Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 14 de 14
Filtrar
1.
Alzheimers Res Ther ; 16(1): 74, 2024 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-38582898

RESUMEN

BACKGROUND: Neuropsychiatric symptoms (NPS) may affect cognition, but their burden in cerebral amyloid angiopathy (CAA), one of the main causes of intracerebral hemorrhage (ICH) and dementia in the elderly, remains unclear. We investigated NPS, with emphasis on apathy and irritability in sporadic (sCAA) and Dutch-type hereditary (D-)CAA. METHODS: We included patients with sCAA and (pre)symptomatic D-CAA, and controls from four prospective cohort studies. We assessed NPS per group, stratified for history of ICH, using the informant-based Neuropsychiatric Inventory (NPI-Q), Starkstein Apathy scale (SAS), and Irritability Scale. We modeled the association of NPS with disease status, executive function, processing speed, and CAA-burden score on MRI and investigated sex-differences. RESULTS: We included 181 participants: 82 with sCAA (mean[SD] age 72[6] years, 44% women, 28% previous ICH), 56 with D-CAA (52[11] years, 54% women, n = 31[55%] presymptomatic), and 43 controls (69[9] years, 44% women). The NPI-Q NPS-count differed between patients and controls (sCAA-ICH+:adj.ß = 1.4[95%CI:0.6-2.3]; sCAA-ICH-:1.3[0.6-2.0]; symptomatic D-CAA:2.0[1.1-2.9]; presymptomatic D-CAA:1.2[0.1-2.2], control median:0[IQR:0-3]), but not between the different CAA-subgroups. Apathy and irritability were reported most frequently: n = 12[31%] sCAA, 19[37%] D-CAA had a high SAS-score; n = 12[29%] sCAA, 14[27%] D-CAA had a high Irritability Scale score. NPS-count was associated with decreased processing speed (adj.ß=-0.6[95%CI:-0.8;-0.4]) and executive function (adj.ß=-0.4[95%CI:-0.6;-0.1]), but not with radiological CAA-burden. Men had NPS more often than women. DISCUSSION: According to informants, one third to half of patients with CAA have NPS, mostly apathy, even in presymptomatic D-CAA and possibly with increased susceptibility in men. Neurologists should inform patients and caregivers of these disease consequences and treat or refer patients with NPS appropriately.


Asunto(s)
Apatía , Angiopatía Amiloide Cerebral Familiar , Angiopatía Amiloide Cerebral , Masculino , Humanos , Femenino , Anciano , Niño , Angiopatía Amiloide Cerebral Familiar/complicaciones , Estudios Prospectivos , Angiopatía Amiloide Cerebral/complicaciones , Angiopatía Amiloide Cerebral/diagnóstico por imagen , Hemorragia Cerebral/complicaciones , Imagen por Resonancia Magnética
2.
J Cereb Blood Flow Metab ; 43(12): 2144-2155, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37708241

RESUMEN

Cerebral Amyloid Angiopathy (CAA) is characterized by cerebrovascular amyloid-ß accumulation leading to hallmark cortical MRI markers, such as vascular reactivity, but white matter is also affected. By studying the relationship in different disease stages of Dutch-type CAA (D-CAA), we tested the relation between vascular reactivity and microstructural white matter integrity loss. In a cross-sectional study in D-CAA, 3 T MRI was performed with Blood-Oxygen-Level-Dependent (BOLD) fMRI upon visual activation to assess vascular reactivity and diffusion tensor imaging to assess microstructural white matter integrity through Peak Width of Skeletonized Mean Diffusivity (PSMD). We assessed the relationship between BOLD parameters - amplitude, time-to-peak (TTP), and time-to-baseline (TTB) - and PSMD, with linear and quadratic regression modeling. In total, 25 participants were included (15/10 pre-symptomatic/symptomatic; mean age 36/59 y). A lowered BOLD amplitude (unstandardized ß = 0.64, 95%CI [0.10, 1.18], p = 0.02, Adjusted R2 = 0.48), was quadratically associated with increased PSMD levels. A delayed BOLD response, with prolonged TTP (ß = 8.34 × 10-6, 95%CI [1.84 × 10-6, 1.48 × 10-5], p = 0.02, Adj. R2 = 0.25) and TTB (ß = 6.57 × 10-6, 95%CI [1.92 × 10-6, 1.12 × 10-5], p = 0.008, Adj. R2 = 0.29), was linearly associated with increased PSMD. In D-CAA subjects, predominantly in the symptomatic stage, impaired cerebrovascular reactivity is related to microstructural white matter integrity loss. Future longitudinal studies are needed to investigate whether this relation is causal.


