A complex case with generalized epilepsy, probable focal seizures, and functional seizures.

In this patient, now 42 years old, genetic generalized epilepsy (juvenile myoclonic epilepsy) manifested itself at the age of 13. At the age of 39, she experienced a status episode with prolonged ICU treatment. She was left with a left-sided hippocampal sclerosis and probably focal seizures. In addition, since the age of 24, the patient also experiences functional seizures on the background of a borderline personality disorder. While generalized epileptic seizures could be controlled with antiseizure medication (ASM), the patient was multiple times admitted to Emergency Departments for her functional seizures with subsequent intensive care treatments, including intubation. As a complication, the patient developed critical illness polyneuropathy and myopathy, resulting in wheelchair dependence. Additionally, she acquired a complex regional pain syndrome after extravasation of ASM. The report demonstrates the uncommon development of hippocampal sclerosis after a generalized tonic-clonic status epilepticus and the poor treatability of functional seizures as compared to generalized and focal seizures.

Autoimmune-associated epilepsy - a challenging concept.

The current International League Against Epilepsy (ILAE) definition and classification guidelines for the first time introduced the category of immune-mediated focal epilepsy in addition to structural, genetic, infectious, and metabolic aetiologies. Moreover, the ILAE Autoimmunity and Inflammation Taskforce recently provided a conceptual framework for the distinction between acute "provoked" seizures in the acute phase of autoimmune encephalitis from chronic "unprovoked" seizures due to autoimmune-associated epilepsy. The first category predominately applies to those autoimmune encephalitis patients with autoantibodies against cell surface neural antigens, in whom autoantibodies are assumed to exert a direct ictogenic effect without overt structural damage. These patients do not exhibit enduring predisposition to seizures after the "acute phase" encephalitis, and thus do not fulfil the definition of epilepsy. The second category applies to those autoimmune encephalitis patients with autoantibodies against intracellular neural antigens and Rasmussen's encephalitis, in whom T cells are assumed to cause epileptogenic effects through immune-inflammation and overt structural damage. These patients do exhibit enduring predisposition to seizures after the "acute phase" of encephalitis and thus fulfil the definition of epilepsy. AAE may result from both, ongoing brain autoimmunity and associated structural brain damage according to the current ILAE definition and classification guideline. We here discuss the difficulties of this concept and suggest an unbiased translationally validated and data-driven approach to predict in an individual encephalitis patient the propensity to develop (or not) AAE and the cognitive and behavioural outcome.

Cardiorespiratory disturbances in focal impaired awareness seizures: Insights from wearable ECG monitoring.

