{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T04:27:31Z","timestamp":1790310451112,"version":"4.1.0"},"reference-count":58,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T00:00:00Z","timestamp":1719532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hashimoto\u2019s encephalopathy (HE) has been a poorly understood disease. It has been described in all age group, yet, there is no specific HE marker. Additionally, the treatment data in the available studies are frequently divergent and contradictory. Therefore, the aim of our systematic and critical review is to evaluate the diagnosis and treatment of HE in view of the latest findings. The databases browsed comprised PubMed, Scopus, and Google Scholar as well as Cochrane Library, and the search strategy included controlled vocabulary and keywords. A total of 2443 manuscripts were found, published since the beginning of HE research until February 2024. In order to determine validity of the data collected from studies, bias assessment was performed using RoB 2 tool. Ultimately, six studies were included in our study. HE should be considered in the differential diagnosis in patients with psychiatric and neurological symptoms. According to our findings, negative thyroid peroxidase antibodies (anti-TPOs) may represent a valuable parameter in ruling out HE. Nonetheless, this result cannot be used to confirm HE. Furthermore, the proposed anti NH2-terminal-\u03b1-enolase (anti-NAE) is non-specific for HE. The effectiveness of glucocorticoid therapy is 60.94%, although relapse occurs in 31.67% of patients following the treatment. Our review emphasizes the significance of conducting further large-scale research and the need to take into account the potential genetic factor.<\/jats:p>","DOI":"10.3390\/ijms25137101","type":"journal-article","created":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T06:51:53Z","timestamp":1719557513000},"page":"7101","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Difficulties in the Diagnostics and Treatment of Hashimoto\u2019s Encephalopathy\u2014A Systematic and Critical Review"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3952-0173","authenticated-orcid":false,"given":"Nikola","family":"Pempera","sequence":"first","affiliation":[{"name":"Students\u2019 Scientific Society, Endocrinology Section at Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9773-1461","authenticated-orcid":false,"given":"Mi\u0142osz","family":"Miedziaszczyk","sequence":"additional","affiliation":[{"name":"Department of General and Transplant Surgery, Poznan University of Medical Sciences, 60-355 Poznan, Poland"},{"name":"Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2386-4795","authenticated-orcid":false,"given":"Katarzyna","family":"Lacka","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/S0140-6736(66)92876-5","article-title":"Hashimoto\u2019s disease and encephalopathy","volume":"2","author":"Brain","year":"1966","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/j.autrev.2016.09.008","article-title":"Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT): Characteristics, treatment and outcome in 251 cases from the literature","volume":"15","author":"Laurent","year":"2016","journal-title":"Autoimmun. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.beem.2004.11.006","article-title":"Hashimoto\u2019s encephalopathy: Myth or reality? An endocrinologist\u2019s perspective","volume":"19","author":"Fatourechi","year":"2005","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1212\/WNL.0000000000008776","article-title":"The neuromythology of Hashimoto encephalopathy: The emperor has no clothes","volume":"94","author":"Tyler","year":"2020","journal-title":"Neurology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"799","DOI":"10.2165\/00023210-200721100-00002","article-title":"Hashimoto\u2019s encephalopathy: Epidemiology, pathogenesis and management","volume":"21","author":"Mocellin","year":"2007","journal-title":"CNS Drugs"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.jns.2003.09.007","article-title":"Hashimoto\u2019s encephalopathy: Epidemiologic data and pathogenetic considerations","volume":"217","author":"Ferracci","year":"2004","journal-title":"J. Neurol. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jns.2013.05.009","article-title":"Diagnostic and therapeutic aspects of Hashimoto\u2019s encephalopathy","volume":"331","author":"Olmez","year":"2013","journal-title":"J. Neurol. