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.

The purpose of this research was to analyze and quantify the association between alcohol consumption and epilepsy as an independent disease, in part operationalized by the occurrence of unprovoked seizures, as well as to examine causality.

Systematic review, meta-analysis.

A strong and consistent association between alcohol consumption and epilepsy/unprovoked seizures was found with an overall relative risk (RR) of 2.19 [95% confidence interval (CI) 1.83-2.63]. There was a dose-response relationship between the amount of alcohol consumed daily and the probability of the onset of epilepsy. Individuals consuming an average of four, six, and eight drinks daily had RRs of 1.81 (95% CI 1.59-2.07), 2.44 (95% CI 2.00-2.97), and 3.27 (95% CI 2.52-4.26), respectively, compared to nondrinkers. Several pathogenic mechanisms for the development of epilepsy in alcohol users were identified. Most of the relevant studies found that a high percentage of alcohol users with epilepsy would qualify for the criteria of alcohol dependence. Data were inconclusive regarding a threshold for the effect of alcohol, but most studies suggest that the effect may only hold for heavy drinking (four and more drinks daily).

The relationship between alcohol consumption and epilepsy and unprovoked seizures was quantified and several pathogenic mechanisms were suggested, although none of them has been proven to be the unique causative pathway for epilepsy. Certain limitations underlying this study require further research to clarify the outstanding statistical issues and pathogenesis of epilepsy in heavy drinkers.

The relationships between alcohol usage and a number of neurological syndromes are reviewed. These are often complex and incompletely understood. Multiple rather than single factors are the rule rather than the exception. The correct diagnosis may be missed particularly where the aetiological role of alcohol is overlooked. Multiple diagnoses are not uncommon. Issues of differential diagnosis and diagnostic procedures are discussed. Management, including a number of its pitfalls, is outlined.

A previous magnetic resonance imaging study from our laboratory reported significant temporal lobe volume deficits in cortical gray matter, white matter, and anterior hippocampus in chronic alcoholic men relative to controls. In the present study, we reexamined these data and asked whether withdrawal seizure history was predictive of either the hippocampal or the extrahippocampal volume deficits. A review of the medical charts indicated that 11 alcoholics had experienced one or more alcohol-related seizures and 35 were seizure-free; no patient had a seizure disorder unrelated to alcohol. The two alcoholic groups did not differ significantly in age, education, alcohol consumption variables, premorbid intelligence, Memory Quotient, Trail Making, or detection of hidden figures. Although each alcoholic group showed significant bilateral volume deficits of the anterior hippocampus and frontal-parietal and temporal gray matter, relative to controls, the seizure group had significantly smaller temporal lobe white matter volumes than either the control or the seizure-free groups; the latter two groups did not differ from each other. Both alcoholic groups, however, had white matter volume deficits in the frontal-parietal region. Thus, the seizure group accounted for the white matter volume deficits in the temporal lobe previously reported in the full sample of alcoholics. It seems, then, that reduced white matter volume in the temporal lobes may be either a risk factor for or sequela of alcohol withdrawal seizures.

From a neuropsychological point of view, hypotheses are offered on the possible action of the brain in the processing of mnemonic information for long-term storage (or for retrieval of long-term stored information). It is argued that strict relations between damage of circumscribed brain structures and amnesia, as they have been suggested in recent case reports, are questionable for several reasons: Firstly, the involved regions differ between cases; secondly, there is some counter-evidence from other cases in which similar neuronal damage failed to result in lasting amnesic disturbances; thirdly, it is hypothesized that even from circumscribed brain damage it is not justifiable to conclude that the lesioned structure is solely or principally responsible for the observed mnemonic changes, as the brain acts in an integrative way, that is, on the basis of a wide-spread network of neuronal information processing. On the basis of these and related arguments, hypotheses and models on mnemonic information processing in the intact and in the damaged brain are derived. With these hypotheses even the frequent observation of interindividual differences in mnemonic information processing finds a possible explanation which is in conformity to known anatomical circuits and connections and to principles of neuronal coding.

