tacrolimus and Leukoencephalopathy--Progressive-Multifocal

Immunosuppressive-associated leukoencephalopathy is a significant complication of cyclosporine (CsA) or tacrolimus therapy. However, the precise time of onset, role of putative risk factors, differences, if any, in presentation in various types of organ transplantation and outcome of this entity, remain poorly defined. Fifty cases of immunosuppressive-associated leukoencephalopathy reported in the literature in organ transplant recipients, were reviewed. Of 50 cases, 31 occurred in liver, 8 in renal, 6 in lung, and 5 in heart transplant recipients. Median time to onset was 28 days (range 3-1512 days); 82% occurred within 90 days of transplantation. Lesions tended to occur earlier in the liver transplant recipients, compared with other organ transplant recipients (median 9 vs. 29 days, P=.19). Seizures 74%, altered mental status 50%, and visual abnormalities 28% were the most frequently presenting features. Ten percent of the patients had fever with no documented source of infection. Systemic hypertension (P=.001), and lesions in the presence of therapeutic drug levels (P=.11) were more likely to occur with CsA than tacrolimus. Neuroimaging and clinical abnormalities were reversible on cessation or reduction of CsA or tacrolimus in all but two cases. Resolution of neurologic signs/symptoms occurred a median of 4 days and neuroimaging abnormalities in a median of 20 days on reduction/cessation of the drug. Immunosuppressive-associated leukoencephalopathy is a unique entity that can usually be diagnosed on the basis of its distinctive time of onset, and clinical and neuroimaging characteristics, and it is potentially reversible if promptly diagnosed. Despite identical clinical presentation of this syndrome in the recipients of CsA and tacrolimus, above noted variations in risk factors suggest that a difference in pathophysiologic mechanism may exist.

Topics: Cyclosporine; Humans; Immunosuppressive Agents; Leukoencephalopathy, Progressive Multifocal; Organ Transplantation; Tacrolimus

Topics: Combined Modality Therapy; Delirium; Diagnosis, Differential; Humans; Immunosuppressive Agents; Kidney Transplantation; Leukoencephalopathy, Progressive Multifocal; Magnetic Resonance Imaging; Male; Middle Aged; Pancreas Transplantation; Postoperative Complications; Severity of Illness Index; Tacrolimus; Treatment Outcome

Progressive multifocal leukoencephalopathy (PML) is a rare, opportunistic and often fatal disease of the CNS which may occur under immunosuppression in transplant patients. Brain stem PML is associated with a particularly bad prognosis. Here, we present a case of a renal transplant patient treated with mycophenolate mofetil (MMF) and tacrolimus who developed brain stem PML with limb ataxia, dysarthria and dysphagia. Diagnosis was established by typical MRI features and detection of JCV-DNA in the CSF. Immune reconstitution after stopping MMF and tacrolimus led to a complete and sustained remission of symptoms with improvement of the brain stem lesion over a follow-up over 20months. In summary, early detection of PML and consequent treatment may improve neurological outcomes even in brain stem disease with a notorious bad prognosis.

Topics: Adult; Antibiotics, Antitubercular; Brain Stem; DNA; Early Diagnosis; Female; Humans; Immunosuppressive Agents; JC Virus; Kidney Failure, Chronic; Kidney Transplantation; Leukoencephalopathy, Progressive Multifocal; Magnetic Resonance Imaging; Mycophenolic Acid; Tacrolimus

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Antirheumatic Agents; Humans; Immunosuppressive Agents; Isoxazoles; JC Virus; Leflunomide; Leukoencephalopathy, Progressive Multifocal; Mycophenolic Acid; Natalizumab; Rituximab; Sirolimus; Tacrolimus

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

A 46-year-old woman with Hodgkin's disease who underwent nonmyeloablative allogeneic stem cell transplantation developed cortical blindness, seizures, and left hemiparesis on day 100 while receiving tacrolimus (FK506) and prednisone for the treatment of graft-versus-host disease (GVHD). Magnetic resonance imaging revealed multiple changes, mainly in the bilateral occipital lobes, suggesting FK506-related leukoencephalopathy. These abnormalities improved after discontinuation of FK506. However, 3 days after the episode, cerebral hemorrhage in the left occipital lobe with perforation to the left subdural space occurred. Although FK506-induced leukoencephalopathy with cerebral hemorrhage is considered the more severe form of such leukoencephalopathy, the patient's neurological symptoms almost completely resolved and radiographic findings improved after discontinuation of FK506, tapering of methylprednisolone, and initiation of mycophenolate mofetil. FK506-related leukoencephalopathy is a rare complication after allogeneic stem cell transplantation. Although the symptoms usually subside after discontinuation of FK506, therapeutic intervention in many cases may result in severe complications, including GVHD and vascular disease. We consider it important to use immunosuppressive agents without vascular endothelial toxicity for preventing the development of fatal GVHD after discontinuation of FK506.

Topics: Cerebral Hemorrhage; Disease-Free Survival; Female; Graft vs Host Disease; Hodgkin Disease; Humans; Leukoencephalopathy, Progressive Multifocal; Middle Aged; Peripheral Blood Stem Cell Transplantation; Remission Induction; Tacrolimus; Transplantation Conditioning

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: Herpesviridae Infections; Herpesvirus 6, Human; Humans; Iatrogenic Disease; Immunosuppressive Agents; Leukoencephalopathy, Progressive Multifocal; Tacrolimus

Tacrolimus (FK506) has recently been approved for immunosuppression in organ transplantation, although its use is accompanied by a wide spectrum of neurotoxic side effects. We describe the clinical, radiological, and pathological features of 3 cases of tacrolimus-related leukoencephalopathy. The syndrome of immunosuppression-related leukoencephalopathy is proposed as an uncommon neurological syndrome occurring in patients with organ transplants involving demyelination, in particular in the parieto-occipital region and centrum semiovale. Although the syndrome is not associated with a particular (absolute) serum level of tacrolimus, it resolves spontaneously upon decreasing the dose. The tacrolimus-related syndrome has a similar radiographic and pathologic appearance as the analogous syndrome that occurs in patients taking cyclosporine.

Topics: Adult; Blindness; Dose-Response Relationship, Drug; Female; Graft Rejection; Humans; Immunosuppressive Agents; Leukoencephalopathy, Progressive Multifocal; Liver Transplantation; Magnetic Resonance Imaging; Male; Middle Aged; Occipital Lobe; Parietal Lobe; Remission, Spontaneous; Tacrolimus; Tomography, X-Ray Computed