Evaluation of clinical diagnostic criteria for neurofibromatosis 2

TLDR

Four clinical diagnostic criteria sets for neurofibromatosis 2 exist, but their sensitivity—especially for patients lacking bilateral vestibular schwannomas—has never been formally evaluated. This study empirically assesses the diagnostic performance of those four criteria sets. Using 163 UK NF2 registry patients without bilateral vestibular schwannomas, the authors applied each criterion at initial presentation and after an average 13‑year follow‑up. At the most recent assessment, NIH criteria captured 78 % of definite NF2 cases with negative family history, whereas NNFF and Manchester criteria identified 91 % and 93 % respectively, yet all sets missed most cases at initial assessment, underscoring the need for a revised, unified diagnostic standard.

Abstract

<b><i>Background:</i></b> Four sets of clinical diagnostic criteria for neurofibromatosis 2 (NF2) have been developed by groups of expert clinicians, but sensitivity has never been formally assessed. The sets of criteria differ for people without bilateral vestibular schwannomas, which are pathognomonic for NF2. <b><i>Objective: </i></b> To empirically evaluate the four existing sets of clinical diagnostic criteria for NF2. <b><i>Methods: </i></b> The study was based on 163 of 403 people in the United Kingdom NF2 registry (41%) who presented without bilateral vestibular schwannomas. The authors applied the sets of criteria to each person at initial assessment and at the most recent clinical evaluation (mean ± SE length of follow-up, 13 ± 1 years). <b><i>Results: </i></b> In people with "definite NF2" and a negative family history of NF2, the 1987 US NIH and 1991 NIH criteria each identify 78% of people at the most recent clinical evaluation but 0% at initial assessment. The National Neurofibromatosis Foundation (NNFF) criteria and the Manchester criteria each identify higher proportions at both time points (NNFF criteria, 91% and 10%; Manchester criteria, 93% and 14%), but the proportions at initial assessment are still low. <b><i>Conclusions: </i></b> None of the existing sets of criteria are adequate at initial assessment for diagnosing people who present without bilateral vestibular schwannomas as having NF2, particularly people with a negative family history of NF2. The authors recommend that a single, revised set of diagnostic criteria be devised to replace all of the existing sets of criteria.