{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:13:20Z","timestamp":1790964800253,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca Corrente 2022\u20102024"],"award-info":[{"award-number":["Ricerca Corrente 2022\u20102024"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The \u201cinsular knife\u2010cut\u201d sign is a sharp demarcation between hyperintense insular lesions on fluid\u2010attenuated inversion recovery axial images and the basal ganglia, detected on brain MRI. This sign has been associated with herpes simplex virus encephalitis (HSVE); however, its specificity remains unknown. We assessed the frequency and specificity of the insular knife\u2010cut sign in a real\u2010life cohort of patients with suspected HSVE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrospectively identified patients admitted for suspected HSVE over the past 10\u2009years at three Neurology Units in Italy. Inclusion criteria were cerebrospinal fluid (CSF) tested for HSV\u20101\/2 PCR and acute brain MRI available.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 188 patients were included: HSVE, 44; alternative diagnoses, 144 (autoimmune encephalitis, 51; infectious encephalitis, 22; other acute encephalopathies, 71). The insular knife\u2010cut sign was present on the initial brain MRI in 23\/44 (52.3%) HSVE patients and 1\/144 (0.7%) patients with alternative diagnoses (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). The specificity and sensitivity of the sign were 99.3% (95% CI, 96\u2013100) and 52% (95% CI, 38\u201366), respectively. In eight HSVE patients, the insular knife\u2010cut sign appeared on subsequent MRIs obtained acutely, raising the sensitivity to 70.5% (95% CI, 56\u201382). On multivariate regression, the insular knife\u2010cut sign was the strongest independent predictor (odds ratio [95% CI]) of HSVE (68.9 [11.42\u2013415.54]), followed by temporal pole involvement (8.44 [2.06\u201334.6]), and CSF pleocytosis (6 [1.7\u201321.18]).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In patients with suspected encephalitis, the insular knife\u2010cut sign on MRI strongly predicts a diagnosis of HSVE. Its detection should prompt consideration of HSVE, even when other diagnostic tests are equivocal\/unavailable.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.70152","type":"journal-article","created":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T02:41:12Z","timestamp":1755916872000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Diagnostic Value of the \u201cInsular Knife\u2010Cut\u201d Sign in Patients With Suspected Herpes Simplex Virus Encephalitis"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4982-1662","authenticated-orcid":false,"given":"Sofia","family":"Marini","sequence":"first","affiliation":[{"name":"Department of Neuroscience Catholic University of the Sacred Heart  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Luisa","family":"Usai","sequence":"additional","affiliation":[{"name":"Neurology Unit University Hospital of Sassari  Sassari Italy"},{"name":"Department of Medical Sciences and Public Health University of Cagliari  Cagliari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Falso","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Catholic University of the Sacred Heart  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Turilli","sequence":"additional","affiliation":[{"name":"Radiology Unit University Hospital of Sassari  Sassari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrine","family":"Othmani","sequence":"additional","affiliation":[{"name":"Neurology Unit University Hospital of Sassari  Sassari Italy"},{"name":"Department of Medical Sciences and Public Health University of Cagliari  Cagliari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossella","family":"Meloni","sequence":"additional","affiliation":[{"name":"Neurology Unit University Hospital of Sassari  Sassari Italy"},{"name":"Department of Medical Sciences and Public Health University of Cagliari  Cagliari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Businaro","sequence":"additional","affiliation":[{"name":"Neuroimmunology Laboratory and Neuroimmunology Research Section, IRCCS Mondino Foundation  Pavia Italy"},{"name":"Department of Brain and Behavioural Sciences University of Pavia  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8097-0565","authenticated-orcid":false,"given":"Giacomo","family":"Greco","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioural Sciences University of Pavia  Pavia Italy"},{"name":"Multiple Sclerosis Centre, IRCCS Mondino Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariangela","family":"Puci","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology and Medical Statistics Unit University Hospital of Sassari  Sassari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Marini","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Catholic University of the Sacred Heart  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Pichiecchio","sequence":"additional","affiliation":[{"name":"Neuroradiology Department IRCCS Mondino Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Paoletti","sequence":"additional","affiliation":[{"name":"Neuroradiology Department IRCCS Mondino Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Zara","sequence":"additional","affiliation":[{"name":"Neurology Unit University Hospital of Sassari  Sassari Italy"},{"name":"Department of Medical Sciences and Public Health University of Cagliari  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