RARE DISEASE
Superficial siderosis
Superficial siderosis
Superficial siderosis
Synonyms: Hemosiderosis of the central nervous system, Superficial hemosiderosis of the CNS, Superficial hemosiderosis of the central nervous system, Superficial siderosis of the CNS, Superficial siderosis of the central nervous system
Synonyms: Hemosiderosis of the central nervous system, Superficial hemosiderosis of the CNS, Superficial hemosiderosis of the central nervous system, Superficial siderosis of the CNS, Superficial siderosis of the central nervous system
Synonyms: Hemosiderosis of the central nervous system, Superficial hemosiderosis of the CNS, Superficial hemosiderosis of the central nervous system, Superficial siderosis of the CNS, Superficial siderosis of the central nervous system
Drug discovery
1
drug
With orphan designation
Overview
Superficial siderosis (SS) is a rare neurodegenerative disorder caused by chronic subarachnoid hemorrhage, leading to iron deposition in the CNS. It presents with progressive sensorineural hearing loss (80-95% of cases), cerebellar ataxia, and myelopathy. Diagnosis relies on MRI showing characteristic hemosiderin deposits, particularly on susceptibility-weighted imaging [1][4][16]. Management involves identifying and repairing bleeding sources (e.g., dural defects) and iron chelation therapy [1][3][13].
Burden
Progressive disability from irreversible hearing loss, gait impairment, and cognitive decline [4][16][17].
Associated with 7-fold increased dementia risk in Alzheimer’s cohorts and higher stroke incidence [9][12].
Limited treatment efficacy: 60% of patients experience functional decline despite therapy [4][13][17].
Therapies
Surgical intervention: Repair of dural tears or pseudomeningoceles to halt bleeding [1][13].
Iron chelation: Deferiprone (30 mg/kg/day) reduces hemosiderin deposition but lacks robust efficacy data [3][8].
Multidisciplinary care: Coordinated management of hearing, balance, cognition, and bladder dysfunction [1][6].
Categories: rare neurological diseases
Research Papers
178 drug discovery papers about Superficial siderosis, with 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
178 drug discovery papers about Superficial siderosis, with 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
cell therapies
2025-12-29 | Progressive Bilateral Sensorineural Hearing Loss and Ataxia Caused by Superficial Siderosis Secondary to Chronic Spontaneous Intracranial Hypotension.
Superficial siderosis (SS) is an uncommon neurodegenerative disorder resulting from persistent or repeated bleeding into the subarachnoid space, which causes hemosiderin to accumulate along the subpial surfaces of the brain, brainstem, spinal cord, and cranial nerves. Chronic spontaneous intracranial hypotension (SIH) due to a dural tear is an uncommon but treatable condition. We report a 51-year-old man with a seven-year history of progressive bilateral sensorineural hearing loss, disabling gait ataxia, vertigo, tinnitus, and facial numbness. Ten years earlier, he had experienced a prolonged, classical orthostatic headache lasting four to six months, which resolved after unspecified treatment. Magnetic resonance imaging (MRI) of the brain revealed features of SS involving the posterior fossa, and an MRI whole-spine survey with fat-suppressed sampling perfection with application-optimized contrasts (SPACE) sequence identified a cervicodorsal, longitudinally extensive extradural cerebrospinal fluid (CSF) collection. The brain MRI also demonstrated a reduced ponto-mesencephalic angle, consistent with intracranial hypotension. A diagnosis of SS secondary to chronic SIH from a spinal dural tear was made. He underwent an autologous epidural blood patch, followed by a second patch, which resulted in symptomatic stabilization, along with iron chelation and corticosteroid therapy. This case highlights the importance of recognizing SS as a delayed complication of untreated SIH. Timely identification and repair of dural defects can halt progression and potentially reverse neurological deficits.
