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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors report a case of fatal hepatic failure in a 19-year old young man suffering from absence seizures and treated for two months with valproic acid (VPA). The duration of VPA therapy before onset of clinical manifestations was four weeks. The prodromal symptoms were weakness, anorexia, and vomiting, then in a few weeks occurred a jaundice and an hepatic encephalopathy leading to death. Among laboratory findings disturbance of liver tests and particularly depressed levels of clotting factors were observed. The histologic study of the liver showed an extended centrolobular necrosis associated with fatty change and fibrosis. The mechanism of this hepatic failure remains unknown. The seriousness of this complication necessitates to respect any contraindications.
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PMID:[Fatal hepatic necrosis during treatment with sodium valproate]. 758 2

Felbamate is currently being developed as an antiepileptic agent. Although its mechanism of action has yet to be fully elucidated, felbamate appears to inhibit both the spread of seizures and increase seizure threshold in animal models. Data available in the clinical setting provide evidence that, at doses of up to 3600 mg/day as an adjunct to existing antiepileptic therapy or as monotherapy following substitution for other medications, the drug reduces the frequency of partial onset seizures in adult patients refractory to conventional antiepileptic treatments. Felbamate is also effective in the treatment of Lennox-Gastaut syndrome in children, a severe epilepsy which is usually refractory to antiepileptic agents. The effect of felbamate in the treatment of generalised tonic-clonic seizures in adults with partial onset seizures which are secondarily generalised is promising but requires clarification in large-scale trials. The most common adverse effects occurring during administration of felbamate are mild to moderate gastrointestinal (nausea, vomiting and anorexia) and central nervous system (headache, somnolence, diplopia, dizziness and insomnia) disturbances. Drug interactions with other antiepileptic agents may prove problematic in terms of adverse effects. Thus, at this stage of its development, the antiepileptic efficacy of felbamate in treatment-refractory patients with partial onset seizures and Lennox-Gastaut syndrome has been proven but efficacy in generalised tonic-clonic seizures requires further substantiation in large well controlled and well designed clinical trials. In addition, a more comprehensive base of comparative clinical trials data is necessary to further clarify issues of relative efficacy and tolerability compared with other antiepileptic agents. The clinical implications of the drug interactions associated with felbamate also require more detailed investigation. These data will be awaited with interest and when available will help to place felbamate in perspective in the management of epilepsy.
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PMID:Felbamate. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in epilepsy. 769 93

Methotrexate, a mainstay treatment for children with acute lymphoblastic leukaemia, can cause neurotoxicity, with paralysis, seizures, somnolence, anorexia, and headaches. The pathophysiology of this reaction is unknown. It has been suggested that the anti-inflammatory effect of methotrexate in patients with arthritis is due to adenosine release brought on by inhibition of purine synthesis. Since adenosine is a central nervous system depressant, we wondered whether adenosine release in the central nervous system could account for some of the neurotoxicity due to methotrexate, and whether that toxicity could be lessened by displacement of adenosine from its receptor by aminophylline. 6 patients (age 3-16 years) who had methotrexate-induced neurotoxicity unresponsive to standard treatment received 2.5 mg/kg aminophylline. In addition, the concentration of adenosine in the cerebrospinal fluid (CSF) from 11 children completing a 24-h systemic methotrexate protocol was compared with that in 8 newly diagnosed patients and 12 who had not received any treatment for at least a week. 4 of 6 patients with toxic signs and symptoms attributed to methotrexate and unrelieved by steroids, epidural blood patch, promethazine, 5-hydroytryptamine antagonists, paracetamol, and narcotics, had complete resolution of neurotoxicity after or during a 1-h infusion of aminophylline; 2 others had a pronounced improvement but persistent nausea. CSF adenosine concentrations of patients receiving methotrexate, even when there was very slight or no toxicity, were greatly increased compared with control subjects (mean values of 217 and 51 nmol/L, median 175 and 52 nmol/L). Subacute methotrexate neurotoxicity may be mediated by adenosine and relieved by aminophylline.
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PMID:Aminophylline for methotrexate-induced neurotoxicity. 777 73

A six-week-old female borzoi puppy from a brother-sister mating developed a generalised illness characterised by anorexia, temporary intention tremor, episodic pyrexia, tachypnoea, conjunctivitis, otitis and neck pain. Haematological abnormalities included an inflammatory leukogram and regenerative anaemia. Blood cultures remained sterile; clinical chemistry values were unremarkable. The puppy had recurrent seizures and was euthanased when 18 weeks old. Post mortem examination revealed a multisystemic inflammatory disease involving thyroids, lymph nodes, spleen, pancreas, bladder and lung, but no lesions to account for the neurological signs. The cause of this generalised disease was not recognised. The histological features are unusual and resemble those described in other dogs of this breed.
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PMID:Multisystemic inflammatory disease in a borzoi dog. 781 81

