Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report FK506-induced neurotoxicity in 14 of 44 consecutive patients following orthoptic liver transplantation. In 10 of these 14 patients, postural hand tremors were found in the first weeks following surgery, transient apraxia of speech in 3, and generalized tonic-clonic seizures were noted in 2 patients. Other manifestations included nightmares, agitation, and acute delirium. Reduction of the FK506 dose resulted in resolution of symptoms, but in 1 patient mild speech difficulties and in 3 patients a fine tremor remained. Blood and plasma levels of FK506 were similar in patients with and without neurotoxicity. FK506 neurotoxicity in patients with liver transplantation commonly results in transient neurological manifestations. The incidence of neurotoxicity in FK506 is dramatically reduced in maintenance doses of 0.075 mg/kg twice a day.
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PMID:FK506-induced neurotoxicity in liver transplantation. 751 20

The introduction of cyclosporine A (CsA) and FK506 significantly improved the outcome of liver transplantation. However, the postoperative course and outcome of liver transplant recipients in still compromised by rejection, over-immunosuppression-induced infection and immunosuppression-associated toxicity. In the present study, we evaluated the reason for conversion between immunosuppressive regimens in 121 patients, 60 treated with FK506 and 61 patients treated with CsA-based immunosuppression. Five patients treated primarily with CsA (8.3%) were converted to FK506 therapy because of refractory acute of chronic rejection within 12 months following liver transplantation (LTX). In 2 patients, conversion was performed after Re-LTX. In 4 of these 5 patients, rejection was successfully treated according to histological and laboratory investigations, while in the remaining patient, graft function improved with persisting histological evidence of chronic rejection. Moderate and severe neurologic symptoms during the early postoperative period, i.e. organic brain syndromes (OBS), seizures, hemiparesis, dysphasia, dysathria and cerebellar symptoms were observed in 21.3% of patients treated with FK506 and in 11.7% of patients treated with CsA (p = n.s.). Five patients treated primarily with FK506 were converted to CsA due to severe neurotoxicity. Early postoperative renal insufficiency was observed to a similar extent with 42.6% of FK506- and 36.7% of CsA-treated patients. 8.3% of FK506-treated patients and 11.7% of CsA-treated patients required hemodialysis (p = n.s.) There patients were converted from FK506 to CsA due to persisting renal insufficiency. Moderate and severe neurologic symptoms were observed more frequently under treatment with FK506 than CsA, and all conversions from FK506 to CsA (13.3%) were performed because of neuro- or nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Toxicity versus rejection--or why conversions between cyclosporine A and FK506 were performed after liver transplantation. 754 52

We reviewed retrospectively the clinical records, autopsy protocols and central nervous system tissue sections of 50 patients who underwent orthotopic liver transplantation for end-stage liver disease between 12/83 and 8/93. The postoperative survival period ranged from hours (6), weeks (17), months (17), to years (10). All patients received immunosuppressive drugs from the immediate postoperative period to the time of their death (cyclosporine, steroids; occasionally azathioprine, OKT3, FK506). Nineteen patients had neurological manifestations (hepatic encephalopathy) prior to surgery. Post-transplant neurologic signs and symptoms included: hepatic encephalopathy/altered mental status (11), focal or generalized seizures (9) and stroke (2). In the majority of cases (37) the cause of death was septicemia and/or bleeding diathesis. The neuropathologic findings present in 36 patients could be classified into 3 distinct categories: metabolic disorders: hepatic/anoxic encephalopathy, central pontine myelinolysis (15); cerebrovascular disease: subarachnoid and/or intracerebral hemorrhage, bland or hemorrhagic infarction (23); and infection: bacterial meningitis/cerebritis, multifocal fungal microabscesses, presumptive viral meningitis/encephalomyelitis (10). In conclusion, 72% of 50 patients who came to autopsy after liver transplantation were found to have neuropathologic abnormalities; these abnormalities were predominantly infections and vascular diseases.
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PMID:Neuropathology of liver transplantation. 760 96

