneration in iron-overloaded chronic anemia patients who are treated with deferoxamine. We hypothesize that insufficiently treated iron overloading and not only deferoxamine is the cause of the retinal degeneration. Our case report is based on exposure histories of two anemia patients and literature review. Case presentation Both anemia patients presented with bilateral visual loss secondary to photoreceptor and retinal pigment epithelium degeneration. Chart review showed that visual loss came after a year-long slow, and rather monotonous rise in plasma ferritin concentrations, with no obvious relation to iron chelator exposure. In one patient, the onset of symptomatic visual loss came after a bout of fever followed by two additional febrile episodes, all accompanied by plasma ferritin spikes. Adjustment of iron chelation therapy did not improve visual function. Experimental studies clearly show that both systemic and intraocular exposure to iron ions can induce retinal degeneration. Conclusion The available evidence indicates that retinal degeneration in chronic anemia patients treated by deferoxamine is cause by insufficient iron chelation, not by deferoxamine. The actual role of iron chelating agents may be to promote a long enough survival to allow the slow development of retinal siderosis.

In Alzheimer's disease, the apolipoprotein E gene (APOE) ε2 allele is a protective genetic factor, whereas the APOE ε4 allele is a genetic risk factor. However, both the APOE ε2 and the APOE ε4 alleles are genetic risk factors for lobar intracerebral hemorrhage. The reasons for the high prevalence of lobar intracerebral hemorrhage and the low prevalence of Alzheimer's disease with the APOE ε2 allele remains unknown. Here, we describe the case of a 79-year-old Japanese female with Alzheimer's disease, homozygous for the APOE ε2 allele. This patient presented with recurrent lobar hemorrhages and multiple cortical superficial siderosis. The findings on the 11C-labeled Pittsburgh Compound B-positron emission tomography (PET) were characteristic of Alzheimer's disease. 18F-THK5351 PET revealed that the accumulation of 18F-THK 5351 in the right pyramidal tract at the pontine level, the cerebral peduncle of the midbrain, and the internal capsule, reflecting the lesions of the previous lobar intracerebral hemorrhage in the right frontal lobe. Moreover, 18F-THK5351 accumulated in the bilateral globus pallidum, amygdala, caudate nuclei, and the substantia nigra of the midbrain, which were probably off-target reaction, by binding to monoamine oxidase B (MAO-B). 18F-THK5351 were also detected in the periphery of prior lobar hemorrhages and a cortical subarachnoid hemorrhage, as well as in some, but not all, areas affected by cortical siderosis. Besides, 18F-THK5351 retentions were observed in the bilateral medial temporal cortices and several cortical areas without cerebral amyloid angiopathy or prior hemorrhages, possibly where tau might accumulate. This is the first report of a patient with Alzheimer's disease, carrying homozygous APOE ε2 allele and presenting with recurrent lobar hemorrhages, multiple cortical superficial siderosis, and immunohistochemically vascular amyloid β. The 18F-THK5351 PET findings suggested MAO-B concentrated regions, astroglial activation, Waller degeneration of the pyramidal tract, neuroinflammation due to CAA related hemorrhages, and possible tau accumulation.

Despite declining rates worldwide, autopsy studies remain invaluable tools to expand existing knowledge on the pathophysiology of diseases, especially those with multisystem involvement. β-thalassemia major (β-TM) is a relatively common hemoglobinopathy in India and is characterized by a regular requirement for life-sustaining transfusions and chelation. The iron overload is an invariable side effect. This secondary hemosiderosis leads to several complications, primarily in the heart, liver, pancreas, and endocrine organs. Despite adequate transfusion and chelation, untransplanted patients may show early mortality for several reasons. We report a 10-year-old boy with β-TM who died with clinical possibilities of iron overload-related cardiac failure and pulmonary arterial hypertension. His autopsy revealed certain unique disease pathologies in the form of minimal cardiac fibrosis in the presence of significant cardiac siderosis and widespread endocrine damage due to iron-overload. A null-cell pituitary microadenoma, previously undescribed in thalassemia syndromes, was found. This report highlights the importance of the diminishing art of autopsy, without which these histopathological insights would not have emerged.

