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)

N-Methyl-D-aspartate (NMDA) receptors, members of the glutamate receptor channel superfamily, are generally inhibited by alcohol. The expression and alternative splicing of the obligatory NR1 subunit is altered by alcohol exposure, emphasizing the involvement of the NR1 subunit, which is coded by the GRIN1 gene, in alcohol-mediated effects. We performed an association study in patients with alcohol dependence with the GRIN1 locus. Two independent case control samples consisting of a total of 442 alcohol-dependent patients and 442 unrelated controls were included. There was no overall difference in allele or genotype frequency between patients and controls. However, the 2108A allele and A-containing genotypes were over-represented in the patients with a history of withdrawal-induced seizures when compared to healthy volunteers (allele: chi(2) = 5.412, df = 1, P = 0.020) or an independent sample of patients without a history of seizures (allele: chi(2) = 4.185, df = 1, P = 0.041). Age at onset, years of alcohol dependence, and a history of delirium tremens did not differ between genotype or allele groups. These findings support the hypothesis that the GRIN1 locus may modify the susceptibility to seizures during alcohol withdrawal. This novel finding warrants replication.
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PMID:GRIN1 locus may modify the susceptibility to seizures during alcohol withdrawal. 1563 50

Heavy drinkers who suddenly decrease their alcohol consumption or abstain completely may experience alcohol withdrawal (AW). Signs and symptoms of AW can include, among others, mild to moderate tremors, irritability, anxiety, or agitation. The most severe manifestations of withdrawal include delirium tremens, hallucinations, and seizures. These manifestations result from alcohol-induced imbalances in the brain chemistry that cause excessive neuronal activity if the alcohol is withheld. Management of AW includes thorough assessment of the severity of the patient's symptoms and of any complicating conditions as well as treatment of the withdrawal symptoms with pharmacological and nonpharmacological approaches. Treatment can occur in both inpatient and outpatient settings. Recognition and treatment of withdrawal can represent a first step in the patient's recovery process.
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PMID:Introduction to alcohol withdrawal. 1570 27

Appropriate treatment of alcohol withdrawal (AW) can relieve the patient's discomfort, prevent the development of more serious symptoms, and forestall cumulative effects that might worsen future withdrawals. Hospital admission provides the safest setting for the treatment of AW, although many patients with mild to moderate symptoms can be treated successfully on an outpatient basis. Severe AW requires pharmacological intervention. Although a wide variety of medications have been used for this purpose, clinicians disagree on the optimum medications and prescribing schedules. The treatment of specific withdrawal complications such as delirium tremens and seizures presents special problems and requires further research.
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PMID:Treatment of alcohol withdrawal. 1570 31

Disease processes or events that accompany acute alcohol withdrawal (AW) can cause significant illness and death. Some patients experience seizures, which may increase in severity with subsequent AW episodes. Another potential AW complication is delirium tremens, characterized by hallucinations, mental confusion, and disorientation. Cognitive impairment and delirium may lead to a chronic memory disorder (i.e., Wernicke-Korsakoff syndrome). Psychiatric problems associated with withdrawal include anxiety, depression, and sleep disturbance. In addition, alterations in physiology, mood, and behavior may persist after acute withdrawal has subsided, motivating relapse to heavy drinking. Recent advances in neurobiology may support the development of improved medications to decrease the risk of AW complications and support long-term sobriety.
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PMID:Complications of alcohol withdrawal: pathophysiological insights. 1570 35

Drug- and toxin-associated seizures may result from exposure to a wide variety of agents. Obtaining a comprehensive history behind the exposure is generally more helpful than diagnostic testing. Most DTS may be managed with supportive care, including benzodiazepines, except in the case of agents that require a specific intervention or antidote.
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PMID:Drug- and toxin-associated seizures. 1622 64

As the enzyme dopamine-beta-hydroxylase (DbetaH) converts dopamine to norepinephrine and both transmitters seem to be involved in the pathology of alcoholism and severe alcohol withdrawal symptoms, the gene encoding DbetaH (DBH) was applied to explore the genetic background of alcoholism and severe withdrawal symptoms. 102 healthy control subjects and 208 alcoholics, including 97 patients with a history of mild withdrawal symptoms, 57 with a history of alcohol withdrawal seizure (AWS) and 82 with a history of delirium tremens (DT) were genotyped for the DBH*444G/A polymorphism revealing a significantly elevated frequency of genotypes carrying the A-allele (p = 0.02; after Bonferroni adjustment for multiple tests) in alcoholics compared to healthy controls. Frequencies of alleles and genotypes of individuals with mild withdrawal symptoms did not differ significantly from those of patients with DT or AWS.
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PMID:DBH*444G/A polymorphism of the dopamine-beta-hydroxylase gene is associated with alcoholism but not with severe alcohol withdrawal symptoms. 1625 68

