Epilepsia最新文献

Objective: Patients with anti-leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis frequently exhibit long-term cognitive impairment despite immunotherapy. In this study, we aimed to delineate hippocampal structural and functional alterations that underlie these deficits and examined their clinical correlates.

Methods: We recruited 34 patients with anti-LGI1 encephalitis in the post-acute phase and 34 matched healthy controls. All participants underwent neuropsychological testing, high-resolution T1-weighted magnetic resonance imaging (MRI), and resting-state functional MRI. We assessed group differences in hippocampal volume and its whole-brain functional connectivity (FC) using a seed-based approach. Partial correlation, multivariable linear regression, and mediation analyses were employed to relate imaging metrics to cognitive scores and clinical features.

Results: Patients exhibited significant cognitive impairment, predominantly in verbal memory. This was paralleled by bilateral hippocampal atrophy, which strongly correlated with poorer performance across multiple cognitive domains. In contrast, patients demonstrated significantly increased FC between the left hippocampus and medial orbitofrontal cortex (mOFC). The enhanced connectivity was associated with better memory performance, suggesting a compensatory mechanism. Mediation analyses revealed that ipsilateral hippocampal volume mediated the relationship between acute medial temporal T2/fluid-attenuated inversion recovery (FLAIR) hyperintensity and memory scores. In addition, early immunotherapy was associated with an increase in left hippocampus-mOFC connectivity, contributing to improved cognitive performance.

Significance: Our findings reveal a dual neural mechanism underlying cognitive outcome in anti-LGI1 encephalitis: the hippocampal atrophy correlates with cognitive deficits, whereas enhanced left hippocampal-mOFC connectivity represents a compensatory plastic response. Early immunotherapy may promote this beneficial plasticity, highlighting these structural and functional signatures as potential biomarkers for stratifying patients and monitoring therapeutic efficacy.

Objective: A strong bidirectional relationship exists between epilepsy and sleep, with seizures often occurring more frequently in sleep and, in turn, sleep being disrupted by seizures. However, the mechanistic basis of seizure-sleep interactions is poorly understood. In this study, we characterized the relationship between seizures and sleep in a mouse model of the genetic disorder tuberous sclerosis complex (TSC) and investigated potential mechanisms underlying seizure-sleep interactions related to hypothalamic orexin.

Methods: Tsc1^GFAPCKO mice were used to investigate the relationship between seizures and sleep with video, electroencephalographic (EEG), and electromyographic analysis, including the dependence of seizure frequency on vigilance state (awake, rapid eye movement [REM], non-REM) and the effect of seizures on the wake-sleep cycle. Orexin expression in hypothalamus was assessed by immunohistochemistry in relation to seizure frequency. The effect of orexin antagonists on sleep and seizures was tested by video-EEG.

Results: Overall seizures occurred most commonly in non-REM sleep in Tsc1^GFAPCKO mice but had the highest seizure frequency in REM sleep after normalizing for amount of time spent in each vigilance state. Conversely, seizures were associated with disruptions in the sleep-wake cycle, particularly a decrease in REM sleep. Tsc1^GFAPCKO mice with seizures had increased orexin expression compared with control mice or Tsc1^GFAPCKO mice without seizures. The orexin antagonist suvorexant reversed the decrease in REM sleep but had no significant effect on seizures in Tsc1^GFAPCKO mice.

Significance: A bidirectional relationship between seizures and sleep was demonstrated in a mouse model of TSC, with relative seizure frequency surprisingly being highest in REM sleep and seizures causing a disruption of REM sleep. Hypothalamic orexin may partly mediate these seizure-sleep interactions, and orexin antagonists may represent rational therapies for sleep disorders in TSC.

Objective: Developmental arrest or regression that results in intellectual disability (ID) is a common neurological sequela of infantile epileptic spasms syndrome. Spindles are the hallmark of non-rapid eye movement sleep, and their density correlates with cognitive performance. Recent evidence suggests that ictal and interictal epileptic activities hijack the thalamocortical network. Therefore, we aimed to investigate whether thalamocortical dysfunction, as represented by reduced spindle density, is related to cognitive outcomes.

