Detection of seizures with ictal tachycardia, using heart rate variability and patient adaptive logistic regression machine learning methods: A hospital-based validation study.

OBJECTIVE: Automated seizure detection of focal epileptic seizures is needed for objective seizure quantification to optimize the treatment of patients with epilepsy. Heart rate variability (HRV)-based seizure detection using patient-adaptive threshold with logistic regression machine learning (LRML) methods has presented promising performance in a study with a Danish patient cohort. The objective of this study was to assess the generalizability of the novel LRML seizure detection algorithm by validating it in a dataset recorded from long-term video-EEG monitoring (LTM) in a Brazilian patient cohort. METHODS: Ictal and inter-ictal ECG-data epochs recorded during LTM were analyzed retrospectively. Thirty-four patients had 107 seizures (79 focal, 28 generalized tonic-clonic [GTC] including focal-to-bilateral-tonic-clonic seizures) eligible for analysis, with a total of 185.5 h recording. Because HRV-based seizure detection is only suitable in patients with marked ictal autonomic change, patients with >50 beats/min change in heart rate during seizures were selected as responders. The patient-adaptive LRML seizure detection algorithm was applied to all elected ECG data, and results were computed separately for responders and non-responders. RESULTS: The patient-adaptive LRML seizure detection algorithm yielded a sensitivity of 84.8% (95% CI: 75.6-93.9) with a false alarm rate of .25/24 h in the responder group (22 patients, 59 seizures). Twenty-five of the 26 GTC seizures were detected (96.2%), and 25 of the 33 focal seizures without bilateral convulsions were detected (75.8%). SIGNIFICANCE: The study confirms in a new, independent external dataset the good performance of seizure detection from a previous study and suggests that the method is generalizable. This method seems useful for detecting both generalized and focal epileptic seizures. The algorithm can be embedded in a wearable seizure detection system to alert patients and caregivers of seizures and generate objective seizure counts helping to optimize the treatment of the patients.

The seizure classification of focal epilepsy based on the network motif analysis.

Due to the complexity of focal epilepsy and its risk for transiting to the generalized epilepsy, the development of reliable classification methods to accurately predict and classify focal and generalized seizures is critical for the clinical management of patients with epilepsy. In order to holistically understand the seizure propagation behavior of focal epilepsy, we propose a three-node motif reduced network by respectively simplifying the focal region, surrounding healthy region and their critical regions as the single node. Because three-node motif can richly characterize information evolutions, the motif analysis method could comprehensively investigate the seizure behavior of focal epilepsy. Firstly, we define a new seizure propagation marker value to capture the seizure onsets and intensity. Based on the three-node motif analysis, it is shown that the focal seizure and spreading can be categorized as inhibitory seizure, focal seizure, focal-critical seizure and generalized seizures, respectively. The four types of seizures correspond to specific modal types respectively, reflecting the strong correlation between seizure behavior and information flow evolution. In addition, it is found that the intensity difference of outflow and inflow information from the critical node (connection heterogeneity) and the excitability of the critical node significantly affected the distribution and transition of the four seizure types. In particular, the method of local linear stability analysis also verifies the effectiveness of four types of seizures classification. In sum, this paper computationally confirms the complex dynamic behavior of focal seizures, and the study of criticality is helpful to propose novel seizure control strategies.

Effect of drug treatment changes and seizure outcomes on depression and suicidality in adults with drug-resistant focal epilepsy.

