History Of Alcohol Withdrawal Seizures Research Articles

Long-term outcome of alcohol withdrawal seizures.

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. 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). 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). 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.

1018: SAFETY ANALYSIS OF BENZODIAZEPINE USAGE IN HIGH-RISK PATIENTS WITH SEVERE ALCOHOL WITHDRAWAL

Introduction: Delirium tremens (DTs) and alcohol withdrawal (AW) seizures are severe complications of AW with significant morbidity and mortality. In those with a history of withdrawal seizures or DTs, the administration of a GABAergic agent via a symptom-triggered regimen (STR) or scheduled regimen (SR) is crucial to preventing recurrence of these events. However, some data has shown dosing frequency does not influence these AW complications. The purpose of this study was to assess the safety of STR vs SR benzodiazepine administration in relation to recurrent AW seizures or DTs in patients with severe AW in the intensive care unit (ICU). Methods: Patients were included if admitted to an ICU at our institution between January 1, 2019 and December 31, 2020 with severe AW and a history of AW seizures and/or DTs. Groups were defined based on benzodiazepine dosing schedule: STR vs SR. The primary outcome was rates of recurrent DTs or AW seizures during ICU admission. Secondary outcome(s) include total benzodiazepine exposure. Results: Of 66 encounters identified, 13 patients met inclusion criteria. Six received STR dosing and 7 received SR dosing. Baseline characteristics were similar between groups for age, sex, and race. The STR group had fewer patients with a history of DTs (66% vs 85%) and withdrawal seizures (66% vs 71%) compared to the SR group. No differences were found between groups in incidence of recurrent DTs (16.7% vs 14.3%, p=0.906) and withdrawal seizures (16.7% vs 28.6%, p=0.612). Patients in the STR group received similar median benzodiazepine doses on day 1 (4.5 mg [1 – 11.3] vs 5 mg [3 - 9]) and lower median overall benzodiazepine usage (20.8 mg [7.6 – 41.4] vs 73.5 mg [42.6 – 138]) compared to the SR group. Conclusions: No difference was found in the rate of recurrent DTs or withdrawal seizures between the two dosing groups. However, our study is limited by small sample size and retrospective design. Overall, this study showed that both symptom-triggered and scheduled benzodiazepine dosing may be both safe and effective for patients with AW and a history of DTs or withdrawal seizures.

A Broken Heart: A Rare Complication of Hyponatremia

We present a case of a 47-year-old female with a history of anxiety, depression, and alcohol dependence with history of alcohol withdrawal seizures, who presented after a witnessed seizure episode. She admitted to drinking only copious amounts of black tea 1 week prior to presentation in an attempt to quit alcohol. She was subsequently found to be severely hyponatremic with a serum sodium level of 112 mEq/L and was admitted to the intensive care unit. Approximately 48 h after admission, she experienced sudden-onset of dizziness, diaphoresis, and nausea, with a heart rate of 42 beats/min and blood pressure of 70/40 mm Hg. STAT EKG revealed new T-wave inversions in the lateral and precordial leads and troponin was elevated to 5.99 ng/mL. Treatment was initiated for NSTEMI with continuous heparin infusion, aspirin, clopidogrel, carvedilol, and lisinopril. Transthoracic echocardiogram revealed apical and mid ventricular dyskinesia with hyperkinesis of the basal walls, with an estimated left ventricular ejection fraction of 35%. Cardiac catheterization revealed no significant coronary disease with ejection fraction 30-35% and similar areas of hypo and hyperkinesis, classic for apical ballooning syndrome. This case not only illustrates the rare phenomenon of hyponatremia-induced Takotsubo cardiomyopathy, but is one of the only incidents caused by primary polydipsia. J Med Cases. 2018;9(5):147-150 doi: https://doi.org/10.14740/jmc3050e