Methods: We retrospectively recruited patients diagnosed with infantile epileptic spasms syndrome who were treated at Saitama Children's Hospital. Specifically, we included patients with an unknown etiology to minimize the effects of preceding thalamocortical dysfunction induced by various etiologies before the onset of infantile epileptic spasms syndrome. These cohorts were separated into two groups based on the presence or absence of ID, defined as an intelligence quotient (IQ) or developmental quotient (DQ) of <70, during follow-up. Information concerning patients' background characteristics, treatment response (defined as seizure cessation for at least 3 months), and cognitive performance was extracted. Pre- and posttreatment spindle features were derived from quantitative assessment of spindle features performed using automated algorithms, which were validated against expert human annotations. Additionally, logistic regression was used to validate the independent predictors of cognitive outcomes.

Results: Overall, 45 patients were included (23 and 22 patients in the ID and non-ID groups, respectively). Posttreatment spindle density was significantly higher in the non-ID group than in the ID group. Moreover, spindle density was positively correlated with DQ/IQ values across the entire cohort. Finally, a logistic regression model revealed that spindle density and treatment response were independent predictors of cognitive outcomes.

Significance: Reduced posttreatment spindle density was correlated with cognitive outcome in infantile epileptic spasms syndrome. The thalamocortical network may be a potential treatment target to achieve favorable cognitive outcomes.

Objective: Although subjective symptoms have received less attention than observable manifestations of functional/dissociative seizures (FDS), patient-reported experiences provide important insights for diagnosis and management. This systematic review summarizes and synthesizes studies describing the subjective symptomatology of FDS and narratively discusses their potential diagnostic value.

Methods: MEDLINE, PsycINFO, and CINAHL were searched from January 1990 to May 2025 for studies reporting qualitative or quantitative data on FDS symptoms. The review was registered in International Prospective Register of Systematic Reviews (PROSPERO; CRD420251008332) and reported in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines. Study quality was assessed using Critical Appraisal Skills Programme (CASP) tools. Data were extracted on study design, sample characteristics, data acquisition method, and reported symptoms. Qualitative data were analyzed thematically following Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) principles, whereas quantitative findings were synthesized narratively within the same thematic framework.

Results: Forty-seven studies were included. Subjective symptoms of FDS were highly variable both within and between individuals. Across studies, six broad symptom domains were identified: sensory/pain, arousal, emotional, consciousness-related, cognitive, and motor symptoms. Sensory symptoms (particularly pain and headache), arousal-related symptoms (especially hyperarousal), and emotional symptoms (especially panic and anxiety) were most frequently reported across studies. Symptoms related to altered awareness and dissociation between awareness and responsiveness were described in a smaller number of studies but were more consistently reported as differentiating FDS from epileptic seizures. In contrast, the differential diagnostic value of other subjective symptoms was limited by lack of specificity and insufficient detail regarding context, mode of onset, spread, duration and quality.

Significance: Subjective symptoms in FDS are diverse, but common themes emerge. Detailed descriptions are required to extract differential diagnostic value from subjective FDS symptoms. Future studies should collect structured information about FDS symptoms and study them using systematic, multimodal, and cross-cultural approaches.

Objective: Postictal deficits are a well-recognized phenomenon, yet their mechanisms and predictors remain poorly understood. Distinguishing postictal deficits from recurring nonconvulsive seizures (NCSz) or nonconvulsive status epilepticus (NCSE), their main differential diagnosis, can be challenging. This study aimed to identify clinical and electrographic features predictive of ongoing or recurrent ictal activity and to explore biomarkers associated with the duration and severity of postictal deficits.

Methods: We conducted a retrospective case-control study of patients with prolonged (>1 h) postictal deficits at a tertiary medical center between 2017 and 2022. Based on electroencephalographic (EEG) findings, patients were classified as having uncomplicated Todd's palsy or recurring NCSz. Clinical, imaging, and electrographic characteristics were compared between groups, and factors associated with postictal duration were analyzed.

