Introdução: Existem poucos dados a respeito do diagnóstico e prognóstico de crianças com acidente vascular encefálico isquêmico (AVE-i) devido a arteriopatia/vasculopatia pós-varicela e nenhuma revisão sistemática em crianças com arteriopatia/vasculopatia transitória. Objetivos: Relatar série de casos de sete crianças com AVE-i pós-varicela focando nos aspectos clínico/laboratoriais e no desempenho neuro-cognitivo 4 anos após e realizar revisão sistemática da literatura sobre a associação entre VZV e arteriopatia/vasculopatia transitória. Métodos: Revisão sistemática-Estudos relevantes foram buscados utilizando os seguintes bancos de dados: EMBASES; Pubmed; Bireme; LILACS e Web of Science. As buscas utilizaram as seguintes palavras-chave: arteriopatia transitória / vasculopatia ou pós-varicela ou arteriopatia focal e VZV. Os descritores usados para revisão sistemática foram: Arteriopatia transitória or vasculopatia transitória or arteriopatia pós-varicela or arteriopatia focal e VZV or varicela e aplicada a estratégia de PICO; População: crianças de 1 mês a 17 anos e 11 meses, com vasculopatia/arteriopatia em sistema nervoso central; Fenômeno de Interesse: VZV até 12 meses anterior; Comparação: Vasculopatia/Arteriopatia transitória sem associação com VZV; Outcome: VZV associado a vasculopatia. Os artigos selecionados foram analisados por 2 examinadores que validaram os artigos de acordo com a escala New Castle Otawa. Um terceiro examinador resolveu discrepâncias. Série de relato de casos: envolveu 7 crianças (5 meninos e 2 meninas) de 5 serviços de emergências pediátricas na cidade de São Paulo, Brasil, que apresentaram acidente vascular encefálico isquêmico pós-varicela confirmada com ressonância magnética de encéfalo e angioressonância magnética cerebral. Foi realizado coleta de líquido cefalorraquidiano para detecção do envolvimento do VZ: dosagem de anticorpos IgG e IgM anti-VZV; reação em cadeia de polimerase para DNA viral e detecção do envolvimento do vírus herpes simples tipo 1 e tipo 2 (anticorpos IgG e IgM anti-VHS 1 e 2). Foi aplicado o PSOM-Score na admissão e 4 anos após o AVE-i. Resultados: Na revisão sistemática foram selecionados 1003 artigos sendo que no final das avaliações apenas 11 artigos com moderado nível de evidência para associação entre arteriopatia transitória e VZV foram incluídos na nossa revisão. Em relação à série de casos, os 7 pacientes, com idades variando de 1,3 anos a 4 anos, apresentaram hemiparesia ao exame físico inicial e imagem de isquemia em região submetida à irrigação da artéria cerebral média ou interna após um tempo médio de 5,1 (± 3,5) meses do quadro clínico de varicela. Em 4 pacientes (57%) foram encontradas lesões vasculares e a detecção de IgG anti VZV no liquor ocorreu em 3 pacientes (42%). Nenhum paciente apresentou exantema, febre ou presença de anticorpos anti-herpes vírus tipo 1 e 2. Somente 1 paciente apresentou alteração nos exames de trombofilia (mutação em heterozigose da protombina). Todos apresentaram melhora nos índices de escore para sequelas. Nenhum apresentou novo episódio de AVE-i. Limitacão do nosso estudo: Limitado número de casos e pequeno número de estudos caso-controle ou estudos randomizados para realização de revisão sistemática. Conclusão: Encontramos moderado nível de evidência para associação entre arteriopatia transitória e VZV na revisão sistemática. Nessa série de casos foi observado o caráter não progressivo do AVE-i pós-varicela após 4 anos de seguimento através da avaliação de sequelas motoras, de linguagem e cognitivas. Observamos que a identificação do DNA viral e/ou presença intratecal de IgG anti-VZV não foram determinantes para o diagnóstico. Dessa forma existe necessidade de se buscar melhores marcadores diagnósticos de acidente vascular isquêmico pós-varicela em crianças / Introduction: Few data exist about the diagnosis and prognosis of children who were victims of an arterial ischemic stroke (AIS) caused by post-varicella vasculopathy/artheriopathy and there is no systematic review about children with transitory artheriopathy/vasculopathy. Objetives: To report seven cases of children who suffered post-varicella AIS, with special focus to the clinical/laboratory aspects, in addition to their neuro-cognitive performance after four years. We also perform a systematic review about the association between VZV and transitory artheriopathy/vasculopathy. Methods: Systematic review. Relevant studies were sought using the following data-bases: EMBASES; Pubmed; Bireme; LILACS and Web of Science. Searches used the following keywords: transitory artheriopathy/ vasculopathy or post varicella artheriopathy or focal artheriopathy and VZV. The PICO method was used for the selection of studies. Population: 1 month to 17 years-old, with vasculopathy/ artheriopaty in central nervous system; end-point: VZV up to 12 months before; Comparation: Transitory Vasculopathy/Artheriopaty without VZV; Outcome: VZV associated with vasculopaty/artheriopaty. One examiner performed study selection. The selected articles were analyzed by two examiners who validated the articles according to Newcastle Otawa scale. A third examiner resolved discrepancies. Series of cases: seven children were evaluated (5 boys and 2 girls) from five different pediatric emergency services within the city of Sao Paulo, Brazil, all presenting with arterial ischemic stroke (AIS) caused by post-varicella vasculopathy. Diagnosis was confirmed by Magnetic Resonance Imaging and Nuclear Magnetic Resonance Angiography. Virological diagnosis was determined using cerebrospinal fluid to detect: a) the presence of VZV DNA by polymerase chain reaction and VZV IgG and IgM antibodies and b) the involvement of the Herpes Simplex Virus type 1 and 2 (HSV 1 and 2 IgG and IgM Antibodies). The PSOM-score was applied at admission and four years after the AIS. Results: A total of 1003 publications was selected and at final evaluation