Epilepsia最新文献

Objective: Randomized controlled trials (RCTs) are necessary to evaluate the efficacy of novel treatments for epilepsy. However, there have been concerning increases in the placebo responder rate over time. To understand these trends, we evaluated features associated with increased placebo responder rate.

Methods: Using individual-level data from 20 focal-onset seizure trials provided by seven pharmaceutical companies, we evaluated associations with change in seizure frequency in participants randomized to placebo. We used multivariable logistic regression to evaluate participant and study factors associated with differing rates of 50% reduction in seizure frequency during blinded placebo treatment, as compared to pre-randomization baseline seizure frequency. In addition, we focused on the association of placebo responder rate with pre-randomization baseline seizure frequency and country of recruitment.

Results: In the pooled analysis of 1674 participants randomized to placebo, a higher 50% responder rate (50RR) was associated with a shorter duration of epilepsy (p = .006), lower baseline seizure rate (p = .002), fewer concomitant antiseizure medications (p = .004), absence of adverse events (p < .001), more trial arms (p = .006), and geographic region (p < .001). Mixture modeling indicated a significantly higher 50RR in Bulgaria, Croatia, India, and Canada (42% in the higher group vs 22% in the lower group comprising all 40 other countries, p < 10^-15). In addition, there was a significantly higher 50RR in participants with a baseline seizure frequency of six or fewer seizures per 28 days (29% vs 21%, p = .00018).

Significance: These results can assist future RCTs in estimating the expected placebo responder rate, which may lead to more reliable power estimates. Higher placebo responder rate was associated with markers of less-refractory epilepsy. There were concerning significant differences in placebo responder rate by country and geographic region as well as an elevated placebo responder rate in participants with baseline seizure frequency close to the minimum eligibility criteria.

Objective: The STEPPER (Status Epilepticus in Emilia-Romagna) study aimed to investigate the clinical characteristics, prognostic factors, and treatment approaches of status epilepticus (SE) in adults of the Emilia-Romagna region (ERR), Northern Italy.

Methods: STEPPER, an observational, prospective, multicentric cohort study, was conducted across neurology units, emergency departments, and intensive care units of the ERR over 24 months (October 2019-October 2021), encompassing incident cases of SE. Patients were followed up for 30 days.

Results: A total of 578 cases were recruited (56% female, mean age = 70 years, 32% with previous diagnosis of epilepsy, 43% with in-hospital onset, 35% stuporous/comatose, 46% with nonconvulsive SE). Etiology was known in 87% (acute 43%, remote 24%, progressive 17%, definite epileptic syndrome 3%). The mean pre-SE Rankin Scale score was 2, the Status Epilepticus Severity Score was ≥4 in 33%, the Epidemiology-Based Mortality Score in Status Epilepticus score was ≥64 in 61%, and 34% were refractory. The sequence of treatments followed current clinical practice guidelines in 63%. Benzodiazepines (BDZs) were underused as first-line therapy (71%), especially in in-hospital onset cases; 15% were treated with continuous intravenous anesthetic drugs. Mortality was 24%; 63% of survivors had functional worsening. At the two-step multivariable analysis, incorrect versus correct treatment sequence with correct BDZ dose was the strongest predictor of failure to resolve SE in the in-hospital group (odds ratio [OR] = 4.42, 95% confidence interval [CI] = 1.86-10.5), with a similar trend in the out-of-hospital group (OR = 2.22, 95% CI = .98-5.02). In turn, failure to resolve was the strongest predictor of 30-day mortality (OR = 11.3, 95% CI = 4.16-30.9, out-of-hospital SE; OR = 6.42, 95% CI = 2.79-14.8, in-hospital SE) and functional worsening (OR = 5.83, 95% CI = 2.05-16.6, out-of-hospital SE; OR = 9.30, 95% CI 2.22-32.3, in-hospital SE).

Significance: The STEPPER study offers insights into real-world SE management, highlighting its significant morbidity and functional decline implications. Although nonmodifiable clinical factors contribute to SE severity, modifiable factors such as optimized first-line therapies and adherence to guidelines can potentially influence prognosis.

Objective: Stereotactic laser amygdalohippocampotomy (SLAH) is a minimally invasive procedure for mesial temporal lobe epilepsy that preserves more tissue than open procedures. As a result, although patients have better functional outcomes, more patients do not achieve seizure freedom. The rate at which this occurs is evolving with improved surgical practices. However, the risks and benefits of further surgical management for these patients remains a question with limited data to guide decision-making.

Methods: We retrospectively reviewed a continuous series (2011-2019) of SLAH operations at our institution to determine trends in surgical management, identifying cases where further surgery was performed. Pre-operative and follow-up seizure, cognitive, and functional data, and surgical complications were collated.