PURPOSE: Seizures are characterized by periictal autonomic changes. Wearable devices could help improve our understanding of these phenomena through long-term monitoring. In this study, we used wearable electrocardiogram (ECG) data to evaluate differences between temporal and extratemporal focal impaired awareness (FIA) seizures monitored in the hospital and at home. We assessed periictal heart rate, respiratory rate, heart rate variability (HRV), and respiratory sinus arrhythmia (RSA). METHODS: We extracted ECG signals across three time points - five minutes baseline and preictal, ten minutes postictal - and the seizure duration. After automatic Rpeak selection, we calculated the heart rate and estimated the respiratory rate using the ECG-derived respiration methodology. HRV was calculated in both time and frequency domains. To evaluate the influence of other modulators on the HRV after removing the respiratory influences, we recalculated the residual power in the high-frequency (HF) and low-frequency (LF) bands using orthogonal subspace projections. Finally, 5-minute and 30-second (ultra-short) ECG segments were used to calculate RSA using three different methods. Seizures from temporal and extratemporal origins were compared using mixed-effects models and estimated marginal means. RESULTS: The mean preictal heart rate was 69.95 bpm (95 % CI 65.6 - 74.3), and it increased to 82 bpm, 95 % CI (77.51 - 86.47) and 84.11 bpm, 95 % CI (76.9 - 89.5) during the ictal and postictal periods. Preictal, ictal and postictal respiratory rates were 16.1 (95 % CI 15.2 - 17.1), 14.8 (95 % CI 13.4 - 16.2) and 15.1 (95 % CI 14 - 16.2), showing not statistically significant bradypnea. HRV analysis found a higher baseline power in the LF band, which was still significantly higher after removing the respiratory influences. Postictally, we found decreased power in the HF band and the respiratory influences in both frequency bands. The RSA analysis with the new methods confirmed the lower cardiorespiratory interaction during the postictal period. Additionally, using ultra-short ECG segments, we found that RSA decreases before the electroclinical seizure onset. No differences were observed in the studied parameters between temporal and extratemporal seizures. CONCLUSIONS: We found significant increases in the ictal and postictal heart rates and lower respiratory rates. Isolating the respiratory influences on the HRV showed a postictal reduction of respiratory modulations on both LF and HF bands, suggesting a central role of respiratory influences in the periictal HRV, unlike the baseline measurements. We found a reduced cardiorespiratory interaction during the periictal period using other RSA methods, suggesting a blockade in vagal efferences before the electroclinical onset. These findings highlight the importance of respiratory influences in cardiac dynamics during seizures and emphasize the need to longitudinally assess HRV and RSA to gain insights into long-term autonomic dysregulation.

Distinct profiles of cerebral oxygenation in focal vs. secondarily generalized EEG seizures in children undergoing cardiac surgery.

Objectives: Seizures are common in children undergoing cardiopulmonary bypass (CPB). Cerebral oxygen saturation (ScO2) by near-infrared spectroscopy is routinely monitored in many centers, but the relations between the levels and changes of ScO2 and brain injuries remain incompletely understood. We aimed to analyze the postoperative profiles of ScO2 and cerebral blood flow velocity in different types of EEG seizures in relation to brain injuries on MRI. Methods: We monitored continuous EEG and ScO2 in 337 children during the first 48 h after CPB, which were analyzed in 3 h periods. Cerebral blood flow peak systolic velocity (PSV) in the middle cerebral artery was measured daily by transcranial Doppler. Postoperative cerebral MRI was performed before hospital discharge. Results: Based on the occurrence and spreading types of seizures, patients were divided into three groups as patients without seizures (Group N; n = 309), those with focal seizures (Group F; n = 13), or with secondarily generalized seizures (Group G; n = 15). There were no significant differences in the onset time and duration of seizures and incidence of status epilepticus between the two seizures groups (Ps ≥ 0.27). ScO2 increased significantly faster across Group N, Group G, and Group F during the 48 h (p < 0.0001) but its overall levels were not significantly different among the three groups (p = 0.30). PSV was significantly lower (p = 0.003) but increased significantly faster (p = 0.0003) across Group N, Group G, and Group F. Group F had the most severe brain injuries and the highest incidence of white matter injuries on MRI among the three groups (Ps ≤ 0.002). Conclusion: Postoperative cerebral oxygenation showed distinct profiles in secondarily generalized and particularly focal types of EEG seizures in children after CPB. A state of 'overshooting' ScO2 with persistently low PSV was more frequently seen in those with focal seizures and more severe brain injury. Information from this study may have important clinical implications in detecting brain injuries when monitoring cerebral oxygenation in this vulnerable group of children after CPB.

Circumscribing Laser Cuts Attenuate Seizure Propagation in a Mouse Model of Focal Epilepsy.