only 11 articles were included with a moderate evidence level. Regarding the series of cases, seven patients, ages varying from 1.3 and 4 years, presented with hemiparesis at first physical examination and ischemic zones on imaging tests in areas irrigated by the middle cerebral artery or the internal carotid artery about 5.1 (± 3,5) months after varicella infection. Four patients (57%) had vascular lesions and three patients (42%) tested positive for VZV IgG antibodies in their CSF. No patient showed signs of exanthema, fever or IgG and IgM antibodies for Herpes Simplex Virus type 1 and 2. Thrombophilia testing came back altered for only one patient (heterozygous prothrombin gene mutation). All patients showed improvement on their sequelae scores. None recurred. Limits of this study: limited number of cases and small number of case- control studies or randomized studies for systematic review. Conclusions: We found moderate evidence level of association between transitory artheriopathy and VZV. In the series of cases, we observed the non-progressive aspect of the post-varicella AIS after four years, determined by the evaluation of motor, language and cognitive sequelae. We also observed that anti-viral DNA and/or the presence of intrathecal anti- VZV IgG antibodies were not determinants for the diagnosis. Therefore, we believe better diagnostic markers for post-varicella arterial ischemic stroke are necessary

Перинатальный артериальный ишемический инсульт - это цереброваскулярное заболевание, возникающее между 20-й неделей беременности и 28-м послеродовым днем, вызывающее двигательный и немоторный дефицит, причем церебральный паралич является частым исходом. Молодой мозг реагирует, реорганизуя свои поврежденные сети в ипсилезионное и/или контральезионное полушария, причем последнее больше связано с двигательными нарушениями. Префронтальная кора считается одной из наиболее уязвимых областей с когнитивным дефицитом, возникающим с задержкой, из-за ее длительного развития, достигающего своего пика синаптогенеза после первого послеродового года, в то время как другие области, такие как первичная кора, обычно проходят свою основную фазу синаптогенеза в течение первого послеродового семестра. Таким образом, раннее обнаружение низкого синаптогенеза может быть ранним признаком настоящего или предстоящего дефицита и привести к раннему вмешательству. Бета-диапазон недавно был предложен в качестве возможного биомаркера синаптогенеза, причем активность ГАМК связана с нейропластичностью и синаптогенезом. Основной целью настоящего исследования является установление роли абсолютной бета-1 мощности в синаптогенезе и исследование уязвимости префронтальной коры головного мозга. Были набраны сорок типичных детей и 10 детей с перинатальным артериальным ишемическим инсультом в их подкорковой средней мозговой артерии и были созданы 3 возрастные подгруппы: 5-месячная, 10-месячная и 24-месячная подгруппы. Запись ЭЭГ и тест Бейли-III использовались для измерения их фоновой активности и уровня развития. Хотя статистический анализ с помощью непараметрических инструментов (U-тест Манна-Уитни, тест Крускалла Уоллиса) не показал решающих результатов, потенциальная связь бета-диапазона с синаптогенезом может быть обнаружена при наблюдении низкой мощности бета-1 в моторных и когнитивных областях мозга и низкой моторной и когнитивной производительности, а также при обнаружении заднего или переднего созревания. Кроме того, ранняя уязвимость префронтальной коры может быть обнаружена в снижении двусторонней бета-1 мощности у 24-месячных детей с перинатальным инсультом, по сравнению с типичными детьми и более ранними односторонними различиями, наряду с некоторыми когнитивными дефицитами, которые начинают проявляться в той же группе. / Perinatal Arterial Ischemic Stroke is a cerebrovascular disease occurring between the 20th gestational week and the 28th postnatal day, causing motor and non-motor deficits with cerebral palsy being a frequent outcome. The young brain reacts by reorganizing its injured networks to ipsilesional and/or contralesional hemisphere with the latter relating more to motor impairment. The Prefrontal Cortex is considered one of the most vulnerable areas with cognitive deficits emerging with a delay, due to its lengthy development reaching its synaptogenesis peak after the first postnatal year, while other areas, such as the Primary Cortices undergo generally their major synaptogenesis phase during the first postnatal semester. So early detection of low synaptogenesis could be an early mark of present or upcoming deficits and lead to an early intervention. Beta band has been recently suggested as a possible biomarker of synaptogenesis with GABA’s activity being connected with neuroplasticity and synaptogenesis. The main goal of the current study is to establish the role of of the absolute beta-1 power to synaptogenesis and the investigate the vulnerability of the Prefrontal Cortex. Fourty typical children and 10 children with Perinatal Arterial Ischemic Stroke in their subcortical Middle Cerebral Artery were recruited and were created 3 age subgroups; 5month, 10month and 24month subgroup. EEG recording and Bayley-III test were used to measure their background activity and developmental level. Although the statistical analysis via non-parametric tools (Mann-Whitney U-test, Kruskall Wallis test) didn’t show decisive results, a potential connection of beta-band with synaptogenesis could be detected when observing low beta-1 power in motor and cognitive brain areas and low motor and cognitive performance and also by detecting a posterior to anterior maturation. Moreover the early vulnerability of Prefrontal Cortex may be found in the decreased bilateral beta-1 power in the 24month children with perinatal stroke, when compared with the typical children and the earlier unilateral differences, along with some cognitive deficits which begin to emerge in the same group.