This case report investigates the manifestation of cerebral amyloid angiopathy (CAA) through recurrent Transient Ischemic Attacks (TIAs) in an 82-year-old patient. Despite initial diagnostic complexities, cerebral ang...This case report investigates the manifestation of cerebral amyloid angiopathy (CAA) through recurrent Transient Ischemic Attacks (TIAs) in an 82-year-old patient. Despite initial diagnostic complexities, cerebral angiography-MRI revealed features indicative of CAA. Symptomatic treatment resulted in improvement, but the patient later developed a fatal hematoma. The discussion navigates the intricate therapeutic landscape of repetitive TIAs in the elderly with cardiovascular risk factors, emphasizing the pivotal role of cerebral MRI and meticulous bleeding risk management. The conclusion stresses the importance of incorporating SWI sequences, specifically when suspecting a cardioembolic TIA, as a diagnostic measure to explore and exclude CAA in the differential diagnosis. This case report provides valuable insights into these challenges, highlighting the need to consider CAA in relevant cases.展开更多
BACKGROUND Diagnosis of a dementia subtype can be complex and often requires comprehensive cognitive assessment and dedicated neuroimaging.Clinicians are prone to cognitive biases when reviewing such images.We present...BACKGROUND Diagnosis of a dementia subtype can be complex and often requires comprehensive cognitive assessment and dedicated neuroimaging.Clinicians are prone to cognitive biases when reviewing such images.We present a case of cognitive impairment and demonstrate that initial imaging may have resulted in misleading the diagnosis due to such cognitive biases.CASE SUMMARY A 76-year-old man with no cognitive impairment presented with acute onset word finding difficulty with unremarkable blood tests and neurological examination.Magnetic resonance imaging(MRI)demonstrated multiple foci of periventricular and subcortical microhaemorrhage,consistent with cerebral amyloid angiopathy(CAA).Cognitive assessment of this patient demonstrated marked impairment mainly in verbal fluency and memory.However,processing speed and executive function are most affected in CAA,whereas episodic memory is relatively preserved,unlike in other causes of cognitive impairment,such as Alzheimer’s dementia(AD).This raised the question of an underlying diagnosis of dementia.Repeat MRI with dedicated coronal views demonstrated mesial temporal lobe atrophy which is consistent with AD.CONCLUSION MRI brain can occasionally result in diagnostic overshadowing,and the application of artificial intelligence to medical imaging may overcome such cognitive biases.展开更多
Objective To study the changes of biomarkers in cerebrospinal fluid(CSF) in cerebral amyloid angiopathy(CAA) dementia and Alzheimer's disease.Methods Levels of amyloid protein β(Aβ42,Aβ40) and phosphorylated Ta...Objective To study the changes of biomarkers in cerebrospinal fluid(CSF) in cerebral amyloid angiopathy(CAA) dementia and Alzheimer's disease.Methods Levels of amyloid protein β(Aβ42,Aβ40) and phosphorylated Tau-protein(P-tau) in CSF and ratio of Aβ42/Aβ40 were tested in 5 cases with CAA dementia and 20 cases with Alzheimer's disease collected at Peking Union Medical College Hospital from December 2001 to March 2011.Results The levels of Aβ42,Aβ40,and P-tau in CSF and ratio of Aβ42/Aβ40 were(660.4±265.2) ng/L,(7111.0±1033.4) ng/L,(71.8±51.5) ng/L,and 0.077±0.033,respectively in CAA dementia and(663.6±365.6) ng/L,(5115.0±2931.1) ng/L,(47.7±38.8) ng/L,and 0.192±0.140,respectively in Alzheimer's disease patients.There were no statistically significant differences between CAA dementia and Alzheimer's disease in terms of these CSF biomarkers(all P>0.05).Conclusion Measurements of CSF biomarkers may not be helpful in differential diagnosis of CAA and Alzheimer's disease.展开更多
Background Cerebral amyloid angiopathy is a common cause of subcortical hemorrhage in older adults.Although open hematoma removal may be performed for severe subcortical hemorrhage,its safety in patients with cerebral...Background Cerebral amyloid angiopathy is a common cause of subcortical hemorrhage in older adults.Although open hematoma removal may be performed for severe subcortical hemorrhage,its safety in patients with cerebral amyloid angiopathy has not been established,and postoperative rebleeding may occur.Therefore,this study aimed to investigate factors associated with postoperative rebleeding.Methods Out of 145 consecutive patients who had undergone craniotomy for surgical removal of subcortical intracerebral hemorrhage between April 2010 and August 2019 at a single institution in Japan,we examined 109 patients with subcortical hemorrhage who met the inclusion criteria.After excluding 30 patients whose tissue samples were unsuitable for the study,the final study cohort comprised 79 patients.Results Of the 79 patients,50(63%)were diagnosed