Asunto(s)
Angiopatía Amiloide Cerebral Familiar , Angiopatía Amiloide Cerebral , Sustancia Blanca , Humanos , Adulto , Angiopatía Amiloide Cerebral Familiar/diagnóstico por imagen , Angiopatía Amiloide Cerebral Familiar/complicaciones , Sustancia Blanca/diagnóstico por imagen , Imagen de Difusión Tensora , Estudios Transversales , Angiopatía Amiloide Cerebral/complicaciones , Imagen por Resonancia Magnética/métodos
3.
Trials ; 24(1): 378, 2023 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-37277877

RESUMEN

BACKGROUND: Cerebral amyloid angiopathy (CAA) is a disease caused by the accumulation of the amyloid-beta protein and is a major cause of intracerebral hemorrhage (ICH) and vascular dementia in the elderly. The presence of the amyloid-beta protein in the vessel wall may induce a chronic state of cerebral inflammation by activating astrocytes, microglia, and pro-inflammatory substances. Minocycline, an antibiotic of the tetracycline family, is known to modulate inflammation, gelatinase activity, and angiogenesis. These processes are suggested to be key mechanisms in CAA pathology. Our aim is to show the target engagement of minocycline and investigate in a double-blind placebo-controlled randomized clinical trial whether treatment with minocycline for 3 months can decrease markers of neuroinflammation and of the gelatinase pathway in cerebrospinal fluid (CSF) in CAA patients. METHODS: The BATMAN study population consists of 60 persons: 30 persons with hereditary Dutch type CAA (D-CAA) and 30 persons with sporadic CAA. They will be randomized for either placebo or minocycline (15 sporadic CAA/15 D-CAA minocycline, 15 sporadic CAA/15 D-CAA placebo). At t = 0 and t = 3 months, we will collect CSF and blood samples, perform a 7-T MRI, and collect demographic characteristics. DISCUSSION: The results of this proof-of-principle study will be used to assess the potential of target engagement of minocycline for CAA. Therefore, our primary outcome measures are markers of neuroinflammation (IL-6, MCP-1, and IBA-1) and of the gelatinase pathway (MMP2/9 and VEGF) in CSF. Secondly, we will look at the progression of hemorrhagic markers on 7-T MRI before and after treatment and investigate serum biomarkers. TRIAL REGISTRATION: ClinicalTrials.gov NCT05680389. Registered on January 11, 2023.


Asunto(s)
Angiopatía Amiloide Cerebral Familiar , Angiopatía Amiloide Cerebral , Anciano , Humanos , Péptidos beta-Amiloides , Antibacterianos/farmacología , Angiopatía Amiloide Cerebral/diagnóstico por imagen , Angiopatía Amiloide Cerebral/tratamiento farmacológico , Angiopatía Amiloide Cerebral/complicaciones , Angiopatía Amiloide Cerebral Familiar/complicaciones , Angiopatía Amiloide Cerebral Familiar/patología , Hemorragia Cerebral/etiología , Gelatinasas , Inflamación , Minociclina , Enfermedades Neuroinflamatorias , Ensayos Clínicos Controlados Aleatorios como Asunto
4.
Stroke ; 51(12): 3608-3612, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33148142

RESUMEN

BACKGROUND AND PURPOSE: The Edinburgh computed tomography and genetic criteria enable diagnosis of cerebral amyloid angiopathy (CAA) associated lobar intracerebral hemorrhage (ICH) but have not been validated in living patients. We assessed the sensitivity of the Edinburgh criteria in patients with acute lobar ICH due to Dutch-type hereditary CAA; a genetic and pure form of CAA. METHODS: We retrospectively analyzed computed tomography-scans from a cohort of consecutive Dutch-type hereditary CAA patients who presented with ≥1 episode(s) of acute lobar ICH at the Leiden University Medical Center. Presence of subarachnoid hemorrhage (SAH) and finger-like projections (FLP) were determined. Association of SAH and FLP with ICH volume was analyzed using multivariate linear regression. RESULTS: We included 55 Dutch-type hereditary CAA patients (mean age 56 years, 55% men) with a total of 107 episodes of acute lobar ICH. SAH was present in 82/107 (76%) and FLP in 62/107 (58%), resulting in a sensitivity of 76% for SAH and 58% for FLP. In 56 (52%), both markers were present. Nineteen (18%) lobar ICH showed no SAH extension or FLP. ICH volume was significantly associated with presence of SAH (median volume 4 versus 28 mL; P=0.001) and presence of FLP (median volume 7 versus 39 mL; P<0.001). With an ICH volume of ≥40 mL, the sensitivity of the presence of both SAH and FLP was >81% (95% CI, 70%-92%), whereas in ICH volumes <15 mL the sensitivity was <50%. CONCLUSIONS: The computed tomography-based Edinburgh criteria seem to be a sensitive diagnostic test for CAA-associated lobar ICH, although they should be used with caution in small-sized lobar ICH.


