History Of Withdrawal Seizures Research Articles

Characterization of alcohol-related seizures in withdrawal syndrome.

Alcohol-related seizures (ARS) are one of the most important consequences of alcohol withdrawal syndrome (AWS). However, demographic and clinical characteristics, and furthermore, the relationship of ARS with delirium tremens (DT), have not yet been evaluated in detail. Therefore, the aim of the present study was to reveal the correlates of ARS and examine the interaction of ARS with the occurrence of DT and with the severity of AWS. In the retrospective study (Study 1) 2851 medical charts of inpatient admissions characterized by AWS and DT were listed. Demographic and clinical variables of ARS were assessed. In the follow-up study (Study 2), patients admitted with AWS without (N = 28) and with (N = 18) ARS were enrolled. Study 1 was performed between 2008 and 2023, and Study 2 was performed in 2019 in Hungary. To determine the severity of AWS, the Clinical Institute Withdrawal Assessment Scale for Alcohol, Revised (CIWA-Ar) was used. ARS is a provoked, occasional seizure; therefore, patients with epilepsy syndrome were excluded from the two studies. Statistical analyses were performed by the means of chi-square tests, multinomial logistic regressions, mixed ANOVA, and derivation. The occurrence of DT, the history of ARS, and somatic co-morbidities were found to be risk factors for the appearance of ARS. ARS was proved to be a risk factor for the development of DT. In the follow-up study, there was no difference in the decrease of CIWA-Ar scores between the groups. Our present findings support the likelihood of kindling, which is one of the most important mechanisms underlying the development of ARS, but do not directly prove its presence. Additionally, our results revealed that the severity of AWS is not influenced by the presence of ARS. Provoked, occasional seizures during AWS are defined as ARS. In the present study, predictors and interactions of these seizures with DT-the most severe form of withdrawal-and with the severity of withdrawal were examined in retrospective and follow-up studies. The present study shows that a history of withdrawal seizures, the occurrence of DT, and somatic comorbidities are predictors of the development of seizures. Furthermore, our findings suggest that the presence of seizures does not influence the severity of withdrawal.

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.

P-50 * THE PREVALENCE OF SEIZURES DURING WITHDRAWAL FROM ALCOHOL, BENZODIAZEPINES AND OPIATES IN MEDICALLY MONITORED DETOXIFICATION CENTER

Generalized tonic-clonic seizures are the common severe complication of drug withdrawal. Efforts to prevent occurrence of seizures is an important factor in improvement of safety and quality of patient care. Medically monitored detoxification centers admit patients with known history of withdrawal seizures as well as history of seizure disorders for detoxification from alcohol benzodiazepines and opioids. Over last two years 12356 patients were admitted for inpatient detoxification, 260 patients had known history of seizures due to variety of etiologies. Patients underwent detoxification using chlordiazepoxide, phenobarbital and methadone. During last 2 years 38 patients developed seizures during detoxification. All occurrences were reviewed on the monthly basis as a part of quality of patient care monitoring. Majority of seizures are early onset events and occur within 48 hours from time of admission due to alcohol, and combined alcohol/ benzodiazepine withdrawal. Minority of seizures were related to benzodiazepine/opioid withdrawal, and use of medication lowering the seizure threshold like bupropion and antipsychotics, and were of late onset. In conclusion majority of tonic-clonic seizures in patients undergoing detoxification in medically monitored are an early onset seizures occurring in patients withdrawing from alcohol or alcohol/benzodiazepine combination. Detoxification using log acting benzodiazepines or phenobarbital is a safe therapy for patients with prior history of seizures. Avoidance of medication reducing seizure threshold may further reduce incidence of seizures.

Comparison of Two Oral Symptom-triggered Pharmacological Inpatient Treatments of Acute Alcohol Withdrawal: Clomethiazole vs. Clonazepam

To compare two inpatient symptom-triggered pharmacological treatments of acute alcohol withdrawal (AWS) (clomethiazole vs. clonazepam). Prospective observational comparison within a quality improvement project. Because of a need for extra precautions against complications such as seizures and severe respiratory complaints, patients with a history of withdrawal seizures or complications with clomethiazole in their history were automatically assigned to the clonazepam group. The remaining patients were alternately assigned either to the clonazepam group (n = 38 altogether) or the clomethiazole group (n = 36). Rescue medication could consist of adding either extra clonazepam or clomethiazole. Effectiveness was measured by Clinical Global Impression Scale, Revised Clinical Institute Withdrawal Assessment for Alcohol Scale, Mainz Alcohol Withdrawal Scale, Essen Self-Assessment-Alcohol Withdrawal and attrition rate. Safety and tolerability was estimated from adverse clinical events. Secondary outcome values were heart rate, blood and pulse pressure. There were no significant differences between the treatments with respect to primary and secondary effectiveness measures, safety or tolerability or duration of medication treatment. Both reduced the severity of initial withdrawal symptoms below 20% up to the ending of withdrawal medications. No withdrawal seizure or delirium occurred. Both score-driven treatments were equally effective, safe and well tolerated in this setting. This is the first study demonstrating the utility of clonazepam in the treatment of AWS syndrome.