with cerebral amyloid angiopathy(cerebral amyloid angiopathy group)and 29(37%)were not diagnosed with noncerebral amyloid angiopathy(noncerebral amyloid angiopathy group).Postoperative rebleeding occurred in 12 patients(24%)in the cerebral amyloid angiopathy group and in 2 patients(7%)in the noncerebral amyloid angiopathy group.Preoperative prothrombin time-international normalized ratio and intraoperative bleeding volume were significantly associated with postoperative rebleeding in the cerebral amyloid angiopathy group(odds ratio=42.4,95%confidence interval=1.14-1578;p=0.042 and odds ratio=1.005,95%confidence interval=1.001-1.008;p=0.007,respectively).Conclusions Patients with cerebral amyloid angiopathy-related cerebral hemorrhage who are receiving antithrombotic therapy,particularly warfarin therapy,are at a high risk of postoperative rebleeding.Trial registration Registry and Registration Number of the study:19-220,2019/12/23,retrospectively registered.展开更多
Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a rare but increasingly recognized subtype of CAA. CAA-RI consists of two subtypes: inflammatory cerebral amyloid angiopathy and amyloid β (Aβ)-related an...Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a rare but increasingly recognized subtype of CAA. CAA-RI consists of two subtypes: inflammatory cerebral amyloid angiopathy and amyloid β (Aβ)-related angiitis. Acute or subacute onset of cognitive decline or behavioral changes is the most common symptom of CAA-RI. Rapid progressive dementia, headache, seizures, or focal neurological deficits, with patchy or confluent hyperintensity on T2 or fluid-attenuated inversion recovery sequences and evidence of strictly lobar microbleeds or cortical superficial siderosis on susceptibility-weighted imaging imply CAA-RI. The gold standard for diagnosis is autopsy or brain biopsy. However, biopsy is invasive;consequently, most clinically diagnosed cases have been based on clinical and radiological data. Other diagnostic indexes include the apolipoprotein E ε4 allele, Aβ and anti-Aβ antibodies in cerebral spinal fluid and amyloid positron emission tomography. Many diseases with similar clinical manifestations should be carefully ruled out. Immunosuppressive therapy is effective both during initial presentation and in relapses. The use of glucocorticoids and immunosuppressants improves prognosis. This article reviews the pathology and pathogenesis, clinical and imaging manifestations, diagnostic criteria, treatment, and prognosis of CAA-RI, and highlights unsolved problems in the existing research.展开更多
Cerebral amyloid angiopathy(CAA)is characterized by the deposition of amyloid β-protein(Aβ)in the leptomeningeal and cortical blood vessels,which is an age-dependent risk factor for intracerebral hemorrhage(ICH),isc...Cerebral amyloid angiopathy(CAA)is characterized by the deposition of amyloid β-protein(Aβ)in the leptomeningeal and cortical blood vessels,which is an age-dependent risk factor for intracerebral hemorrhage(ICH),ischemic stroke and contributes to cerebrovascular dysfunction leading to cognitive impairment.However clinical prevention and treatment of the disease is very difficult because of its occult onset and severity of the symptoms.In recent years,many anti-amyloid β immunotherapies have not demonstrated clinical efficacy in subjects with Alzheimer’s disease(AD),and the failure may be due to the deposition of Aβ in the cerebrovascular export pathway resulting in further damage to blood vessels and aggravating CAA.So decreased clearance of Aβ in blood vessels plays a crucial role in the development of CAA and AD,and identification of the molecular pathways involved will provide new targets for treatment.In this review,we mainly describe the mechanisms of Aβ clearance through vessels,especially in terms of some proteins and receptors involved in this process.展开更多
Objective: The purpose of this study was to differentiate between cerebral amyloid angiopathy (CAA) and hypertension (HTN) based on hemorrhage pattern interpretation. Methods: From June 1994 to Oct., 2000, 83 patients...Objective: The purpose of this study was to differentiate between cerebral amyloid angiopathy (CAA) and hypertension (HTN) based on hemorrhage pattern interpretation. Methods: From June 1994 to Oct., 2000, 83 patients admitted to our service with acute intracerebral hemorrhage (ICH) were investigated retrospectively; 41 patients with histologically proven diagnosis of cerebral amyloid angiography and 42 patients with clear history of hypertension were investigated. Results: Patients with a CAA-related ICH were significantly older than patients with a HTN-related ICH (74.0 years vs 66.5 years, P<0.05). There was a significantly higher number of hematomas≥30ml in CAA (85.3%) when compared with HTN (59.5%). No basal ganglional hemorrhage was seen in CAA, but in 40.5% in HTN. In CAA-related ICH, subarachnoid hemorrhage (SAH) was