{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T11:51:57Z","timestamp":1780487517915,"version":"3.54.1"},"reference-count":37,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T00:00:00Z","timestamp":1664496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: We investigated the potential use of SPECT quantification in addition to qualitative brain perfusion analysis for the detection of anti-NMDAR encephalitis. The question is how to normalize brain activity to be able to quantitatively detect perfusion patterns. Usually, brain activity is normalized to a structure considered unaffected by the disease. Methods: Brain [99mTc]-HMPAO SPECT was performed as a method to detect brain perfusion patterns. The patterns of abnormal brain perfusion cannot always be reliably and qualitatively assessed when dealing with rare diseases. Recent advances in SPECT quantification using commercial software have enabled more objective and detailed analysis of brain perfusion. The cerebellum and whole brain were used as the normalization structures and were compared with visual analysis. Results: The quantification analysis performed with whole brain normalization confirmed right parietal lobe hypoperfusion while also detecting statistically significant left-to-right perfusion differences between the temporal lobe and thalamus. Whole brain normalization further described bilateral frontal lobe hyperperfusion, predominantly of the left lobe, and was in accordance with visual analysis. Conclusion: SPECT quantitative brain perfusion analysis, using the whole brain as the normalization structure rather than the cerebellum, in this case, improved confidence in the visual detection of anti-NMDAR encephalitis and provided unexpected solutions to atypical psychiatric dilemmas.<\/jats:p>","DOI":"10.3390\/diagnostics12102377","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T01:52:21Z","timestamp":1665193941000},"page":"2377","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Psychiatric Illness or Immune Dysfunction\u2014Brain Perfusion Imaging Providing the Answer in a Case of Anti-NMDAR Encephalitis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6425-0701","authenticated-orcid":false,"given":"Ines","family":"\u0160i\u0161ko Marko\u0161","sequence":"first","affiliation":[{"name":"Department of Oncology and Nuclear Medicine, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia"},{"name":"School of Medicine, Catholic University of Croatia, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Bla\u017eekovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Oncology and Nuclear Medicine, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4163-6411","authenticated-orcid":false,"given":"Vjekoslav","family":"Peitl","sequence":"additional","affiliation":[{"name":"School of Medicine, Catholic University of Croatia, 10000 Zagreb, Croatia"},{"name":"Department of Psychiatry, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomislav","family":"Juki\u0107","sequence":"additional","affiliation":[{"name":"Department of Oncology and Nuclear Medicine, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia"},{"name":"School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0538-5993","authenticated-orcid":false,"given":"Vi\u0161nja","family":"Supanc","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6538-7240","authenticated-orcid":false,"given":"Dalibor","family":"Karlovi\u0107","sequence":"additional","affiliation":[{"name":"School of Medicine, Catholic University of Croatia, 10000 Zagreb, Croatia"},{"name":"Department of Psychiatry, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Fr\u00f6be","sequence":"additional","affiliation":[{"name":"Department of Oncology and Nuclear Medicine, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia"},{"name":"School of Dental Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/S1474-4422(08)70224-2","article-title":"Anti-NMDA-receptor encephalitis: Case series and analysis of the effects of antibodies","volume":"7","author":"Dalmau","year":"2008","journal-title":"Lancet Neurol."},{"key":"ref_2","unstructured":"Agarwal, R., and Gupta, V. (2021). Anti-NMDA Receptor Encephalitis in Children. StatPearls, StatPearls Publishing."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1056\/NEJMra1708712","article-title":"Antibody-Mediated Encephalitis","volume":"378","author":"Dalmau","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1001\/jamaneurol.2013.3216","article-title":"Frequency and characteristics of isolated psychiatric episodes in anti\u2013N-methyl-d-aspartate receptor encephalitis","volume":"70","author":"Kayser","year":"2013","journal-title":"JAMA Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1002\/ana.20614","article-title":"Paraneoplastic encephalitis, psychiatric symptoms, and hypoventilation in ovarian teratoma","volume":"58","author":"Vitaliani","year":"2005","journal-title":"Ann. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.nrl.2010.03.007","article-title":"Diagn\u00f3stico diferencial en la encefalitis por anticuerpos contra el receptor NMDA [Differential diagnosis of encephalitis due to anti-NMDA receptor antibodies]","volume":"25","author":"Rosenfeld","year":"2010","journal-title":"Neurologia"},{"key":"ref_7","first-page":"1047","article-title":"Anti-nMDA receptor encephalitis--clinical manifestations and pathophysiology","volume":"60","author":"Iizuka","year":"2008","journal-title":"Brain Nerve."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.tins.2016.02.006","article-title":"NMDA Receptor Internalization by Autoantibodies: A Reversible Mechanism Underlying Psychosis?","volume":"39","author":"Masdeu","year":"2016","journal-title":"Trends Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.psym.2015.01.003","article-title":"Psychiatric Autoimmunity: N-Methyl-D-Aspartate Receptor IgG and Beyond","volume":"56","author":"Kruse","year":"2015","journal-title":"Psychosomatics"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1002\/ana.21756","article-title":"Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents","volume":"66","author":"Florance","year":"2009","journal-title":"Ann. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.soc.2015.08.006","article-title":"Pheochromocytoma and Paraganglioma: Diagnosis, Genetics, and Treatment","volume":"25","author":"Kiernan","year":"2016","journal-title":"Surg. Oncol. Clin. North Am."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/5584_2016_76","article-title":"Phaeochromocytoma and Paraganglioma","volume":"956","author":"Gunawardane","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"406","DOI":"10.4158\/EP14481.RA","article-title":"Pheochromocytoma and paraganglioma","volume":"21","author":"Pacak","year":"2015","journal-title":"Endocr. Pract."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"191","DOI":"10.2478\/enr-2019-0020","article-title":"Pheochromocytoma","volume":"53","author":"Farrugia","year":"2019","journal-title":"Endocr. Regul."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1111\/dmcn.13448","article-title":"Herpes simplex virus-induced anti-N-methyl-d-aspartate receptor encephalitis: A systematic literature review with analysis of 43 cases","volume":"59","author":"Nosadini","year":"2017","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1001\/2013.jamapsychiatry.86","article-title":"Increased prevalence of diverse N-methyl-D-aspartate glutamate receptor antibodies in patients with an initial diagnosis of schizophrenia: Specific relevance of IgG NR1a antibodies for distinction from N-methyl-D-aspartate glutamate receptor encephalitis","volume":"70","author":"Steiner","year":"2013","journal-title":"JAMA Psychiatry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1007\/s00415-010-5788-9","article-title":"Disease-relevant autoantibodies in first episode schizophrenia","volume":"258","author":"Zandi","year":"2011","journal-title":"J. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1016\/B978-0-444-52910-7.00045-3","article-title":"Anti-NMDA receptor encephalitis in children: The disorder, its diagnosis, and treatment","volume":"112","author":"Peery","year":"2013","journal-title":"Handb. Clin. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S1474-4422(13)70282-5","article-title":"Antibody titres at diagnosis and during follow-up of anti-NMDA receptor encephalitis: A retrospective study","volume":"13","author":"Titulaer","year":"2014","journal-title":"Lancet Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1136\/jnnp-2011-300411","article-title":"Cognitive deficits following anti-NMDA receptor encephalitis","volume":"83","author":"Finke","year":"2012","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.3174\/ajnr.A5086","article-title":"Autoimmune Encephalitis: Pathophysiology and Imaging Review of an Overlooked Diagnosis","volume":"38","author":"Kelley","year":"2017","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S1474-4422(12)70310-1","article-title":"Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: An observational cohort study","volume":"12","author":"Titulaer","year":"2013","journal-title":"Lancet Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"892242","DOI":"10.3389\/fneur.2022.892242","article-title":"Cerebral gray matter volume changes in patients with anti-N-methyl-D-aspartate receptor encephalitis: A voxel-based morphometry study","volume":"13","author":"Long","year":"2022","journal-title":"Front. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.psym.2019.08.007","article-title":"A Metabolic Brain Pattern Associated With Anti-N-Methyl-D-Aspartate Receptor Encephalitis","volume":"61","year":"2020","journal-title":"Psychosomatics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e01540","DOI":"10.1002\/brb3.1540","article-title":"Different FDG-PET metabolic patterns of anti-AMPAR and anti-NMDAR encephalitis: Case report and literature review","volume":"10","author":"Wei","year":"2020","journal-title":"Brain Behav."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1002\/gps.4102","article-title":"Concordance between (99m)Tc-ECD SPECT and 18F-FDG PET interpretations in patients with cognitive disorders diagnosed according to NIA-AA criteria","volume":"29","author":"Ito","year":"2014","journal-title":"Int. J. Geriatr. Psychiatry"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1212\/01.wnl.0000278388.90370.c3","article-title":"Anti-NMDA receptor encephalitis in Japan: Long-term outcome without tumor removal","volume":"70","author":"Iizuka","year":"2008","journal-title":"Neurology"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"World Medical Association (2013). World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subject. JAMA, 310, 2191\u20132194.","DOI":"10.1001\/jama.2013.281053"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"11S","DOI":"10.2967\/jnumed.108.057182","article-title":"Standards for PET image acquisition and quantitative data analysis","volume":"50","author":"Boellaard","year":"2009","journal-title":"J. Nucl. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.neuroimage.2007.12.057","article-title":"Normalization in PET group comparison studies\u2014The importance of a valid reference region","volume":"40","author":"Borghammer","year":"2008","journal-title":"Neuroimage"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"94","DOI":"10.3389\/fninf.2018.00094","article-title":"An Automated Pipeline for the Analysis of PET Data on the Cortical Surface","volume":"12","author":"Marcoux","year":"2018","journal-title":"Front. Neuroinform."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1006\/nimg.2002.1259","article-title":"Statistical parametric mapping of (99m)Tc-HMPAO-SPECT images for the diagnosis of Alzheimer\u2019s disease: Normalizing to cerebellar tracer uptake","volume":"17","author":"Soonawala","year":"2002","journal-title":"Neuroimage"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1159\/000484200","article-title":"Dystonic Seizures and Intense Hyperperfusion of the Basal Ganglia in a Patient with Anti-N-Methyl-D-Aspartate Receptor Encephalitis","volume":"9","author":"Matsumoto","year":"2017","journal-title":"Case Rep Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.nrl.2016.05.019","article-title":"Brain perfusion SPECT with 99mTc-HMPAO in the diagnosis and follow-up of patients with anti-NMDA receptor encephalitis. SPECT cerebral de perfusi\u00f3n con 99mTc-HMPAO en el diagn\u00f3stico y seguimiento de la encefalitis con anticuerpos contra el receptor NMDA","volume":"33","author":"Portilla","year":"2018","journal-title":"Neurologia"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.braindev.2012.03.014","article-title":"Acute limbic encephalitis with focal hyperperfusion on single photon emission computed tomography","volume":"35","author":"Igarashi","year":"2013","journal-title":"Brain Dev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.clineuro.2013.12.006","article-title":"Brain perfusion SPECT in limbic encephalitis associated with autoantibody against the glutamate receptor epsilon 2","volume":"118","author":"Kimura","year":"2014","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"196","DOI":"10.5692\/clinicalneurol.48.196","article-title":"Subacute encephalitis associated with anti-glutamate receptor antibodies: Serial studies of MRI, 1H-MRS and SPECT","volume":"48","author":"Yamamoto","year":"2008","journal-title":"Rinsho Shinkeigaku"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/10\/2377\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:44:34Z","timestamp":1760143474000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/10\/2377"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,30]]},"references-count":37,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["diagnostics12102377"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics12102377","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,30]]}}}