Successful Synergistic Use of Gabapentin With Other Antiepileptic Drugs in the Management of Lance-Adams Syndrome Complicated by Alcohol Withdrawal Seizures: A Case Report.

OBJECTIVE: Lance-Adams syndrome is a rare and debilitating disorder characterized by successful cardiopulmonary resuscitation resulting in myoclonus activity. Alcohol withdrawal seizures from alcohol use disorder may further exacerbate Lance-Adams syndrome. We aim to present a case of Lance-Adams syndrome complicated by alcohol withdrawal seizures and successfully treated with a combination of valproate, clonazepam, and gabapentin. MATERIALS AND METHODS: The patient's electronic medical record, direct patient care experiences, and a comprehensive literature search were used for this case report. We report a 41-year-old male patient with Lance-Adams syndrome with concurrent alcohol use disorder. Treatment was improved when adding gabapentin for alcohol use disorder treatment, alongside combination antiepileptic therapy. A PubMed search was conducted to examine Lance-Adams syndrome case reports of successful combination antiepileptic therapy, with a secondary evaluation of patients with concurrent alcohol use disorder. RESULTS: The literature search yielded 18 articles, which resulted in 21 individual cases in which combination antiepileptic drug therapy was successful in treating myoclonus secondary to Lance-Adams syndrome; however, none of the case reports utilized gabapentin synergistically. One case described Lance-Adams syndrome complicated by alcohol consumption and similar to our patient, the patient used alcohol to abolish myoclonic activity. CONCLUSIONS: To the best of our knowledge, this is the first case report documenting a patient with Lance-Adams syndrome and concurrent alcohol use disorder, with a positive effect of gabapentin use. Gabapentin, when used for alcohol use disorder treatment, may be an appropriate adjunct agent in the management of patients receiving combination antiepileptic therapy for the treatment of Lance-Adams syndrome.

Long-term outcome of alcohol withdrawal seizures.

BACKGROUND AND PURPOSE: Alcohol withdrawal seizures (AWS) are a well-known complication of chronic alcohol abuse, but there is currently little knowledge of their long-term relapse rate and prognosis. The aims of this study were to identify risk factors for AWS recurrence and to study the overall outcome of patients after AWS. METHODS: In this retrospective single-center study, we included patients who were admitted to the Emergency Department after an AWS between January 1, 2013 and August 10, 2021 and for whom an electroencephalogram (EEG) was requested. AWS relapses up until April 29, 2022 were researched. We compared history, treatment with benzodiazepines or antiseizure medications (ASMs), laboratory, EEG and computed tomography findings between patients with AWS relapse (r-AWS) and patients with no AWS relapse (nr-AWS). RESULTS: A total of 199 patients were enrolled (mean age 53 ± 12 years; 78.9% men). AWS relapses occurred in 11% of patients, after a median time of 470.5 days. Brain computed tomography (n = 182) showed pathological findings in 35.7%. Risk factors for relapses were history of previous AWS (p = 0.013), skull fractures (p = 0.004) at the index AWS, and possibly epileptiform EEG abnormalities (p = 0.07). Benzodiazepines or other ASMs, taken before or after the index event, did not differ between the r-AWS and the nr-AWS group. The mortality rate was 2.9%/year of follow-up, which was 13 times higher compared to the general population. Risk factors for death were history of AWS (p < 0.001) and encephalopathic EEG (p = 0.043). CONCLUSIONS: Delayed AWS relapses occur in 11% of patients and are associated with risk factors (previous AWS >24 h apart, skull fractures, and pathological EEG findings) that also increase the epilepsy risk, that is, predisposition for seizures, if not treated. Future prospective studies are mandatory to determine appropriate long-term diagnostic and therapeutic strategies, in order to reduce the risk of relapse and mortality associated with AWS.

Alcohol withdrawal produces changes in excitability, population discharge probability, and seizure threshold.