seen in 26 patients (63.4%) compared to only 11 patients (26.2%) in HTN-related ICH. Intraventricular hemorrhage was seen in 24.4% in CAA, and in 26.2% in HTN. Typical features of CAA-related ICH included lobar distribution affecting mainly the lobar superficial areas, lobulated appearance, rupture into the subarachnoid space, and secondary IVH from the lobar hemorrhage. More specifically, multiplicity of hemorrhage, bilaterality, and repeated episodes also strongly suggest the diagnosis of CAA. Multiple hemorrhages, defined as 2 or more separate hematomas in multiple lobes, accounted for 17.1% in CAA-related ICH. Conclusion: There are certain features in CAA on CT and MRI and in clinical settings. To some extent, these features may contribute to distinguishing CAA from HTN related ICH.展开更多
AIM:To report on the clinical features of patients with retinal amyloid angiopathy(RAA)who were identified to be caused by the transthyretin(TTR)Gly83Arg variant.METHODS:Case series of five patients diagnosed with RAA...AIM:To report on the clinical features of patients with retinal amyloid angiopathy(RAA)who were identified to be caused by the transthyretin(TTR)Gly83Arg variant.METHODS:Case series of five patients diagnosed with RAA was collected at Affiliated Hospital of Zunyi Medical University from January 2010 to December 2021.The clinical features,therapeutic strategies,and prognoses of all patients were reviewed.RESULTS:Five patients with a mean age of 52.00±7.23y were diagnosed as RAA.These patients were previously diagnosed with hereditary transthyretin amyloidosis caused by the TTR Gly83Arg variant.Vitreous opacity was found in all 10 eyes,and 7 eyes developed RAA 2 to 20y after the onset of hereditary transthyretin amyloidosis.The clinical manifestations were recurrent vitreous hemorrhage in 2 eyes(29%),neovascular glaucoma in 2 eyes(29%),and iris neovascularization in 1 eye(14%).Microangioma lesions were found in all affected eyes that underwent fundus fluorescein angiography(FFA)in this group of cases,and the incidence of the retinal non-perfusion area was 67%.Although no cases of retinal neovascularization were found,the prognosis of visual acuity was not ideal.CONCLUSION:This is the first report of RAA in patients with the TTR Gly83Arg variant.Complications such as RAA and glaucoma will seriously affect the visual prognosis of patients.Thereafter,regular ophthalmic follow-up of patients with hereditary transthyretin amyloidosis is essential.And FFA after vitrectomy is very important,which can help ophthalmologists detect RAA earlier and treat it in time.展开更多
BACKGROUND Cerebral proliferative angiopathy(CPA)is a rare subtype of arteriovenous malformation.It is extremely rare in pediatric patients and has serious implications for developing children.However,reports of these...BACKGROUND Cerebral proliferative angiopathy(CPA)is a rare subtype of arteriovenous malformation.It is extremely rare in pediatric patients and has serious implications for developing children.However,reports of these disorders worldwide are limited,and no uniform reference for diagnosis and treatment options exists.We report the case of a 6-year-old with CPA having predominantly neurological dysfunction and review the literature on pediatric CPA.CASE SUMMARY We report the case of a pediatric patient with CPA analyzed using digital subtraction angiography(DSA)who presented initially with a neurological disorder as the main manifestation.This case is the basis for further discussion of the clinical presentation,pathogenesis,diagnosis,and treatment of CPA in children.After the cerebral DSA,the patient was treated conservatively with sedation,fluid replacement,and blood anticoagulation.She could not cooperate with the followup magnetic resonance imaging examination because of her young age,and her family declined further treatment because of the surgery’s high risk.She was followed up for 3 months;her symptoms did not worsen.CONCLUSION This report of rare pediatric CPA can inform and advance clinical research on congenital cerebrovascular diseases.展开更多
Cerebral ischemia was induced using photothrombosis 1 hour after intraperitoneal injection of the p38 mitogen-activated protein kinase (MAPK) inhibitor SB239063 into Swedish mutant amyloid precursor protein (APP/SWE) ...Cerebral ischemia was induced using photothrombosis 1 hour after intraperitoneal injection of the p38 mitogen-activated protein kinase (MAPK) inhibitor SB239063 into Swedish mutant amyloid precursor protein (APP/SWE) transgenic and non-transgenic mice. The number of surviving neurons in the penumbra was quantified using Nissl staining, and the activity of p38 MAPKs was measured by western blotting. The number of surviving neurons in the penumbra was significantly reduced in APP/SWE transgenic mice compared with non-transgenic controls 7 days after cerebral ischemia, but the activity of p38 MAPKs was significantly elevated compared with the non-ischemic hemisphere in the APP/SWE transgenic mice. SB239063 prevented these changes. The APP/SWE mutation exacerbated ischemic brain injury, and this could be alleviated by inhibiting p38 MAPK activity.展开更多
