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Steven M. Greenberg - One of the best experts on this subject based on the ideXlab platform.
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Neuropathological correlates of cortical superficial siderosis in Cerebral Amyloid Angiopathy.
Brain : a journal of neurology, 2020Co-Authors: Andreas Charidimou, Steven M. Greenberg, Valentina Perosa, Matthew P. Frosch, Ashley A. Scherlek, Susanne J. Van VeluwAbstract:Cortical superficial siderosis is an established haemorrhagic neuroimaging marker of Cerebral Amyloid Angiopathy. In fact, cortical superficial siderosis is emerging as a strong independent risk factor for future lobar intraCerebral haemorrhage. However, the underlying neuropathological correlates and pathophysiological mechanisms of cortical superficial siderosis remain elusive. Here we use an in vivo MRI, ex vivo MRI, histopathology approach to assess the neuropathological correlates and vascular pathology underlying cortical superficial siderosis. Fourteen autopsy cases with Cerebral Amyloid Angiopathy (mean age at death 73 years, nine males) and three controls (mean age at death 91 years, one male) were included in the study. Intact formalin-fixed Cerebral hemispheres were scanned on a 3 T MRI scanner. Cortical superficial siderosis was assessed on ex vivo gradient echo and turbo spin echo MRI sequences and compared to findings on available in vivo MRI. Subsequently, 11 representative areas in four cases with available in vivo MRI scans were sampled for histopathological verification of MRI-defined cortical superficial siderosis. In addition, samples were taken from predefined standard areas of the brain, blinded to MRI findings. Serial sections were stained for haematoxylin and eosin and Perls' Prussian blue, and immunohistochemistry was performed against Amyloid-β and GFAP. Cortical superficial siderosis was present on ex vivo MRI in 8/14 cases (57%) and 0/3 controls (P = 0.072). Histopathologically, cortical superficial siderosis corresponded to iron-positive haemosiderin deposits in the subarachnoid space and superficial cortical layers, indicative of chronic bleeding events originating from the leptomeningeal vessels. Increased severity of cortical superficial siderosis was associated with upregulation of reactive astrocytes. Next, cortical superficial siderosis was assessed on a total of 65 Perls'-stained sections from MRI-targeted and untargeted sampling combined in Cerebral Amyloid Angiopathy cases. Moderate-to-severe cortical superficial siderosis was associated with concentric splitting of the vessel wall (an advanced form of Cerebral Amyloid Angiopathy-related vascular damage) in leptomeningeal vessels (P < 0.0001), but reduced Cerebral Amyloid Angiopathy severity in cortical vessels (P = 0.048). In terms of secondary tissue injury, moderate-to-severe cortical superficial siderosis was associated with the presence of microinfarcts (P = 0.025), though not microbleeds (P = 0.973). Collectively, these data suggest that cortical superficial siderosis on MRI corresponds to iron-positive deposits in the superficial cortical layers, representing the chronic manifestation of bleeding episodes from leptomeningeal vessels. Cortical superficial siderosis appears to be the result of predominantly advanced Cerebral Amyloid Angiopathy of the leptomeningeal vessels and may trigger secondary ischaemic injury in affected areas.
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Abstract WP344: Basal Ganglia Atrophy in Cerebral Amyloid Angiopathy
Stroke, 2018Co-Authors: Panagiotis Fotiadis, Andreas Charidimou, Steven M. Greenberg, M. Edip Gurol, Anand Viswanathan, Kristin Schwab, Marco Pasi, Jonathan Rosand, Myung Joo Lee, Alzheimer’s Disease Neuroimaging InitiativeAbstract:Background/Purpose: Cerebral Amyloid Angiopathy (CAA) is associated with cortical and white matter atrophy. We hypothesized that atrophy in CAA extended into the subcortical gray matter as well and...
