tacrolimus and Mental-Disorders

Topics: Central Nervous System Diseases; Cerebrovascular Disorders; Cyclosporine; Humans; Immunosuppressive Agents; Kidney Transplantation; Mental Disorders; Neuromuscular Diseases; Seizures; Tacrolimus

Between 10%-28% of patients who receive the immunosuppressant cyclosporine (CsA) experience some form of neurotoxic adverse event. Both sensorial motoric functions may be adversely affected, and thus patients present with a wide range of neurological and psychiatrical disorders. Mild symptoms are common and include tremor, neuralgia, and peripheral neuropathy. Severe symptoms affect up to 5 % of patients and include psychoses, hallucinations, blindness, seizures, cerebellar ataxia, motoric weakness, or leukoencephalopathy. Tacrolimus is associated with similar neurotoxic adverse events. Neurotoxicity may result in serious complications for some patients, particularly recipients of orthotopic liver transplants. Factors that may promote the development of serious complications include advanced liver failure, hypertension, hypocholesterolemia, elevated CsA or tacrolimus blood levels, hypomagnesemia, and methylprednisolone. Occipital white matter appears to be uniquely susceptible to the neurotoxic effects of CsA; injury to both the major and minor vasculature may cause hypoperfusion or ischemia and local secondary toxicity in the white matter. Calcineurin inhibition by CsA and tacrolimus alters sympathetic outflow, which may play a role in the mediation of neurotoxic and hypertensive adverse events. The symptoms of CsA- and tacrolimus-associated neurotoxicity may be reversed in most patients by substantially reducing the dosage of immunosuppressant or discontinuing these drugs. However, some patients have experienced permanent or even fatal neurological damage even after dose reduction or discontinuation. CsA-sparing and tacroli-mus-sparing drug regimens that use the immunosuppressant mycophenolate mofetil, which has no neurotoxic effects, may reduce the incidence and severity of neurotoxic adverse events while maintaining an adequate level of immunoisuppression.

Topics: Calcineurin Inhibitors; Cyclosporine; Humans; Immunosuppressive Agents; Mental Disorders; Nervous System Diseases; Neurotoxins; Postoperative Complications; Tacrolimus; Transplantation Immunology

Topics: Adult; Cognition Disorders; Cyclosporine; Female; Humans; Liver Transplantation; Male; Mental Disorders; Morbidity; Tacrolimus

The relevance of the immunosuppressive drug tacrolimus in the prevention of rejection and graft-versus-host disease in transplanted patients is beyond all doubt. However, tacrolimus often has neurotoxic effects, including severe conditions such as posterior reversible leukoencephalopathy syndrome.. A 75-year-old male who had undergone a kidney transplantation five years earlier, for which he was receiving treatment with tacrolimus and mycophenolate. He also had advanced Parkinson's disease, treated with several dopamine agonists. The patient visited the emergency department after a week-long history of visual hallucinations, delirium, expansive mood, confusion and headache. The focal psychogeriatric examination revealed psychosis secondary to dopaminergic agonists as the first diagnostic option, without excluding other possible iatrogenic causes despite the tacrolimus being within the therapeutic range (8.3 ng/mL). Both cranial computed tomography, which did not show any significant findings, and a magnetic resonance scan, in which a bilateral parietooccipital oedema was observed, were performed, this latter finding being compatible with posterior reversible leukoencephalopathy syndrome. While the patient was in hospital, tacrolimus was replaced by everolimus, and the dopaminergic medication was adjusted, resulting in a swift and full remission of the clinical signs and symptoms.. The diagnosis of posterior reversible leukoencephalopathy syndrome should be considered in patients with a history of organ transplantation treated with immunosuppressive drugs who have an acute onset condition with neurological or psychiatric symptoms.. Sindrome de leucoencefalopatia posterior reversible en un paciente con enfermedad de Parkinson y sintomatologia inicial psiquiatrica: una presentacion clinica compleja.. Introduccion. La relevancia del farmaco inmunosupresor tacrolimus en la prevencion del rechazo y la enfermedad de injerto contra huesped en pacientes trasplantados es indiscutible. Sin embargo, con frecuencia, el tacrolimus presenta efectos neurotoxicos, incluyendo cuadros graves, como el sindrome de leucoencefalopatia posterior reversible. Caso clinico. Varon de 75 años, con antecedentes de trasplante renal hace cinco años, en tratamiento con tacrolimus y micofenolato, y de enfermedad de Parkinson avanzada, en tratamiento con varios agonistas dopaminergicos. Acudio a urgencias por un cuadro de una semana de evolucion consistente en alucinaciones visuales, delirios, animo expansivo, confusion y cefalea. La exploracion psicogeriatrica por focos mostro como primera opcion diagnostica una psicosis secundaria a agonistas dopaminergicos, sin excluir otras causas yatrogenas a pesar de encontrarse el tacrolimus en el rango terapeutico (8,3 ng/mL). Se realizaron una tomografia computarizada craneal, que no mostro hallazgos significativos, y una resonancia magnetica, en la que se visualizo un edema parietooccipital bilateral, hallazgo compatible con un sindrome de leucoencefalopatia posterior reversible. Durante el ingreso se sustituyo el tacrolimus por everolimus y se ajusto la medicacion dopaminergica, con lo que se produjo de forma rapida una remision completa del cuadro. Conclusiones. El diagnostico de sindrome de leucoencefalopatia posterior reversible debe considerarse en los pacientes con antecedentes de trasplante de organo en tratamiento con farmacos inmunosupresores que presentan un cuadro de instauracion aguda con sintomas neurologicos o psiquiatricos.