Amyloid β-peptide,a major component of senile plaques in Alzheimer’s disease,has been implicated in neuronal cell death and cognitive impairment.Recently,studies have shown that the pathogenesis of cerebral ischemia...Amyloid β-peptide,a major component of senile plaques in Alzheimer’s disease,has been implicated in neuronal cell death and cognitive impairment.Recently,studies have shown that the pathogenesis of cerebral ischemia is closely linked with Alzheimer’s disease.In this study,a rat model of global cerebral ischemia-reperfusion injury was established via occlusion of four arteries;meanwhile,fibrillar amyloidβ-peptide was injected into the rat lateral ventricle.The Morris water maze test and histological staining revealed that administration of amyloidβ-peptide could further aggravate impairments to learning and memory and neuronal cell death in the hippocampus of rats subjected to cerebral ischemia-reperfusion injury.Western blot showed that phosphorylation of tau protein and the activity of glycogen synthase kinase 3βwere significantly stronger in cerebral ischemia-reperfusion injury rats subjected to amyloid β-peptide administration than those undergoing cerebral ischemia-reperfusion or amyloidβ-peptide administration alone.Conversely,the activity of protein phosphatase 2A was remarkably reduced in rats with cerebral ischemia-reperfusion injury following amyloidβ-peptide administration.These findings suggest that amyloidβ-peptide can potentiate tau phosphorylation induced by cerebral ischemia-reperfusion and thereby aggravate cognitive impairment.展开更多
BACKGROUND Cerebral proliferative angiopathy(CPA)is a rare vascular disease characterized by the presence of diffuse vascular proliferation,progressive vascular hyperflow and vasodilation of multiple vessels in the no...BACKGROUND Cerebral proliferative angiopathy(CPA)is a rare vascular disease characterized by the presence of diffuse vascular proliferation,progressive vascular hyperflow and vasodilation of multiple vessels in the normal brain parenchyma.Unlike cerebral arteriovenous malformations,CPA has a mixed appearance between that of lesions with cell proliferation and endothelial proliferation.To date,the pathogenesis of CPA is unclear,in which changes induced by cortical ischemia in the elastic layer of the blood supply artery and smooth muscle cells may be involved.CASE SUMMARY In this article,we retrospectively analyzed a case of hemorrhagic transformation of ischemic CPA diagnosed by digital subtraction angiography and reviewed the related literature for further exploration of its pathogenesis,diagnosis and treatment.CONCLUSION The information in the present case report may facilitate further clinical research on this cerebrovascular disease.展开更多
Neurovascular dysfunction,as an integral part of Alzheimer's disease,may have an important influence on the onset and progression of chronic neurodegenerative processes.The bloodbrain barrier(BBB)pathway is one of...Neurovascular dysfunction,as an integral part of Alzheimer's disease,may have an important influence on the onset and progression of chronic neurodegenerative processes.The bloodbrain barrier(BBB)pathway is one of the main pathways that mediates the clearance of amyloidbeta(Aβ)in the brain parenchyma.A large number of studies have shown that receptors and ATPbinding cassette transporte rs expressed on endothelial cells play an important role in Aβtransport across the BBB,but the specific mechanism is not clear.In this review,we summarize the possible mechanisms of Aβproduction and clearance,and in particular the relationship between Aβand brain capillary endothelial cells.Aβis produced by abnormal cleavage of the amyloid precursor protein via amyloidogenic processing under pathological conditions.Dys regulation of Aβclearance is considered to be the main reason for the massive accumulation of Aβin the brain parenchyma.Several pathways mediating Aβclearance from the brain into the periphery have been identified,including the BBB pathway,the blood-cerebros pinal fluid barrier and arachnoid granule pathway,and the lymphoidrelated pathway.Brain ca pilla ry endothelial cells are the key components of Aβclearance mediated by BBB.Receptors(such as LRP1,RAGE,and FcRn)and ATP-binding cassette transporters(such as P-gp,ABCA1,and ABCC1)expressed on endothelial cells play a critical role in Aβtranscytosis across the BBB.The toxic effects of Aβcan induce dysregulation of receptor and transpo rter expression on endothelial cells.Excessive Aβexerts potent detrimental cerebrovascular effects by promoting oxidative stress,inducing chronic inflammation,and impairing endothelial structure and functions.All of these are main causes for the reduction in Aβclearance across the BBB and the accumulation of Aβin the brain parenchyma.Therefo re,studies on the intera ctions between Aβand brain capillary endothelial cells,including their receptors and transporters,studies on inhibition of the toxic effects of Aβon endothelial cells,and studies on promoting the ability of endothelial cells to mediate Aβclearance may provide new therapeutic strategies for Aβclearance in Alzheimer's disease.展开更多
