{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:01:46Z","timestamp":1789542106847,"version":"build-2803163510"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cyclosporine and tacrolimus belong to the immunosuppressive drugs of the calcineurin inhibitors group. They are widely used in the treatment of patients after organ transplants. One of their complications is neurotoxicity, the mechanism of which is still not fully understood. The main risk factor for neurotoxicity is hypertension. The most common symptoms include muscle tremors, which are more common in the upper limbs, as well as migraine headaches and peripheral neuropathies. The diagnosis of neurotoxicity is based on imaging tests (magnetic resonance imaging being the most commonly used) and assessment of clinical symptoms. Preventive measures should be initiated as soon as possible to prevent permanent damage to the nerve tissue. The possible preventive methods include reduction of the dose of the administered drug, temporary or complete discontinuation of drugs, or conversion to another immunosuppressive drug. It is also essential to monitor the patient\u2019s condition, correct hypertension, electrolyte disturbances, and fight possible infections. So far, effective methods of preventing calcineurin inhibitor-induced neurotoxicity have not been demonstrated.<\/jats:p>","DOI":"10.4103\/aian.aian_614_24","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T02:00:09Z","timestamp":1738634409000},"page":"505-511","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":13,"title":["Neurotoxicity of Calcineurin Inhibitors"],"prefix":"10.4103","volume":"28","author":[{"given":"Aleksander","family":"Bajon","sequence":"first","affiliation":[{"name":"Student\u2019s Research Group of Department of General and Transplant Surgery, Poznan University of Medical Sciences, Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u0119drzej","family":"Sikora","sequence":"additional","affiliation":[{"name":"Student\u2019s Research Group of Department of General and Transplant Surgery, Poznan University of Medical Sciences, Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Siwek","sequence":"additional","affiliation":[{"name":"Student\u2019s Research Group of Department of General and Transplant Surgery, Poznan University of Medical Sciences, Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Wiecanowska","sequence":"additional","affiliation":[{"name":"Student\u2019s Research Group of Department of General and Transplant Surgery, Poznan University of Medical Sciences, Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi\u0142osz","family":"Miedziaszczyk","sequence":"additional","affiliation":[{"name":"Department of General and Transplant Surgery, Poznan University of Medical Sciences, Poznan, Poland"},{"name":"Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilona","family":"Idasiak-Piechocka","sequence":"additional","affiliation":[{"name":"Department of General and Transplant Surgery, Poznan University of Medical Sciences, Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Mania","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Child Neurology, Poznan University of Medical Sciences, Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,1,31]]},"reference":[{"issue":"(Suppl 2)","key":"R1-20250821","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/ajt.16982","article-title":"OPTN\/SRTR 2020 annual data report: Kidney","volume":"22","author":"Lentine","year":"2022","journal-title":"Am J Transplant"},{"key":"R3-20250821","article-title":"Tacrolimus pharmacotherapy: Infectious complications and toxicity in organ transplant recipients;An updated review","author":"Tolou Ghamari","year":"2023","journal-title":"Curr Drug Res Rev"},{"key":"R4-20250821","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1053\/j.ackd.2019.08.006","article-title":"The many faces of calcineurin inhibitor toxicity-What the FK?","volume":"27","author":"Farouk","year":"2020","journal-title":"Adv Chronic Kidney Dis"},{"key":"R5-20250821","doi-asserted-by":"crossref","first-page":"100610","DOI":"10.1016\/j.trre.2021.100610","article-title":"Identifying the association between tacrolimus exposure and toxicity in heart and lung transplant recipients: A systematic review","volume":"35","author":"Braithwaite","year":"2021","journal-title":"Transplant Rev (Orlando)"},{"key":"R6-20250821","doi-asserted-by":"crossref","first-page":"101589","DOI":"10.1016\/j.jbc.2022.101589","article-title":"Immunosuppressive