Considering both age-related and spontaneous fluctuation in seizure frequency and the unknown impact of many AEDs or KD on cognition, our data may help defining realistic treatment goals and avoiding overtreatment in patients with CDKL5 mutations. There is a strong need to develop new treatment strategies for patients with this rare mutation.

SUMMARYPurpose: Psychogenic nonepileptic seizure (PNES) is an important differential diagnostic problem in patients with or without epilepsy. There are many studies that have analyzed PNES in adults; currently, however, there is no systematic assessment of purely childhood PNES semiology. Our study based on a large pediatric video-electroencephalography (EEG) monitoring (VEM) cohort, provides a detailed analysis of childhood PNES and assesses the usability of the current classification system described in adults. Methods: Medical and video-EEG records of 568 consecutive children (younger than 18 years) who underwent video-EEG monitoring (VEM) at our hospital were reviewed. Aura, type of movement, anatomic distribution, synchrony, symmetry, eye movement, responsiveness, vocalization, hyperventilation, vegetative and emotional signs, presence of eyewitness, and duration of the event were recorded among children with the diagnosis of PNES. We also compared our data with those of earlier adult studies. Key Findings: Seventy-five archived PNES of 27 children (21 girls; age 8-18 years) were reanalyzed. Nine children (33%) had the diagnosis of epilepsy currently or in the past. Mean age at the time of PNES onset was 11.6 (standard deviation 3.2) years. Mean duration of PNES was longer (269 s) compared to seizures of the epileptic group (83 s; p = 0.002). Eyewitnesses (mostly parents) were present in 89% of cases. Eighty percent of PNES had an abrupt start, with 68% also ending abruptly. In only 15% of events were the patients eyes closed at the beginning of the attack.Patients were unresponsive in 34%. The most frequent motor sign was tremor (25%) with the upper, rather than lower limbs more frequently involved. Pelvic thrusting was seen in only two attacks. Emotional-mostly negative-signs were observed during 32 PNES (43%). Based on Seneviratne et al.'s classification, 18 events (24%) were classified as rhythmic motor PNES, only half the frequency of that previously described in adults. No hypermotor PNES was found. The frequency of complex motor PNES (13%) and mixed PNES (4%) showed similar frequency in children as in adults. Dialeptic PNES was found more frequently among younger children. All PNES belonged to the same semiologic type in 23 patients (85%). Significance: Because homogeneity of PNES within a patient was high in the pediatric population, we found it useful to classify PNES into different semiologic categories. Dialeptic PNES seems to be more frequent among younger children. Tremor is the most frequent motor sign and usually accompanied by preserved responsiveness in childhood. Negative emotion is commonly seen in pediatric PNES, but pelvic thrusting is a rare phenomenon. We, therefore, suggest a modification of the present classification system in which PNES with motor activity is divided into minor and major motor PNES, and the latter group is subdivided into synchron rhythmic motor and asynchron motor PNES. We believe that our study, a detailed analysis on the semiology and classification of purely ch...

Epilepsy and mental retardation limited to females (EFMR), caused by PCDH19 mutations, has a variable clinical expression that needs further exploration. Onset of epilepsy may be provoked by fever and can resemble Dravet syndrome. Furthermore, transmitting males have no seizures, but are reported to have rigid personalities suggesting possible autism spectrum disorders (ASD). Therefore, this study aimed to determine the phenotypic spectrum associated with PCDH19 mutations in Dravet-like and EFMR female patients and in males with ASD. We screened 120 females suffering from Dravet-like epilepsy, 136 females with EFMR features and 20 males with ASD. Phenotypes and genotypes of the PCDH19 mutation carriers were compared with those of 125 females with EFMR reported in the literature. We report 15 additional patients with a PCDH19 mutation. Review of clinical data of all reported patients showed that the clinical picture of EFMR is heterogeneous, but epilepsy onset in infancy, fever sensitivity and occurrence of seizures in clusters are key features. Seizures remit in the majority of patients during teenage years. Intellectual disability and behavioural disturbances are common. Fifty percent of all mutations are missense mutations, located in the extracellular domains only. Truncating mutations have been identified in all protein domains. One ASD proband carried one missense mutation predicted to have a deleterious effect, suggesting that ASD in males can be associated with PCDH19 mutations.

