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We report detailed functional analyses and genotype-phenotype correlations in 392 individuals carrying disease-causing variants in SCN8A, encoding the voltage-gated Na+ channel Nav1.6, with the aim of describing clinical phenotypes related to functional effects. Six different clinical subgroups were identified: Group 1, benign familial infantile epilepsy (n = 15, normal cognition, treatable seizures); Group 2, intermediate epilepsy (n = 33, mild intellectual disability, partially pharmaco-responsive); Group 3, developmental and epileptic encephalopathy (n = 177, severe intellectual disability, majority pharmaco-resistant); Group 4, generalized epilepsy (n = 20, mild to moderate intellectual disability, frequently with absence seizures); Group 5, unclassifiable epilepsy (n = 127); and Group 6, neurodevelopmental disorder without epilepsy (n = 20, mild to moderate intellectual disability). Those in Groups 1–3 presented with focal or multifocal seizures (median age of onset: 4 months) and focal epileptiform discharges, whereas the onset of seizures in patients with generalized epilepsy was later (median: 42 months) with generalized epileptiform discharges. We performed functional studies expressing missense variants in ND7/23 neuroblastoma cells and primary neuronal cultures using recombinant tetrodotoxin-insensitive human Nav1.6 channels and whole-cell patch-clamping. Two variants causing developmental and epileptic encephalopathy showed a strong gain-of-function (hyperpolarizing shift of steady-state activation, strongly increased neuronal firing rate) and one variant causing benign familial infantile epilepsy or intermediate epilepsy showed a mild gain-of-function (defective fast inactivation, less increased firing). In contrast, all three variants causing generalized epilepsy induced a loss-of-function (reduced current amplitudes, depolarizing shift of steady-state activation, reduced neuronal firing). Functional effects were known for 170 individuals. All 136 individuals carrying a functionally tested gain-of-function variant had either focal (n = 97, Groups 1–3) or unclassifiable (n = 39) epilepsy, whereas 34 individuals with a loss-of-function variant had either generalized (n = 14), no (n = 11) or unclassifiable (n = 6) epilepsy; only three had developmental and epileptic encephalopathy. Computational modelling in the gain-of-function group revealed a significant correlation between the severity of the electrophysiological and clinical phenotypes. Gain-of-function variant carriers responded significantly better to sodium channel blockers than to other anti-seizure medications, and the same applied for all individuals in Groups 1–3. In conclusion, our data reveal clear genotype-phenotype correlations between age at seizure onset, type of epilepsy and gain- or loss-of-function effects of SCN8A variants. Generalized epilepsy with absence seizures is the main epilepsy phenotype of loss-of-function variant carriers and the extent of the electrophysiological dysfunction of the gain-of-function variants is a main determinant of the severity of the clinical phenotype in focal epilepsies. Our pharmacological data indicate that sodium channel blockers present a treatment option in SCN8A-related focal epilepsy with onset in the first year of life.

This survey analyzed data obtained through a questionnaire on the clinical approaches used by veterinarians to treat dogs with epileptic seizures. We found that neurological examinations were performed by 12% of the respondents, blood tests by 85%, and computed tomography by 72%. In addition, serology for infectious disease detection was mentioned by 30% of the respondents, and 72% did not classify epileptic seizures. According to the answers, the treatment of choice was phenobarbital in 100% of cases which was combined with potassium bromide in 19%. Moreover, 51% of the respondents mentioned that they monitored the serum phenobarbital levels. The study results showed disagreements on the conduct and care recommended by the International Veterinary Epilepsy Task Force consensus. RESUMO: O objetivo deste estudo foi analisar a conduta clínica de médicos veterinários no atendimento de cães apresentando crises epilépticas por meio de um questionário. 12% afirmaram realizar exame neurológico, enquanto 85% realizam exames hematológicos; 72% solicitam tomografia computadorizada e 30% pedem sorologias para investigação de doenças infecciosas. Todos os veterinários prescrevem fenobarbital para o tratamento. O brometo de potássio foi citado por 19% dos entrevistados em associação ao fenobarbital. A dosagem sérica de fenobarbital é realizada por 51% dos entrevistados. Os resultados apontaram que não houve homogeneidade na conduta preconizada pelas diretrizes científicas sobre o tema.

Objective For epilepsy patients with drug-resistant, unresectable epilepsy, vagus nerve stimulation (VNS) is an option for seizure control. Approximately 40-70% of patients will achieve ≥50% seizure reduction with VNS. New closed loop VNS models detect ictal tachycardia and responsively stimulate the vagus nerve. The effectiveness of closed loop VNS compared to traditional VNS for pediatric epilepsy is unknown. Methods An 11-year retrospective electronic medical record review at Children's Hospital of Pittsburgh was performed. Patients with drug-resistant epilepsy who underwent VNS implantation were included. Patients were divided into groups based on VNS model: traditional versus closed loop. Those who transitioned from traditional to closed loop VNS were excluded. Given potential for selection bias, propensity scores matching was utilized to compare traditional to closed loop VNS patients. Patients with focal versus generalized epilepsy were also separately analyzed. The primary outcome was “VNS response”, defined as at least 50% seizure frequency reduction from baseline. Results A total of 320 patients were included in this sample. The percentage of matched patients (total n=220: n=179 traditional VNS, n=41 closed loop VNS) who responded to VNS after one year of therapy was 43% for traditional VNS and 39% for closed loop VNS (p=0.64). After two years of therapy, a higher proportion of closed loop VNS patients than traditional VNS patients responded to VNS among all subgroups, though no differences were statistically significant (p>0.05). Notably, for those with generalized epilepsy, 73% of closed loop patients responded to VNS compared to only 46% of traditional patients (p=0.10). After two years of VNS therapy, patients were taking approximately the same quantity of antiseizure medications as baseline (0.074 ± 0.90) with no difference between VNS models (p=0.87). Significance Among pediatric patients with drug-resistant epilepsy, closed loop VNS trends towards a higher rate of VNS response after two years of treatment, especially among generalized epilepsy patients. Neither model of VNS allows patients to reduce antiseizure medication quantity after two years.

Hintergrund: Die Epilepsie ist durch ihre facettenreichen Symptome, Formen und Verläufe oftmals schwierig zu diagnostizieren. Eine Erleichterung schuf unter anderem die Klassifikation der ILAE, welche allgemeingültige diagnostische Kriterien etablierte. Um eine erfolgreiche Behandlung zu ermöglichen, werden regelmäßig im Rahmen pharmakologischer Studien die wirksamsten Medikamente getestet und ermittelt. Hierbei ging nach aktuellem Wissenstand Valproinsäure als Mittel der Wahl für generalisierte und Lamotrigin für fokale Epilepsien hervor. Trotz der beschriebenen Entwicklungen stellt vor allem die Differenzierung zwischen fokalen und generalisierten Epilepsien oftmals ein Hindernis für eine erfolgreiche Behandlung dar. Mitunter ausschlaggebend hierfür sind sogenannte „fokale Zeichen“, welche in vergangenen Studien vor allem im Zusammenhang mit idiopathisch generalisierten Epilepsien (IGE) dokumentiert wurden. In diesem Zusammenhang wurden fokale Zeichen in der Elektroenzephalografie (EEG) sowie semiologisch während des Anfalls, wie manuelle und orale Automatismen, lateralisierte Myokloni/Kloni, einseitige dystone Haltungen und Kopfversionen bzw. -deviationen und Augendeviationen. Ziel: Im Zuge dieser Studie soll herausgefunden werden, wie häufig bei Betroffenen einer IGE fokale motorische Symptome im Video-EEG-Monitoring (VEEG) in der Klinik Hietzing auftraten. Darauf aufbauend soll der Einfluss dieser fokalen Zeichen auf die Behandlung und Diagnosestellung der Patient*innen analysiert werden. Patient*innen und Methoden: Im Fokus der Arbeit stand die retrospektive Analyse der Anfallsvideos, welche auf die in der Literatur beschriebenen fokalen motorischen Symptome überprüft wurden. Hierfür wurden 406 Anfälle von 34 Patient*innen mit IGE herangezogen. Darauf aufbauend wurde die Häufigkeit der verschiedenen fokalen Symptomgruppen eruiert. Es wurden zudem Unterschiede in der Häufigkeit der Einnahme von Valproinsäure zwischen Patient*innen mit fokalen Zeichen und jenen ohne untersucht. Weiters wurde eruiert, ob bei Personen mit fokalen Zeichen öfter Unklarheit in der Frage der Differentialdiagnose (fokale oder generalisierte Epilepsie) bestand. Ergebnisse: Die Mehrheit der Stichprobe (n=34 Patient*innen mit IGE) zeigte während des VEEG-Monitorings fokale motorische Symptome (n= 26). Diese konnten in 80 von den 143 (55,9%) auswertbaren Anfällen dokumentiert werden. Die Symptome kamen einzeln und in Gruppen vor, wobei ihre Häufigkeit variierte. Das am häufigsten detektierte Symptom, welches bei 78,1 % der Betroffenen und in 58 Anfällen beobachtet wurde, waren lateralisierte Myokloni/Kloni. Es konnte kein signifikanter Unterschied bei der Häufigkeit der Einnahme von Valproinsäure (p=0,654) und einer unklaren Differentialdiagnose (p=0,370) zwischen Personen mit und ohne fokale Zeichen nachgewiesen werden. Jedoch ließ sich angesichts der prozentuellen Häufigkeit erkennen, dass Patient*innen mit fokalen Zeichen tendenziell öfter nicht mit dem geeignetsten Wirkstoff für generalisierte Epilepsien, nämlich Valproinsäure, behandelt wurden. Zudem wurde beobachtet, dass bei Patient*innen mit fokalen Zeichen öfter Unklarheiten bei der differentialdiagnostischen Abklärung bestanden. Conclusio: Aus den Ergebnissen der Studie geht hervor, dass fokale Zeichen bei generalisierten Epilepsien in jedem Fall beachtet werden müssen, um eine richtige Diagnose und folglich eine zielführende Behandlung ermöglichen zu können. Background: Epilepsy is often difficult to diagnose due to its symptoms, forms and causes. The classification of the ILAE, which established universally valid diagnostic criteria, is a step to make the situation easier. To enable successful treatment, the most effective drug treatment is regularly tested in pharmacological studies. According to current knowledge, valproic acid is the drug of choice for generalized epilepsy and lamotrigine for focal epilepsy. Despite the developments described above, the differentiation between focal and generalized epilepsies is often an obstacle to successful treatment. Crucial for this are so called “focal signs”, which have been documented in past studies in patients with idiopathic generalized epilepsy (IGE). In this context, focal signs in the electroencephalography (EEG) and motor symptoms, such as manual and oral automatisms, lateralized myocloni and cloni, unilateral dystonic postures and head inversions or gaze deviations were observed in previous studies. Aim: The aim of this study is to investigate how often focal motor symptoms occurred in patients with IGE during past stays in the Video-EEG monitoring (VEEG) of the hospital Klinik Hietzing. Based on this, the influence of the lateralizing signs on the treatment and diagnosis of the affected persons will be analyzed. Patients and methods: The focus of this work was the retrospective analysis of seizure videos during VEEG, which were reviewed for focal motor symptoms described in the literature. For this purpose, 406 seizures of 34 patients with IGE were screened. Comparisons were then made between patients with focal signs and those without regarding differences in the frequency of valproic acid use and unclear differential diagnosis (focal or generalized epilepsy) of those patients. Results: Most of the 34 patients with IGE showed focal motor symptoms during VEEG monitoring (n=26). These could be documented in 80 of the 143 (55,9%) evaluable seizures. Symptoms occurred singly and in groups, and their frequency varied. The most frequently detected symptom, observed in 78.1% of the subjects and in 58 seizures, was lateralized myocloni/cloni. No significant difference in the frequency of valproic acid use (p=0.654) and an unclear differential diagnosis (p=0.370) was demonstrated between subjects with and without focal signs. However, given the percentage frequency, it could be seen that patients with focal signs were more often not treated with the most appropriate substance for generalized epilepsy, valproic acid, than those without focal signs. In addition, we observed that differential diagnosis was more often uncertain in patients with focal signs. Conclusion: The results of the study show that focal signs in generalized epilepsies must be considered in any case to enable a correct differential diagnosis and targeted treatment.

