{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T20:22:36Z","timestamp":1787602956947,"version":"build-2736575974"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82501733"],"award-info":[{"award-number":["82501733"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Secondary hemophagocytic lymphohistiocytosis (sHLH) with central nervous system (CNS) involvement poses significant diagnostic and therapeutic challenges. This study aimed to characterize the clinical features, laboratory profiles, and prognostic impact of neurological involvement in adult\u2010onset sHLH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed 130 adult sHLH patients, comparing 28 with CNS involvement to 102 without neurological manifestations. Clinical parameters, neuroimaging, cerebrospinal fluid (CSF) profiles, cytokine levels, treatment responses, and survival outcomes were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Patients with CNS involvement were older (median age, 54\u00a0vs. 46 years;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.013) and had higher disease severity (median HScore, 250\u00a0vs. 210;\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001). Malignancy\u2010associated sHLH was more prevalent in the CNS\u2010positive group (42.9%\u00a0vs. 29.4%;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.038). Neurological manifestations included altered mental status, impaired consciousness, and seizures. Neuroimaging revealed abnormalities in 71.4% of the cases, primarily T2\u2010weighted fluid\u2010attenuated inversion recovery hyperintensities and leptomeningeal enhancement. CNS\u2010positive patients exhibited markedly elevated inflammatory markers, most notably CSF Interleukin\u20106 (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001). In multivariable analysis adjusted for malignancy, age, ferritin, and HScore, CNS involvement independently predicted mortality (adjusted HR = 2.0, 95% CI: 1.1\u20133.7,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.023), with a significantly shorter median overall survival (6.5\u00a0vs. 11.5 months,\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.0001). Malignancy\u2010associated etiology and HScore \u2265 250 were also independent prognostic factors. The\u00a0DEP (dexamethasone, etoposide, and polyethylene glycol\u2010asparaginase) regimen\u00a0achieved a faster median time to initial response than the\u00a0HLH\u201094 protocol\u00a0(9\u00a0vs. 14 days,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.02).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CNS involvement defines a severe phenotype of adult\u2010onset sHLH, characterized by malignancy\u2010prone etiology, intense neuroinflammation, and poor prognosis. We establish CNS involvement as an independent predictor of mortality, underscoring the critical need for early recognition and CNS\u2010directed therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71228","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T07:29:42Z","timestamp":1769758182000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neurological Involvement in Adult\u2010Onset Secondary Hemophagocytic Lymphohistiocytosis: Clinical Features and Prognostic Implications"],"prefix":"10.1002","volume":"16","author":[{"given":"Xue","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology Capital Medical University Affiliated Beijing Friendship Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurology Capital Medical University Affiliated Beijing Friendship Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfei","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Neurology Capital Medical University Affiliated Beijing Friendship Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongbo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology Capital Medical University Affiliated Beijing Friendship Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,29]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2021.08.002"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12883\u2010024\u201003840\u20108"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665\u20109913(23)00273\u20104"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radcr.2022.12.053"},{"issue":"5","key":"e_1_2_11_6_1","article-title":"Central Nervous System Involvement in Adult\u2010Onset Hemophagocytic Lymphohistiocytosis","volume":"13","author":"Fohle E.","year":"2021","journal-title":"Cureus"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.12998\/wjcc.v7.i21.3394"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010021\u201002621\u20104"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21039"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102141.2007.06922.x"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11940\u2010017\u20100439\u20104"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-031-59815-9_2"},{"issue":"9","key":"e_1_2_11_13_1","first-page":"2998","article-title":"Emapalumab as Salvage Therapy for Adults With Malignancy\u2010Associated Hemophagocytic Lymphohistiocytosis","volume":"109","author":"Johnson W. 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