The cerebral formation of Amyloid β(Aβ) is a critical pathological feature of Alzheimer's disease(AD).An accumulation of this peptide as senile plaques(SP) was already reported by Alois Alzheimer,the discoverer ...The cerebral formation of Amyloid β(Aβ) is a critical pathological feature of Alzheimer's disease(AD).An accumulation of this peptide as senile plaques(SP) was already reported by Alois Alzheimer,the discoverer of the disease.Yet the exact contribution of Aβ to AD development remains elusive.Moreover,while extensive cerebral Aβ formation leads to fibril formation in many species,AD-like symptoms apparently depend on the highly conserved N-terminal residues R5,Y10 and H13.The amino acids were also shown to lead to the formation of Aβ-heme complexes,which exhibit peroxidase activity in the presence of H_2O_2.Taking together these observations we propose that the formation and enzymatic activity of the named complexes may represent an essential aspect of AD pathology.Furthermore,Aβ is also known to lead to cerebral micro-vessel destruction(CAA) as well as to hemolytic events.Thus we suggest that the Aβ-derived cerebral accumulation of blood-derived free heme represents a likely precondition for the subsequent formation of Aβ-heme complexes.展开更多
文摘This case report investigates the manifestation of cerebral amyloid angiopathy (CAA) through recurrent Transient Ischemic Attacks (TIAs) in an 82-year-old patient. Despite initial diagnostic complexities, cerebral angiography-MRI revealed features indicative of CAA. Symptomatic treatment resulted in improvement, but the patient later developed a fatal hematoma. The discussion navigates the intricate therapeutic landscape of repetitive TIAs in the elderly with cardiovascular risk factors, emphasizing the pivotal role of cerebral MRI and meticulous bleeding risk management. The conclusion stresses the importance of incorporating SWI sequences, specifically when suspecting a cardioembolic TIA, as a diagnostic measure to explore and exclude CAA in the differential diagnosis. This case report provides valuable insights into these challenges, highlighting the need to consider CAA in relevant cases.
文摘BACKGROUND Diagnosis of a dementia subtype can be complex and often requires comprehensive cognitive assessment and dedicated neuroimaging.Clinicians are prone to cognitive biases when reviewing such images.We present a case of cognitive impairment and demonstrate that initial imaging may have resulted in misleading the diagnosis due to such cognitive biases.CASE SUMMARY A 76-year-old man with no cognitive impairment presented with acute onset word finding difficulty with unremarkable blood tests and neurological examination.Magnetic resonance imaging(MRI)demonstrated multiple foci of periventricular and subcortical microhaemorrhage,consistent with cerebral amyloid angiopathy(CAA).Cognitive assessment of this patient demonstrated marked impairment mainly in verbal fluency and memory.However,processing speed and executive function are most affected in CAA,whereas episodic memory is relatively preserved,unlike in other causes of cognitive impairment,such as Alzheimer’s dementia(AD).This raised the question of an underlying diagnosis of dementia.Repeat MRI with dedicated coronal views demonstrated mesial temporal lobe atrophy which is consistent with AD.CONCLUSION MRI brain can occasionally result in diagnostic overshadowing,and the application of artificial intelligence to medical imaging may overcome such cognitive biases.
文摘Objective To study the changes of biomarkers in cerebrospinal fluid(CSF) in cerebral amyloid angiopathy(CAA) dementia and Alzheimer's disease.Methods Levels of amyloid protein β(Aβ42,Aβ40) and phosphorylated Tau-protein(P-tau) in CSF and ratio of Aβ42/Aβ40 were tested in 5 cases with CAA dementia and 20 cases with Alzheimer's disease collected at Peking Union Medical College Hospital from December 2001 to March 2011.Results The levels of Aβ42,Aβ40,and P-tau in CSF and ratio of Aβ42/Aβ40 were(660.4±265.2) ng/L,(7111.0±1033.4) ng/L,(71.8±51.5) ng/L,and 0.077±0.033,respectively in CAA dementia and(663.6±365.6) ng/L,(5115.0±2931.1) ng/L,(47.7±38.8) ng/L,and 0.192±0.140,respectively in Alzheimer's disease patients.There were no statistically significant differences between CAA dementia and Alzheimer's disease in terms of these CSF biomarkers(all P>0.05).Conclusion Measurements of CSF biomarkers may not be helpful in differential diagnosis of CAA and Alzheimer's disease.
