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)

(1) When people who are physically dependent on alcohol stop drinking, they experience an alcohol withdrawal syndrome. The symptoms generally resolve spontaneously within a week, but more severe forms may be associated with generalised seizures, hallucinations and delirium tremens, which can be fatal. (2) We carried out a literature review in order to obtain answers to the following questions: how to predict or rapidly diagnose a severe alcohol withdrawal syndrome; how to prevent and treat this syndrome; how to manage severe forms; and how to deal with the risk of vitamin B1 deficiency. (3) The main risk factors for severe withdrawal syndrome are: chronic heavy drinking; a history of generalised seizures; and a history of delirium tremens. (4) Anxiety, agitation, tremor, excessive sweating, altered consciousness and hallucinations are signs of a severe withdrawal syndrome. (5) Individual support and effective communication seem to reduce the risk of severe withdrawal syndrome. (6) Oral benzodiazepines are the best-assessed drugs for preventing a severe alcohol withdrawal syndrome, particularly the risk of seizures. When given for a maximum of 7 days, the adverse effects are usually mild. (7) Clinical trials of other antiepileptics suggest they are less effective than benzodiazepines, and their addition to benzodiazepine therapy offers no tangible advantage. (8) Betablockers increase the risk of hallucinations, and clonidine increases the risk of nightmares, and the efficacy of these two drugs is not well documented. Neuroleptics increase the risk of seizures. There are no convincing data to support the use of magnesium sulphate or meprobamate (the latter carries a risk of serious adverse effects). Acamprosate, naltrexone and disulfiram are not beneficial in alcohol withdrawal. (9) Gradual withdrawal, i.e. ingestion of decreasing amounts of alcohol, has not been compared with other methods but is generally not recommended. (10) There are no specific recommendations on hydration. Note that excessive water-sodium intake carries a risk of pulmonary oedema in patients with heart disease. (11) As vitamin B1 deficiency is frequent and can lead to serious complications in alcohol-dependent patients, oral vitamin B1 supplementation is widely recommended, despite the absence of comparative trials. High doses must be used to compensate for poor absorption. Intravenous administration is best if patients have very poor nutritional status or severe complications such as Gayet-Wernicke encephalopathy (a medical emergency), even though rare anaphylactic reactions have been reported after vitamin B1 injection. (12) Planned alcohol withdrawal in specialised hospital units has been extensively studied. Outpatient withdrawal may be more appropriate for patients who are at low risk of developing severe withdrawal syndrome. (13) A large proportion of alcohol-dependent patients were excluded from trials of withdrawal strategies. These include elderly patients, patients with serious psychiatric or somatic disorders, and patients who are also dependent on other substances. (14) An oral benzodiazepine is the best-assessed treatment for a single episode of generalised seizures or hallucinations during alcohol withdrawal. (15) In randomised comparative trials benzodiazepines were more effective than neuroleptics in preventing delirium-related mortality. Currently, with appropriate fluid-electrolyte support, continuous monitoring of vital signs, and respiratory support if necessary, the mortality rate for delirium tremens is under 3%. (16) In practice, patients who are attempting to stop drinking alcohol need close personal support and communication, and a reassuring environment, as well as regular monitoring for early signs of a withdrawal syndrome; the latter may require benzodiazepine therapy.
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PMID:Alcohol withdrawal syndrome: how to predict, prevent, diagnose and treat it. 1732 38

Alcohol dependence is a chronic, relapsing biobehavioral disease mediated by various parts of the brain, including reward systems, memory circuits, and the prefrontal cortex. It is characterized by loss of the ability to drink alcohol in moderation and continued drinking despite negative consequences. The alcohol withdrawal syndrome is a common but not universal diagnostic feature of alcohol dependence. Benzodiazepine detoxification of the alcohol withdrawal syndrome prevents the development of withdrawal seizures and delirium tremens, and makes patients more comfortable, which promotes engagement in treatment. Symptom-triggered dosing, based on a withdrawal rating scale such as the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised, is optimal for minimizing the total benzodiazepine dosage. Use of a long-acting benzodiazepine (eg, chlordiazepoxide) is preferred in uncomplicated patients. Thiamine should be administered routinely before the administration of intravenous fluids to prevent the development of Wernicke's encephalopathy and Wernicke-Korsakoff syndrome. In combination with psychosocial treatment, disulfiram, naltrexone, and acamprosate can reduce the frequency of relapse. Naltrexone may be more effective for reduction of loss of control with the first drink and cue-related craving, and acamprosate may be more effective for stabilizing the physiology of post-acute withdrawal. Disulfiram, an aversive deterrent, can be useful if administration can be monitored and tied to meaningful contingencies or when used prophylactically for situations anticipated to carry high risk of relapse. Psychiatric comorbidity, especially depression, is common and is best addressed concurrently, although definitive diagnosis may have to await a period of prolonged sobriety. Prescription of addictive substances, including benzodiazepines beyond the period of acute detoxification, should be avoided, and if necessary should be closely monitored (eg, by frequent visits with small prescriptions, clinic-administered disulfiram, and/or urine or breath alcohol screenings). Abstinence from alcohol is recommended for persons with alcohol dependence. Psychosocial treatment and participation in Alcoholics Anonymous can help patients achieve and maintain abstinence.
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PMID:The psychiatric management of patients with alcohol dependence. 1771 2

