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)

The aim of this study was to evaluate the hypothetical role of kindling phenomenon in the development and course of alcohol withdrawal (AW) seizures and delirium tremens (DT). The 2186 medical records of 1179 patients hospitalized in Nowowiejski Hospital in Warsaw from 1973 to 1987 were reviewed using a structured questionnaire. Investigating the role of kindling, a course of consecutive AW episodes of patients hospitalized several times was analyzed. The relationships of withdrawal seizures with the duration of alcohol abuse, the number of prior detoxification episodes, and other variables were also studied. Increasing severity of AW symptoms was observed during the course of consecutive episodes in 22.5% of patients. The first episode of DT was preceded by withdrawal seizures in 11% of cases. First-ever withdrawal seizures occurred more frequently in patients with head injury in the past and with coexisting symptoms of alcohol liver disease. Occurrence of withdrawal seizures and DTs did not correlate with the number of previous withdrawal episodes or with the length of period of intensive drinking. We concluded that the kindling model could be applied only to some cases in the development of AW seizures and DTs. Kindling should be considered as one of the multiple mechanisms involved in the pathogenesis of AW delirium.
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PMID:Assessment of the role of kindling in the pathogenesis of alcohol withdrawal seizures and delirium tremens. 1006 46

Delirium is common among cancer patients, especially those with advanced disease. Typical treatment involves addressing the underlying cause if possible; eliminating nonessential and/or other drugs that can worsen confusion, manipulating the environment; and administering antipsychotic drugs to control symptoms and agitated behavior, and attempt to clear the patient's sensorium. The newer atypical antipsychotics may have potential in the treatment of delirium and also have the added benefit of causing less akithisia and other extrapyramidal side effects. This is illustrated by the case of a 59-year-old woman with leukemia and pain of unclear etiology who developed a delirium and a moderate to severe extrapyramidal syndrome (EPS) in the setting of escalation of her pain medications and concomitant escalation of prochlorperazine. The patient presented with confusion and moderate to severe cogwheeling rigidity, masked facies, bradykinesia, and tremor. Additionally, the patient had a relatively recent history of subdural hematoma and one seizure. Conservative management including eliminating multiple nonessential medications (including the prochlorperazine); changing her opioid analgesic; providing a 24-hour companion: and administering low doses of haloperidol (0.5 mg-2.0 mg) were not effective in treating the patient's delirium. The patient's EPS was dramatically worse following haloperidol doses. After approximately I week without improvement, the patient was started on olanzapine 5 mg daily with initial improvement but with residual confusion in the evenings and overnight. The dose was titrated up to 10 mg nightly with 2.5 mg as needed during the day. After 3 days on this regimen, the patient's mental status exam was normal and she was discharged home. We discuss the potential utility of this atypical antipsychotic in the palliative care setting.
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PMID:Complicated delirium in a cancer patient successfully treated with olanzapine. 1009 65

Quantitative trait analyses in mice suggest a vulnerability locus for physiological alcohol withdrawal severity on a chromosomal segment that harbors the genes encoding the alpha1, alpha6, beta2, and gamma2 subunits of the gamma-aminobutyric acid type-A receptor (GABR). We tested whether genetic variation at the human GABA(A) alpha6, beta2, and gamma2 gene cluster on chromosome 5q33 confers vulnerability to alcohol dependence. The genotypes of three nucleotide substitution polymorphisms of the GABRA6, GABRB2, and GABRG2 genes were assessed in 349 German alcohol-dependent subjects and in 182 ethnically matched controls. To eliminate some of the genetic variance, three more homogeneous subgroups of alcoholics were formed by: (1) a history of alcohol withdrawal seizure or delirium (n = 106); (2) a history of parental alcoholism (n = 120); and (3) a comorbidity of dissocial personality disorder (n = 57). We found no evidence that any of the investigated allelic variants confers vulnerability to either alcohol dependence or severe physiological alcohol withdrawal symptoms or familial alcoholism (p > 0.05). The frequency of the T allele of the GABRA6 polymorphism was significantly increased in dissocial alcoholics [f(T) = 0.799] compared with the controls [f(T) = 0.658; p = 0.002; OR(T+) = 7.26]. Taking into account the high a priori risk of false-positive association findings due to multiple testing, further replication studies are necessary to examine the tentative phenotype-genotype relationship of GABRA6 gene variants and dissocial alcoholism.
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PMID:Association analysis of sequence variants of GABA(A) alpha6, beta2, and gamma2 gene cluster and alcohol dependence. 1019 14