Hyponatremia and Central Pontine Myelinolysis as a Result of Beer Potomania

Hyponatremia and Central Pontine Myelinolysis as a Result of Beer Potomania

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.

EFNS guideline on the diagnosis and management of alcohol‐related seizures: report of an EFNS task force

Despite being a considerable problem in neurological practice and responsible for one-third of seizure-related admissions, there is little consensus as to the optimal investigation and management of alcohol-related seizures. The final literature search was undertaken in September 2004. Consensus recommendations are given graded according to the EFNS guidance regulations. To support the history taking, use of a structured questionnaire is recommended. When the drinking history is inconclusive, elevated values of carbohydrate-deficient transferrin and/or gammaglutamyl transferase can support a clinical suspicion. A first epileptic seizure should prompt neuroimaging (CT or MRI). Before starting any carbohydrate containing fluids or food, patients presenting with suspected alcohol overuse should be given prophylactic thiamine parenterally. After an alcohol withdrawal seizure (AWS), the patient should be observed in hospital for at least 24 h and the severity of withdrawal symptoms needs to be followed. For patients with no history of withdrawal seizures and mild to moderate withdrawal symptoms, routine seizure preventive treatment is not necessary. Generally, benzodiazepines are efficacious and safe for primary and secondary seizure prevention; diazepam or, if available, lorazepam, is recommended. The efficacy of other drugs is insufficiently documented. Concerning long-term recommendations for non-alcohol dependent patients with partial epilepsy and controlled seizures, small amounts of alcohol may be safe. Alcohol-related seizures require particular attention both in the diagnostic work-up and treatment. Benzodiazepines should be chosen for the treatment and prevention of recurrent AWS.

Alcoholism-Associated Hyperhomocysteinemia and Previous Withdrawal Seizures

Higher homocysteine levels were found in actively drinking alcoholics as well as in early abstinent patients. Furthermore, it has been shown that high homocysteine levels predicted first-onset alcohol withdrawal seizures. The aim of the present study was to determine plasma homocysteine levels in actively drinking alcoholics and patients with early abstinence in order to evaluate whether there is an additional association between elevated plasma homocysteine levels and a history of alcohol withdrawal seizures. Two groups of patients with an established diagnosis of alcohol dependence were studied. Group A comprised 56 consecutively admitted alcoholics who had been abstinent from alcohol between 24 to 72 hours before hospitalization. Group B consisted of 144 consecutively recruited alcoholics who were admitted - acutely intoxicated - for withdrawal treatment. Furthermore, groups were divided into two subgroups: patients with and without a history of alcohol withdrawal seizures. Alcoholics of GROUP B with a history of withdrawal seizures had significantly (p<.0001) higher homocysteine levels than actively drinking patients without seizures in their history: 42.0 micromol/l (SD 26.4) versus 22.5 micromol/l (SD 11.4). Using a logistic regression analysis, history withdrawal seizures in Group B but not in Group A patients were best predicted by a high homocysteine level at admission (Wald chi2=15.5, p<.0001; odds ratio 1.11, 95% CI 1.05-1.20). Homocysteine levels on admission may be a useful screening method to identify actively drinking patients with a higher risk of alcohol withdrawal seizures.

Pharmacological Management of Alcohol Withdrawal

<h3>Objective.</h3> —To provide an evidence-based practice guideline on the pharmacological management of alcohol withdrawal. <h3>Data Soureces.</h3> —English-language articles published before July 1, 1995, identified through MEDLINE search on "substance withdrawal—ethyl alcohol" and review of references from identified articles. <h3>Study Selection.</h3> —Articles with original data on human subjects. <h3>Data Abstraction.</h3> —Structured review to determine study design, sample size, interventions used, and outcomes of withdrawal severity, delirium, seizures, completion of withdrawal, entry into rehabilitation, adverse effects, and costs. Data from prospective controlled trials with methodologically sound end points corresponding to the<i>Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition</i>, were abstracted by 2 independent reviewers and underwent meta-analysis. <h3>Data Synthesis.</h3> —Benzodiazepines reduce withdrawal severity, reduce incidence of delirium (-4.9 cases per 100 patients; 95% confidence interval, -9.0 to -0.7;<i>P</i>=.04), and reduce seizures (-7.7 seizures per 100 patients; 95% confidence interval, -12.0 to -3.5;<i>P</i>=.003). Individualizing therapy with withdrawal scales results in administration of significantly less medication and shorter treatment (<i>P</i>&lt;.001). β-Blockers, clonidine, and carbamazepine ameliorate withdrawal severity, but evidence is inadequate to determine their effect on delirium and seizures. Phenothiazines ameliorate withdrawal but are less effective than benzodiazepines in reducing delirium (<i>P</i>=.002) or seizures (<i>P</i>&lt;.001). <h3>Conclusions.</h3> —Benzodiazepines are suitable agents for alcohol withdrawal, with choice among different agents guided by duration of action, rapidity of onset, and cost. Dosage should be individualized, based on withdrawal severity measured by withdrawal scales, comorbid illness, and history of withdrawal seizures. β-Blockers, clonidine, carbamazepine, and neuroleptics may be used as adjunctive therapy but are not recommended as monotherapy.

