Ischemic stroke in young adults: an overview of etiological aspects

VIEWS AND REVIEWS Ischemic stroke in young adults: an overview of etiological aspects Acidente vascular cerebral isquêmico em adultos jovens: considerações etiológicas Fábio Iuji Yamamoto Abstract Stroke affects mainly people aged over 65 years, and atherosclerosis predominates as the main etiopathogenic factor in ischemic stroke (IS). On the other hand, cardiac embolism and arterial dissection are the most frequent causes of IS in patients aged less than 45 years. However, inappropriate control of traditional vascular risk factors in young people may be causing a significant increase of atherosclerosis-related IS in this population. Furthermore, a variety of etiologies, many of them uncommon, must be investigated. In endemic regions, neurocysticercosis and Chagas’ disease deserve consideration. Undetermined cause has been still reported in as many as one third of young stroke patients. Key words: stroke, brain ischemia, young adult. Resumo A doença aterosclerótica é o fator etiopatogênico mais importante no acidente vascular cerebral isquêmico (AVCI), afecção que acomete predominantemente pessoas acima da sétima década de vida. Entretanto, nos adultos jovens a aterosclerose exibe frequência menor, sendo a embolia de origem cardíaca e as dissecções arteriais as causas mais comuns de AVCI em pacientes com até 45 anos de idade. Porém, o controle inadequado dos fatores de risco vascular nas faixas mais jovens da população pode estar levando à elevação significativa no número de infartos cerebrais associados à aterosclerose nessa faixa etária.Uma ampla gama de fatores etiológicos, muitos deles raros, deve ser considerada no seu diagnóstico diferencial. Em áreas endêmicas, doenças infecciosas como a neurocisticercose e a doença de Chagas devem ser lembradas ao se estabelecer o diagnóstico etiológico. Os infartos cerebrais de causa indeterminada ainda são parcela significativa nos AVCIs em adultos jovens. Palavras-Chave: acidente vascular cerebral, isquemia cerebral, adulto jovem. Ischemic stroke (IS) in young adults is reported as uncommon, comprising less than 10% of all stroke patients1. However, In our clinical practice, we are faced not infrequently with patients aged less than 45 years who suffered a stroke, many of them with no risk factors for atherosclerosis and no ultimate clear etiological diagnosis even after a thorough investigation. This diagnostic challenge is one of the main scopes of studying and researching mechanisms of brain ischemia in young adults in addition to the dramatic personal, familial, and socio-economic consequences by affecting individuals at the top of their productive age. Although cardioembolism and cervicocephalic arterial dissection have been established as principal etiological factors of IS in young adults2, a systematic diagnostic approach must be applied to all patients, regarding the great number of potential causes in this group and the multifactorial nature in many of these patients. Despite more accurate diagnostic tools recently acquired in vascular imaging, hematological and genetic studies, currently, the number of young patients with cryptogenic IS remains high, performing 30–40%3,4. Considered an unusual cause of IS in the young two decades ago5, atherosclerosis has gaining projection by recent reports of significant raise in traditional risk factors as hypertension, diabetes, obesity, dyslipidemia and tabagism among hospitalized adolescents and young adults6. Table 1 shows the main categorizations of etiologic subtypes of IS in young adults that must be considered in every young patient with IS. Nonatherosclerotic angiopathies Cervicocephalic arterial dissections are by far the commonest cause of IS within the nonatherosclerotic angiopathies Cerebrovascular Diseases Study Group, Division of Neurology, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo SP, Brazil. Correspondence: Fábio Iuji Yamamoto; Avenida Dr. Eneas de Carvalho Aguiar 255/5084; 05403-000 São Paulo SP - Brasil; E-mail: Conflict of interest: There is no conflict of interest to declare. Received 09 January 2012; Accepted 17 January 2012 462 and rank first or second regarding all etiologies of IS in young adults5,7-9. The increased awareness and the routine use of less invasive neuroimaging studies, as computed tomography and magnetic resonance imaging, have permitted to establish this diagnosis in a raising number of patients. Angiographic evidence of fibromuscular dysplasia (FMD) is found in about 15% of the patients with cervical internal carotid dissection10,11, and simultaneous bilateral carotid dissection was described in 14% of the patients, most with an underlying arteriopathy, mainly FMD12. Table1. Etiology of ischemic stroke in young adults. Nonatherosclerotic Cervicocephalic arterial dissection angiopathies Fibromuscular dysplasia Cardioembolism Moyamoya disease Angiitis Genetic and hereditary diseases (Fabry’s disease, CADASIL, MELAS, HERNS) Reversible cerebral vasoconstriction syndrome Susac’s syndrome Sneddon’s syndrome Rheumatic valvular disease Patent foramen ovale Atrial septal aneurysm Prosthetic valve Infective endocarditis Arrhythmia (atrial fibrillation) Dilated cardiomyopathy (Chagas’ disease) Mitral valve prolapse Atrial myxoma Marantic and Libman-Sacks endocarditis Large-artery atherosclerosis Small-vessel disease Hematologic conditions (prothrombotic states) Antiphospholipid syndrome Hyperhomocysteinemia Sickle cell disease Myeloproliferative disorders Factor V Leiden Prothrombin 20210A mutation Protein C, protein S deficiency Antithrombin III deficiency Migraine stroke Cryptogenic stroke On the other hand, FMD as a rare nonatheromatous, noninflammatory systemic angiopathy more common in young and middle-aged women, may be an incidental finding in asymptomatic patients13. Moyamoya disease affects mainly Asian people, but is described throughout the world14. Ischemic stroke predominates in children whereas intracranial hemorrhage is usually seen in adults. Our personal experience through multiethnic population in Brazil points to a greater frequency of moyamoya disease in Japanese descendants. Vasculitides of the central nervous system (CNS) are often reminded when differential diagnosis of IS in young adults is discussed, however their diagnostic confirmation seldom occurs. The main reasons for this failure lie on their rarity and pleomorphic clinical symptomatology since cerebral angiitis usually reveals a subacute or progressive encephalopathy with multifocal neurologic deficits15. Therefore, isolated angiitis of the CNS and systemic vasculitides uncommonly open with acute stroke episodes. In endemic regions, neurocysticercosis must be considered in young adults with small or large-vessel angiitis. Subarachnoid cysts near the ischemic lesion, associated with inflammatory changes in the wall of neighbouring intracranial arteries, are the hallmark of this condition16. Table 2 shows (...truncated)