A Broken Heart: A Rare Complication of Hyponatremia

We present a case of a 47-year-old female with a history of anxiety, depression, and alcohol dependence with history of alcohol withdrawal seizures, who presented after a witnessed seizure episode. She admitted to drinking only copious amounts of black tea 1 week prior to presentation in an attempt to quit alcohol. She was subsequently found to be severely hyponatremic with a serum sodium level of 112 mEq/L and was admitted to the intensive care unit. Approximately 48 h after admission, she experienced sudden-onset of dizziness, diaphoresis, and nausea, with a heart rate of 42 beats/min and blood pressure of 70/40 mm Hg. STAT EKG revealed new T-wave inversions in the lateral and precordial leads and troponin was elevated to 5.99 ng/mL. Treatment was initiated for NSTEMI with continuous heparin infusion, aspirin, clopidogrel, carvedilol, and lisinopril. Transthoracic echocardiogram revealed apical and mid ventricular dyskinesia with hyperkinesis of the basal walls, with an estimated left ventricular ejection fraction of 35%. Cardiac catheterization revealed no significant coronary disease with ejection fraction 30-35% and similar areas of hypo and hyperkinesis, classic for apical ballooning syndrome. This case not only illustrates the rare phenomenon of hyponatremia-induced Takotsubo cardiomyopathy, but is one of the only incidents caused by primary polydipsia. J Med Cases. 2018;9(5):147-150 doi: https://doi.org/10.14740/jmc3050e

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.

Functional Role of the Polymorphic 647 T/C Variant of ENT1 (SLC29A1) and Its Association with Alcohol Withdrawal Seizures

BackgroundAdenosine is involved in several neurological and behavioral disorders including alcoholism. In cultured cell and animal studies, type 1 equilibrative nucleoside transporter (ENT1, slc29a1), which regulates adenosine levels, is known to regulate ethanol sensitivity and preference. Interestingly, in humans, the ENT1 (SLC29A1) gene contains a non-synonymous single nucleotide polymorphism (647 T/C; rs45573936) that might be involved in the functional change of ENT1.Principal FindingsOur functional analysis showed that prolonged ethanol exposure increased adenosine uptake activity of mutant cells (ENT1-216Thr) compared to wild-type (ENT1-216Ile) transfected cells, which might result in reduced extracellular adenosine levels. We found that mice lacking ENT1 displayed increased propensity to ethanol withdrawal seizures compared to wild-type littermates. We further investigated a possible association of the 647C variant with alcoholism and the history of alcohol withdrawal seizures in subjects of European ancestry recruited from two independent sites. Analyses of the combined data set showed an association of the 647C variant and alcohol dependence with withdrawal seizures at the nominally significant level.ConclusionsTogether with the functional data, our findings suggest a potential contribution of a genetic variant of ENT1 to the development of alcoholism with increased risk of alcohol withdrawal-induced seizures in humans.

Sequence Variations of the Human MPDZ Gene and Association With Alcoholism in Subjects With European Ancestry

Mpdz gene variations are known contributors of acute alcohol withdrawal severity and seizures in mice. To investigate the relevance of these findings for human alcoholism, we resequenced 46 exons, exon-intron boundaries, and 2 kilobases in the 5' region of the human MPDZ gene in 61 subjects with a history of alcohol withdrawal seizures (AWS), 59 subjects with a history of alcohol withdrawal without AWS, and 64 Coriell samples from self-reported nonalcoholic subjects [all European American (EA) ancestry] and compared with the Mpdz sequences of 3 mouse strains with different propensity to AWS. To explore potential associations of the human MPDZ gene with alcoholism and AWS, single SNP and haplotype analyses were performed using 13 common variants. Sixty-seven new, mostly rare variants were discovered in the human MPDZ gene. Sequence comparison revealed that the human gene does not have variations identical to those comprising Mpdz gene haplotype associated with AWS in mice. We also found no significant association between MPDZ haplotypes and AWS in humans. However, a global test of haplotype association revealed a significant difference in haplotype frequencies between alcohol-dependent subjects without AWS and Coriell controls (p = 0.015), suggesting a potential role of MPDZ in alcoholism and/or related phenotypes other than AWS. Haplotype-specific tests for the most common haplotypes (frequency > 0.05), revealed a specific high-risk haplotype (p = 0.006, maximum statistic p = 0.051), containing rs13297480G allele also found to be significantly more prevalent in alcoholics without AWS compared with nonalcoholic Coriell subjects (p = 0.019). Sequencing of MPDZ gene in individuals with EA ancestry revealed no variations in the sites identical to those associated with AWS in mice. Exploratory haplotype and single SNP association analyses suggest a possible association between the MPDZ gene and alcohol dependence but not AWS. Further functional genomic analysis of MPDZ variants and investigation of their association with a broader array of alcoholism-related phenotypes could reveal additional genetic markers of alcoholism.

