Real-Life Experience With Purified Cannabidiol Treatment for Refractory Epilepsy: A Multicenter Retrospective Study.

BACKGROUND: Drug-resistant epilepsy (DRE) affects the development and quality of life of children and young adults. We analyzed the effectiveness and safety of purified CBD in this population. METHODS: A retrospective analysis of medical records of 139 children and young adults (54.7% female, median age 12.0 years) with DRE treated with purified CBD from 2018 to 2022 at five medical centers in Israel. RESULTS: The most common diagnosis was Lennox-Gastaut syndrome (37.4%) followed by Dravet syndrome (16.5%) and tuberous sclerosis complex (16.5%). Median purified CBD dose was 12.5 mg/kg (range 2.5 to 20.0), and median treatment duration was 9.0 months (range 0.5 to 48.0). Most patients (92.2%) had a reduced seizure frequency following treatment initiation; 41.1% had >50% reduction. Fifty-three patients (38.1%) had positive effects: improved alertness (31.7%), improved speech (10.1%), and achievement of new developmental milestones (2.2%). A multivariate linear model assessing predictive factors for seizure reduction demonstrated that patients previously treated with CBD oils, especially those with >50% seizure reduction on prior treatment, were also more likely to have a reduced seizure frequency while they were treated with purified CBD (P = 0.01, P < 0.0001). Development, diagnosis, age, purified CBD dose (0 to 10 mg/kg/day vs 10 to 20 mg/kg/day), and concomitant treatment with clobazam, valproic acid, or everolimus did not affect seizure reduction by purified CBD. The most common adverse events were irritability (20.9%) and drowsiness (12.9%). CONCLUSION: Purified CBD is well-tolerated and effective in reducing seizure frequency in children and young adults with DRE.

Therapeutic drug monitoring of lacosamide among children: is it helpful?

Objective: This study aimed to investigate the efficacy and tolerability of Lacosamide (LCM) in a pediatric population with epilepsy using LCM serum concentration and its correlation to the age of the participants and the dosage of the drug. Methods: Demographic and clinical data were collected from the medical records of children with epilepsy treated with LCM at Shamir Medical Center between February 2019 to September 2021, in whom medication blood levels were measured. Trough serum LCM concentration was measured in the biochemical laboratory using High-Performance Liquid Chromatography (HPLC) and correlated with the administered weight-based medication dosing and clinical report. Results: Forty-two children aged 10.43 ± 5.13 years (range: 1-18) were included in the study. The average daily dose of LCM was 306.62 ± 133.20 mg (range: 100-600). The average number of seizures per day was 3.53 ± 7.25 compared to 0.87 ± 1.40 before and after LCM treatment, respectively. The mean LCM serum concentration was 6.74 ± 3.27 mg/L. No statistically significant association was found between LCM serum levels and the clinical response (p = 0.58), as well as the correlation between LCM dosage and the change in seizure rate (p = 0.30). Our study did not find a correlation between LCM serum concentration and LCM dosage and the gender of the participants: males (n = 17) females (n = 23) (p = 0.31 and p = 0.94, respectively). A positive trend was found between age and LCM serum concentrations (r = 0.26, p = 0.09). Conclusion: Based on the data that has been obtained from our study, it appears that therapeutic drug monitoring for LCM may not be necessary. Nonetheless, further research in this area is needed in the light of the relatively small sample size of the study.

Missed meal boluses and poorer glycemic control impact on neurocognitive function may be associated with white matter integrity in adolescents with type 1 diabetes.

