Seizures after liver transplantation

Estol, Conrado J.; López, Olga; Brenner, Ronald; Martinez, A. J.

doi:10.1212/wnl.39.10.1297

Cited by 57 publications

(35 citation statements)

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“…Although cyclosporin A neurotoxicity cannot be predicted in a dosedependent manner, it is generally associated with serum concentrations higher than 1 M (12)(13)(14). These cyclosporin A serum concentrations at the equilibrium status are trough levels; a higher peak level may be achieved temporarily even in the same patient under certain conditions (2). Moreover, cyclosporin A is lipophilic and has a high affinity to cyclophilin and calcineurin, which are highly concentrated in cortical neurons (15,16).…”

Section: Discussionmentioning

confidence: 99%

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Change of Hyperexcitability of Hippocampus by Cyclosporin A and Its Modulatory Action by Fentanyl

Choi

Whang

2002

J Korean Med Sci

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Cyclosporin A is used to treat patients with immune-mediated diseases, chronic diseases requiring organ transplantation, or malignancies. These conditions often require higher cyclosporin A doses, which may be toxic to the central nervous system. Fentanyl is also used in clinical conditions that have a risk of hypoxic neurosusceptibility, which suggests that the drug may be a neuroprotective agonist against brain ischemic injury. Fentanyl is an opioid agonist and appears to play an important role in regulating the excitability of the hippocampus under electroconvulsion. In this study, the effects of fentanyl on modulating cyclosporin A-induced neurotoxicity was investigated. Treatment with 3 micrometer of cyclosporin A was found to reduce the electroconvulsive activity threshold. Fifty ng/mL of fentanyl reduced the electroconvulsive activity, and 1 micrometer of DAGO ([D-Ala2, N-Me-Phe4, Gly-ol]-enkephalin) also decreased the electroconvulsive activity. Fifty ng/mL of fentanyl was also found to reduce cyclosporin A-induced electroconvulsive activity. Although cyclosporin A neurotoxicity may be observed in various conditions, the opioid effect of neuroprotection may be involved in an interrelated mechanism. The exogenous opioid agonist suppressed cyclosporin A-induced electroconvulsive activity. Furthermore, there may be a functional anticonvulsant effect on cyclosporin A-induced neurotoxicity with an increased opioid agonist concentration.

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Section: Discussionmentioning

confidence: 99%

“…These diseases often require higher cyclosporin A doses, which may cause central nervous system (CNS) problems (1)(2)(3). Seizures frequently poses a physical threat to patients, who often suffer from pain requiring appropriate control.…”

Section: Introductionmentioning

confidence: 99%

Change of Hyperexcitability of Hippocampus by Cyclosporin A and Its Modulatory Action by Fentanyl

Choi

Whang

2002

J Korean Med Sci

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“…However, a substantial number of patients also have focal (20,21) or myoclonic (3,11,21) seizures, and both convulsive (3,4) and nonconvulsive (4) status epilepticus have been observed. One of the most common causes of seizures in transplant patients has been claimed to be the use of CsA (2,3,5,6).…”

Section: Discussionmentioning

confidence: 99%

Cyclosporin A and Brain Excitability Studied In Vitro

1998

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Summary:Purpose: Seizures are frequently observed after organ transplantations. This has been attributed to a direct effect of cyclosporin A (CsA) on the brain, although other mechanisms may also be of importance. The aim of this study was to investigate possible acute and direct effects of CsA on neuronal excitability.Methods: Female rat hippocampal slices were perfused with CsA solutions containing 400 (n = 4), 1,000 (n = 4), 2,000 (n = 6), 8,000 (n = 8) bg/L CsA or control (n = 8) for 30 min, or penicillin, 2,000 IEfml (n = 7). Actual concentrations of CsA were measured in the perfusate drawn from the slice chamber. To study CsA accumulation in the slices, uptake of radioactive CsA was measured in 12 living and 11 dead slices.Results: Despite a significant accumulation of CsA in the living neuronal slices, no effects were observed on prevolley, field excitatory postsynaptic potential (EPSP), or population spike amplitude. Penicillin, however, led to epileptiform activity within 10 min in all cases. Concentrations of CsA in the perfusate from the slice chamber were about half the calculated levels, demonstrating that the slices had been exposed to actual CsA concentrations in the range of -200-4,000 bg/L CsA. Conclusions:Our results demonstrate a lack of acute effects of CsA on neuronal excitability within clinically relevant concentrations despite an active accumulation of the drug in the slices. Long-term effects on brain tissue, indirect metabolic effects, or synergistic effects may be responsible for the neurotoxicity of the drug. Key Words: Cyclosporin A-Seizures-Transplantation-Hippocampal slice.Cyclosporin A (CsA) is today the major immunosuppressant after all kinds of organ transplantations and is also successfully used in the treatment of various immune-mediated diseases (1). However, 30-60% of organ-transplant recipients develop neurologic complications (2), and seizures are one of the most frequent (3,4).Several studies in humans (3,5,6) and animals (7-10) suggest a seizure-inducing effect of CsA itself, even in the absence of complicating factors like metabolic disturbances and concomitant treatment. The possibility of an acute effect of the drug on brain excitability is supported by the observation that seizures occur more frequently after intravenous administration of CsA (3,ll). Seizures also have been observed even during the intravenous infusion (3,12) in patients who had not previously had seizures.The human data could thus indicate an acute and direct epileptogenic effect on neuronal excitability, whereas studies in intact animals (7-10) and cell cultures (13) suggest an effect evolving with time over days or weeks.The aim of this study was therefore to investigate whether CsA exerts direct effects on neuronal excitabilAccepted January 16, 1998. Address correspondence and reprint requests to Dr. E. Tauboll at Department of Neurology, Rikshospitalet, 0027 Oslo, Norway. ity, by using a hippocampal slice technique devoid of blood-brain barrier. METHODSFemale Sprague-Dawley rats (150-250 g; M...