Asunto(s)
Angiopatía Amiloide Cerebral Familiar/diagnóstico por imagen , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Subaracnoidea/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Apolipoproteínas E/genética , Angiopatía Amiloide Cerebral Familiar/complicaciones , Hemorragia Cerebral/clasificación , Hemorragia Cerebral/etiología , Hemorragia Cerebral/genética , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X
5.
Neurology ; 87(8): 773-81, 2016 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-27466465

RESUMEN

OBJECTIVE: To investigate the prevalence and clinical features of posttransplant CNS symptoms in patients with hereditary ATTR amyloidosis and their Pittsburgh compound B (PiB)-PET imaging correlates. METHODS: We monitored prevalence and type of CNS symptoms in 53 consecutive posttransplant patients with hereditary ATTR amyloidosis. (11)C-PiB-PET was performed in 15 patients with various disease durations. We also analyzed pathologic and biochemical characteristics of ATTR amyloid deposition in the brain of a posttransplant patient. RESULTS: Transient focal neurologic episodes (TFNEs) attributed to ATTR-type cerebral amyloid angiopathy (CAA) were found in 11.3% of posttransplant hereditary ATTR amyloidosis patients. TFNE occurred on average 16.8 years after onset of the disease. Patients with longer duration of illness (≥10 years) showed increased (11)C-PiB retention in the brain. The (11)C-PiB accumulation pattern in hereditary ATTR amyloidosis was unique and different from those in Alzheimer disease or Aß-type CAA. In the autopsy case, ATTR amyloid deposition was mainly localized to leptomeningeal vessels and leptomeninges of the brain. Amyloid fibrils in the brain were almost completely composed of variant transthyretin (TTR). CONCLUSIONS: TFNE due to ATTR-type CAA occurred frequently in posttransplant patients with long disease durations. (11)C-PiB-PET is a useful diagnostic tool for ATTR-type CAA. ATTR amyloid deposition in the CNS, as measured by PiB-PET, was detected approximately 10 years before onset of TFNE.


Asunto(s)
Compuestos de Anilina , Enfermedades del Sistema Nervioso Central/etiología , Angiopatía Amiloide Cerebral Familiar/complicaciones , Trasplante de Hígado/métodos , Tomografía de Emisión de Positrones/métodos , Prealbúmina/metabolismo , Tiazoles , Enfermedades del Sistema Nervioso Central/metabolismo , Enfermedades del Sistema Nervioso Central/fisiopatología , Angiopatía Amiloide Cerebral Familiar/metabolismo , Angiopatía Amiloide Cerebral Familiar/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prealbúmina/genética , Estudios Retrospectivos , Factores de Tiempo
6.
Stroke ; 47(7): 1702-9, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27245348

RESUMEN

BACKGROUND AND PURPOSE: Lombardia GENS is a multicentre prospective study aimed at diagnosing 5 single-gene disorders associated with stroke (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, Fabry disease, MELAS [mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes], hereditary cerebral amyloid angiopathy, and Marfan syndrome) by applying diagnostic algorithms specific for each clinically suspected disease METHODS: We enrolled a consecutive series of patients with ischemic or hemorrhagic stroke or transient ischemic attack admitted in stroke units in the Lombardia region participating in the project. Patients were defined as probable when presenting with stroke or transient ischemic attack of unknown etiopathogenic causes, or in the presence of <3 conventional vascular risk factors or young age at onset, or positive familial history or of specific clinical features. Patients fulfilling diagnostic algorithms specific for each monogenic disease (suspected) were referred for genetic analysis. RESULTS: In 209 patients (57.4±14.7 years), the application of the disease-specific algorithm identified 227 patients with possible monogenic disease. Genetic testing identified pathogenic mutations in 7% of these cases. Familial history of stroke was the only significant specific feature that distinguished mutated patients from nonmutated ones. The presence of cerebrovascular risk factors did not exclude a genetic disease. CONCLUSIONS: In patients prescreened using a clinical algorithm for monogenic disorders, we identified monogenic causes of events in 7% of patients in comparison to the 1% to 5% prevalence reported in previous series.


