Epilepsia最新文献

Objective: Tuberous sclerosis complex (TSC) causes focal drug-resistant epilepsy. Prediction of which tubers are epileptogenic remains challenging. We used stereoelectroencephalography (SEEG) to investigate epileptogenic zone (EZ) organization in TSC-related epilepsy, focusing on epileptogenicity of different tuber radiological subtypes.

Methods: We retrospectively studied consecutive patients with TSC-related epilepsy explored by SEEG. Presence of "focal EZ" (comprising "focal tuber," "tuber-plus," and "focal nontuber") or "diffuse EZ" was determined. In focal EZ involving tubers, interictal and ictal epileptogenic biomarkers were compared to the radiological appearance of tubers. In addition to four previously described tuber subtypes, we propose a novel subtype: type E (focal cortical depression, hypointense base on T2/fluid-attenuated inversion recovery).

Results: Among 63 patients, 55 (87.3%) patients exhibited focal EZ, including focal tuber (n = 32, 50.8%), tuber-plus (n = 11, 17.5%), and focal nontuber (n = 12, 19.0%, of which 7/12 involved focal cortical dysplasia [FCD]). In the 43 of 63 (68.3%) patients with focal EZ involving at least one tuber, epileptogenicity of 265 explored tubers was analyzed with regard to radiological subtypes. Tuber subtypes A and B were most prevalent (186/265, 70.2%) but among the least epileptogenic on SEEG. The highest ictal epileptogenicity was in subtypes D (77.8%) and E (77.5%) compared to type A/B/C (Fisher exact test; all p < .05). Type D/E tubers exhibited higher interictal biomarkers than type A/B/ C (linear mixed model; p < .05). In patients with focal EZ, following surgical intervention, 36 of 55 (65.5%) achieved Engel class I outcomes, with a higher odds ratio of Engel I in the combined group of focal tuber/focal nontuber compared to tuber-plus EZ (p < .05).

Significance: Most TSC-related epilepsy represents focal EZ related to tubers, but focal extratuber EZ can also occur (FCD or hippocampus). Radiologically, calcified tubers (type D) and tubers with focal cortical depression and central hypointensity (type E) exhibit the highest epileptogenicity, similar to FCD type II.

Objective: This study aimed to assess the performance of the Nelli seizure monitoring system in detecting and classifying seizures during sleep or while at rest in bed in patients with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS).

Methods: We conducted a non-interventional, single-center feasibility study from August 2023 to March 2024, involving 20 patients aged ≥2 years diagnosed with DS or LGS. Participants used Nelli for home-based seizure monitoring during sleep or while at rest in bed for 4 weeks. Seizures were detected and classified by Nelli, and results were compared to epileptologist reviews and seizure diaries.

Results: Of 20 enrolled patients, 14 (70%) who experienced seizures at rest were included in the analyses. Among them, Nelli detected 368 seizures, with an accuracy of 97.8%, as confirmed by independent reviewers. Eight seizures (2.2%) detected by Nelli were false positives, identified as part of a single seizure episode. Of the 14 patients, only 35.7% reported experiencing seizures in their diaries, and only 26.1% of the seizures were documented. Seizure durations ranged from 6 to 396 s, with considerable variation. Nelli demonstrated high accuracy in seizure classification (Gwet agreement coefficient [AC1] = .81-1.00) in nine of 14 cases. However, in three of 14 patients, moderate accuracy (AC1 = .41-.60) was observed due to challenges in classifying seizures in patients with high seizure frequency or suboptimal device positioning. The average classification accuracy of Nelli for tonic-clonic seizures was .99 (150/152 seizures), tonic seizures .55 (102/186), clonic seizures 1.00 (3/3), focal motor seizures .89 (16/18), and myoclonic seizures 1.00 (1/1).

Significance: Nelli demonstrated high sensitivity and classification accuracy for detecting and categorizing seizures in bed in patients with DS and LGS, outperforming seizure diaries and providing a reliable tool for seizure monitoring in home settings.

Objective: Bottom-of-sulcus dysplasia (BOSD) is a diagnostically challenging subtype of focal cortical dysplasia, 60% being missed on magnetic resonance imaging (MRI). Automated MRI-based detection methods have been developed for focal cortical dysplasia, but not BOSD specifically, and few methods incorporate fluorodeoxyglucose positron emission tomography (FDG-PET) alongside MRI features. We report the development and performance of an automated BOSD detector using combined MRI + PET.

