{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T13:46:55Z","timestamp":1768916815666,"version":"3.49.0"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T00:00:00Z","timestamp":1634256000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T00:00:00Z","timestamp":1634256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100018936","name":"Universit\u00e4tsklinikum Heidelberg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100018936","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Neuroradiol"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>To examine long-term alterations of the dorsal root ganglia (DRG) and the peripheral nerve in patients with neurofibromatosis type\u00a02 (NF2) by in vivo high-resolution magnetic resonance neurography (MRN) and their correlation to histology.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In this prospective study the lumbosacral DRG, the right sciatic, tibial, and peroneal nerves were examined in 6\u00a0patients diagnosed with NF2 and associated polyneuropathy (PNP) by a\u00a0standardized MRN protocol at 3\u202fT. Volumes of DRG L3\u2013S2 as well as peripheral nerve lesions were assessed and compared to follow-up examinations after 14\u2013100\u00a0months. In one patient, imaging findings were further correlated to histology.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Follow-up MRN examination showed a\u00a0non-significant increase of volume for the DRG L3: +0.41% (<jats:italic>p<\/jats:italic>\u202f=\u20090.10), L4: +22.41% (<jats:italic>p<\/jats:italic>\u202f=\u20090.23), L5: +3.38% (<jats:italic>p<\/jats:italic>\u202f=\u20090.09), S1: +10.63% (<jats:italic>p<\/jats:italic>\u202f=\u20090.05) and S2: +1.17% (<jats:italic>p<\/jats:italic>\u202f=\u20090.57). Likewise, peripheral nerve lesions were not significantly increased regarding size (2.18\u202fmm<jats:sup>2<\/jats:sup> vs. 2.15\u202fmm<jats:sup>2<\/jats:sup>, <jats:italic>p<\/jats:italic>\u202f=\u20090.89) and number (9.00 vs. 9.33, <jats:italic>p<\/jats:italic>\u202f=\u20090.36). Histological analyses identified schwannomas as the major correlate of both DRG hyperplasia and peripheral nerve lesions. For peripheral nerve microlesions additionally clusters of onion-bulb formations were identified.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Peripheral nervous system alterations seem to be constant or show only a\u00a0minor increase in adult NF2. Thus, symptoms of PNP may not primarily attributed to the initial schwannoma growth but to secondary long-term processes, with symptoms only occurring if a\u00a0certain threshold is exceeded. Histology identified grouped areas of Schwann cell proliferations as the correlate of DRG hyperplasia, while for peripheral nerve lesions different patterns could be found.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00062-021-01102-5","type":"journal-article","created":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T14:28:36Z","timestamp":1634308116000},"page":"277-285","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Long-term Follow-up and Histological Correlation of Peripheral Nervous System Alterations in Neurofibromatosis Type\u00a02"],"prefix":"10.1007","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4997-3076","authenticated-orcid":false,"given":"Tim","family":"Godel","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp","family":"B\u00e4umer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Said","family":"Farschtschi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"P\u00fcschel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Hofstadler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Heiland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathias","family":"Gelderblom","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Bendszus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Hagel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor-Felix","family":"Mautner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,10,15]]},"reference":[{"key":"1102_CR1","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/j.expneurol.2017.06.006","volume":"299","author":"A Schulz","year":"2018","unstructured":"Schulz A, Grafe P, Hagel C, B\u00e4umer P, Morrison H, Mautner VF, Farschtschi S. Neuropathies in the setting of Neurofibromatosis tumor syndromes: Complexities and opportunities. Exp Neurol. 