{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T07:59:12Z","timestamp":1787990352277,"version":"build-2784847793"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T00:00:00Z","timestamp":1614643200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T00:00:00Z","timestamp":1614643200000},"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":["Pediatr Res"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>The mammillary bodies (MBs) have repeatedly been shown to be critical for memory, yet little is known about their involvement in numerous neurological conditions linked to memory impairments, including neonatal encephalopathy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We implemented a multicentre retrospective study, assessing magnetic resonance scans of 219 infants with neonatal encephalopathy who had undergone hypothermia treatment in neonatal intensive care units located in the Netherlands and Italy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Abnormal MB signal was observed in ~40% of infants scanned; in half of these cases, the brain appeared otherwise normal. MB involvement was not related to the severity of encephalopathy or the pattern\/severity of hypoxic\u2013ischaemic brain injury. Follow-up scans were available for 18 cases with abnormal MB signal; in eight of these cases, the MBs appeared severely atrophic.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This study highlights the importance of assessing the status of the MBs in neonatal encephalopathy; this may require changes to scanning protocols to ensure that the slices are sufficiently thin to capture the MBs. Furthermore, long-term follow-up of infants with abnormal MB signal is needed to determine the effects on cognition, which may enable the use of early intervention strategies. Further research is needed to assess the role of therapeutic hypothermia in MB involvement in neonatal encephalopathy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Impact<\/jats:title>\n                <jats:p><jats:list list-type=\"bullet\">\n                  <jats:list-item>\n                    <jats:p>The MBs are particularly sensitive to hypoxia in neonates.<\/jats:p>\n                  <\/jats:list-item>\n                  <jats:list-item>\n                    <jats:p>Current hypothermia treatment provides incomplete protection against MB injury.<\/jats:p>\n                  <\/jats:list-item>\n                  <jats:list-item>\n                    <jats:p>MB involvement is likely overlooked as it can often occur when the rest of the brain appears normal.<\/jats:p>\n                  <\/jats:list-item>\n                  <jats:list-item>\n                    <jats:p>Given the importance of the MBs for memory, it is necessary that this region is properly assessed in neonatal encephalopathy. This may require improvements in scanning protocols.<\/jats:p>\n                  <\/jats:list-item>\n                <\/jats:list><\/jats:p>\n              <\/jats:sec>","DOI":"10.1038\/s41390-021-01436-3","type":"journal-article","created":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T13:03:10Z","timestamp":1614690190000},"page":"174-179","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Mammillary body injury in neonatal encephalopathy: a multicentre, retrospective study"],"prefix":"10.1038","volume":"92","author":[{"given":"Maarten. H.","family":"Lequin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylke. J.","family":"Steggerda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariasavina","family":"Severino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Tortora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Parodi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca A.","family":"Ramenghi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floris","family":"Groenendaal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karlijn M. E.","family":"Meys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon J. N. L.","family":"Benders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda S.","family":"de Vries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6709-8773","authenticated-orcid":false,"given":"Seralynne D.","family":"Vann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,2]]},"reference":[{"key":"1436_CR1","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1192\/bjp.166.2.154","volume":"166","author":"MD Kopelman","year":"1995","unstructured":"Kopelman, M. D. The Korsakoff syndrome. Br. J. Psychiatry 166, 154\u2013173 (1995).","journal-title":"Br. J. Psychiatry"},{"key":"1436_CR2","first-page":"1829","volume":"40","author":"M Molavi","year":"2019","unstructured":"Molavi, M., Vann, S. D., de Vries, L. S., Groenendaal, F. & Lequin, M. Signal change in the mammillary bodies after perinatal asphyxia. Am. J. Neuroradiol. 40, 1829\u20131834 (2019).","journal-title":"Am. J. Neuroradiol."},{"key":"1436_CR3","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1089\/neu.2008.0678","volume":"26","author":"S Shankaran","year":"2009","unstructured":"Shankaran, S. Neonatal encephalopathy: treatment with hypothermia. J. Neurotrauma 26, 437\u2013443 (2009).","journal-title":"J. Neurotrauma"},{"key":"1436_CR4","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/S1474-4422(09)70295-9","volume":"9","author":"M Rutherford","year":"2010","unstructured":"Rutherford, M. et al. Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy: a nested substudy of a randomised controlled trial. Lancet Neurol. 9, 39\u201345 (2010).","journal-title":"Lancet Neurol."},{"key":"1436_CR5","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1136\/archdischild-2018-316509","volume":"105","author":"R Lee-Kelland","year":"2020","unstructured":"Lee-Kelland, R. et al. School-age outcomes of children without cerebral palsy cooled for neonatal hypoxic-ischaemic encephalopathy in 2008\u20132010. Arch. Dis. Child Fetal Neonatal Ed. 105, 8\u201313 (2020).","journal-title":"Arch. Dis. Child Fetal Neonatal Ed."