OBJECTIVE: To investigate changes in depressive and suicidality status and their relationship with seizure outcomes after the addition or substitution of another antiseizure medication (ASM) in adults with drug-resistant focal epilepsy. METHODS: Seven hundred seventy consecutively enrolled patients were assessed and followed prospectively for seizure outcome and depressive status over a 6-month period after starting treatment with a newly introduced ASM. The Neurological Disorders Depression Inventory for Epilepsy (NDDIE) was used to screen for depression and suicidality. Correlations of NDDIE results with clinical and treatment-related variables were assessed by using a stepwise logistic regression model. RESULTS: At baseline, 50% of patients had a positive screening test result for depression and 13% had a positive screening test result for suicidal ideation. A psychiatric comorbidity at baseline was associated with a 2.3 times increased risk of an initially negative NDDIE screening result becoming positive at re-assessment after 6 months. In addition, the number of ASMs taken at baseline correlated with an increased risk of a change in depression screening test results from negative to positive during follow-up, whereas no association was identified with sociodemographic and epilepsy-related variables, including seizure outcomes. Approximately 6% of patients who were initially negative at screening for suicidal ideation became positive at the 6-month re-assessment. The risk of switch from a negative to a positive screening test result for suicidal ideation was increased more than two-fold in individuals who screened positive for depression at baseline, and was unrelated to the type of ASM introduced, sociodemographic variables, or seizure outcomes. SIGNIFICANCE: Almost 1 in 5 adults with drug-resistant focal epilepsy who screen negative for depression become positive when re-assessed 6 months after a treatment change. At re-assessment 6 months later, 6.1% who screen initially negative for passive suicidal ideation become positive. These changes in screening status are independent of type of ASM introduced or seizure outcomes but correlate with psychiatric status at baseline.

Shorter duration of slow wave sleep is related to symptoms of depression in patients with epilepsy.

Slow wave sleep duration and spectral abnormalities are related to both epilepsy and depression, but it is unclear how depressive symptoms in patients with epilepsy are affected by slow wave sleep duration and clinical factors, and how the spectral characteristics of slow wave sleep reflect a potential interaction of epilepsy and depression. Long-term video-EEG monitoring was conducted in 51 patients with focal epilepsy, 13 patients with generalized epilepsy, and 9 patients without epilepsy. Slow wave sleep segments were manually marked in the EEG and duration as well as EEG power spectra were extracted. Depressive symptoms were documented with the Beck Depression Inventory (BDI). At least mild depressive symptoms (BDI > 9) were found among 23 patients with focal epilepsy, 5 patients with generalised epilepsy, and 6 patients who had no epilepsy diagnosis. Slow wave sleep duration was shorter for patients with at least mild depressive symptoms (p =.004), independently from epilepsy diagnosis, antiseizure medication, age, and sex. Psychoactive medication was associated with longer slow wave sleep duration (p =.008). Frontal sigma band power (13-15 Hz) during slow wave sleep was higher for patients without epilepsy and without depressive symptoms as compared to patients without depressive symptoms but with focal epilepsy (p =.005). Depressive symptoms affect slow wave sleep duration of patients with epilepsy similarly as in patients without epilepsy. Since reduced slow wave sleep can increase the likelihood of seizure occurrence, these results stress the importance of adequate treatment for patients with epilepsy who experience depressive symptoms.

Drug-resistant focal epilepsy in a girl with SETD5-related intellectual disability.

None.

Genetic testing in children enrolled in epilepsy surgery program. A real-life study.

OBJECTIVE: Although genetic causes of drug-resistant focal epilepsy and selected focal malformations of cortical development (MCD) have been described, a limited number of studies comprehensively analysed genetic diagnoses in patients undergoing pre-surgical evaluation, their outcomes and the effect of genetic diagnosis on surgical strategy. METHODS: We analysed a prospective cohort of children enrolled in epilepsy surgery program over January 2018-July 2022. The majority of patients underwent germline and/or somatic genetic testing. We searched for predictors of surgical outcome and positive result of germline genetic testing. RESULTS: Ninety-five patients were enrolled in epilepsy surgery program and 64 underwent resective epilepsy surgery. We ascertained germline genetic diagnosis in 13/74 patients having underwent germline gene testing (pathogenic or likely pathogenic variants in CHRNA4, NPRL3, DEPDC5, FGF12, GRIA2, SZT2, STXBP1) and identified three copy number variants. Thirty-five patients underwent somatic gene testing; we detected 10 pathogenic or likely pathogenic variants in genes SLC35A2, PTEN, MTOR, DEPDC5, NPRL3. Germline genetic diagnosis was significantly associated with the diagnosis of focal epilepsy with unknown seizure onset. SIGNIFICANCE: Germline and somatic gene testing can ascertain a definite genetic diagnosis in a significant subgroup of patients in epilepsy surgery programs. Diagnosis of focal genetic epilepsy may tip the scales against the decision to proceed with invasive EEG study or surgical resection; however, selected patients with genetic focal epilepsies associated with MCD may benefit from resective epilepsy surgery and therefore, a genetic diagnosis does not disqualify patients from presurgical evaluation and epilepsy surgery.

