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1.
Acta Neurol Scand ; 136(6): 668-671, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28608406

RESUMO

OBJECTIVES: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral small vessel disease caused by NOTCH3 gene mutations. CADASIL women are frequently considered at high risk of systemic vascular events during pregnancy and often prescribed with antithrombotic drugs. This decision is not evidence-based considering the lack of data about pregnancy outcome in CADASIL. We describe our experience on pregnancy in CADASIL patients. MATERIALS AND METHODS: We reviewed records of 50 CADASIL females followed in our center, and we collected prospective information in six patients for a total of 93 pregnancies. RESULTS: No woman had the disease onset or suffered from cerebral vascular ischemic events during pregnancy. Sixteen miscarriages (17.2%) were recorded. There were 72 vaginal births, and five cesarean sections. Considering the six patients followed prospectively (for a total of eight pregnancies), data on fetal growth and newborns weight were in line with those from the general population. Considering gestational complications, we recorded mild proteinuria without hypertension in one patient and hyperinsulinemia and pre-eclampsia in another affected by a known nephropathy. Antithrombotic drugs were used in three patients, in one for an unrelated coexisting prothrombotic condition. CONCLUSIONS: CADASIL does not seem to be associated with an unfavorable outcome of pregnancy either for women and fetuses. Patients and treating physicians should be reassured that pregnancy can be safely initiated in CADASIL, as there is no evidence to support a specific preventive antithrombotic treatment during pregnancy in CADASIL. Larger studies are needed to definitively confirm these conclusions.


Assuntos
CADASIL/epidemiologia , Complicações na Gravidez/epidemiologia , Adulto , Peso ao Nascer , CADASIL/diagnóstico , CADASIL/terapia , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/terapia , Resultado da Gravidez
2.
Acta Neurol Scand ; 132(6): 430-4, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25819272

RESUMO

BACKGROUND: CADASIL is an inherited systemic small vessel disease, the affected status of brain vessels leading to subcortical vascular dementia. The defective gene is NOTCH3 in which over 230 different pathogenic mutations have been identified. The clinical course of CADASIL is highly variable even within families. Previous studies have shown that additional genetic factors modify the phenotype. AIMS AND METHODS: Altogether, 134 Finnish CADASIL patients with p.Arg133Cys mutation were analysed for possible associations between the apolipoprotein E (APOE) genotype, angiotensinogen (AGT) p.Met268Thr polymorphism or neutral p.Ala202Ala NOTCH3 polymorphism and earlier first-ever stroke or migraine. RESULTS: We found no association between the APOE genotypes, AGT polymorphism, NOTCH3 polymorphism and earlier first-ever stroke or migraine. CONCLUSIONS: The APOE, AGT and NOTCH3 polymorphism did not modify the onset of strokes or migraine in our CADASIL sample, which is one of the largest mutationally homogenous CADASIL populations published to date. International collaboration, pooled analyses and genomewide approaches are warranted to identify the genetic factors that modify the highly variable CADASIL phenotype.


Assuntos
Angiotensinogênio/genética , Apolipoproteínas E/genética , CADASIL/epidemiologia , CADASIL/genética , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Feminino , Finlândia/epidemiologia , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/etiologia , Mutação , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Receptor Notch3 , Receptores Notch/genética , Acidente Vascular Cerebral/epidemiologia , Adulto Jovem
3.
Acta Neurol Scand ; 131(1): 30-6, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25109394

RESUMO

OBJECTIVES: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small vessel disease caused by NOTCH3 mutations. There are no clinical and neuroimaging findings pathognomonic of the disease. The aim of this paper was to provide a description of a group of NOTCH3-negative patients with a phenotype closely resembling that of CADASIL. MATERIALS AND METHODS: We performed NOTCH3 analysis (exons 2-23) in 117 probands because of a clinician's suspicion of CADASIL. The CADASIL scale, a recently developed tool that allows to better select patients for NOTCH3 analysis, was retrospectively applied to NOTCH3-negative patients; the patient subgroup that scored higher than the screening cutoff for CADASIL was defined as CADASIL-like. RESULTS: Thirty-four CADASIL-like patients (mean age at onset 57.8 years [52.1-63.4], 50% males) were identified. Compared with 25 patients with CADASIL for clinical, familial, and neuroimaging features, only the following variables were significantly (α level <0.05) different in frequency between patients with CADASIL and CADASIL-like patients: a positive family history for stroke at age ≤ 60 years, more frequent in patients with CADASIL, and hypertension, more frequent in CADASIL-like patients. CONCLUSIONS: Our experience highlights the growing number of patients presenting with a high suspicion of a cerebral small vessel disease with an autosomal dominant pattern of inheritance and a phenotype closely similar to that of CADASIL but without NOTCH3 mutations. This group remains to be characterized from the genetic point of view. The role of other genes or NOTCH3 alterations on exons other than 2-23 or introns has to be further assessed.