calcineurin inhibitor cyclosporine A induces proapoptotic endoplasmic reticulum stress in renal tubular cells","volume":"298","author":"Yilmaz","year":"2022","journal-title":"J Biol Chem"},{"key":"R7-20250821","doi-asserted-by":"crossref","first-page":"F336","DOI":"10.1152\/ajprenal.00262.2020","article-title":"Calcineurin inhibitors: A double-edged sword","volume":"320","author":"Ume","journal-title":"Am J Physiol Renal Physiol 202"},{"key":"R8-20250821","first-page":"191","article-title":"Mechanisms of calcineurin inhibitor nephrotoxicity in chronic allograft injury","author":"Slattery","year":"2012","journal-title":"Chronic Kidney Disease and Renal Transplantation. IntechOpen"},{"key":"R9-20250821","doi-asserted-by":"crossref","first-page":"513","DOI":"10.2174\/1389200219666180129151948","article-title":"Pharmacokinetics, pharmacodynamics and pharmacogenetics of tacrolimus in kidney transplantation","volume":"19","author":"Yu","year":"2018","journal-title":"Curr Drug Metab"},{"key":"R10-20250821","doi-asserted-by":"crossref","first-page":"93","DOI":"10.2147\/OAEM.S241501","article-title":"Cyclosporine-A-based immunosuppressive therapy-induced neurotoxicity: A case report. Vol. 12","author":"Teimouri","year":"2020","journal-title":"Open Access Emerg Med"},{"key":"R11-20250821","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/s41401-018-0070-2","article-title":"Biomarkers for individualized dosage adjustments in immunosuppressive therapy using calcineurin inhibitors after organ transplantation","volume":"40","author":"Fu","year":"2019","journal-title":"Acta Pharmacol Sin"},{"key":"R12-20250821","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/B978-0-444-63599-0.00030-2","article-title":"Neurologic complications of transplantation","volume":"141","author":"Dhar","year":"2017","journal-title":"Handb Clin Neurol"},{"key":"R13-20250821","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s13052-021-01037-0","article-title":"Cyclosporine A-related neurotoxicity after haploidentical hematopoietic stem cell transplantation in children with hematopathy","volume":"47","author":"Wang","year":"2021","journal-title":"Ital J Pediatr"},{"key":"R14-20250821","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1016\/j.transproceed.2017.07.013","article-title":"Clinical challenges of tacrolimus for maintenance immunosuppression post-lung transplantation","volume":"49","author":"Ivulich","year":"2017","journal-title":"Transplant Proc"},{"key":"R15-20250821","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1186\/s12883-021-02479-z","article-title":"Tacrolimus-induced neurotoxicity from bipolar disorder to status epilepticus under the therapeutic serum level: A case report","volume":"21","author":"Jin","year":"2021","journal-title":"BMC Neurol"},{"key":"R16-20250821","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/j.ncl.2020.07.009","article-title":"Neurologic toxicities associated with tumor necrosis factor inhibitors and calcineurin inhibitors","volume":"38","author":"Coe","year":"2020","journal-title":"Neurol Clin"},{"key":"R17-20250821","doi-asserted-by":"crossref","first-page":"3210","DOI":"10.3390\/ijms20133210","article-title":"Recent topics on the mechanisms of immunosuppressive therapy-related neurotoxicities","volume":"20","author":"Zhang","year":"2019","journal-title":"Int J Mol Sci"},{"key":"R18-20250821","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1136\/bmj.38569.471007.AE","article-title":"Tacrolimus versus ciclosporin as primary immunosuppression for kidney transplant recipients: Meta-analysis and meta-regression of randomised trial data","volume":"331","author":"Webster","year":"2005","journal-title":"BMJ"},{"key":"R19-20250821","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1007\/s00415-009-5366-1","article-title":"Incidence and risk factors for seizures after heart transplantation","volume":"257","author":"Navarro","year":"2010","journal-title":"J Neurol"},{"key":"R20-20250821","first-page":"642","article-title":"Posterior reversible encephalopathy syndrome in organ transplantation","volume":"20","author":"Jeelani","year":"2022","journal-title":"Exp Clin"},{"key":"R21-20250821","doi-asserted-by":"crossref","first-page":"924","DOI":"10.3174\/ajnr.A0960","article-title":"Posterior reversible encephalopathy syndrome after solid organ transplantation","volume":"29","author":"Bartynski","year":"2008","journal-title":"AJNR Am J