Altered amygdala volumes and microstructure in focal epilepsy patients with tonic-clonic seizures, ictal, and post-convulsive central apnea.

OBJECTIVES: Sudden unexpected death in epilepsy (SUDEP) is a leading cause of death for patients with epilepsy; however, the pathophysiology remains unclear. Focal-to-bilateral tonic-clonic seizures (FBTCS) are a major risk factor, and centrally-mediated respiratory depression may increase the risk further. Here, we determined the volume and microstructure of the amygdala, a key structure that can trigger apnea in people with focal epilepsy, stratified by the presence or absence of FBTCS, ictal central apnea (ICA), and post-convulsive central apnea (PCCA). METHODS: Seventy-three patients with focal impaired awareness seizures without FBTC seizures (FBTCneg group) and 30 with FBTCS (FBTCpos group) recorded during video electroencephalography (VEEG) with respiratory monitoring were recruited prospectively during presurgical investigations. We acquired high-resolution T1-weighted anatomic and multi-shell diffusion images, and computed neurite orientation dispersion and density imaging (NODDI) metrics in all patients with epilepsy and 69 healthy controls. Amygdala volumetric and microstructure alterations were compared between three groups: healthy subjects, FBTCneg and FBTCpos groups. The FBTCpos group was further subdivided by the presence of ICA and PCCA, verified by VEEG. RESULTS: Bilateral amygdala volumes were significantly increased in the FBTCpos cohort compared to healthy controls and the FBTCneg group. Patients with recorded PCCA had the highest increase in bilateral amygdala volume of the FBTCpos cohort. Amygdala neurite density index (NDI) values were decreased significantly in both the FBTCneg and FBTCpos groups relative to healthy controls, with values in the FBTCpos group being the lowest of the two. The presence of PCCA was associated with significantly lower NDI values vs the non-apnea FBTCpos group (p = 0.004). SIGNIFICANCE: Individuals with FBTCpos and PCCA show significantly increased amygdala volumes and disrupted architecture bilaterally, with greater changes on the left side. The structural alterations reflected by NODDI and volume differences may be associated with inappropriate cardiorespiratory patterns mediated by the amygdala, particularly after FBTCS. Determination of amygdala volumetric and architectural changes may assist identification of individuals at risk.

Hippocampal and neocortical BRAF mutant non-expansive lesions in focal epilepsies.

OBJECTIVE: Mesial Temporal Lobe Epilepsy-associated Hippocampal Sclerosis (MTLE-HS) is a syndrome associated with various aetiologies. We previously identified CD34-positive extravascular stellate cells (CD34+ cells) possibly related to BRAFV600E oncogenic variant in a subset of MTLE-HS. We aimed to identify the BRAFV600E oncogenic variants and characterise the CD34+ cells. METHODS: We analysed BRAFV600E oncogenic variant by digital droplet Polymerase Chain Reaction in 53 MTLE-HS samples (25 with CD34+ cells) and nine non-expansive neocortical lesions resected during epilepsy surgery (five with CD34+ cells). Ex vivo multi-electrode array recording, immunolabelling, methylation microarray and single nuclei RNAseq were performed on BRAFwildtype MTLE-HS and BRAFV600E mutant non-expansive lesion of hippocampus and/or neocortex. RESULTS: We identified a BRAFV600E oncogenic variant in five MTLE-HS samples with CD34+ cells (19%) and in five neocortical samples with CD34+ cells (100%). Single nuclei RNAseq of resected samples revealed two unique clusters of abnormal cells (including CD34+ cells) associated with senescence and oligodendrocyte development in both hippocampal and neocortical BRAFV600E mutant samples. The co-expression of the oncogene-induced senescence marker p16INK4A and the outer subventricular zone radial glia progenitor marker HOPX in CD34+ cells was confirmed by multiplex immunostaining. Pseudotime analysis showed that abnormal cells share a common lineage from progenitors to myelinating oligodendrocytes. Epilepsy surgery led to seizure freedom in eight of the 10 patients with BRAF mutant lesions. INTERPRETATION: BRAFV600E underlies a subset of MTLE-HS and epileptogenic non-expansive neocortical focal lesions. Detection of the oncogenic variant may help diagnosis and open perspectives for targeted therapies.