BACKGROUND: Alcohol withdrawal syndrome (AWS) results from the sudden cessation of chronic alcohol use and is associated with high morbidity and mortality. Alcohol withdrawal-induced central nervous system (CNS) hyperexcitability results from complex, compensatory changes in synaptic efficacy and intrinsic excitability. These changes in excitability counteract the depressing effects of chronic ethanol on neural transmission and underlie symptoms of AWS, which range from mild anxiety to seizures and death. The development of targeted pharmacotherapies for treating AWS has been slow, due in part to the lack of available animal models that capture the key features of human AWS. Using a unique optogenetic method of probing network excitability, we examined electrophysiologic correlates of hyperexcitability sensitive to early changes in CNS excitability. This method is sensitive to pharmacologic treatments that reduce excitability and may represent a platform for AWS drug development. METHODS: We applied a newly developed method, the optogenetic population discharge threshold (oPDT), which uses light intensity response curves to measure network excitability in chronically implanted mice. Excitability was tracked using the oPDT before, during, and after the chronic intermittent exposure (CIE) model of alcohol withdrawal (WD). RESULTS: Alcohol withdrawal produced a dose-dependent leftward shift in the oPDT curve (denoting increased excitability), which was detectable in as few as three exposure cycles. This shift in excitability mirrored an increase in the number of spontaneous interictal spikes during withdrawal. In addition, Withdrawal lowered seizure thresholds and increased seizure severity in optogenetically kindled mice. CONCLUSION: We demonstrate that the oPDT provides a sensitive measure of alcohol withdrawal-induced hyperexcitability. The ability to actively probe the progression of excitability without eliciting potentially confounding seizures promises to be a useful tool in the preclinical development of next-generation pharmacotherapies for AWS.

Quantitative electroencephalographic analysis of delirium tremens development following alcohol-withdrawal seizure based on a small number of male cases.

INTRODUCTION: Seizures and delirium tremens (DTs) are recognized as severe alcohol-withdrawal symptoms. Prolonged admission and serious complications associated with alcohol withdrawal are responsible for increased costs and use of medical and social resources. This study investigated the predictive value of quantitative electroencephalography (QEEG) for developing alcohol-related DTs after alcohol-withdrawal seizure (AWS). METHODS: We compared differences in QEEG in patients after AWS (n = 13). QEEG was performed in the intensive care unit within 48 h of admission, including in age- and sex-matched healthy controls. We also investigated the prognostic value of QEEG for the development of alcohol DTs after AWS in a retrospective, case-control study. The spectral power of each band frequency and the ratio of the theta to alpha band (TAR) in the electroencephalogram were analyzed using iSyncBrain® (iMediSync, Inc., Korea). RESULTS: The beta frequency and the alpha frequency band power were significantly higher and lower, respectively, in patients than in age- and sex-matched healthy controls. In AWS patients with DTs, the relative beta-3 power was lower, particularly in the left frontal area, and the TAR was significantly higher in the central channel than in those without DTs. CONCLUSION: Quantitative EEG showed neuronal excitability and decreased cognitive activities characteristic of AWS associated with alcohol-withdrawal state, and we demonstrated that quantitative EEG might be a helpful tool for detecting patients at a high risk of developing DTs during an alcohol-dependence period.

Delirium Tremens in the Older Adult.

INTRODUCTION: Caring for patients experiencing alcohol withdrawal syndrome can be challenging. Patients 65 and older are at increased risk for alcohol withdrawal syndrome related complications. The higher prevalence of co-morbidities, including cognitive impairment, longer drinking history and greater sensitivity to alcohol withdrawal syndrome treatment are the result of decreased ability of the brain to adapt to stressors such as illness, trauma, or surgery. DELIRIUM TREMENS: Symptoms may appear earlier from the last drink and present with a wide range of symptoms. The most effective interventions require high-quality nursing care delivery to prevent, decrease the severity and shorten the duration of delirium. NURSING IMPLICATIONS: Strategies that help minimize these challenges starts with obtaining the patient's selfreport of their alcohol use history. Nurses should be diligent in their monitoring for signs of active alcohol withdrawal. Screening and assessment tools such as the Clinical Institute Withdrawal Assessment for Alcohol-Revised should guide pharmacological management. To support nurses in identifying delirium tremens, this manuscript seek to describe the underlying pathophysiology, key assessment components and nursing management of delirium tremens in the older adult.

Development of disturbance of consciousness is associated with increased severity in acute pancreatitis.