The chemistry, pharmacology, pharmacokinetics, clinical use, adverse effects, drug interactions, and dosage of felbamate are discussed. Felbamate (2-phenyl-1,3-propanediol dicarbamate) is chemically unrelated to any of the other currently marketed antiepileptic drugs (AEDs). It appears that felbamate, like phenobarbital and valproic acid, decreases the frequency of seizures by decreasing seizure spread and increasing seizure threshold. Oral felbamate is at least 90% absorbed, and peak concentrations are reached in one to six hours. The half-life is a little less than one day. A therapeutic range of plasma concentrations has not been determined. Felbamate has been used effectively as monotherapy and adjunctive therapy in patients with partial seizures with or without secondary generalization and as adjunctive therapy in children with partial or generalized seizures associated with Lennox-Gastaut syndrome. Felbamate may also be safe and effective in patients with generalized, absence, atypical absence, juvenile myoclonic, infantile, and gelastic seizures. The most frequently reported adverse effects of felbamate include nausea, anorexia, vomiting, headache, fatigue, somnolence, insomnia, and increased serum aspartate aminotransferase levels. The frequency of adverse effects is greater in patients receiving other AEDs in addition to felbamate. Felbamate affects the pharmacokinetics of phenytoin, carbamazepine, valproic acid, and methsuximide; other AEDs also affect the pharmacokinetics of felbamate. The dosage of felbamate should begin at 400 mg orally three times daily and then increase by 600 mg/day every two weeks to up to 3600 mg/day. If the patient is receiving other AEDs concurrently, their dosage should be decreased as the dosage of felbamate is increased. If the goal is to switch to felbamate, the dosage should be increased weekly as the dosages of other AEDs are reduced. Felbamate offers a safe and effective alternative to other AEDs in the treatment of partial and secondarily generalized seizures; partial and generalized seizures associated with Lennox-Gastaut syndrome; and atypical absence seizures, gelastic seizures, and other difficult to control seizures.
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PMID:Felbamate: a new antiepileptic drug. 794 90

Canine distemper virus (CDV) infection occurred in captive leopards (Panthera pardus), tigers (Panthera tigris), lions (Panthera leo), and a jaguar (Panthera onca) in 1991 and 1992. An epizootic affected all 4 types of cats at the Wildlife Waystation, San Fernando, California, with 17 mortalities. CDV-infected raccoons were thought to be the source of infection in these cats. Two black leopards died at the Naibi Zoo, Coal Valley, Illinois, and 2 tigers died at the Shambala Preserve, Acton, California. Initial clinical signs were anorexia with gastrointestinal and/or respiratory disease followed by seizures. Canine distemper virus was isolated from 3 leopards, 3 tigers, and 3 lions that died or were euthanized when moribund. Monoclonal antibody testing identified the virus isolates as CDV. Gross and histopathologic findings were similar to those found in canids with distemper with a few exceptions. There were fewer lesions in the brain, and there was a pronounced type 2 cell proliferation in the lung, with inclusion bodies and CDV antigen demonstrated by immunohistology. Neutralizing antibody to CDV was found in high titers in serum from most animals but was absent or was found only in low titers in some cats that succumbed after CDV infection. There was a marked difference in neutralizing antibody titers when tests were done with different strains of CDV.
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PMID:Canine distemper epizootic in lions, tigers, and leopards in North America. 794 95

After two seizures, a 13 year-old boy experienced headache, fatigue and loss of appetite over a period of 3 weeks. There was a bilateral papilledema with normal visual acuity. CT and MRI disclosed two ischemic foci, that were interpreted as evidence of vasculitis. High serum levels of IgG and IgM antibodies specific to Borrelia burgdorferi, were present. The patient had attended an outdoor scout camp in a area, in south-east Belgium, known to be endemic for tick-born borreliosis. The clinical symptoms, the levels of the specific antibodies and the radiologic abnormalities responded dramatically to treatment. We believe that seizures in this case were related to cerebral vasculitis. This case confirms the extreme diversity of the neurological manifestations of Borreliosis.
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PMID:[Epilepsy disclosing neuroborreliosis]. 800 48