Sudden Unexpected Death in Epilepsy and Respiratory Defects in a Mouse Model of DEPDC5-Related Epilepsy.

OBJECTIVES: DEPDC5 is a common causative gene in familial focal epilepsy with or without malformations of cortical development. Its pathogenic variants also confer a significantly higher risk for sudden unexpected death in epilepsy (SUDEP), providing opportunities to investigate the pathophysiology intersecting neurodevelopment, epilepsy, and cardiorespiratory function. There is an urgent need to gain a mechanistic understanding of DEPDC5-related epilepsy and SUDEP, identify biomarkers for patients at high risk, and develop preventive interventions. METHODS: Depdc5 was specifically deleted in excitatory or inhibitory neurons in the mouse brain to determine neuronal subtypes that drive epileptogenesis and SUDEP. Electroencephalogram (EEG), cardiac, and respiratory recordings were performed to determine cardiorespiratory phenotypes associated with SUDEP. Baseline respiratory function and the response to hypoxia challenge were also studied in these mice. RESULTS: Depdc5 deletion in excitatory neurons in cortical layer 5 and dentate gyrus caused frequent generalized tonic-clonic seizures and SUDEP in young adult mice, but Depdc5 deletion in cortical interneurons did not. EEG suppression immediately following ictal offset was observed in fatal and non-fatal seizures, but low amplitude rhythmic theta frequency activity was lost only in fatal seizures. In addition, these mice developed baseline respiratory dysfunction prior to SUDEP, during which ictal apnea occurred long before terminal cardiac asystole. INTERPRETATION: Depdc5 deletion in excitatory neurons is sufficient to cause DEPDC5-related epilepsy and SUDEP. Ictal apnea and respiratory dysregulation play critical roles in SUDEP. Our study also provides a novel mouse model to investigate the underlying mechanisms of DEPDC5-related epilepsy and SUDEP. ANN NEUROL 2023;94:812-824.

Epilepsy surgery in patients with hypothalamic hamartomas - Population-based two-year and long-term outcomes.

OBJECTIVE: Hypothalamic hamartomas are benign lesions associated with drug resistant epilepsy. Surgical treatment has become an increasingly utilised approach with promising results. This study aims to evaluate seizure outcome and complications after surgery in a population-based series of patients with intractable epilepsy and hypothalamic hamartoma. METHODS: All patients with hypothalamic hamartoma treated with epilepsy surgery in Sweden since 1995 with at least two years of follow-up were included. Preoperative, two-, five- and ten-year prospective longitudinal data were collected from The Swedish National Epilepsy Surgery Register. Data included seizure types and frequency, duration of epilepsy, clinical characteristics, neurological deficits, cognitive level and complications. In a subgroup from Gothenburg, we also analysed data not included in the register such as classification of hamartomas, surgical procedures and gelastic seizures. RESULTS: Eighteen patients were operated on during the period 1995-2020. The median age at epilepsy onset was 6 months and age at surgery 13 years. Four were seizure free and another four had ≥75% reduction in seizure frequency at the two-year follow-up. Two of the 13 patients with a long-term follow-up (five or ten years) were seizure-free and four had ≥75% reduction in seizure frequency. Three had an increased seizure frequency. No major complications were seen. Five had minor complications. In the Gothenburg subgroup all had open pterional disconnection or intraventricular endoscopic disconnection. Six of 12 were free from gelastic seizures at the two-year follow-up and six of eight at the long-term follow-up. CONCLUSION: This study supports surgical treatment of hypothalamic hamartomas as a safe method with a low risk of permanent complications. The seizure reduction seems to be persistent over time.

Longitudinal evolution of electroencephalogram (EEG): Findings over five years of follow-up in children with Zika-related microcephaly from the Microcephaly Epidemic Research Group Pediatric Cohort (2015-2020).