基金The Hidaka Research Projects(grant number:01-D-1-07)
文摘Background Cerebral amyloid angiopathy is a common cause of subcortical hemorrhage in older adults.Although open hematoma removal may be performed for severe subcortical hemorrhage,its safety in patients with cerebral amyloid angiopathy has not been established,and postoperative rebleeding may occur.Therefore,this study aimed to investigate factors associated with postoperative rebleeding.Methods Out of 145 consecutive patients who had undergone craniotomy for surgical removal of subcortical intracerebral hemorrhage between April 2010 and August 2019 at a single institution in Japan,we examined 109 patients with subcortical hemorrhage who met the inclusion criteria.After excluding 30 patients whose tissue samples were unsuitable for the study,the final study cohort comprised 79 patients.Results Of the 79 patients,50(63%)were diagnosed with cerebral amyloid angiopathy(cerebral amyloid angiopathy group)and 29(37%)were not diagnosed with noncerebral amyloid angiopathy(noncerebral amyloid angiopathy group).Postoperative rebleeding occurred in 12 patients(24%)in the cerebral amyloid angiopathy group and in 2 patients(7%)in the noncerebral amyloid angiopathy group.Preoperative prothrombin time-international normalized ratio and intraoperative bleeding volume were significantly associated with postoperative rebleeding in the cerebral amyloid angiopathy group(odds ratio=42.4,95%confidence interval=1.14-1578;p=0.042 and odds ratio=1.005,95%confidence interval=1.001-1.008;p=0.007,respectively).Conclusions Patients with cerebral amyloid angiopathy-related cerebral hemorrhage who are receiving antithrombotic therapy,particularly warfarin therapy,are at a high risk of postoperative rebleeding.Trial registration Registry and Registration Number of the study:19-220,2019/12/23,retrospectively registered.
基金National Key Research and Development Program of China(No.2016YFC1300500-505)。
文摘Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a rare but increasingly recognized subtype of CAA. CAA-RI consists of two subtypes: inflammatory cerebral amyloid angiopathy and amyloid β (Aβ)-related angiitis. Acute or subacute onset of cognitive decline or behavioral changes is the most common symptom of CAA-RI. Rapid progressive dementia, headache, seizures, or focal neurological deficits, with patchy or confluent hyperintensity on T2 or fluid-attenuated inversion recovery sequences and evidence of strictly lobar microbleeds or cortical superficial siderosis on susceptibility-weighted imaging imply CAA-RI. The gold standard for diagnosis is autopsy or brain biopsy. However, biopsy is invasive;consequently, most clinically diagnosed cases have been based on clinical and radiological data. Other diagnostic indexes include the apolipoprotein E ε4 allele, Aβ and anti-Aβ antibodies in cerebral spinal fluid and amyloid positron emission tomography. Many diseases with similar clinical manifestations should be carefully ruled out. Immunosuppressive therapy is effective both during initial presentation and in relapses. The use of glucocorticoids and immunosuppressants improves prognosis. This article reviews the pathology and pathogenesis, clinical and imaging manifestations, diagnostic criteria, treatment, and prognosis of CAA-RI, and highlights unsolved problems in the existing research.
基金This work was supported by national natural science grant(81570035).
文摘Cerebral amyloid angiopathy(CAA)is characterized by the deposition of amyloid β-protein(Aβ)in the leptomeningeal and cortical blood vessels,which is an age-dependent risk factor for intracerebral hemorrhage(ICH),ischemic stroke and contributes to cerebrovascular dysfunction leading to cognitive impairment.However clinical prevention and treatment of the disease is very difficult because of its occult onset and severity of the symptoms.In recent years,many anti-amyloid β immunotherapies have not demonstrated clinical efficacy in subjects with Alzheimer’s disease(AD),and the failure may be due to the deposition of Aβ in the cerebrovascular export pathway resulting in further damage to blood vessels and aggravating CAA.So decreased clearance of Aβ in blood vessels plays a crucial role in the development of CAA and AD,and identification of the molecular pathways involved will provide new targets for treatment.In this review,we mainly describe the mechanisms of Aβ clearance through vessels,especially in terms of some proteins and receptors involved in this process.
文摘Objective: The purpose of this study was to differentiate between cerebral amyloid angiopathy (CAA) and hypertension (HTN) based on hemorrhage pattern interpretation. Methods: From June 1994 to Oct., 2000, 83 patients admitted to our service with acute intracerebral hemorrhage (ICH) were investigated retrospectively; 41 patients with histologically proven diagnosis of cerebral amyloid angiography and 42 patients with clear history of hypertension were investigated. Results: Patients with a CAA-related ICH were significantly older than patients with a HTN-related ICH (74.0 years vs 66.5 years, P<0.05). There was a significantly higher number of hematomas≥30ml in CAA (85.3%) when compared with HTN (59.5%). No basal ganglional hemorrhage was seen in CAA, but in 40.5% in HTN. In CAA-related ICH, subarachnoid hemorrhage (SAH) was seen in 26 patients (63.4%) compared to only 11 patients (26.2%) in HTN-related ICH. Intraventricular hemorrhage was seen in 24.4% in CAA, and in 26.2% in HTN. Typical features of CAA-related ICH included lobar distribution affecting mainly the lobar superficial areas, lobulated appearance, rupture into the subarachnoid space, and secondary IVH from the lobar hemorrhage. More specifically, multiplicity of hemorrhage, bilaterality, and repeated episodes also strongly suggest the diagnosis of CAA. Multiple hemorrhages, defined as 2 or more separate hematomas in multiple lobes, accounted for 17.1% in CAA-related ICH. Conclusion: There are certain features in CAA on CT and MRI and in clinical settings. To some extent, these features may contribute to distinguishing CAA from HTN related ICH.