People with focal epilepsies are known to under-document their seizures, but there is no data on self-documentation in adults with genetic (idiopathic) generalized epilepsy (GGE/IGE). We assessed the accuracy of self-evaluation of typical absences (TA) or myoclonic seizures (MS) in adults with IGE based on home video-EEG telemetry (HVET). Patients' own estimates were compared to the objective count of definite TA and MS, performed visually. We considered definite TA as generalized spike-wave discharges (GSWD) that met any of the following criteria: 1) coinciding with clear behavioural arrest on video, 2) followed after a few seconds by positive indication that an absence occurred, or 3) in the absence of video, consistently coinciding with clear motor arrest, as evidenced by interruption of continuous muscle activity. For each patient, we also classified probable TA as GSWDs that were longer than those corresponding to the shortest definite TA on HVET or based on the most recent sleep-deprived EEG (SDEEG). From the first 300 consecutive adults who had HVET, 24 had IGE with TA and / or MS; 23 were women. Only one patient had newly diagnosed IGE. Erroneous self-assessment of TA and MS was noted in 16/24 patients (66.7%). Seizures were overestimated in nine (37.5%) and underestimated in seven (29.2%). Only one patient (4.2%) documented all her TA and MS without false-positive estimates. Overestimation (but not underestimation) of TA on HVET could be predicted when patients reported daily or multiple weekly TA and a recent SDEEG was either normal or contained only subclinical GSWD (p=0.0095). Under- and over-self-documentation of TA and MS occurred in two thirds of adults with GGE/IGE, with substantial impact on their outpatient management and treatment. Diagnostic HVET is a useful tool for the detection of erroneous self-evaluation in these patients.

Objective: to evaluate the role of seizure severity and epileptiform activity index (IEA) assessment in newly-diagnosed idiopathic generalized epilepsy with generalized tonic-clonic awakening seizures (GTCS).Material and methods. The study included 31 patients with newly-diagnosed generalized epilepsy with GTCS aged 14–52 years (mean age 25.06±9.3 years), which were divided into two groups depending on seizure severity: Group 1 (n=9, 29%) with 50% (responders), seizure rate decrease by Results. Total EAI at baseline was significantly higher in patients from Group 2 (p=0.019). Despite markedly reduced EAI level in both groups, in Group 1 (less than 18 points by NHS3) EAI was significantly lower compared to Group 2 (≥18 points) at all subsequent visits: visit 2 (p=0.038), visit 3 (p=0.035), visit 4 (p=0.047), and visit 5 (p=0.022).Conclusions. Assessing seizure severity may become an additional objective criterion while evaluating treatment efficacy.

Introduction Levetiracetam (LEV) is a second-generation antiseizure medicine (ASM) with broad-spectrum efficacy and tolerability. Few studies have compared the efficacy of valproate (VPA) and LEV as monotherapy in the pediatric population. Herein, we compare the efficacy, tolerability and safety of LEV monotherapy with those of VPA monotherapy in ASM-naive pediatric patients with idiopathic generalized epilepsy with tonic-clonic (GTC) seizures. Methods We retrospectively analyzed the clinical and electroencephalographic (EEG) data of these ASM-naive pediatric patients who were treated with either oral VPA or oral LEV as monotherapy for over 2 years at our center. Results This study included 60 patients with a seizure onset age between 2 months and 12 years. The patients on VPA (29 patients) and LEV monotherapy (31 patients) showed similar favorable 6-month treatment outcomes (complete seizure control in 79.31% vs 80.64%, p = 0.468052). Age at epilepsy onset, epilepsy syndrome, EEG features and ASM dose were not significant predictors of the 6-month treatment outcomes in either group. Lower seizure frequency at presentation was a predictor of favorable 6-month treatment outcomes in the LEV group but not in the VPA group. VPA and LEV treatment showed similar favorable 6-month treatment outcomes in the febrile seizures plus and patients with unidentified epilepsy syndrome subgroups. None of the patients discontinued VPA or LEV due to treatment-associated adverse effects. Discussion Our study showed that compared to VPA monotherapy, LEV monotherapy in ASM-naive infants and children with idiopathic generalized epilepsy with GTC seizures has a similarly favorable efficacy and tolerability, independent of age, EEG features and epilepsy syndrome.

OBJECTIVE Several small series have described stereotactic MRI-guided laser interstitial thermal therapy for partial callosotomy of astatic and generalized tonic-clonic (GTC) seizures, especially in association with Lennox-Gastaut syndrome. Larger case series and comparison of distinct stereotactic methods for stereotactic laser corpus callosotomy (SLCC), however, are currently lacking. The objective of this study was to report seizure outcomes in a series of adult patients with epilepsy following anterior, posterior, and complete SLCC procedures and to compare the results achieved with a frameless stereotactic surgical robot versus direct MRI guidance frames. METHODS The authors retrospectively reviewed sequential adult epilepsy surgery patients who underwent SLCC procedures at a single institution. They describe workflows, stereotactic errors, percentage disconnection, hospitalization durations, adverse events, and seizure outcomes after performing anterior, posterior, and complete SLCC procedures using a frameless stereotactic surgical robot versus direct MRI guidance platforms. RESULTS Thirteen patients underwent 15 SLCC procedures. The median age at surgery was 29 years (range 20–49 years), the median duration of epilepsy was 21 years (range 9–48 years), and median postablation follow-up was 20 months (range 4–44 months). Ten patients underwent anterior SLCC with a median 73% (range 33%–80%) midsagittal length of callosum acutely ablated. Following anterior SLCC, 6 of 10 patients achieved meaningful (> 50%) reduction of target seizures. Four patients underwent posterior (completion) SLCC following prior anterior callosotomy, and 1 patient underwent complete SLCC as a single procedure; 3 of these 5 patients experienced meaningful reduction of target seizures. Overall, 8 of 10 patients in whom astatic seizures were targeted and treated by anterior and/or posterior SLCC experienced meaningful improvement. SLCC procedures with direct MRI guidance (n = 7) versus a frameless surgical robot (n = 8) yielded median radial accuracies of 1.1 mm (range 0.2–2.0 mm) versus 2.4 mm (range 0.6–6.1 mm; p = 0.0011). The most serious adverse event was a clinically significant intraparenchymal hemorrhage in a patient who underwent the robotic technique. CONCLUSIONS This is the largest reported series of SLCC for epilepsy to date. SLCC provides seizure outcomes comparable to open surgery outcomes reported in the literature. Direct MRI guidance is more accurate, which has the potential to reduce the risks of SLCC. Methodological advancements and larger studies are needed.

Small fiber neuropathy (SFN) is a common condition affecting thinly myelinated A delta and unmyelinated C fibers, often resulting in excruciating pain and dysautonomia. SFN has been associated with several conditions, but a significant number of cases have no discernible cause. Recent genetic studies have identified potentially pathogenic gain-of-function mutations in several poreforming voltage-gated sodium channel alpha subunits (Na-v) in a subset of patients with SFN, but the auxiliary sodium channel beta-subunits have been less implicated in the development of the disease. beta subunits modulate Na-v trafficking and gating, and several mutations have been linked to epilepsy and cardiac dysfunction. Recently, we provided the first evidence for the contribution of a mutation in the beta 2 subunit to pain in human painful diabetic neuropathy. Here, we provide the first evidence for the involvement of a sodium channel beta subunit mutation in the pathogenesis of SFN with no other known causes. We show, through current-clamp analysis, that the newly identified Y69H variant of the beta(2) subunit induces neuronal hyperexcitability in dorsal root ganglion neurons, lowering the threshold for action potential firing and allowing for increased repetitive action potential spiking. Underlying the hyperexcitability induced by the beta(2)-Y69H variant, we demonstrate an upregulation in tetrodotoxin-sensitive, but not tetrodotoxin-resistant sodium currents. This provides the first evidence for the involvement of beta(2) subunits in SFN and strengthens the link between sodium channel beta subunits and the development of neuropathic pain in humans.NEW & NOTEWORTHY Small fiber neuropathy (SFN) often has no discernible cause, although mutations in the voltage-gated sodium channel alpha subunits have been implicated in some cases. We identify a patient suffering from SFN with a mutation in the auxiliary beta 2 subunit and no other discernible causes for SFN. Functional assessment confirms this mutation renders dorsal root ganglion neurons hyperexcitable and upregulates tetrodotoxin-sensitive sodium currents. This study strengthens a newly emerging link between sodium channel beta 2 subunit mutations and human pain disorders.