Transgenic mice lacking a functional 5-HT2c receptor gene are extremely susceptible to audiogenic seizures, suggesting that 5-HT2c receptors mediate inhibition of neuronal network excitability. The present association study tested the hypothesis that a Cys23Ser substitution polymorphism within the human 5-HT2c receptor gene modulates neuronal excitability. Genotypes of the Cys23Ser polymorphism were assessed in 454 subjects of German descent, comprising: 1) 93 severely affected alcohol-dependent males with a history of alcohol withdrawal seizure or delirium, 2) 119 patients affected by an idiopathic generalized epilepsy, and 3) 242 controls. Both sexes were analyzed separately because of the X-chromosomal location of the 5-HT2c receptor gene. The allele frequencies of the Cys23Ser variants did not differ significantly between the controls and either the severely affected alcohol-dependent males (P = 0.34), or patients with idiopathic generalized epilepsy (P > 0.57). Our results suggest that the common Cys23Ser substitution polymorphism of the human 5-HT2c receptor gene does not confer susceptibility to neuronal hyperexcitability in either idiopathic generalized epilepsy or alcohol withdrawal seizure or delirium.
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PMID:Association analysis between a Cys23Ser substitution polymorphism of the human 5-HT2c receptor gene and neuronal hyperexcitability. 1020 30

Barbiturates can produce psychological and physical dependence and produce a withdrawal syndrome on the second to fourth day after the drug is suspended. Symptoms include anxiety, restlessness, insomnia, rhythmic intention tremor, dizziness, seizures, and psychosis. If the syndrome is not recognized and correctly treated, hyperthermia, circulatory failure, and death may ensue. Although barbiturates are less frequently used nowadays, they are employed in combination with other drugs in many medications used for the treatment of headache. We report the case of a 54-year-old woman who developed a barbiturate abstinence syndrome when she suspended self-administration of a drug containing butalbital. The patient had been using barbiturates, 900 mg/die, for 2+ years for persistent headache. She was admitted to the hospital because of seizures, hallucinations and delirium not controlled by benzodiazepine and phenothiazine administration. Her symptoms resolved after parenteral phenobarbital administration.
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PMID:[Barbiturate withdrawal syndrome: a case associated with the abuse of a headache medication]. 1034 6

Psychotropic drugs, as well as some psychiatric disorders, can produce neurotoxic and life-threatening abnormalities of water and electrolyte balance that require prompt and appropriate medical intervention. Compulsive fluid intake by psychotic patients (primary polydipsia) can produce delirium due to water intoxication with hyponatremia. Several psychotropic drugs cause water retention by decreasing renal clearance, as in the syndrome of inappropriate antidiuretic hormone secretion. Lithium and other agents interfere with renal resorption of water to cause nephrogenic diabetes insipidus. Clinical signs in these disorders range from lethargy and confusion to stupor, seizures, coma, and death. This overview provides a conceptual framework for differentiating among and safely managing these relatively common disorders.
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PMID:Primary and drug-induced disorders of water homeostasis in psychiatric patients: principles of diagnosis and management. 1037 Apr 44

Brain circuits for infrequently employed memories are reinforced largely during sleep by self-induced, electrical slow-waves, a process referred to as "dynamic stabilization" (DS). The essence of waking brain function in the absence of volitional activity is sensory input processing, an enormous amount of which is visual. These two functions: circuit reinforcement by DS and sensory information processing come into conflict when both occur at a high level, a conflict that may have been the selective pressure for sleep's origin. As brain waves are absent at the low temperatures of deep torpor, essential circuitry of hibernating small mammals would lose its competence if the animals did not warm up periodically to temperatures allowing sleep and circuit reinforcement. Blind, cave-dwelling vertebrates require no sleep because their sensory processing does not interfere with DS. Nor does such interference arise in continuously-swimming fishes, whose need to process visual information is reduced greatly by life in visually relatively featureless, pelagic habitats, and by schooling. Dreams are believed to have their origin in DS of memory circuits. They are thought to have illusory content when the circuits are partially degraded (incompetent), with synaptic efficacies weakened through infrequent use. Partially degraded circuits arise normally in the course of synaptic efficacy decay, or pathologically through abnormal regimens of DS. Organic delirium may result from breakdown of normal regimens of DS of circuitry during sleep, leaving many circuits incompetent. Activation of incompetent circuits during wakefulness apparently produces delirium and hallucinations. Some epileptic seizures may be induced by abnormal regimens of DS of motor circuitry. Regimens of remedial DS during seizures induced by electroconvulsive therapy (ECT) apparently produce temporary remission of delirium by restoring functional or 'dedicated' synaptic efficacies in incompetent circuitry. Sparing of sensory circuitry in fatal familial insomnia seemingly owes to supernormal circuit use in the virtual absence of sleep. ECT shocks and cardioverter defibrillation may have analogous remedial influences.
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PMID:Adaptations and pathologies linked to dynamic stabilization of neural circuitry. 1039 56

