{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T07:01:33Z","timestamp":1771657293741,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,12,12]],"date-time":"2018-12-12T00:00:00Z","timestamp":1544572800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Psychiatry Clin Neurosci"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Cefepime, a fourth\u2010generation cephalosporin, acts as a GABA<jats:sub>A<\/jats:sub> receptor antagonist. Cefepime\u2010induced encephalopathy (CIE) is frequently overlooked. We aimed to clarify the clinical features, characteristic electroencephalography (EEG), and mechanisms of CIE to aid in its early recognition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>CIE cases documented by a single\u2010center consultation\u2013liaison team between April 2015 and March 2017 were retrospectively reviewed. For further investigation, neural mass modeling was performed <jats:italic>in silico.<\/jats:italic><\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three patients with CIE refused medication\/examination and showed overt pain, palilalia, and much greater deterioration of eye and verbal response than the motor response, which was possibly related to GABAergic dysfunction. Triphasic wave\u2010like generalized periodic discharges with a high negative component (Tri\u2010HNC) were identified on the EEG of all three cases. The simulation reproduced the characteristic feature of 2\u20133\u2009Hz Tri\u2010HNC and recovery course on EEG, and a possible involvement of individual differences in pharmacological intervention. It also suggested that auto\u2010inhibition (synaptic inputs from interneuron to interneuron) dysregulation contributed to generating Tri\u2010HNC in CIE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>As CIE is iatrogenic and continues unless cefepime is stopped, early recognition is crucial. Physicians should be vigilant about altered mental status, pain, and verbal changes in patients taking cefepime. Tri\u2010HNC on EEG can expedite the diagnosis of CIE, and the association between Tri\u2010HNC and CIE suggests that an excitatory and inhibitory imbalance due to the dysfunction of GABAergic interneurons is the underlying mechanism. This modeling may offer a new method of investigating disorders related to GABAergic dysfunction.<\/jats:p><\/jats:sec>","DOI":"10.1111\/pcn.12795","type":"journal-article","created":{"date-parts":[[2018,10,30]],"date-time":"2018-10-30T08:49:58Z","timestamp":1540889398000},"page":"34-42","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Cefepime\u2010induced encephalopathy: Neural mass modeling of triphasic wave\u2010like generalized periodic discharges with a high negative component (Tri\u2010HNC)"],"prefix":"10.1111","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5581-5720","authenticated-orcid":false,"given":"Hidetaka","family":"Tamune","sequence":"first","affiliation":[{"name":"Department of Neuropsychiatry Tokyo Metropolitan Tama Medical Center  Tokyo Japan"},{"name":"Department of Neuropsychiatry, Graduate School of Medicine The University of Tokyo  Tokyo Japan"},{"name":"Department of Cellular Neurobiology, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Hamamoto","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry Tokyo Metropolitan Tama Medical Center  Tokyo Japan"},{"name":"Department of Neuropsychiatry, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naofumi","family":"Aso","sequence":"additional","affiliation":[{"name":"Department of Earth and Planetary Science, Graduate School of Science The University of Tokyo  Tokyo Japan"},{"name":"School of Science Tokyo Institute of Technology  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry Tokyo Metropolitan Tama Medical Center  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,12,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002455"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(03)00188-6"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc13094"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2015.04.007"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/net.13.1.67.113"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2013.08.005"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2017.06.245"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNP.0b013e3182a73e16"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0987-7053(00)00234-3"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(01)00767-7"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2005.16305.x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1L307"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12028-008-9166-8"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/44579"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-29-09664.2003"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.54.11.2153"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfm713"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ensci.2017.08.001"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410100502"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2015.07.018"},{"key":"e_1_2_8_22_1","first-page":"356","article-title":"Severely abnormal electroencephalogram in two patients who were treated with cefepime","volume":"52","author":"Shirota Y","year":"2012","journal-title":"Clin. 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