OBJECTIVE: To assess the longitudinal evolution of EEG findings in children with Zika related-microcephaly (ZRM) and to evaluate the associations of these patterns with the children's clinical and neuroimaging characteristics. METHODS: As part of the follow-up of the Microcephaly Epidemic Research Group Pediatric Cohort (MERG-PC) in Recife, Brazil, we performed serial EEG recordings in a subgroup of children with ZRM to evaluate changes in background rhythms and epileptiform activity (EA). Latent class analysis was used to identify patterns in the evolution of EA over time; clinical and neuroimaging findings were compared across the identified groups. RESULTS: Out of the 72 children with ZRM who were evaluated during 190 EEGs/videoEEGs, all participants presented with abnormal background activity, 37.5% presented with an alpha-theta rhythmic activity, and 25% presented with sleep spindles, which were less commonly observed in children with epilepsy. EA changed over time in 79.2% of children, and three distinct trajectories were identified: (i) multifocal EA over time, (ii) no discharges/focal EA evolving to focal/multifocal EA, and (iii) focal/multifocal EA evolving to epileptic encephalopathy patterns (e.g., hypsarrhythmia or continuous EA in sleep). The multifocal EA over time trajectory was associated with periventricular and thalamus/basal ganglia calcifications, brainstem and corpus callosum atrophy and had less focal epilepsy, whereas the children in the trajectory which evolved to epileptic encephalopathy patterns had more frequently focal epilepsy. SIGNIFICANCE: These findings suggest that, in most children with ZRM, trajectories of changes in EA can be identified and associated with neuroimaging and clinical features.

Sudden unexpected death in epilepsy during cenobamate clinical development.

OBJECTIVE: We assessed mortality, sudden unexpected death in epilepsy (SUDEP), and standardized mortality ratio (SMR) among adults treated with cenobamate during the cenobamate clinical development program. METHODS: We retrospectively analyzed deaths among all adults with uncontrolled focal (focal to bilateral tonic-clonic [FBTC], focal impaired awareness, focal aware) or primary generalized tonic-clonic (PGTC) seizures who received ≥1 dose of adjunctive cenobamate in completed and ongoing phase 2 and 3 clinical studies. In patients with focal seizures from completed studies, median baseline seizure frequencies ranged from 2.8 to 11 seizures per 28 days and median epilepsy duration ranged from 20 to 24 years. Total person-years included all days that a patient received cenobamate during completed studies or up to June 1, 2022, for ongoing studies. All deaths were evaluated by two epileptologists. All-cause mortality and SUDEP rates were expressed per 1000 person-years. RESULTS: A total of 2132 patients (n = 2018 focal epilepsy; n = 114 idiopathic generalized epilepsy) were exposed to cenobamate for 5693 person-years. Approximately 60% of patients with focal seizures and all patients in the PGTC study had tonic-clonic seizures. A total of 23 deaths occurred (all in patients with focal epilepsy), for an all-cause mortality rate of 4.0 per 1000 person-years. Five cases of definite or probable SUDEP were identified, for a rate of .88 per 1000 person-years. Of the 23 overall deaths, 22 patients (96%) had FBTC seizures, and all 5 of the SUDEP patients had a history of FBTC seizures. The duration of exposure to cenobamate for patients with SUDEP ranged from 130 to 620 days. The SMR among cenobamate-treated patients in completed studies (5515 person-years of follow-up) was 1.32 (95% confidence interval [CI] .84-2.0), which was not significantly different from the general population. SIGNIFICANCE: These data suggest that effective long-term medical treatment with cenobamate may reduce excess mortality associated with epilepsy.

Volumetric and microstructural abnormalities of the amygdala in focal epilepsy with varied levels of SUDEP risk.

