allopurinol and Seizures

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are mucocutaneous hypersensitivity reactions, usually to drugs or their metabolites. TEN is the most severe involving greater than 30% of the total body surface area (TBSA). Management of these patients usually benefits from a large multidisciplinary team for both wound and medical management. Treatment of these patients varies between centers and physicians and there is lack of a standardized treatment protocol in the medical literature.. To review the literature and complete a retrospective review of patients treated at Vancouver General Hospital over a 11-year period.. A retrospective chart review of all patients diagnosed with SJS/TEN and treated at Vancouver General Hospital from 2001 to 2011 was completed. Data collected include patient demographics, time to transfer to a burn center, SCORTEN calculation, suspected cause of TEN, %TBSA involved, length of stay in hospital and ICU, medications, dressings, infections/cultures, fluids, mucosal involvement, teams involved, associated complications, morbidity and mortality. Data is reported quantitatively.. A total of 67 patients were identified (28 SJS, 21 SJS/TEN overlap, 18 TEN). In SJS/TEN overlap and TEN patients, oral mucosa and trunk were the primary sites involved. SCORTEN calculations were highest in the TEN group. Plastic surgery was consulted in 53% of TEN cases, 52% of SJS/TEN cases and 25% of SJS cases. Patients were admitted to a burn unit in 74% of TEN cases, 57% of TEN/SJS cases and 21% of SJS cases. Time from symptoms to diagnosis and transfer to a burn unit was highest for TEN patients. Time from presentation to diagnosis was highest in SJS/TEN overlap. Triggers were identified in 67-82% of cases. Treatment varied widely. Patients were treated conservatively, with steroids, IVIg, and cyclosporine alone or in combination. Observed mortality was higher than predicted by SCORTEN for patients treated with IVIg and lower for those treated with Cyclosporin. Dressings varied greatly and were often changed throughout a patients stay. Total mortality was 20.9% being the highest in the TEN group (35%).. SJS and TEN are a spectrum of severe mucocutaneous reactions that have unclear treatment recommendations within the literature and within our Level 1 hospital. Information gleaned from this research will help educate physicians involved in the treatment and management of patients with these diagnoses and has resulted in development of treatment guidelines in our hospital.

Topics: Adrenal Cortex Hormones; Allopurinol; Anti-Bacterial Agents; Anticonvulsants; Bandages; British Columbia; Comorbidity; Cyclosporine; Dermatologic Agents; Dermatology; Diabetes Mellitus; Dietetics; Disease Management; Female; Gout; Gout Suppressants; Humans; Immunocompromised Host; Immunoglobulins, Intravenous; Immunologic Factors; Intensive Care Units; Length of Stay; Male; Middle Aged; Mouth Mucosa; Neoplasms; Patient Care Team; Retrospective Studies; Seizures; Stevens-Johnson Syndrome; Surgery, Plastic; Torso

Topics: Adenylosuccinate Lyase; Allopurinol; Humans; Lesch-Nyhan Syndrome; Psychomotor Disorders; Purine-Pyrimidine Metabolism, Inborn Errors; Seizures; Self Mutilation

Hereditary xanthinuria is a rare autosomal recessive disorder, with xanthine oxidase deficiency. Patients often display renal symptoms because they excrete a large amounts of xanthine in urine. An high-fluid-intake, alow-purine-food, and alkalinization of urine are effective in the patients. Molybdenum cofactor is essential for xanthine oxidase, sulfite oxidase and aldehyde oxidase. Patients with molybdenum cofactor deficiency display severe neurological symptoms, such as severe convulsions. The patients increase urinary excretions of xanthine and sulfite. Treatments are ineffective for neurological symptoms.

Topics: Central Nervous System Diseases; Coenzymes; Diagnosis, Differential; Diet Therapy; Humans; Infant, Newborn; Metalloproteins; Molybdenum Cofactors; Pteridines; Purine-Pyrimidine Metabolism, Inborn Errors; Seizures; Uric Acid; Xanthine; Xanthine Oxidase; Xanthines