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Emerging concepts in sporadic Cerebral Amyloid Angiopathy
Brain : a journal of neurology, 2017Co-Authors: Andreas Charidimou, M. Edip Gurol, Gregoire Boulouis, Cenk Ayata, Brian J. Bacskai, Matthew P. Frosch, Anand Viswanathan, Steven M. GreenbergAbstract:Sporadic Cerebral Amyloid Angiopathy is a common, well-defined small vessel disease and a largely untreatable cause of intraCerebral haemorrhage and contributor to age-related cognitive decline. The term 'Cerebral Amyloid Angiopathy' now encompasses not only a specific cerebrovascular pathological finding, but also different clinical syndromes (both acute and progressive), brain parenchymal lesions seen on neuroimaging and a set of diagnostic criteria-the Boston criteria, which have resulted in increasingly detected disease during life. Over the past few years, it has become clear that, at the pathophysiological level, Cerebral Amyloid Angiopathy appears to be in part a protein elimination failure Angiopathy and that this dysfunction is a feed-forward process, which potentially leads to worsening vascular Amyloid-β accumulation, activation of vascular injury pathways and impaired vascular physiology. From a clinical standpoint, Cerebral Amyloid Angiopathy is characterized by individual focal lesions (microbleeds, cortical superficial siderosis, microinfarcts) and large-scale alterations (white matter hyperintensities, structural connectivity, cortical thickness), both cortical and subcortical. This review provides an interdisciplinary critical outlook on various emerging and changing concepts in the field, illustrating mechanisms associated with Amyloid cerebrovascular pathology and neurological dysfunction.
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Sporadic Cerebral Amyloid Angiopathy: Pathophysiology, Neuroimaging Features, and Clinical Implications
Seminars in Neurology, 2016Co-Authors: Gregoire Boulouis, Andreas Charidimou, Steven M. GreenbergAbstract:Sporadic Cerebral Amyloid Angiopathy is a small vessel disorder defined pathologically by progressive Amyloid deposition in the walls of cortical and leptomeningeal vessels resulting from disruption of a complex balance between production, circulation, and clearance of Amyloid-β peptide (Aβ) in the brain. Cerebral Amyloid Angiopathy is a major cause of lobar symptomatic intraCerebral hemorrhage, transient focal neurologic episodes, and a key contributor to vascular cognitive impairment. The mechanisms and consequences of Amyloid-β deposition at the pathological level and its neuroimaging manifestations, clinical consequences, and implications for patient care are addressed in this review.
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Cerebral Amyloid Angiopathy severity is linked to dilation of juxtacortical perivascular spaces.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2015Co-Authors: Susanne J. Van Veluw, Geert Jan Biessels, M. Edip Gurol, Willem H. Bouvy, Wim G. M. Spliet, Jaco J.m. Zwanenburg, Peter R. Luijten, Eric A. Macklin, Annemieke J.m. Rozemuller, Steven M. GreenbergAbstract:Perivascular spaces are an emerging marker of small vessel disease. Perivascular spaces in the centrum semiovale have been associated with Cerebral Amyloid Angiopathy. However, a direct topographical relationship between dilated perivascular spaces and Cerebral Amyloid Angiopathy severity has not been established. We examined this association using post-mortem magnetic resonance imaging in five cases with evidence of Cerebral Amyloid Angiopathy pathology. Juxtacortical perivascular spaces dilation was evaluated on T2 images and related to Cerebral Amyloid Angiopathy severity in overlying cortical areas on 34 tissue sections stained for Amyloid β. Degree of perivascular spaces dilation was significantly associated with Cerebral Amyloid Angiopathy severity (odds ratio = 3.3, 95% confidence interval 1.3-7.9, p = 0.011). Thus, dilated juxtacortical perivascular spaces are a promising neuroimaging marker of Cerebral Amyloid Angiopathy severity.
Andreas Charidimou - One of the best experts on this subject based on the ideXlab platform.
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Peak Width of Skeletonized Mean Diffusivity as Neuroimaging Biomarker in Cerebral Amyloid Angiopathy.