BACKGROUND: Disturbance of consciousness (DOC) may develop in acute pancreatitis (AP). In clinical practice, it is known that DOC may worsen the patient's condition, but we have no exact data on how DOC affects the outcome of AP. METHODS: From the Hungarian Pancreatic Study Groups' AP registry, 1220 prospectively collected cases were analyzed, which contained exact data on DOC, included patients with confusion, delirium, convulsion, and alcohol withdrawal, answering a post hoc defined research question. Patients were separated to Non-DOC and DOC, whereas DOC was further divided into non-alcohol related DOC (Non-ALC DOC) and ALC DOC groups. For statistical analysis, independent sample t-test, Mann-Whitney, Chi-squared, or Fisher exact test were used. RESULTS: From the 1220 patients, 47 (3.9%) developed DOC, 23 (48.9%) cases were ALC DOC vs. 24 (51.1%) Non-ALC DOC. Analysis between the DOC and Non-DOC groups showed a higher incidence of severe AP (19.2% vs. 5.3%, p < 0.001), higher mortality (14.9% vs. 1.7%, p < 0.001), and a longer length of hospitalization (LOH) (Me = 11; IQR: 8-17 days vs. Me = 9; IQR: 6-13 days, p = 0.049) respectively. Patients with ALC DOC developed more frequently moderate AP vs. Non-ALC DOC (43.5% vs. 12.5%), while the incidence of severe AP was higher in Non-ALC vs. ALC DOC group (33.3% vs. 4.4%) (p < 0.001). LOH showed a tendency to be longer in Non-ALC DOC compared to ALC DOC, respectively (Me:13; IQR:7-20 days vs. Me:9.5; IQR:8-15.5 days, p = 0.119). CONCLUSION: DOC during AP is associated with a higher rate of moderate and severe AP and increases the risk of mortality.

Alcohol-induced thrombocytopenia: Current review.

Thrombocytopenia is a decrease in the platelet count below 150,000 in a microliter of blood, i.e., below the lower limit of the reference range, which is 150,000-400,000/µL. The phenomenon of thrombocytopenia related to heavy drinking began to arouse interest in the 1960s and 1970s. It was initially described in case reports and clinical studies on small groups. In the following years, the phenomenon itself and the significance of alcohol-induced thrombocytopenia was studied. Many methodological difficulties inhibiting objective conclusions from research were encountered. Model pathological mechanisms of alcohol thrombocytopenia and the effects of alcohol on the structure and function of platelets were described. Furthermore, the phenomenon of rapid normalization of the number of platelets in people who stopped drinking was described. Relationships between alcohol use, its intensity and occurrence, and intensity of thrombocytopenia have been demonstrated. Predictive platelet counts for alcohol withdrawal syndrome complications have been proven and calculated. The risk of occurrence of withdrawal seizures or delirium tremens in alcohol withdrawal syndrome increases significantly when the platelet count is less than 119,000/µL. The knowledge of the nature of the phenomenon of alcohol-induced thrombocytopenia in a clinical environment allows decisions that are more rational. The attention of clinicians should be drawn to the importance of results of blood tests routinely collected on admission.

Affective Behavior in Withdrawal Seizure-Prone and Withdrawal Seizure-Resistant Mice during Long-Term Alcohol Abstinence.

BACKGROUND: While the acute alcohol withdrawal syndrome has been well characterized both in human clinical studies and in experimental animals, much less is known regarding long-term affective disturbances that can sometimes persist during protracted abstinence. Nevertheless, since relapse often occurs long after acute detoxification and may be predicted by persistent affective disruption, a better understanding of the long-term behavioral consequences of prior alcohol dependence may lead to improved strategies for relapse prevention. METHODS: Male and female Withdrawal Seizure-Prone and Withdrawal Seizure-Resistant mice from the second selection replicate (WSP-2, WSR-2) were exposed to a 10-day chronic-intermittent ethanol vapor protocol (CIE) or plain air and then tested repeatedly on the sucrose preference test (SPT), marble burying test (MBT), and the light-dark box test (LDT) over 7 weeks of (forced) abstinence. RESULTS: While WSP and WSR mice differed significantly on tests of anxiety-like behavior (LDT, MBT), we found little evidence for long-term affective disruption following CIE in either line. The major exception was in the LDT, in that WSP but not WSR mice displayed longer latencies to enter the light compartment following CIE relative to air-controls. CONCLUSIONS: Selective breeding for acute withdrawal severity has resulted in differences in anxiety-like behavior between WSP and WSR mice. In contrast, however, genes contributing to the severity of acute withdrawal convulsions appear to have little overlap with those predisposing to affective disruption during long-term abstinence.

Topiramate-induced acute liver injury: A rare adverse effect.

Idiosyncratic drug-induced liver injury (DILI) is damage to liver occurring at recommended dose of a drug in contrast to toxic or predictable DILI. Although it is common in first-generation antiepileptic drugs (AEDs), it is rare in newer AEDs such as topiramate. Topiramate commonly causes neurological adverse effects such as psychomotor slowing and somnolence. Hepatotoxicity by topiramate is rare and has been previously reported in combination with other drugs such as valproate and carbamazepine. Here, we report a case of topiramate-induced asymptomatic elevation of liver enzymes in an adult man diagnosed with alcohol dependence syndrome and alcohol withdrawal complicated with seizures.