Assuntos
CADASIL/complicações , CADASIL/genética , CADASIL/patologia , Idade de Início , Encéfalo/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Fenótipo , Receptor Notch3 , Receptores Notch/genética , Estudos Retrospectivos
4.
Aging Clin Exp Res ; 27(3): 345-50, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25365954

RESUMO

BACKGROUND: Mild cognitive impairment (MCI) is an abnormal condition defined by the presence of cognitive decline not severe enough to fit dementia criteria. According to Winblad et al.'s criteria, the clinical distinction of MCI subtypes (amnestic/non-amnestic, single/multiple domain) is based on the cognitive profiling (conventional diagnosis) and infers possible different MCI etiologies. MCI prodromic of vascular dementia (Vasc-MCI) is thought to be characterized by a multiple domain profile. In our outpatient clinic (the "Florence VAS-COG clinic"), the diagnosis of MCI and of its different subtypes (vascular, degenerative, mixed) is based on a comprehensive evaluation of clinical and neuroimaging features (pragmatic diagnosis). AIMS: To compare the pragmatic and conventional diagnoses in terms of etiologic subtyping of MCI. METHODS: We retrospectively assessed the agreement between the two diagnoses in 30 MCI patients. Agreement was considered present when degenerative MCI was of the amnestic type (single or multiple domain) and Vasc-MCI was of the multiple domain type (amnestic or non-amnestic MCI). RESULTS: In 15/30 (50 %) patients, the diagnoses were in disagreement: 5/9 (56 %) patients diagnosed with a degenerative MCI type presented a non-amnestic cognitive profile (4 single domain and 1 multiple domain); 10/21 (48 %) Vasc-MCI were classified as non-amnestic single domain. CONCLUSIONS: The application of MCI etiologic subtyping using pragmatic or conventional diagnoses leads to different results. In our setting, not all the Vasc-MCI patients have a multiple domain profile. Our preliminary study suggests that the cognitive profile of Vasc-MCI is more heterogeneous than previously suggested.


Assuntos
Disfunção Cognitiva/etiologia , Idoso , Disfunção Cognitiva/classificação , Demência/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
5.
Eur J Neurol ; 21(1): 65-71, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23869710

RESUMO

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral small vessel disease that may lead to disability and whose phenotype modulators are still unknown. METHODS: In the MIcrovascular LEukoencephalopathy Study (MILES), we assessed the influence of vascular risk factors and the effect of different cognitive domains (memory, psychomotor speed and executive functions) performances on functional abilities in CADASIL in comparison with age-related leukoencephalopathy (ARL). RESULTS: We evaluated 51 CADASIL patients (mean age 50.3 ± 13.8 years, 47.1% males) and 68 ARL patients (70.6 ± 7.4 years, 58.8% males). Considering vascular risk factors, after adjustment for age, CADASIL patients had higher mean BMI values than ARL patients. Stroke history frequency was similar in the two groups. After adjustment for age, more CADASIL patients were disabled (impaired on ≥ 2 items of the Instrumental Activities of Daily Living scale) in comparison with ARL patients, and CADASIL patients had worse functional performances evaluated with the Disability Assessment for Dementia (DAD) scale. In CADASIL patients, hypertension was related to both DAD score and disability. The cognitive profile of CADASIL and ARL patients was similar, but on a stepwise linear regression analysis functional performances were mainly associated with the memory index (ß = -0.418, P < 0.003) in CADASIL patients and the executive function index (ß = -0.321, P = 0.028) in ARL. CONCLUSIONS: This study suggests that hypertension may contribute to functional impairment in CADASIL and that memory impairment has a large influence on functional decline in contrast with that observed in a sample of subjects with ARL.