In partial onset epilepsy, seizures arise focally in the brain and often propagate. Patients frequently become refractory to medical management, leaving neurosurgery, which can cause neurologic deficits, as a primary treatment. In the cortex, focal seizures spread through horizontal connections in layers II/III, suggesting that severing these connections can block seizures while preserving function. Focal neocortical epilepsy is induced in mice, sub-surface cuts are created surrounding the seizure focus using tightly-focused femtosecond laser pulses, and electrophysiological recordings are acquired at multiple locations for 3-12 months. Cuts reduced seizure frequency in most animals by 87%, and only 5% of remaining seizures propagated to the distant electrodes, compared to 80% in control animals. These cuts produced a modest decrease in cortical blood flow that recovered and left a ≈20-µm wide scar with minimal collateral damage. When placed over the motor cortex, cuts do not cause notable deficits in a skilled reaching task, suggesting they hold promise as a novel neurosurgical approach for intractable focal cortical epilepsy.

Population-based study of rare epilepsy incidence in a US urban population.

OBJECTIVE: This study was undertaken to estimate incidence of rare epilepsies and compare with literature. METHODS: We used electronic health record text search to identify children with 28 rare epilepsies in New York City (2010-2014). We estimated cumulative incidence and compared with literature. RESULTS: Eight of 28 rare epilepsies had five or more prior estimates, and our measurements were within the published range for all. The most common were infantile epileptic spasms syndrome (1 in 2920 live births), Lennox-Gastaut syndrome (1 in 9690), and seizures associated with tuberous sclerosis complex (1 in 14 300). Fifteen of 28 had fewer than five prior estimates, and of these, we provided additional estimates for early infantile developmental and epileptic encephalopathy (1 in 32 700), epilepsy with myoclonic-atonic seizures (1 in 34 100), Sturge-Weber syndrome plus seizures/epilepsy (1 in 40 900), epilepsy in infancy with migrating focal seizures (1 in 54 500), Aicardi syndrome plus seizures/epilepsy (1 in 71 600), hypothalamic hamartoma with seizures (1 in 225 000), and Rasmussen syndrome (1 in 450 000). Five of 28 rare epilepsies had no prior estimates, and of these, we provided a new estimate for developmental/epileptic encephalopathy with spike-and-wave activation in sleep and/or continuous spikes and waves during sleep (1 in 34 100). Data were limited for the remaining 12 rare epilepsies, which were all genetic epilepsies, including PCDH19, CDKL5, Alpers disease, SCN8A, KCNQ2, SCN2A, GLUT1 deficiency, Phelan-McDermid syndrome, myoclonic epilepsy with ragged-red fibers, dup15q syndrome, ring chromosome 14, and ring chromosome 20. SIGNIFICANCE: We estimated the incidence of rare epilepsies using population-based electronic health record data and literature review. More research is needed to better estimate the incidence of genetic epilepsies with nonspecific clinical features. Electronic health records may be a valuable data source for studying rare epilepsies and other rare diseases, particularly as genetic testing becomes more widely adopted.

Perampanel for Treatment of People with a Range of Epilepsy Aetiologies in Clinical Practice: Evidence from the PERMIT Extension Study.

INTRODUCTION: It is important to assess the effectiveness of an antiseizure medication in treating different epilepsy aetiologies to optimise individualised therapeutic approaches. Data from the PERaMpanel pooled analysIs of effecTiveness and tolerability (PERMIT) Extension study were used to assess the effectiveness and safety/tolerability of perampanel (PER) when used to treat individuals with a range of epilepsy aetiologies in clinical practice. METHODS: A post hoc analysis was conducted of PERMIT Extension data from individuals with a known aetiology. Retention was assessed after 3, 6 and 12 months. Effectiveness was assessed after 3, 6 and 12 months and at the last visit (last observation carried forward). Effectiveness assessments included responder rate (≥ 50% seizure frequency reduction) and seizure freedom rate (no seizures since at least the prior visit). Safety/tolerability was assessed by evaluating adverse events (AEs) and AEs leading to discontinuation. RESULTS: PERMIT Extension included 1945 individuals with structural aetiology, 1012 with genetic aetiology, 93 with an infectious aetiology, and 26 with an immune aetiology. Retention rates at 12 months were 61.1% (structural), 65.9% (genetic), 56.8% (infectious) and 56.5% (immune). At the last visit, responder rates (total seizures) were 43.3% (structural), 68.3% (genetic), 37.0% (infectious) and 20.0% (immune), and corresponding seizure freedom rates were 15.8%, 46.5%, 11.1% and 5.0%, respectively. AE incidence rates were 58.0% (structural), 46.5% (genetic), 51.1% (infectious) and 65.0% (immune), and corresponding rates of discontinuation due to AEs over 12 months were 18.9%, 16.4%, 18.5% and 21.7%, respectively. The types of AEs reported were generally consistent across aetiology subgroups, with no idiosyncratic AEs emerging. CONCLUSION: Although PER was effective and generally well tolerated when used to treat individuals with a range of epilepsy aetiologies in clinical practice, variability in its effectiveness and tolerability across the subgroups indicates that PER may be particularly useful for individuals with specific epilepsy aetiologies.

