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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ifosfamide, a nitrogen mustard derived alkylating agent commonly used in the treatment of solid tumors, has been associated with neurotoxicity in 5-33% of treated patients. Encephalopathy most often occurs during or shortly following drug administration, with increased drowsiness or irritability, confusion, hallucinations, visual blurring, extrapyramidal dysfunction, cranial nerve abnormalities, incontinence, generalized muscle twitching, seizures, and coma reported in infants, children, and older adults. While most reported neurologic abnormalities associated with ifosfamide have been reversible, encephalopathy resulting in death has occurred. We now report an infant who developed ifosfamide-induced encephalopathy, loss of developmental milestones, progressive brain atrophy, and cessation of cranial growth. This is the first case of cerebral atrophy and loss of developmental milestones that has been reported in a pediatric patient treated with ifosfamide. Given the efficacy of this anti-neoplastic agent and its increasing use in pediatrics, further investigation is indicated, especially in infants where brain growth is ongoing.
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PMID:Cerebral atrophy in an infant following treatment with ifosfamide. 805 12

Three patients with stage 4 neuroblastoma were treated with a schedule comprising alternating modules of myelosuppressive (ifosfamide, etoposide, doxorubicin) and less myelosuppressive (vincristine, cisplatin) drugs given every 10 days regardless of the neutrophil count. A partial response was seen in two patients, and a very good partial response, in one patient. Extensive blood-component support was required. Non-haemopoietic toxicity was severe and led to treatment delays in two patients. Ifosfamide-related encephalopathy was seen in one patient and nephrotoxicity, in two patients. Mucositis was severe in two patients, may have contributed to the high rate of sepsis observed, and precluded the use of doxorubicin in one patient. As ifosfamide and doxorubicin were felt to be responsible for much of the toxicity, a subsequent schedule did not include these agents.
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PMID:Prohibitive toxicity of a dose-intense regime for metastatic neuroblastoma containing ifosfamide, doxorubicin and cisplatin. 843 77

Oral treatment with ifosfamide results in dose-limiting encephalopathy. Methylene blue is effective in reversal and prophylaxis of this side effect. In the present study, the pharmacokinetics of ifosfamide after iv and po therapy in combination with prophylactic administration of methylene blue were investigated. Nine patients with metastatic non-small cell lung cancer were treated by a combination of ifosfamide (3 days), sodium 2-mercaptoethane sulfonate (4 days), and etoposide (8 days). Cycles were repeated every 28 days. Ifosfamide was administered orally, with the exception of one of the first two cycles, when it was administered as a short infusion (randomly assigned). The patients received methylene blue in doses of 50 mg po 3 times daily; an initial dose of 50 mg was given the evening before chemotherapy. Urine samples were collected over the entire treatment period, and concentrations of ifosfamide and its major metabolite, 2-chloroethylamine, were measured by gas liquid chromatography. By the same technique, 2- and 3-dechloroethylifosfamide were determined in plasma and urine. Overall alkylating activity in urine was assayed by reaction of the alkylating metabolites with 4-(4'-nitrobenzyl)-pyridine. The chemotherapeutic regimen was well-tolerated by all of the patients studied. There was no evidence of a shift in the metabolic pattern dependent on the route of administration. From the data, we conclude that methylene blue has a neuroprotective effect and that the pharmacokinetics of ifosfamide are not influenced by its comedication.
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PMID:Comparative pharmacokinetics of oral and intravenous ifosfamide/mesna/methylene blue therapy. 973 67

Ifosfamide is an alkylating agent which has poorly understood toxic side effects such as encephalopathy. We hypothesized that ifosfamide and concomitantly applied mesna could have an influence on the flow properties of blood, and thus carried out an in vitro study. Whole blood was incubated in vitro with increasing concentrations of ifosfamide (0-50 mg/ml), mesna (0-20 mg/ml) and combinations thereof. Chloroacetaldehyde, a major metabolite of ifosfamide, was also studied (0-5 mmol/l). Ifosfamide led to a dose-dependent stomatocytic shape transformation and mesna to an echinocytic shape transformation of erythrocytes. These shape changes were reversible upon removal of the causing agent. Both shape changes increased whole blood viscosity. Erythrocyte aggregation was decreased by both drugs at high concentration. Erythrocyte deformability, as measured with the transit time through 5-microm pores, was decreased by mesna and remained unaffected by ifosfamide. These effects were seen at concentrations which may be reached in vivo at the infusion site of the drugs into a vein and in the urinary tract. We conclude that ifosfamide and mesna interact with the lipid bilayer of the cell membrane, which may contribute to the toxicity of the compounds.
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PMID:Ifosfamide-induced stomatocytosis and mesna-induced echinocytosis: influence on biorheological properties of blood. 1022 55

