OBJECTIVE: To describe the association between preoperative ictal scalp electroencephalogram (EEG) results and surgical outcomes in patients with focal epilepsies.
METHODS: The data of consecutive patients with focal epilepsies who received surgical treatments at our center from January 2012 to December 2021 were retrospectively analyzed.
RESULTS: Our data showed that 44.2% (322/729) of patients had ictal EEG recorded on video EEG monitoring during preoperative evaluation, of which 60.6% (195/322) had a concordant ictal EEG results. No significant difference of surgery outcomes between patients with and without ictal EEG was discovered. Among MRI-negative patients, those with concordant ictal EEG had a significantly better outcome than those without ictal EEG (75.7% vs. 43.8%, p = 0.024). Further logistic regression analysis showed that concordant ictal EEG was an independent predictor for a favorable outcome (OR = 4.430, 95%CI 1.175-16.694, p = 0.028). Among MRI-positive patients, those with extra-temporal lesions and discordant ictal EEG results had a worse outcome compared to those without an ictal EEG result (44.7% vs. 68.8%, p = 0.005). Further logistic regression analysis showed that discordant ictal EEG was an independent predictor of worse outcome (OR = 0.387, 95%CI 0.186-0.807, p = 0.011) in these patients. Furthermore, our data indicated that the number of seizures was not associated with the concordance rates of the ictal EEG, nor the surgical outcomes.
CONCLUSIONS: The value of ictal scalp EEG for epilepsy surgery varies widely among patients. A concordant ictal EEG predicts a good surgical outcome in MRI-negative patients, whereas a discordant ictal EEG predicts a poor postoperative outcome in lesional extratemporal lobe epilepsy.

UNASSIGNED: We tested the hypothesis that epileptic, but not non-epileptic, seizures would produce an improvement in comorbid depression and anxiety symptoms in the peri-ictal period, much like the antidepressant effects of electroconvulsive therapy.
UNASSIGNED: We examined depression and anxiety symptoms in patients admitted to an inpatient unit for continuous video electroencephalography as part of routine clinical care. Patients completed three questionnaires that included the Beck Depression Inventory-II (BDI), Montgomery Asberg Depression Rating Scale (MADRS), and Beck Anxiety Inventory (BAI) after admission, in the 24 h following a seizure, then again 2 weeks after the last seizure.
UNASSIGNED: In patients with epilepsy, depression and anxiety scores improved in the 24 hrs following a seizure (change in BDI = 24%; change in MADRS = 19%; change in BAI = 21%) but returned toward baseline after 2 weeks. In patients with non-epileptic seizures, depression and anxiety scores also improved in the 24 hrs following a psychogenic non-epileptic seizure (change in BDI = 17%, change in MADRS = 27%, change in BAI = 36%). There was a greater improvement in depression and anxiety scores in patients with focal-onset epilepsy (BDI = 30%, MADRS = 22%, BAI = 30%) compared to generalized seizure onset (BDI = 6%, MADRS = 12%, BAI = 8%).
UNASSIGNED: We conclude that single seizures can result in transient improvements in mood. Because seizures need not be generalized or epileptic to exert this effect, the underlying mechanisms are uncertain.

Objective: Whilst stimulation of the anterior nucleus of the thalamus has shown efficacy for reducing seizure frequency in adults, alterations in thalamic connectivity have not been explored in children. We tested the hypotheses that (a) the anterior thalamus has increased functional connectivity in children with focal epilepsy, and (b) this alteration in the connectome is a persistent effect of the disease rather than due to transient epileptiform activity. Methods: Data from 35 children (7-18 years) with focal, drug-resistant epilepsy and 20 healthy children (7-17 years) were analyzed. All subjects underwent functional magnetic resonance imaging (fMRI) whilst resting and were simultaneously monitored with scalp electroencephalography (EEG). The fMRI timeseries were extracted for each Automated Anatomical Labeling brain region and thalamic subregion. Graph theory metrics [degree (DC) and eigenvector (EC) centrality] were used to summarize the connectivity profile of the ipsilateral thalamus, and its thalamic parcellations. The effect of interictal epileptiform discharges (IEDs) captured on EEG was used to determine their effect on DC and EC. Results: DC was significantly higher in the anterior nucleus (p = 0.04) of the thalamus ipsilateral to the epileptogenic zone in children with epilepsy compared to controls. On exploratory analyses, we similarly found a higher DC in the lateral dorsal nucleus (p = 0.02), but not any other thalamic subregion. No differences in EC measures were found between patients and controls. We did not find any significant difference in DC or EC in any thalamic subregion when comparing the results of children with epilepsy before, and after the removal of the effects of IEDs. Conclusions: Our data suggest that the anterior and lateral dorsal nuclei of the thalamus are more highly functionally connected in children with poorly controlled focal epilepsy. We did not detect a convincing change in thalamic connectivity caused by transient epileptiform activity, suggesting that it represents a persistent alteration to network dynamics.

