Treating status epilepticus in adults. / Behandling av status epilepticus hos voksne.

This clinical review examines the treatment of status epilepticus, a condition in which epileptic seizures are prolonged and pose a significant risk of brain damage and death. International guidelines recommend the use of benzodiazepines as first-line treatment, and these should be administered promptly and in appropriate doses. Second-line treatment involves the use of high-dose anti-seizure medications to stop and prevent seizures. If seizure activity persists, general anaesthesia should be administered as soon as possible. All neurological hospital departments should have established and rehearsed protocols for treating status epilepticus.

Disentangling the cascade of seizure precipitants: A prospective observational study.

BACKGROUND: The management of epilepsy includes appropriate antiseizure medication (ASM) treatment and careful avoidance of seizure precipitating factors. Seizure precipitants may be multiple occurring with low intensity adding to each other, thus leaving essential elements unrecognized. The aim of this study was to reveal the patients' subjective perceptions of the most important factors and to compare them with standardized measurements. METHODS: The study included 152 acute hospital admissions for seizures. The patients were asked to score the impact of various seizure precipitants as perceived by themselves on a visual analogue scale (VAS). The following items related to seizure occurrence were quantified: sleep deprivation by sleep diaries, ASM adherence by therapeutic drug monitoring, the Alcohol Use Identification Test, and the Hospital Anxiety and Depression Scale. Statistical analyses, including multiple regression, were performed to discover relationships between various parameters. RESULTS: The interaction of the various factors was high. The association between lack of sleep and hazardous drinking and anxiety was highly significant. Perceived stress correlated well with anxiety and depression. Relatively low VAS scores for missed medication in patients with identified non-adherence suggest that insufficient patient awareness is common. Low VAS-scores for alcohol in patients with harmful drinking also suggest low acknowledgment of alcohol-related seizures. High alcohol scores were associated with sleep deprivation, anxiety and depression. CONCLUSION: The circumstances leading to an epileptic seizure are complex. Stress, sleep loss, alcohol intake, and missed medication are among the most commonly reported seizure precipitants. They are often combined, and various facets of the same underlying cause may be at play. Their sequence and relative impact are often difficult to establish. Improved understanding of the cascade of events preceding a seizure can improve comprehensive personalized management of uncontrolled epilepsy.

Nonadherence to treatment causing acute hospitalizations in people with epilepsy: an observational, prospective study.

The aim was to assess the clinical relevance of antiepileptic drug (AED) nonadherence by means of therapeutic drug concentration monitoring (TDM). Two hundred eighty-two consecutive patients with epilepsy acutely admitted to hospital for seizures were included. Nonadherence was defined as having a serum concentration/dose ratio at admission of <75% of the patient's own control value (probable nonadherence: 50-75%; definite: <50%). Nonadherence was identified in 39% of patients (definite 24%; probable 15%). It was significantly more common in patients with generalized seizures compared to those with focal onset seizures, and in patients <30 years compared to older patients. When specifically asked, 44% of nonadherent patients claimed regular intake. Nonadherence is a major cause of seizure breakthrough in patients with epilepsy, particularly in young adults. Many patients seem to be unaware of missed drug intake. Prompt measurements of AED serum concentrations should be available as part of the emergency care for patients acutely hospitalized for seizures to permit this issue to be thoroughly addressed prior to discharge.

Is dietary caffeine involved in seizure precipitation?

Caffeine acts as a central nervous stimulant by blocking A1 and A2A adenosine receptors. Its effect on seizures is complex. Animal studies and case reports indicate that acute caffeine exposure may induce seizures, whereas chronic exposure might have an opposite effect. Patients acutely hospitalized for seizures (n = 174) were asked for their consumption of caffeinated beverages 24 h prior to admission as well as their habitual caffeine intake. Twenty-four-hour caffeine consumption was also recorded in a later telephone interview on a seizure-free day (n = 154). Thus, the patients served as their own controls. Categorized data were analyzed using the Wilcoxon's signed-ranks test. No difference was found between the intake of caffeine 24 h prior to the seizure and the habitual consumption (p = 0.37) or the consumption on a seizure-free day (p = 0.13). Thus, caffeine does not appear to be a common seizure precipitant.

A characteristic occipital epileptiform EEG pattern in ADCK3-related mitochondrial disease.

OBJECTIVE: ADCK3-related disease is a mitochondrial disorder associated with an abnormality of coenzyme Q10 metabolism. Ataxia and epilepsy are common, and the phenotype overlaps with other mitochondrial encephalopathies, particularly POLG-related disease. CoQ10 supplementation may be beneficial. We have noted a remarkable epileptiform pattern in ADCK3-related encephalopathy, and since EEG studies in this rare condition are limited, we wished to assess the evolution of EEG characteristics in patients with this disorder. METHODS: All EEG recordings of the four known patients from Mid-Norway were systematically reviewed. EEG graphoelements were classified according to the standardized computer-based organized reporting of EEG (SCORE) and international glossary terms. The evolution of EEG features was assessed. A total of 96 recordings spanning over 15-32 years were available, with a mean of 24 per patient (range: 17-28). Altogether, 50 digital recordings were reviewed, including four long-term and 46 selected paper segments. RESULTS: In three patients, EEG showed prominent bilateral asynchronous and synchronous epileptiform discharges in occipital and posterior-temporal regions. This intense activity included multiple epileptiform graphoelements, which occurred continuously, nearly continuously or in prolonged runs. The findings remained stable over many years. SIGNIFICANCE: Although the number of patients is small, we suggest that interictal EEG findings of continuous/nearly continuous bi-occipital spike-waves may serve as a biomarker for this potentially treatable condition. This peculiar EEG pattern might help to differentiate ADCK3-related disease from the more common POLG-related disease, which is usually characterized by lateralized or focal slowing with more sporadic epileptiform elements of similar topography.

The impact of gender, puberty, and pregnancy in patients with POLG disease.

OBJECTIVE: To study the impact of gender, puberty, and pregnancy on the expression of POLG disease, one of the most common mitochondrial diseases known. METHODS: Clinical, laboratory, and genetic data were collected retrospectively from 155 patients with genetically confirmed POLG disease recruited from seven European countries. We used the available data to study the impact of gender, puberty, and pregnancy on disease onset and deterioration. RESULTS: We found that disease onset early in life was common in both sexes but there was also a second peak in females around the time of puberty. Further, pregnancy had a negative impact with 10 of 14 women (71%) experiencing disease onset or deterioration during pregnancy. INTERPRETATION: Gender clearly influences the expression of POLG disease. While onset very early in life was common in both males and females, puberty in females appeared associated both with disease onset and increased disease activity. Further, both disease onset and deterioration, including seizure aggravation and status epilepticus, appeared to be associated with pregnancy. Thus, whereas disease activity appears maximal early in life with no subsequent peaks in males, both menarche and pregnancy appear associated with disease onset or worsening in females. This suggests that hormonal changes may be a modulating factor.

Epilepsy patients with and without perceived benefit from vagus nerve stimulation: A long-term observational single center study.

PURPOSE: Vagus nerve stimulaton (VNS) has been used for adjunctive treatment of drug-resistant epilepsy for more than 25 years. The true efficacy has been debated, as blinded randomized controlled trials are unavailable. The aim of this study was to evaluate the patient-reported perceived benefit of VNS and to compare clinical characteristics of patients with and without benefit. METHODS: Observational study of all 43 adult patients receiving VNS for >2 years at one single center. Mean duration of treatment was 9 years. At inclusion, a semi-structured interview on VNS effectiveness was performed. In patients without benefit, the VNS was turned off. The outcome was evaluated after an observation period of one year. RESULTS: 21 patients (49%) reported no clear benefit and stopped VNS. Only one of them resumed treatment within one year. Patients without benefit had received more new antiepileptic drugs (AEDs) during VNS treatment than those reporting benefit (p = 0.05). Other differences between the two groups were not found. Ten patients (23%) had been seizure free >1 year at inclusion (5 in the benefit and 5 in the non-benefit group). Seizure control was attributed to the response of another new treatment in the majority of these patients. CONCLUSION: Half of the patients had not perceived clear benefit from VNS, and all but one terminated VNS without worsening of seizures within one year. The true outcome of long-term VNS is difficult to assess in real-world practice. The effect may be overestimated due to confounding factors, particularly the common introduction of novel AEDs and the natural course of the disorder. Patients without perceived benefit from long-term VNS should not routinely remain on treatment and be subject to undue generator re-implantations.

The seizure precipitating effect of alcohol: A prospective observational cross-over study.

PURPOSE: The aim of this study was to investigate the association between alcohol use and seizures in acutely hospitalized patients. We wished to study the extent of the problem as well as the clinical characteristics of people with various forms of alcohol-related seizures, including their drinking pattern. METHOD: After admission, a semi-structured interview took place with 134 consecutive patients (epilepsy 92, single seizures 42). Alcohol use was assessed by the Alcohol Use Disorders Identification Test (AUDIT) and by the number of alcohol units consumed during 6 days prior to the seizure. Sleep time was recorded during the previous 3 days and nights. A follow-up telephone interview covering the same weekdays was performed on a seizure-free day at least 4 weeks later. RESULTS: 28% of patients had AUDIT scores ≥8 (hazardous drinking); 22% in epilepsy, 43% in single seizures (p = .012). Non-focal seizures were increased in single seizures, suggesting a withdrawal mechanism. In the 58 epilepsy patients with social drinking (excluded hazardous drinking or excessive binging), the alcohol intake was not different prior to seizure compared to follow-up, downgrading the role of modest alcohol intake as a seizure precipitant in epilepsy. On the other hand, a high percentage of binge drinkers had epilepsy (57%), and in the subgroup of Idiopathic Generalized Epilepsy (IGE) even social drinking was associated with seizures. Seizures peaked on Sundays and Mondays. Less sleep prior to the seizure was associated with hazardous drinking. CONCLUSION: Alcohol is a major seizure precipitant in the context of hazardous drinking and withdrawal. In people with epilepsy, occasional binge drinking is associated with loss of seizure control. Social drinking is an uncommon cause of seizure breakthrough in predominantly focal epilepsy, but caution is warranted in IGE. Alcohol intake prior to a seizure is often accompanied by other triggers, such as sleep loss. Alcohol alone should not always be blamed.