Epilepsy is a group of painful conditions caused by brain disorders, which are characterized by a persistent predisposition to epileptic seizures, as well as neurobiological, cognitive, psychological and social consequences. Currently, the overall prevalence of epilepsy in the world's population is 0.88% and ranges from 0.64% in developed countries to 1.00% in other countries. The prevalence of epilepsy in men is slightly higher than in women, and heredity varies between 25%-70%. According to the current classification, epilepsy includes four main forms: focal epilepsy, generalized epilepsy, combined focal and generalized epilepsy, and indeterminate epilepsy. The most common form of epilepsy is focal epilepsy, which accounts for 60% of all epilepsies. Currently, 14 genes associated with the development of epilepsy have been described, the functions of which are impaired by the presence of single nucleotide polymorphisms (SNPs). These SNPs can be located not only in the coding regions of genes (exons) or regulatory regions (eg., promoters), but also in their non-coding regions (introns), as well as in intergenic regions of DNA near a particular gene. Further research into the genetics of epilepsy should focus on developing new analytical approaches that will help uncover the unknown molecular genetic mechanisms of this group of disorders. Advances in the genetics of epilepsy will have a positive impact on clinical practice., Епілепсія – це група хворобливих станів, спричинених порушеннями функцій головного мозку, які характеризуються стійкою схильністю до епілептичних нападів, а також нейробіологічними, когнітивними, психологічними і соціальними наслідками. Нині загальна поширеність епілепсії серед населення світу становить 0,88% і варіює в межах від 0,64% в розвинених країнах до 1,00% у решті країн. Поширеність епілепсії серед чоловіків дещо вища, ніж серед жінок, а успадковуваність варіює в межах 25-70%. За сучасною класифікацією епілепсія включає чотири основні форми: фокальна епілепсія, генералізована епілепсія, комбінована фокальна та генералізована епілепсія та невизначена епілепсія. Найпоширенішою формою епілепсії є фокальна епілепсія, яка складає 60% усіх епілепсій. Нині описано 14 генів, пов’язаних із розвитком епілепсії, функції яких порушені наявністю однонуклеотидних поліморфізмів (ОНПів). Ці ОНПи можуть бути розташовані не лише в кодуючих ділянках генів (екзонах) чи регулюючих ділянках (наприклад, промоторі), а й в їхніх некодуючих ділянках (інтронах), а також у міжгенних ділянках ДНК недалеко від конкретного гена. Подальші дослідження генетики епілепсії мають бути спрямовані на розробку нових аналітичних підходів, які допоможуть розкрити невідомі молекулярно-генетичні механізми цієї групи розладів. Прогрес у генетиці епілепсії матиме позитивний вплив на клінічну практику.

Aim. To study gender and age aspects of epilepsy in patients with localization-related and generalized forms of epilepsy in the village of Mashtaga, Baku city.Material and methods. The gender structure of epilepsy in the village study was conducted simultaneously with a cohort pro- and retrospective research of its epidemiology at the United City Hospital (OGB) No. 7 in the village of Mashtaga and at the Department of Neurology of the Educational and Therapeutic Corps of AMU during the period from 2016 till 2019. Psychoemotional state (Ziqmond scale), severity of seizures (NHS3 scale), quality of life (QOLIE-10 questionnaire) were studied. For statistical processing, Fisher LSD and Pearson’s rank correlation coefficient were used at the level of significant results — p < 0.05.Results and discussion. Among 197 patients with epilepsy, 121 (61.4%) men and 76 (38.6%) women were examined. Most of them were accounted for localization-related epilepsy — 129 people (65.4%). 68 patients (33.5%) suffered from generalized epilepsy. The indigenous (37,505 people) and nonindigenous (8295 people) population were represented mainly by Azerbaijanis. The number of male patients with SPE exceeded the number of females (χ2 = 8.515; p = 0.004), (p < 0.05). There were more male patients with HE (41 (60.3%)) than females (27 (39.7%)). The severity of seizures, evaluated with the use of the NHS3 scale, was higher in male patients than in females. The psychoemotional state according to the Ziqmond scale in female patients from non-indigenous inhabitants was lower (9.05 ± 0.30; m = 6, M = 13) than in those of indigenous (8.83 ± 0.21; m = 5, M = 12), (p = 0.046). Assessment of the quality of life of patients with epilepsy according to QOLIE-10, did not reveal any gender diff erence.Conclusions. A gender-specific approach to the condition of patients with epilepsy will contribute to the improvement of both, clinical and psychoemotional parameters, thereby having a positive effect on the quality of life.

CSNK2B has recently been implicated as a disease gene for neurodevelopmental disability (NDD) and epilepsy. Information about developmental outcomes has been limited by the young age and short follow-up for many of the previously reported cases, and further delineation of the spectrum of associated phenotypes is needed. We present 25 new patients with variants in CSNK2B and refine the associated NDD and epilepsy phenotypes. CSNK2B variants were identified by research or clinical exome sequencing, and investigators from different centers were connected via GeneMatcher. Most individuals had developmental delay and generalized epilepsy with onset in the first 2 years. However, we found a broad spectrum of phenotypic severity, ranging from early normal development with pharmacoresponsive seizures to profound intellectual disability with intractable epilepsy and recurrent refractory status epilepticus. These findings suggest that CSNK2B should be considered in the diagnostic evaluation of patients with a broad range of NDD with treatable or intractable seizures.

Epilepsy is one of the greatest common neurological disorders characterized by epileptic seizures. The present study aims to investigate the protective effects of pomegranate juice with and without valproic acid on epileptic rats. Pomegranate juice (PJ) used in popular folk medicine for the treatment of various diseases due to its antioxidants content. Valproic acid (VPA) is a well-established anticonvulsant drug used in the treatment of many forms of generalized epilepsy and psychiatric disorders to control epileptic seizures. Pentylenetetrazol (PTZ) is a central nervous system convulsant which induce seizures and used as a routine test for screening of anticonvulsants. In the present study 35 rats were divided into 7 groups: control group, PTZ group, PJ group, VPA group, VPA+PTZ group, PJ+PTZ group, and PJ+VPA+PTZ group. Groups treated with pomegranate juice received daily oral doses of 10 µL/g of body weight for 28 days. Groups treated with valproic acid received daily intraperitoneal (IP) doses of 500 mg/kg body weight for 14 days. At the last day of the experiment groups treated with PTZ were injected with a single IP dose of PTZ (60 mg/kg B.W), while other groups without PTZ received the same dose of sterile isotonic saline solution. After 30 minutes animals were decapitated. Injection of rats with PTZ or VPA resulted in significant increase in liver functions and lipid profile except HDL-c. Results showed significant decrease in antioxidants while treatment with pomegranate juice showed significant decrease in liver functions and lipid profile and significant increase in antioxidants.

Generalized-onset seizures originate at a point within the brain and rapidly engage bilaterally distributed networks, whilst focal-onset seizures originate within networks limited to one hemisphere which may be discretely localized or more widely distributed. Challenges in data capturing have resulted in a lack of consistency across incidence and prevalence studies for estimates of generalized versus focal epilepsies in population groups, with a preponderance of unclassified cases. Infants and young children can further challenge delineation due to variable expression at different stages of brain maturation and impaired ability to express sensory seizure semiology. Focal seizures are divided into those in which the affected person is aware and those with impaired awareness; these events can be motor or non-motor. Generalized seizures are also categorized as motor and non-motor, but loss of awareness occurs with most events. Delineation between generalized and focal epilepsies is important for ongoing management. EEG, neuroimaging and other investigations (genetics, immune markers, etc.) can support the outcome but distinction between focal and generalized epilepsy in isolation is rarely achieved using such techniques. Certain clinical settings such as age, underlying aetiologies, and co-morbidities may be more predisposed to specific types of epilepsy. The differentiation between generalized and focal seizures remains a clinical process based on meticulous clinical history and examination, and is of relevance for the selection of antiseizure medications and identification of patients who may be viable for epilepsy surgery.

Objective: To evaluate the prevalence and patterns of psychiatric disorders in epilepsy patients at the Korle-Bu Teaching hospital, Accra, Ghana.Design: The study design was a cross-sectional surveySetting: The study was conducted at the Neurology Clinic of the Department of Medicine and Therapeutics, Korle-nBu Teaching hospital, Accra, Ghana.Participants: A total of one hundred and sixty-six patients diagnosed with epilepsy aged at least 18 years and accessing services at the neurology clinic participated in the study.Main Outcome Measure: Prevalence and patterns of psychiatric disorders among patients diagnosed with epilepsy using the Brief Symptom Inventory.Results: The mean age for onset of epilepsy was 20.1 ± 16.9 years, and generalized epilepsy (73.2%) was the major type of epilepsy identified. The aetiology of the epilepsy condition was unknown in most patients (71.1%). The estimated mean Brief Symptom Inventory scores in all the nine diagnostic psychiatry characteristics (Depression, Anxiety, Somatization, Hostility, Phobic Anxiety, Obsessive Compulsive Disorder, Psychoticism, Interpersonal Sensitivity, and Paranoid Ideation) were higher in the epilepsy patients compared to the normative data scores for non-patients. Global Severity Index scores for females were significantly higher (p=0.002) than the scores for males on all the psychological outcomes except hostility.Conclusion: Psychological disorders were prevalent among epilepsy patients, with females more likely to experience psychological problems than males. The findings call for a holistic approach in managing epilepsy to highlight and manage some exceptional psychological comorbidities.

