{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T20:46:06Z","timestamp":1768596366917,"version":"3.49.0"},"reference-count":8,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2022,8,6]],"date-time":"2022-08-06T00:00:00Z","timestamp":1659744000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,8,6]],"date-time":"2022-08-06T00:00:00Z","timestamp":1659744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurooncol"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Introduction<\/jats:title>\n                <jats:p>Side-effects during convection enhanced delivery (CED) are poorly understood. We intended to determine the frequency of side-effects during brain stem infusion and determine risk factors for side-effects persisting longer than 24\u00a0h.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Children with a radiological diagnosis of brain stem diffuse midline glioma\/Diffuse Intrinsic Pontine Glioma were treated on compassionate grounds with awake infusion of carboplatin and sodium valproate into the brain stem using the 4-catheter (2 trans-cerebellar 2 trans-frontal) chronic, intermittent Renishaw Drug Delivery System. We used change in the Pontine Neurological Observation Score (PONScore), a standardised neurological assessment tool, to identify side-effects during infusion. Recovery was determined by retrospective chart review.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>55 infusions were performed in 8 children (3\u201311\u00a0years). Mean PONScore increased during infusion from 3.3 to 5.7 (p-value\u2009&gt;\u20090.001). One hundred and fifty-seven infusion-related side-effects were identified including headache (33\/157) and limb weakness (49\/157). Fifty-four side-effects persisted\u2009&gt;\u200924\u00a0h. Side-effects that had occurred during a previous infusion and those that occurred during infusion via trans-cerebellar catheters were more likely to be persistent with OR 2.333 (95% CI 1.094\u20134.976; p-value\u2009=\u20090.028) and 2.155 (1.029\u20134.513; p-value\u2009=\u20090.042) respectively. If infusion was stopped or titrated at onset rather than continued, the side-effect was less likely to persist\u2009&gt;\u200924\u00a0h, OR 0.473 (95% CI 0.177\u20130.948; p-value\u2009=\u20090.037). Most side-effects developed within the first three millilitre of infusion.\n<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Side-effects during brainstem infusion are common, can be transient or persist longer than 24\u00a0h. Neurological injury during infusion may be time dependent and accumulative rather than volume dependent.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s11060-022-04077-6","type":"journal-article","created":{"date-parts":[[2022,8,6]],"date-time":"2022-08-06T16:02:45Z","timestamp":1659801765000},"page":"417-424","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Infusion-related side-effects during convection enhanced delivery for brainstem-diffuse midline glioma\/diffuse intrinsic pontine glioma"],"prefix":"10.1007","volume":"159","author":[{"given":"Milo","family":"Hollingworth","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stergios","family":"Zacharoulis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,8,6]]},"reference":[{"key":"4077_CR1","doi-asserted-by":"publisher","first-page":"31","DOI":"10.3389\/fonc.2019.00031","volume":"9","author":"BT Himes","year":"2019","unstructured":"Himes BT, Zhang L, Daniels DJ (2019) Treatment strategies in diffuse midline gliomas with the H3K27M mutation: the role of convection-enhanced delivery in overcoming anatomic challenges. Front Oncol 9:31","journal-title":"Front Oncol"},{"issue":"8","key":"4077_CR2","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1016\/S1470-2045(18)30322-X","volume":"19","author":"MM Souweidane","year":"2018","unstructured":"Souweidane MM, Kramer K, Pandit-Taskar N, Zhou Z, Haque S, Zanzonico P et al (2018) Convection-enhanced delivery for diffuse intrinsic pontine glioma: a single-centre, dose-escalation, phase 1 trial. Lancet Oncol 19(8):1040\u20131050","journal-title":"Lancet Oncol"},{"issue":"4","key":"4077_CR3","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1007\/s10147-020-01853-0","volume":"26","author":"E Szychot","year":"2021","unstructured":"Szychot E, Walker D, Collins P, Hyare H, Shankar A, Bienemann A et al (2021) Clinical experience of convection-enhanced delivery (CED) of carboplatin and sodium valproate into the pons for the treatment of diffuse intrinsic pontine glioma (DIPG) in children and young adults after radiotherapy. Int J Clin Oncol 26(4):647\u2013658","journal-title":"Int J Clin Oncol"},{"issue":"2","key":"4077_CR4","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1007\/s11060-020-03594-6","volume":"149","author":"MA Hollingworth","year":"2020","unstructured":"Hollingworth MA, Zacharoulis S (2020) Development of a clinical scale for assessment of patients with diffuse intrinsic pontine glioma (DIPG) receiving experimental therapy: the PONScore. J Neurooncol 149(2):263\u2013272","journal-title":"J Neurooncol"},{"issue":"8","key":"4077_CR5","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1007\/s00701-013-1700-6","volume":"155","author":"N Barua","year":"2013","unstructured":"Barua N, Lowis S, Woolley M, O\u2019Sullivan S, Harrison R, Gill S (2013) Robot-guided convection-enhanced delivery of carboplatin for advanced brainstem glioma. Acta Neurochir 155(8):1459\u20131465","journal-title":"Acta Neurochir"},{"issue":"1","key":"4077_CR6","doi-asserted-by":"publisher","first-page":"167","DOI":"10.3109\/10717544.2014.908248","volume":"23","author":"NU Barua","year":"2016","unstructured":"Barua NU, Hopkins K, Woolley M, O\u2019Sullivan S, Harrison R, Edwards RJ et al (2016) A novel implantable catheter system with transcutaneous port for intermittent convection-enhanced delivery of carboplatin for recurrent glioblastoma. Drug Delivery 23(1):167\u2013173","journal-title":"Drug Delivery"},{"issue":"1","key":"4077_CR7","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/s11060-012-0833-4","volume":"108","author":"E White","year":"2012","unstructured":"White E, Bienemann A, Pugh J, Castrique E, Wyatt M, Taylor H et al (2012) An evaluation of the safety and feasibility of convection-enhanced delivery of carboplatin into the white matter as a potential treatment for high-grade glioma. J Neurooncol 108(1):77\u201388","journal-title":"J Neurooncol"},{"issue":"7","key":"4077_CR8","doi-asserted-by":"publisher","first-page":"1450","DOI":"10.3174\/ajnr.A3421","volume":"34","author":"J Sedlacik","year":"2013","unstructured":"Sedlacik J, Winchell A, Kocak M, Loeffler R, Broniscer A, Hillenbrand C (2013) MR imaging assessment of tumor perfusion and 3D segmented volume at baseline, during treatment, and at tumor progression in children with newly diagnosed diffuse intrinsic pontine glioma. Am J Neuroradiol 34(7):1450\u20131455","journal-title":"Am J Neuroradiol"}],"container-title":["Journal of Neuro-Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11060-022-04077-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11060-022-04077-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11060-022-04077-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T10:12:04Z","timestamp":1661767924000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11060-022-04077-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,6]]},"references-count":8,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,9]]}},"alternative-id":["4077"],"URL":"https:\/\/doi.org\/10.1007\/s11060-022-04077-6","relation":{},"ISSN":["0167-594X","1573-7373"],"issn-type":[{"value":"0167-594X","type":"print"},{"value":"1573-7373","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,6]]},"assertion":[{"value":"25 May 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 June 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 August 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors report no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"Ethics approval for treatment on compassionated grounds was granted by the institutional ethics committee.","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":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}