Background: The notion that pediatric type 1 diabetes impacts brain function and structure early in life is of great concern. Neurological manifestations, including neurocognitive and behavioral symptoms, may be present from childhood, initially mild and undetectable in daily life. Despite intensive management and technological therapeutic interventions, most pediatric patients do not achieve glycemic control targets for HbA1c. One of the most common causes of such poor control and frequent transient hyperglycemic episodes may be lifestyle factors, including missed meal boluses. Objective: The aim of this study was to assess the association between specific neurocognitive accomplishments-learning and memory, inhibition ability learning, and verbal and semantic memory-during meals with and without bolusing, correlated to diffusion tensor imaging measurements of major related tracts, and glycemic control in adolescents with type 1 diabetes compared with their healthy siblings of similar age. Study design and methods: This is a case-control study of 12- to 18-year-old patients with type 1 diabetes (N = 17, 8 male patients, diabetes duration of 6.53 ± 4.1 years) and their healthy siblings (N = 13). All were hospitalized for 30 h for continuous glucose monitoring and repeated neurocognitive tests as a function of a missed or appropriate pre-meal bolus. This situation was mimicked by controlled, patient blinded manipulation of lunch pre-meal bolus administration to enable capillary glucose level of <180 mg/dl and to >240 mg/d 2 hours after similar meals, at a similar time. The diabetes team randomly and blindly manipulated post-lunch glucose levels by subcutaneous injection of either rapid-acting insulin or 0.9% NaCl solution before lunch. A specific neurocognitive test battery was performed twice, after each manipulation, and its results were compared, along with additional neurocognitive tasks administered during hospitalization without insulin manipulation. Participants underwent brain imaging, including diffusion tensor imaging and tractography. Results: A significant association was demonstrated between glycemic control and performance in the domains of executive functions, inhibition ability, learning and verbal memory, and semantic memory. Inhibition ability was specifically related to food management. Poorer glycemic control (>8.3%) was associated with a slower reaction time. Conclusion: These findings highlight the potential impairment of brain networks responsible for learning, memory, and controlled reactivity to food in adolescents with type 1 diabetes whose glycemic control is poor.

FIRDA, refractory epilepsy, and SEEG-guided RF: A case report.

OBJECTIVES: We will demonstrate that FIRDA (frontal intermittent rhythmic delta activity)-otherwise related to systemic disorders and encephalopathy-has a role as an epileptic biomarker of deep-seated midline SOZ. Its abolishment following SEEG-guided radiofrequency of such SOZ correlates with clinical improvement suggesting its role as a noninvasive biomarker of otherwise inaccessible SOZs. METHODS: We report the case of AK who was admitted with "psychiatric and gastrointestinal complaints." AK's complaints were further associated with FIRDA during VEEG. His previous refractoriness to AEDs, the clinico-electroencephalographic correlation, MRI showing bilateral hippocampal atrophy (more to the left) and severe memory deficits, prompted us to suggest a left temporo-mesial SOZ, for which SEEG was done. Dual SEEG and scalp electrodes were used primarily for diagnostic purposes but taking into account an option for a therapeutic action by RF ablation. RESULTS: The dual array demonstrated a clear association between left hippocampal high voltage spikes and HFOs on SEEG recordings with FIRDA on concomitant scalp EEG parallel to behavioral changes, as suspected in our preliminary hypothesis. A further RF ablation eliminated the epileptiform activity (Spikes, HFOs, and FIRDA) followed by clinical improvement. SIGNIFICANCE: This is the first report showing the clinical significance of FIRDA associated with behavioral changes as a marker for latent refractory mesial epilepsy. SEEG exploration has the potential to uncover deep sources, which are manifested as FIRDA on scalp EEG. These abnormalities and clinical symptoms can be eliminated by RF ablation.

Medical cannabis for the treatment of comorbid symptoms in children with autism spectrum disorder: An interim analysis of biochemical safety.

