{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T17:14:03Z","timestamp":1794071643775,"version":"4.8.0"},"reference-count":13,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007653","name":"Universit\u00e4tsklinikum Jena","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007653","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>NF2-related schwannomatosis (NF2) is associated with various tumors of the central and peripheral nervous system. There is a wide range of disabilities these patients may suffer from and there is no validated clinical classification for disease severity. We propose a clinical classification consisting of three severity grades to assist in patient management.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Patient records from 168 patients were screened for most common diagnoses with severe impact on everyday tasks, social interactions and life expectancy. Eight main categories were identified. One point was assigned to each category. Three severity grades were differentiated as follows: grade 1 (mild NF2): 0 points; grade 2 (moderate NF2): &lt; 3 points; grade 3 (severe NF2): \u2265 3 points. This grading system was then evaluated with respect to inter-rater reliability and clinical significance.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The patients were grouped according to our new clinical grading system into grade 1 in 48% (<jats:italic>n<\/jats:italic>\u2009=\u200980), grade 2 in 43% (<jats:italic>n<\/jats:italic>\u2009=\u200972), and grade 3 in 10% of patients (<jats:italic>n<\/jats:italic>\u2009=\u200916). There was substantial inter-rater reliability between 3 raters with different levels of clinical experience (Fleiss\u2019 kappa\u2009=\u20090.62). The severity grades correlated significantly with hospitalization, number of operations and dependency on implants (such as cochlear implant, auditory brain-stem implants or ventriculoperitoneal shunts).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Clinical disease severity of NF2 patients is reflected in a simplified and rater-independent score with three grades. The score facilitates communication for medical personnel of varying experience and backgrounds, and adds a clinical tool to decision-making and research.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13023-024-03512-3","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T12:57:45Z","timestamp":1736168265000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Clinical severity grading of NF2-related schwannomatosis"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3146-4241","authenticated-orcid":false,"given":"Anna C.","family":"Lawson McLean","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"L\u00f6schner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Said","family":"Farschtschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora F.","family":"Dengler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen K.","family":"Rosahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,6]]},"reference":[{"key":"3512_CR1","first-page":"354","volume":"117","author":"S Farschtschi","year":"2020","unstructured":"Farschtschi S, Mautner VF, Lawson McLean AC, et al. The neurofibromatoses. Dtsch Arztebl Int. 2020;117:354\u201360.","journal-title":"Dtsch Arztebl Int"},{"key":"3512_CR2","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1007\/s00415-014-7303-1","volume":"261","author":"RE Ferner","year":"2014","unstructured":"Ferner RE, Shaw A, Evans DG, et al. Longitudinal evaluation of quality of life in 288 patients with neurofibromatosis 2. J Neurol. 2014;261:963\u20139.","journal-title":"J Neurol"},{"issue":"10","key":"3512_CR3","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1136\/jmedgenet-2017-104519","volume":"54","author":"D Halliday","year":"2017","unstructured":"Halliday D, Emmanouil B, Pretorius P, MacKeith S, et al. Genetic severity score predicts clinical phenotype in NF2. J Med Genet. 2017;54(10):657\u201364.","journal-title":"J Med Genet"},{"issue":"2","key":"3512_CR4","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1055\/s-0032-1301396","volume":"73","author":"RE Hornigold","year":"2012","unstructured":"Hornigold RE, Golding JF, Leschziner G, et al. The NFTI-QOL: a Disease-Specific Quality of Life Questionnaire for neurofibromatosis 2. J Neurol Surg B Skull Base. 2012;73(2):104\u201311.","journal-title":"J Neurol Surg B Skull Base"},{"issue":"5","key":"3512_CR5","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1007\/s00415-014-7303-1","volume":"261","author":"RE Ferner","year":"2014","unstructured":"Ferner RE, Shaw A, Evans DG, et al. Longitudinal evaluation of quality of life in 288 patients with neurofibromatosis 2. J Neurol. 2014;261(5):963\u20139.","journal-title":"J Neurol"},{"issue":"4","key":"3512_CR6","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1212\/CPJ.0000000000000648","volume":"9","author":"A Shukla","year":"2019","unstructured":"Shukla A, Fang-Chi H, Slobogean B, et al. Association between patient-reported outcomes and objective disease indices in people with NF2. Neurol Clin Pract. 2019;9(4):322\u20139.","journal-title":"Neurol Clin Pract"},{"issue":"4","key":"3512_CR7","first-page":"281","volume":"3","author":"KA Morris","year":"2016","unstructured":"Morris KA, Golding JF, Axon PR, et al. Bevacizumab in neurofibromatosis type 2 (NF2) related vestibular schwannomas: a nationally coordinated approach to delivery and prospective evaluation. Neurooncol Pract. 2016;3(4):281\u20139.","journal-title":"Neurooncol Pract"},{"issue":"1","key":"3512_CR8","doi-asserted-by":"publisher","first-page":"62","DOI":"10.3109\/00016489.2015.1079925","volume":"136","author":"K Lundin","year":"2016","unstructured":"Lundin K, Stillesj\u00f6 F, Nyberg G, et al. Self-reported benefit, sound perception, and quality-of-life in patients with auditory brainstem implants (ABIs). Acta Otolaryngol. 2016;136(1):62\u20137.","journal-title":"Acta Otolaryngol"},{"issue":"1","key":"3512_CR9","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s13023-022-02607-z","volume":"18","author":"AC Lawson McLean","year":"2023","unstructured":"Lawson McLean AC, Freier A, Lawson McLean A, et al. The German version of the neurofibromatosis 2 impact on quality of life questionnaire correlates with severity of depression and physician-reported disease severity. Orphanet J Rare Dis. 2023;18(1):3. https:\/\/doi.org\/10.1186\/s13023-022-02607-z. PMID: 36604703; PMCID: PMC9817379.","journal-title":"Orphanet J Rare Dis"},{"key":"3512_CR10","unstructured":"WHO Programme for the Prevention of Blindness and Deafness. (2003). Consultation on development of standards for characterization of vision loss and visual functioning: Genveva, 4\u20135 September 2003. World Health Organization. https:\/\/apps.who.int\/iris\/handle\/10665\/68601"},{"issue":"1","key":"3512_CR11","doi-asserted-by":"publisher","first-page":"159","DOI":"10.2307\/2529310","volume":"33","author":"JR Landis","year":"1977","unstructured":"Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33(1):159\u201374.","journal-title":"Biometrics"},{"issue":"4","key":"3512_CR12","doi-asserted-by":"publisher","first-page":"e35711","DOI":"10.1371\/journal.pone.0035711","volume":"7","author":"SR Plotkin","year":"2012","unstructured":"Plotkin SR, Bredella MA, Cai W, et al. Quantitative Assessment of whole-body tumor burden in adult patients with neurofibromatosis. PLoS ONE. 2012;7(4):e35711.","journal-title":"PLoS ONE"},{"key":"3512_CR13","doi-asserted-by":"publisher","unstructured":"Faria SH. Assessment of immobility hazards. Home Care Provid. 1998;3(4):189\u2009\u2013\u200991. https:\/\/doi.org\/10.1016\/s1084-628x(98)90124-1. PMID: 9814195.","DOI":"10.1016\/s1084-628x(98)90124-1"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-024-03512-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-024-03512-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-024-03512-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T13:06:47Z","timestamp":1736168807000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-024-03512-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,6]]},"references-count":13,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["3512"],"URL":"https:\/\/doi.org\/10.1186\/s13023-024-03512-3","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,6]]},"assertion":[{"value":"12 November 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 December 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 January 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"This study was approved by the local institutional review board.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The authors report no conflict of interest.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"4"}}