Epilepsia最新文献

Febrile infection-related epilepsy syndrome (FIRES) is a rare clinical presentation of refractory status epilepticus following a febrile infection. This study analyzes data from the NORSE/FIRES Family Registry, an international web-based registry available in six languages with data entered by patients, families, and clinicians to explore clinical presentations, survivorship, and long-term outcomes in adult and pediatric FIRES patients. We characterize and examine differences in demographics, prodromal symptoms, seizure frequency, anti-seizure medications (ASMs), quality of life, cognition, mood, and anxiety in adults vs pediatric populations with FIRES. Eighty-six participants were included in the study. Pediatric patients (n = 54) were predominantly male (77.8%) and experienced a significantly higher post-FIRES seizure burden than adult survivors (67.7% ≥12 seizures/month in pediatrics vs 11.8% in adults, p <.001). Adults (n = 32) were more likely to be female (59.4%) and have flu-like prodromal symptoms (90.6%). At ≥6 months post-FIRES, both groups exhibited high ASM use, with the majority (87.5%) taking three or more medications. Pediatric patients reported worse mood and anxiety outcomes compared to adults (p <.005). Self-reported quality of life and cognition were rated as moderate across in adults (5.2/10) and pediatric (4.7/10) patients, although pediatric patients indicated poorer cognition. Our findings highlight the challenges in managing post-FIRES outcomes across different age groups, particularly in pediatric patients who face a higher seizure burden and report worse cognitive outcomes.

Objective: To evaluate iron deposition patterns in patients with cerebral cavernous malformation-related epilepsy (CRE) using quantitative susceptibility mapping (QSM) for detailed analysis of iron distribution associated with a history of epilepsy and severity.

Methods: This study is part of the Quantitative Susceptibility Biomarker and Brain Structural Property for Cerebral Cavernous Malformation Related Epilepsy (CRESS) cohort, a prospective multicenter study. QSM was used to quantify iron deposition in patients with sporadic cerebral cavernous malformation (CCMs). Lesions were segmented into intralesional, perilesional, and extralesional areas, with mean susceptibility values calculated for each subregion and analyzed in relation to epilepsy severity and duration.

Results: Among the 46 patients studied, those with a history of epilepsy had significantly higher iron deposition values in the perilesional (p =.012) and extralesional areas (p =.01), as well as a greater extent of iron deposition (p <.001) compared to those without epilepsy. The extent of iron deposition effectively distinguished patients with and without epilepsy, with an area under the curve (AUC) of 0.901 (95% confidence interval [CI]: 0.816-0.985). Among patients with epilepsy, iron deposition in the extralesional area was positively correlated with the severity of epilepsy (r² = 0.181, p =.043), and the extent of iron deposition was positively correlated with the duration of epilepsy (r² =.214, p =.026).

Significance: This study highlights QSM as a non-invasive tool for assessing iron deposition in CRE, identifying distinct subregional iron deposition patterns linked to epilepsy status and severity.

Objective: Identifying factors influencing cannabidiol (CBD) exposure can optimize treatment efficacy and safety. We aimed to describe the population pharmacokinetics of CBD in children with drug-resistant developmental and epileptic encephalopathies (DEEs) and assess the influence of environmental, pharmacological, and clinical characteristics on CBD systemic exposure.

Methods: Data from two pharmacokinetic studies of patients aged 2-18 years with DEEs were included (N = 48 patients). Serial blood samples were collected during maintenance treatment, before and after the morning dose, and up to 6 h after a dose of a purified CBD oil formulation, with or without a normocaloric breakfast. CBD plasma concentrations were also available following administration of a CBD-enriched formulation. Samples were quantified using a validated liquid chromatography/tandem mass spectrometry assay. A CBD population pharmacokinetic model was developed using nonlinear mixed-effects modeling. The effects of formulation, concomitant food intake, and demographic, clinical, and pharmacological factors on CBD pharmacokinetics were evaluated. Simulated maximum plasma concentration (C_max) and area under the concentration-time curve between 0 and 12 h (AUC_0-12) were calculated.

Results: A one-compartment model with transit compartments and first-order elimination best described CBD pharmacokinetics. Mean values for CBD apparent clearance (CL/F) and volume of distribution (V/F) were 143.5 L/h and 1892.4 L, respectively. Weight was allometrically scaled for V/F and CL/F, sex was associated with V/F, and both formulation and food condition were associated with F (relative bioavailability). CBD C_max increased by 41% and AUC_0-12 by 45% when CBD was administered with food compared to fasting. Dose-normalized AUC_0-12 was approximately 50% lower with CBD-enriched oil compared to purified CBD.