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“…7 A widely studied explanation is the rapid correction of hyponatremia in the immediate postoperative period, leading to osmotic demyelination. [64][65][66][67] Hyponatremia also may affect neurotransmission, contributing to the development of hepatic encephalopathy. 1,31 Treatment Treatment of hyponatremia is defined by several variables including clinical presentation (symptomatic vs asymptomatic), chronicity (acute vs chronic), and cause of hyponatremia.…”

Section: Clinical Associationsmentioning

confidence: 99%

Hyponatremia: Clinical Associations, Prognosis, and Treatment in Cirrhosis

Sharma²,

Saab³

2012

Exp Clin Transplant

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Hyponatremia has long been associated with worsened clinical outcomes in patients with cirrhosis and those awaiting liver transplant. However, in the last several years, new modalities of therapy, particularly aquaretics known as "vaptans," and comprehensive prognostic models have been increasingly studied in the hopes of bolstering serum sodium levels and altering liver transplant candidate status. To examine the most recent, comprehensive, and pertinent data, a systematic review of both prospective and retrospective studies available on MEDLINE was completed, which provided information detailing clinical associations, treatment, and prognoses seen in those with hyponatremia in cirrhosis. Clinical associations with hyponatremia in cirrhosis including hepatorenal syndrome and hepatic encephalopathy were identified. For hyponatremia in those awaiting liver transplant, tolvaptan is an effective agent in temporarily normalizing serum sodium levels with minimal risk of osmotic demyelination. Prognostic models incorporating serum sodium levels were better able to predict urgency and need for transplant; yet the benefits and posttransplant effects of redefining a liver allocation score have yet to be established. Key words: Hyponatremia, Cirrhosis, Outcomes IntroductionHyponatremia is a common electrolyte disturbance in patients with advanced liver disease. [1][2][3][4] In the setting of cirrhosis, hyponatremia can be classified as either hypovolemic hyponatremia, which occurs in the setting of overtreatment with diuretics or excessive losses from the gastrointestinal tract, or hypervolemic hyponatremia, which results in decreased effective circulating volume from increased arterial from splanchnic vasodilatation leading to excessive secretion of arginine vasopressin. 1,5,6 Hyponatremia can occur both before and after liver transplant. Pretransplant, it is associated with several clinical manifestations of decompensation, 4,7,8 and the degree of hyponatremia may increase the accuracy of the model for end-stage liver disease (MELD) score to predict survival. [8][9][10][11] Treatment of hyponatremia has not been demonstrated to improve survival in patients with advanced liver disease, and rapid correction can lead to life-threatening neurologic complications. 12,13 This systematic review focuses on the prevalence, clinical associations, treatment, and prognosis of hypervolemic hyponatremia in patients with liver disease. An algorithm will be developed to guide management based on best available data. Methods Search strategy and identification of studiesWe searched database MEDLINE for all studies on hyponatremia in the setting of cirrhosis as related to clinical implications, prognosis, and treatment. We used combinations of the key words: "hyponatremia," "sodium," "liver cirrhosis," "prevalence," "incidence," "intensive care units," "hepatorenal syndrome," "ascites," "central pontine myelinolysis," "therapeutics," "prognosis," and "liver Experimental and Clinical Transplantation (2013) 1: 3-11Christine Yu et a...

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Seizures after liver transplantation

Cited by 57 publications

References 0 publications

Change of Hyperexcitability of Hippocampus by Cyclosporin A and Its Modulatory Action by Fentanyl

Change of Hyperexcitability of Hippocampus by Cyclosporin A and Its Modulatory Action by Fentanyl

Cyclosporin A and Brain Excitability Studied In Vitro

Hyponatremia: Clinical Associations, Prognosis, and Treatment in Cirrhosis

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