Background This article explores the role of initial treatment on control of spasms and other epilepsies at four years in children previously treated for West syndrome. Methods The Sri Lanka Infantile Spasm Study is a prospective clinical trial evaluating response to intra-muscular adrenocorticotropic hormone (ACTH) versus oral prednisolone. A previous report documented response through age 12 months. This article provides four-year follow-up data. Results At age four years, 65 of the original 97 were available for follow-up; another 13 had died, and 19 moved and could not be contacted. Of the 65 children, 37 (57%) continued to have seizures and 28 were seizure free. In the 37 children with ongoing epilepsy, 32.4% continued to have spasms, either alone or in combination with other seizure types. The epilepsy types seen in these children were focal epilepsy (59.4%), mixed focal and generalized epilepsy (24%), generalized epilepsy only (10.8%), and uncertain (5%). The majority of those still having epilepsy (66.7%) were controlled on medication. There was no significant difference in the rate of epilepsy or spasms or their control by medication between those treated with ACTH or oral prednisolone. Spasm control at day 14 did not influence the four-year spasm or epilepsy outcome. Conclusions A majority of children diagnosed with West syndrome continued to have seizures at age four years, although most were controlled on antiseizure medication. The long-term risk of developing epilepsy or its control was the same, regardless of whether ACTH or prednisolone was initially used as treatment.

Background The description of childhood absence epilepsy (CAE) a benign self-limited generalized epilepsy has become a matter of debate. The objectives of this work were to evaluate the existence of psychiatric and cognitive impairments among patients with typical CAE and to correlate their possible relation to seizure frequency, duration of epilepsy, IISL, and valproate therapy. Methods The study was conducted on 19 typical CAE patients receiving valproate therapy, 11 newly diagnosed CAE patients not receiving AEDs, and 30 healthy control subjects (HCS). Participants were subjected to medical history taking, EEG monitoring, child behavior checklist (CBCL), Stanford Binet Intelligence Scale 5th edition, and computerized psychometric tests that assess cognitive domains and executive functions. Results The study revealed a high rate of cognitive and psychiatric dysfunctions in CAE patients. 53.3% of patients had psychiatric problems versus 16.6% in HCS. Attention deficit hyperactive disorder (ADHD) (26.6%), anxiety (16.6%), and depression (6.6%) were the most common psychiatric disorders in the patient group. Withdrawn/depressed symptoms, thought problems, social problems, and attention problems in CAE patients were significantly increased compared to HCS. At the same time, CAE patients perform worse in cognitive scales than HCS with comparable intelligent quotient (IQ) scores. Conclusion Cognitive and psychiatric impairments in typical CAE patients appear multifactorial in origin with epilepsy-related factors including the duration of epilepsy and interictal spike load (IISL).

Aim We retrospectively examined patients with childhood-onset epilepsy who transitioned from pediatric to adult care to reveal the clinical characteristics and evaluate the complexity of transitioning. Methods The subjects were 220 patients (89 males, 131 females) who had been treated at our pediatric epilepsy clinic and had transferred to adult care between 2014 and 2018 without attending a transition clinic or program. The demographic data of the patients were retrospectively analyzed. Results The ages at transition ranged from 15 to 54 years (median: 27 years old). There were 91 patients with focal epilepsies (FEs) and 129 patients with generalized epilepsies [genetic generalized epilepsy (GGE) n = 30, generalized epilepsy of various etiologies (GEv) n = 99]. A most frequent epileptic syndrome was temporal lobe epilepsy followed by frontal lobe epilepsy in FEs, GTCS only followed by juvenile myoclonic epilepsy in GGE and Lennox-Gastaut syndrome followed by Dravet syndrome in GEv. At the age of transition, a total of 77 of the 96 patients with developmental and epileptic encephalopathies (DEE) had pharmacoresistant seizures, which was positively correlated with a late transition age (P≤0.05). More than monthly seizures and greater than moderate disabilities were noted in 45% and 55% of the patients, respectively. Conclusion The patients with childhood-onset epilepsy transitioned to adult care from the hospital-based pediatric epilepsy clinic were characterized by generalized>focal epilepsy, a frequent complication of DEE, more than monthly seizures, and worse than moderate intellectual disabilities. The complication of DEE made a smooth transition difficult and delayed the transition age.

Deep brain stimulation (DBS), specifically thalamic DBS, has achieved promising results to reduce seizure severity and frequency in pharmacoresistant epilepsies, thereby establishing it for clinical use. The mechanisms of action are, however, still unknown. We evidenced the brain networks directly modulated by centromedian (CM) nucleus-DBS and responsible for clinical outcomes in a cohort of patients uniquely diagnosed with generalized pharmacoresistant epilepsy. Preoperative imaging and long-term (2–11 years) clinical data from ten generalized pharmacoresistant epilepsy patients (mean age at surgery = 30.8 ± 5.9 years, 4 female) were evaluated. Volume of tissue activated (VTA) was included as seeds to reconstruct the targeted network to thalamic DBS from diffusion and functional imaging data. CM-DBS clinical outcome improvement (> 50%) appeared in 80% of patients and was tightly related to VTAs interconnected with a reticular system network encompassing sensorimotor and supplementary motor cortices, together with cerebellum/brainstem. Despite methodological differences, both structural and functional connectomes revealed the same targeted network. Our results demonstrate that CM-DBS outcome in generalized pharmacoresistant epilepsy is highly dependent on the individual connectivity profile, involving the cerebello-thalamo-cortical circuits. The proposed framework could be implemented in future studies to refine stereotactic implantation or the parameters for individualized neuromodulation. Supplementary Information The online version contains supplementary material available at 10.1007/s13311-021-01057-y.

Focal cortical dysplasia (FCD) is one of the most common causes in developing pharmacoresistant epilepsy. We present the clinical case of the patient with generalized seizures. Routine electroencephalography (EEG) data registered diffuse epileptiform activity that allowed to diagnose genetic eneralized epilepsy and pharmacoresistant course of seizures.After performing magnetic resonance imaging using the epileptological program and video-EEG-monitoring, the diagnosis was revised: structural focal epilepsy with seizures with focal onset with oroalimentary, gesture automatisms in the right hand, bilateral tonic-clonic, uncompensated by levetiracetam monotherapy (1500 mg/day). Background disease: congenital malformation of the brain: FCD in the basal parts of the left temporal lobe. Lacosamide was added to the therapy in the drug dose 300 mg/day, and the frequency of epileptic seizures decreased. Differential diagnosis between genetic generalized epilepsy and structural epilepsy with FCD usually poses no obstacles. However, in some cases, structural epilepsy occurs under the “mask” of generalized epilepsy. Hence, this clinical case demonstrates the importance of diagnostic measures in the differential diagnostics of various forms of epilepsy to determine further tactics of patient management.

Perioral myoclonia with absences (POMA) is not recognized as a unique electro-clinical syndrome and studies suggest its inclusion under the genetic generalized epilepsy (GGE) spectrum. The aim of this study was to explore the prevalence and electro-clinical homogeneity of this disorder in an epilepsy monitoring unit. Between 2013 and 2019, among drug-resistant epilepsy patients who were referred for video-telemetry, those diagnosed with POMA based on the presence of documented absences with prominently observed peri-oral muscular contractions accompanied by generalized EEG features were included. Among 62 patients who were diagnosed with absence epilepsy, five finally met the criteria for POMA (8.1%) with late childhood or adolescent onset of epilepsy. Four (80%) had a referral diagnosis of focal epilepsy based on historical focal features with exacerbation of seizures on oxcarbazepine. All five patients demonstrated brief absences with orbicularis oris muscle contractions accompanied by subtle focal phenomenology. One patient had concurrent axial-appendicular myoclonic jerks precipitated by hyperventilation. While four patients had strikingly identical interictal and ictal characteristics of typical absence epilepsy, one patient demonstrated additional atypical generalized polyspike discharges without a "dart-dome" morphology. Therapeutic response to introduction of sodium valproate was noted in all five patients. Features that were not consistent with the diagnosis were apparent in one patient who was re-classified with combined focal and generalized epilepsy. Differentiating aspects in this patient included multifocal discharges, background slowing, fast-recruiting ictal rhythms and valproate resistance. This is one of the largest case series of POMA. This entity, which falls under the spectrum of GGE, remains under-diagnosed and its distinctive electro-clinical features need to be recorded in order to prevent misclassification as focal epilepsy of probable opercular origin. Background-slowing, atypical ictal rhythms and valproate unresponsiveness are not consistent with the diagnosis of this unique absence epilepsy. [Published with video sequences].

Objectives Juvenile myoclonic epilepsy (JME) is the most prevalent form of generalized epilepsy in the community. Though the response to medication is good in most patients, long-term medication usage may lead to poor compliance, side effects, and other epilepsy-related social issues. The aim of this study was to describe the demography, clinical features, and therapeutic response in patients with JME who have had at least 10 years of duration of epilepsy. Materials and Methods A retrospective study of 56 patients (M:F=26:30; mean age: 14.5 ± 5.1 years) with JME attending neurological services in a tertiary care neurological center in South India with more than 10 years disease duration was performed. Results All patients had myoclonic jerks, 94% had generalized tonic–clonic seizure, and only 7.1% had features of absence seizures. Seizures were controlled in 60% of cases at the end of 10 years of epilepsy. Thirty-eight patients (67.8%) were on valproate. Control of seizures at the end of the first and fifth years of epilepsy, frequent myoclonic jerks at the onset, and treatment with valproate in the first year of disease resulted in controlled seizures at the end of 10 years. No patient was off medications at the end of 10 years of epilepsy or at the last follow-up. Conclusion About 40% of our patients continued to have seizures even 10 years after the onset of epilepsy. Regular and long-term medication may be required in JME. Early control of seizures, response to valproate, and frequent myoclonia at onset were found to confer better prognosis.