Asunto(s)
CADASIL/genética , Angiopatía Amiloide Cerebral Familiar/genética , Enfermedad de Fabry/genética , Pruebas Genéticas , Síndrome MELAS/genética , Síndrome de Marfan/genética , Accidente Cerebrovascular/genética , Adulto , Anciano , CADASIL/complicaciones , Angiopatía Amiloide Cerebral Familiar/complicaciones , Análisis Mutacional de ADN , Enfermedad de Fabry/complicaciones , Femenino , Humanos , Síndrome MELAS/complicaciones , Masculino , Síndrome de Marfan/complicaciones , Persona de Mediana Edad , Mutación , Sistema de Registros , Accidente Cerebrovascular/etiología
7.
Neuromolecular Med ; 18(1): 99-108, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26661731

RESUMEN

The involvement of apolipoproteins, such as the ApoE4 isoform, in Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) highlights the fact that certain lipid carriers may participate in soluble ß-amyloid (Aß) transport. Our general aim was to characterize the soluble levels of the apolipoproteins apoE, apoA1 and apoJ/clusterin and their genotype status in patients with CAA. We analyzed the genotypes frequency of APOA1 (rs5069, rs670), CLU (rs11136000, rs1532278, rs7012010, rs9331888) and APOE (rs429358, rs7412) in a cohort of patients with CAA-associated intracerebral hemorrhage (ICH) (n = 59) and compared the results with those from hypertension-associated ICH (n = 42), AD patients (n = 73) and controls (n = 88). In a subgroup of patients, we also determined the plasma concentrations of apoE, apoA1 and apoJ/clusterin. We found increased plasma apoJ/clusterin levels in CAA patients compared to AD patients or controls after adjusting for sex and age (CAA vs. controls, p = 0.033; CAA vs. AD, p = 0.013). ApoA1 levels were not altered between groups, although a strong correlation was observed between plasma Aß(1-40) and apoA1 among CAA patients (r = 0.583, p = 0.007). Regarding plasma apoE concentration, a robust association between circulating levels and genotype status was confirmed (p < 0.001). Whereas the APOE4 frequency was higher in AD (p < 0.001) and CAA (p = 0.013), the APOA1 and CLU genotypes were not different among groups. In the CAA cohort, the risk-linked CLU variant (C) rs11136000 was associated with white matter hyperintensities (p = 0.045) and the presence of lobar microbleeds (p = 0.023) on MRI. In summary, our findings suggest that apoA1 may act as a physiological transporter of Aß(1-40) and that apoJ/clusterin appears to be a chaperone related to distinctive lesions in CAA brains.


Asunto(s)
Apolipoproteína A-I/genética , Apolipoproteínas E/genética , Angiopatía Amiloide Cerebral/genética , Clusterina/genética , Polimorfismo de Nucleótido Simple , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/genética , Apolipoproteína A-I/sangre , Apolipoproteínas E/sangre , Angiopatía Amiloide Cerebral/sangre , Angiopatía Amiloide Cerebral/complicaciones , Angiopatía Amiloide Cerebral/diagnóstico por imagen , Angiopatía Amiloide Cerebral Familiar/sangre , Angiopatía Amiloide Cerebral Familiar/complicaciones , Angiopatía Amiloide Cerebral Familiar/diagnóstico por imagen , Angiopatía Amiloide Cerebral Familiar/genética , Hemorragia Cerebral/etiología , Clusterina/sangre , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Hipertensión/sangre , Hipertensión/complicaciones , Hipertensión/genética , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Sustancia Blanca/patología
8.
Funct Neurol ; 27(2): 107-17, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23158583