Background: Autistic Spectrum Disorder (ASD) is a common neurodevelopmental disorder and no effective treatment for the core symptoms is currently available. The present study is part of a larger clinical trial assessing the effects of cannabis oil on autism co-morbidities. Objectives: The aim of the present study was to assess the safety of a CBD-rich oil treatment in children and adolescents with ASD. Methods: Data from 59 children and young adults (ages 5-25 years) from a single-arm, ongoing, prospective, open-label, one center, phase III study was analyzed. Participants received the Nitzan Spectrum® Oil, with cannabis extracts infused in medium chain triglyceride (MCT) oil with a cannabidiol:THC ratio of 20:1, for 6 months. Blood analysis was performed before treatment initiation, and after 3 months. Complete blood count, glucose, urea, creatinine, electrolytes, liver enzymes (AST, ALT, gamma glutamyl transferase), bilirubin, lipid profile, TSH, FT4, thyroid antibodies, prolactin, and testosterone measurements were performed at baseline, prior to starting treatment and at study midpoint, after 3 months of treatment. Results: 59 children (85% male and 15% female) were followed for 18 ± 8 weeks (mean ±SD). The mean total daily dose was 7.88 ± 4.24 mg/kg body weight. No clinically significant differences were found in any of the analytes between baseline and 3 months follow up. Lactate dehydrogenase was significantly higher before treatment (505.36 ± 95.1 IU/l) as compared to its level after 3 months of treatment (470.55 ± 84.22 IU/L) (p = 0.003). FT4 was significantly higher after 3 months of treatment (15.54 ± 1.9) as compared to its level before treatment (15.07 ± 1.88) (p = 0.03), as was TSH [(2.34 ± 1.17) and (2.05 ± 1.02)] before and after 3 months of treatment, respectively (p = 0.01). However, all these values were within normal range. A comparison of the group with additional medications (n = 14) to those who received solely medical cannabis (n = 45) showed no difference in biochemical analysis, including liver enzymes, which remained stable, except for change in potassium level which was significantly higher in the group that did not receive additional medications (0.04 ± 0.37) compared to the group receiving concomitant drug therapy (-0.2 ± 0.33) (p = 0.04). A comparison of patients who received a high dose of the cannabis oil (upper quartile-16 patients), with those receiving a low dose (lower quartile-14 patients) showed no significant difference between the two groups, except for the mean change of total protein, which was significantly higher among patients receiving high dose of CBD (0.19 ± 2.74) compared to those receiving a low dose of CBD (1.71 ± 2.46 (p = 0.01), and mean change in number of platelets, that was significantly lower among patients who received high dose of CBD (13.46 ± 31.38) as compared to those who received low dose of CBD (29.64 ± 26.2) (p = 0.0007). However, both of these changes lack clinical significance. Conclusion: CBD-rich cannabis oil (CBD: THC 20:1), appears to have a good safety profile. Long-term monitoring with a larger number of participants is warranted.

Children and adolescents with ASD treated with CBD-rich cannabis exhibit significant improvements particularly in social symptoms: an open label study.

In recent years there has been growing interest in the potential benefits of CBD-rich cannabis treatment for children with ASD. Several open label studies and one double-blind placebo-controlled study have reported that CBD-rich cannabis is safe and potentially effective in reducing disruptive behaviors and improving social communication. However, previous studies have mostly based their conclusions on parental reports without the use of standardized clinical assessments. Here, we conducted an open label study to examine the efficacy of 6 months of CBD-rich cannabis treatment in children and adolescents with ASD. Longitudinal changes in social communication abilities and restricted and repetitive behaviors (RRB) were quantified using parent report with the Social Responsiveness Scale and clinical assessment with the Autism Diagnostic Observation Schedule (ADOS). We also quantified changes in adaptive behaviors using the Vineland, and cognitive abilities using an age-appropriate Wechsler test. Eighty-two of the 110 recruited participants completed the 6-month treatment protocol. While some participants did not exhibit any improvement in symptoms, there were overall significant improvements in social communication abilities as quantified by the ADOS, SRS, and Vineland with larger improvements in participants who had more severe initial symptoms. Significant improvements in RRB were noted only with parent-reported SRS scores and there were no significant changes in cognitive scores. These findings suggest that treatment with CBD-rich cannabis can yield improvements, particularly in social communication abilities, which were visible even when using standardized clinical assessments. Additional double-blind placebo-controlled studies utilizing standardized assessments are highly warranted for substantiating these findings.

Reduction in seizure burden in a child with a A350V IQSEC2 mutation using heat therapy with a Jacuzzi.

A child with a A350V IQSEC2 missense mutation resulting in drug-resistant epilepsy stops having seizures when he has a fever. We demonstrate that raising the body temperature of the child using a commercial Jacuzzi dramatically reduces his seizures and appears to improve his social behavioral interactions.

Novel perspectives of super-high dose sulfonylurea and high-dose oral prednisolone in an infant with DEND syndrome due to V64M heterozygote KCNJ11 mutation.

