[Assessment of alcohol withdrawal syndrome: new perspectives]. / Az alkoholmegvonásos szindróma ellátása: új perspektívák.

Alcohol withdrawal syndrome is one of the most important consequences of alcohol use disorder, a complex neuropsychiatric disorder, which is firstly treated in non-specific and secondly in psychiatric/addictive in- or outpatient units. On the other hand, alcohol withdrawal syndrome is one of the most important outcomes of the severity of alcohol use disorder, further, it can lead to the development of alcohol-related seizure and delirium tremens. Hence, early recognition and optimal treatment of alcohol withdrawal syndrome have a critical importance. Therefore, the main goal of the present review was - by systematically summarizing the scientific data published during the past two decades - to form a unique diagnostic and therapeutic algorithm. During the recognition and the course of alcohol withdrawal syndrome, the Clinical Institute Withdrawal Assessment for Alcohol, Revised scale, while in the risk assessment the Prediction of Alcohol Withdrawal Severity Scale are the recommended psychometric tools. Benzodiazepines are the key elements of the pharmacotherapy of alcohol withdrawal syndrome. Many studies have evaluated that diazepam, chlordiazepoxide, lorazepam and oxazepam with distinct indications have sufficient evidence in the treatment of alcohol withdrawal syndrome. However, in the past few years some authors have recommended the importance of non-benzodiazepine medications. The efficacy of propofol, phenobarbital, carbamazepin, oxcarbamazepin and alpha-2 receptor agonists in the treatment of alcohol withdrawal syndrome have been revealed. Furthermore, it has been evaluated that benzodiazepines are recommended in the treatment of alcohol-related seizure and delirium tremens. In the present review, our aim was to construct a unique, up-to-date diagnostic and therapeutic algorithm by summarizing the related papers published during the past two decades. Hence this scheme may be useful in the optimal treatment of patients diagnosed with alcohol use disorder and it could help to conduct further clinical researches. Orv Hetil. 2023; 164(38): 1487-1496.

A machine learning approach to risk assessment for alcohol withdrawal syndrome.

At present, risk assessment for alcohol withdrawal syndrome relies on clinical judgment. Our aim was to develop accurate machine learning tools to predict alcohol withdrawal outcomes at the individual subject level using information easily attainable at patients' admission. An observational machine learning analysis using nested cross-validation and out-of-sample validation was applied to alcohol-dependent patients at two major detoxification wards (LMU, n = 389; TU, n = 805). 121 retrospectively derived clinical, blood-derived, and sociodemographic measures were used to predict 1) moderate to severe withdrawal defined by the alcohol withdrawal scale, 2) delirium tremens, and 3) withdrawal seizures. Mild and more severe withdrawal cases could be separated with significant, although highly variable accuracy in both samples (LMU, balanced accuracy [BAC] = 69.4%; TU, BAC = 55.9%). Poor outcome predictions were associated with higher cumulative clomethiazole doses during the withdrawal course. Delirium tremens was predicted in the TU cohort with BAC of 75%. No significant model predicting withdrawal seizures could be found. Our models were unique to each treatment site and thus did not generalize. For both treatment sites and withdrawal outcome different variable sets informed our models' decisions. Besides previously described variables (most notably, thrombocytopenia), we identified new predictors (history of blood pressure abnormalities, urine screening for benzodiazepines and educational attainment). In conclusion, machine learning approaches may facilitate generalizable, individualized predictions for alcohol withdrawal severity. Since predictive patterns highly vary for different outcomes of withdrawal severity and across treatment sites, prediction tools should not be recommended for clinical practice unless adequately validated in specific cohorts.

Derivation and validation of a multivariable model, the alcohol withdrawal triage tool (AWTT), for predicting severe alcohol withdrawal syndrome.