AJNR. American journal of neuroradiology, 2021Co-Authors: N. Raposo, Andreas Charidimou, Gregoire Boulouis, M.c. Zanon Zotin, Dorothee Schoemaker, Li Xiong, Panagiotis Fotiadis, M. Pasi, K. Schwab, Markus D. SchirmerAbstract:BACKGROUND AND PURPOSE Whole-brain network connectivity has been shown to be a useful biomarker of Cerebral Amyloid Angiopathy and related cognitive impairment. We evaluated an automated DTI-based method, peak width of skeletonized mean diffusivity, in Cerebral Amyloid Angiopathy, together with its association with conventional MRI markers and cognitive functions. MATERIALS AND METHODS We included 24 subjects (mean age, 74.7 [SD, 6.0] years) with probable Cerebral Amyloid Angiopathy and mild cognitive impairment and 62 patients with MCI not attributable to Cerebral Amyloid Angiopathy (non-Cerebral Amyloid Angiopathy-mild cognitive impairment). We compared peak width of skeletonized mean diffusivity between subjects with Cerebral Amyloid Angiopathy-mild cognitive impairment and non-Cerebral Amyloid Angiopathy-mild cognitive impairment and explored its associations with cognitive functions and conventional markers of Cerebral small-vessel disease, using linear regression models. RESULTS Subjects with Cerebral Amyloid Angiopathy-mild cognitive impairment showed increased peak width of skeletonized mean diffusivity in comparison to those with non-Cerebral Amyloid Angiopathy-mild cognitive impairment (P < .001). Peak width of skeletonized mean diffusivity values were correlated with the volume of white matter hyperintensities in both groups. Higher peak width of skeletonized mean diffusivity was associated with worse performance in processing speed among patients with Cerebral Amyloid Angiopathy, after adjusting for other MRI markers of Cerebral small vessel disease. The peak width of skeletonized mean diffusivity did not correlate with cognitive functions among those with non-Cerebral Amyloid Angiopathy-mild cognitive impairment. CONCLUSIONS Peak width of skeletonized mean diffusivity is altered in Cerebral Amyloid Angiopathy and is associated with performance in processing speed. This DTI-based method may reflect the degree of white matter structural disruption in Cerebral Amyloid Angiopathy and could be a useful biomarker for cognition in this population.
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Neuropathological correlates of cortical superficial siderosis in Cerebral Amyloid Angiopathy.
Brain : a journal of neurology, 2020Co-Authors: Andreas Charidimou, Steven M. Greenberg, Valentina Perosa, Matthew P. Frosch, Ashley A. Scherlek, Susanne J. Van VeluwAbstract:Cortical superficial siderosis is an established haemorrhagic neuroimaging marker of Cerebral Amyloid Angiopathy. In fact, cortical superficial siderosis is emerging as a strong independent risk factor for future lobar intraCerebral haemorrhage. However, the underlying neuropathological correlates and pathophysiological mechanisms of cortical superficial siderosis remain elusive. Here we use an in vivo MRI, ex vivo MRI, histopathology approach to assess the neuropathological correlates and vascular pathology underlying cortical superficial siderosis. Fourteen autopsy cases with Cerebral Amyloid Angiopathy (mean age at death 73 years, nine males) and three controls (mean age at death 91 years, one male) were included in the study. Intact formalin-fixed Cerebral hemispheres were scanned on a 3 T MRI scanner. Cortical superficial siderosis was assessed on ex vivo gradient echo and turbo spin echo MRI sequences and compared to findings on available in vivo MRI. Subsequently, 11 representative areas in four cases with available in vivo MRI scans were sampled for histopathological verification of MRI-defined cortical superficial siderosis. In addition, samples were taken from predefined standard areas of the brain, blinded to MRI findings. Serial sections were stained for haematoxylin and eosin and Perls' Prussian blue, and immunohistochemistry was performed against Amyloid-β and GFAP. Cortical superficial siderosis was present on ex vivo MRI in 8/14 cases (57%) and 0/3 controls (P = 0.072). Histopathologically, cortical superficial siderosis corresponded to iron-positive haemosiderin deposits in the subarachnoid space and superficial cortical layers, indicative of chronic bleeding events originating from the leptomeningeal vessels. Increased severity of cortical superficial siderosis was associated with upregulation of reactive astrocytes. Next, cortical superficial siderosis was assessed on a total of 65 Perls'-stained sections from MRI-targeted and untargeted sampling combined in Cerebral Amyloid Angiopathy cases. Moderate-to-severe cortical superficial siderosis was associated with concentric splitting of the vessel wall (an advanced form of Cerebral Amyloid Angiopathy-related vascular damage) in leptomeningeal vessels (P < 0.0001), but reduced Cerebral Amyloid Angiopathy severity in cortical vessels (P = 0.048). In terms of secondary tissue injury, moderate-to-severe cortical superficial siderosis was associated with the presence of microinfarcts (P = 0.025), though not microbleeds (P = 0.973). Collectively, these data suggest that cortical superficial siderosis on MRI corresponds to iron-positive deposits in the superficial cortical layers, representing the chronic manifestation of bleeding episodes from leptomeningeal vessels. Cortical superficial siderosis appears to be the result of predominantly advanced Cerebral Amyloid Angiopathy of the leptomeningeal vessels and may trigger secondary ischaemic injury in affected areas.