基金Supported by the National Natural Science Foundation of China(No.31871261)the Guizhou Science and Technology Cooperation Foundation[No.ZK(2021)general 423]the Research Initiation Fund for Masters in Affiliated Hospital of Zunyi Medical University(No.2016-43)。
文摘AIM:To report on the clinical features of patients with retinal amyloid angiopathy(RAA)who were identified to be caused by the transthyretin(TTR)Gly83Arg variant.METHODS:Case series of five patients diagnosed with RAA was collected at Affiliated Hospital of Zunyi Medical University from January 2010 to December 2021.The clinical features,therapeutic strategies,and prognoses of all patients were reviewed.RESULTS:Five patients with a mean age of 52.00±7.23y were diagnosed as RAA.These patients were previously diagnosed with hereditary transthyretin amyloidosis caused by the TTR Gly83Arg variant.Vitreous opacity was found in all 10 eyes,and 7 eyes developed RAA 2 to 20y after the onset of hereditary transthyretin amyloidosis.The clinical manifestations were recurrent vitreous hemorrhage in 2 eyes(29%),neovascular glaucoma in 2 eyes(29%),and iris neovascularization in 1 eye(14%).Microangioma lesions were found in all affected eyes that underwent fundus fluorescein angiography(FFA)in this group of cases,and the incidence of the retinal non-perfusion area was 67%.Although no cases of retinal neovascularization were found,the prognosis of visual acuity was not ideal.CONCLUSION:This is the first report of RAA in patients with the TTR Gly83Arg variant.Complications such as RAA and glaucoma will seriously affect the visual prognosis of patients.Thereafter,regular ophthalmic follow-up of patients with hereditary transthyretin amyloidosis is essential.And FFA after vitrectomy is very important,which can help ophthalmologists detect RAA earlier and treat it in time.
文摘BACKGROUND Cerebral proliferative angiopathy(CPA)is a rare subtype of arteriovenous malformation.It is extremely rare in pediatric patients and has serious implications for developing children.However,reports of these disorders worldwide are limited,and no uniform reference for diagnosis and treatment options exists.We report the case of a 6-year-old with CPA having predominantly neurological dysfunction and review the literature on pediatric CPA.CASE SUMMARY We report the case of a pediatric patient with CPA analyzed using digital subtraction angiography(DSA)who presented initially with a neurological disorder as the main manifestation.This case is the basis for further discussion of the clinical presentation,pathogenesis,diagnosis,and treatment of CPA in children.After the cerebral DSA,the patient was treated conservatively with sedation,fluid replacement,and blood anticoagulation.She could not cooperate with the followup magnetic resonance imaging examination because of her young age,and her family declined further treatment because of the surgery’s high risk.She was followed up for 3 months;her symptoms did not worsen.CONCLUSION This report of rare pediatric CPA can inform and advance clinical research on congenital cerebrovascular diseases.
基金supported by the National Natural Science Foundation of China, No. 81171191Shenzhen Bureau of Science Technology and Information, No. 201002013+1 种基金Guangdong Province Medical Science Fund, No. A2008601 and Jinan University Scientific Research Foundation for Creation and Cultivation, No. 21609708
文摘Cerebral ischemia was induced using photothrombosis 1 hour after intraperitoneal injection of the p38 mitogen-activated protein kinase (MAPK) inhibitor SB239063 into Swedish mutant amyloid precursor protein (APP/SWE) transgenic and non-transgenic mice. The number of surviving neurons in the penumbra was quantified using Nissl staining, and the activity of p38 MAPKs was measured by western blotting. The number of surviving neurons in the penumbra was significantly reduced in APP/SWE transgenic mice compared with non-transgenic controls 7 days after cerebral ischemia, but the activity of p38 MAPKs was significantly elevated compared with the non-ischemic hemisphere in the APP/SWE transgenic mice. SB239063 prevented these changes. The APP/SWE mutation exacerbated ischemic brain injury, and this could be alleviated by inhibiting p38 MAPK activity.
基金supported by the National High Technology Research and Development Program of China("863"Program),No.2012AA020905the National Natural Science Foundation of China,No.81171143 and30971011+1 种基金National Natural Science Foundation of China(NSFC)/Research Grants Council(RGC) Joint Research Scheme,No.81161160570TsinghuaYue-Yuen Medical Sciences Fund
文摘Amyloid β-peptide,a major component of senile plaques in Alzheimer’s disease,has been implicated in neuronal cell death and cognitive impairment.Recently,studies have shown that the pathogenesis of cerebral ischemia is closely linked with Alzheimer’s disease.In this study,a rat model of global cerebral ischemia-reperfusion injury was established via occlusion of four arteries;meanwhile,fibrillar amyloidβ-peptide was injected into the rat lateral ventricle.The Morris water maze test and histological staining revealed that administration of amyloidβ-peptide could further aggravate impairments to learning and memory and neuronal cell death in the hippocampus of rats subjected to cerebral ischemia-reperfusion injury.Western blot showed that phosphorylation of tau protein and the activity of glycogen synthase kinase 3βwere significantly stronger in cerebral ischemia-reperfusion injury rats subjected to amyloid β-peptide administration than those undergoing cerebral ischemia-reperfusion or amyloidβ-peptide administration alone.Conversely,the activity of protein phosphatase 2A was remarkably reduced in rats with cerebral ischemia-reperfusion injury following amyloidβ-peptide administration.These findings suggest that amyloidβ-peptide can potentiate tau phosphorylation induced by cerebral ischemia-reperfusion and thereby aggravate cognitive impairment.