Upregulation of glutamatergic neurotransmission resulting from chronic ethanol intoxication may cause a hyperexcitable state during alcohol withdrawal, which may lead to seizures and delirium tremens. The aim of our study was to evaluate the association between a history of alcohol withdrawal-induced seizures and delirium tremens, and a functional polymorphism (Ser310Ala) of the GRIK3 gene coding for the glutamatergic kainate receptor subunit GlurR7 in a sample of well-characterized alcoholics compared to controls. In total, 233 patients meeting DSM-IV alcohol dependence criteria and 309 controls, all of German descent, were investigated. GRIK3 functional polymorphism was determined using PCR (polymerase chain reaction) of lymphocyte DNA. History of alcohol withdrawal-induced delirium tremens and seizures were obtained using the SSAGA (Semi-Structured Assessment for the Genetics of Alcoholism). Data were cross-checked with in-patients' clinical files. While a significant relationship between history of delirium tremens and the Ser310 allele was detected, no significant results were obtained for alcohol withdrawal-related seizures. Although this result is suggestive for a significant role of this polymorphism in the pathogenesis of delirium tremens in alcohol-dependent individuals, further investigation and confirmation are warranted.
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PMID:Ionotropic glutamate receptor gene GRIK3 SER310ALA functional polymorphism is related to delirium tremens in alcoholics. 1631 83

The aim of this study was to evaluate the role of the GRIK3 functional polymorphism (Ser310Ala) in the pathogenesis of alcoholism. This polymorphism was investigated in two types of studies: (1) the association study in a whole group of alcoholics (116 patients fulfilling ICD-10 alcohol dependence (AD) criteria and 255 controls, Polish descent) and homogenous overlapping subgroups of patients with: a history of delirium tremens and/or alcohol seizures, early age of onset of alcoholism (AOO<26 years), a co-occurrence of dissocial personality disorder, a history of familial alcoholism; (2) the family-based study (using Transmission Disequilibrium Test (TDT) in 100 Polish families with alcohol dependence). The history of alcoholism was obtained using SSAGA (Polish version). GRIK3 functional polymorphism was determined using PCR. TDT revealed an adequate transmission of both alleles to the affected offspring in the whole group of alcohol families (29 x Ser, 24 x Ala; chi2=0.472; d.f.=1; p=0.492) and in the homogenous subgroups of families. No significant associations between any of the above mentioned alcohol phenotypes and Ser310 allele were observed (the whole AD group: p=0.66 AD with delirium and/or seizures: p=0.521; early onset AD: p=0.868; AD with familial history of alcoholism: p=0.798 and AD with dissocial personality disorder: p=0.618). These findings do not seem to support the hypothesis of the role of this polymorphism in the pathogenesis of alcoholism.
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PMID:Family-based and case-control association studies of glutamate receptor GRIK3 Ser310Ala polymorphism in Polish patients and families with alcohol dependence. 1635 44

This was a retrospective study to examine the efficacy, practicability and medical safety of a combination of tiapride and unretarded (fast acting formula) carbamazepine in the treatment of alcohol withdrawal syndrome. In five hospitals using this combination for treatment of alcohol withdrawal, 540 patients who had been treated with this combination were identified. An intensive evaluation of patients files and charts was performed. Details of alcohol history and comorbid disorders were extracted from patient files. Severity of alcohol withdrawal had been assessed using the CIWA-A-Score. Gender differences and differences between patients in their first and at least second withdrawal were computed by means of variance analyses (GLM). At baseline (day 1) mean dosage given was 796 for tiapride and 543 mg for carbamazepine. A pooled analysis of the results showed that, in general, medication was well tolerated. Withdrawal symptomatology as indicated by CIWA-A scores clearly decreased over time. Although a significant number of patients had a history of alcohol withdrawal delirium (103) and epileptic seizures (151), few patients suffered from them during treatment (8 and 5, respectively). Only 24 (4.4%) patients dropped out because of lack of efficacy or change of medication, 15 (2.8%) because of side effects. No case of malignant neuroleptic syndrome was recorded. Data analysis showed gender differences and differences between patients in their first and at least second withdrawal for side effects, complications, and in some CIWA-A-scores. In general, severe complications of withdrawal syndrome were more frequent in men compared to women and in patients with repeated inpatient treatment. In line with previous research, the results from this study give further evidence that a combination of the anticonvulsant carbamazepine and tiapride is an effective and safe treatment for alcohol withdrawal treatment.
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PMID:Treatment of alcohol withdrawal syndrome with a combination of tiapride/carbamazepine: results of a pooled analysis in 540 patients. 1691 85

Gamma-aminobutyric acid (GABA) A receptors are believed to mediate some of the physiological and behavioral actions of ethanol. Recent studies have suggested that genetic variants of the GABA-A receptor alpha2 subunit gene (GABRA2) are associated with alcohol dependence. The aim of this study is to confirm and extend the role of GABRA2 haplotypes in the liability to alcohol dependence. 291 (231 male) treatment-seeking alcohol-dependent individuals and 295 (153 male) control subjects were enrolled into the study. Characteristics of alcohol dependence were obtained using the SSAGA (semi-structured assessment of the genetics of alcoholism, German Version). Genotyping of 10 SNPs across the GABRA2 gene was performed following previous reports and using PCR. One genetic variant was detected to significantly differ between alcohol-dependent subjects and controls. Two common 8 SNP haplotypes and their complementary alleles were identified containing this SNP and were present in 89.9% of controls and 93.4% of the alcohol-dependent individuals. One of the haplotypes (T-C-A-C-A-T-T-C) was significantly associated with alcohol dependence and characteristics of alcohol withdrawal and severity of alcohol dependence (delirium tremens, withdrawal seizures). These findings support and extend the three previous studies implicating a GABA-A receptor subunit as contributing to the genetic risk for alcohol dependence. Possible implications of these findings are discussed.
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PMID:GABA-A2 receptor subunit gene (GABRA2) polymorphisms and risk for alcohol dependence. 1720 17


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