BACKGROUND: Alcohol withdrawal and its consequences are a common concern for the large numbers of patients who present to emergency departments (EDs) with alcohol use disorders. While the majority of patients who go on to develop alcohol withdrawal experience only mild symptoms, a small proportion will experience seizures or delirium tremens. The aim of this study was to develop a tool to predict the need for hospital admission in patients at risk for alcohol withdrawal using only objective criteria that are typically available during the course of an ED visit. METHODS: We conducted a retrospective study at an academic medical center. Our primary outcome was severe alcohol withdrawal syndrome (SAWS), which we defined as a composite of delirium tremens, seizure, or use of high benzodiazepine doses. All candidate predictors were abstracted from the electronic health record. A logistic regression model was constructed using the derivation dataset to create the alcohol withdrawal triage tool (AWTT). RESULTS: Of the 2038 study patients, 408 20.0 %) developed SAWS. We identified eight independent predictors of SAWS. Each of the predictors in the regression model was assigned one point. Summing the points for each predictor generated the AWTT score. An AWTT score of 3 or greater was defined as high risk based on sensitivity of 90 % and specificity of 47 % for predicting SAWS. CONCLUSIONS: We were able to identify a set of objective, timely, independent predictors of SAWS. The predictors were used to create a novel clinical prediction rule, the AWTT.

Alcohol-related seizures may be associated with more severe depression, alcohol dependence syndrome, and more pronounced alcohol-related problems.

Severe alcohol abuse and related medical and social functioning risks, as well as clinically significant depression, are common in patients who are admitted to hospital with alcohol-related seizures (ARS) and significantly affect the quality of life of the patient. Compared with studies involving patients with alcohol dependence, no large-scale studies with the aim of finding the prevalence and severity of depression and its most commonly affected aspects for patients with ARS have been carried out in Latvia yet. The habits and frequency of alcohol use in correlation to depression and its severity are also not known. One hundred ten patients were included in the study - 60 patients with ARS and 50 patients with alcohol use disorder (AUD) - without ARS. The research population consists mainly of working-age adults; however, most patients with ARS have significantly impaired daily activity and social life. Compared with patients who only have alcohol dependence, a more common problem in patients with ARS is having an alcohol dependence level that requires additional clinical examinations and consultations by a narcologist using the Alcohol Use Disorder Identification Test (AUDIT) scale, and this level is more often related to depression particularly characterized by pronounced suicidal thoughts (exhibited by almost 1 out of every 4 patients). According to the Hamilton Depression Rating Scale (HAM-D), depression has affected 81.7% of patients with ARS and 96% of patients with AUD. Seizures negatively affect patients' physical and emotional well-being in over 80% of cases; moreover, it is common for most patients to feel depressed after the seizures. Over half of the patients with ARS scored 20-40 points according to the AUDIT scale, indicating serious alcohol abuse disorder. Our research data can help bring awareness of the need to more carefully evaluate patients with ARS for an early detection of alcohol abuse disorder and depression with a risk of self-harm and unintentional harm to others as well as to decrease the burden on social care and healthcare. This article is part of the Special Issue "Individualized Epilepsy Management: Medicines, Surgery and Beyond".

Alcohol withdrawal syndrome: mechanisms, manifestations, and management.

The alcohol withdrawal syndrome is a well-known condition occurring after intentional or unintentional abrupt cessation of heavy/constant drinking in patients suffering from alcohol use disorders (AUDs). AUDs are common in neurological departments with patients admitted for coma, epileptic seizures, dementia, polyneuropathy, and gait disturbances. Nonetheless, diagnosis and treatment are often delayed until dramatic symptoms occur. The purpose of this review is to increase the awareness of the early clinical manifestations of AWS and the appropriate identification and management of this important condition in a neurological setting.

Convulsões relacionadas ao alcoolismo: atualização / Seizures related to alcoholism: update

OBJETIVO: Revisão sobre crises convulsivas relacionadas ao alcoolismo,discutindo sua classificação, fisiopatologia, investigação diagnóstica e seu tratamento. MÉTODO: Revisão não sistemática de artigos utilizando-se os unitermos: "alcoholism", "alcohol", "seizures" e "withdrawal". Priorizou-se a utilização de artigos que apresentassem associação desses unitermos no título. Foram utilizadas as bases de dados do PubMed, Lilacs e Google Scholar. RESULTADOS: Foram encontrados 2.362 artigos associando os unitermos no título, tendo sido escolhidos 26 artigos em inglês, 3 em português, 1 manual e 1 tese em inglês para a elaboração desta revisão. CONCLUSÃO: As crises convulsivas relacionadas ao álcool representam uma das mais graves complicações do alcoolismo. O diagnóstico e o tratamento corretos melhoram o prognóstico desses indivíduos, diminuindo o risco de complicações, a recorrência de crises, a ocorrência de status epilepticus ou a evolução para um quadro de delirium tremens.

