Association between neurofibromatosis type 1 and cerebrovascular diseases in children: A systematic review

Abstract

Background 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. Methods Two independent investigators performed a systematic review on the PubMed and EMBASE search platforms, using the following key terms: “neurofibromatosis type 1”, “Von Recklinghausen’s disease”, "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. Results 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. Conclusion 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.

ERN GENTURIS tumour surveillance guidelines for individuals with neurofibromatosis type 1

“… 3 , 4 An additional common manifestation associated with NF1 is neurocognitive impairment, such as learning disability, attention-deficit hyperactivity disorder, autism spectrum disorder, behavioural problems and specific learning difficulties. 5 , 6 , 7 , 8 , 9 Furthermore, patients with NF1 may experience other organ specific manifestations such as vascular changes (amongst others moyamoya type vasculopathy 10 , 11 ), and several skeletal defects. 12 , 13 , 14 Therefore, it is a disease that cuts across multiple disciplines and considerably affects quality of life.…”

Cerebral Vasculopathy in Children with Neurofibromatosis Type 1

“…There is lack of consensus as to the association of CVD and causality due to other manifestations of NF1. Moyamoya can occur in individuals with or without NF1, although there is clearly an increased risk to those with NF1 [3,14,19,20]. Moyamoya is also the most frequently observed cerebrovascular abnormality in NF1 and is characterized by progressive stenosis of the internal carotid artery as well as stenosis of the other major intracranial arteries affecting anterior greater than posterior circulation.…”

The Genetic Basis of Strokes in Pediatric Populations and Insight into New Therapeutic Options

“…Besides the predisposition to certain types of neoplasms, NF1 may include vascular abnormalities, usually developing early in life. Vascular malformations can affect any organ, but the effect on vessels from the CNS has the most prominent effects on morbidity and mortality [57,58]. An association with vascular abnormalities including moyamoya arteriopathy, cerebral aneurysms, and stenotic or ectatic cerebral vessels increases the risk of ischemic and hemorrhagic stroke in affected individuals [59].…”