Nalmefeno: ¿un nuevo enfoque en el manejo del trastorno por uso de alcohol? / Nalmefene: a new approach in the management of alcohol dependence disorders?

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Clinical predictors for delirium tremens in patients with alcohol withdrawal seizures.

BACKGROUND: Delirium tremens (DT) is the severest form of alcohol withdrawal syndrome, frequently after alcohol withdrawal seizures. Delirium tremens occurs in a small proportion of patients with alcohol withdrawal seizures; nevertheless, early identification of high-risk patients is important for intensive preventive management of unexpected episodes due to agitation and its associated increased mortality. However, there are limited studies on clinical predictors of the development of DT in patients with alcohol withdrawal seizures. METHODS: Patients who visited the emergency department with acute seizures were included in the study when alcohol withdrawal was the only or the strongest precipitating factor for seizures. All patients were carefully observed for at least 48 hours in the intensive care unit after the initial assessment to closely monitor vital signs and development of DT. Clinical and laboratory findings were analyzed for predicting the development of DT. RESULTS: Of the 97 patients (82 males; mean age, 48.6 ± 13.3 years) with alcohol withdrawal seizures, 34 (35.1%) developed DT. Low platelet count, high blood level of homocysteine, and low blood level of pyridoxine were associated with the subsequent development of DT. Low platelet count and high blood level of homocysteine were independent risk factors with high diagnostic sensitivity and specificity for the development of DT. CONCLUSIONS: The study indicated that some easily determined parameters are potential clinical predictors for the development of DT in patients with alcohol withdrawal seizures. These findings would be helpful in clinical identification and management patients at high risk for DT.

The "Prediction of Alcohol Withdrawal Severity Scale" (PAWSS): systematic literature review and pilot study of a new scale for the prediction of complicated alcohol withdrawal syndrome.

BACKGROUND: To date, no screening tools for alcohol withdrawal syndromes (AWS) have been validated in the medically ill. Although several tools quantify the severity of AWS (e.g., Clinical Institute Withdrawal Assessment for Alcohol [CIWA]), none identify subjects at risk of AWS, thus missing the opportunity for timely prophylaxis. Moreover, there are no validated tools for the prediction of complicated (i.e., moderate to severe) AWS in the medically ill. OBJECTIVES: Our goals were (1) to conduct a systematic review of the published literature on AWS to identify clinical factors associated with the development of AWS, (2) to use the identified factors to develop a tool for the prediction of alcohol withdrawal among patients at risk, and (3) to conduct a pilot study to assess the validity of the tool. METHODS: For the creation of the Prediction of Alcohol Withdrawal Severity Scale (PAWSS), we conducted a systematic literature search using PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines for clinical factors associated with the development of AWS, using PubMed, PsychInfo, MEDLINE, and Cochrane Databases. Eligibility criteria included: (i) manuscripts dealing with human subjects, age 18 years or older, (ii) manuscripts directly addressing descriptions of AWS or its predisposing factors, including case reports, naturalistic case descriptions, and all types of clinical trials (e.g., randomized, single-blind, or open label studies), (iii) manuscripts describing characteristics of alcohol use disorder (AUD), and (iv) manuscripts dealing with animal data (which were considered only if they directly dealt with variables described in humans). Obtained data were used to develop the Prediction of Alcohol Withdrawal Severity Scale, in order to assist in the identification of patients at risk for complicated AWS. A pilot study was conducted to assess the new tool's psychometric qualities on patients admitted to a general inpatient medicine unit over a 2-week period, who agreed to participate in the study. Blind to PAWSS results, a separate group of researchers retrospectively examined the medical records for evidence of AWS. RESULTS: The search produced 2802 articles describing factors potentially associated with increased risk for AWS, increased severity of withdrawal symptoms, and potential characteristics differentiating subjects with various forms of AWS. Of these, 446 articles met inclusion criteria and underwent further scrutiny, yielding a total of 233 unique articles describing factors predictive of AWS. A total of 10 items were identified as correlated with complicated AWS (i.e., withdrawal hallucinosis, withdrawal-related seizures, and delirium tremens) and used to construct the PAWSS. During the pilot study, a total of 68 subjects underwent evaluation with PAWSS. In this pilot sample the sensitivity, specificity, and positive and negative predictive values of PAWSS were 100%, using the threshold score of 4. DISCUSSION: The results of the literature search identified 10 items which may be correlated with risk for complicated AWS. These items were assembled into a tool to assist in the identification of patients at risk: PAWSS. The results of this pilot study suggest that PAWSS may be useful in identifying risk of complicated AWS in medically ill, hospitalized individuals. PAWSS is the first validated tool for the prediction of severe AWS in the medically ill and its use may aid in the early identification of patients at risk for complicated AWS, allowing for prophylaxis against AWS before severe alcohol withdrawal syndromes develop.