Significance: In the present study, we described the effects of food and formulation on CBD exposure in children with DEEs. Increased CBD exposure with food intake and significant changes in drug exposure when switching between CBD formulations should be considered in patient management.

Objective: Interhospital transfers for status epilepticus (SE) are common, and some are avoidable and likely lower yield. The use of interhospital transfer may differ in emergency department (ED) and inpatient settings, which contend with differing clinical resources and financial incentives. However, transfer from these two settings is understudied, leaving gaps in our ability to improve the hospital experience, cost, and triage for this neurologic emergency. We aimed to describe interhospital transfer for SE and examine the relationship between the site of transfer and hospital length of stay.

Methods: We performed a cross-sectional study of adult patients with SE who underwent interhospital transfer using data from the State Emergency Department Databases and State Inpatient Databases of Florida (2016-2019) and New York (2018-2019). The primary outcome was discharge after undergoing transfer. Secondary outcomes were discharge within 1 day, discharge after 30 days, receipt of electroencephalography (EEG), and discharge disposition.

Results: There were 10 461 encounters for SE. Of 1790 ED encounters without admission to the same hospital, 324 (18.1%) resulted in transfer. Of 8671 hospitalizations, 629 (7.3%) resulted in transfer. Patients transferred from the ED were younger, more likely were White, more likely were in a metro area, and had fewer medical comorbidities than patients transferred from the inpatient setting. The median time to discharge was 5 days (interquartile range [IQR] = 2.0-9.0) after ED transfer and 10 days (IQR = 4.0-20.0) after inpatient transfer. There were 58 (17.9%) patients who were discharged within 1 day after undergoing transfer from an ED. ED transfers had higher rates of discharge at 30 days and higher likelihood of undergoing EEG at the receiving hospital and being discharged home.

Significance: A high proportion of patients with SE are discharged shortly after undergoing interhospital transfer, particularly those transferred from the ED. Understanding reasons for transfer is a crucial next step in triaging limited inpatient epilepsy resources and reducing costs associated with interhospital transfer.

Objective: This study was undertaken to describe incidence and distribution of seizures, etiologies, and epilepsy syndromes in the general child and youth population, using the current International League Against Epilepsy (ILAE) classifications.

Methods: The study platform is the Norwegian Mother, Father, and Child Cohort Study (MoBa). Epilepsy cases were identified through registry linkages facilitated by Norway's universal health care system and mandatory reporting to the Norwegian Patient Registry. A standardized protocol guided medical record review, leading to validation of diagnoses and classification of seizures, epilepsy types, syndromes, and etiologies based on the latest ILAE criteria.

Results: MoBa included 111 365 participants aged 12-21 years by the end of follow-up on December 31, 2020. We identified 1053 children and youth with epilepsy (CYE). A defined epilepsy syndrome and/or identified etiology was found in 76% of CYE in this population-based study. Seizure types exhibited variation by age at onset. Focal epilepsies were predominant, occurring in 61% of CYE, whereas generalized epilepsies were identified in 24% of CYE. Standard clinical assessment identified etiology in 30% of CYE and in 55% with onset age < 2 years. Structural and identified genetic etiologies constituted 21% and 10%, respectively. Including presumed genetic and rare etiologies, 53% exhibited known etiology. A defined ILAE epilepsy syndrome was found in 53% of CYE. The cumulative incidence per 1000 children of the following ILAE epilepsy syndrome groups were as follows: self-limited epilepsies, 2.25; idiopathic generalized epilepsies, 1.75; and developmental and/or epileptic encephalopathies, 2.62.

Significance: Using the new ILAE classifications, this population-based childhood study provides incidences of seizures, epilepsies, and epilepsy syndromes. Half of epilepsy cases are classified as an ILAE epilepsy syndrome with its prognostic and therapeutic implications, but a substantial proportion of cases still have unknown etiology.

Objective: The pulvinar nucleus of the thalamus has extensive cortical connections with the temporal, parietal, and occipital lobes. Deep brain stimulation (DBS) targeting the pulvinar nucleus, therefore, carries the potential for therapeutic benefit in patients with drug-resistant posterior quadrant epilepsy (PQE) and neocortical temporal lobe epilepsy (TLE). Here, we present a single-center experience of patients managed via bilateral DBS of the pulvinar nucleus.