基金Supported by National Natural Science Foundation of China,No.81771154.
文摘BACKGROUND Cerebral proliferative angiopathy(CPA)is a rare vascular disease characterized by the presence of diffuse vascular proliferation,progressive vascular hyperflow and vasodilation of multiple vessels in the normal brain parenchyma.Unlike cerebral arteriovenous malformations,CPA has a mixed appearance between that of lesions with cell proliferation and endothelial proliferation.To date,the pathogenesis of CPA is unclear,in which changes induced by cortical ischemia in the elastic layer of the blood supply artery and smooth muscle cells may be involved.CASE SUMMARY In this article,we retrospectively analyzed a case of hemorrhagic transformation of ischemic CPA diagnosed by digital subtraction angiography and reviewed the related literature for further exploration of its pathogenesis,diagnosis and treatment.CONCLUSION The information in the present case report may facilitate further clinical research on this cerebrovascular disease.
基金Shanxi Provincial Special Fund for the Transformation of Scientific and Technological Achievements,No.201704D13111584(to JHG)。
文摘Neurovascular dysfunction,as an integral part of Alzheimer's disease,may have an important influence on the onset and progression of chronic neurodegenerative processes.The bloodbrain barrier(BBB)pathway is one of the main pathways that mediates the clearance of amyloidbeta(Aβ)in the brain parenchyma.A large number of studies have shown that receptors and ATPbinding cassette transporte rs expressed on endothelial cells play an important role in Aβtransport across the BBB,but the specific mechanism is not clear.In this review,we summarize the possible mechanisms of Aβproduction and clearance,and in particular the relationship between Aβand brain capillary endothelial cells.Aβis produced by abnormal cleavage of the amyloid precursor protein via amyloidogenic processing under pathological conditions.Dys regulation of Aβclearance is considered to be the main reason for the massive accumulation of Aβin the brain parenchyma.Several pathways mediating Aβclearance from the brain into the periphery have been identified,including the BBB pathway,the blood-cerebros pinal fluid barrier and arachnoid granule pathway,and the lymphoidrelated pathway.Brain ca pilla ry endothelial cells are the key components of Aβclearance mediated by BBB.Receptors(such as LRP1,RAGE,and FcRn)and ATP-binding cassette transporters(such as P-gp,ABCA1,and ABCC1)expressed on endothelial cells play a critical role in Aβtranscytosis across the BBB.The toxic effects of Aβcan induce dysregulation of receptor and transpo rter expression on endothelial cells.Excessive Aβexerts potent detrimental cerebrovascular effects by promoting oxidative stress,inducing chronic inflammation,and impairing endothelial structure and functions.All of these are main causes for the reduction in Aβclearance across the BBB and the accumulation of Aβin the brain parenchyma.Therefo re,studies on the intera ctions between Aβand brain capillary endothelial cells,including their receptors and transporters,studies on inhibition of the toxic effects of Aβon endothelial cells,and studies on promoting the ability of endothelial cells to mediate Aβclearance may provide new therapeutic strategies for Aβclearance in Alzheimer's disease.
基金supported by the Alzheimer Forschung Initiative e.V.(AFI 13810)
文摘The cerebral formation of Amyloid β(Aβ) is a critical pathological feature of Alzheimer's disease(AD).An accumulation of this peptide as senile plaques(SP) was already reported by Alois Alzheimer,the discoverer of the disease.Yet the exact contribution of Aβ to AD development remains elusive.Moreover,while extensive cerebral Aβ formation leads to fibril formation in many species,AD-like symptoms apparently depend on the highly conserved N-terminal residues R5,Y10 and H13.The amino acids were also shown to lead to the formation of Aβ-heme complexes,which exhibit peroxidase activity in the presence of H_2O_2.Taking together these observations we propose that the formation and enzymatic activity of the named complexes may represent an essential aspect of AD pathology.Furthermore,Aβ is also known to lead to cerebral micro-vessel destruction(CAA) as well as to hemolytic events.Thus we suggest that the Aβ-derived cerebral accumulation of blood-derived free heme represents a likely precondition for the subsequent formation of Aβ-heme complexes.