Summary:Purpose: Complex partial seizure is the characteristic seizure type observed in epilepsy arising from temporal lobe structures. The seizure evolution in adult patients is quite stereotyped and well characterized, manifesting initially with an aura, behavioral arrest, and oroalimentary and gestural automatism. A greater variability of semiology including motor features with tonic or myoclonic components, as well as a paucity of automatism, has been reported in young children with temporal lobe epilepsy. The aim of our study was to examine in more detail the effects of age on individual ictal features to be able to determine the critical age when lesional temporal lobe seizure semiology undergoes transition from the pediatric to the more adult-type clinical pattern.Methods: We performed a video analysis of 83 seizures from 15 children (aged 11-70 months) selected by post-temporal lobectomy seizure-free outcome, looking specifically at the motor and behavioral (nonmotor) manifestations in relation to age of the children.Results: All of the children younger than 42 months had seizures with early and marked motor features, which included tonic and myoclonic components and epileptic spasms. Parallel with age, the frequency of these motor components decreased, and in five of 11 children older than 3 years, motor features were totally absent. Analyzed quantitatively, we saw a linear and inverse correlation of the ratio of motor components with age at monitoring.Conclusions: These findings support the hypothesis that events in brain maturation significantly affect clinical seizure semiology and may override the more typical localizing features seen in adult-type temporal lobe epilepsy. These findings are important to consider in the early diagnosis of childhood temporal lobe epilepsy. Key Words: Temporal lobe epilepsy-Children-Seizure semiology-Age-Brain maturation-Lateralization.Temporal lobe (TL) structures are frequently involved in the genesis of partial epilepsy. In adults, TL epilepsy is characterized by a somewhat stereotypic and welldescribed semiology consisting of epigastric auras, arrest of activity, staring, altered consciousness, and oroalimentary and hand automatisms, reflecting activation of limbic structures (1-4).In contrast, the semiology of TL seizures in young children is not that homogeneous, and various agedependent motor phenomena, including tonic, clonic, hypermotor components, and epileptic spasms (ESs) have been reported (5-16).The aim of this cross-sectional study was to investigate and describe seizures of young children with "pure" temporal lobe origin, and also to determine the likely age when the transition of lesional TL seizure semiology from the pediatric to the adult-type clinical pattern occurs. PATIENTS AND METHODS PatientsFifteen consecutive patients younger than 6 years (nine girls and six boys) with refractory lesional TL epilepsy who underwent long-term video-EEG monitoring and became seizure free after temporal lobectomy were selected [postoperative follow-up was between ...

Characteristics considered to be typical of IA (focal, left temporal seizures appearing on grounds of a long-lasting, intractable epilepsy) seem only partially legitimate. We suggest that in new-onset IA, female gender and a preexisting heart condition could serve as predispositions in an otherwise benign epilepsy. We speculate that in late-onset IA, male-predominant changes in neuronal networks in chronic, intractable epilepsy and an accompanying autonomic dysregulation serve as facilitating factors.

The most effective drugs in patients with PCDH19 mutations were bromide and clobazam. Although epilepsy in PCDH19 mutations is often pharmacoresistant, three quarters of the patients became seizure-free for at least for 3 months and half of them for at least one year. However, assessing the effectiveness of the drugs is difficult because a possible age-dependent spontaneous seizure remission must be considered.

Objective: Study 311 (NCT02849626) was a global, multicenter, open-label, singlearm study that assessed safety, tolerability, pharmacokinetics, and pharmacokinetics/ pharmacodynamics of once-daily adjunctive perampanel oral suspension in pediatric patients (aged 4 to <12 years) with focal seizures (FS) (with/without focal to bilateral tonic-clonic seizures [FBTCS]) or generalized tonic-clonic seizures (GTCS). Methods: In the 311 Core Study, a 4-week Pre-treatment Period (Screening/Baseline) preceded a 23-week Treatment Period (11-week Titration; 12-week Maintenance)and 4-week Follow-up. Endpoints included safety/tolerability (primary endpoint), median percent change in seizure frequency per 28 days from Baseline (Treatment Period), and 50% responder and seizure-freedom rates (Maintenance Period). Patients were stratified by age (4 to <7; 7 to <12 years) and concomitant enzyme-inducing anti-seizure drug (EIASD) use. Results: One hundred eighty patients were enrolled (FS, n = 149; FBTCS, n = 54; GTCS, n = 31). The Core Study was completed by 146 patients (81%); the most common primary reason for discontinuation was adverse event (AE) (n = 14 [8%]). Mean (standard deviation) daily perampanel dose was 7.0 (2.6) mg/day and median (interquartile range) duration of exposure was 22.9 (2.0) weeks. The overall incidence of treatment-emergent AEs (TEAEs; 89%) was similar between patients with FS (with/ without FBTCS) and GTCS. The most common TEAEs were somnolence (26%) and nasopharyngitis (19%). There were no clinically important changes observed for cognitive function, laboratory, or electrocardiogram (ECG) parameters or vital signs.Median percent reductions in seizure frequency per 28 days from Baseline were as follows: 40% (FS), 59% (FBTCS), and 69% (GTCS). Corresponding 50% responder and seizure-freedom rates were as follows: FS, 47% and 12%; FBTCS, 65% and 19%; 126 | FOGARASI et Al. | 127 FOGARASI et Al.

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