Assuntos
CADASIL/complicações , CADASIL/psicologia , Hipertensão/complicações , Idoso , Transtornos Cognitivos/etiologia , Feminino , Humanos , Leucoencefalopatias/complicações , Leucoencefalopatias/psicologia , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fenótipo , Fatores de Risco
6.
Acta Neurol Scand ; 124(6): 390-5, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21428968

RESUMO

OBJECTIVE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral microangiopathy characterized by migraine, cerebrovascular events, and cognitive impairment. Although recognized as a cardinal feature of the disease, psychiatric disturbances have rarely been the object of focused studies. We performed a structured evaluation of mood disorders in CADASIL. MATERIALS AND METHODS: Twenty-three patients with CADASIL (five men and 18 women) were assessed by psychiatrists using the Structured Clinical Interview for the DSM-IV, clinician version. For the quantitative assessment of current mood disorder symptoms, the Hamilton Rating Scale for Depression (HRSD) and the Young Mania Rating Scale (YMRS) were used. RESULTS: A lifetime depressive episode was recorded in 17/23 (73.9%) patients with CADASIL. Six (26.1%) patients with CADASIL reported a current depressive episode. A diagnosis of manic lifetime episode was made in 6 (26.1%) patients with CADASIL. The HRSD mean score in patients with current depression was 9.1 ± SD 8.1. The YMRS mean score was 14.2 ± SD 4.1 for manic CADASIL. CONCLUSION: This study confirms that mood disorders are frequent in CADASIL. The use of a structured psychiatric interview outlines a frequency of depression higher than that previously reported but also reveals a considerable frequency of bipolar disorders. If confirmed in larger series, these data suggest that a greater attention should be paid to the psychiatric aspects in CADASIL.


Assuntos
Transtorno Bipolar/etiologia , CADASIL/psicologia , Transtorno Depressivo Maior/etiologia , Transtorno Bipolar/epidemiologia , CADASIL/complicações , CADASIL/epidemiologia , Transtorno Depressivo Maior/epidemiologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
7.
Eur J Neurol ; 18(5): 686-94, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-20840380

RESUMO

BACKGROUND: Randomized trials and meta-analyses indicate positive effects of stroke unit (SU) care on survival and dependency of patients with stroke. However, data on the advantages of SU in 'real-world' settings are limited. We prospectively assessed, in a large University Hospital, the effect of SU versus other conventional wards (OCW) care on all-cause mortality, death or dependency, death or institutionalization. METHODS: In a prospective observational study in the European Registers of Stroke Project, patients hospitalized for first-in-a-lifetime stroke were evaluated for demographics, risk factors, clinical presentation, resource use, 3-month and 1-year survival, and functional outcome. RESULTS: Overall, 355 patients (54.1% men, mean age 73.4 ± 14.5 years) were registered, 140 (39.4%) admitted to the SU, and 215 (60.6%) to OCW. OCW patients were older, whilst SU patients had more severe strokes according to NIHSS (P for trend = 0.025). SU patients were significantly more often treated by specialists in stroke medicine, stroke nurses, physiotherapists and speech therapists (all P < 0.001), psychologists (P = 0.025), dietitians (P < 0.001), and social workers (P = 0.003). MRI, carotid, and transcranial Doppler were significantly more often performed in SU patients (all P < 0.001). Intravenous fluids (P = 0.003) and intravenous anticoagulation (P < 0.001) were more often prescribed in SU. Controlling for case-mix, SU significantly reduced 1-year mortality (P = 0.020), death or dependency at 3 months (P = 0.006) and 1 year (P = 0.043), and death or institutionalization at 3 months (P = 0.001) and 1 year (P = 0.009). CONCLUSIONS: We confirmed the benefits of SU care in a clinical setting. Further analyses should define the contribution of individual components of care to stroke outcome.


Assuntos
Centros Médicos Acadêmicos/métodos , Unidades de Terapia Intensiva , Sistema de Registros , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/terapia , Idoso , Idoso de 80 Anos ou mais , Europa (Continente)/epidemiologia , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
8.
J Chemother ; 22(2): 134-6, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20435575

RESUMO

Testicular germ-cell tumors are the most common solid tumor in young men, with an incidence peak between the ages of 20 and 35 years. Even if rare, arterial thromboembolism is a serious and possible complication during cisplatin-based chemotherapy in young patients. The strong association between rapid treatment and favorable outcome is well known. Oncologists need to recognize the symptoms and to alert a stroke unit as soon as possible. We report the management of a young patient affected by non seminomatous testicular neoplasm without cardiovascular risk factors who developed an ischemic stroke during cisplatin-based treatment. We also review the relevant literature.