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Cerebellar Microbleed Distribution Patterns and Cerebral Amyloid Angiopathy.
Stroke, 2019Co-Authors: Marco Pasi, Andreas Charidimou, Gregoire Boulouis, Li Xiong, Thanakit Pongpitakmetha, Sanjula Singh, Hsin-hsi Tsai, Andrew D. Warren, Jonathan Rosand, Matthew P. FroschAbstract:Background and Purpose— Hematoma location within the cerebellum may help identify the dominant small vessel disease type (Cerebral Amyloid Angiopathy [CAA] versus nonAmyloid small vessel disease). ...
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Abstract WP344: Basal Ganglia Atrophy in Cerebral Amyloid Angiopathy
Stroke, 2018Co-Authors: Panagiotis Fotiadis, Andreas Charidimou, Steven M. Greenberg, M. Edip Gurol, Anand Viswanathan, Kristin Schwab, Marco Pasi, Jonathan Rosand, Myung Joo Lee, Alzheimer’s Disease Neuroimaging InitiativeAbstract:Background/Purpose: Cerebral Amyloid Angiopathy (CAA) is associated with cortical and white matter atrophy. We hypothesized that atrophy in CAA extended into the subcortical gray matter as well and...
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Cerebral Amyloid Angiopathy, Cerebral microbleeds and implications for anticoagulation decisions: The need for a balanced approach.
International journal of stroke : official journal of the International Stroke Society, 2017Co-Authors: Andreas Charidimou, Rustam Alshahi Salman, Charlotte Cordonnier, Ashkan Shoamanesh, Jonathan Rosand, Luke A Perry, Kevin N. Sheth, Alessandro Biffi, Anand ViswanathanAbstract:Cerebral Amyloid Angiopathy is a common hemorrhagic small vessel disease of the brain, often associated with high risk of spontaneous lobar intraCerebral hemorrhage. When the suspicion of Cerebral Amyloid Angiopathy is raised, clinicians are hesitant in prescribing oral anticoagulation in patients in whom it is otherwise indicated, including the case of non-valvular atrial fibrillation. This is one of the thorniest clinical dilemmas in the field currently. In this short Leading Opinion piece by an international panel of clinicians-researchers active in the field, we present our consistent approach and future outlook on oral anticoagulation post intraCerebral hemorrhage and in the setting of clinical-radiologic evidence of Cerebral Amyloid Angiopathy. We discuss recent advances and support a more balanced approach with implications for the wider neurological clinical community in regards to successful recruiting this patient population in ongoing and future randomized trials.
Eric E. Smith - One of the best experts on this subject based on the ideXlab platform.
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Cortical Microinfarcts on 3T Magnetic Resonance Imaging in Cerebral Amyloid Angiopathy.
Stroke, 2018Co-Authors: Hilde Van Den Brink, Geert Jan Biessels, Angela Zwiers, Aaron R. Switzer, Anna Charlton, Cheryl R. Mccreary, Bradley G. Goodyear, Richard Frayne, Eric E. SmithAbstract:Background and Purpose— Cerebral microinfarcts are small ischemic lesions that are found in Cerebral Amyloid Angiopathy (CAA) patients at autopsy. The current study aimed to detect cortical microin...
