{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:14:21Z","timestamp":1791897261626,"version":"4.3.4"},"reference-count":34,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JNS"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:sec>\n                    <jats:title>Object<\/jats:title>\n                    <jats:p>The tumors most frequently associated with von Hippel-Lindau (VHL) disease are hemangioblastomas. While they are associated with significant neurological impairment and mortality, their natural history and optimal management have not been fully defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with VHL were enrolled in a prospective study designed to define the natural history of CNS hemangioblastomas. In the present analysis, serial imaging, laboratory, genetic, and clinical data were evaluated in those with at least 2 years of follow-up data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At study entrance 225 patients (111 males, 114 females) harbored 1921 CNS hemangioblastomas in the supratentorial compartment (21 tumors [1%]), cerebellum (865 [45%]), brainstem (129 [7%]), spinal cord (689 [36%]), cauda equina (212 [11%]), and nerve roots (5 [0.3%]; follow-up 15,819 hemangioblastoma-years). Increased tumor burden was associated with partial deletions in the\n                      <jats:italic>VHL<\/jats:italic>\n                      gene (p = 0.005) and male sex (p = 0.002). Hemangioblastoma development (median 0.3 new tumors\/year) was associated with younger age (p &lt; 0.0001) and more tumors at study entrance (p &lt; 0.0001). While 1278 hemangioblastomas (51%) did not grow, 1227 hemangioblastomas (49%) grew in a saltatory (886 [72%]), linear (76 [6%]), or exponential (264 [22%]) pattern. Faster tumor growth was associated with male sex (p = 0.001), symptomatic tumors (p &lt; 0.0001), and tumors associated with cysts (p &lt; 0.0001). Location-dependent tumor size was the primary predictor of eventual symptom formation (159 symptomatic tumors [6.3%]; area under the curve &gt; 0.9).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Central nervous system hemangioblastoma burden in VHL is associated with partial germline deletions and male sex. Unpredictable growth of hemangioblastomas compromises assessment of nonsurgical therapies. The judicious treatment of symptom-producing hemangioblastomas, while avoiding unnecessary treatment of asymptomatic tumors that may not progress, can provide clinical stability. Clinical trial registration no.: NCT00005902 (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"ClinicalTrials.gov\" xlink:type=\"simple\">ClinicalTrials.gov<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3171\/2014.1.jns131431","type":"journal-article","created":{"date-parts":[[2014,2,28]],"date-time":"2014-02-28T10:17:49Z","timestamp":1393582669000},"page":"1055-1062","source":"Crossref","is-referenced-by-count":171,"title":["Prospective natural history study of central nervous system hemangioblastomas in von Hippel-Lindau disease"],"prefix":"10.3171","volume":"120","author":[{"given":"Russell R.","family":"Lonser","sequence":"first","affiliation":[{"name":"Surgical Neurology Branch and"},{"name":"Department of Neurological Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Butman","sequence":"additional","affiliation":[{"name":"Neuroradiology Section, Diagnostic Radiology, Clinical Center at the National Institutes of Health;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Huntoon","sequence":"additional","affiliation":[{"name":"Surgical Neurology Branch and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok R.","family":"Asthagiri","sequence":"additional","affiliation":[{"name":"Surgical Neurology Branch and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianxia","family":"Wu","sequence":"additional","affiliation":[{"name":"Office of the Clinical Director, National Institute of Neurological Disorders and Stroke;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamran D.","family":"Bakhtian","sequence":"additional","affiliation":[{"name":"Surgical Neurology Branch and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily Y.","family":"Chew","sequence":"additional","affiliation":[{"name":"Division of Epidemiology and Clinical Applications, National Eye Institute;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengping","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Surgical Neurology Branch and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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