Superficial siderosis is a rare neurodegenerative disease caused by hemosiderin deposition on the brain surface. Although the efficacy of the iron chelator—deferiprone—in superficial siderosis has recently been documented, a comparative study of patients who underwent surgical ablation of their bleeding source and subsequently received treatment with or without deferiprone has not yet been conducted. Fifteen postoperative patients with superficial siderosis were recruited, and seven patients were administered deferiprone (combination therapy group). Quantitative changes in the hypointense signals on T2*-weighted magnetic resonance images were acquired; additionally, cerebellar ataxia was assessed (International Cooperative Ataxia Rating Scale score and Scale for the Assessment and Rating of Ataxia). Audiometry was performed and the results were compared with those of patients who did not receive deferiprone (surgical treatment group; controls). Significant improvements in signal contrast ratios were noted in the lateral orbitofrontal gyrus, superior temporal lobe, insular lobe, brainstem, lingual gyrus, and cerebellar lobe in the combination therapy group. The scores of patients in the combination therapy group on the cerebellar ataxia scales significantly improved. The degree of signal improvement in the cerebellar lobe correlated with the improvement of cerebellar ataxia scores. Early deferiprone administration after disease onset and long-term administration were correlated with greater signal improvements on magnetic resonance imaging. No adverse effects were observed in the clinical or laboratory parameters. Deferiprone administration significantly improved radiological and clinical outcomes in patients with postoperative superficial siderosis. Earlier and longer courses of deferiprone could result in better patient prognosis.

Cardiac hemosiderosis is the primary factor to derive the pathogenesis of cardiac dysfunction in patients with transfusion dependent thalassemia. Biomarkers assessment along with T2 * MRI study could be employed to evaluate the severity of iron deposition-related damage and determination of the diagnostic and prognostic value of these inflammatory factors. The study was conducted on 62 patients (12–44 years old) with major thalassemia. The patients were under regular blood transfusion and they had no signs of cardiac defects, and chronic diseases. The serum levels of inflammatory factors (NT-proBNP, CRP, Copeptin HS) were determined before routine transfusion. Cardiac iron overload was assessed by T2* MRI (within the last three months), and T2* lower than 20 ms was considered as cardiac siderosis. The obtained results were analyzed using statistical methods. 92% of patients showed an increased level of hs-CRP (> 2 µg/dL). All cases showed increased levels of NT-proBNP (> 150 pg/mL). Only 29% of subjects showed high level of Copeptin, 25.8% of patients demonstrated cardiac siderosis based on the T2* MRI (

Superficial siderosis describes haemosiderin deposition on the surface of the brain. When present on infratentorial structures, it can cause ataxia, sensorineural hearing loss and pyramidal signs. There is no proven treatment and patients experience slow progression of symptoms. Iron-chelating agents have been suggested as a therapeutic option and deferiprone is suited as it crosses the blood-brain barrier. However, deferiprone is reported to have a 1–2% risk of agranulocytosis. We performed a systematic review on treatment of infratentorial superficial siderosis with deferiprone based on PRISMA guidelines. Studies were included if in English or an English language translation was available, were about human subjects and referred to patients with ataxia. Studies were excluded if they did not possess an English translation, included animal studies or did not have ataxia. Studies were excluded if they discussed cerebral amyloid angiopathy or siderosis of other regions. Eleven papers were included. We identified 69 patients. Seventeen patients (25%) discontinued the drug. The most encountered adverse effect was anaemia (21.7%). Neutropaenia was observed in 8.7% and agranulocytosis in 5.8% of patients. Clinically, response varied, and stability or improvement was seen across neurological domains in 6 studies while 5 showed a mixed response. On imaging, 13 (28.9%) patients improved, 24 (53.3%) stabilised and 8 (17.8%) deteriorated. A prospective international centralised register of patients should be developed to inform the design and conduct of a multicentre, placebo-controlled, randomised clinical trial to evaluate the efficacy of deferiprone. The evidence from this systematic review is that deferiprone is a promising intervention.