Introduction. Video-electroencephalography (EEG) monitoring (VEEGM) is an indispensable functional method in epileptology. However, virtually no trials on assessing efficacy of antiepileptic drugs (AED) by using VEEGM are available.Objective: to improve efficacy of EEG-diagnostics and evaluate the epileptiform activity index (EAI) in newly-diagnosed idiopathic generalized epilepsy in adult patients receiving alproic acid and levetiracetam.Material and methods. T here w ere e nrolled 130 p atients: 6 0 (46.2%) m ales a nd 7 0 (53.8%) f emales w ith n ewlydiagnosedidiopathic generalized epilepsy (IGE), aged 22.51±8.9 years. All patients underwent VEEGM with quantitative EAI analysis at baseline visit and 1 3, 6 and 12 months later after treatment. Each seizure episode developed during the VEEGM study were assessed for type, time of seizure onset, relation to wake-sleep cycle, duration, ictal EEG pattern followed by diagnosing epileptic syndrome. Valproic acid and levetiracetam were used for initial therapy in groups per 65 patients in each. Treatment efficacy was assessed using parameters such as retention on therapy, absence of seizures, decrease of seizure frequency by >50%, decrease of seizure frequency by Results. It was found that seizures during baseline VEEGM were recorded in 43.1% (n=56) patients, who were assigned to group 1, whereas remaining 74 (56.9%) patients were assigned to group 2. EAI was significantly higher in patients with seizures recoded at baseline VEEGM, compared to those lacking seizure episodes during initial VEEGM (pConclusion. Long-term VEEGM allows unbiased assessment of treatment dynamics based on EAI analysis. The first 6 months of initial treatment titration in represent most crucial period for patients with newly-diagnosed IGE.

The increasing incidence of epilepsy has led to the need for automatic systems that can provide accurate diagnoses in order to improve the life quality of people suffering from this neurological disorder. This paper proposes a method to automatically classify epilepsy types using EEG recordings from two databases. This approach uses the spectral power density of intrinsic mode functions (IMFs) that are obtained through the empirical mode decomposition (EMD) of EEG signals. The spectral power density of IMFs has been applied as features for the classification of focal and non-focal, as well as of focal and generalized EEG signals. The data are then classified using K-nearest Neighbor (KNN) and Naïve Bayes (NB) classifiers. The focal and non-focal data were classified with high accuracy, with KNN and NB classifiers achieving a maximum classification rate of 99.90% and 99.80%, respectively. Focal and generalized epilepsy data were classified with high rates of accuracy during wakefulness and sleep stages, with KNN achieving a maximum rate of 99.49% and NB achieving 99.20%. This method shows significant improvements in the classification of EEG signals in epilepsy compared to previous studies. It could potentially aid clinical decisions for epilepsy patients.

Epilepsy treatment is challenging because of multiple impediments like lack of efficacy of monotherapy, adverse drug reactions, and different comorbidities. Add-on therapy to first-line antiepileptics may be the option to overcome therapeutic hurdles. The present randomized, double-blind, add-on placebo-controlled clinical trial was conducted to evaluate the effect of add-on melatonin in the treatment of generalized epilepsy with generalized onset motor seizure in adults. The control group (n = 52) received add-on placebo, and the test group (n = 52) received add-on melatonin (3 mg/day) with valproate (20 mg/kg in two divided doses). Clinical evaluation of seizure frequency, Chalfont-National Hospital seizure severity scale (NHS3), Pittsburgh sleep quality index (PSQI), quality of life in epilepsy inventory, Epworth sleepiness scale (ESS), and biochemical estimation of serum neuron-specific enolase (NSE) and glutathione reductase were done at baseline and compared with follow-up at 8 weeks. Among 104 patients randomized [mean (SD) age of 27.6 (11.5); 84 (80.8%) male], 88 (84.6%) completed the trial. The responder rate and seizure-free rate in the test group were significantly (p = 0.006 and 0.034) higher than the control group. There was a significantly higher reduction in the frequency of seizures (p = 0.016) and NHS3 (-2.39; 95%CI: -4.56 to -0.21; p = 0.032) in the test group compared to the control group. Similarly, improvement in PSQI (-1.40; 95%CI: -2.64 to -0.15; p = 0.029) was significantly better in the test group. There was no significant difference in the change in ESS (p = 0.621) and quality of life scoring (p = 0.456) between the study groups. The decrease in serum NSE was significantly higher with the test group compared to the control group (-2.01; 95% CI: -3.74 to -0.27; p = 0.024). Add-on melatonin increased serum glutathione reductase significantly (p = 0.038), but there was no significant difference between the groups (p = 0.685). Add-on melatonin with valproate for generalized epilepsy with generalized onset motor seizures in adults can achieve a significantly better clinical outcome by reducing the seizure frequency, severity and attaining a better seizure-free rate in comparison to the control group.

As early in 1935, Gibbs et al described electroencephalogram (EEG) features of large slow waves seen in “petit mal” seizures and change in background rhythm to a higher frequency, greater amplitude pattern in “grand mal” seizures. Studies have shown many typical EEG features in focal onset as well as generalized epilepsies.2 3 It is usually easy to delineate focal epilepsy cases when EEG onset of seizures is clear as seen in Benign focal epileptiform discharges of childhood.4 However, it is not uncommon to see cases where epileptiform discharges are not very clear. For example, there can be secondary bilateral synchrony or generalized onset of epileptiform discharges in some cases of focal epilepsy5 and nongeneralized EEG features is cases of generalized epilepsy like absence seizures.6 The awareness of occurrence of focal clinical and EEG features in generalized epilepsy is particularly important to help to select appropriate AEDs and also to avoid inappropriate consideration for epilepsy surgery.7 Lüders et al8 have shown that multiple factors like electroclinical seizure evolution, neuroimaging (both functional and anatomical) have to be analyzed in depth before defining an epileptic syndrome. Here, we are providing few examples of different situations where it is still mysterious to figure out focal onset seizures with secondary generalization versus primary generalized epilepsy.

Neuroimaging plays an increasingly crucial role in delineating the pathophysiology, and guiding the evaluation, management and monitoring of epilepsy. Imaging contributes to adequately categorizing seizure/epilepsy types in complex clinical situations by demonstrating anatomical and functional changes associated with seizure activity. This article reviews the current status of multimodality neuroimaging in the pediatric population, including focal lesions which may result in focal epileptic findings, focal structural abnormalities that may manifest as generalized epileptiform discharges, and generalized epilepsy without evidence of detectable focal abnormalities.

For a subset of children with medically intractable epilepsy, surgery may provide the best chances of seizure freedom. Whereas the indications for epilepsy surgery are commonly thought to be limited to patients with focal epileptogenic foci, modern imaging and surgical interventions frequently permit successful surgical treatment of generalized epilepsy. Resection continues to be the only potentially curative intervention; however, the advent of various neuromodulation interventions provides an effective palliative strategy for generalized or persistent seizures. Although the risks and benefits vary greatly by type and extent of intervention, the seizure outcomes appear to be uniformly favorable. Advances in both resective and nonresective surgical interventions provide promise for improved seizure freedom, function, and quality of life. This review summarizes the current trends and recent advancements in pediatric epilepsy surgery from diagnostic workup and indications through surgical interventions and postoperative outcomes.

Objectives: To assess the etiology of status epilepticus (SE) among the pediatric patients of a tertiary center in Jeddah, Kingdom of Saudi Arabia (KSA). Methods: Data from 88 cases was obtained retrospectively from 2006 to 2017 from King Abdulaziz University Hospital (KAUH). Patients aged between 28 days and 14 years with the symptoms of SE were selected for this study. Results: The data show that the proportions of SE etiologies were 30.5% for febrile seizure, 11.9% for electrolytes imbalance, 8.5% for hydrocephalus, 6.8% for CNS infections, and 6.8% for neoplasm. The other etiologies of SE were trauma, fever, intractable epilepsy, cerebrovascular accident, hemorrhagic stroke, etc. There were no clear etiologies in 8 cases. Most of the patients were not of Saudi origin (64.3%), boys (67.8%), and had generalized epilepsy types (91.8%), and 58.6% of the patients complied with epilepsy medications. Conclusion: The most prevalent etiology of convulsive status epilepticus was a febrile seizure, followed by electrolyte imbalance and hydrocephalus. However, a nationwide study in KSA must be conducted to determine the major etiologies of SE for its effective management and prevention. Educating families and patients regarding antiepileptic drugs is necessary.

Objective ‘First seizure’ clinics (FSCs) aim to achieve early expert assessment for individuals with possible new‐onset epilepsy. These clinics also have substantial potential for research into epilepsy evolution, outcomes, and costs. However, a paucity of FSCs details has implications for interpretation and utilization of this research. Methods We reviewed investigation findings over 11 years (2000‐2010) from two established independent FSCs at Austin Health (AH) and Royal Melbourne Hospital (RMH), Australia. These adult clinics are in major public hospitals and operate with similar levels of expertise. Organizational differences include screening and dedicated administration at AH. Included were N = 1555 patients diagnosed with new‐onset unprovoked seizures/epilepsy (AH n = 901, RMH n = 654). Protocol‐driven interviews and investigations had been recorded prospectively and were extracted from medical records for study. Results Median patient age was 37 (IQR 26‐52, range 18‐94) years (AH 34 vs RMH 42 years; P

Background: Anterior Corpus Callosotomy is a palliative treatment for drug-resistant generalized or multifocal epilepsy patients where focus excision is not an option for management. Callosotomy prevents propagation of epileptic discharge from one cerebral hemisphere to the other. Objective: To describe Al-Azhar University Hospitals experience and clinical outcome of Anterior Corpus Callosotomy for management of drug-resistant generalized epilepsy patients as an inexpensive palliative method. Patients and Methods: In this study, there are 15 patients admitted to Neurosurgery Department in Al-Azhar University Hospitals with drug-resistant generalized epilepsy. These patients were not candidates for lesionectomy. They were managed by anterior two thirds Corpus Callosotomy between February 2017 and December 2019. They were followed at outpatient clinic for at least 14 months. Clinical outcome regarding seizure control was assessed using Engel classification. Results: All 15 patients in this study underwent anterior two thirds corpus callosotomy and followed for at least 14 months. The post-operative improvement of seizure frequency has been evaluated using Engel outcome scale with 12 patients (80%) of the patients becoming Engel class II and 3 patients (20%) becoming Engel class III. Only 3 patients (20%) had minor transient postoperative complications; one patient (6.67%) had contra-lateral lower limb heaviness Grade 4 which was transient, one patient (6.67%) had contra-lateral lower limb Jacksonian focal fits and one patient (6.67%) had behavioral changes for one month. Conclusion: Corpus callosotomy is a palliative procedure and inexpensive method for management of patients with intractable focal with generalization and generalized drug-resistant epilepsy who are not suitable for resective surgery and with good outcome.

