Cerebral vasculopathy in childhood neurofibromatosis type 2: cause for concern?

Abstract

Unlike adult neurofibromatosis type 2 (NF2), which presents with symptoms related to bilateral vestibular schwannomas, children with NF2 most frequently present with ocular, dermatological, and neurological symptoms. Arteriopathy, a well-established feature in neurofibromatosis type 1, is not a widely recognized feature of NF2. Here we report three children with NF2 with cerebral arteriopathy and/or arterial ischaemic stroke. Bevacizumab, a vascular endothethial growth factor inhibitor, is an established treatment for rapidly growing vestibular schwannomas; however, it carries a risk of both ischaemic and haemorrhagic stroke. Thus, the role of screening and risk to benefit ratio of bevacizumab in NF2 merit further consideration. WHAT THIS PAPER ADDS: Children with neurofibromatosis type 2 (NF2) may be at increased risk of cerebral vasculopathy and arterial ischaemic stroke. Targeted magnetic resonance angiography should be performed in children with NF2 who are being considered for bevacizumab therapy.

Brainstem ischemic syndrome in juvenile NF2

“…Multicase analysis was undertaken to observe common features in 16 predetermined categories. [3][4][5][6]…”

Trends in phenotype in the English paediatric neurofibromatosis type 2 cohort stratified by genetic severity

“…The clinical significance of these features is uncertain but may suggest a role for Merlin in brain development. Vascular anomalies were seen both intracranially, previously described in detail 46 and in major vessels, and three patients had features suggestive of brainstem or cerebellar peduncle lacunar infarcts, further suggesting that vascular abnormality is a feature of NF2.…”

Stroke in childhood neurofibromatosis type 2

“…All the infarcts reported were in the posterior circulation, but the available arterial imaging of the vertebrobasilar system was normal. As only one case had conventional angiography soon after the acute stroke, it is possible that dissection or small vessel pathology was missed.…”

“…Interestingly, hemiplegia was reported in nearly 25% of patients presenting aged less than 20 years in the Japanese NF2 registry . One of the cases from the literature reported by Lascelles et al underscores the difficulty in distinguishing focal ischaemia from tumour. In addition, stroke may present before the characteristic vestibular schwannomas can be diagnosed clinically or radiologically.…”

“…Alternatively, the infarcts could be venous, generally considered rare in the posterior fossa because of the collateralization, although there are few data available in cases of NF2. There is no evidence of venous sinus thrombosis (VST) or haemorrhage, but this pathology may also reverse quickly. Fever, anaemia, and dehydration are triggers for VST, which has been reported after surgery for vestibular schwannoma in adults .…”