Status epilepticus and alcohol abuse: an analysis of 82 status epilepticus admissions.

In 1979-80, 82 cases of grand mal status epilepticus (71 patients, 39 male and 32 female) were admitted to the Casualty Department of Meilahti University Hospital in Helsinki, Finland. The cause of the underlying epilepsy was symptomatic in 43 cases (52.4%) and idiopathic in 19 cases (23.2%). In 6 cases (7.3%), there was a history of alcohol withdrawal seizures, and in 14 cases (17.1%) there was no earlier history of convulsions. Status epilepticus was associated with an acute or progressive cerebral disorder in 14 episodes. These comprised 6 bouts of status with brain tumour, 4 with acute stroke and 4 with brain injury. Alcohol abuse preceded the status in 29 episodes (35.4%), 23 of which occurred in men (53.5% of the male cases). Excessive use of alcohol was the only obvious precipitating factor for status in 16 cases, and in 6 cases the status presented as a prolonged alcohol withdrawal seizure. A change or irregularity of anticonvulsive drug therapy could be documented in 14 cases and an acute infection outside the central nervous system in 7 cases. Intravenous diazepam, used as the only therapy for status epilepticus, was effective in 58 of 78 episodes. In 7 cases of prolonged status, a thiopental sodium anaesthesia proved effective. The total mortality was 4.2%, including 2 deaths from concomitant extracerebral disorders and one late death from brain metastasis.

Apolipoprotein E gene polymorphism and previous alcohol withdrawal seizures

Aim of this study was to investigate the possible association of apolipoprotein E (ApoE) gene polymorphism with a history of alcohol withdrawal seizures. We included 194 patients with alcohol dependence who were divided into patients with (SZ+) and without (SZ−) previous alcohol withdrawal seizures. ApoE genotypes were determined using PCR. For statistical analysis we examined the number of ApoE alleles (ApoE2: n = 36; ApoE3: n = 311; ApoE4: n = 41). A significant positive association with a positive history of withdrawal seizures (SZ+) was found in the ApoE3 allele group (Fisher’s exact test: p = 0.006) while a significant negative association was observed in the ApoE2 allele group (Fisher’s exact test: p = 0.029). For the ApoE4 allele group no significant differences were found regarding a history of withdrawal seizures. Our findings suggest an association between the apolipoprotein E3 gene variant and an elevated risk of alcohol withdrawal seizures. These preliminary results must be validated in further studies.

The polymorphism GABABR1 T1974C [rs29230] of the GABABreceptor gene is not associated with the diagnosis of alcoholism or alcohol withdrawal seizures

As the inhibitory neurotransmitter gamma aminobutyric acid (GABA) modulates ethanol consumption, alcohol withdrawal symptoms and seizure generation by interacting with the GABAB receptor, the genes encoding for the GABAB receptor can be considered as candidate genes for alcoholism and alcohol withdrawal seizures (AWS). As the polymorphism GABABR1 T1974C[rs29230] of the GABAB receptor gene had been associated with alcoholism and EEG abnormalities in prior studies, the present examination investigated if the polymorphism is associated with the diagnosis of alcoholism or AWS. After genotyping the allele and genotype frequencies of a group of alcoholics with a history of AWS (n = 69) were compared with the results of a group of alcoholics with only mild withdrawal symptoms (n = 97). Additionally a group of healthy controls (n = 101) was compared with individuals with the diagnosis of alcoholism (n = 220). As no significant differences were found between the compared groups, this study gave no further evidence for GABABR1 T1974C[rs29230] as a candidate for alcoholism or AWS.

Elevated prolactin serum levels and history of alcohol withdrawal seizures

Background Prolactin has been discussed to be useful for differential diagnosis in epilepsia. Aim of the present study was to investigate the association between prolactin serum levels and previous alcohol withdrawal seizures. Methods We assessed 118 male patients admitted for detoxification treatment. Previous withdrawal seizures were recorded and prolactin serum levels were measured using an enzymatic immunoassay. Results Patients with a history of alcohol withdrawal seizures had significantly higher prolactin levels (17.8 ng/ml, SD = 12.1) than patients without previous seizures (13.0 ng/ml, SD = 8.1, p < 0.05). Logistic regression revealed significant predictive qualities for prolactin serum levels ( B = 0.05, Wald = 5.30, p = 0.021, OR = 1.06, 95%CI = 1.01–1.11). Conclusions The present findings show an association between elevated prolactin serum levels and a history of withdrawal seizures. Hence, the results suggest that prolactin elevation at admission may be a clinical marker for an increased risk of withdrawal seizures.