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1001\/archneur.60.2.164","article-title":"Hashimoto encephalopathy: Syndrome or myth?","volume":"60","author":"Chong","year":"2003","journal-title":"Arch. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"506","DOI":"10.5812\/ijem.4174","article-title":"Hashimoto encephalopathy: A rare intricate syndrome","volume":"10","author":"Payer","year":"2012","journal-title":"Int. J. Endocrinol. Metab."},{"key":"ref_10","first-page":"87","article-title":"The role of apoptosis in the etiopathogenesis of autoimmune thyroiditis","volume":"32","author":"Maciejewski","year":"2012","journal-title":"Pol. Med. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1136\/jcp.2010.086553","article-title":"Changes of B and T lymphocytes and selected apopotosis markers in Hashimoto\u2019s thyroiditis","volume":"64","author":"Kaczmarek","year":"2011","journal-title":"J. Clin. Pathol."},{"key":"ref_12","unstructured":"Chiarello, P., Talarico, V., Nicoletti, A., Rodio, B., Arcuri, P.P., Bosco, D., Gigliotti, F., Galati, M.C., and Raiola, G. (2020). Hashimoto encephalopathy: A case report and a short revision of current literature. Acta Biomed., 91."},{"key":"ref_13","first-page":"1039","article-title":"Correlation and presentation of thyroid functional status with thyroid autoantibodies in long-term follow-up of autoimmune thyroiditis: A study of 116 cases","volume":"20","author":"Chou","year":"2013","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e6181","DOI":"10.1097\/MD.0000000000006181","article-title":"Limbic encephalitis associated with anti-NH2-terminal of \u03b1-enolase antibodies: A clinical subtype of Hashimoto encephalopathy","volume":"96","author":"Kishitani","year":"2017","journal-title":"Medicine"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.ejpn.2012.11.003","article-title":"Hashimoto\u2019s encephalopathy: Identification and long-term outcome in children","volume":"17","author":"Mamoudjy","year":"2013","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2377-12-60","article-title":"Hashimoto\u2019s encephalopathy cases: Chinese experience","volume":"12","author":"Tang","year":"2012","journal-title":"BMC Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"309","DOI":"10.4103\/0976-3147.158753","article-title":"Hashimoto encephalopathy: A study of the clinical profile, radiological and electrophysiological correlation in a Tertiary Care Center in South India","volume":"6","author":"Sharma","year":"2015","journal-title":"J. Neurosci. Rural Pract."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Dumrikarnlert, C., Thakolwiboon, S., and Senanarong, V. (2023). Clinical presentations and treatment outcomes of Hashimoto encephalopathy at Siriraj Hospital\u2013Thailand\u2019s largest national tertiary referral center. BMC Neurol., 23.","DOI":"10.1186\/s12883-023-03305-4"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e217","DOI":"10.1212\/WNL.0000000000008785","article-title":"Hashimoto encephalopathy in the 21st century","volume":"94","author":"Mattozzi","year":"2020","journal-title":"Neurology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s12020-014-0441-5","article-title":"A comprehensive score to diagnose Hashimoto\u2019s thyroiditis: A proposal","volume":"49","author":"Grani","year":"2015","journal-title":"Endocrine."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.ejim.2003.06.002","article-title":"Encephalopathy associated with Hashimoto\u2019s thyroiditis: An additional case","volume":"14","author":"Bertoni","year":"2003","journal-title":"Eur. J. Intern. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1212\/WNL.53.7.1579","article-title":"Nonvasculitic autoimmune inflammatory meningoencephalitis (NAIM): A reversible form of encephalopathy","volume":"53","author":"Caselli","year":"1999","journal-title":"Neurology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1212\/WNL.54.3.769","article-title":"Hashimoto encephalopathy: A brainstem vasculitis?","volume":"54","author":"Nolte","year":"2000","journal-title":"Neurology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1097\/00000441-199511000-00005","article-title":"Case report: Thyrotropin-releasing hormone-induced myoclonus and tremor in a patient with Hashimoto\u2019s encephalopathy","volume":"310","author":"Ishii","year":"1995","journal-title":"Am. J. Med. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.jneuroim.2005.02.004","article-title":"Autoantibodies against the amino terminal of \u03b1-enolase are a useful diagnostic marker of Hashimoto\u2019s encephalopathy","volume":"162","author":"Fujii","year":"2005","journal-title":"J. Neuroimmunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jneuroim.2007.08.012","article-title":"Anti-thyroperoxidase antibodies from patients with Hashimoto\u2019s encephalopathy bind to cerebellar astrocytes","volume":"192","author":"Blanchin","year":"2007","journal-title":"J. Neuroimmunol."},{"key":"ref_27","first-page":"706843","article-title":"High serum IgG4 concentrations in patients with Hashimoto\u2019s thyroiditis","volume":"2015","author":"Siewko","year":"2015","journal-title":"Int. J. Endocrinol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1089\/thy.2013.0211","article-title":"A classification of Hashimoto\u2019s thyroiditis based on immunohistochemistry for IgG4 and IgG","volume":"24","author":"Zhang","year":"2014","journal-title":"Thyroid"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1111\/j.1365-2249.2008.03756.x","article-title":"Distribution of immunoglobulin G subclasses of anti-thyroid peroxidase antibody in sera from patients with Hashimoto\u2019s thyroiditis with different thyroid functional status","volume":"154","author":"Xie","year":"2008","journal-title":"Clin. Exp. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1007\/s00415-013-6878-2","article-title":"Hashimoto\u2019s encephalopathy associated with an elevated intrathecal IgG4 level","volume":"260","author":"Hosoi","year":"2013","journal-title":"J. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0014-5793(02)03307-0","article-title":"Proteomic analysis of human brain identifies alpha-enolase as a novel autoantigen in Hashimoto\u2019s encephalopathy","volume":"528","author":"Ochi","year":"2002","journal-title":"FEBS Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.aninu.2016.02.005","article-title":"Progress in the biological function of alpha-enolase","volume":"2","author":"Ji","year":"2016","journal-title":"Anim. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.autrev.2006.10.004","article-title":"Alpha-enolase: A target of autoantibodies in infectious and autoimmune diseases","volume":"6","author":"Terrier","year":"2007","journal-title":"Autoimm. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.ajoc.2018.09.005","article-title":"Autoimmune retinopathy and optic neuropathy associated with enolase-positive renal oncocytoma","volume":"12","author":"Cheng","year":"2018","journal-title":"Am. J. Ophthalmol. Case Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1080\/03009740701607075","article-title":"Elevated anti-\u03b1-enolase antibody levels in Kawasaki disease","volume":"37","author":"Chun","year":"2008","journal-title":"Scand. J. Rheumatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/cen3.12772","article-title":"Expanding clinical spectrum from Hashimoto\u2019s encephalopathy to anti-NAE antibody-associated disorders (NAEAD)","volume":"15","author":"Matsunaga","year":"2024","journal-title":"Clin. Exp. Neuroimmunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1503\/cmaj.100007","article-title":"Progressive impairment of cognition and motor function: Hashimoto encephalopathy","volume":"183","author":"Tzakas","year":"2011","journal-title":"CMAJ"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e100502","DOI":"10.1136\/gpsych-2021-100502","article-title":"Hashimoto\u2019s encephalopathy presented with mutism: A case report","volume":"34","author":"Das","year":"2021","journal-title":"Gen. Psychiatr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.yebeh.2011.09.023","article-title":"Recurrent partial seizures with ictal yawning as atypical presentation of Hashimoto\u2019s encephalopathy","volume":"22","author":"Casciato","year":"2011","journal-title":"Epilepsy Behav."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/S1474-4422(15)00401-9","article-title":"A clinical approach to diagnosis of autoimmune encephalitis","volume":"15","author":"Graus","year":"2016","journal-title":"Lancet Neurol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1007\/s40618-020-01477-1","article-title":"An update on the pathogenesis of Hashimoto\u2019s thyroiditis","volume":"44","author":"Weetman","year":"2021","journal-title":"J. Endocrinol. Investig."