Purpose Eating epilepsy was previously known as a kind of focal reflex epilepsy. However, the development of eating-induced multiple generalized seizures and the associated EEG changes were rarely reported. Herein, we present a 13-year-old generalized epilepsy patient with eating-induced generalized seizures since the age of 5. Case presentation The 13-year-old male patient had suffered from late-onset eating-induced epileptic spasms during the meal since the age of 5. Meanwhile, he also experienced spontaneous epileptic spasms during the period of sleep. The seizure frequency and type gradually increased from 7 years of age. In addition to epileptic spasms, he started experiencing atypical absence with myoclonic jerks during the meal. Ictal EEG presented as the appearance of an irregular slow-wave mixed with generalized polyspike wave with the intake of food, and gradually evolved to bursts of generalized polyspike wave complexes. At the end of the meal, the EEG returned to normal. Nevertheless, at the age of 13, his seizure frequency increased and appeared new seizure type, and besides epileptic spasm and atypical absence, he began to experience myoclonic seizure during sleep and awaking-generalized tonic-clonic seizure in the morning. In this period he started taking valproic acid, topiramate and clonazepam, and his seizure frequency was reduced. Conclusion In conclusion, this case demonstrated the variability of eating induced multiple generalized seizure types, and eight years follow-up also indicates that generalized epilepsy progressed with age. The EEG and clinical changes of our patient contribute to a better understanding of the electro-clinical features of eating-induced multiple generalized seizures and the course of generalized epilepsy with such seizures.

Introduction: The epilepsy classification in under developed countries faces many difficulties in reporting, work-up and management strategies. Exploring local practice in general hospitals will positively add to the welfare of patients with epilepsy. The objectives of this study were to assess the current medical practice in epilepsy work up and to study the selection of AEDs as per ILAE guidelines. Methods: This was a cross sectional-retrospective hospital based study, conducted between April and September 2016 in Omdurman Teaching Hospital, Khartoum, Sudan. Patients aged 18 years old and above were enrolled. Epilepsy was defined as having at least two non-provoked seizures in the least 6 months in a patient who was assessed by clinical review and electroencephalogram (EEG). Epilepsy was classified as generalized, focal or unclassified. Medications refer to all internationally licensed antiepileptic medications (AEDs) in 2016. Results: One hundred adult Sudanese patients were enrolled for this study. The most common event described during the ictal phase was tongue biting in 50% of participants followed by body stiffness in 46%. Epilepsy was classified as generalized in 84%, focal in 11% and unclassified in 5% patients. In generalized epilepsy, the MRI detected 23.3% abnormal findings higher than the CT which detected 14.8% (4/27), p value = 0.032. In focal epilepsy, the CT detected 75% abnormal findings higher than the MRI which detected 33.3%, p value = 0.02. The AEDs used were as follows: Carbamazepine (CBZ) 48%, Na valproate (VP) 33%, Lamotrigine (LMT) 2%, Levetricetan (LVT) 1%, CBZ + VP 14% and CBZ + Oxcarbazepine (OXC) 2%. Conclusion: The current medical practice in Omdurman teaching hospital should be modified to match the international league against epilepsy (ILAE) guidelines in workup, management, AEDs selection and classification of epilepsy.

Objectives To determine the clinical features and anti-seizure medication (ASM) strategies associated with an unanticipated substantial improvement in seizure control in patients with drug-resistant epilepsy (DRE). Methods This retrospective analysis of patients attending a tertiary care epilepsy clinic between 2008 and 2017 identified all patients with active DRE (at least 1 seizure per month for 6 months, despite treatment with 2 different ASMs). All treatment interventions were recorded from when DRE was first identified to the end of the study. The primary end points were seizure freedom or meaningful reduction in seizure frequency (greater than 75 %) sustained for at least 12 months after a treatment intervention. Results Three hundred and twenty-two patients were included in the analysis. Overall, 10 % became seizure free following ASM adjustment and an additional 10 % had a greater than 75 % improvement in seizure control (median follow-up, 4 years). An ASM introduction was ten times more likely than an ASM dose increase to improve seizure control. Combined focal and generalized epilepsy, intellectual disability and prior treatment with more than 5 ASMs were more frequently observed in those with continued pharmacoresistance. ASM responders were more likely to have primary generalized epilepsy. Rational polytherapy (combining ASMs with different mechanisms of action) was almost ubiquitous amongst ASMs responders (95 % taking at least 2 drugs with different mechanistic targets). Of the ASM additions that heralded improved seizure control, 85 % were maintained at submaximal doses. Conclusions This retrospective analysis of a large number of ‘real-world’ patients provides evidence to persist with ASM trials in DRE. Early rotation of ASMs if a clinical response is not observed at a substantial dose and rational ASM polytherapy may yield better clinical outcomes in patients with DRE, although a prospective study would need to be conducted to validate these findings.

We present a rare patient clinically suspected to have mixed idiopathic generalized and focal epilepsy, which was supported by BOLD pattern based on EEG-fMRI. A 37-year-old female with three types of refractory seizures starting at age six - tonic with breathing difficulties and confusion, generalized tonic-clonic, and focal with brief impairment of awareness and versive head movement, initially thought to represent atypical absences - was evaluated by EEG-fMRI. She was also shown to have three types of interictal epileptic discharges: generalized spike or polyspikes and slow waves, and left fronto-temporal and right fronto-temporal discharges. We assessed BOLD activation and deactivation for each type. For generalized patterns, the BOLD activation and deactivation were typical of that seen in primary generalized epilepsy. Whereas maximum activation for left fronto-temporal EEG patterns was observed in the left superior frontal gyrus and posterior superior temporal gyrus, maximum activation for right fronto-temporal patterns was bilateral in the right posterior middle temporal gyrus and left posterior middle temporal gyrus. The EEG-fMRI results suggested that the patient had both refractory idiopathic generalized and focal epilepsy, and not a generalized epilepsy originating from a focus.

Neurological disorders are often accompanied by impairment of memory, attention deficit that cause learning difficulties. Better understanding of learning problems in neurological patients might help to improve the quality of their life. Here we studied the character of fear-based associative learning using the standard active avoidance test in WAG/Rij rats with genetic predisposition to absence epilepsy. Electroencephalographic properties of spike-wave seizures (i.e., hallmarks of absence epilepsy) were examined at the age of 5 and 7 m. Around 24 % of rats did not express epileptic activity despite genetic predisposition. In the active avoidance test, 6 m old rats with the epileptic phenotype needed more trails to obtain the first avoidance than non-epileptic rats, but showed the same number of avoidances to reach the learning criterion. The total time of spike-wave activity positively correlated with the outcomes of avoidance performance only in subjects with severe epilepsy, but not in subjects with mild epilepsy. In order to evaluate early sensory (epigenetic) factors governing cognitive comorbidities in adult WAG/Rij rats, we performed bilateral whisker trimming during PN1-8 and PN9-16. This led to a quicker development of SWD, but did not influence cognitive abilities at the age of 6 m. In summary, epileptic WAG/Rij rats had difficulties with executive functions before the first avoidance of adverse stimulus, rather than impairment of memory after the first avoidance. Our data assume that cognitive comorbidities in epileptic WAG/Rij rats primarily may relate to executive deficit during the initial stage of avoidance test and secondary - to impairment of short-term memory. This fits well to outcomes of clinical studies in patients with generalized epilepsy.

Background and Purpose Epilepsy is a neuropsychological disorder which can lead to various cognitive deficits of varying levels. Primary generalized epilepsy is characterized by bilateral ictal electroencephalography patterns and excessive neural activity found in both hemispheres of the brain. There is dearth of research on primary generalized epilepsy in adult population. The present study investigates the visual motor and executive functioning deficits in patients with primary generalized epilepsy. Methods Study was conducted on 30 participants (n=30) divided into target and normal control group. Target group consisted of patients diagnosed with primary generalized epilepsy with minimum 5 years of illness. Bender-Gestalt test (BGT) and Wisconsin's Card Sorting Test (WCST) was administered on both the groups. Results A significant difference was found between target group and control group's performances on BGT which indicates that visual motor functioning of control group was better than target group. A significant difference in executive functioning was found in performance of epilepsy patients and non-patients on the domains of WCST. Conclusions Both executive and visuomotor functioning are significantly affected in patients of primary generalized epilepsy in adult patients.