Methods: A single-institution retrospective review of five patients who underwent bilateral pulvinar DBS for drug-resistant TLE or PQE was performed. Stimulation parameters were adjusted monthly as needed, and side effects were monitored. The primary outcome was the percentage reduction in patient-reported seizure frequency in comparison to the preimplant baseline. The location of the active electrode contacts in relation to pulvinar thalami that produced the best seizure outcome was identified. Chronic sensing of the pulvinar local field potentials (LFPs) and circadian pattern of modulation of the LFP amplitudes were analyzed.

Results: Four patients (80%) experienced a >70% reduction in seizure frequency, whereas one patient had >50% reduction in seizure. Mean seizure reduction was 79% at a median follow-up of 13 months (range = 9-21 months). No significant side effects were noted. Of all the pulvinar subnuclei, stimulation of the medial pulvinar nucleus (MPN) produced the best seizure outcome in all patients except for two, in whom active contacts in the MPN but also in more lateral and inferior locations resulted in the most significant reduction in seizures. Chronic timeline data identified changes in LFP amplitude associated with stimulation and seizure occurrences.

Significance: In this first ever report on a series of patients undergoing bilateral pulvinar DBS for drug-resistant epilepsy, we demonstrate that stimulation of the pulvinar and in particular the MPN is a safe and viable option for patients with nonlesional PQE or TLE. The optimal target for stimulation and relative merits of open versus closed loop stimulation should be delineated in future studies.

Objective: This study was undertaken to test the following hypotheses in the Atp1a3^Mashl/+ mouse (which carries the most common human ATP1A3 (the major subunit of the neuronal Na⁺/K⁺-adenosine triphosphatase [ATPase]) mutation, D801N): sudden unexpected death in epilepsy (SUDEP) occurs during seizures and is due to terminal apneas in some and due to lethal cardiac arrhythmias in others; and Atp1a3^Mashl/+ mice have central cardiorespiratory dysregulation and abnormal respiratory drive.

Methods: Comparison was made of littermate wild-type and Atp1a3^Mashl/+ groups using (1) simultaneous in vivo video-telemetry recordings of electroencephalogram, electrocardiogram, and breathing; (2) whole-body plethysmography; and (3) hypoglossal nerve recordings.

Results: In Atp1a3^Mashl/+ mice, (1) SUDEP consistently occurred during seizures that were more severe than preterminal seizures; (2) seizure clustering occurred in periods preceding SUDEP; (3) slowing of breathing rate (BR) and heart rate was observed preictally before preterminal and terminal seizures; and (4) the sequence during terminal seizures was as follows: bradypnea with bradycardia/cardiac arrhythmias, then terminal apnea, followed by terminal cardiac arrhythmias. Compared to wild-type, mutants showed (1) abnormal resting BR variability but no difference in cardiac PR, QRS, QTc, or RR intervals; (2) abnormal hypoglossal nerve firing in response to hypoxia; and (3) abnormal whole-body plethysmography, consisting of baseline predisposition to apnea and abnormal responses to respiratory challenge.

Significance: Atp1a3^Mashl/+, an alternating hemiplegia of childhood (AHC) model, is also a revealing SUDEP model of Na⁺/K⁺-ATPase mutation resulting in abnormal central respiratory drive and in progressive cardiorespiratory dysregulation concurrent with worsening epilepsy. SUDEP results from seizure-triggered bradypnea/bradycardia followed by terminal apnea, then terminal cardiac arrhythmias. Because many epilepsy/SUDEP models of other etiologies manifest secondary ATPase deficiency, future studies in those models may benefit from considering possible contributions of ATPase dysfunction to SUDEP in those models too.

Objective: Cognitive deficits are one of the most debilitating comorbidities in epilepsy and other neurodegenerative, neuropsychiatric, and neurodevelopmental brain disorders. Current diagnostic and therapeutic options are limited and lack objective measures of the underlying neural activities. In this study, electrophysiological biomarkers that reflect cognitive functions in clinically validated batteries were determined to aid diagnosis and treatment in specific brain regions.

Methods: We employed the Cambridge Neuropsychological Test Automated Battery (CANTAB) tasks to probe memory and executive functions in 86 patients with epilepsy undergoing clinical electroencephalography (EEG) monitoring. EEG electrode signals during performance of particular battery tasks were decomposed to identify specific frequency bands and cortical areas that differentiated patients with impaired, normal, and good standardized performance according to their age and gender.