A 38-year-old man receiving cyclosporine A after bilateral lung transplantation for cystic fibrosis presented with cortical blindness, generalized seizures, and cerebellar edema. Progressive brainstem compression necessitated emergency posterior fossa decompression. Replacement of cyclosporine A with an alternative immunosuppressive agent, FK506, was followed by rapid neurological recovery and dramatic resolution of radiographic abnormalities. The etiology, clinical features, and radiographic findings of cyclosporine A neurotoxicity are discussed. The pertinent literature is reviewed.
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PMID:Cyclosporine A toxicity presenting with acute cerebellar edema and brainstem compression. Case report. 776 Jan 81

Neurological complications are important contributors to morbidity and mortality after liver transplantation. We reviewed 391 patients who underwent 427 consecutive orthotopic liver transplantations to analyze the clinical features of patients who experienced one or more neurological complication (74 patients [19%]) and to compare postoperative neurological problems in adults versus children. Neurological complications were more frequent in adults (64 of 273 patients [23%]) than children (10 of 118 patients [8%]) (P < 0.01). The most common neurological complication was encephalopathy (59%), which ranged widely in severity and occurred with similar frequency in adults and children. Other common neurological complications were seizures (12 patients), brachial plexus and peripheral nerve injuries (16 patients, 15 of whom were adults), stroke (5 patients), and central nervous system infections (5 patients). In 27 patients, drug toxicity was the primary cause of neurological complications, all of which reversed with dosage reduction or discontinuation of drug. Cyclosporine and FK506, primarily during intravenous administration for induction of immunosuppression, accounted for 25 of 27 drug-induced neurological complications, which included encephalopathy, seizures, severe tremor, and severe headache. Despite a higher rate of neurological complications in adults, those in children were more severe and associated with a higher mortality rate. When compared with liver transplant recipients without neurological complications, patients with neurological complications had a higher posttransplant mortality rate (14% vs. 5% for adults, and 50% vs. 7% for children). In conclusion, neurological complications after liver transplantation are more common in adults, more severe and associated with a higher mortality rate in children, and associated with a higher mortality rate in both children and adults when compared with transplant recipients without neurological complications.
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PMID:Neurological complications of liver transplantation in adult versus pediatric patients. 807 14

Previous studies found that seizures in orthotopic liver transplantation (OLT) herald a catastrophic neurologic event, but the studies were done of patients who later died and came to autopsy. We studied 630 OLT patients. Laboratory values, electroencephalography, neuroimaging, and levels of cyclosporine or FK506 were reviewed. Neurotoxicity from immunosuppression was considered a trigger for seizures when toxic blood level or increases > or = to 100% were documented, or when white matter lesions or confusional state or tremors were present. Generalized tonic-clonic seizures occurred in 28 of 630 patients (4%). In 7 patients seizures were part of an agonal event (central nervous system infection [n = 3], anoxic encephalopathy [n = 1], cerebral edema with fulminant hepatic failure [n = 1], intracranial hemorrhage [n = 1], and sepsis [n = 1]. In 17 patients cyclosporine (n = 11) or FK506 (n = 6) could be implicated. Remaining causes were acute uremia (n = 1), meningioma (n = 1), and unknown (n = 2). All patients were initially treated with anticonvulsants. Median follow-up of 2 years did not reveal seizure recurrence after discontinuation of anticonvulsants. We conclude that the majority of new-onset seizures after OLT are not indicative of a poor prognosis. Immunosuppression neurotoxicity is the most frequent cause. Anticonvulsant therapy is not necessary for favorable long-term outcome.
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PMID:Causes and outcome of seizures in liver transplant recipients. 896 Jul 38

FK506 is being used increasingly to prevent rejection after organ transplantation. Its use is associated with a wide spectrum of neurotoxicity, which has been described after most solid organ transplantations, but reports after lung transplantation are extremely rare. This is a report of the pathologic correlation of the clinical and radiologic features of delayed FK506-induced fulminant leukoencephalopathy after single-lung transplantation. The patient presented with neurologic symptoms that progressed to seizure activity. Neuroimaging showed diffuse changes in the brain, and results of a brain biopsy were consistent with leukoencephalopathy with microglial and astrocytic activation. The patient had a remarkable improvement in clinical status after discontinuation of FK506 administration, with resolution of the changes seen on neuroimaging.
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PMID:FK506-induced fulminant leukoencephalopathy after single-lung transplantation. 938 23