RESUMEN

The Italian region of Lombardy, with its existing stroke centers and high-technology laboratories, provides a favorable context for studying monogenic diseases associated with stroke. The Lombardia GENS project was set up to create a regional network for the diagnosis of six monogenic diseases associated with stroke: CADASIL, Fabry disease, MELAS, familial and sporadic hemiplegic migraine, hereditary cerebral amyloid angiopathy and Marfan syndrome. The network comprises 36 stroke centers and seven high-technology laboratories, performing molecular analysis. In this context, all stroke/TIA patients fulfilling clinical criteria for monogenic diseases are currently being included in an ongoing study. Demographic, clinical and family data and diagnostic criteria are collected using standardized forms. On the basis of stroke incidence in Lombardy and the reported prevalence of the diseases considered, we expect, during the course of the study, to collect datasets and DNA samples from more than 200 stroke patients suspected of having monogenic diseases. This will allow evaluation of the regional burden and better phenotype characterization of monogenic diseases associated with stroke.


Asunto(s)
CADASIL/complicaciones , Angiopatía Amiloide Cerebral Familiar/complicaciones , Enfermedad de Fabry/complicaciones , Síndrome MELAS/complicaciones , Síndrome de Marfan/complicaciones , Accidente Cerebrovascular/complicaciones , CADASIL/genética , Angiopatía Amiloide Cerebral Familiar/genética , Enfermedad de Fabry/genética , Humanos , Italia , Síndrome MELAS/genética , Síndrome de Marfan/genética , Sistema de Registros , Accidente Cerebrovascular/genética
9.
Amyloid ; 15(4): 275-7, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19065301

RESUMEN

A patient with Down's syndrome (DS) died of cerebral hemorrhage at age 52. At autopsy, a large sub-cortical hematoma was present in the right frontal lobe, and microscopic examination showed numerous senile plaques and neurofibrillary tangles in an extensive area of neocortex and also disclosed heavy involvement of vascular walls by amyloid deposition. These senile plaque and vascular amyloid deposits were specifically stained with an antibody to Abeta. His APOE genotype was epsilon4/epsilon4. This is a rare case of DS with cerebral amyloid angiopathy (CAA)-related cerebral hemorrhage. Genetic factors, such as APOE genotype, conceivably determine the risk of vascular rupture in individuals with CAA, even among patients with DS.


Asunto(s)
Angiopatía Amiloide Cerebral Familiar/complicaciones , Hemorragia Cerebral/etiología , Síndrome de Down/complicaciones , Péptidos beta-Amiloides/genética , Apolipoproteínas E/genética , Angiopatía Amiloide Cerebral Familiar/genética , Angiopatía Amiloide Cerebral Familiar/patología , Hemorragia Cerebral/patología , Síndrome de Down/genética , Síndrome de Down/patología , Genotipo , Humanos , Masculino , Persona de Mediana Edad
10.
J Neurosci Res ; 85(13): 2917-23, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17628026

RESUMEN

Hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D), is an autosomal dominant disorder caused by the Dutch mutation (E693Q) in the beta-amyloid precursor protein. This mutation produces an aberrant amyloid beta (Abeta) species (AbetaE22Q) and causes severe meningocortical vascular Abeta deposition. We analyzed the Abeta composition of the vascular amyloid in the brains of HCHWA-D patients. Immunohistochemistry demonstrated that the vascular amyloid contained both Abeta40 and Abeta42, with a high Abeta40/Abeta42 ratio. In Western blotting of cerebral microvessel fractions isolated from the brains, both wild-type and Dutch-type Abeta40 were observed as major species. Reverse-phase HPLC-mass spectrometric analysis of the fractions revealed both wild-type and Dutch-type Abeta38 as the other main components of the vascular amyloid. Moreover, we detected peaks corresponding to Dutch-type Abeta42 but not to wild-type Abeta42. These results suggest a pathogenic role for the mutant Abeta42 in addition to the mutant Abeta40 in the cerebral amyloid angiopathy of HCHWA-D.