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outcome markers for clinical trials in Cerebral Amyloid Angiopathy
Lancet Neurology, 2014Co-Authors: Steven M. Greenberg, Geert Jan Biessels, Eric E. Smith, Rustam Alshahi Salman, Mark A Van Buchem, Charlotte Cordonnier, Jinmoo Lee, Joan Montaner, Julie A Schneider, Meike W VernooijAbstract:Efforts are underway for early-phase trials of candidate treatments for Cerebral Amyloid Angiopathy, an untreatable cause of haemorrhagic stroke and vascular cognitive impairment. A major barrier to these trials is the absence of consensus on measurement of treatment effectiveness. A range of potential outcome markers for Cerebral Amyloid Angiopathy can be measured against the ideal criteria of being clinically meaningful, closely representative of biological progression, efficient for small or short trials, reliably measurable, and cost effective. In practice, outcomes tend either to have high clinical salience but low statistical efficiency, and thus more applicability for late-phase studies, or greater statistical efficiency but more limited clinical meaning. The most statistically efficient markers might be those that are potentially reversible with treatment, although their clinical significance remains unproven. Many of the candidate outcomes for Cerebral Amyloid Angiopathy trials are probably applicable also to other small-vessel brain diseases.
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The Lancet Neurology - Outcome markers for clinical trials in Cerebral Amyloid Angiopathy
The Lancet. Neurology, 2014Co-Authors: Steven M. Greenberg, Geert Jan Biessels, Eric E. Smith, Rustam Alshahi Salman, Mark A Van Buchem, Charlotte Cordonnier, Jinmoo Lee, Joan Montaner, Julie A Schneider, Meike W VernooijAbstract:Efforts are underway for early-phase trials of candidate treatments for Cerebral Amyloid Angiopathy, an untreatable cause of haemorrhagic stroke and vascular cognitive impairment. A major barrier to these trials is the absence of consensus on measurement of treatment effectiveness. A range of potential outcome markers for Cerebral Amyloid Angiopathy can be measured against the ideal criteria of being clinically meaningful, closely representative of biological progression, efficient for small or short trials, reliably measurable, and cost effective. In practice, outcomes tend either to have high clinical salience but low statistical efficiency, and thus more applicability for late-phase studies, or greater statistical efficiency but more limited clinical meaning. The most statistically efficient markers might be those that are potentially reversible with treatment, although their clinical significance remains unproven. Many of the candidate outcomes for Cerebral Amyloid Angiopathy trials are probably applicable also to other small-vessel brain diseases.
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Cerebral Amyloid Angiopathy in East and West.
International journal of stroke : official journal of the International Stroke Society, 2010Co-Authors: Yu-wei Chen, Ming-jen Lee, Eric E. SmithAbstract:Cerebral Amyloid Angiopathy, a vasculopathy characterised by the deposition of Amyloid fibrils in the arteries and arterioles in the Cerebral cortex and meninges, has been reported to be associated with intraCerebral haemorrhage and cognitive impairment in the elderly. Advances in neuroimaging and validation of the clinical diagnostic criteria aid in making a correct clinical diagnosis. Associations with Alzheimer's disease, asymptomatic microbleeds and white matter changes on neuroimaging have an influence on the clinical treatment for patients with probable Cerebral Amyloid Angiopathy. Reviewing the reports from Asian countries, we found that patients with Cerebral Amyloid Angiopathy have a strong age-related prevalence and a consistent association with dementia, but a weaker correlation with intraCerebral haemorrhage, most likely due to a higher incidence of hypertensive intraCerebral haemorrhage. Involvement of the occipital lobe arteries by CAA is common in all races and ethnicities, while frontal lobe arteries may be more frequently involved in the East compared to the West. The clinical impact of Cerebral Amyloid Angiopathy on intraCerebral haemorrhage and cognitive impairment could be increasingly obvious in Asian countries with ageing populations, especially with improving control of hypertension, the leading cause of intraCerebral haemorrhage.