Results: Of 108 patients undergoing primary SLAH, 21 (19%) underwent further surgery (23 procedures). Stereo-electroencephalography (SEEG) informed seven procedures (30%). There was a trend for quicker SLAH failure in the earlier patients. Similarly, surgical chronology was associated with progression to repeat surgery (p = .007). At 1-year follow-up, 6 of 13 patients (46%) achieved seizure freedom after repeat SLAH and 5 of 8 patients (63%) achieved seizure freedom after anterior temporal lobectomy (ATL), one of whom had failed two SLAHs. Two of three patients undergoing an ablation outside the mesial temporal lobe achieved seizure freedom at 1 year. Neuropsychological sequelae were more prevalent with ATL than SLAH, including decline in visual naming (p = .01) and functional status (p = .007).

Significance: Repeat SLAH and ATL post-SLAH are both practicable and can be effective. Surgical experience, risk to cognition, and marginal benefit relative to existing improvement are principal considerations for further surgery.

Objective: Status epilepticus (SE) is a neurological emergency in childhood, often leading to neuronal damage and long-term outcomes. The study aims to identify barriers in the pre-hospital and in-hospital management of community-onset pediatric SE and to evaluate the effectiveness of pediatric scores on outcomes prediction.

Methods: This monocentric observational retrospective cohort study included patients treated for community-onset pediatric SE in a tertiary care hospital between 2010 and 2021. Data were extracted following Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Inclusion criteria were community-onset SE (according to the International League Against Epilepsy [ILAE] Task Force on SE Classification), admission to the pediatric emergency department (PED), age: 1 month to 18 years. Pre-hospital, in-hospital management and outcomes were analyzed. Pediatric scores for prediction of clinical worsening (Pediatric Early Warning Score - PEWS) and SE outcome (Status Epilepticus in Pediatric patients Severity Score - STEPSS; Pre-status Epilepticus PCPCS, background Electroencephalographic abnormalities, Drug refractoriness, Semiology and critical Sickness Score - PEDSS) were retrospectively assessed for their accuracy in predicting short-term and long-term outcomes.

Results: A total of 103 consecutive episodes of SE were included. Out-of-hospital rescue medications administration occurred in 54.4% of cases and was associated with higher SE resolution rate before PED admission (48.2% vs 27.6%, p = .033). Longer in-PED time to treatment was observed in case of delay to PED referral (r = 0.268, p = .048) or non-red triage labels (12 vs 5 min, p = 0.032), and was associated with longer in-PED duration of SE (r = 0.645, p < .001). Longer SE duration was observed in episodes leading to hospitalization compared to those discharged (50 vs 16 min, p < .001). In-PED electroencephalography (EEG) recordings were available in 39.8% of events. Predictive scores varied in accuracy, with PEWS ≥5 showing high sensitivity for intensive care unit (ICU) admission but low specificity. No patients died, 6.3% of SE was refractory.

Significance: Effective pre-hospital administration of rescue medications and prompt PED management are crucial to reduce SE duration and improve outcomes. Predictive scores can aid in assessment of the severity and prognosis of SE; their utility is still not defined. Identifying and addressing actionable care barriers in SE management pathways is essential to enhance patient outcomes in pediatric SE.

Objective: In onchocerciasis-endemic areas, limited access to antiseizure medications (ASMs) contributes to a high epilepsy burden. This study evaluated the impact of a community-based epilepsy care program in Mahenge, Tanzania, an onchocerciasis-endemic area with high epilepsy prevalence.

Methods: A baseline survey (2017-2018) identified persons with epilepsy (PWE) in four rural villages. Subsequently, PWE were invited to enroll in the epilepsy treatment program (2019-2022), where trained community health workers (CHWs) screened for epilepsy, promoted ivermectin intake to treat onchocerciasis, distributed ASMs, and monitored seizure frequency and ASM adherence monthly under supervision from the project clinician trained in epilepsy diagnosis and treatment. A concluding survey (2022) collected sociodemographic data and participants' status as alive, deceased, or lost to follow-up. Mixed-effects negative binomial regression analyzed risk factors for weekly seizure incidence rate.