Results: The anterior prefrontal cortical EEG power in the theta frequency band was consistently lower in patients with impaired memory and executive function performance (z-score < -1). This effect was evident in all four behavioral measures of executive, visual, spatial, and working memory functions and was confined to the cortical area of all four frontal pole electrodes (Nz, Fpz, Fp1, and Fp2).

Significance: Theta EEG power in the anterior prefrontal cortex provides simple, accessible, and objective electrophysiological measure of memory and executive functions in epilepsy. Our results suggest a feasible clinical biomarker for diagnosis, monitoring, and treatment of cognitive deficits with emerging targeted neuromodulation approaches.

Objective: Seizures are a recognized complication of critical cardiovascular illness in infants and children. We assessed the diagnostic yield of continuous video-electroencephalography (cEEG) in a pediatric and neonatal cardiovascular intensive care unit (CVICU) by the symptoms and risk factors prompting cEEG evaluation.

Methods: This retrospective case series included all consecutive cEEGs in patients ≤21 years old performed in one CVICU over 38 months. cEEG indications were categorized as (1) index symptoms of concern and/or (2) clinical risk factors. Index symptoms were divided into (1) vital sign symptoms (i.e., heart rate, blood pressure, oxygen, respiration, or temperature) and (2) non-vital sign symptoms (i.e., mental status, abnormal movements, eye findings, weakness, or failed extubation). Indications for cEEG were extracted by manual chart review. The presence of seizures was established electrographically from neurophysiologist reports.

Results: There were 605 cEEGs from 411 patients. The median study was 26 h (25%-75%, interquartile range = 20-41 h). Seizures were detected in 57 of 605 (9%) cEEGs overall; in 34 of 356 (10%) cEEGs obtained for risk factors alone (odds ratio [OR] = 1.03, 95% confidence interval [CI] = .60-1.82, p = .90), 0 of 104 (0%) for isolated vital sign changes (p < .001), 10 of 101 (10%) for symptoms not involving vital signs (OR = 1.06, 95% CI = .52-2.09, p = .88), and in 13 of 44 (30%) for both vital sign and non-vital sign symptoms (OR = 4.93, 95% CI = 2.45-9.77, p < .001). On univariate analysis, symptoms involving gaze deviation, abnormal limb movements, or intermittent oxygen desaturation, and the risk factors of preexisting epilepsy, recent neurosurgery, acute stroke, and cardiac air embolism were associated with seizures (p < .05).

Significance: There were zero electrographic seizures in cEEGs obtained for isolated vital sign changes, whereas cEEGs obtained for the combination of vital sign changes and other non-vital sign symptoms were five times more likely to detect electrographic seizures than cEEGs obtained based on risk factors alone.

Contemporary studies report nonconvulsive status epilepticus (NCSE) in Creutzfeldt-Jakob disease (CJD), based on benzodiazepine (BZP)-responsive epileptiform discharges on the electroencephalogram (EEG), with the following false syllogism: (1) intravenous (IV) administration of BZPs usually suppress ictal activity in NCSE; (2) in CJD, periodic sharp wave complexes (PSWCs) are suppressed by IV BZPs; (3) therefore, these patients have NCSE. This is a simplistic and invalid conclusion, because authors of 20th-century science reports have clearly shown that IV BZPs, short-acting barbiturates, and drugs with no antiseizure effects, such as chloral hydrate and IV naloxone, suppress PSWCs, but patients fall asleep with no clinical improvement. In contrast, IV methylphenidate transiently improves both the EEG and clinical states. Unlike NCSE, which is unlikely to be stopped by external stimuli, PSWCs can be transiently stopped by sensory or painful stimulation. Since the end of the 1970s, the effect of spontaneous sleep on the disappearance of PSWCs has been well documented, with a description of a cycling alternating pattern. Phase A features periodic discharges and is associated with increased arousal, whereas phase B exhibits a reduction or suppression of the PSWCs and is associated with a reduction in the arousal level and hypotonia (non-rapid eye movement sleep). When considering the use of IV BZP administration during EEG as a diagnostic test, the sequence of disappearance of PSWCs at sleep onset and reappearance after each stimulation or sleep apnea episode is compelling evidence against NCSE, as is the observation of a pattern of stimulus-induced wakefulness with transient improvement of the EEG. The cycling alternating pattern during sleep and reactivity to sensory or painful stimulation disappear with increasing disease severity; however, this occurs in the later stages of the disease, where there is no diagnostic doubt.