This pharmacologic protection trial was conducted to test the hypothesis that allopurinol, a scavenger and inhibitor of oxygen free radical production, could reduce death, seizures, coma, and cardiac events in infants who underwent heart surgery using deep hypothermic circulatory arrest (DHCA).. This was a single center, randomized, placebo-controlled, blinded trial of allopurinol in infant heart surgery using DHCA. Enrolled infants were stratified as having hypoplastic left heart syndrome (HLHS) and all other forms of congenital heart disease (non-HLHS). Drug was administered before, during, and after surgery. Adverse events and the clinical efficacy endpoints death, seizures, coma, and cardiac events were monitored until infants were discharged from the intensive care unit or 6 weeks, whichever came first.. Between July 1992 and September 1997, 350 infants were enrolled and 348 subsequently randomized. A total of 318 infants (131 HLHS and 187 non-HLHS) underwent heart surgery using DHCA. There was a nonsignificant treatment effect for the primary efficacy endpoint analysis (death, seizures, and coma), which was consistent over the 2 strata. The addition of cardiac events to the primary endpoint resulted in a lack of consistency of treatment effect over strata, with the allopurinol treatment group experiencing fewer events (38% vs 60%) in the entire HLHS stratum, compared with the non-HLHS stratum (30% vs 27%). In HLHS surgical survivors, 40 of 47 (85%) allopurinol-treated infants did not experience any endpoint event, compared with 27 of 49 (55%) controls. There were fewer seizures-only and cardiac-only events in the allopurinol versus placebo groups. Allopurinol did not reduce efficacy endpoint events in non-HLHS infants. Treated and control infants did not differ in adverse events.. Allopurinol provided significant neurocardiac protection in higher-risk HLHS infants who underwent cardiac surgery using DHCA. No benefits were demonstrated in lower risk, non-HLHS infants, and no significant adverse events were associated with allopurinol treatment.congenital heart defects, hypoplastic left heart syndrome, induced hypothermia, ischemia-reperfusion injury, neuroprotective agents, allopurinol, xanthine oxidase, free radicals, seizures, coma.

Topics: Allopurinol; Cardiac Surgical Procedures; Coma; Death, Sudden, Cardiac; Female; Free Radical Scavengers; Heart Arrest, Induced; Heart Defects, Congenital; Humans; Hypothermia, Induced; Infant; Male; Neuroprotective Agents; Oxygen; Seizures; Single-Blind Method; Treatment Outcome; Uric Acid; Xanthine Oxidase

During status epilepticus, severe seizures can occur, generating recurrent cycles of excitotoxicity and oxidative stress that cause neuronal damage and cell death. The administration of agents with antioxidant properties represents a therapeutic alternative aimed at reducing the severity of status epilepticus and mitigating the neurobiological consequences that precede them.. The objective of this work was to evaluate the antiseizure effect of the antioxidants allopurinol (ALL) and ellagic acid during status epilepticus induced by pilocarpine (PILO).. Male Wistar rats (200-250 g) were injected with ALL (50 mg/kg) or ellagic acid (50 mg/kg), 30 min before PILO administration (pretreatment) or 60 min after the beginning of status epilepticus, to evaluate the antiseizure effect of these drugs on epileptiform activity and convulsive behavior.. ALL or ellagic acid administration before or after PILO significantly decreased the epileptiform activity and the severity of convulsive behavior. Better efficacy was observed when the drugs were administered as a pretreatment, increasing the latency time of the appearance of status epilepticus from 27.2 ± 2.6 to 45.8 ± 3.31 min, and significantly reducing the amplitude of epileptiform discharges by 53.5% with ALL and 68.9% with ellagic acid.. The antioxidants ALL and ellagic acid showed an antiseizure effect, representing an alternative to reduce epileptiform activity and severity of convulsive behavior during status epilepticus, an effect that may be used as adjuvants to mitigate or reduce oxidative damage processes.

Topics: Allopurinol; Animals; Antioxidants; Ellagic Acid; Male; Pilocarpine; Rats; Rats, Wistar; Seizures; Status Epilepticus

Allopurinol, a uric-acid-lowering medication, has shown its efficacy in several studies suggesting that allopurinol can be prescribed as adjunctive cure meant for intractable epilepsy. The exact mechanism of allopurinol is still unknown. This study evaluates allopurinol's effect on seizure threshold, seizure incidence, and mortality rate in mice models. Moreover, the possible involvement of nitric oxide (NO) pathway and N-methyl-D-aspartate (NMDA) receptors are investigated. To evaluate the effect of allopurinol on seizure, we used the pentylenetetrazole (PTZ)-induced seizure along with maximal electroshock (MES)-induced seizure. To assess the underlying mechanism behind the allopurinol activity, we used nitric oxide synthase (NOS) substrate (L-arginine), NOS inhibitors (L-NAME, aminoguanidine, 7-nitroindazole), and NMDA receptor antagonist (MK-801). Intraperitoneal allopurinol administration at a dose of 50 mg/kg in mice showed a significant (p < 0.001) anti-convulsant activity in the PTZ-induced seizure. Even though pre-treatment with L-Arginine (60 mg/kg) potentiates allopurinol's anti-convulsant effect in the PTZ-induced seizure, pre-treatment with L-NAME (10 mg/kg), aminoguanidine (100 mg/kg), and 7-nitroindazole (30 mg/kg) reversed the anti-convulsant effect of allopurinol in the PTZ-induced seizure. In addition, pre-treatment with MK-801 also decreased the anti-convulsant effect of allopurinol in the PTZ-induced seizure. While allopurinol at a dose of 50 mg/kg and 100 mg/kg did not induce protection against seizure incidence in the MES-induced seizure, it revealed a remarkable effect in reducing the mortality rate in the MES-induced seizure. Allopurinol increases the seizure threshold in PTZ-induced seizure and enhances the survival rate in MES-induced seizure. Allopurinol exerts its anti-convulsant effect, possibly through targeting NO pathway and NMDA receptors.

