allopurinol and Epilepsy

Perinatal asphyxia is characterized by oxygen deprivation and lack of perfusion in the perinatal period, leading to hypoxic-ischemic encephalopathy and sequelae such as cerebral palsy, mental retardation, cerebral visual impairment, epilepsy and learning disabilities. On cellular level PA is associated with a decrease in oxygen and glucose leading to ATP depletion and a compromised mitochondrial function. Upon reoxygenation and reperfusion, the renewed availability of oxygen gives rise to not only restoration of cell function, but also to the activation of multiple detrimental biochemical pathways, leading to secondary energy failure and ultimately, cell death. The formation of reactive oxygen species, nitric oxide and peroxynitrite plays a central role in the development of subsequent neurological damage. In this review we give insight into the pathophysiology of perinatal asphyxia, discuss its clinical relevance and summarize current neuroprotective strategies related to therapeutic hypothermia, ischemic postconditioning and pharmacological interventions. The review will also focus on the possible neuroprotective actions and molecular mechanisms of the selective neuronal and inducible nitric oxide synthase inhibitor 2-iminobiotin that may represent a novel therapeutic agent for the treatment of hypoxic-ischemic encephalopathy, both in combination with therapeutic hypothermia in middle- and high-income countries, as well as stand-alone treatment in low-income countries.

Topics: Allopurinol; Asphyxia Neonatorum; Biotin; Cerebral Palsy; Clinical Trials as Topic; Epilepsy; Erythropoietin; Female; Humans; Hypothermia, Induced; Hypoxia-Ischemia, Brain; Infant, Newborn; Intellectual Disability; Ischemic Postconditioning; Melatonin; Neuroprotective Agents; Pregnancy; Reactive Nitrogen Species; Reactive Oxygen Species

The aim of this study is to investigate the effects of epilepsy, valproic acid and oxcarbazepine on nitric oxide levels, lipid peroxidation and xanthine oxidase levels in newly diagnosed epileptic children and healthy controls. A total of 49 patients with newly diagnosed idiopathic epilepsy and 15 healthy children were enrolled in this study. Of these 49 patients, 16 children were treated with valproate and 16 treated with oxcarbazepine. Nitric oxide, malondialdehyde and xanthine oxidase levels prior to antiepileptic drug therapy were measured in the serum. Blood samples were drawn before antiepileptic drug therapy and after 3 and 6 months of the antiepileptic drug treatment. Nitric oxide levels were statistically higher in the newly diagnosed epileptic patients. In oxcarbazepine group, the nitric oxide and malondialdehyde levels were found to be decreased. No statistically significant differences were noted in nitric oxide, malondialdehyde and xanthine oxidase levels in valproic acid treated group. Oxcarbazepine which is a frequently used new antiepileptic drug in childhood epilepsy may modify nitric oxide levels and lipid peroxidation. These results suggest that decreased lipid peroxidation would play a role in the mechanism of antiepileptic effects by oxcarbazepine treatment.

Topics: Anticonvulsants; Carbamazepine; Child; Child, Preschool; Epilepsy; Female; Humans; Lipid Peroxidation; Male; Nitric Oxide; Oxcarbazepine; Valproic Acid; Xanthine Oxidase

Adenosine has been proposed to be an endogenous anticonvulsant agent. It inhibits glutamate release from excitatory neurons and neuronal firing. Therefore, adenosine agonists have potential clinical application as antiepileptics. In this double-blind randomized, placebo-controlled trial, we assessed the antiepileptic effect of allopurinol as an adjuvant agent in 38 patients with refractory epilepsy.. Thirty eight patients were randomly allocated equally to allopurinol+preexisting antiepileptic (Group A) or placebo+preexisting antiepileptic (Group B) for a 6-month, double-blind, placebo-controlled study. The dose of allopurinol was titrated up to 300 mg/day (100 mg TDS). The dose of preexisting medications was maintained without change over the trial. The effect of allopurinol was evaluated by a reduction in the total number of seizures per month and duration of seizure attacks.. Of 38 participants, 32 patients completed the study. There were significant differences between the two groups in terms of reduction in the total number of seizure over the trial. Seizures reduction of >30% in 66%, >50% in 55%, and >60% in 44% of cases in the allopurinol group was achieved after 2 months and persisted during the study. Nevertheless, only during month 4 was there a significant difference between the two groups regarding reduction in seizure duration. In the allopurinol group, two patients had transient rashes, two patients had mild nausea, and two experienced dizziness, but only one patient discontinued the drug due to dizziness. In the placebo group, one patient had rash and one patient had nausea. In addition, no significant hematological or hepatic changes were found during the trial in both groups.. The results suggest allopurinol as a safe and effective adjuvant agent in refractory epilepsy. Based on this study, we suggest that purine metabolism pathways and the specific use of allopurinol should be further investigated with regards to neurobiology and treatment of refractory epilepsy.