AIMS: To report a novel mutation associated with developmental delay, epilepsy, and neonatal diabetes-DEND Syndrome, responsive to a novel management combination. METHODS: We describe the investigation, treatment, and genetic diagnosis of a newborn diagnosed with DEND syndrome. RESULTS: The patient was found to be de-novo heterozygous for pathogenic KCNJ11 missense variant: c.190G > A, p. (Val64Met), associated with DEND syndrome, responsive to a combination of super high doses of sulfonylurea (SU) and oral high-dose steroids. A single case was reported so far due to this mutation, presenting with severe DEND syndrome, treated by insulin only. His phenotypic description and management during 18 months, demonstrates this mutation is responsive to super-high doses of SU combined with high dose 6 weeks steroids protocol. CONCLUSIONS: We have identified a heterozygous missense mutation as the etiology for severe DEND syndrome in a one-day old neonate, presenting with asymptomatic hyperglycemia, responsive to a novel management combination.

ATP6V0A1 encoding the a1-subunit of the V0 domain of vacuolar H+-ATPases is essential for brain development in humans and mice.

Vacuolar H+-ATPases (V-ATPases) transport protons across cellular membranes to acidify various organelles. ATP6V0A1 encodes the a1-subunit of the V0 domain of V-ATPases, which is strongly expressed in neurons. However, its role in brain development is unknown. Here we report four individuals with developmental and epileptic encephalopathy with ATP6V0A1 variants: two individuals with a de novo missense variant (R741Q) and the other two individuals with biallelic variants comprising one almost complete loss-of-function variant and one missense variant (A512P and N534D). Lysosomal acidification is significantly impaired in cell lines expressing three missense ATP6V0A1 mutants. Homozygous mutant mice harboring human R741Q (Atp6v0a1R741Q) and A512P (Atp6v0a1A512P) variants show embryonic lethality and early postnatal mortality, respectively, suggesting that R741Q affects V-ATPase function more severely. Lysosomal dysfunction resulting in cell death, accumulated autophagosomes and lysosomes, reduced mTORC1 signaling and synaptic connectivity, and lowered neurotransmitter contents of synaptic vesicles are observed in the brains of Atp6v0a1A512P/A512P mice. These findings demonstrate the essential roles of ATP6V0A1/Atp6v0a1 in neuronal development in terms of integrity and connectivity of neurons in both humans and mice.

A novel PAK1 variant causative of neurodevelopmental disorder with postnatal macrocephaly.

p21-activated kinases (PAKs) are protein serine/threonine kinases stimulated by Rho-family p21 GTPases such as CDC42 and RAC. PAKs have been implicated in several human disorders, with pathogenic variants in PAK3 associated with intellectual disability and several PAK members, especially PAK1 and PAK4, overexpressed in human cancer. Recently, de novo PAK1 variants were reported to be causative of neurodevelopmental disorder (ND) with secondary macrocephaly in three patients. We herein report a fourth patient with ND, epilepsy, and macrocephaly caused by a de novo PAK1 missense variant. Two previously reported missense PAK1 variants functioned as activating alleles by reducing PAK1 homodimerization. To examine the pathogenicity of the identified novel p.Ser110Thr variant, we carried out in silico structural analysis. Our findings suggest that this variant also prevents PAK1 homodimerization, leading to constitutive PAK1 activation.

Lacosamide for SCN2A-related intractable neonatal and infantile seizures.

Voltage-gated sodium channel alpha subunit 2 (SCN2A) gene mutations are associated with neonatal seizures and a wide range of epilepsy syndromes. Previous reports suggest that traditional sodium channel blockers (SCBs) such as phenytoin, carbamazepine, and lamotrigine have a beneficial effect on SCN2A-related neonatal seizures, as they counteract the gain-of-function effect of mutated Nav1.2 channels. Additionally, SCBs are beneficial against other sodium and potassium channel-related neonatal seizures. There are, however, few reports describing the effect of the new SCB lacosamide against neonatal and infantile epileptic seizures. We report herein two neonates with intractable neonatal seizures with SCN2A pathogenic missense variants. Both infants showed temporary seizure relief following IV administrations of phenytoin, but were resistant to a combination of antiepileptic drugs, while complete seizure control was achieved following lacosamide administration. We suggest that SCBs, e.g. phenytoin, should be introduced early for refractory neonatal seizures of non-lesional and presumably genetic origin. If any beneficial response to a SCB is noted, this should prompt an initiation of additional SCBs. New clinical trials will provide data on the efficacy and safety of the new SCB lacosamide for genetic neonatal seizures and perhaps neonatal seizures in general.