Topics: Allopurinol; Animals; Anticonvulsants; Arginine; Convulsants; Dizocilpine Maleate; Electroshock; Enzyme Inhibitors; Mice; NG-Nitroarginine Methyl Ester; Nitric Oxide; Pentylenetetrazole; Receptors, N-Methyl-D-Aspartate; Seizures

We report on a male patient with Tuberous Sclerosis Complex (TSC), which was prenatally diagnosed. At the age of 3 months the patient developed acute renal failure with excessive hyperuricemia. Kidney function improved after rehydration and application of rasburicase, however without full recovery. Due to the inappropriate high levels of uric acid compared to kidney function, screening of hypoxanthine-guanine phosphoribosyltransferase (HPRT) related diseases was initiated. Mutation analysis revealed a deletion of exon 2 and 3 of the HPRT gene confirming the diagnosis of Lesch-Nyhan Disease (LND). After initiation of allopurinol therapy renal function further improved. In the following months the patient developed clinically a typical neurological phenotype of LND and TSC with seizures, severe dystonia and developmental delay.. Acute renal failure is a rare complication of HPRT related diseases. Combination of two inherited diseases may lead to a delayed diagnosis due to a mixed and maybe misleading phenotype.

Topics: Acute Kidney Injury; Allopurinol; Developmental Disabilities; Dystonia; Exons; Fluid Therapy; Gout Suppressants; Humans; Hyperuricemia; Hypoxanthine Phosphoribosyltransferase; Infant; Lesch-Nyhan Syndrome; Male; Phenotype; Seizures; Tuberous Sclerosis; Urate Oxidase

Seizure activity has been proposed to result in the generation of reactive oxygen species (ROS), which then contribute to seizure-induced neuronal damage and eventually cell death. Although the mechanisms of seizure-induced ROS generation are unclear, mitochondria and cellular calcium overload have been proposed to have a crucial role. We aim to determine the sources of seizure-induced ROS and their contribution to seizure-induced cell death. Using live cell imaging techniques in glioneuronal cultures, we show that prolonged seizure-like activity increases ROS production in an NMDA receptor-dependent manner. Unexpectedly, however, mitochondria did not contribute to ROS production during seizure-like activity. ROS were generated primarily by NADPH oxidase and later by xanthine oxidase (XO) activity in a calcium-independent manner. This calcium-independent neuronal ROS production was accompanied by an increase in intracellular [Na(+)] through NMDA receptor activation. Inhibition of NADPH or XO markedly reduced seizure-like activity-induced neuronal apoptosis. These findings demonstrate a critical role for ROS in seizure-induced neuronal cell death and identify novel therapeutic targets.

Topics: Animals; Apoptosis; Calcium; Humans; Mitochondria; NADP; NADPH Oxidases; Neurons; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Receptors, N-Methyl-D-Aspartate; Seizures; Sodium; Xanthine Oxidase

Topics: Adult; Allopurinol; Electroconvulsive Therapy; Gout Suppressants; Humans; Hyperuricemia; Male; Schizophrenia; Seizures

The role of oxygen-derived free radicals has been suggested in genesis of epilepsy and in the post seizure neuronal death. The aim of this study was to investigate whether erdosteine has a preventive effect against epilepsy and postepileptic oxidative stress. The mice (n=27) were divided into three groups: (i) PTZ-induced-epilepsy group (n=9); (ii) PTZ-induced-epilepsy+erdosteine group (n=9); (iii) control group (n=9). The animals were observed for a period of 30 min for latency to first seizure onset, total seizure duration, the number of seizure episodes. Then they were sacrificed and the brains were quickly removed, and frozen for biochemical analysis. Malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD) and xanthine oxidase (XO) activities were carried out in the brain tissue. The latent period between PTZ induction and seizure are longer in the PTZ+erdosteine group than in PTZ-induced-epilepsy group (P<0.05). Biochemical analyses of brain tissue, revealed a significant increase in the MDA, XO and NO levels in the PTZ group according to erdosteine group. SOD level did not change in this group. While MDA and XO levels are significantly lower, SOD level is significantly higher in the PTZ+erdosteine group compared to PTZ and control groups (P<0.01). The present study demonstrated that erdosteine treatment both may increase latent interval between seizures and may decrease oxidative stress, thus may ameliorate neuronal death in brain during seizures. It may be used as an adjunct therapy in epilepsy.