The impact of sleep loss on the facilitation of seizures: A prospective case-crossover study.

PURPOSE: The relationship between sleep and seizures is intricate. The aim of this study was to assess whether sleep loss is an independent seizure precipitant in a clinical setting. METHODS: In this prospective, observational cross-over study, 179 consecutive hospital admissions for epileptic seizures were included. A semi-structured interview regarding several seizure precipitants was performed. The sleep pattern prior to the seizure, as well as alcohol, caffeine and drug use, were recorded. The interview was repeated by telephone covering the same weekday at a time when there had been no recent seizure. The Hospital Anxiety and Depression Scale (HADS) and a visual analogue scale for perceived stress were applied at admission. Student's t-test, Fisher exact test and ANOVA were used for statistical analyses. RESULTS: Complete data for analysis were retrieved in 144 patients. The sleep-time during the 24h prior to the seizure was lower (7.3h) compared to follow-up (8.3h; p<0.0005). Caffeine consumption and use of relevant non antiepileptic drugs (AED) were not different. HADS and stress scores at admission did not correlate with sleep-time difference. In ANOVA, controlled for alcohol consumption and AED use, the sleep-time difference remained significant (p=0.008). The interaction with alcohol intake was high, but the sleep-time difference remained highly significant also for the non- and low-consumption (≤2 units per day) subgroup (n=121, 7.50h vs 8.42h, p=0.001). CONCLUSION: Epileptic seizures are often precipitated by a combination of various clinical factors, but sleep loss stands out as an independent seizure trigger.

Treatment non-adherence in pseudo-refractory epilepsy.

Non-adherence to antiepileptic drug treatment strongly affects the outcome of epilepsy and is frequently clinically unrecognized. This review addresses current knowledge on medication-taking behavior in people with epilepsy, as well as the importance of tailoring interventions to the individual patterns of non-adherence. Non-adherence can be categorized as non-initiation, poor execution (accidental or intentional) or non-persistence and are related to clinical characteristics and health care barriers. All available methods to assess adherence are hampered by shortcomings. Self-reports are indirect and subjective. Pill-counts, electronic bottle-tops and pharmacy records are objective, but indirect measures of drug ingestion. Therapeutic drug monitoring is both direct and objective, but pharmacokinetic and diurnal variability must be taken into account. Young adults with generalized epilepsy may be particularly vulnerable to non-adherence. The drug burden in the form of polytherapy, multiple dosing and side effects are obvious obstacles. Poor understanding of the principles of prophylactic treatment as well as drug costs may be important in people with low socioeconomic status. Depression is also associated with low adherence. In people with multihandicaps, failed oral intake may be due to behavioral or physical problems, as well as insufficient education of the caregivers. Non-adherence often results in seizure breakthrough and hospital admissions, but the consequences may be more dramatic. It is the leading cause of status epilepticus in people with epilepsy, and the association with sudden death (SUDEP) is clear. The management of poor drug-taking behavior should be based on the identification of the specific causes in each individual and corresponding multiprofessional interventions. Non-adherence to antiepileptic drugs needs more clinical and scientific attention.

Treatment non-adherence as a trigger for status epilepticus: An observational, retrospective study based on therapeutic drug monitoring.

PURPOSE: To investigate the role of non-adherence to antiepileptic drug treatment as a trigger for status epilepticus (SE). METHODS: 124 consecutive admissions for SE in patients with established epilepsy were studied. Those who had had therapeutic drug monitoring at admission were identified. Non-adherence was defined as a serum concentration/dose ratio at admission of <75% of the patient's own trough control value. RESULTS: In 64 cases serum concentration/dose ratios at admission were available for comparison with morning trough values. Treatment non-adherence was identified in a total of 24 (38%), 50% in children, 32% in patients 16-59 years and in 44% above 60. Missed medication had been reported in only two of these patients. No cases with confirmed non-adherence had a fatal outcome (p=0.05). No significant differences between non-adherent and adherent admissions concerning demographic factors or epilepsy and SE characteristics were found. CONCLUSION: Antiepileptic drug non-adherence is a common cause of SE across all ages, but is not always identified due to the first history-based information often being elusive. Prompt and reliable recognition of non-adherence is imperative for correct management. This is the first study to demonstrate the extent of non-adherence by therapeutic drug monitoring in SE.