Edge-wise analysis reveals white matter connectivity associated with focal to bilateral tonic-clonic seizures.

OBJECTIVE: Focal to bilateral tonic-clonic seizures (FBTCS) represent a challenging subtype of focal temporal lobe epilepsy (TLE) in terms of both severity and treatment response. Most studies have focused on regional brain analysis that is agnostic to the distribution of white matter (WM) pathways associated with a node. We implemented a more selective, edge-wise approach that allowed for identification of the individual connections unique to FBTCS. METHODS: T1-weighted and diffusion-weighted images were obtained from 22 patients with solely focal seizures (FS), 43 FBTCS patients, and 65 age/sex-matched healthy participants (HPs), yielding streamline (STR) connectome matrices. We used diffusion tensor-derived STRs in an edge-wise approach to determine specific structural connectivity changes associated with seizure generalization in FBTCS compared to matched FS and HPs. Graph theory metrics were computed on both node- and edge-based connectivity matrices. RESULTS: Edge-wise analyses demonstrated that all significantly abnormal cross-hemispheric connections belonged to the FBTCS group. Abnormal connections associated with FBTCS were mostly housed in the contralateral hemisphere, with graph metric values generally decreased compared to HPs. In FBTCS, the contralateral amygdala showed selective decreases in the structural connection pathways to the contralateral frontal lobe. Abnormal connections in TLE involved the amygdala, with the ipsilateral side showing increases and the contralateral decreases. All the FS findings indicated higher graph metrics for connections involving the ipsilateral amygdala. Data also showed that some FBTCS connectivity effects are moderated by aging, recent seizure frequency, and longer illness duration. SIGNIFICANCE: Data showed that not all STR pathways are equally affected by the seizure propagation of FBTCS. We demonstrated two key biases, one indicating a large role for the amygdala in the propagation of seizures, the other pointing to the prominent role of cross-hemispheric and contralateral hemisphere connections in FBTCS. We demonstrated topographic reorganization in FBTCS, pointing to the specific WM tracts involved.

Efficacy, tolerability and safety of add-on third-generation antiseizure medications in treating focal seizures worldwide: a network meta-analysis of randomised, placebo-controlled trials.