During normal pregnancy, serum transaminase levels remain within normal limits. An elevated level observed in a pregnant woman always signals a disease process, most often of hepatic origin, but in certain cases, of muscular origin. During the last three months of pregnancy and in the immediate post partum period a large number of liver diseases can cause elevated transaminase levels, depending upon the clinical presentation. In everyday practice, a complete liver battery together with specialized consultation is required for all pregnant women with raised transaminase levels. Toxaemia gravis may be evident in patients with severely raised blood pressure, especially if seizures occur. Epigastric or subcostal pain should suggest hepatic involvement. Hypertension may however be absent and epigastric or left shoulder pain may be the only clinical signs. Acute liver steatosis is 20 to 50 times more rare than toxaemia and may cause nausea and vomiting. Certain non-specific signs such as asthenia, anorexia, polyalgia, abdominal pain, diarrhoea and fever, together with pruritus should suggest acute hepatitis. A 25-fold increase in transaminase level is commonly encountered. The risk of fulminating hepatitis is less than 1/1000 but should always be entertained. All drugs should be stopped and careful research for recent xenobiotic contamination (drugs, infusions, alphamethyldopa, etc.) should be undertaken. Viral hepatitis requires serovaccination of the newborn at birth. Herpetic hepatitis is rare but requires rapid diagnosis (liver biopsy) and treatment with acyclovir in addition to cesarean section and treatment of the newborn at birth. Rare cases of hepatitis E may occur after a stay in North Africa, the Middle-East, Southeast Asia or Mexico. Chronic cases with or without temporary pruritus suggest infectious hepatitis B or C although, in chronic hepatitis C, serum transaminase levels often return to normal during pregnancy. Rare cases of asymptomatic elevations of serum transaminase levels can reveal subclinical chronic hepatitis.
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PMID:[Significance of elevated transaminase levels at the end of pregnancy]. 802 21

Thirty children (2 to 17 years of age) with refractory partial seizures received open-label felbamate as an add-on medication to their background antiepileptic drugs. The dose was increased up to a maximum of 45 mg/kg. Compared with baseline seizure activity, there was a 53% decrease in seizure frequency during felbamate therapy; 50% of the patients had more than a 50% decrease in seizure frequency. Patients older than 10 years of age were more likely to have a favorable response. Age correlated positively with felbamate concentrations and negatively with apparent felbamate clearance. Transient weight loss occurred in 57% of the patients; the weight loss was maximal after 12 weeks of initiation of felbamate, and subsided after the twentieth week of treatment. Anorexia and insomnia were reported in 20% and 16% of the patients, respectively. Adverse effects were generally tolerable; felbamate therapy was discontinued because of side effects in only one patient, because of a rash. We conclude that felbamate can be a useful and well-tolerated medication in the treatment of refractory partial epilepsy in children. However, increased apparent clearance of this drug in younger children should be considered in treatment of this age group.
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PMID:Efficacy of felbamate in therapy for partial epilepsy in children. 807 63

Among some 14 new antiepileptic drugs (AEDs), those most extensively tested in humans include felbamate (FBM), gabapentin (GBP), lamotrigine (LTG), oxcarbazepine (OCBZ), vigabatrin (VGB), and zonisamide (ZNS). All are currently marketed in some but not all countries. Although no large, comparative studies on efficacy have been conducted, all of these new AEDs are effective in adult localization-related epilepsies, and some have activity in specific syndromes. Although these drugs all have some CNS side effects, especially when administered in combination with other AEDs, they also all have low toxicity profiles. The availability of AEDs with different mechanisms of action may facilitate rational polytherapy. FBM is not teratogenic in animals. Half-life of FBM in humans is 11-28 h. Daily FBM dosages are 15-45 mg/kg in children and 2,400-4,800 mg in adults. Side effects include insomnia and anorexia, with weight loss. FBM increases phenytoin (PHT) and valproate (VPA) concentrations, and FBM concentration may be affected by other drugs. It is available in the United States for treatment of Lennox-Gastaut syndrome and partial seizures in adults. GBP is very water soluble. Half-life of GBP in humans is 5-7 h and daily dosages range from 900 to 2,400 mg in adults. Few side effects have been observed. GBP is not metabolized by the liver and has no drug interactions. It is available in the United Kingdom and the United States. LTG has no teratogenicity in animal models. Half-life of LTG in humans depends on co-medication: with enzyme inducers it is 15-24 h, and with VPA it is approximately 60 h. LTG dosages are 100-600 mg/day in adults. LTG is available in Europe. OCBZ is rapidly metabolized to 10,11-dihydro-10-hydroxy-carbazepine (MHD), the active compound. Animal studies have shown similar efficacy but superior toxicity to carbamazepine (CBZ) in animal models. For MHD, half-life ranges from 10 to 15 h in patients. OCBZ dosages range from 300 to 1,800 mg/day. VGB is a potent, irreversible inhibitor of GABA transaminase which elevates GABA levels in the CNS. Daily dosages of 2,000-4,000 mg of VGB are needed in adults. Although intramyelinic edema has developed in rats and dogs, it has not yet presented in other mammals or humans. ZNS is a sulfonamide effective in animal models of epilepsy. Half-life of ZNS is 27-36 h. ZNS daily dosage is 400-600 mg. ZNS has been effective in some cases of Baltic myoclonic epilepsy.
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PMID:Antiepileptic drugs in development: prospects for the near future. 817 17


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