Topics: Adenosine; Adolescent; Adult; Allopurinol; Anticonvulsants; Double-Blind Method; Drug Therapy, Combination; Enzyme Inhibitors; Epilepsy; Female; Humans; Male; Middle Aged; Placebos

Pentylenetetrazole (PTZ) is preferred for experimental epilepsy induction. PTZ damages brain and other organs by elevating oxidative substances. Vitamin U (Vit U) is sulfur derivative substance that proved to be an excellent antioxidant. The current study was intended to determine the protective role of Vit U on PTZ-induced brain damage. Male Sprague-Dawley rats were separated into four groups. The Control group (Group I), was given saline for 7 days intraperitoneally (i.p); Vit U (Group II) was given as 50 mg/kg/day for 7 days by gavage; PTZ was injected into animals (Group III) at a single dose of 60 mg/kg, by i.p; PTZ + Vit U group (Group IV) was administered PTZ and Vit U in same dose and time as aforementioned. After the experiment was terminated, brain tissues were taken for the preparation of homogenates. In the PTZ group, glutathione and lipid peroxidation levels, alkaline phosphatase, myeloperoxidase, xanthine oxidase, acetylcholine esterase, antioxidant enzyme activities, total oxidant status, oxidative stress index, reactive oxygen species, and nitric oxide levels were increased. However, total antioxidant capacity was decreased in the PTZ group. Vit U ameliorated these effects in the PTZ-induced brain damage. Consequently, we can suggest that Vit U protected brain tissue via its antioxidant feature against PTZ kindling epilepsy.

Topics: Alkaline Phosphatase; Animals; Antioxidants; Brain; Brain Injuries; Epilepsy; Glutathione; Male; Nitric Oxide; Oxidants; Oxidative Stress; Pentylenetetrazole; Peroxidase; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Sulfur; Vitamin U; Xanthine Oxidase

The goal of our study was to investigate the incidence of Stevens-Johnson syndrome (SJS), the frequency of SJS diagnosis, and the association between SJS and prior use of allopurinol, carbamazepine or phenytoin. This case-control study utilized data from the National Health Insurance Research Database (NHIRD) of Taiwan. Controls visited the emergency department of the same hospital for trauma or fractures (excluding burns) and used allopurinol, carbamazepine or phenytoin during the past 3 months. We determined whether patients were prescribed a combination of drugs in addition to allopurinol, carbamazepine or phenytoin within the last 3 months. We identified 1 853 985 controls and 7327 SJS-diagnosed patients using the Taiwan NHIRD records for 2000-2008. Higher use of allopurinol (49.8%), carbamazepine (39.1%) or phenytoin (21.3%) was observed among patients (n = 3131) than among controls (n = 2858). The overall SJS incidence rate was 3.6/1 000 000. Drug combinations were uncommon (<10%) in patients or controls taking allopurinol. However, combination drug use exceeded 10% in patients taking carbamazepine or phenytoin. Logistic regression analysis of recent combination drug use revealed that phenobarbital, valproate, non-steroidal anti-inflammatory drugs (NSAIDs) including piroxicam and tenoxicam, and antibiotics including amoxicillin and cephalexin were strongly associated with SJS. Patients with gout or epilepsy taking allopurinol, carbamazepine or phenytoin should be evaluated carefully by physicians. Concurrent use of piroxicam, tenoxicam, phenobarbital, valproate, amoxicillin or cephalexin, in addition to carbamazepine or phenytoin, may increase the incidence of SJS.

Topics: Adult; Aged; Allopurinol; Anticonvulsants; Carbamazepine; Case-Control Studies; Drug Combinations; Epilepsy; Female; Gout; Gout Suppressants; Humans; Incidence; Male; Middle Aged; Phenytoin; Stevens-Johnson Syndrome; Taiwan

Oxidative stress has been implicated in various disorders, including epilepsy. The aim of this study was to investigate the oxidant and antioxidant status of patients with epilepsy using antiepileptic drugs regularly and to compare them with healthy subjects. We investigated serum catalase (CAT), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and xanthine oxidase (XO) levels in 58 epilepsy patients and 25 healthy controls. Patients were divided into polytherapy (n = 17) and monotherapy (n = 41) groups, and antioxidant status was compared between the two groups and controls. There was no significant difference between the patient and control groups in terms of age or gender (p > 0.05). The mean duration of illness in the patients was 14.8 years, and the mean duration of treatment was 11.4 years. Comparison of the patient and control groups in terms of oxidative stress and antioxidant defence parameters revealed significantly higher MDA, GSH-Px, XO and lower level of CAT, SOD levels (p < 0.05). There were no differences in CAT, MDA, GSH-Px or SOD levels between the monotherapy and polytherapy groups; but the XO level was higher in the monotherapy group (p < 0.05). Although the XO level was decreased by polytherapy, it was higher than in controls. Our study found significantly low level of antioxidants in patients with epilepsy as compared to control. Thus, antiepileptic treatment did not improve oxidative stress parameters. Furthermore, our results show that polytherapy does not change the situation as compared with monotherapy. Antioxidant replacement therapy may benefit these patients.