OBJECTIVE: Review alcoholism related seizures, discussing classification,pathophysiology, diagnosis and treatment. METHOD: A non-systematic review was performed of articles using the keywords: "alcoholism", "alcohol", "seizures", and "withdrawal". Articles with the combination of these keywords in the title were favored. The search was performed on PubMed, Lilacs database and Google Scholar. RESULTS: Using these search terms 2,362 articles were found, being selected 26 articles in English, 3 articles in Portuguese, 1 English manual, and 1 thesis in English to elaborate this review. CONCLUSION: Seizures related to alcohol are one of the most serious complications of alcoholism. The correct diagnosis and treatment improves the prognosis of these individuals, decreasing the risk of complications,seizure recurrence, status epilepticus and the progression to delirium tremens.

Neurologic Manifestations of Chronic Liver Disease and Liver Cirrhosis.

The normal functioning of brain is intimately as well as intricately interrelated with normal functioning of the liver. Liver plays a critical role of not only providing vital nutrients to the brain but also of detoxifying the splanchnic blood. Compromised liver function leads to insufficient detoxification thus allowing neurotoxins (such as ammonia, manganese, and other chemicals) to enter the cerebral circulation. In addition, portosystemic shunts, which are common accompaniments of advanced liver disease, facilitate free passage of neurotoxins into the cerebral circulation. The problem is compounded further by additional variables such as gastrointestinal tract bleeding, malnutrition, and concurrent renal failure, which are often associated with liver cirrhosis. Neurologic damage in chronic liver disease and liver cirrhosis seems to be multifactorial primarily attributable to the following: brain accumulation of ammonia, manganese, and lactate; altered permeability of the blood-brain barrier; recruitment of monocytes after microglial activation; and neuroinflammation, that is, direct effects of circulating systemic proinflammatory cytokines such as tumor necrosis factor, IL-1ß, and IL-6. Radiologist should be aware of the conundrum of neurologic complications that can be encountered in liver disease, which include hepatic encephalopathy, hepatocerebral degeneration, hepatic myelopathy, cirrhosis-related parkinsonism, cerebral infections, hemorrhage, and osmotic demyelination. In addition, neurologic complications can be exclusive to certain disorders, for example, Wilson disease, alcoholism (Wernicke encephalopathy, alcoholic cerebellar degeneration, Marchiafava-Bignami disease, etc). Radiologist should be aware of their varied clinical presentation and radiological appearances as the diagnosis is not always straightforward.

Predictors of severe alcohol withdrawal syndrome: a systematic review and meta-analysis.