2018;299:334-44.","journal-title":"Exp Neurol"},{"key":"1102_CR2","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1007\/BF02427564","volume":"19","author":"L Grazzi","year":"1998","unstructured":"Grazzi L, Chiapparini L, Parati EA, Giombini S, D\u2019Amico D, Leone M, Bussone G. Type II neurofibromatosis presenting as quadriceps atrophy. Ital J Neurol Sci. 1998;19:94-6.","journal-title":"Ital J Neurol Sci"},{"key":"1102_CR3","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1002\/ana.24753","volume":"80","author":"S Farschtschi","year":"2016","unstructured":"Farschtschi S, Mautner VF, Pham M, Nguyen R, Kehrer-Sawatzki H, Hutter S, Friedrich RE, Schulz A, Morrison H, Jones DT, Bendszus M, B\u00e4umer P. Multifocal nerve lesions and LZTR1 germline mutations in segmental schwannomatosis. Ann Neurol. 2016;80:625-8.","journal-title":"Ann Neurol."},{"key":"1102_CR4","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1007\/s00415-012-6581-8","volume":"260","author":"P B\u00e4umer","year":"2013","unstructured":"B\u00e4umer P, Mautner VF, B\u00e4umer T, Schuhmann MU, Tatagiba M, Heiland S, Kaestel T, Bendszus M, Pham M. Accumulation of non-compressive fascicular lesions underlies NF2 polyneuropathy. J Neurol. 2013;260:38-46.","journal-title":"J Neurol."},{"key":"1102_CR5","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1093\/brain\/awf115","volume":"125","author":"AD Sperfeld","year":"2002","unstructured":"Sperfeld AD, Hein C, Schr\u00f6der JM, Ludolph AC, Hanemann CO. Occurrence and characterization of peripheral nerve involvement in neurofibromatosis type 2. Brain. 2002;125:996-1004.","journal-title":"Brain."},{"key":"1102_CR6","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1007\/s00401-002-0535-7","volume":"104","author":"C Hagel","year":"2002","unstructured":"Hagel C, Lindenau M, Lamszus K, Kluwe L, Stavrou D, Mautner VF. Polyneuropathy in neurofibromatosis 2: clinical findings, molecular genetics and neuropathological alterations in sural nerve biopsy specimens. Acta Neuropathol. 2002;104:179-87.","journal-title":"Acta Neuropathol."},{"key":"1102_CR7","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1002\/ana.25191","volume":"83","author":"T Godel","year":"2018","unstructured":"Godel T, Mautner VF, Farschtschi S, Pham M, Schwarz D, Kronlage M, Gugel I, Heiland S, Bendszus M, B\u00e4umer P. Dorsal root ganglia volume differentiates schwannomatosis and neurofibromatosis 2. Ann Neurol. 2018;83:854-7.","journal-title":"Ann Neurol."},{"key":"1102_CR8","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1001\/jama.1997.03550010065042","volume":"278","author":"DH Gutmann","year":"1997","unstructured":"Gutmann DH, Aylsworth A, Carey JC, Korf B, Marks J, Pyeritz RE, Rubenstein A, Viskochil D. The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA. 1997;278:51-7.","journal-title":"JAMA"},{"key":"1102_CR9","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1111\/nan.12330","volume":"42","author":"C Hagel","year":"2016","unstructured":"Hagel C, Dornblut C, Schulz A, Wiehl U, Friedrich RE, Huckhagel T, Mautner VF, Morrison H. The putative oncogene CPI-17 is up-regulated in schwannoma. Neuropathol Appl Neurobiol. 2016;42:664-8.","journal-title":"Neuropathol Appl Neurobiol"},{"key":"1102_CR10","doi-asserted-by":"publisher","first-page":"e590","DOI":"10.1212\/WNL.0000000000007898","volume":"93","author":"T Godel","year":"2019","unstructured":"Godel T, B\u00e4umer P, Farschtschi S, Gugel I, Kronlage M, Hofstadler B, Heiland S, Gelderblom M, Bendszus M, Mautner VF. Peripheral nervous system alterations in infant and adult neurofibromatosis type 2. Neurology. 2019;93:e590-8.","journal-title":"Neurology"},{"key":"1102_CR11","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1136\/jmg.2005.031302","volume":"42","author":"ME Baser","year":"2005","unstructured":"Baser ME, Mautner VF, Parry DM, Evans DG. Methodological issues in longitudinal studies: vestibular schwannoma growth rates in neurofibromatosis 2. J Med Genet. 2005;42:903-6.","journal-title":"J Med Genet"},{"key":"1102_CR12","doi-asserted-by":"publisher","first-page":"217","DOI":"10.3171\/jns.2002.96.2.0217","volume":"96","author":"ME Baser","year":"2002","unstructured":"Baser ME, Makariou EV, Parry DM. Predictors of vestibular schwannoma growth in patients with neurofibromatosis Type 2. J Neurosurg. 