Background: Adjunctive newer antiseizure medications (ASMs) are being used in patients with treatment-resistant focal-onset seizures (FOS). An updated network meta-analysis (NMA) was necessary to compile evidence in this critical area. Methods: We systematically searched PubMed, Embase, Cochrane Library, Web of Science, and Scopus from their inception until 17 January 2024, evaluating the efficacy, tolerability, and safety of rufinamide (RUF), brivaracetam (BRV), cenobamate (CNB), eslicarbazepine (ESL), lacosamide (LCM), retigabine (RTG), and perampanel (PER) as adjunctive treatments for FOS. Efficacy outcomes included seizure response and seizure freedom. Tolerability was assessed by discontinuation due to adverse events (AEs). Safety outcomes were evaluated based on the number of patients experiencing at least one AE and serious adverse events (SAEs). This review is registered with PROSPERO (CRD42023485130). Findings: A total of 29 studies involving 11,750 participants were included. For seizure response, all ASMs were significantly superior to placebo, with RTG ranking highest, followed by CNB. Considering dosage, CNB 400 mg/d was top-ranked, followed by RTG 1200 mg/d. For seizure freedom, BRV was highest-ranked, followed by CNB, with BRV 100 mg/d leading, followed by CNB 400 mg/d. Regarding tolerability, LCM 600 mg/d had the lowest ranking, followed by CNB 400 mg/d. For the safety outcome of AEs, ESL 1200 mg/d was ranked lowest, followed by CNB 400 mg/d. Regarding SAEs, LCM 400 mg/d was ranked lowest, followed by RTG 1200 mg/d. Interpretation: ASMs at different dosages have varying efficacy and tolerability profiles. We have provided hierarchical rankings of ASMs for efficacy and safety outcomes. Our findings offer the most comprehensive evidence available to inform patients, families, physicians, guideline developers, and policymakers about the choice of ASMs in patients with treatment-resistant FOS. Funding: None.

Effect of GABAa-receptors on neuronal discharge and ion activity in focal seizures.

Focal seizures are a type of epileptic event that has plagued the medical community for a long time, and the existing drug treatment is mainly based on the modulation of ${GABA}_a$-receptors to affect GABAergic signaling to achieve the therapeutic purpose. The majority of research currently focuses on the impact of ${GABA}_a$-receptors on neuronal firing, failing to analyze the molecular and ionic mechanisms involved. Specifically, the research on deeper-level mechanisms on how ${GABA}_a$-receptors affect neuronal firing by altering ion activity has not been addressed. This research aimed to study the effects of different ${GABA}_a$-receptor structures on ion activity in focal seizures model by adjusting parameters of the ${GABA}_a$-receptors: the rise time constant (${tau}_1$) and decay time constant (${tau}_2$). The research indicates that as the values of ${tau}_1$ and ${tau}_2$ of the ${GABA}_a$-receptor change, the ion concentration will vary based on the change of the ${GABA}_a$-receptor potential. To a certain extent, the duration of epileptic activity will also be affected to a certain extent. In conclusion, the alteration of ${GABA}_a$-receptor structure will affect the inhibitory effect of interneurons on pyramidal neurons, and different parameters of the ${GABA}_a$-receptor will directly impact the therapeutic effect.

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.

Conversion to Brivaracetam Monotherapy in Clinical Practice: A Retrospective Study.

INTRODUCTION: The study aimed to evaluate the effectiveness and safety of brivaracetam (BRV) as conversion monotherapy in adults with focal epilepsy treated in the context of real-world clinical practice. METHODS: This was a retrospective, observational, non-interventional study in adults with focal epilepsy who converted to BRV monotherapy following the withdrawal of background antiseizure medications (ASMs). Primary effectiveness outcome was the retention rate of BRV as single ASM at 6 and 12 months. Secondary outcomes included the 6- and 12-month rates of seizure freedom. Safety and tolerability outcomes included the frequency and type of adverse events (AEs) and the occurrence of treatment discontinuation due to AEs. RESULTS: A total of 44 participants with a median age of 63.5 (interquartile range 44-73.5) years were included; 17 subjects were seizure free at baseline, and 9 of them switched from levetiracetam because of lack of tolerability. The retention rate of BRV monotherapy was 88.6% (39/44) at 6 months and 83.9% (26/31) at 12 months. The rates of seizure freedom were 72.7% (32/44) in subjects with 6-month follow-up and 58.1% (18/31) in subjects with 12-month follow-up. The median maintenance dosage of BRV monotherapy was 150 (100-200) mg/day at 6 months and 125 (100-200) mg/day in subjects with 12-month follow-up. Adverse events were recorded in 6/44 (13.6%) participants and led to BRV discontinuation in 2/44 (4.5%) cases. The reported AEs were somnolence (n = 3), fatigue (n = 2), and irritability (n = 1); no serious AEs were experienced. In 21/44 (47.7%) participants, BRV monotherapy resulted from the direct switch from levetiracetam. The rates of treatment retention and seizure freedom at 6 and 12 months were higher among people who switched from levetiracetam to BRV monotherapy. CONCLUSION: Brivaracetam may be a valuable treatment of focal seizures in people who converted to monotherapy in a real-life setting.

