RESUMO
Spontaneous dissection of the vessels of the neck is one of the main causes of ischemic stroke in young patients under 45 years of age. According to morphological studies, dissection of the vessels of the neck can be based on dysplastic changes in the arterial wall in arteriopathies, Marfan syndrome, Ehlers-Danlos syndrome, undifferentiated connective tissue dysplasia. The article presents a case of spontaneous dissection of the internal carotid artery in a 30-year-old patient with clinical manifestations of undifferentiated connective tissue dysplasia and carriage of homozygous variants of candidate genes: 4G/4G of the PAI-1 (-675, 4G/5G), T/T of the MTHFR C677T, 5A/5A of the MMP-3 (-1171 5A/6A) and A/A of the MMP-9 (8202A/G).
Assuntos
Dissecação da Artéria Carótida Interna/genética , Tecido Conjuntivo/patologia , Adulto , Homozigoto , Humanos , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Acidente Vascular Cerebral/etiologiaRESUMO
We report an autopsy case of a bilateral carotid artery dissection, following cervical manipulation by a chiropractor. To establish the etiology of a cervical artery dissection is important in view of possible legal implications and to exclude hereditary disorders, since cervical artery dissection has been linked to several arteriopathies. The underlying arteriopathy in the presented case was an idiopathic cystic medial degeneration. This report emphasizes the role of the pathologist in defining the underlying arteriopathy in carotid artery dissection.
Assuntos
Dissecação da Artéria Carótida Interna/etiologia , Quiroprática/legislação & jurisprudência , Infarto da Artéria Cerebral Média/complicações , Manipulação da Coluna/efeitos adversos , Adulto , Autopsia , Dissecação da Artéria Carótida Interna/genética , Evolução Fatal , Humanos , Infarto da Artéria Cerebral Média/genética , Infarto da Artéria Cerebral Média/patologia , Masculino , Tomografia Computadorizada por Raios XAssuntos
Dissecação da Artéria Carótida Interna/complicações , Hemocromatose/complicações , Hemocromatose/genética , Dissecação da Artéria Carótida Interna/diagnóstico , Dissecação da Artéria Carótida Interna/genética , Cisteína/genética , Hemocromatose/diagnóstico , Proteína da Hemocromatose , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Ferro/sangue , Angiografia por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Mutação , Tirosina/genéticaRESUMO
BACKGROUND AND PURPOSE: Cervical artery dissections (CAD) can be associated with connective tissue aberrations in skin biopsies. The analysis of healthy relatives of patients suggested that the connective tissue phenotype is familial with an autosomal dominant inheritance. METHODS: We performed genetic linkage studies in 3 families of patients with CAD. Connective tissue phenotypes for the patients and all family members were assessed by electron microscopic study of skin biopsies. A genome-wide linkage analysis of 1 family (1 patient with 8 healthy relatives) indicated 2 candidate loci. Three genes were subsequently studied by sequence analysis. Part of the genome was also studied by linkage analysis in 2 further families. RESULTS: The genome-wide scan in a single family suggested linkage between the hypothetical mutation causing the connective tissue phenotype and informative genetic markers on chromosome 15q24 (logarithm of the odds score: Z= +2.1). A second possible candidate locus (Z=+1.9) was found on chromosome 10q26. Sequence analysis of 3 candidate genes in the suggestive locus (chondroitin sulfate proteoglycan4 [CSPG4], lysyl oxidase-like1 [LOXL1] and fibroblast growth factor receptor2 [FGFR2]) did not lead to the identification of a mutation responsible for connective tissue alterations. In 2 additional smaller families the loci on chromosome 15q24 and 10q26 were excluded by linkage analysis. CONCLUSIONS: Linkage analysis of a large family with CAD-associated connective tissue alterations suggested the presence of a candidate locus on chromosome 15q2 or on chromosome 10q26. Sequence analysis did not lead to the identification of a mutated candidate gene in 1 of these loci. The study of 2 additional pedigrees indicated locus heterogeneity for the connective tissue phenotype of CAD patients.