2010-09-01 | Cochlear implantation in a patient with superficial siderosis: an update
The purpose of this study is to present follow-up on a previously reported case of successful cochlear implantation in a patient with superficial siderosis.Retrospective case review.For the first 6 years after implantation, the patient had maintained a successful result; however, she developed a progressive decline in the benefit from her implant.Benefit from cochlear implants in patients with superficial siderosis is variable and may not be long standing.
2002-07-01 | Cochlear Implantation in a Patient with Superficial Siderosis of the Central Nervous System
Objective To perform an assessment of the viability of cochlear implantation in a patient with superficial siderosis of the brain. Study Design Case review. Setting Tertiary referral center. Patients Patient with superficial siderosis of the brain. Intervention Cochlear implantation. Main Outcome Measures Electrically evoked auditory brainstem responses and fitting strategy for cochlear implant based on patient's subjective responses. Results After some time, C levels and T levels showed a pattern comparable with the evoked auditory brainstem responses. Conclusions Bilateral profound hearing loss after superficial siderosis of the brain is no absolute contraindication for implantation. Furthermore, evoked auditory brainstem measurements can potentially guide the fitting process of the implant in difficult cases.
small molecules
2026-03-06 | Quantitative evaluation of iron chelator effects on central motor and sensory tracts in superficial siderosis.
Superficial siderosis (SS) is a rare neurodegenerative disease characterized by hemosiderin deposition in the central nervous system, leading to progressive neuronal degeneration. Although myelopathy is a main clinical manifestation in SS, objective biomarkers for monitoring disease progression and treatment remain unclarified. We assessed electrophysiology of central motor and sensory conduction in patients with SS before and after iron chelator administration. In this controlled trial, we evaluated 12 patients with SS (mean follow-up: 33.6 months [range: 18.9-36.1]), who underwent dural repair, and 9 with multiple sclerosis as controls. Transcranial magnetic stimulation (TMS) and somatosensory evoked potentials (SEPs) were used to assess motor and sensory conduction, respectively. Eight patients with SS received oral iron chelator deferiprone (1,500 mg/day), whereas four underwent surgical repair without iron chelation. Primary outcomes were changes in central motor conduction time (CMCT), motor evoked potential (MEP) amplitude, and central sensory conduction time (CCT). At baseline, 92 and 100% of patients with SS exhibited prolonged CMCT and CCT, respectively. Prolonged conduction in patients with SS was less severe than in those with multiple sclerosis (MS). Whereas MEP amplitude and the amplitude ratio of MEP to CMAP were relatively preserved in patients with SS. After 36-month iron chelator administration, statistically significant improvement of central motor conduction time was gained in patients with SS. TMS and SEP are sensitive tools for evaluating central conduction impairment in SS. The conduction abnormality, likely caused by a different pathomechanism from that in MS, is partially recoverable by iron chelator administration. CMCT improvement demonstrates partial reversibility of impaired motor pathway and supports the therapeutic potential of iron chelator therapy in SS.
2025-09-25 | Corticosteroid Treatment and Hemorrhage Risk in Cerebral Amyloid Angiopathy with Cortical Superficial Siderosis: A Matched Cohort Analysis
Abstract Cortical superficial siderosis (cSS) is the strongest marker of future intracranial hemorrhage (ICH) in cerebral amyloid angiopathy (CAA), a condition without disease-modifying therapy. Emerging evidence suggests that cSS may reflect meningovascular inflammation potentially amenable to immunosuppression. We conducted a single-center matched cohort study comparing high-dose corticosteroid therapy versus no immunosuppression in patients with probable CAA and cSS. Treated patients were matched 1:2 to untreated patients by demographics, cSS multifocality, and baseline intracerebral hemorrhage. The primary outcome was incident ICH; secondary outcomes were any cerebrovascular event and mortality. Kaplan–Meier analysis assessed event-free survival. cSS progression was evaluated in patients with ≥6 months MRI follow-up, and inflammation in a subgroup with post-contrast vessel-wall-imaging (VWI). Thirty-six patients were included (12 treated, 24 untreated; mean age 77.4 years; 91% disseminated cSS). Over a median follow-up of 2.23 years, 11 patients had cerebrovascular events (15 ICHs, 3 ischemic strokes), all in the untreated group (p=0.041 for ICH; p=0.037 for any event). Mortality did not differ (p=0.634). cSS progressed in 2/6 (33%) treated versus 4/7 (57%) untreated patients. Baseline VWI detected inflammation in 7/9 patients (78%), which regressed after corticosteroids. Corticosteroid therapy was associated with fewer cerebrovascular events in high-risk CAA, supporting prospective controlled validation.
