King's College Hospital NHS Foundation Trust, Denmark Hill, London, United Kingdom,; Department of Pediatric Neurosurgery, Royal Manchester Children's Hospital, Manchester, M13 9WL, UK.
Nationally Comissioned Complex NF1 Service, Manchester Centre for Genomic Medicine, St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
Clin Neurol Neurosurg. 2020 Jun;193:105791. doi: 10.1016/j.clineuro.2020.105791. Epub 2020 Mar 19.
Aqueduct stenosis (AS) and fourth ventricle outflow obstruction are rare associations of neurofibromatosis type 1 (NF1), resulting in ventriculomegaly and hydrocephalus requiring surgical treatment. This study aims to identify the prevalence of AS and its patterns of clinical presentation, aetiology and treatment in the paediatric complex NF1 population.
Patients with NF-1 aged 0-18 years were recruited from the Regional Genetic Family Register, following institutional review board approval. Magnetic resonance imaging data and clinical documents were reviewed with respect to clinical presentation, degree of ventriculomegaly, aetiological factors and management of AS and fourth ventricle outflow obstruction.
24 of the 233 paediatric patients seen within the NHS highly specialised service for complex NF1 were found to have AS or and fourth ventricle outflow obstruction. This included 13 males and 11 females with a mean age of 9 years 5 months (range 8 months - 17 years). The majority of patients with AS or fourth ventricle outflow obstruction presented with symptoms of raised intracranial pressure associated with ventriculomegaly and/or hydrocephalus (n = 18). However, in 25 % of patients, AS was an incidental finding on MRI and was observed both in the presence (n = 2) and absence (n = 4) of ventriculomegaly. In the majority of cases a single cause of AS was identified (n = 16), of which tectal plate thickening (n = 7) was most frequently observed. The remaining 8 patients had multiple causes of AS, in which tectal plate thickening (n = 7) and aqueductal webs (n = 5) were the most common observations. Surgery was performed on all patients with evidence of raised pressure (n = 8) by performing endoscopic third ventriculostomy (ETV) (n = 5) or ventriculoperitoneal (VP)-shunting (n = 3). Tectal plate thickening was most frequently observed in patients who underwent ETV (n = 3), followed by aqueductal web (n = 1) and T2-signal changes in the tectal plate (n = 1). Patients treated with VP-shunt had 4th ventricle outflow obstruction (n = 2) and a tectal plate tumour (n = 1).
This study identifies that AS is more prevalent amongst the paediatric complex NF-1 population than previously reported, occurring in 10 % of cases. Our findings demonstrate that AS is most commonly symptomatic in presentation but can be asymptomatic in 25 % of paediatric complex NF1 patients. In this population, AS can occur both in the presence and absence of ventriculomegaly and therefore requires careful monitoring for development of hydrocephalus. In this study, over one third of patients (9 of 24 patients) with AS eventually required treatment.
神经纤维瘤病 1 型（NF1）可导致导水管狭窄（AS）和第四脑室流出道梗阻，这两种情况均较为罕见，可引起脑积水和需要手术治疗的脑室扩大。本研究旨在确定 NF1 患儿中 AS 的患病率及其临床表现、病因和治疗模式。
在机构审查委员会批准后，从区域遗传家族登记处招募了年龄在 0-18 岁之间的 NF-1 患者。对磁共振成像数据和临床文档进行了回顾，以了解 AS 和第四脑室流出道梗阻的临床表现、脑室扩大程度、病因和治疗。
在 NHS 高度专业化的复杂 NF1 服务中，233 名儿科患者中有 24 名被发现存在 AS 或第四脑室流出道梗阻。这包括 13 名男性和 11 名女性，平均年龄为 9 岁 5 个月（8 个月至 17 岁）。大多数存在 AS 或第四脑室流出道梗阻的患者表现为与脑室扩大和/或脑积水相关的颅内压升高症状（n = 18）。然而，在 25%的患者中，AS 是 MRI 的偶然发现，并且在存在（n = 2）和不存在（n = 4）脑室扩大的情况下都观察到。在大多数情况下，AS 存在单一病因（n = 16），其中最常观察到的是顶盖增厚（n = 7）。其余 8 名患者存在多种 AS 病因，其中最常见的观察结果是顶盖增厚（n = 7）和导水管狭窄（n = 5）。所有有颅内压升高证据的患者（n = 8）均接受了治疗，其中 5 例行内镜第三脑室造瘘术（ETV）（n = 5），3 例行脑室-腹腔（VP）分流术（n = 3）。在接受 ETV 治疗的患者中，最常观察到顶盖增厚（n = 3），其次是导水管狭窄（n = 1）和顶盖 T2 信号改变（n = 1）。接受 VP 分流术治疗的患者有 4 脑室流出道梗阻（n = 2）和顶盖肿瘤（n = 1）。
本研究表明，AS 在儿科复杂 NF1 人群中的发病率高于以往报道，占 10%。我们的研究结果表明，AS 最常见的表现为症状性，但在 25%的儿科复杂 NF1 患者中可能无症状。在该人群中，AS 可在存在和不存在脑室扩大的情况下发生，因此需要密切监测脑积水的发展。在本研究中，超过三分之一的存在 AS 的患者（24 名患者中的 9 名）最终需要治疗。