Ifosfamide is an alkylating agent used in the treatment of a variety of solid tumours. Ten to 15% of patients treated with ifosfamide develop an encephalopathy. Methylene blue (MB) may be used in the treatment of this encephalopathy. The purpose of this study was to evaluate the neuroprotective effect of MB in these patients and to review the literature. Between 1993 and 1997, 52 patients (age 16-77 years) with solid tumours were treated with ifosfamide in dosages ranging from 3 to 5 g m(-2) q3w when given in combination schedules and up to 12 g m(-2) q4w when given as a single agent. Twelve patients developed central nervous system (CNS) depression, defined as National Cancer Institute Common Toxicity Criteria (NCI-CTC) neurocortical toxicity grade 2 or higher. Eight were treated with MB at a dose of 6 x 50 mg day(-1) intravenously (i.v.). Four recovered fully within 24 h, two recovered partially after 24 h and completely after 48 h while two recovered only after 72 h. Four patients did not receive MB and all recovered only after 48 h. Three patients received prophylaxis with MB at a dose of 4 x 50 mg day(-1) i.v. for the subsequent chemotherapy cycles. Two developed milder encephalopathy; one had no CNS depression at all. We conclude that MB is an effective treatment for ifosfamide-induced encephalopathy. Our findings suggest that it may also be used as a prophylactic agent.
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PMID:Methylene blue in the treatment and prevention of ifosfamide-induced encephalopathy: report of 12 cases and a review of the literature. 1064 79

A 5-year-old child with desmoplastic small round-cell tumor was treated with a protocol of very-high-dose, short-term chemotherapy, containing HD-CAV (cyclophosphamide, doxorubicin, vincristine, and mesna), ifosfamide, and etoposide. Two days after the initiation of ifosfamide, he exhibited new-onset lethal encephalopathy manifested by subacutely progressive cerebellar and then temporal and frontocortical degeneration leading to a vegetative state and eventually to death. A full work-up, including brain biopsy, was negative, excluding infections and metabolic or vascular causes. Ifosfamide is known to be capable of causing acute encephalopathy that can be severe but is generally reversible. This child showed a very atypical progressive, lethal course of ifosfamide toxicity. The possibility of this complication should be considered when high-dose ifosfamide treatment is planned for children.
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PMID:Subacute central nervous system degeneration in a child: an unusual manifestation of ifosfamide intoxication. 1092 21

Ifosfamide (IFOS) is used in cancer treatment. Ifosfamide-induced encephalopathy (IIE) can result in treatment delay or discontinuation as well as morbidity and mortality. Cases using methylene blue (MB) in acute and prophylactic treatments are discussed. For acute use, marked central nervous system (CNS) improvement occurred within 24h of MB administration. For prophylactic use, the severity of the symptoms decreased significantly compared with previous treatment cycles, and enabled patients to continue further IFOS therapy. MB has potential use in both the acute treatment and prophylaxis of IIE.
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PMID:Methylene blue for the treatment and prophylaxis of ifosfamide-induced encephalopathy. 1457 94

Ifosfamide is relatively well tolerated but it can be associated occasionally with life-threatening complications such as arrhythmias and heart failure, severe encephalopathy and hemorrhagic cystitis. Mesna administration can control the urothelial toxicity of ifosfamide, but it is without effect on the other complications. Other preventive measures, such as amifostine or methylene blue administration, have not yet been adequately evaluated in a sufficient number of patients. Clinicians prescribing ifosfamide, especially in high doses, should be watchful for early signs of toxicity in order to discontinue ifosfamide administration soon enough to avoid development of major toxicity.
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PMID:Side effects of ifosfamide. 1458 40

Ifosfamide is an alkylating agent with well-demonstrated efficacy against a large number of malignant diseases. With cyclophosphamide it shares a toxicity profile characterized by myelosuppression and urotoxicity, but ifosfamide has additionally disclosed adverse neurological effects. Ifosfamide-related central nervous system toxicity is characterized by metabolic encephalopathy of varying severity. Symptoms have been reported in 5-30% of all patients treated with ifosfamide. The mechanism of ifosfamide-related central nervous system toxicity has not been fully elucidated, although the symptoms have most often been noted when the drug is given at high doses or administered orally. The neurotoxicity is generally self-limiting and reversible between 48 and 72 h after discontinuation of ifosfamide, although fatal sequelae have been reported. Therapeutic options are now available.
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PMID:Neurological toxicity of ifosfamide. 1458 41

Ifosfamide is one of the most widely used alkylating chemotherapeutic agents. Before mesna was introduced, its dose-limiting toxicity was hemorrhagic cystitis, but at present, neurotoxicity is one of its most worrisome side effects. A total of 10%-15% of patients treated with ifosfamide develop an encephalopathy. The exact pathophysiologic mechanisms responsible for the development of ifosfamide-induced encephalopathy (IIE) are not known. However, accumulation of chloracetaldehyde, toxic metabolite of ifosfamide, in the central nervous system is theorized to be the cause of the neurotoxicity. No standard treatment has been available for IIE. Recently, many reports suggested that methylene blue (MB) may be an effective treatment of this lethal complication. We report two cases of IIE and their treatment outcomes. The first patient recovered completely with MB. The other patient showed slow and incomplete improvement without using MB. We suggest that MB can be used as an initial treatment for the encephalopathy related to ifosfamide infusion. Thus, we present these two cases with brief review of related literature.
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PMID:Ifosfamide-induced encephalopathy with or without using methylene blue. 1617 28


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