Methods: The training set comprised 54 patients with focal epilepsy and BOSD. The test sets comprised 17 subsequently diagnosed patients with BOSD from the same center, and 12 published patients from a different center. Across training and test sets, 81% of patients had normal initial MRIs and most BOSDs were <1.5 cm³. In the training set, 12 features from T1-MRI, fluid-attenuated inversion recovery-MRI, and FDG-PET were evaluated to determine which features best distinguished dysplastic from normal-appearing cortex. Using the Multi-centre Epilepsy Lesion Detection group's machine-learning detection method with the addition of FDG-PET, neural network classifiers were then trained and tested on MRI + PET, MRI-only, and PET-only features. The proportion of patients whose BOSD was overlapped by the top output cluster, and the top five output clusters, were determined.

Results: Cortical and subcortical hypometabolism on FDG-PET was superior in discriminating dysplastic from normal-appearing cortex compared to MRI features. When the BOSD detector was trained on MRI + PET features, 87% BOSDs were overlapped by one of the top five clusters (69% top cluster) in the training set, 94% in the prospective test set (88% top cluster), and 75% in the published test set (58% top cluster). Cluster overlap was generally lower when the detector was trained and tested on PET-only or MRI-only features.

Significance: Detection of BOSD is possible using established MRI-based automated detection methods, supplemented with FDG-PET features and trained on a BOSD-specific cohort. In clinically appropriate patients with seemingly negative MRI, the detector could suggest MRI regions to scrutinize for possible BOSD.

Epileptologists can improve outcomes through follow-up and coordination of care for patients with functional seizures. Epileptic and functional seizures share some mechanistic overlap involving interoceptive, emotional, and stress dysregulation, and disorders of agency and perception. Similar psychiatric and neurological comorbidities occur at comparable rates in both functional and epileptic seizure populations. A holistic, biopsychosocial approach benefits all seizure patients and reflects modern models of epilepsy care.

Objectives: Autism spectrum disorder (ASD) and epilepsy commonly co-occur. Surgical interventions are viable treatment options for individuals with drug-resistant epilepsy. However, past research in patients with ASD and epilepsy has yielded mixed results regarding seizure outcomes following epilepsy surgery.

Methods: We adhered to the Preferred Reporting Item for Systematic reviews and Meta-Analyses (PRISMA) standards. Medline, Embase, and PsycInfo were queried from inception to November 2024. Included studies reported seizure frequency following epilepsy surgery in persons with ASD. Forty-six studies reporting on 325 patients with ASD and epilepsy were included for analysis. A total of 137 patients underwent resective surgery, 167 underwent neuromodulation (138 vagus nerve stimulation [VNS], 27 responsive neurostimulation [RNS], 2 deep brain stimulation [DBS]), and 21 underwent other palliative procedures (17 corpus callosotomy and 4 laser interstitial thermal therapy). Outcomes were stratified into four categories based on a combination of Engel classification and percentage seizure reduction at latest follow-up.

Results: Resections yielded seizure freedom in 54% of patients, whereas neuromodulation led to >80% seizure reduction in 33.5% of patients. The incidence proportion of seizure freedom after surgery was higher in patients with MRI abnormalities was .55 (95% confidence interval [CI]: .34-.75) vs patients without MRI abnormalities (.19, 95% CI: .01-.81). Incidence proportion of seizure freedom after temporal resection was .80 (95% CI: .50-.94) vs .66 (95% CI: .48-.80) for extratemporal resection. Improvement in neuropsychiatric or quality of life outcomes was reported in the majority of patients after surgery.

Significance: Our study provides the most comprehensive review to date of epilepsy surgery in ASD. Based on past work, there is potential for properly selected patients with ASD and epilepsy to experience a significant reduction in seizure frequency or seizure freedom, as well as improved quality of life, following epilepsy surgery.

Objective: This study was undertaken to evaluate the diagnostic value of a set of preselected candidate microRNAs (miRNAs) extracted from plasma-based extracellular vesicles (EVs) to identify patients with seizure-related respiratory dysfunction.

Methods: A two-step design was applied. Step 1 entailed selection of the relevant miRNAs based on the combination of a literature review and an exploratory study in epileptic rats with or without interictal respiratory dysfunction. Step 2 involved evaluation of the diagnostic value of this preselected panel of circulating exosomal miRNAs in a case-control study conducted in 25 healthy subjects and 50 patients with drug-resistant focal epilepsy undergoing video-electroencephalographic (EEG) monitoring. Based on video-EEG data, patients were separated into two groups: those with ictal/postictal hypoxemia (PIH; n = 24) and those without (noPIH; n = 26). Blood samples were collected in the interictal period (>24 h after the last seizure). Expression level of each miRNAs in EVs was compared (1) between all patients with epilepsy and controls and (2) between PIH and noPIH. Receiver operating characteristic (ROC) curves were generated, and the area under the curve (AUC) was calculated.