Assuntos
Dissecção Aórtica/genética , Doenças do Tecido Conjuntivo/genética , Tecido Conjuntivo/patologia , Heterogeneidade Genética , Acidente Vascular Cerebral/etiologia , Adulto , Idoso , Aminoácido Oxirredutases/genética , Dissecção Aórtica/complicações , Dissecção Aórtica/patologia , Biópsia , Dissecação da Artéria Carótida Interna/genética , Proteoglicanas de Sulfatos de Condroitina/genética , Mapeamento Cromossômico , Cromossomos Humanos Par 10/genética , Cromossomos Humanos Par 15/genética , Doenças do Tecido Conjuntivo/complicações , Feminino , Predisposição Genética para Doença , Humanos , Escore Lod , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Linhagem , Fenótipo , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Pele/patologiaRESUMO
BACKGROUND AND PURPOSE: Observations in patients with arterial aneurysms, fibromuscular dysplasia, and spontaneous cervical artery dissection (sCAD) indicate that protease inhibitor deficiency might boost the enzymatic destruction of arterial tissue and increase the risk of these arterial wall diseases. Here we present the first large investigation of the protease inhibitor hypothesis in patients with sCAD. METHODS: Eighty patients with sCAD were compared with 80 age- and sex-matched healthy individuals. Alpha1-antitrypsin (alpha1-AT) and alpha2-macroglobulin (alpha2-MG) levels, and alpha1-AT genotypes were assessed and compared between groups. RESULTS: alpha1-AT and alpha2-MG levels as well as alpha1-AT genotypes did not differ significantly between patients and controls. The frequency of Z alleles in the patient group was higher than in the control group and than in other cohorts from Europe; however, the difference remained nonsignificant. All patients with Z alleles had internal carotid artery dissections. CONCLUSIONS: Overall, this data does not support the hypothesis that protease inhibitor levels or alpha1-AT genotypes play an important role in the etiology of sCAD. The present data does not exclude that the Pi-Z allele might have an influence on subgroups of sCAD, such as internal carotid artery dissections.
Assuntos
Dissecação da Artéria Carótida Interna/sangue , Dissecação da Artéria Carótida Interna/genética , Dissecação da Artéria Vertebral/sangue , Dissecação da Artéria Vertebral/genética , alfa 1-Antitripsina/análise , alfa 1-Antitripsina/genética , alfa-Macroglobulinas/análise , Adulto , Alelos , Feminino , Genótipo , Humanos , Masculino , Polimorfismo GenéticoRESUMO
The authors searched for the presence of alpha-1-antitrypsin (AAT) deficiency alleles PiZ and PiS in 74 patients with spontaneous cervical artery dissections (sCADs) and in 74 healthy control subjects. In both groups, the authors found four carriers of deficiency alleles. The connective tissue morphology of one additional patient with sCAD with PiZM genotype and her relatives was studied in skin biopsies. The PiZ allele did not segregate with morphologic alterations of the dermal connective tissue in the family. Therefore, AAT deficiency alleles may not play a role in the etiology of sCAD.
Assuntos
Dissecação da Artéria Carótida Interna/genética , Frequência do Gene , Dissecação da Artéria Vertebral/genética , Deficiência de alfa 1-Antitripsina/genética , Adulto , Biópsia , Dissecação da Artéria Carótida Interna/epidemiologia , Causalidade , Cromossomos/genética , Tecido Conjuntivo/patologia , Derme/patologia , Feminino , Triagem de Portadores Genéticos , Alemanha/epidemiologia , Humanos , Masculino , Linhagem , Polimorfismo Conformacional de Fita Simples , Valores de Referência , Suíça/epidemiologia , Dissecação da Artéria Vertebral/epidemiologia , Deficiência de alfa 1-Antitripsina/epidemiologiaRESUMO
Skin biopsies from a patient with a dissection of the left internal carotid artery and from four of his children were analyzed by electron microscopy. The index patient and three children showed mild but regular electron microscopic connective tissue aberrations. They were considered as carriers of an unknown autosomal dominant mutation. Thirty-four candidate genes involved in the biosynthesis of the extracellular matrix were excluded by genetic linkage analysis as possible sites of a disease-causing mutation in this family (logarithm of odds [LOD]-score less than -2.0).
Assuntos
Dissecação da Artéria Carótida Interna/genética , Mapeamento Cromossômico , Escore Lod , Biópsia , Dissecação da Artéria Carótida Interna/patologia , Criança , Colágeno/ultraestrutura , Doenças do Tecido Conjuntivo/genética , Doenças do Tecido Conjuntivo/patologia , Derme/patologia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Linhagem , FenótipoRESUMO
A young woman 38 years of age underwent Doppler ultrasonography following the spontaneous appearance of cervical pain causing loss of sleep. The examination revealed bilateral dissection of the internal carotid arteries, confirmed by supraaortic arteriography. Two successive CT scans showed no cerebral lesions. A thrombosis of the great saphenous vein was recorded as the only vascular event in her medical history. Thrombophilia was assessed following discovery of the dissection, and upon examination a heterozygotic mutation of Factor V Leiden was revealed. This observation is the second case of carotid dissection occurring in a subject presenting a factor V mutation. At the present time, however, there are no results to justify the assumption of a direct link between these two pathologies.