title: Multiple synchronous sites of origin of vestibular schwannomas in neurofibromatosis Type 2.
abstract: BACKGROUND
  Neurofibromatosis Type 2 (NF2) is a dominantly inherited tumour syndrome with a phenotype which includes bilateral vestibular (eighth cranial nerve) schwannomas. Conventional thinking suggests that these tumours originate at a single point along the superior division of the eighth nerve.
  
  
  METHODS
  High resolution MRI was performed in children genetically proven to have NF2. The superior vestibular nerve (SVN) and inferior vestibular nerve (IVN) were visualised along their course with points of tumour origin calculated as a percentage relative to the length of the nerve.
  
  
  RESULTS
  Out of 41 patients assessed, 7 patients had no identifiable eighth cranial nerve disease. In 16 patients there was complete filling of the internal auditory meatus by a tumour mass such that its specific neural origin could not be determined. In the remaining 18 cases, 86 discrete separate foci of tumour origin on the SVN or IVN could be identified including 23 tumours on the right SVN, 26 tumours on the right IVN, 18 tumours on the left SVN and 19 tumours on the left IVN.
  
  
  CONCLUSIONS
  This study, examining the origins of vestibular schwannomas in NF2, refutes their origin as being from a single site on the transition zone of the superior division of the vestibular nerve. We hypothesise a relationship between the number of tumour foci, tumour biology and aggressiveness of disease. The development of targeted drug therapies in addition to bevacizumab are therefore essential to improve prognosis and quality of life in patients with NF2 given the shortcomings of surgery and radiation treatments when dealing with the multifocality of the disease.
authors.affiliation: Academic Unit of Paediatric Radiology, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK Centre for Imaging Sciences, Institute of Population Health, University of Manchester, Manchester, UK Children's Brain Tumour Research Network, Royal Manchester Children's Hospital, Manchester, UK.
authors.forename: Stavros M
authors.initials: SM
authors.lastname: Stivaros
authors.affiliation: Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Anat O
authors.initials: AO
authors.lastname: Stemmer-Rachamimov
authors.affiliation: National Drug Evidence Centre (NDEC), Centre for Epidemiology, Institute of Population Health, University of Manchester, Manchester, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Alston
authors.affiliation: Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Plotkin
authors.affiliation: Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Nadol
authors.affiliation: Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.
authors.forename: Alicia
authors.initials: A
authors.lastname: Quesnel
authors.affiliation: Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: O'Malley
authors.affiliation: Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester, UK.
authors.forename: Gillian A
authors.initials: GA
authors.lastname: Whitfield
authors.affiliation: Centre for Paediatric, Teenage and Young Adult Cancer, Institute of Cancer Sciences, University of Manchester, Manchester, UK.
authors.forename: Martin G
authors.initials: MG
authors.lastname: McCabe
authors.affiliation: Department of Otolaryngology, Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Freeman
authors.affiliation: Department of Otolaryngology, Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Simon K
authors.initials: SK
authors.lastname: Lloyd
authors.affiliation: Academic Unit of Paediatric Radiology, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Neville B
authors.initials: NB
authors.lastname: Wright
authors.affiliation: Children's Brain Tumour Research Network, Royal Manchester Children's Hospital, Manchester, UK.
authors.forename: John-Paul
authors.initials: JP
authors.lastname: Kilday
authors.affiliation: Children's Brain Tumour Research Network, Royal Manchester Children's Hospital, Manchester, UK Department of Paediatric Neurosurgery, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Kamaly-Asl
authors.affiliation: Department of Neuroradiology, Salford NHS Foundation Trust Hospital, Salford, Greater Manchester, UK.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Mills
authors.affiliation: Department of Neurosurgery, Salford Royal Hospital, Salford, Greater Manchester, UK.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Rutherford
authors.affiliation: Department of Neurosurgery, Salford Royal Hospital, Salford, Greater Manchester, UK.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: King
authors.affiliation: Department of Genomic Medicine, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: D Gareth
authors.initials: DG
authors.lastname: Evans
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D016518:Neurofibromatosis 2 / Q000235:genetics / Q000473:pathology*; D009464:Neuroma, Acoustic / Q000235:genetics / Q000473:pathology*; D011379:Prognosis; D014725:Vestibular Nerve / Q000473:pathology
keywords: Cancer: CNS; Cancer: head and neck; Clinical genetics; Diagnostics; Neurology