},{"key":"ref_42","first-page":"e15697","article-title":"MRI findings of two patients with Hashimoto Encephalopathy","volume":"13","author":"Jegatheeswaran","year":"2021","journal-title":"Cureus"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1159\/000085508","article-title":"Hashimoto encephalopathy and neuralgic amyotrophy-causal link or chance association?","volume":"53","author":"Kastrup","year":"2005","journal-title":"Eur. Neurol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1212\/01.WNL.0000048660.71390.C6","article-title":"Antithyroid antibodies in the CSF: Their role in the pathogenesis of Hashimoto\u2019s encephalopathy","volume":"60","author":"Ferracci","year":"2003","journal-title":"Neurology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1136\/practneurol-2020-002567","article-title":"Autoimmune encephalitis: Clinical spectrum and management","volume":"21","author":"Uy","year":"2021","journal-title":"Pract. Neurol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.seizure.2019.06.020","article-title":"Status epilepticus in Hashimoto\u2019s encephalopathy","volume":"70","author":"Ercoli","year":"2019","journal-title":"Seizure"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e1059","DOI":"10.1097\/MD.0000000000001059","article-title":"Antithyroid antibodies are implicated in epileptogenesis of adult patients with epilepsy","volume":"94","author":"Tsai","year":"2015","journal-title":"Medicine"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jns.2005.07.004","article-title":"A case of Hashimoto\u2019s encephalopathy: Association with sensory ganglionopathy","volume":"238","author":"Cao","year":"2005","journal-title":"J. Neurol. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1159\/000085501","article-title":"A case of Hashimoto\u2019s encephalopathy with demyelinating peripheral neuropathy","volume":"53","author":"Sheng","year":"2005","journal-title":"Eur. Neurol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.autrev.2014.01.007","article-title":"Hashimoto thyroiditis: Clinical and diagnostic criteria","volume":"13","author":"Caturegli","year":"2014","journal-title":"Autoimmun Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1007\/s13311-021-01178-4","article-title":"Antibody Therapies in Autoimmune Encephalitis","volume":"19","author":"Smets","year":"2022","journal-title":"Neurotherapeutics"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s13760-016-0660-z","article-title":"Therapeutic dilemmas in Hashimoto\u2019s encephalopathy","volume":"117","author":"Zadro","year":"2017","journal-title":"Acta Neurol. Belg."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mce.2008.03.006","article-title":"Multigenic control of thyroid hormone functions in the nervous system","volume":"287","author":"Nunez","year":"2008","journal-title":"Mol Cell Endocrinol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1097\/00004836-200110000-00006","article-title":"Side Effects of Corticosteroid Therapy","volume":"33","author":"Buchman","year":"2001","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3603","DOI":"10.1007\/s00415-023-11715-0","article-title":"Steroids for the treatment of viral encephalitis: A systematic literature review and meta-analysis","volume":"270","author":"Hodzic","year":"2023","journal-title":"J Neurol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1046\/j.1528-1157.2001.042suppl.3023.x","article-title":"Epileptic encephalopathy","volume":"42","author":"Dulac","year":"2001","journal-title":"Epilepsia"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1111\/j.1528-1167.2009.02224.x","article-title":"Corticosteroids as treatment of epileptic syndromes with continuous spike-waves during slow-wave sleep","volume":"50","author":"Buzatu","year":"2009","journal-title":"Epilepsia"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"bcr2017221262","DOI":"10.1136\/bcr-2017-221262","article-title":"Case of steroid-responsive encephalopathy from hypoglycaemia","volume":"2017","author":"Mathur","year":"2017","journal-title":"BMJ Case Rep."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/13\/7101\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:06:50Z","timestamp":1760108810000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/13\/7101"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,28]]},"references-count":58,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["ijms25137101"],"URL":"https:\/\/doi.org\/10.3390\/ijms25137101","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,28]]}}}