There is a scarcity of population-based epidemiological investigations concerning the prevalence of epilepsy among alcoholics, and of alcoholism among epileptic patients. Available data seem to suggest that the prevalence of epilepsy among alcoholics is at least triple that in the general population, and that alcoholism may be more prevalent among epileptic patients than in the general population. The term "alcoholic epilepsy" has been used with varying definitions in different investigations. It is suggested that a uniform definition be adopted so as to minimize confusion when comparing data from different laboratories. Although there is general agreement that excessive alcohol intake can increase the frequency of seizures in epileptic patients, limited available data suggest that light to moderate social alcohol drinking may not affect seizure frequency. However, epileptic patients should be warned about the possible adverse effects of alcohol, especially those who have refractory forms of epilepsy. Except for a few anomalous cases, evidence for the direct seizure-provoking effect of alcohol is not strong. This is because it is difficult to pinpoint alcohol as the only etiology; more likely, alcohol is only one factor among others (e.g., head trauma, cerebral infarct, alcohol withdrawal, and metabolic effects of alcohol) in provoking seizures. Because seizures are a symptom and not a disease, it is often difficult to distinguish epileptic seizures from alcohol-withdrawal seizures. Patients with only the latter kind of seizures should not need chronic antiepileptic medication.

Approximately 25% of patients with epilepsy will have their first seizure after the age of 25 years. These individuals will need special attention with regard to etiology. Brain tumor is one of several causes that may be suspected. The present study of 221 patients with late-onset epilepsy from the University Clinic of Neurology, Hvidovre Hospital, Copenhagen, Denmark, was undertaken to look for means to select those cases in which computerized tomography (CT) scan should be performed. Brain tumor was the cause in 16% and cerebrovascular infarctions in 14%. The major etiological group was the one in which no cause could be detected (38%). Alcohol abuse as the etiology--defined as cases with a history of long-standing alcohol overuse, concomitant signs of alcohol intoxication, and spontaneous recurrent epileptic seizures--made up a group of one-fourth of all the patients with late-onset epilepsy. Comparison of the history, clinical symptoms and signs, EEG abnormalities, and CT scan speaks in favor of some consideration being given to the first three parameters before the CT scan is performed.

Relations between brain damage and memory disturbance are outlined with emphasis on the so-called amnesic syndrome. Following a brief introduction into forms of memory and memory failures, the basic causes of brain damaage (with relevance to amnestic failures) are described. Thereafter, the two best-known forms of brain damage-amnesia relations are reviewed: the consequences of damage to medial temporal lobe structures and to diencephalic regions. For the cases with medial temporal lobe damage, evidence is reported in greater detail for H.M., who has been examined more than any other amnesic patient for more than 30 years now, as a considerable amount of literature has accumulated on his behavior in diverse situations. Other cases with more or less circumscribed damage to medial temporal lobe structures are reviewed so as to outline criteria for or against the hypothesis that there are regions within the medial temporal lobe whose damage might be critical for the amnesic syndrome. Two cases of diencephalic amnesia are summarized in particular (cases of Mair et al., 1979) as they have received extensive neuropsychological and neuropathological investigation. Other cases with, for example, Korsakoff's disease are reviewed, as well as cases with diencephalic, or combined mesencephalic-diencephalic damage without nutritional causes. A third group of patients with massive, but still selective amnesic disturbances are then described: cases of basal forebrain damage, followed by descriptions of Alzheimer's disease which has similarities in the underlying neuropathology. This leads over to cases with more generalized intellectual deteriorations (dementia), which may have developed on the basis of primarily cortical damage or damage principally to basal ganglia structures. After reviewing cases with mainly material-specific memory failures--usually as a consequence of restricted neocortical damage--a separate section follows on patients in whom retrograde amnesia is the prominent symptom. The contribution of animal models of human amnesia is critically reviewed and discrepancies are analyzed between human and animal memory disturbances. This section emphasizes the value of investigating inter-dependencies between brain structures by pointing out that relations between memory disturbances and brain damage may be more complicated than apparent from a simple structure-function assignment. This aspect is further followed up in the conclusions.