Neuroradiol"},{"key":"R22-20250821","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1016\/j.bbmt.2017.05.033","article-title":"Posterior reversible encephalopathy syndrome after hematopoietic cell transplantation in children with hemoglobinopathies","volume":"23","author":"Gaziev","year":"2017","journal-title":"Biol blood marrow Transplant J Am Soc Blood Marrow Transplant"},{"key":"R23-20250821","doi-asserted-by":"crossref","first-page":"2200150","DOI":"10.1002\/adtp.202200150","article-title":"Drug permeability: From the blood-brain barrier to the peripheral nerve barriers","volume":"6","author":"Sun","year":"2023","journal-title":"Adv Ther"},{"key":"R24-20250821","first-page":"131","article-title":"D\u0142ugotrwa\u0142e os\u0142abienie funkcji poznawczych u chorej z zespo\u0142em odwracalnej tylnej encefalopatii","volume":"8","author":"Roessler-G\u00f3recka","year":"2013","journal-title":"Neuropsychiatria i Neuropsychologia"},{"key":"R25-20250821","first-page":"1","article-title":"Two decades of tacrolimus in renal transplant: Basic science and clinical evidences","volume":"15","author":"Shrestha","year":"2017","journal-title":"Exp Clin Transplant"},{"key":"R26-20250821","doi-asserted-by":"crossref","first-page":"135","DOI":"10.2169\/internalmedicine.7520-21","article-title":"posterior reversible encephalopathy syndrome: A review of the literature","volume":"61","author":"Ando","year":"2022","journal-title":"Intern Med"},{"key":"R27-20250821","first-page":"517","article-title":"Calcineurin inhibitor encephalopathy","volume":"32","author":"Mammoser","year":"2012","journal-title":"Semin Neurol"},{"key":"R28-20250821","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.carj.2016.08.005","article-title":"Posterior reversible encephalopathy syndrome: A review","volume":"68","author":"Shankar","year":"2017","journal-title":"Can Assoc Radiol J"},{"key":"R29-20250821","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1111\/j.1552-6569.2007.00097.x","article-title":"Neuroimaging and neurologic complications after organ transplantation","volume":"17","author":"Zivkovi\u0107","year":"2007","journal-title":"J Neuroimaging"},{"key":"R30-20250821","doi-asserted-by":"crossref","first-page":"3700","DOI":"10.1016\/S0041-1345(01)02510-6","article-title":"Cyclosporine-associated encephalopathy: A case report and literature review","volume":"33","author":"Chang","year":"2001","journal-title":"Transplant Proc"},{"key":"R31-20250821","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1054\/jocn.2001.0957","article-title":"Magnetic resonance imaging in cases with encephalopathy secondary to immunosuppressive agents","volume":"9","author":"Inoha","year":"2002","journal-title":"J Clin Neurosci"},{"issue":"(2 Suppl)","key":"R32-20250821","doi-asserted-by":"crossref","first-page":"396S","DOI":"10.1016\/j.transproceed.2004.01.013","article-title":"Therapeutic drug monitoring of cyclosporine","volume":"36","author":"Jorga","year":"2004","journal-title":"Transplant Proc"},{"key":"R33-20250821","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0009-9120(98)00049-6","article-title":"Therapeutic drug monitoring of cyclosporine and tacrolimus. Update on Lake Louise Consensus Conference on cyclosporin and tacrolimus","volume":"31","author":"Oellerich","year":"1998","journal-title":"Clin Biochem"},{"issue":"(2 Suppl)","key":"R34-20250821","doi-asserted-by":"crossref","first-page":"420S","DOI":"10.1016\/j.transproceed.2004.01.054","article-title":"Evolution of the therapeutic drug monitoring of cyclosporine","volume":"36","author":"Citterio","year":"2004","journal-title":"Transplant Proc"},{"issue":"(2 Suppl)","key":"R35-20250821","doi-asserted-by":"crossref","first-page":"378S","DOI":"10.1016\/j.transproceed.2004.01.091","article-title":"Therapeutic drug monitoring of cyclosporine: 20 years of progress","volume":"36","author":"Kahan","year":"2004","journal-title":"Transplant Proc"},{"key":"R36-20250821","first-page":"275","article-title":"Cyclosporine: Structure, pharmacokinetics, and therapeutic drug monitoring","volume":"25","author":"Vine","year":"1987","journal-title":"Crit Rev Clin Lab Sci"},{"key":"R37-20250821","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1046\/j.1365-2125.1999.00911.x","article-title":"Therapeutic drug monitoring of immunosuppressant drugs","volume":"47","author":"Johnston","year":"1999","journal-title":"Br J Clin Pharmacol"},{"key":"R38-20250821","doi-asserted-by":"crossref","first-page":"e935938","DOI":"10.12659\/AOT.935938","article-title":"Tacrolimus-induced