Superficial siderosis is a disease in which iron from hemoglobin is deposited in the central nervous system, resulting in conditions such as progressive sensorineural hearing loss, cerebellar ataxia, dementia, and pyramidal signs. A 30-year-old man with superficial siderosis received a cochlear implant in the left ear, which had shown complete hearing loss. Good auditory responses were obtained at 14 days after implantation. The postoperative average hearing level with the cochlear implant was 56.7 dB at 3 months and 55.0 dB at 6 months. However, the patient showed gradual hearing loss, and the dynamic range changed each time the electrode parameters were adjusted. To assess residual hearing ability, single-photon emission computed tomography was performed together with an assessment of electrical auditory brainstem response, which showed a good response and increased blood flow in both the temporal lobes. Based on this result, we asked the patient to continue using the cochlear implant to see whether a perception of speech response would be obtained. However, the patient discontinued using the cochlear implant because he could not hear satisfactorily. Hearing outcomes after cochlear implant surgery for patients with superficial siderosis are not necessarily good. Therefore, the possibility of unsatisfactory results should be fully explained before recommending this surgery to patients.

Patient: Male, 38-year-old Final Diagnosis: Intraocular foreign body Symptoms: Visual field defect Medication: — Clinical Procedure: Intraocular foreign body removal Specialty: Ophthalmology Objective: Unusual clinical course Background: Ocular siderosis is an uncommon cause of vision loss due to a retained ferrous intraocular foreign bodies (IOFB) that cause iron deposition in ocular tissues. The most common manifestations are cataract formation, diffuse pigmentary changes of the retinal pigment epithelium, iris heterochromia, dilated pupils, secondary glaucoma, iritis, and cystoid macular edema. Case Report: We report a case of 38-year-old man who presented with a left dilated pupil and visual field defect. Neurological examination results were normal. Brain magnetic resonance imaging revealed a gross artifact at the site of the left globe. The visual field test showed a peripheral arcuate nasal visual field defect in the left eye. Ophthalmic examination revealed peripheral pigmentary changes and a black elongated and elevated lesion located very anterior and inferior-temporal and attached to the retina with fibrous tissue. A computed tomography scan revealed a 1×1-mm-round hyperdense IOFB in the left vitreous cavity. The diagnosis of siderosis bulbi secondary to a missed IOFB was established. The patient underwent a pars plana vitrectomy for removal of the IOFB. Two weeks later, rhegmatogenous retinal detachment developed, and repair with silicon oil injection was done. One year after the last operation, the best corrected visual acuity in the left eye was 6/120, with normal intraocular pressure and an attached posterior pole. Conclusions: This case highlights the importance of investigating for a retained IOFB in cases of unilateral retinitis pigmentosa changes.

Objective: Cardiac T2* magnetic resonance imaging (MRI) has recently attracted considerable attention as a non-invasive method for detecting iron overload in various organs in thalassemia major patients. This study aimed to identify the prevalence of cardiac siderosis in thalassemia major patients and evaluate cardiac T2* MRI for monitoring cardiac siderosis before and after patients receive iron chelation therapy and its relation to serum ferritin, left ventricular ejection fraction, and liver iron concentration. The information gathered would be used for the direct monitoring, detection, and treatment of complications early on. Methods: A total of 119 thalassemia major patients were recruited in the present study. The cardiac T2* MRI was compared to serum ferritin levels, liver iron concentration (LIC), and left ventricular ejection fraction. All patients were classified into four groups based on their cardiac siderosis as having normal, marginal, mild to moderate, or severe cardiac iron overload. At the follow-up at years one, three, and five, the cardiac T2* MRI, LIC, serum ferritin, and left ventricular ejection fraction (LVEF) were determined. Results: The prevalence of cardiac siderosis with cardiac T2* MRI ≤ 25 ms was 17.6% (n = 21). There was no correlation between cardiac T2* MRI and serum ferritin, liver iron concentration, and LVEF (p = 0.39, 0.54, and 0.09, respectively). During one year to five years’ follow-up periods, cardiac T2* MRI (ms) in patients with severe cardiac siderosis had significantly improved from 8.5 ± 1.49 at baseline to 33.9 ± 1.9 at five years (p &lt, 0.0001). Patients with severe, mild-moderate, marginal, and no cardiac siderosis had median LIC (mg/g dw) of 23.9 ± 6.5, 21.6 ± 13.3, 25.3 ± 7.7, and 19.9 ± 5.5 at baseline, respectively. Conclusions: This study supports the use of cardiac T2* MRI to monitor cardiac iron overload in patients who have had multiple blood transfusions. Early diagnosis and treatment of patients at risk of cardiac siderosis is a reasonable method of reducing the substantial cardiac mortality burden associated with myocardial siderosis. Cardiac T2* MRI is the best test that can identify at-risk patients who can be managed with optimization of their chelation therapy.

