{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T16:28:04Z","timestamp":1772209684640,"version":"3.50.1"},"reference-count":26,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T00:00:00Z","timestamp":1609718400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["Felloswhip"],"award-info":[{"award-number":["Felloswhip"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["PhD fellowship"],"award-info":[{"award-number":["PhD fellowship"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["fellowship"],"award-info":[{"award-number":["fellowship"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["fellowship"],"award-info":[{"award-number":["fellowship"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006181","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado da Bahia","doi-asserted-by":"publisher","award":["fellowship"],"award-info":[{"award-number":["fellowship"]}],"id":[{"id":"10.13039\/501100006181","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006507","name":"Funda\u00e7\u00e3o Oswaldo Cruz","doi-asserted-by":"publisher","award":["Intramural Research Program"],"award-info":[{"award-number":["Intramural Research Program"]}],"id":[{"id":"10.13039\/501100006507","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neurofibromatosis type 1 (NF-1) is an autosomal dominant disease that affects one in every 3000 individuals. This disease can present a wide range of clinical manifestations, ranging from skin abnormalities to severe vascular damage. Although not commonly recognized in the context of NF-1, cerebrovascular disease (CVD), can be often present since childhood and diagnosed just later in life. When present, NF-1-associated CVD clinical manifestations may include headache, cognitive deficits and ultimately aneurysm rupture, causing death. Thus, CVD plays an important role in the clinical manifestations, disease severity and prognosis of patients with NF-1. This systematic review aims to summarize the body of evidence linking NF-1 and CVD in children.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Two independent investigators performed a systematic review on the PubMed and EMBASE search platforms, using the following key terms: \u201cneurofibromatosis type 1\u201d, \u201cVon Recklinghausen\u2019s disease\u201d, \"children\", \"adolescents\", \"stroke\", \"Moyamoya disease\", \"vascular diseases\", \"cerebrovascular disorders\", \"aneurysm\" and \"congenital abnormalities\". Studies focused on assessing the development of CVD in children with NF-1 were included.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Seven studies met the inclusion criteria. Twelve different clinical manifestations have been associated with cerebrovascular changes in children with NF-1; 44,5% of diagnosed patients were asymptomatic.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The available evidence suggests that CVDs are related with the progression of NF-1, even in the absence of a clear clinical manifestation. In addition, improved prognosis was observed when imaging tests were performed to screen for cerebrovascular alterations early during the clinical investigation. Early diagnosis of CVD in NF-1 patients foster implementation of timely interventions, directly impacting clinical outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0241096","type":"journal-article","created":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T14:06:47Z","timestamp":1609769207000},"page":"e0241096","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["Association between neurofibromatosis type 1 and cerebrovascular diseases in children: A systematic review"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9901-8328","authenticated-orcid":true,"given":"Beatriz","family":"Barreto-Duarte","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabiana H.","family":"Andrade-Gomes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda B.","family":"Arriaga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana","family":"Ara\u00fajo-Pereira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Manuel","family":"Cubillos-Angulo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6833-3811","authenticated-orcid":true,"given":"Bruno B.","family":"Andrade","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,1,4]]},"reference":[{"issue":"4","key":"pone.0241096.ref001","first-page":"394","article-title":"[Neurofibromatosis type 1: more frequent and severe then usually thought]","volume":"55","author":"JF Souza","year":"2009","journal-title":"Rev Assoc Med Bras"},{"issue":"2","key":"pone.0241096.ref002","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/ajmg.a.33139","article-title":"Birth incidence and prevalence of tumor-prone syndromes: estimates from a UK family genetic register service","volume":"152A","author":"DG Evans","year":"2010","journal-title":"Am J Med Genet A"},{"key":"pone.0241096.ref003","author":"JM Friedman","year":"1993"},{"key":"pone.0241096.ref004","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/B978-0-444-52902-2.00053-9","article-title":"Neurofibromatosis type 1 (NF1): diagnosis and management","volume":"115","author":"RE Ferner","year":"2013","journal-title":"Handb Clin Neurol"},{"issue":"11","key":"pone.0241096.ref005","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1007\/s00381-012-1790-0","article-title":"Ischemic cerebral infarction in a 5-year-old male child with neurofibromatosis type 1","volume":"28","author":"A Gkampeta","year":"2012","journal-title":"Childs Nerv Syst"},{"key":"pone.0241096.ref006","first-page":"735419","article-title":"Coexistence of Neurofibromatosis Type-1 and MTHFR C677T Gene Mutation in a Young Stroke Patient","volume":"2013","author":"H Yilmaz","year":"2013","journal-title":"A Case Report. 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