Background: Epileptic patients suffer from multiple comorbidities resulting in a poor quality of life. Depression is one of the most important and often under-recognized comorbidity among epileptic patients. We aimed to study the prevalence of depression among epileptic adults and also tried to identify potential risk factors predisposing to depression in epilepsy. Materials and Methods: This was a cross-sectional study on the consecutive epilepsy patients (>18 years) attending our Neurology department between January-2018 to December-2018. All the demographic and clinical details were recorded in the predefined study proforma. Patient Health Questionnaire-9(PHQ-9) was used to screen for depression among epileptic patients. Statistical analysis was done using SPSS software and risk factors associated with depression were considered significant if the p-value 0.05. Results: A total of 300epileptic adults were enrolled in this study. The mean age of the study subjects was 38-years (range:18-85 years) with a male predominance (M:F-1.7:1). Majority in the epileptic cohort (62%) had secondary education and 14% had primary education. Only 3%(8/300) were postgraduates. Almost half of these epileptic patients were unmarried and one third remained unemployed. Eighty-five percent of the study patients had generalized epilepsy while the rest 15%had focal epilepsy. The mean PHQ score was 8.76 (SD-5.99; Range:0-24) with more than two-thirds of the patient (69%) screened positive for depression. Age>50-years (p-0.004), frequent breakthrough seizures(p-0.000), patients on polytherapy(p-0.000), and poor compliance to anticonvulsants (p-0.000) were found to be significant risk factors for depression in epileptic patients. Conclusion: Depression is common in epilepsy and awareness among clinicians about this comorbidity is important. Active screening for depression in epilepsy can lead to early interventions resulting in a better quality of life. Keywords: Depression

Background Stereotactic radiosurgery (SRS) offers a noninvasive technique for division of the corpus callosum, which can confer improved seizure control to patients suffering from frequent atonic seizures due to rapid interhemispheric generalization. This noninvasive approach is well-suited for use in a palliative intervention for improved seizure control in this patient population. To our knowledge, this is the first report of radiosurgical completion corpus callosotomy in an adult in the United States. Case Description A 20-year-old ambidextrous nonverbal man with a history of refractory generalized epilepsy status post open anterior corpus callosotomy at age 10 years, Lennox-Gastaut syndrome, and autism presented after 2 years of incremental, progressive deterioration in seizure control and behavior including 1 year. The family decided to pursue SRS corpus callosotomy. Under general anesthesia, a volume of interest encompassing a full midsagittal plane of the corpus callosum was defined to deliver 60 Gy to the 50% isodose line fully encompassing the target. Gamma Knife was used with 2 isocenters at 90° and 1 at 110° and isodose lines of 60, 20, and 12 Gy. Treatment was carried out without difficulty or complications while the patient remained under close monitoring. The patient was discharged the next day with a 2-week taper of dexamethasone. Conclusions Eight months postradiosurgical corpus callosotomy, the patient is free of atonic seizures and is ambulatory. In carefully selected cases and with protective radiosurgical planning, SRS for completion corpus callosotomy represents an effective option for refractory seizure control.

Epilepsy is a common brain network disorder associated with disrupted large‐scale excitatory and inhibitory neural interactions. Recent resting‐state fMRI evidence indicates that global signal (GS) fluctuations that have commonly been ignored are linked to neural activity. However, the mechanisms underlying the altered global pattern of fMRI spontaneous fluctuations in epilepsy remain unclear. Here, we quantified GS topography using beta weights obtained from a multiple regression model in a large group of epilepsy with different subtypes (98 focal temporal epilepsy; 116 generalized epilepsy) and healthy population (n = 151). We revealed that the nonuniformly distributed GS topography across association and sensory areas in healthy controls was significantly shifted in patients. Particularly, such shifts of GS topography disturbances were more widespread and bilaterally distributed in the midbrain, cerebellum, visual cortex, and medial and orbital cortex in generalized epilepsy, whereas in focal temporal epilepsy, these networks spread beyond the temporal areas but mainly remain lateralized. Moreover, we found that these abnormal GS topography patterns were likely to evolve over the course of a longer epilepsy disease. Our study demonstrates that epileptic processes can potentially affect global excitation/inhibition balance and shift the normal GS topological distribution. These progressive topographical GS disturbances in subcortical–cortical networks may underlie pathophysiological mechanisms of global fluctuations in human epilepsy., This study demonstrated spatial shifts of non‐uniform GS topography across higher‐order prefrontal cortex and sensory areas in generalized and focal epilepsy. We found that these abnormal GS topography patterns were likely to evolve over the course of a longer disease. Our findings have potential implications for understanding the neuronal mechanisms of disrupted global excitation/inhibition balance in epilepsy.

Purpose The aim of this study was to investigate the possible effects of single-nucleotide polymorphisms (SNPs) within SLC1A1, SLC6A1, FAM131B, GPLD1, F2, GABRG2, GABRA1, and CACNG5 genes on response to anti-epileptic drugs (AEDs) and the genetic predisposition of epilepsy in Jordanian patients. Patients and methods A total of 299 healthy individuals and 296 pediatric patients from the Jordanian population were recruited. Blood samples are collected, and genotyping was performed using a custom platform array analysis. Results The SLC1A1 rs10815018 and FAM131B rs4236482 polymorphisms found to be associated with epilepsy susceptibility. Moreover, SLC1A1 rs10815018 and GPLD1 rs1126617 polymorphisms were associated with generalized epilepsy (GE), while FAM131B rs4236482 is associated with the focal phenotype. Regarding the therapeutic response, the genetic polymorphisms of FAM131B rs4236482, GABRA1 rs2279020, and CACNG5 rs740805 are conferred poor response (resistance) to AEDs. There was no linkage of GLPD1 haplotypes to epilepsy, its subtypes, and treatment responsiveness. Conclusion Our findings suggested that SLC1A1, FAM131B, and GPLD1 polymorphisms increasing the risk of generating epilepsy, while FAM131B, GABRA1, and CACNG5 variants may play a role in predicting drug response in patients with epilepsy (PWE).

Laith N AL-Eitan,1,2 Islam M Al-Dalala,3 Afrah K Elshammari,4 Wael H Khreisat,4 Aseel F Nimiri,4 Adan H Alnaamneh,1 Hanan A Aljamal,1 Mansour A Alghamdi5,6 1Department of Applied Biological Sciences, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Blood Banking, King Hussein Medical Centre, Royal Medical Services, Amman, Jordan; 4Queen Rania Hospital for Children, King Hussein Medical Center, Royal Medical Services, Amman, Jordan; 5Department of Anatomy, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia; 6Genomics and Personalized Medicine Unit, College of Medicine, King Khalid University, Abha 61421, Saudi ArabiaCorrespondence: Laith N AL-EitanJordan University of Science and Technology, P.O. Box 3030, Irbid 22110, JordanTel +962-2-7201000 Ext.:23464Fax +962-2-7201071Email lneitan@just.eduPurpose: The aim of this study was to investigate the possible effects of single-nucleotide polymorphisms (SNPs) within SLC1A1, SLC6A1, FAM131B, GPLD1, F2, GABRG2, GABRA1, and CACNG5 genes on response to anti-epileptic drugs (AEDs) and the genetic predisposition of epilepsy in Jordanian patients.Patients and Methods: A total of 299 healthy individuals and 296 pediatric patients from the Jordanian population were recruited. Blood samples are collected, and genotyping was performed using a custom platform array analysis.Results: The SLC1A1 rs10815018 and FAM131B rs4236482 polymorphisms found to be associated with epilepsy susceptibility. Moreover, SLC1A1 rs10815018 and GPLD1 rs1126617 polymorphisms were associated with generalized epilepsy (GE), while FAM131B rs4236482 is associated with the focal phenotype. Regarding the therapeutic response, the genetic polymorphisms of FAM131B rs4236482, GABRA1 rs2279020, and CACNG5 rs740805 are conferred poor response (resistance) to AEDs. There was no linkage of GLPD1 haplotypes to epilepsy, its subtypes, and treatment responsiveness.Conclusion: Our findings suggested that SLC1A1, FAM131B, and GPLD1 polymorphisms increasing the risk of generating epilepsy, while FAM131B, GABRA1, and CACNG5 variants may play a role in predicting drug response in patients with epilepsy (PWE).Keywords: pharmacogenetics, anti-epileptic drugs, generalized epilepsy, focal epilepsy, pharmacotherapy, Jordan

Background Generalized epilepsy and tremor phenotypes have been reported in some genetic disorders. Among them benign adult familial myoclonus epilepsy (BAFME) has been confirmed as a clearly defined clinical and genetic entity. On the other hand, non-progressive tremor and generalized epilepsy phenotypes have also been reported in patients with DHDDS variants. Case presentation. We report on a long term follow-up of patient with de novo missense variant of DHDDS, who revealed non progressive nature. This 18-year-old woman presented non-progressive tremor since her early infancy. She had rare seizures. Her tremor was considered as cortical myoclonic tremor with giant somatosensory evoked potentials. Conclusion In patients with early onset, non-progressive tremor and rare generalized epilepsy phenotypes, DHDDS variants may be considered in the genetic differential diagnosis.

The photoparoxysmal response (PPR) is defined as the occurrence of generalized spike, spike-wave or polyspike-wave discharges consistently elicited by intermittent photic stimulation (IPS). PPR is not well studied in Sub-Saharan African people. We prospectively studied the epidemiological, clinical, and EEG characteristics of PPR among consecutive patients recorded at the clinical neurophysiology unit of Fann University Hospital (Dakar, Senegal). Among 6,808 EEG recordings including 3,065 pathological EEGs, we collected 56 EEGs with PPR (0.8% of all recorded EEGs and 1.8% of anormal EEGs), from 31 women and 25 men (sex ratio: 0.8). The mean age was 13.3 years (range: 8 months to 59 years). The peak of photosensitivity was found in the range of 6 to 10 years. Of the PPR cases, 12 had clinical manifestations during IPS. Generalized epilepsy was diagnosed in 23 (41%) patients and 18 (32%) had focal epilepsies. The most epileptogenic stimulation frequencies were between 12 and 24 Hz (range: 1-28 Hz). PPR were mainly triggered during eye closure (64%), and 41 patients (73% of PPR cases) were classified as Type 4 (Waltz classification). Our results confirm lower rates of photosensitivity in African Sub-Saharan people compared with others. Although the current data do not support a role of short-term ambient light levels, subject to consistent data from larger cohorts, it may be interesting to study the probable epigenetic-mediated protective role of sunshine against photosensitivity.

