{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:56:56Z","timestamp":1760151416499,"version":"build-2065373602"},"reference-count":21,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T00:00:00Z","timestamp":1647993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Purpose To examine the spatial distribution and long-term alterations of peripheral nerve lesions in patients with schwannomatosis by in vivo high-resolution magnetic resonance neurography (MRN). Methods In this prospective study, the lumbosacral plexus as well as the right sciatic, tibial, and peroneal nerves were examined in 15 patients diagnosed with schwannomatosis by a standardized MRN protocol at 3 Tesla. Micro-, intermediate- and macrolesions were assessed according to their number, diameter and spatial distribution. Moreover, in nine patients, peripheral nerve lesions were compared to follow-up examinations after 39 to 71 months. Results In comparison to intermediate and macrolesions, microlesions were the predominant lesion entity at the level of the proximal (p &lt; 0.001), mid- (p &lt; 0.001), and distal thigh (p &lt; 0.01). Compared to the proximal calf level, the lesion number was increased at the proximal (p &lt; 0.05), mid- (p &lt; 0.01), and distal thigh level (p &lt; 0.01), while between the different thigh levels, no differences in lesion numbers were found. In the follow-up examinations, the lesion number was unchanged for micro-, intermediate and macrolesions. The diameter of lesions in the follow-up examination was decreased for microlesions (p &lt; 0.01), not different for intermediate lesions, and increased for macrolesions (p &lt; 0.01). Conclusion Microlesions represent the predominant type of peripheral nerve lesion in schwannomatosis and show a rather consistent distribution pattern in long-term follow-up. In contrast to the accumulation of nerve lesions, primarily in the distal nerve segments in NF2, the lesion numbers in schwannomatosis peak at the mid-thigh level. Towards more distal portions, the lesion number markedly decreases, which is considered as a general feature of other types of small fiber neuropathy.<\/jats:p>","DOI":"10.3390\/diagnostics12040780","type":"journal-article","created":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T12:20:25Z","timestamp":1648038025000},"page":"780","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Spatial Distribution and Long-Term Alterations of Peripheral Nerve Lesions in Schwannomatosis"],"prefix":"10.3390","volume":"12","author":[{"given":"Tim","family":"Godel","sequence":"first","affiliation":[{"name":"Department of Neuroradiology, Neurological University Clinic, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp","family":"B\u00e4umer","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Neurological University Clinic, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Center for Radiology dia.log, Vinzenz-von-Paul Str. 8, 84503 Altotting, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3596-5932","authenticated-orcid":false,"given":"Said","family":"Farschtschi","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center Hamburg-Eppendorf, Martinistra\u00dfe 52, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Hofstadler","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Neurological University Clinic, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Heiland","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Neurological University Clinic, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathias","family":"Gelderblom","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center Hamburg-Eppendorf, Martinistra\u00dfe 52, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Bendszus","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Neurological University Clinic, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor-Felix","family":"Mautner","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center Hamburg-Eppendorf, Martinistra\u00dfe 52, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,23]]},"reference":[{"key":"ref_1","first-page":"354","article-title":"The Neurofibromatoses","volume":"117","author":"Farschtschi","year":"2020","journal-title":"Dtsch. Arztebl. Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1007\/s00415-012-6581-8","article-title":"Accumulation of non-compressive fascicular lesions underlies NF2 polyneuropathy","volume":"260","author":"Baumer","year":"2013","journal-title":"J. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s00401-002-0535-7","article-title":"Polyneuropathy in neurofibromatosis 2: Clinical findings, molecular genetics and neuropathological alterations in sural nerve biopsy specimens","volume":"104","author":"Hagel","year":"2002","journal-title":"Acta Neuropathol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Farschtschi, S.C., Mainka, T., Glatzel, M., Hannekum, A.L., Hauck, M., Gelderblom, M., Hagel, C., Friedrich, R.E., Schuhmann, M.U., and Schulz, A. (2020). C-Fiber Loss as a Possible Cause of Neuropathic Pain in Schwannomatosis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103569"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1111\/bpa.12780","article-title":"Distinctive low epidermal nerve fiber density in schwannomatosis patients provides a major parameter for diagnosis and differential diagnosis","volume":"30","author":"Farschtschi","year":"2020","journal-title":"Brain Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1002\/ana.24753","article-title":"Multifocal nerve lesions and LZTR1 germline mutations in segmental schwannomatosis","volume":"80","author":"Farschtschi","year":"2016","journal-title":"Ann. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1093\/brain\/awf115","article-title":"Occurrence and characterization of peripheral nerve involvement in neurofibromatosis type 2","volume":"125","author":"Sperfeld","year":"2002","journal-title":"Brain"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e590","DOI":"10.1212\/WNL.0000000000007898","article-title":"Peripheral nervous system alterations in infant and adult neurofibromatosis type 2","volume":"93","author":"Godel","year":"2019","journal-title":"Neurology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/hmg\/ddu414","article-title":"A murine model of neurofibromatosis type 2 that accurately phenocopies human schwannoma formation","volume":"24","author":"Gehlhausen","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1007\/BF00686907","article-title":"Ultrastructure of the onion bulb-like lamellated structure observed in the sural nerve in a case of von Recklinghausen\u2019s disease","volume":"20","author":"Onishi","year":"1972","journal-title":"Acta Neuropathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s00062-021-01102-5","article-title":"Long-term Follow-up and Histological Correlation of Peripheral Nervous System Alterations in Neurofibromatosis Type 2","volume":"32","author":"Godel","year":"2021","journal-title":"Clin. Neuroradiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"217","DOI":"10.3171\/jns.2002.96.2.0217","article-title":"Predictors of vestibular schwannoma growth in patients with neurofibromatosis Type 2","volume":"96","author":"Baser","year":"2002","journal-title":"J. Neurosurg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1136\/jmg.2005.031302","article-title":"Methodological issues in longitudinal studies: Vestibular schwannoma growth rates in neurofibromatosis 2","volume":"42","author":"Baser","year":"2005","journal-title":"J. Med. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1634\/theoncologist.2012-0162","article-title":"Clinical features of schwannomatosis: A retrospective analysis of 87 patients","volume":"17","author":"Merker","year":"2012","journal-title":"Oncologist"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1002\/ana.25191","article-title":"Dorsal root ganglia volume differentiates schwannomatosis and neurofibromatosis 2","volume":"83","author":"Godel","year":"2018","journal-title":"Ann. Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1002\/ana.24524","article-title":"Magnetic resonance neurography detects diabetic neuropathy early and with Proximal Predominance","volume":"78","author":"Pham","year":"2015","journal-title":"Ann. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/0306-4522(96)00127-3","article-title":"Schwann cells produce tumor necrosis factor alpha: Expression in injured and non-injured nerves","volume":"73","author":"Wagner","year":"1996","journal-title":"Neuroscience"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7947","DOI":"10.1073\/pnas.1331358100","article-title":"Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2","volume":"100","author":"Abbadie","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/978-981-32-9636-7_22","article-title":"Schwann Cells as Crucial Players in Diabetic Neuropathy","volume":"1190","author":"Naruse","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.amjsurg.2006.08.026","article-title":"Effects of collagen nerve guide on neuroma formation and neuropathic pain in a rat model","volume":"193","author":"Tyner","year":"2007","journal-title":"Am. J. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9120","DOI":"10.1007\/s00330-021-08072-9","article-title":"Reliability and reproducibility of sciatic nerve magnetization transfer imaging and T2 relaxometry","volume":"31","author":"Preisner","year":"2021","journal-title":"Eur. Radiol."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/4\/780\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:41:18Z","timestamp":1760136078000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/4\/780"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,23]]},"references-count":21,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["diagnostics12040780"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics12040780","relation":{},"ISSN":["2075-4418"],"issn-type":[{"type":"electronic","value":"2075-4418"}],"subject":[],"published":{"date-parts":[[2022,3,23]]}}}