Risk assessment of moderate to severe alcohol withdrawal--predictors for seizures and delirium tremens in the course of withdrawal.

AIMS: To develop a prediction model for withdrawal seizures (WS) and delirium tremens (DT) during moderate to severe alcohol withdrawal syndrome (AWS) in a large cohort of inpatients treated for AWS (n = 827). METHODS: Re-analysis of a cohort study population treated between 2000 and 2009. All patients received a score-guided and symptom-triggered therapy for AWS. Multivariable binary logistic regression models with stepwise variable selection procedures were conducted providing odds ratio (OR) estimates. RESULTS: In the multivariable regression, significant predictors of WS during AWS therapy were a delayed climax of withdrawal severity since admission [OR/10 h: 1.23; 95% confidence interval (CI): 1.1-1.4; P < 0.001)], prevalence of structural brain lesions in the patient's history (OR 6.5; 95% CI: 3.0-14.1; P < 0.001) and WS as the cause of admittance (OR 2.6; 95% CI: 1.4-4.8; P = 0.002). Significant predictors at admission for the occurrence of DT were lower serum potassium (OR/1 mmol/l 0.33; 95% CI: 0.17-0.65; P = 0.001), a lower platelet count (OR/100.000 0.42; 95% CI: 0.26-0.69; P = 0.001) and prevalence of structural brain lesions (OR 5.8; 95% CI: 2.6-12.9; P < 0.001). CONCLUSION: In this large retrospective cohort, some easily determinable parameters at admission may be useful to predict a complicated course of alcohol withdrawal regarding the occurrence of WS or DT. Using the provided nomograms, clinicians can estimate the percentage likelihood of patients to develop either WS or DT during their course of withdrawal. Prevalence of structural brain lesions in the patient's history does strongly warrant a careful observation of patients.

Carbamazepine and valproate as adjuncts in the treatment of alcohol withdrawal syndrome: a retrospective cohort study.

AIMS: To compare the clinical course, incidence of withdrawal seizures (WS) or delirium tremens (DT) and side effects during treatment of alcohol withdrawal in patients treated with either carbamazepine (CBZ) or valproate (VPA) as an adjunct to clomethiazole and clonidine therapy. METHODS: Retrospective analysis of charts of two cohorts of inpatients treated during 2000-2009: CBZ 374 patients, VPA 453 patients. RESULTS: At baseline, those treated with VPA and those treated with CBZ were similar except for a trend to younger age and a higher incidence of previous WS in the CBZ group. The median duration of pharmacological treatment (91 vs. 76 h; P < 0.001) and the length of stay (8 vs. 6 days; P < 0.001) as well as the need for intensive care treatment (7 vs. 2%; P = 0.001) were significantly higher in the CBZ than the VPA group. Additionally, withdrawal-related complications such as WS occurred more often in the CBZ group (9.6 vs. 5.5%; not significant after adjusting for potential confounders); the incidence of DT in the CBZ group was insignificantly higher (6.6 vs. 4.4%; P = 0.52). Admittance with seizures and older age were predictors of WS and DT, respectively. Adverse drug reactions, mainly affecting the central nervous system, were significantly more frequent with CBZ than VPA (7.6 vs. 2%; P < 0.001). CONCLUSION: During alcohol withdrawal, VPA may offer some benefits compared with CBZ due to favorable tolerability, possibly less incidence of WS and a shorter duration of pharmacological treatment.

Alcohol-related seizures.

The term alcohol-related seizures (ARS) is used to refer to all seizures in the aggregate associated with alcohol use, including the subset of alcohol withdrawal seizures (AWS). From 20% to 40% of patients with seizure who present to an emergency department have seizures related to alcohol abuse. However, it is critical to avoid prematurely labeling a seizure as being caused by alcohol withdrawal before performing a careful diagnostic evaluation. Benzodiazepines alone are sufficient to prevent AWS. The alcoholic patient with a documented history of ARS, who experiences a single seizure or a short burst of seizures should be treated with lorazepam, 2 mg intravenously.