Topics: Animals; Anticonvulsants; Brain Chemistry; Cerebral Cortex; Convulsants; Disease Models, Animal; Drug Interactions; Female; Malondialdehyde; Mice; Nitric Oxide; Oxidative Stress; Pentylenetetrazole; Reaction Time; Seizures; Superoxide Dismutase; Thioglycolates; Thiophenes; Xanthine Oxidase

Nigella sativa oil (NSO), a herbaceous plant, has been used for thousands of years for culinary and medical purposes. This study aimed to investigate the anticonvulsant and antioxidant activities of NSO on pentylenetetrazol (PTZ) kindling seizures in mice. Nigella sativa oil was tested for its ability (i) to suppress the convulsive and lethal effects of PTZ in kindled mice (anti-epileptogenic effect), (ii) to attenuate the PTZ-induced oxidative injury in the brain tissue (antioxidant effect) when given as a pretreatment prior to each PTZ injection during kindling acquisition. Valproate, a major antiepileptic drug, was also tested for comparison. Both substances studied significantly decreased oxidative injury in the mouse brain tissue in comparison with the PTZ-kindling group. Nigella sativa oil was found to be the most effective in preventing PTZ-induced seizures relative to valproate. Nigella sativa oil showed anti-epileptogenic properties as it reduced the sensitivity of kindled mice to the convulsive and lethal effects of PTZ; valproate was ineffective in preventing development of any of these effects. The data obtained support the hypothesis that neuroprotective action of NSO may correlate with its ability to inhibit not only excessive reactive oxygen species (ROS) formation but also seizure generation.

Topics: Adenosine Deaminase; Analysis of Variance; Animals; Anticonvulsants; Antioxidants; Dose-Response Relationship, Drug; Drug Interactions; Glutathione Peroxidase; Kindling, Neurologic; Male; Malondialdehyde; Mice; Nitric Oxide; Pentylenetetrazole; Plant Oils; Seizures; Time Factors; Valproic Acid; Xanthine Oxidase

Topics: Adenosine; Allopurinol; Cardioplegic Solutions; Electroconvulsive Therapy; Europe; Glutathione; History, 20th Century; Humans; Insulin; Netherlands; Organ Preservation Solutions; Periodicals as Topic; Psychiatry; Raffinose; Seizures; Treatment Failure; United States

Since overexcitation of excitatory amino acid is an important mechanism in seizure genesis wherein free radicals have recently been suggested to play a critical role, we explored the effects of caffeic acid phenethyl ester (CAPE) administration in pentylenetetrazole (PTZ)-induced seizure in mice. CAPE prevents the oxidative damage in brain tissue induced by PTZ, scavenging reactive oxygen species (ROS). Our results demonstrate that CAPE treatment which prevents free radical production and ameliorates seizure severity may be useful at least as an adjunctive treatment of seizure disorders.

Topics: Animals; Antioxidants; Biomarkers; Caffeic Acids; Central Nervous System; Convulsants; Female; Malondialdehyde; Mice; Nerve Tissue Proteins; Neuroprotective Agents; Nitric Oxide; Oxidants; Oxidative Stress; Pentylenetetrazole; Phenylethyl Alcohol; Reactive Oxygen Species; Seizures; Superoxide Dismutase; Xanthine Oxidase

The effect of piperonyl butoxide or allopurinol on cyanide-induced lipid peroxidation was investigated using homogenates from whole brain of mice. The brain homogenate exposed to a low concentration of potassium cyanide (10, 50, or 100 microM) was significantly increased in their concentration of malondialdehyde (MDA) + 4-hydroxyalkenals (4-MDA) as compared to control samples, in a concentration-dependent manner. The increased lipid peroxidation induced by cyanide was inhibited by piperonyl butoxide (1 mM), an inhibitor of mixed function oxidase, but not by allopurinol (0.1 mM), an inhibitor of xanthine oxidase. Furthermore, when a brain homogenate heated at 86 degrees C for 1 min was incubated with or without cyanide at 37 degrees C for 20 min, MDA + 4-MDA levels in the homogenate were not changed between cyanide treatment and untreated. An intraperitoneal injection of piperonyl butoxide (1 g/kg) significantly inhibited cyanide-induced seizures in mice. These results suggest that cyanide-induced seizures may be partly involved in the lipid peroxidation produced by the heat unstable and piperonyl butoxide dependent factors in brain.