Results: Of 206 participants, 77.7% reported bilateral tonic-clonic seizures, and 32.0% reported focal seizures. More than one third (38.5%) were suspected of having nodding syndrome. Weekly seizure frequency decreased significantly from a mean of 1.9 seizures (interquartile range [IQR] = 0-2) at enrollment to .4 seizures (IQR = 0-0) at the last follow-up (Wilcoxon test p < .0001), with significantly improved ASM adherence (57.5%-94.7%, McNemar test p < .0001). Factors associated with lower weekly seizure incidence included longer program participation, ASM adherence, carbamazepine use compared to phenobarbital, and ivermectin intake in 2022. ASM adverse events were associated with increased seizure frequency. The mortality rate was 32.7 deaths per 1000 person-years, with most deceased not fully adhering to ASM (88%) and having epilepsy-related causes of death (60%).

Significance: The community-based program using CHWs was associated with a significant reduction in seizure frequency and improved ASM adherence. In onchocerciasis-endemic areas, it should be investigated whether carbamazepine should be a preferred ASM in PWE. Ivermectin's impact on seizure frequency merits further investigation in onchocerciasis-endemic areas. Community-based epilepsy care is a promising strategy for scaling up epilepsy care in rural areas in Africa.

Despite the high prevalence of cognitive deficits in older people with epilepsy (PWE), their ability to judge and make decisions in daily life remains unexplored. In 61 older PWE (55-90 years) from the multicenter BRain Aging and Cognition in Epilepsy (BrACE) study, we examined everyday judgment, as measured by the Test of Practical Judgment (TOP-J: 9 questions, score range = 0-27; higher score = better judgment) and evaluated its association with clinical and demographic characteristics, global cognition, neuropsychological performance, subjective cognition, and quality of life (QOL). In our participants (mean age ± standard deviation [SD] = 66.3 ± 6.57 years; 57.4% female), >50% scored in the range observed in individuals with mild cognitive impairment (≤21) and 10% in the range similar to people with dementia (≤16). Multivariable analysis revealed that education was the only demographic factor associated with TOP-J performance. Pearson correlation analysis revealed that lower TOP-J scores were associated with lower global cognition, language, and abstraction/executive function. Lower TOP-J scores were also associated with poorer QOL and self-reported cognitive complaints. These data suggest that the TOP-J may be a viable screening tool for early identification of reduced judgment. This could guide appropriate interventions in clinical practice, especially when older PWE present with deficits in language and executive function.

Objective: Studies have shown that a growing number of people with epilepsy belong to minority groups and experience health disparities. Inclusivity in clinical trial enrollment is essential for advancing health access but has not been well studied among epilepsy trials. The objective of this study was to analyze US epilepsy clinical trials to identify the prevalence and trends associated with race and sex enrollment disparities.

Methods: We queried the Clinicaltrials.gov registry to identify completed epilepsy clinical trials with results reported between 2006 and 2022. Studies were assessed for reporting of participant race and sex information, and measures of trial diversity including the participation to prevalence ratio (PPR), representation ratio (RR), and representation quotient (RQ) were calculated. Other data including funding source, intervention type, location, and trial dates were also extracted.

Results: Ninety trials met inclusion criteria, of which 89 (99%) and 53 (59%) reported participant sex and race, respectively. Three trials included only female participants and were excluded from further sex-specific analyses. Females were underrepresented in 10 of the remaining 86 trials reporting sex information (PPR < .8, 12%). We found that industry-funded trials were more likely to have equal female representation among participants (p = .0197). Of trials reporting participant race, 52 (98%) exhibited a lack of racial diversity (RQ < 1). Black participants were the most frequently underrepresented racial group (RR < 1, 42 of 53 trials, 79%).

Significance: Our findings highlight significant disparities in epilepsy clinical trial enrollment, particularly for Black participants. Lack of diversity and underrepresentation of historically marginalized populations may contribute to research biases and perpetuate health inequities. More inclusive research practices are needed to ensure all people with epilepsy have access to effective care.

Objectives: Resective surgery in drug-resistant focal epilepsy (DRFE) requires extensive evaluation to localize the epileptogenic zone (EZ). When non-invasive phase 1 assessments (electroencephalography, EEG; magnetic resonance imaging, MRI; and ¹⁸F-Fluorodeoxyglucose-positron emission tomography, [¹⁸F]FDG-PET) are inconclusive for EZ localization, invasive investigations such as stereo-EEG (SEEG) are necessary. Epileptogenicity maps (Ems) visualize the EZ using SEEG-identified ictal high-frequency oscillations (iHFOs). PET imaging with radioligands targeting the18-kDa translocator protein (TSPO), a marker of glial activation, may aid EZ localization. This study investigates the correlation between TSPO-PET imaging and SEEG iHFOs in DRFE to determine the utility of TSPO-PET in pre-surgical assessments, especially in complex or non-lesional cases.