2025-09-02 | When Blood Leaves a Trace: Diagnosing Superficial Siderosis in a Geriatric Patient.
Superficial siderosis (SS) is a rare neurodegenerative condition caused by chronic or recurrent bleeding into the subarachnoid space, leading to the deposition of hemosiderin in the subpial layers of the brain, brainstem, spinal cord, or cranial nerves. SS is categorized into two main forms based on its anatomical distribution: cortical superficial siderosis (cSS) and infratentorial superficial siderosis (iSS). Among these, iSS is further subdivided into Type 1 (classical iSS) and Type 2 (secondary iSS). Classical iSS refers to cases in which there is no radiologically confirmed single spontaneous or traumatic intracranial hemorrhage and is typically associated with chronic bleeding sources, such as cranial or spinal dural defects. In contrast, secondary iSS is characterized by the presence of a radiologically identifiable single intracranial hemorrhagic event, either spontaneous or traumatic, which is considered the likely cause of the siderosis. Patients typically present with SS in the fourth to sixth decades of life. The prevalence of SS has been increasing in recent years due to the more widespread use of magnetic resonance imaging (MRI). Early imaging and diagnosis are crucial for identifying the bleeding source and enabling timely intervention, which may prevent further neurological deterioration. We report the case of a 69-year-old woman with a history of subdural hematoma and surgical intervention who presented with progressive bilateral hearing loss, imbalance, headache, and hypogeusia. MRI of the brain revealed classical imaging features of SS. Although further evaluation was recommended, the patient declined extensive diagnostic work-up. Empirical treatment with the iron-chelating agent deferiprone was initiated. This case highlights the diagnostic challenges of SS and emphasizes the importance of comprehensive imaging and early intervention.
2025-08-27 | An Unusual Case Report: Superficial Siderosis of Bilateral Internal Auditory Canal Presenting as Temporary Facial Palsy
A 33-year-old woman with a history of heart valve replacement on warfarin presented with brief history of facial weakness and hearing loss. MRI showed superficial siderosis (SS) affecting both internal auditory canals-an uncommon and localized finding, as SS usually causes permanent nerve damage. Her recovery with conservative treatment suggests such damage may be reversible. This case highlights the need for early MRI diagnosis.