The alcohol withdrawal syndrome is common in elderly individuals who are alcohol dependent and who decrease or stop their alcohol intake. While there have been few clinical studies to directly support or refute the hypothesis that withdrawal symptom severity, delirium and seizures increase with advancing age, several observational studies suggest that adverse functional and cognitive complications during alcohol withdrawal do occur more frequently in elderly patients. Most elderly patients with alcohol withdrawal symptoms should be considered for admission to an inpatient setting for supportive care and management. However, elderly patients with adequate social support and without significant withdrawal symptoms at presentation, comorbid illness or past history of complicated withdrawal may be suitable for outpatient management. Although over 100 drugs have been described for alcohol withdrawal treatment, there have been no studies assessing the efficacy of these drugs specifically in elderly patients. Studies in younger patients support benzodiazepines as the most efficacious therapy for reducing withdrawal symptoms and the incidence of delirium and seizure. While short-acting benzodiazepines, such as oxazepam and lorazepam, may be appropriate for elderly patients given the risk for excessive sedation from long-acting benzodiazepines, they may be less effective in preventing seizures and more prone to produce discontinuation symptoms if not tapered properly. To ensure appropriate benzodiazepine treatment, dose and frequency should be individualised with frequent monitoring, and based on validated alcohol withdrawal severity measures. Selected patients who have a history of severe or complicated withdrawal symptoms may benefit from a fixed schedule of benzodiazepine provided that medication is held for sedation. beta-Blockers, clonidine, carbamazepine and haloperidol may be used as adjunctive agents to treat symptoms not controlled by benzodiazepines. Lastly, the age of the patient should not deter clinicians from helping the patient achieve successful alcohol treatment and rehabilitation.
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PMID:Managing alcohol withdrawal in the elderly. 1040 40

The present association study tested whether genetic variation of the GABAB receptor (GABABR1) gene confers vulnerability to alcohol dependence. The genotypes of three DNA sequence variants in exons 1a1, 7 and 11 of the GABABR1 gene were assessed in 234 German controls and 350 German alcohol-dependent subjects, including three more homogeneous subgroups of alcoholics, marked by (1) history of parental alcoholism (n = 121); (2) history of alcohol withdrawal seizure or delirium (n = 108); and (3) comorbidity of dissocial personality disorder (n = 60). The allele frequencies of none of the investigated GABABR1 variants differed significantly between the controls and the groups of alcoholics when a correction for multiple testing was taken into account (P > 0.004). However, trends (P < 0.10) towards an excess of the Ser489 allele of the exon 7 polymorphism were found in the subgroups of alcoholics, and of the common allele of the exon 11 polymorphism in the entire sample of alcoholics (P = 0.032), alcoholics with parental alcoholism (P = 0.084) and the dissocial alcoholics (P = 0.037). Our findings suggest that the investigated GABABR1 variants do not contribute a substantial effect (RR > 3) to the genetic variance of alcohol dependence. Nevertheless, the hints towards potential allelic associations of the exon 7 and 11 polymorphisms with dissocial alcoholism emphasize further studies to test more defined phenotype-genotype relationships.
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PMID:Association analysis of exonic variants of the gene encoding the GABAB receptor and alcohol dependence. 1041 85

Although heavy alcohol intake is known to be one of the most common causative factors of liver disease, pancreatitis, upper gastrointestinal and neurological disorders, the influence of the drinking pattern is largely unknown. The study investigated the relationship of alcohol-related medical disorders in alcoholics and their drinking pattern. Two hundred and forty-one chronic alcoholics were referred consecutively for detoxification and their drinking pattern was sufficient for them to be included in this study. History of alcohol abuse as well as drinking behaviour in the last 6 months were assessed by a semi-structured interview. Findings included intensive clinical examination with abdominal ultrasound in most subjects. Heavy drinking with frequent inebriation was most often found in our sample (44.4%), whereas continuous heavy alcohol consumption without intoxication (33.6%), and an episodic drinking style (22.0%) were less frequent. The heavy drinkers suffered more often from pancreatitis, oesophageal varices, polyneuropathy or erectile dysfunction than episodic drinkers. They also showed more upper gastrointestinal disorders, although the estimated life-time alcohol intake was comparable to continuous drinkers. No difference relating to withdrawal delirium or seizures could be found between the groups of alcoholics. Frequent heavy drinkers showed a trend to more alcohol-related medical disorders than alcoholics with a different drinking pattern, although they were younger and their estimated life-time alcohol intake was comparable to that of continuous drinkers. Thus, the drinking pattern, particularly frequent inebriation, has an influence on the occurrence of alcohol-related disorders.
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PMID:Drinking pattern and alcohol-related medical disorders. 1041 7


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