Cause of Death in Neurofibromatosis 2: A 12-Year Experience from a Single Specialist Unit

Introduction: Neurofibromatosis 2 (NF2) is a rare neurocutaneous disorder characterized by the development of multiple intracranial and spinal tumors. It has a birth incidence of approximately 1 in 25,000, and up to 95% will develop bilateral vestibular schwannomas. Other related tumors include central and peripheral schwannomas, meningiomas, and ependymomas. Eye problems are common and include early-onset subcapsular lens opacities and retinal hamartomas.

Long-term survival rates in patients with NF2 have been documented. Mean actuarial survival in patients with NF2 has been reported to be 62 years. However, there is a large range of disease severity, and it is apparent that age of diagnosis is the most convincing predictor of long-term survival, with patients diagnosed at a younger age doing less well. In a large database analysis of 368 UK patients, 74 (20%) died during follow-up, and in 51 of these the cause of death was reported as tumor burden. The aim of this study was to identify mortality rates and causes of death in our NF2 patients and compare them to previously published findings.

Methods: The specialist multidisciplinary NF2 clinic at Guy's Hospital has been in existence for 12 years. We have produced a database of patients who have been personally managed in this clinic by the senior author. Each patient has been seen regularly by the same clinicians, with all imaging performed at the same site and reported by the same specialist neuroradiologist, and all procedures were performed by the same surgeons. The database of patients with a confirmed diagnosis of NF2 who were managed in the specialist clinic between 1992 and 2008 was analyzed. A further cohort of patients that are at risk of NF2 due to family history but do not have a confirmed diagnosis were excluded from this study.

Results: A total of 58 patients with a diagnosis of somatic or mosaic NF2 were identified (26 male and 32 female). The mean age at the time of database analysis was 36 years, with a range of 4–80 years. A total of 5 patients had died during follow-up (8.6%). Of this group, none died as a direct result of tumor burden. One patient died intraoperatively during the excision of a vestibular schwannoma. One died of a lower respiratory tract infection, which was secondary to a suspected radiation-associated encephalopathy, many years after irradiation of a frontal meningioma. One patient died of vascular disease, and another of lower respiratory chest infection. One patient died due to malignant chondrosarcoma.

Discussion: Management of the NF2 patient is complex and challenging. It has been previously reported that around half of patients die due to tumor burden. In our series of patients managed in a single unit, our experience differed. Two patients died as a direct consequence of treatment for their disease, and it is necessary to carefully balance risks and benefits of intervention in this group of patients.