{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T15:25:34Z","timestamp":1794324334263,"version":"4.9.0"},"reference-count":23,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["PED"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECT<\/jats:title>\n                    <jats:p>Cerebral cavernous malformations (CMs) are a source of neurological morbidity from seizures and focal neurological deficits due to mass effect and hemorrhage. Although several natural history reports exist for adults with CMs, similar data for pediatric patients are limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>The authors reviewed hospital databases to identify children with CMs who had not been treated surgically and who had clinical and radiological follow-up. Annual hemorrhage rates were calculated in lesion-years, and risk factors were assessed using the Cox proportional hazards model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>In a cohort of 167 patients with 222 CMs, the mean patient age at the time of diagnosis was 10.1 years old (SD 6.0). Ninety patients (54%) were male. One hundred four patients (62%) presented with hemorrhage from at least 1 CM, 58 (35%) with seizures with or without CM hemorrhage, and 43 (26%) with incidental lesions. Twenty-five patients (15%) had multiple CMs, 17 (10%) had a family history of CMs, and 33 (20%) had radiologically apparent developmental venous anomalies (DVAs). The overall annual hemorrhage rate was 3.3%. Permanent neurological morbidity was 29% per hemorrhage, increasing to 45% for brainstem, thalamic, or basal ganglia CM and decreasing to 15% for supratentorial lobar or cerebellar lesions. The annual hemorrhage rate for incidental CMs was 0.5%; for hemorrhagic CMs, it was 11.3%, increasing to 18.2% within the first 3 years. Hemorrhage clustering within 3 years was statistically significant (HR 6.1, 95% CI 1.72\u201321.7, p = 0.005). On multivariate analysis, hemorrhagic presentation (HR 4.63, 95% CI 1.53\u201314.1, p = 0.007), brainstem location (HR 4.42, 95% CI 1.57\u201312.4, p = 0.005), and an associated radiologically apparent DVA (HR 2.91, 95% CI 1.04\u20138.09, p = 0.04) emerged as significant risk factors for hemorrhage, whereas age, sex, CM multiplicity, and CM family history did not.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>Prior hemorrhage, brainstem location, and associated DVAs are significant risk factors for symptomatic hemorrhage in children with CMs. Hemorrhage clustering within the first 3 years of a bleed can occur, a potentially important factor in patient management and counseling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3171\/2015.2.peds14541","type":"journal-article","created":{"date-parts":[[2015,10,16]],"date-time":"2015-10-16T12:07:26Z","timestamp":1444997246000},"page":"123-128","source":"Crossref","is-referenced-by-count":91,"title":["The natural history of cerebral cavernous malformations in children"],"prefix":"10.3171","volume":"17","author":[{"given":"Bradley A.","family":"Gross","sequence":"first","affiliation":[{"name":"Department of Neurological Surgery, Brigham and Women\u2019s Hospital;"},{"name":"Department of Neurological Surgery; and"},{"name":"Division of Neurointerventional Radiology, Boston Children\u2019s Hospital,"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Brigham and Women\u2019s Hospital;"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren B.","family":"Orbach","sequence":"additional","affiliation":[{"name":"Division of Neurointerventional Radiology, Boston Children\u2019s Hospital,"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Michael","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery; and"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward R.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery; and"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1-peds14541","series-title":"Neurosurgery","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1097\/00006123-199901000-00020","article-title":"A comparison of the clinical profile of cavernous malformations with and without associated venous malformations","volume":"44","author":"Abdulrauf","year":"1999"},{"key":"b2-peds14541","series-title":"J Neurosurg Pediatr","doi-asserted-by":"publisher","first-page":"198","DOI":"10.3171\/2011.11.PEDS11390","article-title":"Natural history and imaging prevalence of cavernous malformations in children and young adults","volume":"9","author":"Al-Holou","year":"2012"},{"key":"b3-peds14541","series-title":"Lancet Neurol","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/S1474-4422(12)70004-2","article-title":"Untreated clinical course of cerebral cavernous malformations: a prospective, population-based cohort study","volume":"11","author":"Al-Shahi Salman","year":"2012"},{"key":"b4-peds14541","series-title":"Neurosurgery","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1097\/00006123-199806000-00013","article-title":"Stereotactic radiosurgery for cavernous malformations: Kjellberg\u2019s experience with proton beam therapy in 98 cases at the Harvard Cyclotron","volume":"42","author":"Amin-Hanjani","year":"1998"},{"key":"b5-peds14541","series-title":"Neurosurgery","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1227\/00006123-199308000-00001","article-title":"Mixed vascular malformations of the brain: clinical and pathogenetic considerations","volume":"33","author":"Awad","year":"1993"},{"key":"b6-peds14541","series-title":"Neurosurgery","first-page":"15","article-title":"Temporal clustering