Safety and efficacy of levetiracetam and carbamazepine monotherapy in the management of pediatric focal epilepsy: a randomized clinical trial.

Due to the limited number of studies in children with focal epilepsy and the importance of choosing the most suitable drug to control seizures in children, the administration of the most effective medication with the most negligible adverse events is vital. This study aimed to evaluate the effectiveness and adverse events of carbamazepine vs. levetiracetam monotherapy in children with focal seizures. A monocentric, randomized, controlled, double-blind, parallel-group clinical trial was designed. This study was approved by the Iranian Registry of Clinical Trials (registration number: IRCT20170216032603N2) on June 19, 2020, and conducted at the neurology department of Imam Ali Hospital, Karaj, Iran, from February 2020 to March 2021. This study assessed 120 patients with recently diagnosed focal seizures aged 2 to 14. Patients were randomly divided into two groups, who received carbamazepine (CBZ) 15 to 20 mg/kg and levetiracetam (LEV) 20 to 40 mg/kg daily, respectively. Patients were evaluated for improvement and complications at weeks 4, 12, and 24. Out of 120 patients included in the study, six patients were excluded due to various complications of CBZ. The mean number of seizures at the end of the fourth, twelfth, and twenty-fourth weeks were 1.09 ± 0.75, 0.62 ± 0.27, and 0.39 ± 0.12 in the carbamazepine group and 1.11 ± 0.63, 0.52 ± 0.21, and 0.37 ± 0.11 in the LEV group, respectively (P > 0.05). Similarly, the number of seizure-free patients was 34, 44, and 48 in the CBZ group compared to 41, 50, and 54 in the LEV group, respectively (P > 0.05). On the other hand, the frequency of somnolence, dermatologic complications, and agitation was considerably higher in the CBZ group (P < 0.05). Although both medicines were equally effective in seizure control, CBZ was associated with considerably more adverse events and less patient compliance. Physicians should be aware of this difference to prevent unwanted consequences.

Selective striatal fast-spiking interneuron inhibition induces cortical seizure.

Whether striatal fast-spiking interneurons are involved in cortical synchronization remains elusive. We performed acute microinjections of a selective FSI-AMPA receptor antagonist into the sensorimotor striatum of non-human primates to verify whether selective FSI inhibition within the sensorimotor striatum could potentially modify cortical excitability, thereby triggering focal seizures. Experiments were performed on three fascicularis monkeys. During each experimental session, low volumes of IEM-1460 (4-8 µL) were injected slowly at 1 µL/min. Spontaneous behavioral changes were classified according to the Racine scale modified for primates. These induced motor behaviors were correlated with electroencephalographic (EEG and EMG) measures. Power spectrum and time-frequency analysis were performed and compared between each period of interest. Pharmacological selective inhibition of striatal fast-spiking INs induced focal motor seizures. Back averaging confirmed that myoclonic activity was closely linked to cortical spikes-and-waves epileptic activity, with a significant increase in cortical EEG power in all studied frequency bands (p < .0001). Thus, striatal FSIs likely play a role in controlling cortical excitability through the cortico-striato-thalamo-cortical pathway. They may contribute to the pathophysiology of focal motor epilepsies by modulating the threshold at which focal motor seizures are triggered.

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.

Hyperventilation Induced Seizures in Focal Epilepsy: Two Cases and a Review of Literature.