Results: Following Step 1, the final set of miRNAs selected for evaluation in the case-control study included 24 miRNAs, with nine selected from published data in patients because of their potential regulatory role in the serotoninergic pathway, brain response to hypoxia, or epilepsy and 15 selected from the preclinical study in epileptic rats. Three miRNAs significantly differed between patients with epilepsy and controls (ROC curve AUC: hsa-miR-22-3p, .74 [95% confidence interval (CI) = .63-.85]; hsa-miR-106b-5p, .69 [95% CI = .57-.82]; and hsa-miR-26a-5p, .72 [95% CI = .58-.85]). Only a trend toward higher expression levels was observed for hsa-miR-140-3p in PIH compared to noPIH (+5%, p = .064).

Significance: Whereas three miRNAs were robustly associated with epilepsy, none was significantly associated with seizure-related respiratory dysfunction. Additional studies are required, including analysis of the expression of plasmatic cell-free miRNAs, especially the miRNAs associated with interictal respiratory dysfunction in epileptic rats.

Objective: This study aims to better characterize the long-term neurological quality of life (QOL) outcomes (using the Neuro-QOL scale) in survivors of new onset refractory status epilepticus (NORSE), including its subtype febrile infection-related epilepsy syndrome (FIRES), and provide guidance for psychological and social support strategies.

Methods: Utilizing data from a multicenter prospective study of NORSE/FIRES led by Yale University, we enrolled patients who completed the validated, patient-reported Neuro-QOL scale at least once at 3-6 months (n = 37), 12 months (n = 29), 24 months (n = 23), or ≥36 months (n = 9) following discharge. The Neuro-QOL scale assesses physical, mental, and social health in patients with neurological disorders. QOL impairment (QOL-I) scores were calculated, with higher scores indicating greater impairment. T-scores enabled comparisons with reference populations.

Results: In adults, median QOL-I improved from 44.1% at 3-6 months to 37.6% at 36+ months. Paired analysis showed significant improvement in QOL-I between 3-6 and 24 months (p = .016), with specific improvements in communication, satisfaction with social roles, fatigue, and mobility. Greater improvement was also observed for participation in social roles (5.5-point T-score gain) compared to the reference population, suggesting meaningful change. A gradual improvement in overall QOL-I scores was also observed in pediatric participants, despite a modest sample size (n = 5 with data at 3-6 and 12 months). Measures of fatigue and anxiety persisted in adults, and cognitive difficulties persisted in both adults and children. In adults, longer status epilepticus duration and intensive care unit stay were associated with poorer QOL. Additionally, a higher number of antiseizure medications was associated with more depression, cognitive impairments, and perceived stigma.

Significance: These findings highlight the potential for recovery following an acute episode of NORSE, although many patients continue to face challenges requiring ongoing support, and the clinical meaning of the reported QOL improvement remains unclear. Furthermore, the findings underscore the importance of strategic multidisciplinary support systems in the years following discharge.

Objective: Naming and verbal memory are key components of epilepsy evaluations, as impairments often reflect left temporal dysfunction, and baseline performance helps estimate postsurgical risk. The utility of naming tests in bilingual individuals with epilepsy, however, has been questioned. We examined whether naming and verbal memory performance reflects seizure laterality in bilingual adults, how bilingualism affects baseline scores, and whether bilingual factors moderate the effects of seizure laterality on cognition.

Methods: We analyzed naming and verbal memory data from 148 monolingual and 63 bilingual adults with unilateral epilepsy across two centers. Participants completed English-based tests of visual naming, story recall, and word-list recall. Analyses of covariance and Bayesian models tested effects of seizure laterality, bilingual status, and their interaction. Regressions tested the moderating effects of bilingual factors (e.g., age at acquisition, proficiency, English immersion).

Results: Bilinguals scored lower on naming than monolinguals, but both groups showed worse naming in left versus right hemisphere epilepsy (nonsignificant interaction). Using monolingual norms, naming impairment was far more frequent in bilinguals (90%-92% left onset, 63%-71% right onset) than monolinguals, but rates normalized after adjusting for the bilingual naming disadvantage. Among non-US-born bilinguals, greater immersion was associated with better naming in right-but not left-hemisphere epilepsy. For verbal memory, seizure laterality effects were present in story recall, and in word-list recall among patients with mesial temporal sclerosis, but did not differ by bilingual status.

Significance: Naming and verbal memory remain reliable markers of seizure laterality in bilingual adults with epilepsy. For naming, however, improved measures and bilingual-specific norms are essential to avoid misclassification and support accurate clinical decision-making.