Although the mechanisms of sudden unexpected death in epilepsy (SUDEP) are not yet well understood, generalised- or focal-to-bilateral tonic-clonic seizures (TCS) are a major risk factor. Previous studies highlighted alterations in structures linked to cardio-respiratory regulation; one structure, the amygdala, was enlarged in people at high risk of SUDEP and those who subsequently died. We investigated volume changes and the microstructure of the amygdala in people with epilepsy at varied risk for SUDEP since that structure can play a key role in triggering apnea and mediating blood pressure. The study included 53 healthy subjects and 143 patients with epilepsy, the latter separated into two groups according to whether TCS occur in years before scan. We used amygdala volumetry, derived from structural MRI, and tissue microstructure, derived from diffusion MRI, to identify differences between the groups. The diffusion metrics were obtained by fitting diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) models. The analyses were performed at the whole amygdala level and at the scale of amygdaloid nuclei. Patients with epilepsy showed larger amygdala volumes and lower neurite density indices (NDI) than healthy subjects; the left amygdala volumes were especially enhanced. Microstructural changes, reflected by NDI differences, were more prominent on the left side and localized in the lateral, basal, central, accessory basal and paralaminar amygdala nuclei; basolateral NDI lowering appeared bilaterally. No significant microstructural differences appeared between epilepsy patients with and without current TCS. The central amygdala nuclei, with prominent interactions from surrounding nuclei of that structure, project to cardiovascular regions and respiratory phase switching areas of the parabrachial pons, as well as to the periaqueductal gray. Consequently, they have the potential to modify blood pressure and heart rate, and induce sustained apnea or apneusis. The findings here suggest that lowered NDI, indicative of reduced dendritic density, could reflect an impaired structural organization influencing descending inputs that modulate vital respiratory timing and drive sites and areas critical for blood pressure control.

Selective surgical mamillo-thalamic tract disconnection in hypothalamic hamartoma results in complete disappearance of gelastic seizures.

Hypothalamic hamartoma is a less common condition characterized by the several types of epileptic seizures including the gelastic type. It is reported that gelastic seizures are resistant to medical treatment with anticonvulsants, while stereotactic thermocoagulation or Gamma Knife radiosurgery are effective for seizure control. Here, we report an individual case where direct surgical resection disconnecting hypothalamic hamartoma from mammillothalamic tract resulted in complete disappearance of gelastic seizures without deterioration of cognitive function. A 6-year-old boy developed gelastic seizures at the age of 2 and suffered from precocious puberty. Anticonvulsants including carbamazepine and zonisamide failed to control seizures. The patient underwent direct division of the mammillothalmic tract by removal of hypothalamic hamartoma partially via anterior interhemispheric approach. It was observed that gelastic seizures disappeared completely after the surgical treatment without any endocrine and cognitive dysfunction for a follow-up period of 14 years. The mammillothalamic tract which connects anterior nucleus of thalamus and mammillary bodies plays a key role in gelastic seizures related to hypothalamic hamartoma. In this case, we disconnected the hamartoma specifically from the mammillary bodies and not from the rest of hypothalamus. Effectively, it enabled permanent control of seizures. This result shows that fibers connecting other hypothalamic structures and the dorsomedial nucleus of thalamus are not involved in gelastic seizure propagation from the hypothalamic hamartoma. When surgical treatment of hypothalamic hamartomas is performed it has high morbidity associated with hypothalamic disorders. Therefore, disconnection between hypothalamic hamartoma and mammillary bodies presents a possibility of reducing hypothalamic damage. Surgical disconnection between hamartoma and mammillothalamic tract carries minimal hypothalamic injury risk and our results suggest that it has the potential of seizure control for intractable gelastic seizures with less complications.

Before the first seizure: The developmental imprint of infant epilepsy on neurodevelopment.

In light of the heterogeneity of epilepsy, both from a clinical and from an etiological perspective, it is difficult to establish a link between epilepsy and development that can be generalized to all infantile epilepsies. In general however, early-onset epilepsy has a poor developmental prognosis that is significantly linked to several parameters: age at first seizure, drug resistance, treatment, and etiology. This paper discusses the relationship between visible epilepsy parameters (those that allow the diagnosis of epilepsy) and neurodevelopment in infants, with special focus on Dravet syndrome and KCNQ2-related epilepsy, two common developmental and epileptic encephalopathies; and focal epilepsy caused by focal cortical dysplasia, which often begins during infancy. There are a number of reasons why it is difficult to dissect the relationship between seizures and their causes, and we suggest a conceptual model in which epilepsy is a neurodevelopmental disorder whose severity is determined by how the disease imprints itself on the developmental process rather than by the symptoms or etiology. The precocity of this developmental imprint may explain why treating seizures once they occur can have a very slight beneficial effect on development.