Topics: Aged; Humans; Immunosuppressive Agents; Male; Mental Disorders; Parkinson Disease; Posterior Leukoencephalopathy Syndrome; Tacrolimus

To determine risk factors for early neurologic complications (NCs) after liver transplantation from perspective of recipient, donor, and surgeon.. In all, 295 adult recipients were enrolled consecutively between August 2001 and February 2014 from a single medical center in Taiwan. Any NC in the first 30 d post-liver transplantation, and perioperative variables from multiple perspectives were collected and analyzed. The main outcome was a 30-d NC. Generalized additive models were used to detect the non-linear effect of continuous variables on outcome, and to determine cut-off values for categorizing risk. Risk factors were identified using multiple logistic regression analysis.. In all, 288 recipients were included, of whom 142 (49.3%) experienced at least one NC, with encephalopathy being the most common 106 (73%). NCs prolonged hospital stay (35.15 ± 43.80 d vs 20.88 ± 13.58 d, P < 0.001). Liver recipients' age < 29 or ≥ 60 years, body mass index < 21.6 or > 27.6 kg/m(2), Child-Pugh class C, history of preoperative hepatoencephalopathy or mental disorders, day 7 tacrolimus level > 8.9 ng/mL, and postoperative intra-abdominal infection were more likely associated with NCs. Novel risk factors for NCs were donor age < 22 or ≥ 40 years, male-to-male gender matching, graft-recipient weight ratio 0.9%-1.9%, and sequence of transplantation between 31 and 174.. NCs post- liver transplantation occurs because of factors related to recipient, donor, and surgeon. Our results provide a basis of risk stratification for surgeon to minimize neurotoxic factors during transplantation.

Topics: Adrenal Cortex Hormones; Adult; Age Factors; Body Mass Index; Brain Diseases; Case-Control Studies; Consciousness Disorders; Delirium; Female; Graft Rejection; Hepatic Encephalopathy; Humans; Immunosuppressive Agents; Intraabdominal Infections; Length of Stay; Liver Transplantation; Male; Mental Disorders; Middle Aged; Mycophenolic Acid; Myelinolysis, Central Pontine; Neurotoxicity Syndromes; Posterior Leukoencephalopathy Syndrome; Postoperative Complications; Preoperative Period; Psychotic Disorders; Risk Assessment; Risk Factors; Seizures; Sex Factors; Stroke; Tacrolimus; Taiwan; Tissue Donors

Topics: Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Mental Disorders; Middle Aged; Posterior Leukoencephalopathy Syndrome; Tacrolimus

Liver transplantation is a well-established treatment for liver failure. Prolongation in survival is accepted, but long-term effects of liver transplantation on cognitive and psychological outcome are unclear. In the present study, psychological data were prospectively collected for 164 patients who were assessed for liver transplantation. Memory impairment, psychomotor slowing, anxiety, and depression were commonly observed. Severity of liver disease at assessment was significantly associated with slowing of reaction time. Memory impairment distinguished those who were not listed for transplantation because of illness severity. One year posttransplantation, follow-up data from transplant recipients showed significant improvement in most psychological domains relative to both healthy comparison participants and patients with chronic liver disease who did not undergo transplantation. Immunosuppression (cyclosporine versus tacrolimus) did not have differential effects on quality of life, fatigue, or affective status, although those administered cyclosporine showed greater improvements at 1-year follow-up on simple and choice reaction times. Elevated levels of anxiety and neuroticism at pretransplantation assessment were associated with worse psychosocial outcome at 1 year posttransplantation. Severity of liver disease was not related to psychological outcome at 1 year. Good psychological outcome at 1 year was maintained at the 3-year follow-up.

Topics: Adaptation, Psychological; Adult; Cyclosporine; Female; Humans; Immunosuppressive Agents; Liver Failure; Liver Transplantation; Male; Mental Disorders; Middle Aged; Predictive Value of Tests; Prospective Studies; Psychological Tests; Quality of Life; Scotland; Tacrolimus; Treatment Outcome