The alcohol withdrawal syndrome (AWS) is a common management problem in hospital practice for neurologists, psychiatrists and general physicians alike. Although some patients have mild symptoms and may even be managed in the outpatient setting, others have more severe symptoms or a history of adverse outcomes that requires close inpatient supervision and benzodiazepine therapy. Many patients with AWS have multiple management issues (withdrawal symptoms, delirium tremens, the Wernicke-Korsakoff syndrome, seizures, depression, polysubstance abuse, electrolyte disturbances and liver disease), which requires a coordinated, multidisciplinary approach. Although AWS may be complex, careful evaluation and available treatments should ensure safe detoxification for most patients.
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PMID:The alcohol withdrawal syndrome. 1798 99

The topic of alcohol withdrawal syndrome (AWS), including delirium tremens and especially seizures, is reviewed. From mice and rat studies, it is known that both N-methyl-d-aspartate (NMDA) and gamma-aminobutyric acid (GABA) receptors are involved in AWS. During alcohol intoxication chronic adaptations of NMDA and GABA receptors occur, and during alcohol withdrawal a hyperexcitable state develops. In studies on humans, during intoxication the NMDA receptors are activated and mediate tonic inhibition. In withdrawal, a rebound activation of these receptors occurs. Both GABA-A and GABA-B receptors, especially the alpha2 subunit of GABA-A receptors, are also likely involved. Homocysteine increases with active drinking, and in withdrawal, excitotoxicity likely is induced by a further increase in homocysteine, viewed as a risk factor for AWS and also as a screening tool. The dopamine transporter gene is also associated with AWS. Characteristics involves changes in the ECG, especially an increase in QT interval, and EEG changes, including abnormal quantified EEG, at times periodic lateralized epileptiform discharges, and especially seizures, usually occurring 6-48h after the cessation of drinking. Therapy has emphasized benzodiazepines, mainly diazepam and lorazepam, but more standard antiepileptic drugs, like carbamazepine and topiramate, are also effective and safe.
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PMID:Alcohol withdrawal seizures. 1924 88

Dopamine neurotransmission has been a key player in attempts to identify genetic factors involved in alcohol dependence. The dopamine transporter terminates dopaminergic neurotransmission, making the gene encoding the transporter (SLC6A3/DAT1) an attractive candidate in clinical studies on alcohol dependence. We conducted a systematic review of 18 studies examining associations between polymorphisms in DAT1 and alcohol dependence. The DAT1 variable number tandem repeat, the most frequent studied polymorphism in DAT1, did not show a direct association with alcohol dependence in general. Several, but not all, studies found that the DAT1 variable number tandem repeat (9-repeat allele) was associated with alcohol-withdrawal symptoms, such as seizures and delirium tremens. We discuss shortcomings, such as lack of power and disregarding moderating variables, as well as future challenges of gene association studies.
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PMID:Polymorphisms in the dopamine transporter gene (SLC6A3/DAT1) and alcohol dependence in humans: a systematic review. 1945 Jan 32

Alcohol withdrawal syndrome (AWS) is a major cause of morbidity and mortality in the acute care setting. We describe a 28-year-old man who was brought to the emergency department with a new-onset seizure and clinical signs and symptoms consistent with advanced delirium tremens. A symptom-triggered intensive care unit treatment protocol consisting of a benzodiazepine and antiadrenergic agents was started. The manifestations of delirium tremens persisted with titration of a lorazepam infusion in excess of 40 mg/hour. Intravenous phenobarbital was administered in escalating doses of 65 mg followed by 130 mg 15 minutes later, resulting in control of severe agitation in the face of benzodiazepine resistance. Subsequent scheduled phenobarbital administration allowed for a successful and orderly weaning of the continuous benzodiazepine infusion and adjunctive agents used in AWS management. With continued clearing of consciousness, the patient was successfully discharged. The administration of phenobarbital in this patient allowed improved symptom control, minimized the potential for propylene glycol toxicity, was not associated with respiratory depression, and facilitated successful weaning of benzodiazepines. Barbiturates offer a mechanism of action that is different from that of benzodiazepines. Although the cornerstone of treatment for AWS remains benzodiazepines, this case highlights the potential utility of phenobarbital in patients with resistant AWS.
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PMID:Phenobarbital treatment in a patient with resistant alcohol withdrawal syndrome. 1955 62