We report two cases of temporo-perisylvian epilepsy with habitual seizures consistently inducible by hyperventilation (HV). One case was non-lesional, while the other was a lesional temporo-perisylvian epilepsy. Both underwent surgical resection and were seizure-free or nearly seizure-free thereafter. We discuss the pathophysiological changes evoked by HV in healthy brains, and those with generalized and focal epilepsy. We provide a comprehensive and critical review of the literature on the role of HV in focal epilepsy. We suggest HV should be considered an activation method for patients with focal epilepsy during epilepsy monitoring unit admissions and may help in the localization of the epileptogenic network/zone.

Cathodal HD-tDCS and attention: A study on patients with intractable left lateral frontal lobe epilepsy.

OBJECTIVE: Defects in the attentional network in patients with epilepsy are influenced by factors such as the location of epileptic foci. Examining the impact of cathodal high-definition transcranial direct current stimulation (HD-tDCS) on attention components could provide insights into potential attention-related side effects of tDCS. This study aimed to investigate the effect of cathodal HD-tDCS on interictal epileptiform discharges (IEDs), auditory/visual (A/V) attention components, and reaction time (RT) in patients with intractable focal left lateral frontal lobe epilepsy (LFLE). METHODS: To control for variations in individual epilepsy syndrome, 12 adult participants diagnosed with drug-resistant left LFLE with focal cortical IEDs on C3 underwent repeated measurements at pretest, posttest, and follow-up steps. 4 × 1 ring electrodes (cathode on C3 and four anodes on F3, P3, T3, and Cz) delivered 2 mA DC for 20 min per session for 10 consecutive days. The integrated visual and auditory continuous performance test (IVA+) assessed the A/V attention components and RT. One-way repeated-measure ANOVA was used. RESULTS: The findings suggest a significant effect in reducing IEDs. The IVA+ results showed a significant improvement in auditory divided attention and visual selective and focused attention (p < 0.05). In the follow-up, these changes demonstrated lasting efficacy. A/V speed scales increased (p < 0.05), showing a significant decrease in reaction time. CONCLUSIONS: Cathodal HD-tDCS significantly reduced IEDs and improved the components of auditory divided attention, visual focused attention, and visual selective attention, with a reduction in patient reaction time. A significant lasting, side-effect-free positive effect was observed for up to one month after the intervention.

Understanding Focal Seizures in Adults: A Comprehensive Review.

Focal or partial seizures are a common neurological disorder affecting adults. This review aims to provide an in-depth understanding of focal seizures in adults, including their classification, clinical presentation, etiology, diagnosis, and management. This article seeks to enhance awareness and knowledge among medical professionals and the general public by exploring the latest research and clinical insights. Standard electroencephalography (EEG) and recordings in presurgical electrode depth in humans provide a clear definition of patterns similar to focal seizures. Models of animals with partial seizures and epilepsy mimic seizure patterns with comparable characteristics. However, the network factors supporting interictal spikes, as well as the start, development, and end of seizures remain obscure. According to recent research, inhibitory networks are heavily implicated at the beginning of seizures, and extracellular potassium alterations help start and maintain seizure continuation. An increase in network synchronization, which may be caused by both excitatory and inhibitory pathways, is correlated with the cessation of a partial seizure. Recent research on temporal lobe focal seizures in human and animal models leads to the hypothesis that the active blocking of subcortical arousal processes brings on unconsciousness. Brainstem, basal forebrain, and thalamic arousal networks' neuronal firing is diminished during focal limbic seizures, and cortical arousal can be recovered when subcortical arousal circuits are engaged. These results suggest that thalamic neurostimulation may be therapeutic to restore arousal and consciousness during and after seizures. Targeted subcortical stimulation may increase arousal and consciousness when current treatments cannot halt seizures, enhancing safety and psychosocial function for epileptic patients. We embark on an investigation into adult focal seizures in this thorough review that goes beyond a cursory knowledge of their clinical symptoms.