Assuntos
Antineoplásicos/efeitos adversos , Isquemia Encefálica/induzido quimicamente , Cisplatino/efeitos adversos , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Acidente Vascular Cerebral/induzido quimicamente , Neoplasias Testiculares/tratamento farmacológico , Adulto , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/uso terapêutico , Humanos , Masculino
10.
Neurology ; 74(1): 57-63, 2010 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-20038773

RESUMO

OBJECTIVE: To report the characteristics of patients suspected to have cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) but in whom no NOTCH3 gene pathogenic mutation was found. METHODS: Between 2002 and 2008, we performed NOTCH3 gene analysis (exons 2-23) in 81 probands because CADASIL was clinically suspected. A retrospective analysis and comparison of clinical, familial, and neuroimaging features of patients with and without pathogenic mutations was performed. RESULTS: CADASIL was diagnosed in 16/81 (20%) probands by finding a mutation leading to a cysteine substitution within the epidermal growth factor (EGF)-like repeats of the NOTCH3 receptor. In the remaining 65 patients, no pathogenic mutation was found. Some features were significantly (Fisher exact test p < 0.05) more frequent in CADASIL than in NOTCH3-negative patients: history of migraine (73 vs 39%), stroke before the age of 60 among relatives (71 vs 32%), severe leukoencephalopathy (94 vs 62%), white matter changes extended to the anterior temporal lobes (93 vs 45%), external capsule involvement (100 vs 50%), and presence of lacunar infarcts (100 vs 65%). The frequency of vascular risk factors was balanced between the 2 groups. No feature was peculiar to either group. CONCLUSIONS: Although certain clinical and neuroimaging features are more frequent in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) than in NOTCH3-negative patients, none is pathognomonic. Clinicians should be aware that when diagnosing CADASIL, a number of patients with a cerebral disease phenotypically similar to CADASIL emerge. The genetic profile of these diseases and the full phenotypic difference with CADASIL remain to be further defined.


Assuntos
CADASIL , Imageamento por Ressonância Magnética , Mutação/genética , Receptores Notch/genética , Adulto , Idoso , Infarto Encefálico/patologia , CADASIL/complicações , CADASIL/genética , CADASIL/patologia , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/patologia , Análise Mutacional de DNA , Éxons/genética , Saúde da Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/patologia , Receptor Notch3 , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/patologia
11.
Mult Scler ; 15(4): 472-8, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19153171

RESUMO

BACKGROUND: McDonald Criteria (MDC) have been validated in selected patients at high risk for multiple sclerosis (MS). However, possible overdiagnosis of MS can represent critical issues in less controlled clinical settings. OBJECTIVE: To assess the contribution of oligoclonal bands (OB) to MS diagnosis in current clinical practice. METHODS: We included all the patients admitted to our Department since 2001 who had undergone diagnostic workup for a possible MS diagnosis, followed up for at least 1 year. We assessed the accuracy of MDC, OB, and two MDC definitions of dissemination in space (DIS-MRI: fulfillment of MRI criteria, DIS-OB: two MRI lesions+OB). RESULTS: We included 118 patients (median follow-up 4.0 years). Twenty-eight cases received an alternative diagnosis, whereas none of these presented OB, 43% fulfilled the DIS-MRI criteria. OB were present in 70% of the remaining 90 patients. By the end of the follow-up, 56% of the diagnoses had converted to clinically definite MS and OB showed higher accuracy than DIS-MRI fulfillment (70% vs 58%). Moreover, after 1 year and at the end of the follow-up, DIS-OB yielded a higher Specificity level in comparison with DIS-MRI. CONCLUSION: OB can improve overall diagnostic Accuracy by increasing Specificity and negative predictive value.


