Objective: Tacrolimus a calcineurin inhibitor is the most widely used immunosuppressant in post transplant patients. Mild adverse effects like tremors and parasthesia and occasionally major  side effects like seizures,akinetic mutism and speech disorders are well known. However, Parkinson’s disease as a complication of Tacrolimus is very rare. Freezing of gait and speech as a presenting feature is exceptional. We describe an alcohol induced cirrhosis patient who underwent liver transplantation on Tacrolimus, subsequently presented as primary freezing of gait and speech

Background: 42 year man with AIC underwent cadaveric liver transplantation in our centre at 2014.There was no neurological symptoms prior to transplantation. Post procedure, he was started on Tacrolimus.Three months later, he has developed repetition of words and occasional falls. On examination he had palilalia, bilateral rigidity, bradykinesia, left hand tremor and significant Freezing. His liver function test was elevated and Tacrolimus level was normal. MRI brain showed T1 hyper intensity in basal ganglia. He had a poor response to levodopa trial. Subsequently he was diagnosed as Tacrolimus induced parkinsonism and switched over to cyclosporine & started on dopamine agonists. Gradually, his gait and speech partially improved

Methods: Not applicable

Results: Our patient underwent liver transplantation and three months later,he developed freezing of gait and speech. Initially cirrhosis induced hepato-cerebral degeneration was considered and started on levodopa which was unresponsive.  Tacrolimus induced neurotoxicity often occurs early after transplantation even within normal therapeutic range. If it was not discontinued, it can produce irreversible changes. Dose dependent blood brain barrier damage, endothelin mediated vasospasm, alteration in mitochondrial function were hypothesized as mechanism of TaC induced neurotoxicity. In our patient, the onset and progression after transplantation with improvement after stopping Tacrolimus favoured drug induced Parkinsonism. Hence,he was changed to cyclosporine and improvement in his symptoms corroborated with the diagnosis

Conclusions: Our patient highlights that freezing of gait and speech can be a sole presenting feature of tacrolimus induced parkinsonism. Early recognition and appropriate treatment can prevent irreversible parkinsonism

References: 1)    Progressive Neurological Disease Induced by TaC in a Renal Transplant Recipient: Case Presentation.Marjan Chegounchi; Michael G. Hanna;Guy H. Neild. BMC Nephrology. 2006;7

2)    Neurotoxicity of Immunosuppressive Therapies in Organ Transplantation. Daniela ANGHEL, Radu TANASESCU, Ana CAMPEANU, Ioana LUPESCU, Giulio PODDA and Ovidiu BAJENARU. Maedica (Buchar). 2013 Jun; 8(2): 170–175. PMCID: PMC3865126.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/tacrolimus-induced-parkinsonism-presenting-as-freezing-of-gait-and-speech/