The purpose of this review is to describe the functional anatomy of the precuneal cortex and outline some semiological features of precuneal seizures. The precuneal cortex is a structure that occupies the posterior medial portion of the parietal lobe, and it has broad cortical and subcortical connections. Neuroanatomical tracing, functional imaging, as well as electrical stimulation studies of humans and other primates have elucidated many complex integrative functions of the precuneus including visuo-spatial imagery, sensorimotor functions, and consciousness. Based on the understanding of its functions and connectivity, descriptions of potential seizure semiologies are hypothesized and compared to what is available in the literature. The latter is mostly in the form of case reports or case series. Seizures may involve simple or complex motor or sensory manifestations including abnormal eye movements, visual hallucinations, sensation of motion, or medial temporal-like seizures.

Increasing availability of surgically resected brain tissue from patients with focal epilepsy and focal cortical dysplasia or low-grade glioneuronal tumors has fostered large-scale genetic examination. However, assessment of pathogenicity of germ line and somatic variants remains difficult. Here, we present a state-of-the-art evaluation of reported genes and variants associated with epileptic brain lesions.
We critically reevaluated the pathogenicity for all neuropathology-associated variants reported to date in the PubMed and ClinVar databases, including 101 neuropathology-associated missense variants encompassing 11 disease-related genes. We assessed gene variant tolerance and classified all identified missense variants according to guidelines from the American College of Medical Genetics and Genomics (ACMG). We further extended the bioinformatic variant prediction by introducing a novel gene-specific deleteriousness ranking for prediction scores.
Application of ACMG guidelines and in silico gene variant tolerance analysis classified only seven of 11 genes to be likely disease-associated according to the reported disease mechanism, whereas 61 (60.4%) of 101 variants of those genes were classified as of uncertain significance, 37 (36.6%) as being likely pathogenic, and 3 (3%) as being pathogenic.
We concluded that the majority of neuropathology-associated variants reported to date do not have enough evidence to be classified as pathogenic. Interpretation of lesion-associated variants remains challenging, and application of current ACMG guidelines is recommended for interpretation and prediction.

Epileptogenic networks are defined by the brain regions involved in the production and propagation of epileptic activities. In this review we describe the historical, methodologic, and conceptual bases of this model in the analysis of electrophysiologic intracerebral recordings. In the context of epilepsy surgery, the determination of cerebral regions producing seizures (i.e., the \"epileptogenic zone\") is a crucial objective. In contrast with a traditional focal vision of focal drug-resistant epilepsies, the concept of epileptogenic networks has been progressively introduced as a model better able to describe the complexity of seizure dynamics and realistically describe the distribution of epileptogenic anomalies in the brain. The concept of epileptogenic networks is historically linked to the development of the stereoelectroencephalography (SEEG) method and subsequent introduction of means of quantifying the recorded signals. Seizures, and preictal and interictal discharges produce clear patterns on SEEG. These patterns can be analyzed utilizing signal analysis methods that quantify high-frequency oscillations or changes in functional connectivity. Dramatic changes in SEEG brain connectivity can be described during seizure genesis and propagation within cortical and subcortical regions, associated with the production of different patterns of seizure semiology. The interictal state is characterized by networks generating abnormal activities (interictal spikes) and also by modified functional properties. The introduction of novel approaches to large-scale modeling of these networks offers new methods in the goal of better predicting the effects of epilepsy surgery. The epileptogenic network concept is a key factor in identifying the anatomic distribution of the epileptogenic process, which is particularly important in the context of epilepsy surgery.