Asunto(s)
Péptidos beta-Amiloides/metabolismo , Vasos Sanguíneos/metabolismo , Cerebelo/patología , Angiopatía Amiloide Cerebral Familiar/metabolismo , Hemorragia Cerebral/metabolismo , Fragmentos de Péptidos/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Péptidos beta-Amiloides/genética , Angiopatía Amiloide Cerebral Familiar/complicaciones , Angiopatía Amiloide Cerebral Familiar/patología , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/patología , Cromatografía Líquida de Alta Presión/métodos , Femenino , Humanos , Masculino , Espectrometría de Masas/métodos , Persona de Mediana Edad , Fragmentos de Péptidos/genética
11.
Clin Nephrol ; 67(3): 182-7, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17390743

RESUMEN

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary systemic arteriopathy presenting with migraines, mood disorders, focal neurologic deficits, recurrent ischemic attacks and dementia in young adults. The genesis of this disease relates to missense mutation of the Notch3 gene. We report here a newly identified CADASIL patient and discuss unique vascular lesions observed in the kidney. A 64-year-old female was admitted to our hospital for the investigation of proteinuria, hematuria and progressive neurological abnormalities. Her mother and brother died of cerebral infarction at a relatively young age despite a lack of apparent risk factors for arteriosclerosis. Over the past 4 months before admission, she had suffered from frequent transient ischemic attacks despite appropriate antiplatelet therapy. Blood examination revealed mild renal insufficiency and urinalysis revealed moderate protein excretion and dysmorphic hematuria. Magnetic resonance imaging of the brain revealed multiple infarcts and leukoencephalopathy. Histopathological analysis of the kidney revealed focal segmental mesangial proliferation, the loss and degeneration of arterial medial smooth muscle cells and arterial intimal thickening. Immunofluorescence analysis of glomeruli revealed IgA deposition in the mesangial area. Electron microscope analysis revealed electron-dense deposition also in the mesangial area. In addition, granular osmophilic material (GOM) was observed in the extraglomerular mesangial area and around the vascular smooth muscle cells. Genetic analysis of Notch3 revealed an R141C missense mutation and she was diagnosed with CADASIL complicated with IgA nephropathy. In immunohistological analysis, Notch3 stains were positive in vascular smooth muscle cells of the interlobular arteries and both afferent and efferent arterioles, and weak in the glomerular mesangial area. Antihypertensive treatment using angiotensin II receptor blocker and a low protein diet were initiated, and her urinary protein excretion decreased to 0.2 g/day. However, due to the progression of her neurological abnormalities, she became socially withdrawn. In CADASIL, GOM, abnormal accumulation of Notch3 ectodomain, is thought to induce the degeneration and loss of vascular smooth muscle cells and subsequent intimal thickening. Analysis of our cases provided that these morphological abnormalities were also observed in the CADASIL patient kidney.


Asunto(s)
CADASIL/complicaciones , Angiopatía Amiloide Cerebral Familiar/complicaciones , Glomerulonefritis por IGA/etiología , Antagonistas de Receptores de Angiotensina , Antihipertensivos , Biopsia , CADASIL/diagnóstico , CADASIL/genética , Angiopatía Amiloide Cerebral Familiar/diagnóstico , Angiopatía Amiloide Cerebral Familiar/genética , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Glomerulonefritis por IGA/tratamiento farmacológico , Glomerulonefritis por IGA/patología , Humanos , Inmunohistoquímica , Imagen por Resonancia Magnética , Células Mesangiales/ultraestructura , Microscopía Electrónica , Persona de Mediana Edad , Mutación Missense , Receptor Notch3 , Receptores Notch/genética , Piel/ultraestructura
12.
Pathologica ; 98(1): 44-7, 2006 Feb.
Artículo en Italiano | MEDLINE | ID: mdl-16789686

RESUMEN

Cerebral amyloidotic angiopathy represents the most frequent cause of lobar haematoma in young patients and represents 5-10% of the non-traumatic cerebral haemorrhages. In the present work, we describe one autoptic case of recurrent cerebral haemorrhages in a 58-year-old woman. Macroscopically in the brain multiple haemorragic areas were present in the right frontal pole, right frontal and temporo-parietal lobes with homolateral ventricular inundation. The histological, histochemical, immunohistochemical, ultrastructural and biomolecular investigations confirmed the presence of amyloid deposits in the middle-size and little-size cerebral arteries. We report, moreover, a novel mutation (Leu705Val) within the Abeta sequence of a AbetaPP in a family with autosomal dominant, recurrent intracerebral hemorrhages beginning in the sixth decade of life.