of hemorrhages from untreated cavernous malformations of the central nervous system","volume":"49","author":"Barker","year":"2001"},{"key":"b7-peds14541","series-title":"Neurosurg Rev","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s101430100179","article-title":"Cerebral cavernomas in the adult. Review of the literature and analysis of 72 surgically treated patients","volume":"25","author":"Bertalanffy","year":"2002"},{"key":"b8-peds14541","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"981","DOI":"10.3171\/jns.2000.93.6.0981","article-title":"Dynamic nature of cavernous malformations: a prospective magnetic resonance imaging study with volumetric analysis","volume":"93","author":"Clatterbuck","year":"2000"},{"key":"b9-peds14541","series-title":"Neurology","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1212\/WNL.0b013e318248de9b","article-title":"Prospective hemorrhage risk of intracerebral cavernous malformations","volume":"78","author":"Flemming","year":"2012"},{"issue":"6","key":"b10-peds14541","series-title":"Neurosurg Focus","doi-asserted-by":"publisher","first-page":"E24","DOI":"10.3171\/2011.3.FOCUS1165","article-title":"The natural history of intracranial cavernous malformations","volume":"30","author":"Gross","year":"2011"},{"key":"b11-peds14541","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"293","DOI":"10.3171\/jns.1998.88.2.0293","article-title":"Radiosurgery for cavernous malformations","volume":"88","author":"Karlsson","year":"1998"},{"key":"b12-peds14541","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"820","DOI":"10.3171\/jns.1995.83.5.0820","article-title":"The natural history of cerebral cavernous malformations","volume":"83","author":"Kondziolka","year":"1995"},{"key":"b13-peds14541","series-title":"J Neurosurg Pediatr","doi-asserted-by":"publisher","first-page":"471","DOI":"10.3171\/2014.2.PEDS13487","article-title":"Clinical course of untreated pediatric brainstem cavernous malformations: hemorrhage risk and functional recovery","volume":"13","author":"Li","year":"2014"},{"key":"b14-peds14541","series-title":"Neurosurgery","first-page":"1166","article-title":"The natural history of cavernous malformations: a prospective study of 68 patients","volume":"44","author":"Moriarity","year":"1999"},{"key":"b15-peds14541","series-title":"Neurol Med Chir (Tokyo)","doi-asserted-by":"publisher","first-page":"397","DOI":"10.2176\/nmc.48.397","article-title":"De novo formation of cavernoma after radiosurgery for adult cerebral arteriovenous malformation\u2014case report","volume":"48","author":"Motegi","year":"2008"},{"issue":"1","key":"b16-peds14541","series-title":"Neurosurg Focus","first-page":"e4","article-title":"Review of the literature on de novo formation of cavernous malformations of the central nervous system after radiation therapy","volume":"21","author":"Nimjee","year":"2006"},{"key":"b17-peds14541","series-title":"World Neurosurg","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.wneu.2010.09.017","article-title":"Radiosurgery for radiosurgery-induced cavernous malformation","volume":"75","author":"Park","year":"2011"},{"issue":"5","key":"b18-peds14541","series-title":"Neurosurg Focus","doi-asserted-by":"publisher","first-page":"E16","DOI":"10.3171\/2009.2.FOCUS0923","article-title":"Radiosurgery for angiographically occult vascular malformations","volume":"26","author":"Pham","year":"2009"},{"key":"b19-peds14541","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"987","DOI":"10.3171\/jns.2000.93.6.0987","article-title":"Stereotactic radiosurgery for cavernous malformations","volume":"93","author":"Pollock","year":"2000"},{"key":"b20-peds14541","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"190","DOI":"10.3171\/jns.1997.87.2.0190","article-title":"Cerebral cavernous malformations: natural history and prognosis after clinical deterioration with or without hemorrhage","volume":"87","author":"Porter","year":"1997"},{"key":"b21-peds14541","series-title":"Neurosurgery","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1227\/00006123-199604000-00006","article-title":"Growth, subsequent bleeding, and de novo appearance of cerebral cavernous angiomas","volume":"38","author":"Pozzati","year":"1996"},{"key":"b22-peds14541","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"709","DOI":"10.3171\/jns.1991.75.5.0709","article-title":"Natural history of the cavernous angioma","volume":"75","author":"Robinson","year":"1991"},{"key":"b23-peds14541","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"38","DOI":"10.3171\/jns.1992.76.1.0038","article-title":"Cavernous angiomas of the central nervous system in children","volume":"76","author":"Scott","year":"1992"}],"container-title":["Journal of Neurosurgery: Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg-pediatr\/17\/2\/article-p123.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg-pediatr\/17\/2\/article-p123.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg-pediatr\/17\/2\/article-p123.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,15]],"date-time":"2023-04-15T09:19:41Z","timestamp":1681550381000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg-pediatr\/17\/2\/article-p123.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2]]},"references-count":23,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.3171\/2015.2.peds14541","relation":{},"ISSN":["1933-0707","1933-0715"],"issn-type":[{"value":"1933-0707","type":"print"},{"value":"1933-0715","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2]]}}}