BACKGROUND: Severity of alcohol withdrawal syndrome (AWS) is associated with hospital mortality and length of stay. However, as there is no consensus regarding how to predict the development of severe alcohol withdrawal syndrome (SAWS), we sought to determine independent predictors of SAWS. METHODS: We conducted a systematic review and meta-analysis of studies evaluating hospitalized patients with AWS versus SAWS-delirium tremens (DT) and/or seizures. Random-effects meta-analysis [PRISMA guidelines] was performed on common baseline variables and predictive effects for development of SAWS were calculated using RevMan v5.2. Funnel plots were constructed, and tests of heterogeneity were performed. RESULTS: Of 226 studies screened, 17 met criteria and 15 were included in the meta-analysis. The primary findings were that an incident occurrence of DT or alcohol withdrawal seizures was significantly predicted by history of a similar event (OR 2.58 for DT vs. no-DT, 95% CI 1.41, 4.7; OR 2.8 for seizure vs. no-seizure, 95% CI 1.09, 7.19). Both a lower initial platelet count and serum potassium level were predictive of an incident occurrence of DT (platelet count mean difference [MD] -45.64/mm(3) vs. no-DT, 95% CI -75.95, -15.33; potassium level MD -0.26 mEq/l vs. no-DT, 95% CI -0.45, -0.08), seizures, and SAWS. Higher initial alanine aminotransferase was seen in patients with SAWS (MD 20.97 U/l vs. no-SAWS, 95% CI 0.89, 41.05). Higher initial serum gamma-glutamyl transpeptidase was seen in patients with incident alcohol withdrawal seizures (MD 202.56 U/l vs. no-seizure, 95% CI 3.62, 401.5). Significant heterogeneity was observed, and there was evidence of publication bias. Notably, neither gender nor comorbid liver disease was predictive. CONCLUSIONS: The course of prior episodes of AWS is the most reliable predictor of subsequent episodes. Thrombocytopenia and hypokalemia also correlate with SAWS. We propose further research into drinking patterns, gender, and medical comorbidities.

Outpatient management of alcohol withdrawal syndrome.

Approximately 2% to 9% of patients seen in a family physician's office have alcohol dependence. These patients are at risk of developing alcohol withdrawal syndrome if they abruptly abstain from alcohol use. Alcohol withdrawal syndrome begins six to 24 hours after the last intake of alcohol, and the signs and symptoms include tremors, agitation, nausea, sweating, vomiting, hallucinations, insomnia, tachycardia, hypertension, delirium, and seizures. Treatment aims to minimize symptoms, prevent complications, and facilitate continued abstinence from alcohol. Patients with mild or moderate alcohol withdrawal syndrome can be treated as outpatients, which minimizes expense and allows for less interruption of work and family life. Patients with severe symptoms or who are at high risk of complications should receive inpatient treatment. In addition to supportive therapy, benzodiazepines, either in a fixed-dose or symptom-triggered schedule, are recommended. Medication should be given at the onset of symptoms and continued until symptoms subside. Other medications, including carbamazepine, oxcarbazepine, valproic acid, and gabapentin, have less abuse potential but do not prevent seizures. Typically, physicians should see these patients daily until symptoms subside. Although effective treatment is an initial step in recovery, long-term success depends on facilitating the patient's entry into ongoing treatment.

Repeated seizures in an elderly patient with alcohol dependence and mild cognitive impairment.

A 69-year-old man with alcohol dependence and mild cognitive impairment (MCI) suffered from repeated tonic-clonic seizures. The seizures typically occurred several hours after his last alcohol intake at home (early withdrawal seizure) and 22 days after his last intake of alcohol (14 days after the last dose of diazepam substituting for alcohol: late withdrawal seizure) on the ward. Psychiatrists in charge of this patient found it difficult to attribute his seizures to alcohol withdrawal syndrome (AWS) because of the atypical onset. The patient responded to diazepam resumption and valproate combination. This case highlights the need to always consider AWS as a possible cause of seizures and to gradually decrease diazepam as a substitute for alcohol. Moreover, in this patient, MCI may have induced vulnerability in the brain for AWS and the patients' older age might have decreased liver function leading to delayed onset of the seizures after diazepam withdrawal.

Alcohol withdrawal.

Alcohol withdrawal is a common clinical condition that has a variety of complications and morbidities. The manifestations can range from mild agitation to withdrawal seizures and delirium tremens. The treatments for alcohol withdrawal include benzodiazepines, anticonvulsants, beta-blockers and antihypertensives. Although benzodiazepines are presently a first-line therapy, there is controversy regarding the efficacies of these medications compared with others. Treatment protocols often involve one of two contrasting approaches: symptom-triggered versus fixed-schedule dosing of benzodiazepines. We describe these protocols in our review and examine the data supporting symptom-triggered dosing as the preferred method for most patients in withdrawal.The Clinical Institute Withdrawal Assessment for Alcohol scoring system for alcohol withdrawal streamlines care, optimizes patient management, and is the best scale available for withdrawal assessment. Quality improvement implications for inpatient management of alcohol withdrawal include increasing training for signs of withdrawal and symptom recognition, adding new hospital protocols to employee curricula, and ensuring manageable patient-to-physician and patient-to-nurse ratios.