Methods: Patients with DRFE and inconclusive phase 1 assessments were recruited from Bicêtre Hospital (AP-HP) for a prospective study (Eudract 2017-003381-27). They underwent SEEG and [¹⁸F]DPA-714 (N,N-diethyl-2-(2-(4-(2-(fluoro-¹⁸F)ethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide) (TSPO radioligand) PET imaging. Statistical parametric mapping (SPM) techniques analyzed significant [¹⁸F]DPA-714-PET uptake (TSPO-map) and generated epileptogenicity maps (EM-map). Correlation analyses at regional and voxel-of-interest (VOI) levels assessed the relationship between TSPO-map and EM-map.

Results: We were able to obtain and analyze both maps in 12 of 17 patients recruited. A significant positive correlation between EM-map and TSPO-map in focal epilepsies was found regionally (r = .81, p < .00004) and at the VOI level (r = .79, p < .00003). Temporal, insular, parietal, and occipital regions showed particularly strong correspondence. In frontal epilepsies, TSPO-map was more focal than EM-map, suggesting increased specificity for SEEG planning. This study also demonstrated the benefit of the TSPO-map in identifying multiple foci in multifocal epilepsies, with or without lesions.

Significance: These findings suggest that neuroinflammation may be a molecular substrate of the EZ in non-lesional focal epilepsy. Identifying the EZ inpatients with complex DRFE and inconclusive MRI/[¹⁸F]FDG-PET imaging is essential to improve resective surgery outcomes. Combining TSPO-PET imaging with SEEG recordings may help bridge this gap.

Objective: Patients with newly diagnosed epilepsy exhibit brain white matter (WM) abnormalities, but the temporal dynamics of these are unknown. The literature suggests these alterations might be present before diagnosis. This study investigates WM microstructural integrity using diffusion imaging in non-lesional (NL), interictal epileptiform discharge (IED)-free, unmedicated patients who experienced a first unprovoked seizure compared to healthy controls. Furthermore, we evaluated whether the patients who developed epilepsy within a 1-year follow-up had a divergent pattern of WM alterations in contrast to those who did not. We also evaluated patients with established epilepsy.

Methods: We performed a diffusion imaging analysis in a cohort of 82 subjects. Twenty patients recently experienced a first unprovoked seizure (first-seizure group), 32 patients had chronic epilepsy (chronic-epilepsy group), and 30 healthy controls. The first-seizure patients were later classified into patients who developed epilepsy (early-epilepsy) and those who did not (single-seizure). Fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) were calculated. Group differences were analyzed using tract-based spatial statistics and permutation analysis of linear models.

Results: Compared to controls, first-seizure patients showed decreased FA (p < .05, d = 1.3) in the corpus callosum and forceps minor, among other tracts. Similar changes were found in the single-seizure group (p < .05, d = 1.3), whereas the early-epilepsy patients showed decreases only in the corpus callosum (p < .05, d = 2.4). We confirmed that patients with chronic epilepsy have widespread FA decreases (p < .05, d = 1).

Significance: We provide evidence that, as early as after the first unprovoked seizure, patients considered NL by conventional methods harbor marked microstructural abnormalities detectable with diffusion magnetic resonance imaging (MRI). These findings suggest that WM alterations are present very early in the epileptogenic process even before the diagnosis can currently be made. These results have important implications for better understanding the epileptogenic process and preexisting structural difference in patients after a first seizure.

Periventricular nodular heterotopia (PVNH) is a neuronal migration disorder often associated with drug-resistant epilepsy. The epileptogenic zone network (EZN) in PVNH is generally large, contraindicating surgery. Stereoelectroencephalography (SEEG) can be proposed to map the EZN and perform radiofrequency thermocoagulation (THC) with an efficacy rate of approximately 65%. There are genetic forms of PVNH, particularly with mutations in the filamin A gene (FLNA). However, data on SEEG-guided THC in these patients still have not been described. We report four patients with FLNA-positive PVNH who underwent SEEG-guided THC. All were women with several types of seizures and psychiatric comorbidities. EZN was extensive and often bilateral, including a part of the heterotopias. The outcomes of SEEG-guided THC varied; two patients experienced significant seizure reduction and improvement in psychiatric symptoms (Engel class I-II), one showed partial improvement (Engel class III), and one had no significant benefit (Engel class IV). Psychiatric comorbidities, including posttraumatic stress disorder, depression, and anxiety, were present in all cases, with some patients showing symptom improvement alongside seizure reduction. Despite genetic origin, SEEG-guided THC can be proposed in FLNA-positive PVNH-related epilepsy, although outcomes vary. The presence of FLNA mutations should not contraindicate surgical intervention but may influence the therapeutic response. Further research is needed to understand the impact of genetic variants on epilepsy outcome.