How autoimmunity changed our diagnostic practice in epileptology?

Since few years, a new etiology of epilepsy emerges with the labelling of new autoantibodies against the central nervous system. In 2017, the International League Against Epilepsy (ILAE) concluded that autoimmunity is one of six etiologies contributing to epilepsy and that autoimmune epilepsy is directly caused by immune disorders in which seizures constitute a core symptom. Epileptic disorders of immune origin are now distinguished in two different entities: acute symptomatic seizures secondary to autoimmune (ASS) and autoimmune-associated epilepsy (AAE) with different expected clinical outcome under immunotherapy. If acute encephalitis is usually related to ASS with a classic good control of the disease under immunotherapy, clinical phenotype characterized by isolated seizures (new onset seizures and chronic focal epilepsy patients) may be due to either ASS or to AAE. Decision of Abs testing and early immunotherapy initiation needs the development of clinical scores able to select patients with high risk of positive Abs testings. If this selection is now included in the usual medical care of encephalitic patients, specifically with NORSE, the actual bigger challenge is in patients with non or only mild encephalitic symptoms followed for new onset seizures or chronic focal epilepsy patients of unknown origin. The emergence of this new entity provides new therapeutic strategies with specific etiologic and probably anti epileptogenic medication rather than the usual and nonspecific ASM. In the world of the epileptology, this new autoimmune entity appears as a big challenge with an exciting chance to improve or even definitely cure patients of their epilepsy. However, the detection of these patients has to be done in the early phase of the disease to offer the best outcome.

Which is more deleterious to cognitive performance? Interictal epileptiform discharges vs anti-seizure medication.

Children with epilepsy commonly have comorbid neurocognitive impairments that severely affect their psychosocial well-being, education, and future career prospects. Although the provenance of these deficits is multifactorial, the effects of interictal epileptiform discharges (IEDs) and anti-seizure medications (ASMs) are thought to be particularly severe. Although certain ASMs can be leveraged to inhibit IED occurrence, it remains unclear whether epileptiform discharges or the medications themselves are most deleterious to cognition. To examine this question, 25 children undergoing invasive monitoring for refractory focal epilepsy performed one or more sessions of a cognitive flexibility task. Electrophysiological data were recorded to detect IEDs. Between repeated sessions, prescribed ASMs were either continued or titrated to <50% of the baseline dose. Hierarchical mixed-effects modeling assessed the relationship between task reaction time (RT), IED occurrence, ASM type, and dose while controlling for seizure frequency. Both presence (ß ± SE = 49.91 ± 16.55 ms, p = .003) and number of IEDs (ß ± SE = 49.84 ± 12.51 ms, p < .001) were associated with slowed task RT. Higher dose oxcarbazepine significantly reduced IED frequency (p = .009) and improved task performance (ß ± SE = -107.43 ± 39.54 ms, p = .007). These results emphasize the neurocognitive consequences of IEDs independent of seizure effects. Furthermore, we demonstrate that inhibition of IEDs following treatment with select ASMs is associated with improved neurocognitive function.

Ocular motility as a measure of cerebral dysfunction in adults with focal epilepsy.

OBJECTIVE: Using objective oculomotor measures, we aimed to: (1) compare oculomotor performance in patients with drug-resistant focal epilepsy to healthy controls, and (2) investigate the differential impact of epileptogenic focus laterality and location on oculomotor performance. METHODS: We recruited 51 adults with drug-resistant focal epilepsy from the Comprehensive Epilepsy Programs of two tertiary hospitals and 31 healthy controls to perform prosaccade and antisaccade tasks. Oculomotor variables of interest were latency, visuospatial accuracy, and antisaccade error rate. Linear mixed models were performed to compare interactions between groups (epilepsy, control) and oculomotor tasks, and between epilepsy subgroups and oculomotor tasks for each oculomotor variable. RESULTS: Compared to healthy controls, patients with drug-resistant focal epilepsy exhibited longer antisaccade latencies (mean difference = 42.8 ms, P = 0.001), poorer spatial accuracy for both prosaccade (mean difference = 0.4°, P = 0.002), and antisaccade tasks (mean difference = 2.1°, P < 0.001), and more antisaccade errors (mean difference = 12.6%, P < 0.001). In the epilepsy subgroup analysis, left-hemispheric epilepsy patients exhibited longer antisaccade latencies compared to controls (mean difference = 52.2 ms, P = 0.003), while right-hemispheric epilepsy was the most spatially inaccurate compared to controls (mean difference = 2.5°, P = 0.003). The temporal lobe epilepsy subgroup displayed longer antisaccade latencies compared to controls (mean difference = 47.6 ms, P = 0.005). SIGNIFICANCE: Patients with drug-resistant focal epilepsy exhibit poor inhibitory control as evidenced by a high percentage of antisaccade errors, slower cognitive processing speed, and impaired visuospatial accuracy on oculomotor tasks. Patients with left-hemispheric epilepsy and temporal lobe epilepsy have markedly impaired processing speed. Overall, oculomotor tasks can be a useful tool to objectively quantify cerebral dysfunction in drug-resistant focal epilepsy.