ASSOCIATION OF THE DOPAMINE TRANSPORTER GENE WITH ALCOHOLISM

It was investigated whether the allele A9 of the dopamine transporter gene (DAT1; SLC6A3) is associated with alcoholism, delirium tremens (DT), alcohol withdrawal seizures (AWS), or the daily alcohol intake. A group of 102 healthy subjects and 216 alcoholics, including 97 patients with a history of mild withdrawal symptoms, 65 with a history of AWS and 83 with a history of DT were genotyped and personal data were achieved for statistical evaluation in a case-control design. The frequency of individuals carrying the allele A9 [f(A9+)] was significantly higher (P = 0.01) in the group of alcoholics [f(A9+) = 0.48] compared with healthy controls [f(A9+) = 0.32]. There was no significant association of the allele A9 with severe withdrawal symptoms or the daily amount of alcohol consumed. Our results reveal that the allele A9 is strongly associated with alcoholism but not with withdrawal symptoms or daily alcohol intake.

Homocysteine levels in patients classified according to Lesch's typology.

It has been suggested that elevated total plasma homocysteine levels might be useful to predict alcohol withdrawal seizures. The typology by Lesch distinguishes between four subtypes of which type 1 suffers from marked withdrawal symptoms, including alcohol withdrawal seizures. This study was undertaken to investigate total plasma homocysteine levels in actively drinking patients with alcoholism who were classified according to Lesch's typology. We determined total plasma homocysteine levels in 144 non-abstinent chronic alcoholics (115 men, 29 women; aged 22-67 years). Patients were classified in Lesch's typology (LT) and were divided into two groups: LT 1 (n = 27) and LT 2-4 (n = 117). Within the groups, patients with or without a history of alcohol withdrawal seizures were differentiated. All patients with a history of alcohol withdrawal seizures had significantly elevated plasma homocysteine concentrations at admission when compared with those without seizures (Mann-Whitney U, P < 0.001). Furthermore, patients classified as LT 1 who suffered from an alcohol withdrawal seizure (n = 12) had significantly higher plasma homocysteine levels (Z = -2.31, P = 0.02) when compared to the corresponding types 2-4 (n = 24). Using a logistic regression analysis, withdrawal seizures were best predicted by a high homocysteine level at admission but even more pronounced in LT 1 (Wald's chi-squared [chi(2)] = 10.7; odds ratio [OR] 1.24; 95% confidence interval [CI] 1.03-1.51; P < 0.001) when compared with LT 2-4 (chi(2) = 10.6; OR 1.06; 95%CI 1.03-1.14; P = 0.004). To our knowledge, this is the first study evaluating homocysteine levels in patients who were classified according to Lesch's typology. Homocysteine levels on admission may be a useful screening method to identify actively drinking patients at risk of alcohol withdrawal seizures, especially in alcoholics with Lesch type 1.

IS DAILY SINGLE DOSAGE OF DIAZEPAM AS EFFECTIVE AS CHLORDIAZEPOXIDE IN DIVIDED DOSES IN ALCOHOL WITHDRAWAL -- A PILOT STUDY

We report on a pilot double-blind study on the effectiveness of divided doses of chlordiazepoxide and a single daily dose of diazepam in the treatment of the alcohol-withdrawal syndrome. While a variety of drugs (chlormethiazole, propranolol and clonidine) have been used for treatment of alcohol-withdrawal symptoms, benzodiazepines remain the drugs of choice for alcohol detoxification (Mayo-Smith, 1997). Diazepam and chlordiazepoxide are both longer-acting benzodiazepines, and preferred for detoxification (Williams and McBride, 1998). Traditionally, chlordiazepoxide has been the benzodiazepine of choice due to its lower dependence and abuse potential, whereas diazepam has been used in patients with a history of alcohol-withdrawal seizures. In view of the accent on community detoxification, we undertook this pilot study to evaluate the effectiveness of a single daily dose of diazepam in …