The efficacy of lamotrigine in the treatment of focal epilepsies have already been reported in several case reports and open studies, which is thought to act by inhibiting glutamate release through voltage-sensitive sodium channels blockade and neuronal membrane stabilization. However, recent findings have also illustrated the importance of lamotrigine in alleviating the depressive symptoms of bipolar disorder, without causing mood destabilization or precipitating mania. Currently, no mood stabilizers are available having equal efficacy in the treatment of both mania and depression, two of which forms the extreme sides of the bipolar disorder. Lamotrigine, a well established anticonvulsant has received regulatory approval for the treatment and prevention of bipolar depression in more than 30 countries worldwide. Lamotrigine, acts through several molecular targets and overcomes the major limitation of other conventional antidepressants by stabilizing mood from \"below baseline\" thereby preventing switches to mania or episode acceleration, thus being effective for bipolar I disorder. Recent studies have also suggested that these observations could also be extended to patients with bipolar II disorder. Thus, lamotrigine may supposedly fulfill the unmet requirement for an effective depression mood stabilizer.

The definition of reflex epileptic seizures is that specific seizure types can be triggered by certain sensory or cognitive stimuli. Simple triggers are sensory (most often visual, more rarely tactile or proprioceptive; simple audiogenic triggers in humans are practically nonexistent) and act within seconds, whereas complex triggers like praxis, reading and talking, and music are mostly cognitive and work within minutes. The constant relation between a qualitatively, often even quantitatively, well-defined stimulus and a specific epileptic response provides unique possibilities to investigate seizure generation in natural human epilepsies. For several reflex epileptic mechanisms (REMs), this has been done. Reflex epileptic mechanisms have been reported less often in focal lesional epilepsies than in idiopathic \"generalized\" epilepsies (IGEs) which are primarily genetically determined. The key syndrome of IGE is juvenile myoclonic epilepsy (JME), where more than half of the patients present reflex epileptic traits (photosensitivity, eye closure sensitivity, praxis induction, and language-induced orofacial reflex myocloni). Findings with multimodal investigations of cerebral function concur to indicate that ictogenic mechanisms in IGEs largely (ab)use preexisting functional anatomic networks (CNS subsystems) normally serving highly complex physiological functions (e.g., deliberate complex actions and linguistic communication) which supports the concept of system epilepsy. Whereas REMs in IGEs, thus, are primarily function-related, in focal epilepsies, they are primarily localization-related. This article is part of a Special Issue entitled \"Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic\".

Rare multiplex families with autosomal dominant focal epilepsies have been described with specific age-related and electroclinical syndromes: autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), familial temporal lobe epilepsy (FTLE), and familial focal epilepsy with variable foci (FFEVF). Molecular genetic advances in inherited focal epilepsies have pinpointed their genetic heterogeneity and the fact that they are mediated by different biological pathways: ion channel subunit genes have been linked to ADNFLE (CHRNA4, CHRNA2, CHRNB2, and KCNT1, encoding, respectively, the α4, α2, and β2 subunits of the neuronal nicotinic acetylcholine receptor, and a potassium channel subunit); neuronal secreted protein (LGI1-encoding epitempin) has been linked to autosomal dominant epilepsy with auditory features; and mTORC1-repressor DEPDC5 (DEP domain-containing protein 5) gene has recently been reported in a broad spectrum of inherited focal epilepsies (ADNFLE, FTLE, FFEVF). This chapter focuses on DEPDC5, a newly identified gene.

OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) are often used in the treatment of depressive disorders in patients with epilepsy. Pro- and anti-convulsive effects of SSRIs are discussed controversially. The aim of this study was to investigate a possible impact of SSRIs-treatment on duration of EEG and clinical features in epilepsy patients.
METHODS: We studied video-EEG data from 162 patients with focal epilepsies between January 2006 and March 2008 using a case-control study design. Eleven patients with 19 complex focal seizures (CFSs) and 16 secondary generalized tonic-clonic seizures (sGTCSs) treated with SSRIs (SSRIs+) were matched to 13 patients without SSRIs-treatment (SSRIs-). We compared duration of ictal EEG in CFSs and sGTCSs, duration of convulsions in sGTCSs and duration of postictal EEG suppression after sGTCSs in SSRIs+ and SSRIs- patients.
RESULTS: Ictal EEG duration of both, CFSs and sGTCSs, was significantly longer in SSRIs+ patients than in SSRIs- patients (p=0.004 and p=0.015, respectively). No significant difference was found between convulsive phase duration of sGTCSs as well as duration of postictal EEG suppression after sGTCSs in both groups.
CONCLUSIONS: Seizures last significantly longer in patients with epilepsy and SSRIs as co-medication. A causative role of SSRIs in ictal activity has to be explored in prospective studies.