neurotoxicity in early post-liver transplant saudi patients: Incidence and risk factors","volume":"27","author":"Alissa","year":"2022","journal-title":"Ann Transplant"},{"key":"R39-20250821","doi-asserted-by":"crossref","first-page":"768","DOI":"10.23876\/j.krcp.22.218","article-title":"Treatment of acute tacrolimus toxicity with phenytoin after Paxlovid (nirmatrelvir\/ritonavir) administration in a kidney transplant recipient","volume":"41","author":"Kwon","year":"2022","journal-title":"Kidney Res Clin Pract"},{"key":"R40-20250821","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1097\/PRA.0000000000000425","article-title":"catatonia due to tacrolimus toxicity 16 years after renal transplantation: Case report and literature review","volume":"25","author":"Sikavi","year":"2019","journal-title":"J Psychiatr Pract"},{"key":"R41-20250821","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s12883-018-1052-1","article-title":"Tacrolimus-induced parkinsonism in a patient after liver transplantation \u2013 case report","volume":"18","author":"Gmitterov\u00e1","year":"2018","journal-title":"BMC Neurol"},{"key":"R42-20250821","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1002\/ajh.23402","article-title":"Tacrolimus-associated posterior reversible encephalopathy syndrome in hematopoietic allogeneic stem cell transplantation","volume":"88","author":"Hammerstrom","year":"2013","journal-title":"Am J Hematol"},{"key":"R43-20250821","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/S0140-6736(02)07875-3","article-title":"Efficacy and safety of tacrolimus compared with ciclosporin microemulsion in renal transplantation: A randomised multicentre study","volume":"359","author":"Margreiter","year":"2002","journal-title":"Lancet (London, England)"},{"key":"R44-20250821","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1080\/15563650.2017.1375511","article-title":"Opsoclonus-myoclonus syndrome following long-term use of cyclosporine","volume":"56","author":"Kang","year":"2018","journal-title":"Clin Toxicol"},{"key":"R45-20250821","doi-asserted-by":"crossref","first-page":"2426","DOI":"10.1111\/ajt.12324","article-title":"Association between calcineurin inhibitor treatment and peripheral nerve dysfunction in renal transplant recipients","volume":"13","author":"Arnold","year":"2013","journal-title":"Am J Transplant"},{"key":"R46-20250821","first-page":"375263","article-title":"Treatment of acute tacrolimus toxicity with phenytoin in solid organ transplant recipients","author":"Jantz","year":"2013","journal-title":"Case Rep Transplant 2013"},{"key":"R47-20250821","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1177\/1060028014546184","article-title":"Rapid resolution of tacrolimus intoxication-induced AKI with a corticosteroid and phenytoin","volume":"48","author":"Bax","year":"2014","journal-title":"Ann Pharmacother"},{"key":"R48-20250821","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1111\/jcpt.12829","article-title":"Treatment of prolonged tacrolimus toxicity using phenytoin in a haemodialysis patient","volume":"44","author":"Meaney","year":"2019","journal-title":"J Clin Pharm Ther"},{"key":"R49-20250821","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1007\/s004670100662","article-title":"Use of rapamycin in a transplant patient who developed cyclosporin neurotoxicity","volume":"16","author":"Hodges","year":"2001","journal-title":"Pediatr Nephrol (Berlin, West)"},{"key":"R50-20250821","doi-asserted-by":"crossref","first-page":"116112","DOI":"10.1016\/j.taap.2022.116112","article-title":"Neuroprotective effects of ibudilast against tacrolimus induced neurotoxicity","volume":"449","author":"Zhang","year":"2022","journal-title":"Toxicol Appl Pharmacol"}],"container-title":["Annals of Indian Academy of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/aian.aian_614_24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:44:47Z","timestamp":1787067887000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/aian.aian_614_24"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,31]]},"references-count":49,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.4103\/aian.aian_614_24","relation":{},"ISSN":["0972-2327","1998-3549"],"issn-type":[{"value":"0972-2327","type":"print"},{"value":"1998-3549","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,31]]},"assertion":[{"value":"2024-07-29","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-21","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}