Late Auditory Evoked Potentials in Alcoholics

The N1-P2 wave of the auditory evoked potential was studied in 19 alcoholics, six of whom had withdrawal seizures on previous admissions. The recordings were made at 1 and 5 days after cessation of drinking. Eight nonalcoholic volunteers were used as controls. The latencies of N1 and P2 were slightly prolonged in alcoholics, but during the detoxification period they frequently shortened (p less than 0.05), occasionally attaining the values of the controls. One day after withdrawal, the amplitude of N1-P2 was consistently reduced in the alcoholics compared to the controls (p less than 0.05 and p less than 0.01), but higher in alcoholics with a seizure history compared to alcoholics without seizures (p less than 0.05 and p less than 0.001). Five days after cessation of drinking, the amplitude in the alcoholic groups always increased from the admission values (p less than 0.05 and p less than 0.01). By that time, the alcoholics with a history of withdrawal seizures had significantly (p less than 0.05 and p less than 0.01) higher amplitudes than those of the controls or the alcoholics without seizures. Large N1-P2 amplitude during alcohol withdrawal may reflect increased cerebral excitability and contribute to the identification of alcoholics with high risk for withdrawal seizures.

Acute, Withdrawal, and Chronic Alcohol Effects in Man: Event-Related Potential and Quantitative EEG Techniques

The results presented here strongly suggest that quantitative electroencephalography and event-related potentials are excellent research tools and may be clinically useful as non-invasive monitors of psychotropic drug action and encephalopathies. Our initial data with acute mild alcohol intoxication show that acute tolerance may be reflected in qEEG but not in P3 latency. Since predictably some brain functions may show tolerance, and others not, these approaches may be useful probes. The amplitude of N1-P2 appears to differentiate alcoholics with and without a history of withdrawal seizures. This technique may thus prove useful in determining treatment and monitoring treatment effects in alcohol withdrawal. P3 latency appears to be normal in Korsakoff's syndrome, unlike in Alzheimer's disease. The combination of the event-related potentials with neuropsychology and magnetic resonance imaging scans should be invaluable for future research in these patient groups. Many patients with severe liver disease superficially appear mentally intact. The event-related potential and quantitative electroencephalography findings we have demonstrated may indicate those at greater risk for alterations in brain functioning. These techniques may also prove useful in diagnosing other "subclinical" encephalopathies and further our understanding of the underlying brain pathophysiology.

Effect of short- and long-term alcohol use on phenytoin kinetics in chronic alcoholics.

Phenytoin kinetics during long-term alcohol use and withdrawal were studied in 11 male alcoholics with a history of withdrawal seizures and no evidence of chronic liver disease. Ethanol, 20% v/v, was given for 6 days after admission to maintain the blood alcohol level between 500 and 800 mg/l and phenytoin suspension, 150 mg, was given orally or intravenously (on three occasions) every 12 hr for 20 days. The mean (+/- SD) total phenytoin clearance in 9 of 11 subjects was 0.023 +/- 0.006 l/kg/hr during the alcohol ingestion period. Clearance rose to 0.033 +/- 0.013 l/kg/hr (P less than 0.05) during alcohol withdrawal. Total steady-state concentration after 3 wk ranged from 3.4 to 29.9 mg/l, while the weight-corrected dose range was only 3.7 to 5.5 mg/kg/day. Inter- and intra-subject variation in bioavailability was small (0.93 to 1.03). Phenytoin free fractions ranged from 9.09% to 17.75% and changes in total and free phenytoin concentration correlated (r2 = 0.92, P less than 0.001). The data are compatible with the hypothesis that increased phenytoin clearance during alcohol withdrawal is due to the increased metabolic rate of the drug secondary to enzyme induction by ethanol, which becomes unmasked on cessation of drinking. In most alcoholics standard-dose phenytoin (300 mg/l) will induce lower than usual plasma concentrations.