Unlicensed and Off-Label Medication Use in Pediatric and Neonatal Intensive Care Units: No Change Over a Decade.

INTRODUCTION: Many of the medications prescribed to children are off-label and/or unlicensed because pharmacologic evaluations have not been performed in this age group. METHODS: All drugs prescribed to patients admitted to the neonatal intensive care units (NICU) (n = 134) and pediatric intensive care units (PICU) (n = 56) during a 2-month observation period were recorded and classified according to patient age, drug license status, indicated use, and typical dosing, frequency and way of administration. Results were compared with prior data collected in 2002, from the same units. RESULTS: In the NICU, among the 1064 prescriptions for 49 medications, 312 (29.2%) were licensed and 63 (5.9%) unlicensed, and 693 (64.8%) were off-label use. For the neonates, 23.9% and 96.3% received at least one unlicensed medication and one off-label medication, respectively. While the difference in off-label use between the two time periods was not statistically significant, unlicensed medications were less frequently prescribed in 2016 (5.9 versus 16.6%, p = 0.001). Regarding the PICU, among the 388 prescriptions for 75 medications, 205 (52%) were licensed and 13 (3.4%) unlicensed, and 170 (43.8%) were off-label. In contrast, in 2002, none of the medications prescribed were unlicensed (p = 0.001). The number of off-label medications (41%) and number of PICU patients receiving at least one unlicensed/off-label medication in these two time periods (88.7% versus 90.5% for 2016 and 2002, respectively) were similar. CONCLUSIONS: The current study confirms the high prevalence of unlicensed and off-label drug use in a PICU and NICU setting. Compared with a similar study conducted in the same PICU in 2002, despite regulatory efforts conducted in this area, the prevalence of unlicensed medications was surprisingly higher.

Neurological results of the modified treatment of epilepsy by stimulation of the vagus nerve.

INTRODUCTION: The vagus nerve stimulation (VNS) is used for treatment of drug-resistant epilepsy but laryngeal side effects are common. We tried to improve VNS by modifying the implantation procedure. The aim was to reduce the rate of side effects that have prevented using VNS to its full capacity. METHODS: We operated on 74 pediatric patients for VNS device implantation using a modified surgical protocol incorporating lower neck incision for electrode placement and 36 patients who were operated by standard technique were used for control group. We retrospectively analyzed reduction in frequency of seizures, reduction in severity of seizures (assessed by the shortened Ictal/post-ictal subscale of the Liverpool Seizure Severity Scale that included falling to the ground, postictal headache and sleepiness, incontinence, tongue biting, and injury during attack). RESULTS: Using the new implantation technique, side effects related directly to VNS therapy occurred in six cases (8.1%) showing statistically sound improvement over the standard implantation technique (p Ë‚ 0.05). To achieve good results, the maximum stimulation (3.5 mA) was used in 24 patients (32.4%), with no laryngeal side effects detected. Twelve patients (16.2%) were seizure-free after the first year of VNS treatment. 74.3% of patients experienced a 50% reduction in seizure frequency and improved ictal or postictal activity. CONCLUSION: To minimize laryngeal complications in implantation surgery for VNS devices, the surgical technique may be modified, and lower neck incision could be used. A low rate of laryngeal side effects allows using the VNS device to its full electrical capacity.

Tolerability and efficacy of perampanel in children with refractory epilepsy.