Asunto(s)
Precursor de Proteína beta-Amiloide/genética , Angiopatía Amiloide Cerebral Familiar/patología , Hemorragia Cerebral/etiología , Anciano , Sustitución de Aminoácidos , Angiopatía Amiloide Cerebral Familiar/clasificación , Angiopatía Amiloide Cerebral Familiar/complicaciones , Angiopatía Amiloide Cerebral Familiar/diagnóstico , Angiopatía Amiloide Cerebral Familiar/genética , Hemorragia Cerebral/patología , Trastorno Depresivo/complicaciones , Femenino , Genes Dominantes , Heterogeneidad Genética , Hematoma/etiología , Hematoma/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Mutación Missense , Mutación Puntual , Recurrencia , Trastornos del Habla/etiología , Intento de Suicidio , Tomografía Computarizada por Rayos X
13.
Acta Neuropathol ; 107(5): 389-98, 2004 May.
Artículo en Inglés | MEDLINE | ID: mdl-15014955

RESUMEN

Although the amyloid beta protein (Abeta) E693Q mutation enhances Abeta fibrillization in vitro and cerebral amyloid angiopathy (CAA) in vivo, brain parenchymal Abeta deposition and tau pathology in hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D) are limited. To evaluate whether clearance of Abeta by glial cells may play a role in this regard, this immunohistochemical study of frontal cortex of 14 HCHWA-D autopsy brains was performed using double staining with glial markers and end-specific antibodies to Abetax-42 (Abeta42) and Abetax-40 (Abeta40). Tau pathology was also assessed. Numerous microglia and/or astrocytes carrying cytoplasmic Abeta42(+)40(-) granules were scattered among non-fibrillar (Congo red-negative) Abeta deposits, i.e., clouds, fine diffuse plaques, and Abeta42(+)40(-) dense diffuse plaques. On the other hand, activated microglia and reactive astrocytes associated with fibrillar (Congo red-positive) Abeta deposition, i.e., Abeta42(+)40(+) dense diffuse plaques and CAA invading the parenchyma, were virtually devoid of Abeta granules. Tau pathology was scant and most frequently associated with CAA. These results suggest that relatively non-fibrillar parenchymal Abeta deposits may be liable to glial clearance. Abeta sequestration by glial cells may be a factor limiting the levels of neurotoxic soluble Abeta oligomers in HCHWA-D brain.


Asunto(s)
Péptidos beta-Amiloides/metabolismo , Angiopatía Amiloide Cerebral Familiar , Hemorragia Cerebral , Lóbulo Frontal/patología , Neuroglía/patología , Anciano , Anciano de 80 o más Años , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Angiopatía Amiloide Cerebral , Angiopatía Amiloide Cerebral Familiar/complicaciones , Angiopatía Amiloide Cerebral Familiar/metabolismo , Angiopatía Amiloide Cerebral Familiar/patología , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/metabolismo , Hemorragia Cerebral/patología , Femenino , Lóbulo Frontal/metabolismo , Proteína Ácida Fibrilar de la Glía/metabolismo , Transportador de Glucosa de Tipo 5 , Humanos , Inmunohistoquímica/métodos , Masculino , Persona de Mediana Edad , Proteínas de Transporte de Monosacáridos/metabolismo , Neuroglía/clasificación , Fragmentos de Péptidos/metabolismo , Placa Amiloide/metabolismo , Cambios Post Mortem , Proteínas tau/metabolismo
14.
Neurology ; 60(6): 1020-2, 2003 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-12654973

RESUMEN

The authors searched for mutations in the beta-amyloid precursor protein in a Spanish family with a hereditary syndrome of hemorrhagic stroke, dementia, leukoencephalopathy, and occipital calcifications. DNA from two affected members demonstrated the Iowa amyloid precursor protein mutation previously identified as a cause of severe amyloid angiopathy without hemorrhagic stroke. These data point to other genetic or environmental factors that may determine the occurrence of symptomatic hemorrhage in amyloid angiopathy.


Asunto(s)
Precursor de Proteína beta-Amiloide/genética , Angiopatía Amiloide Cerebral Familiar/complicaciones , Hemorragia Cerebral/etiología , Edad de Inicio , Anciano , Sustitución de Aminoácidos , Calcinosis/etiología , Arteria Carótida Externa/patología , Angiopatía Amiloide Cerebral Familiar/epidemiología , Angiopatía Amiloide Cerebral Familiar/genética , Codón/genética , Progresión de la Enfermedad , Humanos , Iowa , Masculino , Persona de Mediana Edad , Lóbulo Occipital/patología , España/epidemiología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA