Epilepsy Research最新文献

Children with epilepsy often experience deficits in both executive functioning (EF) and memory. However, how these two domains interact and relate to specific epilepsy types remains unclear. This study compared two groups of children: those with localization-related epilepsy (LRE) and those with genetic generalized epilepsy (GGE). We aimed to understand how performance-based and parent-reported EF differentially contribute to understanding memory function in each group.

We examined neuropsychological measures assessing memory and EF in 75 children with LRE and 91 with GGE. Multiple linear regressions explored the impact of EF on memory performance.

Performance-based EF scores accounted for greater variance in memory scores than parental EF reports. However, performance-based EF measures explained much more variance in visual memory for LRE than GGE and explained much more variance in verbal memory for the GGE group. Parental reports of EF contributed marginally to understanding variance.

These findings suggest differential relationships between EF and memory based on epilepsy type. Performance-based EF measures appear more reliable at understanding memory variance than did parent reports. Our results have potential clinical implications for tailoring neuropsychological assessment and intervention for children with different epilepsy types.

Responsive neurostimulation (RNS) is a treatment option for patients with refractory epilepsy when surgical resection is not possible due to overlap of the irritative zone and eloquent cortex. Presurgical evaluations for RNS placement typically rely on invasive methods. This study investigated the potential of transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG) to provide key presurgical information non-invasively. We hypothesized that these non-invasive methods may assist in optimizing RNS placement by providing useful information for seizure localization by MEG and eloquent cortex mapping by TMS. A retrospective chart review identified nine patients who underwent RNS placement (mean age = 20.4 years [SD = 5.6], two-thirds were female). Characterization of the irritative zone using MEG was successful in eight of nine patients. Non-invasive mapping of relevant eloquent cortex was attempted in all patients. TMS was successful in eight of nine patients, and MEG was successful in two of six patients. Importantly, patients mapped with non-invasive modalities experienced an average seizure reduction of 77 % at their most recent clinic visit, compared to 75 % seizure reduction in those with invasive evaluations, indicating appropriate RNS placement. These data demonstrate that TMS and MEG can provide key information for RNS and may be feasible alternatives to invasive methods for assisting in decision making regarding RNS placement. Non-invasive methods for determining RNS placement have a high rate of success when data from multiple non-invasive modalities converge and can inform more accurate placement of intracranial electrodes prior to RNS placement or mitigate their need.

Ninety percent of tuberous sclerosis complex (TSC) patients have seizures, with ∼50 % developing drug refractory epilepsy. Surgical intervention aims to remove the seizure onset zone (SOZ). This retrospective study investigated the relationship of SOZ size, ictal pattern, and extent of resection with surgical outcomes. TSC patients undergoing resective/ablative surgery with >1-year follow-up and adequate imaging were included. Preoperative iEEG data were reviewed to determine ictal pattern and SOZ location. For outcomes, an ILAE score of 1–3 was defined as good and 4–6 as poor. Forty-four patients were included (age 117.4 ± 110.8 months). Of these, 59.1 % achieved a good outcome, while 40.9 % had a poor outcome. Size of SOZ was a significant factor (p = 0.009), with the poor outcome group having a larger SOZ (11.9 ± 6.7 electrode contacts) than the good outcome group (7.3 ± 7.2). SOZ number was significant (p = 0.020); >1 SOZ was associated with poor outcome. These results demonstrate extent of SOZ as a predictor of seizure freedom following epilepsy surgery in a mostly pediatric TSC cohort. We hypothesize that these features represent biomarkers of focality of the epileptogenic zone and can be used to sharpen prognosis for epilepsy surgery outcomes in this cohort.

Objectives

People with epilepsy (PWE) continue to suffer from discrimination and often bear the negative attitudes surrounding this condition. The aim of the study was to assess the frequency of perceived stigma and factors associated with it among PWE in tertiary care centre.

Material and methods

A hospital-based, cross-sectional study was conducted using the Kilifi Stigma Scale of Epilepsy (KSSE) to assess the stigma associated with epilepsy and factors related to stigma.

Results

A total of 260 consecutive PWE were recruited, with a mean age of 28.12±9.96 years. The majority of subjects had primarily or secondarily generalized seizures (85 %), and most of PWE don’t know the cause of epilepsy (79.2 %) and feel that epilepsy is a contagious disease. Those with contagious beliefs felt more stigma (27.7 %). Stigma was perceived by 28.5 % of subjects using KSSE. Stigma was more perceived in those who had primarily or secondarily generalized seizures (23.9 %) and longer durations of anti-seizure medication (ASM) (24.4 %). Injury during a seizure was reported in 30 % of subjects and were more stigmatized (p<.01).

Conclusion

Perceived stigma in PWE was found to be correlated with contagious beliefs. There is a need for awareness and educational programs by healthcare professionals at different levels to support and encourage positive beliefs, dispel myths about epilepsy, and inform PWEs of the fact that it is not a contagious disease.

Objective

We retrospectively explored patients with drug-resistant epilepsy (DRE) who previously underwent presurgical evaluation to identify correlations between surgical outcomes and pathogenic variants in epilepsy genes.

Methods

Through an international collaboration, we evaluated adult DRE patients who were screened for surgical candidacy. Patients with pathogenic (P) or likely pathogenic (LP) germline variants in genes relevant to their epilepsy were included, regardless of whether the genetic diagnosis was made before or after the presurgical evaluation. Patients were divided into two groups: resective surgery (RS) and non-resective surgery candidates (NRSC), with the latter group further divided into: palliative surgery (vagus nerve stimulation, deep brain stimulation, responsive neurostimulation or corpus callosotomy) and no surgery. We compared surgical candidacy evaluations and postsurgical outcomes in patients with different genetic abnormalities.

Results

We identified 142 patients with P/LP variants. After presurgical evaluation, 36 patients underwent RS, while 106 patients were NRSC. Patients with variants in ion channel and synaptic transmission genes were more common in the NRSC group (48 %), compared with the RS group (14 %) (p<0.001). Most patients in the RS group had tuberous sclerosis complex. Almost half (17/36, 47 %) in the RS group had Engel class I or II outcomes. Patients with channelopathies were less likely to undergo a surgical procedure than patients with mTORopathies, but when deemed suitable for resection had better surgical outcomes (71 % versus 41 % with Engel I/II). Within the NRSC group, 40 underwent palliative surgery, with 26/40 (65 %) having ≥50 % seizure reduction after mean follow-up of 11 years. Favourable palliative surgery outcomes were observed across a diverse range of genetic epilepsies.

Significance

Genomic findings, including a channelopathy diagnosis, should not preclude presurgical evaluation or epilepsy surgery, and appropriately selected cases may have good surgical outcomes. Prospective registries of patients with monogenic epilepsies who undergo epilepsy surgery can provide additional insights on outcomes.

Objective

We described patterns and trends in ED use among adults with epilepsy in the United States.

Methods

Utilizing inpatient and ED discharge data from seven states, we conducted a cross-sectional analysis to identify adult ED visits diagnosed with epilepsy or seizures from 2010 to 2019. Using ED visit counts and estimates of state-level epilepsy prevalence, we calculated ED visit rates overall and by payer, condition, and year.

Results

Our data captured 304,935 ED visits with epilepsy as a primary or secondary diagnosis in 2019. Across the seven states, visit rates ranged between 366 and 726 per 1000 and were higher than rates for adults without epilepsy in all states but one. ED visit rates were highest among Medicare and Medicaid beneficiaries (vs commercial or self-pay). Adults with epilepsy were more likely to be admitted as inpatients. Visits for nervous system disorders were 6.3–8.2 times higher among people with epilepsy, and visits for mental health conditions were 1.2–2.6 times higher. Increases in ED visit rates from 2010 to 2019 among people with epilepsy exceeded increases among adults without by 6.0–27.3 percentage points.

Conclusion

Adults with epilepsy visit the ED frequently and visit rates have been increasing over time. These results underscore the importance of identifying factors contributing to ED use and designing tailored interventions to improve ambulatory care quality.

Aim

Paediatric patients with drug-resistant focal epilepsy (DRFE) who have no clear focal lesion identified on conventional structural magnetic resonance imaging (MRI) are a particularly challenging cohort to treat and form an increasing part of epilepsy surgery programs. A recently developed deep-learning-based MRI lesion detection algorithm, the Multicentre Lesion Detection (MELD) algorithm, has been shown to aid detection of focal cortical dysplasia (FCD). We applied this algorithm retrospectively to a cohort of MRI-negative children with refractory focal epilepsy who underwent stereoelectroencephalography (SEEG) to determine its accuracy in identifying unseen epileptic lesions, seizure onset zones and clinical outcomes.

Methods

We retrospectively applied the MELD algorithm to a consecutive series of MRI-negative patients who underwent SEEG at our tertiary Paediatric Epilepsy Surgery centre. We assessed the extent to which the identified MELD cluster or lesion area corresponded with the clinical seizure hypothesis, the epileptic network, and the positron emission tomography (PET) focal hypometabolic area. In those who underwent resective surgery, we analysed whether the region of MELD abnormality corresponded with the surgical target and to what extent this was associated with seizure freedom.

Results

We identified 37 SEEG studies in 28 MRI-negative children in whom we could run the MELD algorithm. Of these, 14 (50 %) children had clusters identified on MELD. Nine (32 %) children had clusters concordant with seizure hypothesis, 6 (21 %) had clusters concordant with PET imaging, and 5 (18 %) children had at least one cluster concordant with SEEG electrode placement. Overall, 4 MELD clusters in 4 separate children correctly predicted either seizure onset zone or irritative zone based on SEEG stimulation data. Sixteen children (57 %) went on to have resective or lesional surgery. Of these, only one patient (4 %) had a MELD cluster which co-localised with the resection cavity and this child had an Engel 1 A outcome.

Conclusions

In our paediatric cohort of MRI-negative patients with drug-resistant focal epilepsy, the MELD algorithm identified abnormal clusters or lesions in half of cases, and identified one radiologically occult focal cortical dysplasia. Machine-learning-based lesion detection is a promising area of research with the potential to improve seizure outcomes in this challenging cohort of radiologically occult FCD cases. However, its application should be approached with caution, especially with regards to its specificity in detecting FCD lesions, and there is still work to be done before it adds to diagnostic utility.

Epilepsy, a chronic neurological disorder characterized by recurrent unprovoked seizures, presents a substantial challenge in approximately one-third of cases exhibiting resistance to conventional pharmacological treatments. This study investigated the effect of 4-allyl-2,6-dimethoxyphenol, a phenolic compound derived from various natural sources, in different models of induced seizures and its impact on animal electroencephalographic (EEG) recordings. Adult male Swiss albino mice were pre-treated (i.p.) with a dose curve of 4-allyl-2,6-dimethoxyphenol (50, 100, or 200 mg/kg), its vehicle (Tween), or standard antiepileptic drug (Diazepam; or Phenytoin). Subsequently, the mice were subjected to different seizure-inducing models – pentylenetetrazole (PTZ), 3-mercaptopropionic acid (3-MPA), pilocarpine (PILO), or maximal electroshock seizure (MES). EEG analysis was performed on other animals surgically implanted with electrodes to evaluate brain activity. Significant results revealed that animals treated with 4-allyl-2,6-dimethoxyphenol exhibited increased latency to the first myoclonic jerk in the PTZ and PILO models; prolonged latency to the first tonic-clonic seizure in the PTZ, 3-MPA, and PILO models; reduced total duration of tonic-clonic seizures in the PTZ and PILO models; decreased intensity of convulsive seizures in the PTZ and 3-MPA models; and diminished mortality in the 3-MPA, PILO, and MES models. EEG analysis indicated an increase in the percentage of total power attributed to beta waves following 4-allyl-2,6-dimethoxyphenol administration. Notably, the substance protected from behavioral and electrographic seizures in the PTZ model, preventing increases in the average amplitude of recording signals while also inducing an increase in the participation of theta and gamma waves. These findings suggest promising outcomes for the tested phenolic compound across diverse pre-clinical seizure models, highlighting the need for further comprehensive studies to elucidate its underlying mechanisms and validate its clinical relevance in epilepsy management.

The aim of the present study was to develop a novel formulation of berberine (BBR) and demonstrate its anti-seizure effect in pentylenetetrazole (PTZ) induced kindling model in rats. Nanoparticles of BBR were formulated using Poly Lactic-co-Glycolic Acid (PLGA) as a polymer. Emulsification and solvent evaporation technique was used. PTZ induced kindling model in male wistar rat was used to demonstrate the anti-seizure effect of nano-BBR. The particle size obtained for the final formulation was 242.8 ± 67.35 nm with a PDI of 0.140 ± 0.01. PLGA encapsulated BBR nanoparticles showed the % encapsulation efficiency of 87.33 ± 2.42 % and % drug loading of 48.47 ± 1.34 %. In-vitro drug release data showed sustained release of nano-BBR as compared to BBR. Kinetic study data showed increase in AUC of nano-BBR (35,429.46 h.ng/ml) as compared to BBR (28,211.07 h.ng/ml). Cmax for nano- BBR (2251.90 ng/ml) is approximately 1.6 times greater than BBR (1505.50 ng/ml). Nano- BBR has shown the significant effect on the seizure score. The PLGA encapsulated berberine nanoparticles were prepared by an innovative simple method and offers excellent potential as an antiepileptic agent.