Topics: Adult; Analysis of Variance; Anticonvulsants; Antioxidants; Case-Control Studies; Catalase; Epilepsy; Female; Glutathione Peroxidase; Humans; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Prospective Studies; Superoxide Dismutase; Xanthine Oxidase; Young Adult

Topics: Allopurinol; Antipsychotic Agents; Comorbidity; Drug Resistance; Electroconvulsive Therapy; Epilepsy; Hematoma, Subdural; Humans; Male; Middle Aged; Off-Label Use; Risk Factors; Schizophrenia; Time Factors

Topics: Aged; Allopurinol; Diagnosis, Differential; Drug Eruptions; Eosinophilia; Epilepsy; Gout Suppressants; Humans; Hyperuricemia; Male; Syndrome

Recent reports in clinical literature have suggested an antiepileptic effect of the xanthine oxidase inhibitor Allopurinol (ALL) when added to traditional drugs. However, other reports have failed to confirm beneficial effects of this drug. In view of these conflicting results, we have carried out a study aimed at evaluate the effects of ALL in different forms of epilepsy. The result that ALL possesses some antiepileptic effects in Lennox-Gastaut syndromes, characterized by numerous and severe fits, while it is scarcely effective in other forms of epilepsy, suggests that ALL might be involved in the purinergic-mediated inhibition similar to that described in experimental "status epilepticus" studies in animal models.

Topics: Allopurinol; Anticonvulsants; Epilepsy; Female; Humans; Male

We have studied 64 epileptic subjects aged 2-54 years. The subjects were not hyperuricemic and presented daily or weekly severe seizures not controlled by optimal therapy with antiepileptic drugs maintained at 'therapeutic' plasma concentrations. Allopurinol at doses ranging from 150 to 300 mg daily was added to a preexisting antiepileptic drug treatment which was never modified throughout a study period of 1 year. After about 1 month of therapy, a progressive decrease of the seizure frequency was observed in two thirds of the patients. At the end of follow-up, seizures; were completely controlled in 18.75% of the patients; in 34.37% seizure frequency was reduced by more than 75%; in 15.62% of the subjects, a reduction of the seizure frequency superior to 50% was observed, while 25% of the population studied was unaffected by the treatment and 7.81% worsened.

Topics: Adolescent; Adult; Allopurinol; Anticonvulsants; Child; Child, Preschool; Drug Therapy, Combination; Electroencephalography; Epilepsy; Evoked Potentials; Female; Follow-Up Studies; Humans; Male; Middle Aged

Allopurinol was tested as an antiepileptic drug (AED) in children with progressive history of the disease, frequent severe seizures and ineffective conventional AED treatment. A total of 38 children aged 4 months to 10 years were given allopurinol at daily doses of 4 to 5 mg/kg body weight. The drug had positive effects in 10 out of 28 patients having frequent seizures. Complications were not observed. Allopurinol increased serotonin content in platelets. Biochemical investigations proved the therapy with allopurinol alone or combined with other AEDs to be effective.

Topics: Allopurinol; Anticonvulsants; Blood Platelets; Child; Child, Preschool; Drug Evaluation; Drug Therapy, Combination; Epilepsy; Humans; Infant; Male; Serotonin; Time Factors

Topics: Administration, Oral; Adolescent; Adult; Allopurinol; Child; Child, Preschool; Drug Evaluation; Epilepsy; Humans; Infant; Quinolinic Acids; Xanthine Oxidase

Topics: Allopurinol; Epilepsy; Humans

Forty-one epileptic and not hyperuricemic subjects, aged 2 to 54 years, had epileptic seizures, ranging from 1 to 220 weekly (mean = 21.3). All seizure types were represented. They were already medicated with two or three antiepileptic drugs with plasma drug concentrations maintained in therapeutic range. They were treated with allopurinol in doses ranging from 150 to 300 mg daily. After 20 to 35 days of this regimen, a progressive decrease of the weekly seizure frequency was observed in two-thirds of the cases. After a follow-up of 3 to 9 months, seizures disappeared completely (22%) or decreased more than 50% (47%). Twenty-five percent of subjects continued to have the same seizure frequency, while about 6% were worse than before.

Topics: Adolescent; Adult; Allopurinol; Child; Child, Preschool; Epilepsy; Female; Humans; Male; Middle Aged