Leukoencephalopathy syndromes encompass a variety of neurologic abnormalities that affect cerebral white matter. Known etiologies include malignant hypertension, eclampsia, renal failure, CNS infection, and drug therapy with cyclosporine, tacrolimus (FK506) and interferon-alpha. Symptoms vary according to sites of involvement; they include altered mentation, visual disturbances, focal neurologic signs, and seizures. Characteristic radiologic findings are hypodense areas without contrast enhancement on CT and an increased T2 signal on MRI. The hypodense areas are often symmetric. The clinical symptoms and neuroimaging abnormalities are often reversible with treatment of the underlying condition or removal of the offending drug. We describe a patient with non-Hodgkin's lymphoma treated with conventional cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy and high-dose steroids who developed a rapidly progressive fatal leukoencephalopathy. Her neurologic symptoms and findings on CT are consistent with reported cases of leukoencephalopathy; however, in this instance, the syndrome was not reversible and was ultimately fatal. None of the previously described etiologies could be demonstrated in association with the patient's illness. There are no prior reports of fatal leukoencephalopathy in adult patients treated with standard-dose CHOP. We believe the concurrent immunosuppression from chemotherapy and high-dose steroids resulted in this patient's fatal complication.
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PMID:Fatal leukoencephalopathy in a patient with non-Hodgkin's lymphoma treated with CHOP chemotherapy and high-dose steroids. 951 35

Kainate is a potent agonist of an excitatory amino acid receptor subtype in the central nervous system, and causes neuronal death in several regions of the brain. Neurons are preferentially killed in the hippocampus, especially in the CA1 region, by systemic administration of kainate. It is speculated that functional alterations occur in the neurons preceding death. We examined the effect of FK506 on kainate-induced neuronal death and functional alterations in the rat hippocampal CA1 region. FK506 had no effect on electrographic and behavioral seizure activities induced by kainate; however, it prevented neuronal death measured seven days after administration. Although neither death nor morphological alterations of neurons were observed in the CA1 region 24 h after administration, the neurons exhibited decreased excitatory postsynaptic potentials and enhanced long-term potentiation. This functional alteration was not detected in the rats administered FK506 prior to kainate. Taken together, these observations indicate that functional alteration precedes neuronal death in rats systemically administered kainate and that FK506 prevents both. It is suggested that FK506 exerts its neuroprotective effect not by attenuating electrographic and behavioral seizure activities, but by protecting neurons from kainate-induced functional disorders.
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PMID:An immunosuppressant, FK506, protects against neuronal dysfunction and death but has no effect on electrographic and behavioral activities induced by systemic kainate. 969 22

Currently, limited data exist on the role of tacrolimus (FK506) in pediatric allogeneic marrow transplantation. Forty-one patients who received tacrolimus as prophylaxis were reviewed, with a median age of 9 years (range 0.2-16 years). Twenty-one patients underwent related donor transplants and 20 underwent unrelated donor transplants. All patients received tacrolimus beginning the day prior to transplant at a dose of 0.03 mg/kg/day by continuous i.v. infusion. When clinically possible, patients were switched to oral therapy in two divided doses, at four times the intravenous dose. Tacrolimus levels were monitored twice a week, and dosages adjusted to maintain serum levels 5-15 ng/ml. Common adverse effects included hypomagnesemia (98%), hypertension (49%), nephrotoxicity (34%), and tremors (32%). Less common side-effects (<10% cases) included seizures and hyperglycemia. The median time to ANC recovery (ANC >500 x 106/l) was 15 days. For the related donor group, the incidence of grade II-IV acute GVHD was 33%, and grade III-IV GVHD 19%. For the unrelated donor group, the incidence of grade II-IV acute GVHD was 55%, and grade III-IV GVHD 30%. Overall, tacrolimus therapy was well tolerated as prophylaxis for acute GVHD in pediatric patients undergoing allogeneic transplantation.
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PMID:Tacrolimus (FK506) and methotrexate as prophylaxis for acute graft-versus-host disease in pediatric allogeneic stem cell transplantation. 1091 26


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