2002;96:217-22.","journal-title":"J Neurosurg."},{"key":"1102_CR13","doi-asserted-by":"publisher","first-page":"223","DOI":"10.3171\/jns.2002.96.2.0223","volume":"96","author":"VF Mautner","year":"2002","unstructured":"Mautner VF, Baser ME, Thakkar SD, Feigen UM, Friedman JM, Kluwe L. Vestibular schwannoma growth in patients with neurofibromatosis Type 2: a longitudinal study. J Neurosurg. 2002;96:223-8.","journal-title":"J Neurosurg."},{"key":"1102_CR14","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1038\/nn.3348","volume":"16","author":"A Schulz","year":"2013","unstructured":"Schulz A, Baader SL, Niwa-Kawakita M, Jung MJ, Bauer R, Garcia C, Zoch A, Schacke S, Hagel C, Mautner VF, Hanemann CO, Dun XP, Parkinson DB, Weis J, Schr\u00f6der JM, Gutmann DH, Giovannini M, Morrison H. Merlin isoform 2 in neurofibromatosis type 2-associated polyneuropathy. Nat Neurosci. 2013;16:426-33.","journal-title":"Nat Neurosci"},{"key":"1102_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/hmg\/ddu414","volume":"24","author":"JR Gehlhausen","year":"2015","unstructured":"Gehlhausen JR, Park SJ, Hickox AE, Shew M, Staser K, Rhodes SD, Menon K, Lajiness JD, Mwanthi M, Yang X, Yuan J, Territo P, Hutchins G, Nalepa G, Yang FC, Conway SJ, Heinz MG, Stemmer-Rachamimov A, Yates CW, Wade Clapp D. A murine model of neurofibromatosis type 2 that accurately phenocopies human schwannoma formation. Hum Mol Genet. 2015;24:1-8.","journal-title":"Hum Mol Genet."},{"issue":"11","key":"1102_CR16","first-page":"999","volume":"1986","author":"J Weinstein","year":"1976","unstructured":"Weinstein J. Report of the 1985 ISSLS Traveling Fellowship. Mechanisms of spinal pain. The dorsal root ganglion and its role as a mediator of low-back pain. Spine (Phila Pa 1976). 1986;11:999-1001.","journal-title":"Spine (Phila Pa"},{"key":"1102_CR17","doi-asserted-by":"publisher","first-page":"85","DOI":"10.3109\/00016488709124980","volume":"436","author":"H Felix","year":"1987","unstructured":"Felix H, Hoffmann V, Wright A, Gleeson M. Ultrastructural findings on human Scarpa\u2019s ganglion. Acta Otolaryngol Suppl. 1987;436:85-92.","journal-title":"Acta Otolaryngol Suppl"},{"key":"1102_CR18","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1017\/S1740925X04000110","volume":"1","author":"A Fex Svenningsen","year":"2004","unstructured":"Fex Svenningsen A, Colman DR, Pedraza L. Satellite cells of dorsal root ganglia are multipotential glial precursors. Neuron Glia Biol. 2004;1:85-93.","journal-title":"Neuron Glia Biol."}],"container-title":["Clinical Neuroradiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00062-021-01102-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00062-021-01102-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00062-021-01102-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T10:07:47Z","timestamp":1646302067000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00062-021-01102-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,15]]},"references-count":18,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["1102"],"URL":"https:\/\/doi.org\/10.1007\/s00062-021-01102-5","relation":{},"ISSN":["1869-1439","1869-1447"],"issn-type":[{"value":"1869-1439","type":"print"},{"value":"1869-1447","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,15]]},"assertion":[{"value":"18 July 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 September 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 October 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"T.\u00a0Godel, P.\u00a0B\u00e4umer, S.\u00a0Farschtschi, K.\u00a0P\u00fcschel, B.\u00a0Hofstadler, S.\u00a0Heiland, M.\u00a0Gelderblom, M.\u00a0Bendszus, C.\u00a0Hagel and V.-F.\u00a0Mautner declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All procedures performed in studies involving human participants or on human tissue were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1975 Helsinki declaration and its later amendments or comparable ethical standards. Ethics approval S398-2012. Consent to participate. Informed consent was obtained from all individual participants included in the study. Consent for publication. Patients or their legal representatives for whom identifying information is included in this article signed informed consent regarding publishing their data.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical standards"}}]}}