2025-01-08 | Cerebral Amyloid Angiopathy‐Related Large Intracerebral Lobar Hemorrhage With Subarachnoid Hemorrhage Under the Aspirin Prescribed Conditions
A 64-year-old man developed transient loss of consciousness. Aspirin (100 mg per day) has been prescribed due to the prevention of ischemic heart disease after coronary stenting. Brain computed tomography (CT) taken 3 years previously showed no abnormalities (Figure 1A,B), and no obvious neurological manifestations were noted afterwards. Upon admission, neurological examination was unremarkable. Brain CT (Figure 1C,D) and magnetic resonance imaging (MRI) (Figure 1E,F) revealed diffuse cerebral atrophy showing dilatation of the lateral ventricles and the chronic right frontal lobar hemorrhagic lesions accompanied by the multiple superficial siderosis. Moreover, a small acute infarct in the right frontal white matter was detected. Dilatation of centrum semiovale perivascular spaces was apparent by the T2-weighted MRI images (Figure 1G); however, some spot-like cerebral white matter hyperintense lesions were visible on the fluid-attenuated inversion recovery images (Figure 1H). The three-dimensional CT angiography was unremarkable. Electroencephalogram showed no epileptic discharges. Although probable cerebral amyloid angiopathy (CAA) was suggested based on the current Boston criteria satisfying transient focal neurological episodes (TFNE) and the imaging findings [1], aspirin use was continued for the secondary prevention of cardiovascular events. Brain computed tomography (CT) and magnetic resonance imaging (MRI) images of the patient. Baseline CT images taken 3 years previously are unremarkable (A, B); however, CT images on admission demonstrate the low density areas with cystic changes in the right frontal lobe as well as mild diffuse brain atrophy (C, D). The T2*-weighted brain MRI images on admission show right frontal large intracerebral hemorrhagic lesions with the multiple microbleeds and cortical superficial siderosis (E, F). Dilatation of the perivascular spaces is apparent in the cerebral white matter as well as several cystic lesions in the right frontal lobe on the T2-weighted images on admission (G). Some spot-like cerebral white matter hyperintense lesions are detected on the fluid-attenuated inversion recovery images on admission (H). A recently published case showed that distinguishing TFNE of hemorrhagic origin from cerebral ischemic symptoms was challenging, and antiplatelet medication was terminated in that case due to CAA [2]. The benefits of antiplatelet treatments for cardiovascular disease likely exceed CAA-related hemorrhagic risks [4, 3]. Since aspirin prescription might be related to develop macrohemorrhagic lesions in this patient, further studies in a large number of patients are essential to elucidate the risk–benefit balance of antithrombotic therapies in patients with CAA showing multiple superficial siderosis. This work is partially supported by the Amyloidosis Research Committee, Intractable Disease Division of the Japanese Ministry of Health, Labour, and Welfare (Grant Number 23FC1035 [K.S.]). This study has been approved by our institutional ethics committee and has been performed in accordance with the ethical standards laid down in an appropriate version of the Declaration of Helsinki. Consent for publication was obtained from the patient. The authors declare no conflicts of interest. Further anonymized data are available upon reasonable request.
gene therapies
2025-06-13 | Fetal intracranial hemorrhagic complications following intrauterine transfusion for severe fetal parvovirus B19 infection
The data that support the findings of this study are available from the corresponding author upon reasonable request. Figure S1 Axial T2-weighted magnetic resonance imaging 3 days after delivery in Case 3 showing right frontoparietal porencephalic cyst (a) and superficial siderosis (indicated by hypointensity and arrow) involving brainstem and cerebellum (b). Table S1 Characteristics of study population Table S2 Characteristics of study (intrauterine transfusion (IUT) with intracranial hemorrhage (ICH)) and control (IUT without ICH) groups Table S3 Summary of studies reporting fetal intracranial abnormalities following intrauterine transfusion in congenital parvovirus B19 infection Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
antibodies
2025-12-01 | Disappearing ARIA‐H Microhemorrhages
Abstract Background Amyloid‐Related Imaging Abnormalities (ARIA), an adverse event associated with Alzheimer's disease anti‐amyloid immunotherapies, occur in the form of edema or sulcal effusion (ARIA‐E) and microhemorrhages and superficial siderosis (ARIA‐H). Conventional teaching is that ARIA‐H is permanent hemosiderin staining of the brain. In clinical trials we have noticed that some ARIA‐H microhemorrhages that occur with regional ARIA‐E appear to later resolve. The goal of this study is to illustrate that, opposed to current understanding, some ARIA‐H microhemorrhages may resolve. Methods We identified participants from the Dominantly Inherited Alzheimer's Network Trial Unit (DIAN‐TU) and open label extension (OLE) gantenerumab studies that had ARIA‐E and at least one ARIA‐H microhemorrhage. The T2* GRE sequence from all available MRI exams in a patient were co‐registered and reviewed by a board‐certified neuroradiologist. Individual microhemorrhages were tracked over the serial exams. We defined disappearing/resolving microhemorrhages as those appeared with or following ARIA‐E, were visualized on at least 2 MRI exams, and were subsequently not visualized on at least 2 MRI exams. Results A total of 12 patients met inclusion criteria of which 5 (41%) had microhemorrhages that resolved over 10‐40 months follow‐up after the incident ARIA. These microhemorrhages occurred in clusters in the region of ARIA‐E, and only some of the regional microhemorrhages resolved over follow‐up. Examples are shown in Figures 1‐3. Conclusions The disappearance (resolution) of ARIA‐H microhemorrhages is relevant to the management and continued dosing of patients receiving anti‐amyloid immunotherapies as this is guided by the presence of ARIA (including cumulative treatment emergent microhemorrhages) as well as clinical symptoms. A microhemorrhage number alone may not be indicative of the potentially dynamic nature of ARIA‐H.
