Reversible acute encephalopathy with mutism, induced by calcineurin inhibitors after renal transplantation

Perdomo, Katia Toledo; Cabello, María-Dolores Navarro; Sáez, María-José Pérez; Pérez, Manuel José Ramos; Morales, Maria Luisa Agüera; García, Pedro Aljama

doi:10.5301/jn.5000080

Cited by 11 publications

(6 citation statements)

References 9 publications

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“…Mutism, catatonia, and akinesia may well have been partly or wholly related to treatment with calcineurin inhibitors, as these have been reported with cyclosporin and tacrolimus, 14 even when levels have been within the therapeutic range. 15 Magnesium infusions and pramipexole conferred no significant benefit, whereas amantadine was robustly effective. The use of amantadine to treat these complications of calcineurin inhibitor therapy has never been previously reported.…”

Section: Discussionmentioning

confidence: 99%

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Walker

Hussaini²,

Stowe³

et al. 2018

Exp Clin Transplant

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Although liver transplant for decompensated cirrhosis secondary to Wilson disease is well accepted, the use of transplant for patients with severe neurologic manifestations of this condition remains controversial, and these can be perceived as a contraindication. Here, we describe a 45-year-old woman who presented with an incidental hepatocellular carcinoma at the time of transplant. The patient had severe neurologic manifestations of Wilson disease pretransplant, including dysarthria, hyperreflexia, asymmetrical ataxia, tremor, bradyphrenia, and shuffling gait. She underwent successful transplant from a hepatic and surgical standpoint, but her postoperative course was marked by protracted mutism, hypophonia, and fluctuating akinesia and immobility that did not respond promptly to withdrawal of calcineurin inhibitors or pramipexole but did respond robustly to amantadine. At 9 months posttransplant, there was marked neurologic improvement, and, at 18 months, she exhibited subtle memory and organizational difficulties but was fully ambulatory and otherwise completely functional. Our experience suggests that even patients with severe neurologic Wilson disease may recover after transplant, albeit slowly, demonstrating the need for a multidisciplinary approach, including pre- and posttransplant neurologic and neuropsychiatric consultations.

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Section: Discussionmentioning

confidence: 99%

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Walker

Hussaini²,

Stowe³

et al. 2018

Exp Clin Transplant

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“…Central pontine myelinolysis can occur in as many as 17% of patients after transplantation despite normal laboratory indices [176]. The neurotoxic manifestations are reversible in most instances by reducing the dose of medication or discontinuing the drug, but permanent and fatal neurological damage has occurred [69,[174][175][176]. The frequent and sometimes serious complications of therapy with the calcineurin inhibitors compel a thorough consideration of alternative rescue therapies before their use in autoimmune hepatitis.…”

Section: Calcineurin Inhibitorsmentioning

confidence: 98%

“…Five percent of patients experience psychoses, hallucinations, blindness, seizures, ataxia, muscle weakness, or akinetic mutism [69,175], and they have brain imaging abnormalities that can disclose hypodensity of the occipital white matter, gray matter and cortical changes, cerebral edema, and hypoxic damage [70,174]. Central pontine myelinolysis can occur in as many as 17% of patients after transplantation despite normal laboratory indices [176].…”

Section: Calcineurin Inhibitorsmentioning

confidence: 98%

Nonstandard Drugs and Feasible New Interventions for Autoimmune Hepatitis: Part I

Czaja¹

2012

IADT

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Nonstandard drugs that target critical pathogenic pathways or immune regulatory mechanisms constitute the next generation of treatments for autoimmune hepatitis. Mycophenolate mofetil impairs the proliferation of lymphocytes, decreases autoantibody production, and induces apoptosis of activated immunocytes. Patients treated for azathioprine intolerance improve more frequently than patients treated for refractory liver disease (54% versus 10%), and mycophenolate mofetil is emerging as a rescue therapy for this population. Complete corticosteroid withdrawal is possible in 40% of patients treated with mycophenolate mofetil, and the frequency of side effects ranges from 3-34%. Budesonide in combination with azathioprine has normalized liver tests more frequently (47% versus 18%) and with fewer side effects (28% versus 53%) than standard therapy after 6 months. Budesonide is emerging as a frontline treatment in non-cirrhotic patients with uncomplicated disease or contraindications to conventional corticosteroids. Cyclosporine and tacrolimus are effective salvage agents for steroid-refractory disease, but side effects have been common and occasionally serious. The 6- thioguanine nucleotides and rapamycin are feasible treatments for autoimmune hepatitis, but 6-thioguanine has major obstacles to overcome, especially the risk of liver toxicity or nodular regenerative hyperplasia. The nonstandard drug therapies emerging for autoimmune hepatitis reflect the need to supplement or supplant current treatment regimens. None has been licensed for use in autoimmune hepatitis, and their applications have been based on results from small singlecenter experiences.

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“…Posterior reversible encephalopathy syndrome can occur with therapeutic doses of tacrolimus and is reversible with dose reduction or cessation of therapy. 27,28 Other adverse effects include alopecia and electrolyte imbalances, such as hyperkalemia and hypomagnesemia. 29,30 The cardiovascular effects, such as hypertension and hyperlipidemia, and cosmetic effects, such as gingival hyperplasia and hirsutism, which are frequently associated with cyclosporine, are less frequent with tacrolimus, and modest clinical improvements can occur with switching to tacrolimus.…”

Section: Adverse Effectsmentioning

confidence: 99%

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Shrestha

2017

Exp Clin Transplant

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Tacrolimus, a calcineurin inhibitor, has been the cornerstone of immunosuppressive regimens in renal transplant over 2 decades. This has significantly improved the outcomes of renal transplant, including reduction of acute rejection episodes, improvement of renal function and graft survival, and reduction of some of the adverse effects associated with cy closporine. However, use of tacrolimus is associated with a number of undesirable effects, such as nephrotoxicity, posttransplant diabetes mellitus, neurotoxicity, and cosmetic and electrolyte disturbances. To alleviate these effects, several strategies have been adopted to minimize or eliminate tacrolimus from maintenance regimens of immuno suppression, with some success. This review focuses on advancements in the under standing of the basic science related to tacrolimus and the clinical evidences that have examined the efficacy and safety of tacrolimus in renal transplant over the past 2 decades and highlights the future directions.

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Reversible acute encephalopathy with mutism, induced by calcineurin inhibitors after renal transplantation

Cited by 11 publications

References 9 publications

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Nonstandard Drugs and Feasible New Interventions for Autoimmune Hepatitis: Part I

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