Epilepsy & Behavior最新文献

Objective

To assess the impact of vagus nerve stimulation (VNS) on quality of life contributors such as rescue medications.

Methods

Using the seizure diary application SeizureTracker™ database, we examined trends in rescue administration frequency before and after the first recorded VNS magnet swipe in patients with drug-resistant epilepsy who had 1) At least one VNS magnet swipe recorded in the diary, and 2) Recorded usage of a benzodiazepine rescue medication (RM) within 90 days prior to the first swipe. A paired Wilcoxon rank-sum test was used to assess changes in RM usage frequency between 30-, 60-, 90-, 180- and 360-day intervals beginning 30 days after first magnet swipe. Longitudinal changes in RM usage frequency were assessed with a generalized estimating equation model.

Results

We analyzed data of 95 patients who met the inclusion criteria. Median baseline seizure frequency was 8.3 seizures per month, with median baseline rescue medication usage frequency of 2.1 administrations per month (SD 3.3). Significant reductions in rescue medication usage were observed in the 91 to 180 day interval after first VNS magnet swipe, and at 181 to 360 days and at 361 to 720 days, with the magnitude of reduction increasing over time. Decreases in rescue medication usage were sustained when controlling for patients who did not record rescue medication use after the first VNS magnet swipe (N=91). Significant predictors of reductions in rescue medication included baseline frequency of rescue medication usage and time after first VNS magnet swipe.

Significance

This retrospective analysis suggests that usage of rescue medications is reduced following the start of VNS treatment in patients with epilepsy, and that the magnitude of reduction may progressively increase over time.

Despite burgeoning interest in trials in status epilepticus over the last 20 years, outcomes have yet to improve and a number of high profile studies have failed to deliver for a range of reasons. The range of reasons a trial may fail to meet the intended outcomes are discussed. Recent well designed, adequately powered studies in established status epilepticus failed to meet primary endpoints, but are nonetheless influencing practice, reflecting the importance of interpreting results in the context of broader literature, safety and practical considerations. Studies in refractory and super-refractory status epilepticus have yet to do so, frequently failing to deliver as hoped despite huge financial and human cost. The importance of reviewing regulatory frameworks, and our approach to trial design to address important clinical questions is reviewed, reflecting on lessons from the COVID-19 RECOVERY trials, and other disease areas, together with the potential associated with the use artificial intelligence tools. This paper is based on a presentation made at the 9th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures in April 2024.

Background

Aprepitant (APR), a neurokinin 1 receptor antagonist, is an approved drug for treating chemotherapy-induced nausea and vomiting.

Objectives

Investigate the beneficial roles of APR alone or in combination with sodium valproate (VPA) against lithium pilocarpine [li-pilo]-induced seizures, behavioral changes, and cognitive deficits.

Methods

Thirty male mice were divided into five groups, each containing 6. “Vehicle Group I,” “Control Group II ”li-pilo, “ Valproate (VPA) group III (400 mg/kg/i.p.), ”APR group IV, “ and ”Combination Group V.“ Videos of mice were recorded, and they were watched for episodes of spontaneous recurring seizures (SRS). Behavioral Tests were performed. At the end of the study, animal brains were taken for biochemical assays and gene expression studies.

Results

APR partially protected against SRS with partial restoration of average behavioral and standard cognitive skills associated with a significant increase in brain SOD activity and a significant decrease in MDA, IL-1β, NF-КB, and SP-3 levels in relation to the control group. Interestingly, a combination of APR with VPA in epileptic mice showed complete protection against li-pilo-induced behavioral changes and cognitive deficits, a significant increase in brain SOD activity, and a considerable decrease in MDA, IL-1β, NF-ΚB, and SP levels to normal.

Conclusion

Using APR as an adjuvant to VPA is more effective in protecting against li-pilo-induced seizures, behavioral changes, and cognitive deficits due to its antioxidant, anti-inflammatory, and NK1 antagonist effects than using APR alone as drug therapy.

Objective

The social prognosis for individuals with epilepsy is often poorer than their clinical prognosis, highlighting the significant influence of social factors on the progression of the disease. Relatives of patients with epilepsy (RPEs) generally have more positive attitudes towards epilepsy compared to the general population. This study aimed to examine the effect of being an RPE on the relationship between attitudes toward epilepsy and levels of disease knowledge.

Methods

This cross-sectional analytical study included 217 adult participants, comprising 93 RPEs and 124 controls (non-RPEs), selected through convenience sampling. Data were collected via face-to-face interviews using a questionnaire that included sections on socio-demographic characteristics, the Epilepsy Knowledge Scale, and the Public Attitudes Toward Epilepsy (PATE) Scale. Path analysis was conducted using the Maximum Likelihood method. Due to the non-normal distribution of exogenous variables, the robust Huber/White/sandwich estimator method was used to calculate confidence intervals and fit indices.

Results

The mean age of the participants was 34.7 ± 11.5 years, with 128 (59.0 %) being female. RPEs scored an average of 26.8 ± 9.9 on the PATE Scale, which was significantly lower than the average score of 29.7 ± 11.0 for non-RPEs (p = 0.047). Path analysis indicated that being an RPE indirectly fosters a positive attitude through increased knowledge levels. While the direct effect of being an RPE on attitudes was not statistically significant, the indirect effect mediated by knowledge was significant.

Significance

This study highlights that the level of knowledge about epilepsy, a key predictor of positive attitudes, remains important even among RPEs. In kinship contexts where neurobiological and psychosocial factors are at play, the primary determinant of attitudes toward epilepsy is still the level of knowledge about the condition. Consequently, focusing on increasing knowledge about epilepsy should be the main strategy to promote positive attitudes, providing a more promising avenue for future research and interventions.

Cell replacement therapies using medial ganglionic eminence (MGE)-derived GABAergic precursors reduce seizures by restoring inhibition in animal models of epilepsy. However, how MGE-derived cells affect abnormal neuronal networks and consequently brain oscillations to reduce ictogenesis is still under investigation. We performed quantitative analysis of pre-ictal local field potentials (LFP) of cortical and hippocampal CA1 areas recorded in vivo in the pilocarpine rat model of epilepsy, with or without intrahippocampal MGE-precursor grafts (PILO and PILO+MGE groups, respectively). The PILO+MGE animals had a significant reduction in the number of seizures. The quantitative analysis of pre-ictal LFP showed decreased power of cortical and hippocampal delta, theta and beta oscillations from the 5 min. interictal baseline to the 20 s. pre-ictal period in both groups. However, PILO+MGE animals had higher power of slow and fast oscillations in the cortex and lower power of slow and fast oscillations in the hippocampus compared to the PILO group. Additionally, PILO+MGE animals exhibited decreased cortico-hippocampal synchrony for theta and gamma oscillations at seizure onset and lower hippocampal CA1 synchrony between delta and theta with slow gamma oscillations compared to PILO animals. These findings suggest that MGE-derived cell integration into the abnormally rewired network may help control ictogenesis.

Purpose

Prenatal exposure to antiseizure medications (ASMs) has been associated with an increased risk of major malformations and neurodevelopmental disorders, with the latter being mainly associated with valproate (VPA). Our aim was to compare neurocognitive outcome at age 6–7 years in children exposed prenatally to lamotrigine (LTG), carbamazepine (CBZ), valproate (VPA) or levetiracetam (LEV) monotherapy.

Methods

Eligible mother–child pairs were identified from the observational prospective multinational EURAP cohort study. Assessor-blinded testing was conducted at age 6–7 years using WISC-III and NEPSY-II. Verbal IQ (VIQ), performance IQ (PIQ), full scale IQ (FSIQ) and performance in neuropsychological tasks were compared across ASM groups by ANOVA. Scores were adjusted for maternal IQ, paternal education, maternal epilepsy type and child sex.

Results

Of 169 children enrolled in the study, 162 (LTG n = 80, CBZ n = 37, VPA n = 27, LEV n = 18) had sufficient data from WISC-III, NEPSY-II or both, and were included in the analyses. Observed (unadjusted) PIQ and FSIQ did not differ across exposure groups, but a difference was identified for VIQ (P<0.05), with children exposed to VPA having lower scores than children exposed to LEV (P<0.05) and children from all groups combined (P<0.01). Adjusted VIQ, PIQ and FSIQ scores did not differ significantly across groups, but VPA-exposed children had borderline significantly lower adjusted VIQ scores than children from all groups combined (P=0.051). VPA-exposed children had lower scores in comprehension of instructions before and after adjustment for confounding variables than children exposed to LTG (P<0.001), LEV (P<0.01) or children from all groups combined (p < 0.001). The VPA-exposed group also had lower scores in immediate and delayed memory for faces compared to children exposed to CBZ (P<0.05 and P<0.001, respectively) and LTG (P<0.05 and P<0.02, respectively), and children from all groups combined (P<0.02 and P<0.001, respectively). LEV-exposed children had lower scores in delayed memory for names than children exposed to LTG (P<0.001), CBZ (P<0.001), VPA (P<0.05) and children from all groups combined (P<0.001).

Conclusions

Consistent with previous reports, our results provide evidence for an adverse effect of prenatal exposure to valproate on verbal development. Our finding of relatively weaker performance of VPA-exposed children compared to other ASM exposures in both comprehension of instructions and face memory also suggest that children of mothers treated with VPA are at increased risk for compromised memory functions or altered processing of socially relevant information.

The burden of epilepsy is not only related to seizure frequency; the severity of epileptic seizures considerably affects patient’s lives. A number of seizure severity scales have thus been developed for a systematic assessment. Items considered relevant in these scales mainly pertain to objective features, such as seizure duration, loss of consciousness, and seizure-related injuries. In contrast, subjective experiences of seizures are considered only in their functionality as “warnings”, whereas the quality of subjective perceptions and feelings are disregarded phenomena. This leads to a gap between the often-distressing subjective experiences which people with epilepsy remember from their seizures and the perception of physicians which may negatively impact physician-patient communication and interaction and question their valid use as treatment outcomes. We advocate here to develop new seizure severity assessments in collaboration with patient organizations which integrate also the subjective quality of seizures.

Objectives

Timely access to specialist outpatient clinics can be difficult to achieve as outpatient services are often oversubscribed leading to unacceptable wait times. New patients, or those with emergent issues may wait for appointments whilst existing patients are booked in for routine reviews “just in case” there is a problem, using considerable clinic resources. We investigated routine 12-month review appointments to assess whether these appointments changed patient management.

Methods

The medical records of 100 randomly selected adult patients attending annual review appointments over 12 months at a publicly-funded specialist outpatient epilepsy clinic in Melbourne, Australia were audited. Demographic and clinical data as well as information about the content of each appointment were analysed to determine whether the appointment resulted in changes to epilepsy management (eg medication change), administrative actions (eg drivers license approval) or the provision of information or education. Logistic regression was performed to assess what clinical factors were associated with changes in patient care arising from the 12-month review appointment.

Results

Almost half (47%) of appointments resulted in no change to patient care and 37% had only administrative outcomes, such as the completion of a regulatory driving report. Only 16% of appointments resulted in a change in medical management. The only factor that independently predicted a change in medical management was the occurrence of a seizure in the previous year. The only factor independently associated with not having any change in medical management or administrative action was having an unknown seizure type.

Conclusions/ significance

Only a small number of patients experience a change in medical management when attending a 12-month epilepsy clinic appointment, with a need for management change associated with the presence of ongoing seizure. Outpatient services should limit the use of routine annual follow up to those patients most likely to need intervention or support, creating “just in time” capacity for timely access to review as issues arise.