Problem based review: alcohol-use disorders on the Acute Medical Unit.

Alcohol-use disorders including acute intoxication and withdrawal are common in the acute medical setting. Acute physicians should be aware of the indications for inpatient detoxification, and be able to liase with specialist alcohol services in the hospital and in the community to determine those patients for whom community-based detoxification may be beneficial. Additionally, it is important to recognise the benefit of Brief Interventions for higher-risk drinkers who are not yet dependent. For patients with confusion and a possible history of high alcohol intake and malnutrition, acute physicians should maintain a high index of suspicion for Wernicke's Encephalopathy and treat appropriately with parenteral thiamine.

Tako-tsubo cardiomyopathy precipitated by alcohol withdrawal.

A 57 year-old woman with no history of cardiac disease presented to the emergency department with confusion and seizures secondary to alcohol withdrawal. Elevated troponin levels and an electrocardiogram demonstrating global T-wave inversions prompted coronary angiography, which revealed coronary vessels free of significant disease. An echocardiogram showed both hypokinesis of the left-ventricular mid-segments with apical involvement and a hyperkinetic base consistent with tako-tsubo cardiomyopathy (TCM). Several clinical conditions have been reported as triggers of TCM. We report a case of TCM in a post-menopausal woman that was precipitated by alcohol withdrawal.

Biological markers for alcohol withdrawal seizures: a retrospective analysis.

AIMS: Alcohol withdrawal seizures (AWS) are among the most important possible complications during the detoxification treatment of alcohol-dependent patients. Pharmacological therapy is often used during detoxification, but can cause dangerous side effects [Eur Addict Res 2010;16:179-184]. In separate studies several biological markers have been described as being associated with AWS risk. We investigated the role of homocysteine (HCT), carbohydrate-deficient transferrin (CDT) and prolactin (PRL) as biological markers for the risk of developing AWS. METHODS: The present study included 189 alcohol-dependent patients of whom 51 had a history of AWS. We investigated the HCT, CDT and PRL levels of all patients and calculated sensitivity and specificity. Bayes' theorem was used to calculate positive (PPV) and negative (NPV) predictive values. RESULTS: The highest combined sensitivity and specificity for %CDT was reached at a plasma cutoff value of 3.75%. The combination of HCT at a cutoff value of 23.9 µmol/l and %CDT at a cutoff value of 3.75% showed the best predictive values (sensitivity 47.1%, specificity 88.4%, PPV 0.504, NPV 0.870). CONCLUSION: A combined assessment of HCT and CDT levels can be a useful method to identify patients at a higher risk of AWS, which may lead to a more individualized therapy.

Behavioral characterization of knockin mice with mutations M287L and Q266I in the glycine receptor α1 subunit.

We used behavioral pharmacology to characterize heterozygous knockin mice with mutations (Q266I or M287L) in the α1 subunit of the glycine receptor (GlyR) (J Pharmacol Exp Ther 340:304-316, 2012). These mutations were designed to reduce (M287L) or eliminate (Q266I) ethanol potentiation of GlyR function. We asked which behavioral effects of ethanol would be reduced more in the Q266I mutant than the M287L and found rotarod ataxia to be the behavior that fulfilled this criterion. Compared with controls, the mutant mice also differed in ethanol consumption, ethanol-stimulated startle response, signs of acute physical dependence, and duration of loss of righting response produced by ethanol, butanol, ketamine, pentobarbital, and flurazepam. Some of these behavioral changes were mimicked in wild-type mice by acute injections of low, subconvulsive doses of strychnine. Both mutants showed increased acoustic startle response and increased sensitivity to strychnine seizures. Thus, in addition to reducing ethanol action on the GlyRs, these mutations reduced glycinergic inhibition, which may also alter sensitivity to GABAergic drugs.