Assuntos
Testes Imunológicos/normas , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/imunologia , Bandas Oligoclonais/imunologia , Adolescente , Adulto , Bases de Dados Factuais , Diagnóstico Diferencial , Avaliação da Deficiência , Diagnóstico Precoce , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
12.
Acta Neurol Scand ; 118(5): 291-5, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18384453

RESUMO

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebrovascular disease, clinically characterized by a variable combination of migraine, recurrent transient ischemic attack (TIA) or lacunar strokes, cognitive decline, and mood disturbances. However, the assessment of psychiatric disturbances in this disease has never been carried out systematically. METHODS: This paper presents a brief review of the literature regarding the occurrence of psychiatric disorders in CADASIL patients. RESULTS: The prevalence of psychiatric disorders in CADASIL patients is reported to range from 20% to 41%. The psychiatric disturbances reported with the highest frequency are mood disturbances (9-41%). Pooling together the studies and considering a total of 454 CADASIL patients reported in the literature, 106 of these were affected by mood disturbances (24%). The majority of studies however did not use any defined criteria to assess the presence of psychiatric disorders and diagnoses were mainly based on history or review of clinical records. CONCLUSIONS: The review of CADASIL literature suggests the need for a more structured approach to the investigation of these disturbances that are highly prevalent and may greatly impact quality of life in these patients.


Assuntos
Encéfalo/fisiopatologia , CADASIL/epidemiologia , CADASIL/fisiopatologia , Transtornos Neurocognitivos/epidemiologia , Transtornos Neurocognitivos/fisiopatologia , Adulto , Idoso , Encéfalo/irrigação sanguínea , Encéfalo/patologia , CADASIL/psicologia , Transtornos Cognitivos/patologia , Transtornos Cognitivos/fisiopatologia , Comorbidade , Estudos Transversais , Diagnóstico Diferencial , Feminino , Humanos , Transtornos do Humor/epidemiologia , Transtornos do Humor/patologia , Transtornos do Humor/fisiopatologia , Transtornos Neurocognitivos/patologia , Prevalência
14.
Acta Neurol Scand ; 113(1): 62-3, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16367901

RESUMO

The presence of large vessels malformations has not been reported in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We describe a CADASIL patient in whom a brain cerebellar arteriovenous malformation was revealed by magnetic resonance (MR) imaging. An MR angiogram documented also an aneurysm along the right intracranial vertebral artery at the junction with the posterior-inferior cerebellar artery. The aneurysm was successfully treated by means of endovascular coil embolization. No neurological complication occurred in our patient during the angiographic procedure. In this case, in addition to an incidental coexistence of CADASIL and large vessels abnormalities, a causal role of the Notch pathway alteration could be hypothesized. Dysregulation of the Notch pathway is linked to several human diseases besides CADASIL. In one of these (the Alagille syndrome) intracranial aneurysms are reported. This hypothesis contrasts however with the absence of similar reports in other CADASIL cases and needs corroboration in large series.


Assuntos
CADASIL/patologia , Cerebelo/irrigação sanguínea , Aneurisma Intracraniano/patologia , Malformações Arteriovenosas Intracranianas/patologia , Artéria Vertebral/patologia , Adulto , Angiografia Cerebral , Feminino , Humanos , Imageamento por Ressonância Magnética
15.
Eur J Neurol ; 11(11): 782-7, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15525301

RESUMO

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetically transmitted cerebrovascular disease. Typically, the first clinical manifestation is migraine and the full clinical spectrum of the disease with recurrent strokes of the subcortical type, cognitive, and mood disorders is seen during the fourth and fifth decades of life. Vascular risk factors are usually absent in CADASIL patients and the diagnosis of the disease is particularly suspected in young adults with cerebrovascular events of unknown cause, diffuse leukoencephalopathy on computed tomography or magnetic resonance imaging, and a history of cerebrovascular diseases or dementia in many family members. We describe three Italian CADASIL patients who presented to medical attention for cerebrovascular events occurred after the age of 55 and had, in addition to hypertension and hyperlipidemia, thrombophilic risk factors such as hyperhomocysteinemia, elevated levels of lipoprotein(a), and antiphospholipid antibodies. Symptoms possibly related to cortical involvement, such as dysphasia and visual field deficits, were reported by two of these patients. We conclude that a diagnosis of CADASIL should not be disregarded in patients with vascular risk factors and presenting with symptoms not immediately referable to subcortical damage at ages more advanced than commonly reported.


Assuntos
CADASIL/complicações , Trombofilia/etiologia , Idoso , Encéfalo/patologia , CADASIL/epidemiologia , CADASIL/fisiopatologia , Transtornos Cerebrovasculares/epidemiologia , Transtornos Cerebrovasculares/etiologia , Feminino , Humanos , Itália/epidemiologia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Fatores de Risco , Trombofilia/epidemiologia , Trombofilia/fisiopatologia
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