cell therapies
2025-12-29 | Progressive Bilateral Sensorineural Hearing Loss and Ataxia Caused by Superficial Siderosis Secondary to Chronic Spontaneous Intracranial Hypotension.
Superficial siderosis (SS) is an uncommon neurodegenerative disorder resulting from persistent or repeated bleeding into the subarachnoid space, which causes hemosiderin to accumulate along the subpial surfaces of the brain, brainstem, spinal cord, and cranial nerves. Chronic spontaneous intracranial hypotension (SIH) due to a dural tear is an uncommon but treatable condition. We report a 51-year-old man with a seven-year history of progressive bilateral sensorineural hearing loss, disabling gait ataxia, vertigo, tinnitus, and facial numbness. Ten years earlier, he had experienced a prolonged, classical orthostatic headache lasting four to six months, which resolved after unspecified treatment. Magnetic resonance imaging (MRI) of the brain revealed features of SS involving the posterior fossa, and an MRI whole-spine survey with fat-suppressed sampling perfection with application-optimized contrasts (SPACE) sequence identified a cervicodorsal, longitudinally extensive extradural cerebrospinal fluid (CSF) collection. The brain MRI also demonstrated a reduced ponto-mesencephalic angle, consistent with intracranial hypotension. A diagnosis of SS secondary to chronic SIH from a spinal dural tear was made. He underwent an autologous epidural blood patch, followed by a second patch, which resulted in symptomatic stabilization, along with iron chelation and corticosteroid therapy. This case highlights the importance of recognizing SS as a delayed complication of untreated SIH. Timely identification and repair of dural defects can halt progression and potentially reverse neurological deficits.
2010-09-01 | Cochlear implantation in a patient with superficial siderosis: an update
The purpose of this study is to present follow-up on a previously reported case of successful cochlear implantation in a patient with superficial siderosis.Retrospective case review.For the first 6 years after implantation, the patient had maintained a successful result; however, she developed a progressive decline in the benefit from her implant.Benefit from cochlear implants in patients with superficial siderosis is variable and may not be long standing.
2002-07-01 | Cochlear Implantation in a Patient with Superficial Siderosis of the Central Nervous System
Objective To perform an assessment of the viability of cochlear implantation in a patient with superficial siderosis of the brain. Study Design Case review. Setting Tertiary referral center. Patients Patient with superficial siderosis of the brain. Intervention Cochlear implantation. Main Outcome Measures Electrically evoked auditory brainstem responses and fitting strategy for cochlear implant based on patient's subjective responses. Results After some time, C levels and T levels showed a pattern comparable with the evoked auditory brainstem responses. Conclusions Bilateral profound hearing loss after superficial siderosis of the brain is no absolute contraindication for implantation. Furthermore, evoked auditory brainstem measurements can potentially guide the fitting process of the implant in difficult cases.
small molecules
2026-03-06 | Quantitative evaluation of iron chelator effects on central motor and sensory tracts in superficial siderosis.