Superficial siderosis is a rare disorder characterised by the deposition of haemosiderin on the surface of the central nervous system. Cognitive dysfunction has sporadically been reported in relation with superficial siderosis. We present a 61-year-old man with cognitive dysfunction in the presence of the typical radiological image of temporal and cerebellar superficial siderosis, most likely due to pseudomeningocoele 14 years after resection of a meningioma at the cervicothoracic junction. Xantochromia was present on cerebrospinal fluid investigation and a source of bleeding was seen during surgical exploration. Despite surgical treatment of the suspected bleeding source, the patient deteriorated and neuropsychological examination 1 year after surgery showed progression of cognitive dysfunction to dementia. It is likely that in the absence of other typical symptoms such as cerebellar ataxia and hearing loss, the cognitive dysfunction was not related to the superficial siderosis.

BACKGROUND: Diabetes mellitus affects more than a quarter of patients with thalassemia major (TM) worldwide, and increases the risk for cardiac complications, contributing to significant morbidity. Pancreatic iron overload (IO) and fat infiltration have been correlated with this endocrinal complication in adult TM patients. It has been shown that in adult TM patients, iron accumulation and fat infiltration are found to be heterogeneous in the pancreatic head, body, and tail region. R2* and a fat fraction (FF) generated by gradient-echo imaging can be used as quantitative parameters to assess the iron and fat contents of the pancreas. This study aimed to determine the pattern of pancreatic iron accumulation and fat infiltration in pediatric TM patients with gradient-echo imaging and evaluate the association between pancreatic IO and fat infiltration and glucose disturbances. METHODS: A total of 90 children with TM (10.7±3.1 years) were included. All patients underwent pancreatic magnetic resonance imaging (MRI) using multi-echo gradient-echo sequences. IO was measured by R2* relaxometry in 90 patients, and FF values were measured using iterative decomposition of water and fat with echo asymmetry and the least-squares estimation (IDEAL) method in 40 patients. R2* and FF were assessed in the pancreatic head, body, and tail. The global R2* and global FF values were obtained by averaging the respective values from the pancreatic head, body, and tail. The correlations between global R2*, global FF, and fasting glucose were determined using Spearman’s correlation analysis. The Friedman test was used to compare R2* and FF among different pancreatic regions. Receiver operating characteristic (ROC) analysis was used to determine the performance of global R2* and global FF in discriminating impaired fasting glucose from normal fasting glucose patients. RESULTS: The global R2* was positively correlated with the global FF in the pancreas (r=0.895, P

To define the neuropsychological and neuroimaging characteristics of classical infratentorial superficial siderosis (iSS), a rare but disabling disorder defined by hemosiderin deposition affecting the superficial layers of the cerebellum, brainstem and spinal cord, usually associated with a slowly progressive neurological syndrome of deafness, ataxia and myelopathy. We present the detailed neuropsychological and neuroimaging findings in 16 patients with iSS (mean age 57 years; 6 female). Cognitive impairment was present in 8/16 (50%) of patients: executive dysfunction was the most prevalent (44%), followed by impairment of visual recognition memory (27%); other cognitive domains were largely spared. Disease symptom duration was significantly correlated with the number of cognitive domains impaired (r = 0.59, p = 0.011). Mood disorders were also common (anxiety 62%, depression 38%, both 69%) but not associated with disease symptom duration. MRI findings revealed siderosis was not only in infratentorial brain regions, but also in characteristic widespread symmetrical supratentorial brain regions, independent of disease duration and degree of cognitive impairment. The presence of small vessel disease markers was very low and did not account for the cognitive impairment observed. Neuropsychological disturbances are common in iSS and need to be routinely investigated. The lack of association between the anatomical extent of hemosiderin and cognitive impairment or disease duration suggests that hemosiderin itself is not directly neurotoxic. Additional biomarkers of iSS disease severity and progression are needed for future research and clinical trials.