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course of Cerebral Amyloid Angiopathy related inflammation
Neurology, 2007Co-Authors: Catherine Kinnecom, Eric E. Smith, Matthew P. Frosch, Jonathan Rosand, Michael H Lev, Lauren Wendell, Steven M. GreenbergAbstract:Background: A subset of patients with Cerebral Amyloid Angiopathy (CAA) present with cognitive symptoms, seizures, headaches, T2-hyperintense MRI lesions, and neuropathologic evidence of CAA-associated vascular inflammation. Objective: To analyze the risk factors, diagnostic characteristics, and long-term course of this disorder. Methods: We assessed 14 consecutive patients with pathologically diagnosed CAA-related inflammation, 12 with available neuroimaging and follow-up data. Patients were evaluated for MRI appearance, APOE genotype, and clinical course over a 46.8 ± 29.1-month follow-up. Results: Baseline MRI scans were characterized by asymmetric T2-hyperintense lesions extending to the subcortical white matter and occasionally the overlying gray matter, with signal properties suggesting vasogenic edema. Subjects could be divided into three groups based on response to immunosuppressive treatment: monophasic improvement (7/12), initial improvement followed by symptomatic relapse (3/12), and no evident response to treatment (2/12). The volume of MRI hyperintensities correlated with the severity of clinical symptoms. One patient experienced symptomatic intraCerebral hemorrhage within a region of recurrent MRI hyperintensity. The APOE e4/e4 genotype was strongly associated with CAA-related inflammation, present in 76.9% (10/13) of subjects vs 5.1% (2/39) with symptomatic but noninflammatory CAA ( p Conclusion: Cerebral Amyloid Angiopathy–related inflammation represents a clinically, pathologically, radiographically, and genetically distinct disease subtype with implications for clinical practice and ongoing immunotherapeutic approaches to Alzheimer disease.
David J Werring - One of the best experts on this subject based on the ideXlab platform.
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cortical superficial siderosis detection and clinical significance in Cerebral Amyloid Angiopathy and related conditions
Brain, 2015Co-Authors: Andreas Charidimou, Saloua Akoudad, Hans Rolf Jager, Christian Opherk, Jennifer Linn, Jeanclaude Baron, Steven M. Greenberg, Meike W Vernooij, David J WerringAbstract:Cortical superficial siderosis describes a distinct pattern of blood-breakdown product deposition limited to cortical sulci over the convexities of the Cerebral hemispheres, sparing the brainstem, cerebellum and spinal cord. Although cortical superficial siderosis has many possible causes, it is emerging as a key feature of Cerebral Amyloid Angiopathy, a common and important age-related Cerebral small vessel disorder leading to intraCerebral haemorrhage and dementia. In Cerebral Amyloid Angiopathy cohorts, cortical superficial siderosis is associated with characteristic clinical symptoms, including transient focal neurological episodes; preliminary data also suggest an association with a high risk of future intraCerebral haemorrhage, with potential implications for antithrombotic treatment decisions. Thus, cortical superficial siderosis is of relevance to neurologists working in neurovascular, memory and epilepsy clinics, and neurovascular emergency services, emphasizing the need for appropriate blood-sensitive magnetic resonance sequences to be routinely acquired in these clinical settings. In this review we focus on recent developments in neuroimaging and detection, aetiology, prevalence, pathophysiology and clinical significance of cortical superficial siderosis, with a particular emphasis on Cerebral Amyloid Angiopathy. We also highlight important areas for future investigation and propose standards for evaluating cortical superficial siderosis in research studies. * Abbreviations : CAA : Cerebral Amyloid Angiopathy cSAH : convexity subarachnoid haemorrhage cSS : cortical superficial siderosis GRE : gradient recalled echo ICH : intraCerebral haemorrhage SWI : susceptibility-weighted imaging
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Severe MRI-visible perivascular spaces due to Cerebral Amyloid Angiopathy
Practical neurology, 2014Co-Authors: Sayan Datta, Hawraman Ramadan, David J WerringAbstract:MRI-visible perivascular spaces are a recently recognised neuroimaging marker of Cerebral small vessel diseases1 and centrum semiovale MRI-visible perivascular spaces may be a neuroimaging marker of Cerebral Amyloid Angiopathy.2 We report an elderly woman with speech and memory disturbance, whose MR scan of brain showed severe centrum semiovale perivascular spaces. Subsequent MRI with blood-sensitive sequences showed multiple Cerebral microbleeds, consistent with probable Cerebral Amyloid Angiopathy. Dilated perivascular spaces can be a marker of Cerebral Amyloid Angiopathy. Their recognition may change clinical management, since current recommendations for Cerebral Amyloid Angiopathy treatment involve avoiding antithrombotic drugs and emphasising hypertensive control. A previously healthy 81-year-old woman gave a 3-month history …
Meike W Vernooij - One of the best experts on this subject based on the ideXlab platform.