Superficial siderosis (SS) is a rare neurodegenerative disease characterized by hemosiderin deposition in the central nervous system, leading to progressive neuronal degeneration. Although myelopathy is a main clinical manifestation in SS, objective biomarkers for monitoring disease progression and treatment remain unclarified. We assessed electrophysiology of central motor and sensory conduction in patients with SS before and after iron chelator administration. In this controlled trial, we evaluated 12 patients with SS (mean follow-up: 33.6 months [range: 18.9-36.1]), who underwent dural repair, and 9 with multiple sclerosis as controls. Transcranial magnetic stimulation (TMS) and somatosensory evoked potentials (SEPs) were used to assess motor and sensory conduction, respectively. Eight patients with SS received oral iron chelator deferiprone (1,500 mg/day), whereas four underwent surgical repair without iron chelation. Primary outcomes were changes in central motor conduction time (CMCT), motor evoked potential (MEP) amplitude, and central sensory conduction time (CCT). At baseline, 92 and 100% of patients with SS exhibited prolonged CMCT and CCT, respectively. Prolonged conduction in patients with SS was less severe than in those with multiple sclerosis (MS). Whereas MEP amplitude and the amplitude ratio of MEP to CMAP were relatively preserved in patients with SS. After 36-month iron chelator administration, statistically significant improvement of central motor conduction time was gained in patients with SS. TMS and SEP are sensitive tools for evaluating central conduction impairment in SS. The conduction abnormality, likely caused by a different pathomechanism from that in MS, is partially recoverable by iron chelator administration. CMCT improvement demonstrates partial reversibility of impaired motor pathway and supports the therapeutic potential of iron chelator therapy in SS.
2025-09-25 | Corticosteroid Treatment and Hemorrhage Risk in Cerebral Amyloid Angiopathy with Cortical Superficial Siderosis: A Matched Cohort Analysis
Abstract Cortical superficial siderosis (cSS) is the strongest marker of future intracranial hemorrhage (ICH) in cerebral amyloid angiopathy (CAA), a condition without disease-modifying therapy. Emerging evidence suggests that cSS may reflect meningovascular inflammation potentially amenable to immunosuppression. We conducted a single-center matched cohort study comparing high-dose corticosteroid therapy versus no immunosuppression in patients with probable CAA and cSS. Treated patients were matched 1:2 to untreated patients by demographics, cSS multifocality, and baseline intracerebral hemorrhage. The primary outcome was incident ICH; secondary outcomes were any cerebrovascular event and mortality. Kaplan–Meier analysis assessed event-free survival. cSS progression was evaluated in patients with ≥6 months MRI follow-up, and inflammation in a subgroup with post-contrast vessel-wall-imaging (VWI). Thirty-six patients were included (12 treated, 24 untreated; mean age 77.4 years; 91% disseminated cSS). Over a median follow-up of 2.23 years, 11 patients had cerebrovascular events (15 ICHs, 3 ischemic strokes), all in the untreated group (p=0.041 for ICH; p=0.037 for any event). Mortality did not differ (p=0.634). cSS progressed in 2/6 (33%) treated versus 4/7 (57%) untreated patients. Baseline VWI detected inflammation in 7/9 patients (78%), which regressed after corticosteroids. Corticosteroid therapy was associated with fewer cerebrovascular events in high-risk CAA, supporting prospective controlled validation.
2025-09-02 | When Blood Leaves a Trace: Diagnosing Superficial Siderosis in a Geriatric Patient.