We report on the seizure frequency and attention outcome during thalamic centromedian stimulation (CM-DBS) in patients with refractory generalized epilepsy (GE).Twenty consecutive patients with GE who were submitted to CM-DBS and had at least one year of follow-up were prospectively studied. The CM was targeted bilaterally. Stimulation intensity was ramped up (bipolar, continuous, 130 Hz; 300μsec) until 4.5 V or until side effects developed. Contacts` position was determined on postoperative volumetric MRI scans. Attention was qualitatively evaluated using the SNAP-IV (Swanson, Nolan, and Pelham) questionnaire. Patients were considered responders during CM-DBS if an at least 50% seizure frequency reduction was obtained compared to baseline.Median age was 15.5 years (13 males). Median follow-up time was 2.55 years. EEG disclosed generalized spike-and wave discharges in all patients. MRI was normal in 10 patients, showed diffuse atrophy in 6 patients, and showed abnormalities in 4 patients (3 patients had bilateral cortical development abnormalities and one had unilateral hemispheric atrophy). Patients presented with daily multiple seizure types (8 to 66 per day; median: 37), including tonic, atonic, myoclonic, atypical absence and generalized tonic-clonic seizures. Mean DBS intensity was 4.3 V. An insertional effect was noted in 14 patients. CM-DBS was able to significantly reduce the frequency of tonic (p 0.001), atypical absence seizures (p 0.001), atonic seizures (p = 0.001) and bilateral generalized tonic-clonic seizures (p = 0.004). One patient became seizure-free. Ninety percent of the patients were considered responders (50% seizure frequency reduction). All patients showed some improvement in attention. The mean number of items in which improvement was noted in the SNAP-IV questionnaire was 4.8. There was a significant relationship between overall seizure frequency reduction and improvement of attention (p = 0.033).This prospective, open label study included a large, homogeneous cohort and provided evidence on the efficacy of CM-DBS in reducing the seizure burden and increasing attention in patients with refractory generalized epilepsy.

Herpes simplex encephalitis (HSE) is a medical emergency associated with high mortality and morbidity. Definitive diagnosis is established by history, clinical examination, neuroimaging studies, supportive electroencephalogram (EEG) findings, and cerebrospinal fluid (CSF) analysis. A 7-year-old Malay girl with known case of right hemiplegia secondary to herpes encephalitis presented to the neuropediatric ward, in General Hospital with refractory seizure. She had a moderate learning disability and diagnosed as right hemiparesis secondary to herpes encephalitis complicated with epilepsy. She was planned for the positron emission tomography (PET) scan and to undergo operation if PET scan was feasible (Hemispherectomy). However, the patient refused for operation. Prompt clinical recognition is important in the HSE to prevent progressive brain tissue damage, haemorrhagic changes, and worsening of the encephalitis. Diagnosis is usually confirmed through an extensive evaluation, including a thorough clinical examination with attention to findings on mental status changes, cerebrospinal fluid (CSF) analysis, electroencephalogram (EEG) testing and findings on neuroimaging. Once HSE is suspected, high-dose acyclovir should be started immediately before lumbar puncture (LP), and only stopped once a definitive alternate diagnosis has been established. This case is reported because the patient has generalized epilepsy with right hemiparesis secondary to herpes encephalitis. Herpes encephalitis with right hemiparesis cases are quite rare.

Background.We have accumulated extensive experience in the use of lamotrigine in patients with epilepsy; its mechanism of action, effectiveness, safety, and tolerability are well known. The results of numerous studies indicate its high efficacy and potentially better tolerabilitycompared to other drugs in the treatment of a wide range of epilepsy forms and epileptic syndromes (focal and generalized seizures). Thesecharacteristics of lamotrigine determined its priority administration as initial or alternative monotherapy in women with epilepsy.Objective:to review efficacy and tolerability of Seizar in patients with various forms of epilepsy based on long-term experience of using thisdrug in our center.Materials and methods.We analyzed therapeutic effects of Seizar in 22 patients aged between 3 and 34 years (mean age 15.3 years) treatedin Svt. Luka’s Institute of Child Neurology and Epilepsy. The sample included 8 adults and 14 children (under 18 years of age), including6 children aged from 3 to 12 years. Ten patients were male and twelve patients were female.Study participants were diagnosed with the following forms of epilepsy: idiopathic (genetic) generalized epilepsy (n = 9), idiopathic (genetic)focal epilepsy (n = 2), focal epilepsy of unknown etiology (n = 1), structural and probably structural focal epilepsy (n = 4), genetic and probably genetic epileptic encephalopathies (n = 6).Seizar was used as monotherapy in 9 patients and as an additional drug in 13 patients. Children aged 3 to 12 years received Seizar only as an additional drug in polytherapy (n = 6); patients aged between 12 and 18 years received it either as monotherapy (n = 4) or in addition to othertreatments (n = 4). Five adults received Seizar alone, whereas 3 adults received it as a part of polytherapy. In total, 9 participants receivedmonotherapy with Seizar and 13 participants received Seizar with other treatments. In two patients, combination therapy was successfullychanged to monotherapy with Seizar (they are currently receiving it as monotherapy). Seizar dose varied between 75 and 400 mg per daygiven in 1–2 portions. Importantly, prolonged action of Seizar and convenient dose of 200 mg per tablet allows its administration once a day.Currently, 4 patients (one 15-year-old girl and 3 adults) are receiving Seizar once a day (3 of them at bedtime and one of them in the morning).The follow-up period was between 4 months and 5 years.Results.Therapeutic remission with Seizar was achieved in 7 out of 22 patients (31.8 %); 10 patients (45.5 %) demonstrated at least 50 %reduction in seizure frequency; 5 patients (22,7 %) had no effect. None of the participants had seizure aggravation. Seizar was ceased in 2 patients(9 %) due to its inefficacy.Therefore, therapeutic effect (clinical remission or more than 50 % reduction in seizure frequency) was achieved in 17 out of 22 patients(77 %), which is a very good result considering the fact that all participants had severe forms of epilepsy.Seizar was most effective in patients with idiopathic epilepsy (≥50 % reduction in seizure frequency/clinical remission was observed in 9 out11 patients (81 %), including 5 patients receiving Seizar as monotherapy) and structural focal epilepsy or focal epilepsy of unknown etiology(≥50 % reduction in seizure frequency/clinical remission was observed in 4 out of 5 patients (80 %)). Positive effect was achieved in 4 outof 6 participants (66 %) with epileptic encephalopathies; this group included patients with extremely severe forms of epilepsy and resistanceto many antiepileptic drugs (AED).Seizar was well tolerated by patients: 72.8 % of them had no side effect and only 5 patients (22.7 %) had transient disorders of the centralnervous system and gastrointestinal tract (nausea, loss of appetite) that did not require discontinuation of the drug. Only one patient (4.5 %)required its cessation. In 4 female patients of reproductive age, Seizar was used to optimize therapy as a part of preparation for pregnancy.High efficacy and good tolerability of Seizar are confirmed by patients’ adherence to treatment: 19 of 22 patients included into the study (86 %)still continue to receive Seizar (the duration of follow-up period varies between 4 months and 5 years). Only 3 participants required drugdiscontinuation due to skin rash (n = 1; 4.5 %) and low efficacy (n = 2; 9 %).Conclusions.Over the past decades, clinicians have accumulated evidence of good safety and tolerability of lamotrigine, including such aspectsas its positive effect on cognitive functions, behavior, mood (including that in children), and particularly good safety profile in women of reproductive age.Lamotrigine and levetiracetam are currently considered the safest AED for women of reproductive age in terms of their impact on the neuroendocrine system of women, fertility, and potential teratogenic effect. The number of pregnancies among women receiving lamotrigine is significantly higher than that among women receiving other AED. Thus, the safety of lamotrigine during pregnancy (as well as other aspects of itssafety and tolerability) are studied much better compared to other AED. It is very important that lamotrigine is considered a safe drug.

Transition from pediatric to adult health care is a time of high risk for adolescents and young adults (AYAs) with epilepsy. Our aims are to examine patient, caregiver, and provider perceptions of transition readiness and the influence of patient-provider alliance in the context of transition readiness. Our cross-sectional study included 82 AYAs with epilepsy prior to transition. Patients, caregivers, and providers completed questionnaires (e.g., transition readiness and working alliance). Statistical analyses included independent samples and paired t-tests. Participants were 17.3 ± 2.8 years on average, 54% were females, 84% were White (non-Hispanic), and 38% had generalized epilepsy. Caregivers reported significantly higher transition readiness than their AYAs (t (72) = −10.6, p

Epilepsy is found to be standout amongst the most wellknown and unending neurological issue portrayed by irregular recurring and extreme neuronal discharge within the central nervous system. Objective: The study was an endeavor to find out the relationship of depression and perception of stigma in patients with different types of epilepsy where, stigma go about as a covariate of depression in epilepsy. Methods: A co-relational study was conducted on 100 epileptic patients, chosen from the indoor and outdoor departments of Pakistan Ordinance Factories (POF) Hospital in Wah Cantt, Pakistan Institute of Medical Sciences (PIMS), Islamabad and Benazir Bhutto Shaheed Hospital in Rawalpindi. In order to measure the feelings of stigma and depression in epileptic patients Urdu translation of stigma of epilepsy scale by Jacoby, 1994 was used combined with Siddique Shah Depression scale (SSDS) (1992). Results: Patients with generalized epilepsy score highmon both depression and Stigma scale (M=98.26, SD=28.26), (M=2.60, SD=.66) with most astounding score on subscale hopelessness of depression. Likewise, results demonstrated that stigmatization go about as a covariant of depression (p < .01), finally when impact of stigmatization was controlled noteworthy impact of three distinctive epilepsy types was found on scores of depression (p < .001). A positive relationship between depression and stigma was observed. Conclusions: Higher levels of depression and feelings of stigma were reported by generalized epileptic patients where feelings of stigma were responsible for the development of depression in epileptic patients.