},{"key":"1436_CR6","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1136\/archdischild-2017-313733","volume":"103","author":"H Campbell","year":"2018","unstructured":"Campbell, H. et al. Hypothermia for perinatal asphyxia: trial-based quality of life at 6\u20137 years. Arch. Dis. Child. 103, 654\u2013659 (2018).","journal-title":"Arch. Dis. Child."},{"key":"1436_CR7","doi-asserted-by":"publisher","first-page":"6696","DOI":"10.1523\/JNEUROSCI.0827-19.2019","volume":"39","author":"CM Dillingham","year":"2019","unstructured":"Dillingham, C. M. et al. Mammillothalamic disconnection alters hippocampocortical oscillatory activity and microstructure: Implications for diencephalic amnesia. J. Neurosci. 39, 6696\u20136713 (2019).","journal-title":"J. Neurosci."},{"key":"1436_CR8","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/s00381-020-04795-0","volume":"37","author":"Q Zheng","year":"2020","unstructured":"Zheng, Q., Viaene, A. N., Freeman, C. W. & Hwang, M. Radiologic-pathologic evidence of brain injury: hypoperfusion in the Papez circuit results in poor neurodevelopmental outcomes in neonatal hypoxic ischemic encephalopathy. Childs Nerv. Syst. 37, 63\u201368 (2020).","journal-title":"Childs Nerv. Syst."},{"key":"1436_CR9","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1111\/j.1651-2227.1997.tb08581.x","volume":"86","author":"CM Thompson","year":"1997","unstructured":"Thompson, C. M. et al. The value of a scoring system for hypoxic ischaemic encephalopathy in predicting neurodevelopmental outcome. Acta Paediatr. 86, 757\u2013761 (1997).","journal-title":"Acta Paediatr."},{"key":"1436_CR10","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1002\/ana.410310104","volume":"31","author":"CE Williams","year":"1992","unstructured":"Williams, C. E., Gunn, A. J., Mallard, C. & Gluckman, P. D. Outcome after ischemia in the developing sheep brain: an electroencephalographic and histological study. Ann. Neurol. 31, 14\u201321 (1992).","journal-title":"Ann. Neurol."},{"key":"1436_CR11","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.neubiorev.2014.07.025","volume":"54","author":"CM Dillingham","year":"2015","unstructured":"Dillingham, C. M., Frizzati, A., Nelson, A. J. & Vann, S. D. How do mammillary body inputs contribute to anterior thalamic function? Neurosci. Biobehav. Rev. 54, 108\u2013119 (2015).","journal-title":"Neurosci. Biobehav. Rev."},{"key":"1436_CR12","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.cortex.2016.09.016","volume":"86","author":"AM Dzieciol","year":"2017","unstructured":"Dzieciol, A. M. et al. Hippocampal and diencephalic pathology in developmental amnesia. Cortex 86, 33\u201344 (2017).","journal-title":"Cortex"},{"key":"1436_CR13","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1038\/s41390-019-0569-3","volume":"87","author":"C Cabrera-Mino","year":"2020","unstructured":"Cabrera-Mino, C. et al. Reduced brain mammillary body volumes and memory deficits in adolescents who have undergone the Fontan procedure. Pediatr. Res. 87, 169\u2013175 (2020).","journal-title":"Pediatr. Res."},{"key":"1436_CR14","doi-asserted-by":"publisher","first-page":"5442","DOI":"10.1073\/pnas.0812097106","volume":"106","author":"SD Vann","year":"2009","unstructured":"Vann, S. D. et al. Impaired recollection but spared familiarity in patients with extended hippocampal system damage revealed by 3 convergent methods. Proc. Natl Acad. Sci. USA 106, 5442\u20135447 (2009).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1436_CR15","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1038\/nn.2149","volume":"11","author":"D Tsivilis","year":"2008","unstructured":"Tsivilis, D. et al. A disproportionate role for the fornix and mammillary bodies in recall versus recognition memory. Nat. Neurosci. 11, 834\u2013842 (2008).","journal-title":"Nat. Neurosci."},{"key":"1436_CR16","first-page":"1668","volume":"26","author":"L Kornreich","year":"2005","unstructured":"Kornreich, L. et al. Thiamine deficiency in infants: MR findings in the brain. Am. J. Neuroradiol. 26, 1668\u20131674 (2005).","journal-title":"Am. J. Neuroradiol."},{"key":"1436_CR17","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1007\/s00234-009-0604-x","volume":"52","author":"G Zuccoli","year":"2010","unstructured":"Zuccoli, G., Siddiqui, N., Bailey, A. & Bartoletti, S. C. Neuroimaging findings in pediatric Wernicke encephalopathy: a review. Neuroradiology 52, 523\u2013529 (2010).","journal-title":"Neuroradiology"},{"key":"1436_CR18","unstructured":"Annink, K. et al. Mammillary body atrophy and other MRI correlates of school-age outcome following neonatal hypoxic-ischemic encephalopathy. Scientific Reports. (in press)."}],"container-title":["Pediatric Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41390-021-01436-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41390-021-01436-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41390-021-01436-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T15:04:14Z","timestamp":1661439854000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41390-021-01436-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,2]]},"references-count":18,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["1436"],"URL":"https:\/\/doi.org\/10.1038\/s41390-021-01436-3","relation":{},"ISSN":["0031-3998","1530-0447"],"issn-type":[{"value":"0031-3998","type":"print"},{"value":"1530-0447","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,2]]},"assertion":[{"value":"25 September 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 January 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 February 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 March 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"A waiver of informed consent was obtained, according to European regulations, because the study involved the analysis of retrospective, anonymised data.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent statement"}}]}}