Superficial siderosis (SS) is a rare neurodegenerative condition caused by chronic or recurrent bleeding into the subarachnoid space, leading to the deposition of hemosiderin in the subpial layers of the brain, brainstem, spinal cord, or cranial nerves. SS is categorized into two main forms based on its anatomical distribution: cortical superficial siderosis (cSS) and infratentorial superficial siderosis (iSS). Among these, iSS is further subdivided into Type 1 (classical iSS) and Type 2 (secondary iSS). Classical iSS refers to cases in which there is no radiologically confirmed single spontaneous or traumatic intracranial hemorrhage and is typically associated with chronic bleeding sources, such as cranial or spinal dural defects. In contrast, secondary iSS is characterized by the presence of a radiologically identifiable single intracranial hemorrhagic event, either spontaneous or traumatic, which is considered the likely cause of the siderosis. Patients typically present with SS in the fourth to sixth decades of life. The prevalence of SS has been increasing in recent years due to the more widespread use of magnetic resonance imaging (MRI). Early imaging and diagnosis are crucial for identifying the bleeding source and enabling timely intervention, which may prevent further neurological deterioration. We report the case of a 69-year-old woman with a history of subdural hematoma and surgical intervention who presented with progressive bilateral hearing loss, imbalance, headache, and hypogeusia. MRI of the brain revealed classical imaging features of SS. Although further evaluation was recommended, the patient declined extensive diagnostic work-up. Empirical treatment with the iron-chelating agent deferiprone was initiated. This case highlights the diagnostic challenges of SS and emphasizes the importance of comprehensive imaging and early intervention.
2025-08-27 | An Unusual Case Report: Superficial Siderosis of Bilateral Internal Auditory Canal Presenting as Temporary Facial Palsy
A 33-year-old woman with a history of heart valve replacement on warfarin presented with brief history of facial weakness and hearing loss. MRI showed superficial siderosis (SS) affecting both internal auditory canals-an uncommon and localized finding, as SS usually causes permanent nerve damage. Her recovery with conservative treatment suggests such damage may be reversible. This case highlights the need for early MRI diagnosis.
2025-01-08 | Cerebral Amyloid Angiopathy‐Related Large Intracerebral Lobar Hemorrhage With Subarachnoid Hemorrhage Under the Aspirin Prescribed Conditions
A 64-year-old man developed transient loss of consciousness. Aspirin (100 mg per day) has been prescribed due to the prevention of ischemic heart disease after coronary stenting. Brain computed tomography (CT) taken 3 years previously showed no abnormalities (Figure 1A,B), and no obvious neurological manifestations were noted afterwards. Upon admission, neurological examination was unremarkable. Brain CT (Figure 1C,D) and magnetic resonance imaging (MRI) (Figure 1E,F) revealed diffuse cerebral atrophy showing dilatation of the lateral ventricles and the chronic right frontal lobar hemorrhagic lesions accompanied by the multiple superficial siderosis. Moreover, a small acute infarct in the right frontal white matter was detected. Dilatation of centrum semiovale perivascular spaces was apparent by the T2-weighted MRI images (Figure 1G); however, some spot-like cerebral white matter hyperintense lesions were visible on the fluid-attenuated inversion recovery images (Figure 1H). The three-dimensional CT angiography was unremarkable. Electroencephalogram showed no epileptic discharges. Although probable cerebral amyloid angiopathy (CAA) was suggested based on the current Boston criteria satisfying transient focal neurological episodes (TFNE) and the imaging findings [1], aspirin use was continued for the secondary prevention of cardiovascular events. Brain computed tomography (CT) and magnetic resonance imaging (MRI) images of the patient. Baseline CT images taken 3 years previously are unremarkable (A, B); however, CT images on admission demonstrate the low density areas with cystic changes in the right frontal lobe as well as mild diffuse brain atrophy (C, D). The T2*-weighted brain MRI images on admission show right frontal large intracerebral hemorrhagic lesions with the multiple microbleeds and cortical superficial siderosis (E, F). Dilatation of the perivascular spaces is apparent in the cerebral white matter as well as several cystic lesions in the right frontal lobe on the T2-weighted images on admission (G). Some spot-like cerebral white matter hyperintense lesions are detected on the fluid-attenuated inversion recovery images on admission (H). A recently published case showed that distinguishing TFNE of hemorrhagic origin from cerebral ischemic symptoms was challenging, and antiplatelet medication was terminated in that case due to CAA [2]. The benefits of antiplatelet treatments for cardiovascular disease likely exceed CAA-related hemorrhagic risks [4, 3]. Since aspirin prescription might be related to develop macrohemorrhagic lesions in this patient, further studies in a large number of patients are essential to elucidate the risk–benefit balance of antithrombotic therapies in patients with CAA showing multiple superficial siderosis. This work is partially supported by the Amyloidosis Research Committee, Intractable Disease Division of the Japanese Ministry of Health, Labour, and Welfare (Grant Number 23FC1035 [K.S.]). This study has been approved by our institutional ethics committee and has been performed in accordance with the ethical standards laid down in an appropriate version of the Declaration of Helsinki. Consent for publication was obtained from the patient. The authors declare no conflicts of interest. Further anonymized data are available upon reasonable request.