Topics: Allopurinol; Animals; Brain; Brain Chemistry; Dose-Response Relationship, Drug; Edetic Acid; Enzyme Inhibitors; Lipid Peroxidation; Male; Malondialdehyde; Mice; Mixed Function Oxygenases; Piperonyl Butoxide; Potassium Cyanide; Seizures; Xanthine Oxidase

We have investigated the potential antiepileptic action of superoxide dismutase (SOD) activities in the brain of the epileptic mutant EL mouse. EL mice which experienced frequent seizures (EL[s]) had abnormally low levels of SOD isoenzyme activity in the hippocampal area. Once epileptogenicity was established in these animals, activity of cyanide-sensitive Cu,Zn-SOD was maintained at significantly lower levels than in control mice. However, cyanide-insensitive Mn-SOD activity was not different from non-epileptic controls. In EL mice which had not experienced seizure provoking stimulations and exhibited no seizures (EL[ns]) there was moderately lower levels of SOD isoenzyme activities compared to controls. In spite of the low level of Cu,Zn-SOD activity in EL[s] mice, the Cu,Zn-SOD protein content was high in the hippocampus of these animals, suggesting that inactive Cu,Zn-SOD might be induced during development. After allopurinol (ALP) was given orally to EL[s] mice, Cu,Zn-SOD activities increased dramatically in the hippocampus and seizure activity was decreased. Even after 48 h, when antiepileptic action of ALP was lost, the SOD activity was maintained at the high level associated with initial ALP administration. EL[s] mice also showed DNA fragmentation in the hippocampal CA1 region and the parietal cortex, detected with in situ terminal transferase-mediated dUTP nick labeling with the aid of alkaliphosphatase or peroxidase. The degree of DNA fragmentation was less severe in EL[ns] mice. We propose that abnormalities in region specific Cu,Zn-SOD isoenzyme activity might produce free radicals, leading to DNA fragmentations and cell loss. This might contribute to hippocampal epileptogenesis in EL mice.

Topics: Allopurinol; Animals; Anticonvulsants; Brain; DNA Fragmentation; Enzyme Inhibitors; Hippocampus; Isoenzymes; Mice; Mice, Neurologic Mutants; Organ Specificity; Parietal Lobe; Seizures; Superoxide Dismutase; Time Factors

Topics: Adult; Allopurinol; Anticonvulsants; Humans; Male; Seizures; Status Epilepticus; Substance Withdrawal Syndrome

Experiments on 73 rats with electrochemotrodes implanted into the dorsal portion of the left hippocamp showed that allopurinol (A) injected intraperitoneally in a dose of 25 and 50 mg/kg decreased the activity of the penicillin-induced epileptogenic foci in the hippocamp and significantly increased the content of serotonin (S) in their area at the 40th minute of the epileptogenesis. Thus, all this provided evidence in favour of a shift in tryptophan metabolism toward an elevated S production that inhibited the development of the epileptic process. A is suggested for clinical use in treating patients with epilepsy, especially in those cases that are resistant to common therapy.

Topics: Allopurinol; Animals; Hippocampus; Hydroxyindoleacetic Acid; Male; Penicillins; Rats; Seizures; Serotonin

A 17-year-old boy with partial hypoxanthine-guanine phosphoribosyl transferase deficiency developed a hypersensitivity reaction to allopurinol. The reaction was manifested by the development of bizarre, atypical seizures. The patient had been neurologically normal prior to the reaction. Seizures disappeared following discontinuation of allopurinol therapy. Allopurinol apparently can cause a diffuse vasculitis involving cerebral vessels after many year of therapy, resulting in atypical seizures.

Topics: Adolescent; Allopurinol; Arteritis; Cerebral Arterial Diseases; Drug Hypersensitivity; Humans; Hypoxanthine Phosphoribosyltransferase; Male; Seizures

Topics: Allopurinol; Anticonvulsants; Child; Child, Preschool; Electroencephalography; Humans; Infant; Intellectual Disability; Male; Neurologic Manifestations; Purine-Pyrimidine Metabolism, Inborn Errors; Seizures; Uric Acid

Topics: Allopurinol; Brain Damage, Chronic; Child; Electroencephalography; Humans; Male; Purine-Pyrimidine Metabolism, Inborn Errors; Seizures; Uric Acid