Results: Among 112 patients, 86 (77%) had uncomplicated Todd's palsy and 26 (23%) had recurring NCSz. Patients with NCSz were younger (63 vs. 76 years, p = .022) and had longer deficits (2.5 vs. 1.5 days, p = .024). Sporadic epileptiform discharges (73% vs. 22%, p < .001) and rhythmic or periodic discharges on the ictal-interictal continuum (50% vs. 16%, p = .001) were significantly more frequent in the NCSE group, even when limited to short EEGs or the first 30 min of continuous EEG (96% vs. 40%, p < .001). Consequently, 2HELPS2B scores were higher in NCSE patients (2 vs. 1, p = .0065). In the uncomplicated Todd's palsy group, a preceding focal to bilateral tonic-clonic seizure (1.5 vs. 1.0 days, p = .04) and any rhythmic or periodic discharges on EEG (3.0 vs. 1.5 days, p = .003) were associated with longer deficit duration.

Significance: A notable minority of patients with prolonged postictal deficits have recurring NCSz. In the absence of reliable clinical or imaging predictors, patients with prolonged deficits may benefit from a 30-min EEG followed-when 2HELPS2B score > 1-by extended continuous EEG monitoring.

Objective: To determine whether there are cognitive consequences of bottom-of-sulcus dysplasia (BOSD) when assessed as adults and whether focal resection of these lesions leads to change in cognition.

Methods: We studied 42 adults, of whom 39 underwent focal resection targeting the lesion. Neuropsychological assessments were tailored to the clinical epileptology.

Results: On average, patients were 30 (15-56) years old at the time of assessment. Epilepsy duration was 21 (3-48) years. Seizure onset ranged between 3 months and 26 years. Fifteen patients (36%) had an age of onset of 12 years or older. Older age of seizure onset correlated with fewer cognitive measures impacted (r = -0.34, p = .026). Frontal (52%) and parietal (33%) lobes were common BOSD locations. Confrontation naming was assessed in 20 patients, 11 (55%) of whom were impaired. Of these 11 patients, 8 (73%) had a left-sided BOSD. Verbal fluency was assessed in 23 patients, 13 (57%) of whom were impaired. Of these 13 patients, 11 (85%) had a frontal BOSD. Processing speed and attention were assessed in 35 patients and deficits were seen in 17% to 20%, though milder reductions were more consistently seen. At post-surgical follow-up (M = 8.07 years, SD = 4.91 years), 59% of patients were seizure free. As a group, there was no evidence of post-surgical cognitive decline after focal resection of the BOSD; processing speed (p < .05) improved post-surgically.

Significance: In adults with BOSD, an earlier age of seizure onset is accompanied by a greater degree of cognitive comorbidity. Naming is commonly affected, particularly for those with left sided BOSDs. Executive dysfunction is common, particularly for patients with a frontal BOSD. Focal lesionectomy is associated with favourable seizure outcome and is cognitively safe with potential for improvement in processing speed.

Objective: N-of-1 trials aim to determine the therapeutic effect for a single individual. This individualized approach necessitates collecting multiple data points over time through repeated alternating periods of active treatment and a comparator or control condition. The extended duration of the treatment periods may increase patient burden, prolong placebo exposure, and increase the likelihood of study discontinuation. In theory, treatment responders (or non-responders) can be identified early during the trial if the therapeutic effect is strong (or completely lacking). There are no theoretical constraints to evaluate treatment efficacy more regularly-instead of only after a predetermined number of treatment periods. Regularly updating estimates on treatment effects allows clinicians to accelerate clinical decision-making regarding N-of-1 study termination. This study examined the value of continuous treatment effect estimation using Bayesian hypothesis testing in N-of-1 trials to accelerate and nuance clinical decision-making.

Methods: An N-of-1 trial with severe epilepsy was simulated and three N-of-1 trials in neurological conditions were (re-)analyzed continuously with consecutive data points using Bayesian hypothesis testing and/or a minimally clinically important threshold (30% seizure frequency reduction). Trial duration based on Bayesian testing with strong evidence for treatment effects was compared to original trial duration.

Results: Original trial duration could be reduced between 9.5% and 35% of the trial length by using continuous outcome estimation in two of the analyzed trial examples. The moment that strong evidence supporting beneficial treatment effects using Bayesian hypothesis testing and a significant probability of minimally clinically important differences are achieved during the trial may differ. Obtaining additional data points and alternating interventions over time improve certainty of the estimates of treatment effects.

Significance: Treatment efficacy decisions can be expedited when outcome estimation is performed continuously rather than delayed until the end of the trial. Clinical significance of N-of-1 trial outcome can be improved combining both Bayesian hypothesis testing and a minimally clinically important threshold.