gene therapies
2025-06-13 | Fetal intracranial hemorrhagic complications following intrauterine transfusion for severe fetal parvovirus B19 infection
The data that support the findings of this study are available from the corresponding author upon reasonable request. Figure S1 Axial T2-weighted magnetic resonance imaging 3 days after delivery in Case 3 showing right frontoparietal porencephalic cyst (a) and superficial siderosis (indicated by hypointensity and arrow) involving brainstem and cerebellum (b). Table S1 Characteristics of study population Table S2 Characteristics of study (intrauterine transfusion (IUT) with intracranial hemorrhage (ICH)) and control (IUT without ICH) groups Table S3 Summary of studies reporting fetal intracranial abnormalities following intrauterine transfusion in congenital parvovirus B19 infection Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
antibodies
2025-12-01 | Disappearing ARIA‐H Microhemorrhages
Abstract Background Amyloid‐Related Imaging Abnormalities (ARIA), an adverse event associated with Alzheimer's disease anti‐amyloid immunotherapies, occur in the form of edema or sulcal effusion (ARIA‐E) and microhemorrhages and superficial siderosis (ARIA‐H). Conventional teaching is that ARIA‐H is permanent hemosiderin staining of the brain. In clinical trials we have noticed that some ARIA‐H microhemorrhages that occur with regional ARIA‐E appear to later resolve. The goal of this study is to illustrate that, opposed to current understanding, some ARIA‐H microhemorrhages may resolve. Methods We identified participants from the Dominantly Inherited Alzheimer's Network Trial Unit (DIAN‐TU) and open label extension (OLE) gantenerumab studies that had ARIA‐E and at least one ARIA‐H microhemorrhage. The T2* GRE sequence from all available MRI exams in a patient were co‐registered and reviewed by a board‐certified neuroradiologist. Individual microhemorrhages were tracked over the serial exams. We defined disappearing/resolving microhemorrhages as those appeared with or following ARIA‐E, were visualized on at least 2 MRI exams, and were subsequently not visualized on at least 2 MRI exams. Results A total of 12 patients met inclusion criteria of which 5 (41%) had microhemorrhages that resolved over 10‐40 months follow‐up after the incident ARIA. These microhemorrhages occurred in clusters in the region of ARIA‐E, and only some of the regional microhemorrhages resolved over follow‐up. Examples are shown in Figures 1‐3. Conclusions The disappearance (resolution) of ARIA‐H microhemorrhages is relevant to the management and continued dosing of patients receiving anti‐amyloid immunotherapies as this is guided by the presence of ARIA (including cumulative treatment emergent microhemorrhages) as well as clinical symptoms. A microhemorrhage number alone may not be indicative of the potentially dynamic nature of ARIA‐H.
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Drug Discovery Landscape
1 orphan drug designation for Superficial siderosis.
1 orphan drug designation for Superficial siderosis.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
deferiprone | small molecules | FDA | — | Chiesi USA, Inc. |
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