tacrolimus and Coma

Topics: Child; Coma; Heart Transplantation; Humans; Immunosuppressive Agents; Leukoencephalopathies; Tacrolimus

Posterior leukoencephalopathy due to calcineurin-inhibitor-related neurotoxicity is a rare but severe complication that results from treatment with immunosuppressive agents (primarily those administered after a liver or kidney transplant). The pathophysiologic mechanisms of that disorder remain unknown.. We report the case of a 46-year-old woman who received a liver transplant in our center as treatment for alcoholic cirrhosis and in whom either a fulminant course of posterior leukoencephalopathy or posterior reversible encephalopathy syndrome developed 110 days after transplant. After an initially uneventful course after the transplant, the patient rapidly fell into deep coma.. Cerebral MRI scan showed typical signs of enhancement in the pontine and posterior regions. Switching the immunosuppressive regimen from tacrolimus to cyclosporine did not improve the clinical situation. The termination of treatment with any calcineurin inhibitor resulted in a complete resolution of that complication.. Posterior reversible encephalopathy syndrome after liver transplant is rare. We recommend a complete cessation of any calcineurin inhibitor rather than a dose reduction.

Topics: Calcineurin Inhibitors; Coma; Cyclosporine; Female; Humans; Immunosuppressive Agents; Liver Cirrhosis, Alcoholic; Liver Transplantation; Magnetic Resonance Imaging; Middle Aged; Mycophenolic Acid; Posterior Leukoencephalopathy Syndrome; Prednisolone; Tacrolimus; Time Factors

Topics: Brain; Coma; Female; Humans; Immunosuppressive Agents; Leukoencephalopathy, Progressive Multifocal; Magnetic Resonance Imaging; Middle Aged; Occipital Lobe; Parietal Lobe; Status Epilepticus; Tacrolimus

The leukoencephalopathy induced by tacrolimus is increasingly recognised as an important cause of neurological complications after transplantation. Magnetic resonance imaging (MRI) is of major help in the differential diagnosis of infection or vascular injury. We describe two children with coma and seizures after transplantation, in whom the results of MRI with FLAIR (fluid-attenuated inversion-recovery) and DWI (diffusion-weighted images) were the main positive elements for the diagnosis of drug-induced toxicity. The results of DWI favoured the role of oedema and/or demyelination in the pathophysiology of this disorder. Unlike other reported patients, in whom all symptoms resolved, lesions persisted, albeit improved, on the control MRI, and both children demonstrated learning disabilities after several years of follow-up.

Topics: Acute Disease; Brain; Child, Preschool; Coma; Female; Humans; Immunosuppressive Agents; Magnetic Resonance Imaging; Male; Seizures; Tacrolimus

Neurotoxicity is a well-known side effect of tacrolimus-based immunosuppression after liver transplantation. Until now, only 31 cases of immunosuppression-associated leukoencephalopathy in liver transplant recipients reported in the literature are related to tacrolimus therapy. We report a patient who developed a posterior leukoencephalopathy syndrome, secondary to tacrolimus-based immunosuppression, after living donor liver transplantation. The special features of this case are the sudden and late onset of neurologic symptoms, a persistent comatose state, and increased signal intensity in follow-up MRI.

Topics: Coma; Female; Humans; Immunosuppressive Agents; Leukoencephalopathy, Progressive Multifocal; Liver Transplantation; Living Donors; Magnetic Resonance Imaging; Middle Aged; Postoperative Complications; Tacrolimus

Topics: Brain; Brain Edema; Coma; Consciousness Disorders; Cranial Nerve Diseases; Drug Administration Schedule; Evoked Potentials, Somatosensory; Female; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Magnetic Resonance Imaging; Middle Aged; Neurotoxicity Syndromes; Neurotoxins; Quadriplegia; Recovery of Function; Recurrence; Seizures; Tacrolimus; Tomography, X-Ray Computed

In the present study the time-course of DNA fragmentation following insulin-induced hypoglycemia was examined. In situ localization of DNA breaks were studied by the terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labelling method, and the temporal profile of DNA-fragmentation by agarose gel electrophoresis. Cell nuclei displayed terminal deoxynucleotidyl transferase-deoxyuridine triphosphate nick-end labelling within 3 h of recovery following 30 min of a hypoglycemic insult, and DNA from the hippocampus displayed oligonucleosomal fragmentation. Ultrastructural examination of the dentate granule cells showed mitochondrial swelling during the acute phase of the hypoglycemic insult, which preceded the DNA fragmentation seen in the recovery phase. Cyclosporin A but not tacrolimus, prevented mitochondrial swelling and subsequent DNA fragmentation. We conclude that during severe energy deprivation following hypoglycemia, mitochondrial swelling occurs due to mitochondrial permeability transition and that factors are released, which upon recovery can activate processes leading to DNA fragmentation and cell death.

Topics: Animals; Coma; Cyclosporine; DNA Fragmentation; Electrophoresis, Agar Gel; Hippocampus; Hypoglycemia; In Situ Nick-End Labeling; Male; Mitochondria; Permeability; Rats; Rats, Wistar; Tacrolimus