Several genetic polymorphisms have been reported to be associated with alcohol withdrawal seizures (AWS) and delirium tremens (DT). To replicate and further explore these findings, we investigated the effects of 12 previously reported candidate genetic variations in two groups of alcohol-dependent European Americans with a history of withdrawal, which differed according to the presence (n = 112) or absence (n = 92) of AWS and/or DT. Associations of AWS and/or DT with the genomic and clinical characteristics and gene-gene interaction effects were investigated using logistic regression models. None of the polymorphisms were significantly associated with AWS/DT after correction for multiple testing. However, we found a significant interaction effect of the SLC6A4 promoter polymorphism (5-HTTLPR) and DRD2 exon 8 single nucleotide polymorphism rs6276 on AWS and/or DT history (P = 0.009), which became more significant after adjustment for lifetime maximum number of drinks consumed per 24 hours (P < 0.001). Subsequent analysis revealed an even stronger association of the SLC6A4-DRD2 interaction with DT (P < 0.0001), which remained significant after Bonferroni correction. Results reveal decreased likelihood of DT in alcoholics that carry the DRD2 rs6276 G allele and SLC6A4 LL genotype. This study provides the first evidence to implicate the interaction between serotonin and dopamine neurotransmission in the etiology of DT. Replication is necessary to verify this potentially important finding.
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PMID:Interaction of SLC6A4 and DRD2 polymorphisms is associated with a history of delirium tremens. 2000 20

Sepsis is often complicated by an acute and reversible deterioration of mental status, which is associated with increased mortality and is consistent with delirium but can also be revealed by a focal neurologic sign. Sepsis-associated encephalopathy is accompanied by abnormalities of electroencephalogram and somatosensory-evoked potentials, increased in biomarkers of brain injury (i.e., neuron-specific enolase, S-100 beta-protein) and, frequently, by neuroradiological abnormalities, notably leukoencephalopathy. Its mechanism is highly complex, resulting from both inflammatory and noninflammatory processes that affect all brain cells and induce blood-brain barrier breakdown, dysfunction of intracellular metabolism, brain cell death, and brain injuries. Its diagnosis relies essentially on neurologic examination that can lead one to perform specific neurologic tests. Electroencephalography is required in the presence of seizure; neuroimaging in the presence of seizure, focal neurologic signs or suspicion of cerebral infection; and both when encephalopathy remains unexplained. In practice, cerebrospinal fluid analysis should be performed if there is any doubt of meningitis. Hepatic, uremic, or respiratory encephalopathy, metabolic disturbances, drug overdose, withdrawal of sedatives or opioids, alcohol withdrawal delirium, and Wernicke's encephalopathy are the main differential diagnoses of sepsis-associated encephalopathy. Patient management is based mainly on controlling infection, organ system failure, and metabolic homeostasis, at the same time avoiding neurotoxic drugs.
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PMID:Sepsis-associated encephalopathy and its differential diagnosis. 2004 18

Gamma aminobutyric acid (GABA) represents the major inhibitory neurotransmitter of the central nervous system. Ethanol as well as benzodiazepines (BDZs) and some anticonvulsant drugs directly affect GABAA receptors inducing similar anxiolytic, sedativehypnotic, and anticonvulsant effects. Since BDZs have proven their efficacy in ameliorating symptoms and in decreasing the risk of seizures and delirium tremens, they are the drugs of choice for the treatment of alcohol withdrawal syndrome (AWS). However, due to their addictive potential and lack of safety when combined with alcohol, BDZs are usually not recommended for the maintenance of alcohol abstinence. Other GABA-ergic medications represent potentially promising drugs useful in the treatment of AWS and in maintaining alcohol abstinence. Indeed, available studies have demonstrated that clomethiazole, gabapentin and gamma hydroxybutyrate (GHB) present a similar efficacy to BDZs in suppressing AWS. In addition, current evidence also indicates that gabapentin and GHB do not have significant interactions with ethanol that render them safe to use in maintaining alcohol abstinence. Moreover, gabapentin and valproic acid may be beneficial in maintaining alcohol abstinence in alcoholics with psychiatric co-morbidity. Pregabalin, neurosteroids, tiagabine, and vigabatrin need further clinical evidence of efficacy, safety and tolerability. Thus, given the importance of GABA-ergic mechanisms in the development and maintenance of alcohol dependence, and the very interesting results currently achieved, more research on GABAergic agents is warranted.
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PMID:Medications acting on the GABA system in the treatment of alcoholic patients. 2048 12

Delirium Tremens is quite rare in children and it is usually caused by withdrawal or abstinence from alcohol, barbiturates and other major tranquilizers. The usual symptoms of Delirium Tremens include severe altered mental status with confusion, delusions, hallucinations, and severe agitation. Although psychosis is a recognized manifestation of Phenytoin toxicity, visual hallucinations are not. This study reports the case of a 4-year-old male with febrile seizures plus syndrome who developed acute complex visual hallucinations and psychomotor agitation early after therapy with intravenous Phenytoin was administered. These visual hallucinations mimicked those linked to Delirium Tremens and were not associated with an encephalopathy or other known neuropsychiatric side effects of this drug. Moreover, the hallucinations occurred while serum Phenytoin concentrations were below therapeutic range. We made an extensive investigation in order to exclude a non-convulsive Status Epilepticus, a Central Nervous System infection, a metabolic disorder, an underlying psychiatric disease and a possible drug toxicity. The temporal relationship between initiation of Phenytoin and onset of visual hallucinations and resolution of symptoms with withdrawal of Phenytoin suggests that the visual disturbances were probably due to that antiepileptic drug.
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PMID:Phenytoin-induced visual disturbances mimicking Delirium Tremens in a child. 2072 59


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