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cortical superficial siderosis detection and clinical significance in Cerebral Amyloid Angiopathy and related conditions
Brain, 2015Co-Authors: Andreas Charidimou, Saloua Akoudad, Hans Rolf Jager, Christian Opherk, Jennifer Linn, Jeanclaude Baron, Steven M. Greenberg, Meike W Vernooij, David J WerringAbstract:Cortical superficial siderosis describes a distinct pattern of blood-breakdown product deposition limited to cortical sulci over the convexities of the Cerebral hemispheres, sparing the brainstem, cerebellum and spinal cord. Although cortical superficial siderosis has many possible causes, it is emerging as a key feature of Cerebral Amyloid Angiopathy, a common and important age-related Cerebral small vessel disorder leading to intraCerebral haemorrhage and dementia. In Cerebral Amyloid Angiopathy cohorts, cortical superficial siderosis is associated with characteristic clinical symptoms, including transient focal neurological episodes; preliminary data also suggest an association with a high risk of future intraCerebral haemorrhage, with potential implications for antithrombotic treatment decisions. Thus, cortical superficial siderosis is of relevance to neurologists working in neurovascular, memory and epilepsy clinics, and neurovascular emergency services, emphasizing the need for appropriate blood-sensitive magnetic resonance sequences to be routinely acquired in these clinical settings. In this review we focus on recent developments in neuroimaging and detection, aetiology, prevalence, pathophysiology and clinical significance of cortical superficial siderosis, with a particular emphasis on Cerebral Amyloid Angiopathy. We also highlight important areas for future investigation and propose standards for evaluating cortical superficial siderosis in research studies. * Abbreviations : CAA : Cerebral Amyloid Angiopathy cSAH : convexity subarachnoid haemorrhage cSS : cortical superficial siderosis GRE : gradient recalled echo ICH : intraCerebral haemorrhage SWI : susceptibility-weighted imaging
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outcome markers for clinical trials in Cerebral Amyloid Angiopathy
Lancet Neurology, 2014Co-Authors: Steven M. Greenberg, Geert Jan Biessels, Eric E. Smith, Rustam Alshahi Salman, Mark A Van Buchem, Charlotte Cordonnier, Jinmoo Lee, Joan Montaner, Julie A Schneider, Meike W VernooijAbstract:Efforts are underway for early-phase trials of candidate treatments for Cerebral Amyloid Angiopathy, an untreatable cause of haemorrhagic stroke and vascular cognitive impairment. A major barrier to these trials is the absence of consensus on measurement of treatment effectiveness. A range of potential outcome markers for Cerebral Amyloid Angiopathy can be measured against the ideal criteria of being clinically meaningful, closely representative of biological progression, efficient for small or short trials, reliably measurable, and cost effective. In practice, outcomes tend either to have high clinical salience but low statistical efficiency, and thus more applicability for late-phase studies, or greater statistical efficiency but more limited clinical meaning. The most statistically efficient markers might be those that are potentially reversible with treatment, although their clinical significance remains unproven. Many of the candidate outcomes for Cerebral Amyloid Angiopathy trials are probably applicable also to other small-vessel brain diseases.
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The Lancet Neurology - Outcome markers for clinical trials in Cerebral Amyloid Angiopathy
The Lancet. Neurology, 2014Co-Authors: Steven M. Greenberg, Geert Jan Biessels, Eric E. Smith, Rustam Alshahi Salman, Mark A Van Buchem, Charlotte Cordonnier, Jinmoo Lee, Joan Montaner, Julie A Schneider, Meike W VernooijAbstract:Efforts are underway for early-phase trials of candidate treatments for Cerebral Amyloid Angiopathy, an untreatable cause of haemorrhagic stroke and vascular cognitive impairment. A major barrier to these trials is the absence of consensus on measurement of treatment effectiveness. A range of potential outcome markers for Cerebral Amyloid Angiopathy can be measured against the ideal criteria of being clinically meaningful, closely representative of biological progression, efficient for small or short trials, reliably measurable, and cost effective. In practice, outcomes tend either to have high clinical salience but low statistical efficiency, and thus more applicability for late-phase studies, or greater statistical efficiency but more limited clinical meaning. The most statistically efficient markers might be those that are potentially reversible with treatment, although their clinical significance remains unproven. Many of the candidate outcomes for Cerebral Amyloid Angiopathy trials are probably applicable also to other small-vessel brain diseases.