Sleep homeostasis, seizures, and cognition in children with focal epilepsy.

AIM: To investigate the link between sleep disruption and cognitive impairment in childhood epilepsy by studying the effect of epilepsy on sleep homeostasis, as reflected in slow-wave activity (SWA). METHOD: We examined SWA from overnight EEG-polysomnography in 19 children with focal epilepsy (mean [SD] age 11 years 6 months [3 years], range 6 years 6 months-15 years 6 months; 6 females, 13 males) and 18 age- and sex-matched typically developing controls, correlating this with contemporaneous memory consolidation task scores, full-scale IQ, seizures, and focal interictal discharges. RESULTS: Children with epilepsy did not differ significantly from controls in overnight SWA decline (p = 0.12) or gain in memory performance with sleep (p = 0.27). SWA was lower in patients compared to controls in the first hour of non-rapid eye movement sleep (p = 0.021), although not in those who remained seizure-free (p = 0.26). Full-scale IQ did not correlate with measures of SWA in patients or controls. There was no significant difference in SWA measures between focal and non-focal electrodes. INTERPRETATION: Overnight SWA decline is conserved in children with focal epilepsy and may underpin the preservation of sleep-related memory consolidation in this patient group. Reduced early-night SWA may reflect impaired or immature sleep homeostasis in those with a higher seizure burden. WHAT THIS PAPER ADDS: The decline in slow-wave activity (SWA) across the night, reflecting global synaptic downscaling, was preserved in children with focal lesional epilepsies. Sleep benefited memory consolidation in this group of patients, as in typically developing children. Reduced early-night SWA was associated with increased likelihood of a subsequent seizure.

Sex differences in the relationship between aggression and symptoms of depression and anxiety in adults with refractory focal epilepsy.

PURPOSE: To determine whether sex affects the relationship between aggression and symptoms of depression and anxiety in adults with refractory focal epilepsy. METHODS: This cross-sectional study was conducted in 85 adults with refractory focal seizures, which are defined as one or more seizures recurring per month even when the patient is treated with two or more antiseizure medications. We used the Buss-Perry Aggression Questionnaire (AQ) and the Hospital Anxiety and Depression Scale (HADS) to evaluate aggression and symptoms of depression and anxiety, respectively. We performed multivariate linear regression and analysis of covariance with interaction terms. HADS-depression and HADS-anxiety scores were separately evaluated to avoid multicollinearity between both of them. RESULTS: The HADS-depression and HADS-anxiety scores, male sex, an antiseizure medication load of ≥3, and the use of pregabalin were independently correlated with at least one of the AQ total and subscale scores. These models for depressive and anxiety symptoms explained 34.2% and 32.5%, respectively, of the variance of the AQ total score. Although the AQ total scores did not differ between the sexes, sex significantly affected the relationships between aggression and symptoms of depression and anxiety. Specifically, HADS-depression and HADS-anxiety scores were positively associated with the AQ total scores, especially scores of verbal aggression and anger subtypes, in men but not in women. CONCLUSIONS: These findings support the importance of including anger management and other strategies targeted toward aggression in the development of psychological interventions to reduce anxiety and depression in adults with refractory focal epilepsy. Tailoring those interventions to the needs of males and females will be important to consider. .