AIM: There are few reports on the tolerability and efficacy of perampanel, a new antiepileptic drug with a novel mechanism of action, in children and adolescents. We aimed to describe our experience with perampanel add-on and mono-therapy in children with refractory epilepsy. METHOD: Computerized medical records of children treated with perampanel in the paediatric neurology clinic from December 2012 to October 2015 were reviewed. RESULTS: Twenty-four children treated with perampanel (15 females, 9 males) aged 1 year 6 months to 17 years (mean 10y, standard deviation [SD] 4y 5mo) were identified. Adverse events were more common in children aged 12 years or older (89%) compared to younger children (53%), and were mainly behavioural. Ten (42%) children had 50 per cent or higher seizure reduction, two (8%) children had 33 per cent seizure reduction, and seizures were less severe in one (4%) child. Perampanel was discontinued in 13 (54%) children mostly due to adverse events. The mean duration of follow-up in the remaining 11 children was 8.1 months (SD 5.2) (range 1.3-17mo). INTERPRETATION: Perampanel is associated with a relatively high rate of behavioural adverse events mostly in adolescents with refractory epilepsy.

The molecular and phenotypic spectrum of IQSEC2-related epilepsy.

OBJECTIVE: IQSEC2 is an X-linked gene associated with intellectual disability (ID) and epilepsy. Herein we characterize the epilepsy/epileptic encephalopathy of patients with IQSEC2 pathogenic variants. METHODS: Forty-eight patients with IQSEC2 variants were identified worldwide through Medline search. Two patients were recruited from our early onset epileptic encephalopathy cohort and one patient from personal communication. The 18 patients who have epilepsy in addition to ID are the subject of this study. Information regarding the 18 patients was ascertained by questionnaire provided to the treating clinicians. RESULTS: Six affected individuals had an inherited IQSEC2 variant and 12 had a de novo one (male-to-female ratio, 12:6). The pathogenic variant types were as follows: missense (8), nonsense (5), frameshift (1), intragenic duplications (2), translocation (1), and insertion (1). An epileptic encephalopathy was diagnosed in 9 (50%) of 18 patients. Seizure onset ranged from 8 months to 4 years; seizure types included spasms, atonic, myoclonic, tonic, absence, focal seizures, and generalized tonic-clonic (GTC) seizures. The electroclinical syndromes could be defined in five patients: late-onset epileptic spasms (three) and Lennox-Gastaut or Lennox-Gastaut-like syndrome (two). Seizures were pharmacoresistant in all affected individuals with epileptic encephalopathy. The epilepsy in the other nine patients had a variable age at onset from infancy to 18 years; seizure types included GTC and absence seizures in the hereditary cases and GTC and focal seizures in de novo cases. Seizures were responsive to medical treatment in most cases. All 18 patients had moderate to profound intellectual disability. Developmental regression, autistic features, hypotonia, strabismus, and white matter changes on brain magnetic resonance imaging (MRI) were prominent features. SIGNIFICANCE: The phenotypic spectrum of IQSEC2 disorders includes epilepsy and epileptic encephalopathy. Epileptic encephalopathy is a main clinical feature in sporadic cases. IQSEC2 should be evaluated in both male and female patients with an epileptic encephalopathy.

Feasibility of sleep-deprived EEG in children.

BACKGROUND: Non-sedated EEG recording in children can be technically challenging, particularly when behavioral disorders are present. We aimed to assess the feasibility and the efficacy of non-sedated sleep-deprived EEG in children with behavioral disorders and in young children. METHODS: We retrospectively reviewed the EEG recordings and computerized medical records of all pediatric inpatients at least 2-month-old that had a sleep-deprived EEG during a 5-year period between 2009 and 2014. RESULTS: We present the data of 261 children, 142 (54%) boys, mean age 7.9 ± 4.9 years, 67 (26%) aged 0.5-4 years. Behavioral disorders were reported in 38 (15%) of the patients. Mean recording duration was 50.8 ± 12.5 min, and mean sleep duration- 31.8 ± 15.2 min. Thirty-seven (14%) patients slept less than 15 min during the EEG, including 19 (7%) patients with no sleep during the recording. Sleep duration and the presence of interictal epileptiform discharges did not significantly differ between children with/without behavioral disorders and in those younger/older than 4 years. Patients that did not fall asleep during the EEG did not differ from the others regarding presence of behavioral disorders or age. CONCLUSIONS: These results suggest that non-sedated sleep-deprived EEG is feasible in young children and in those with behavioral disorders. Further studies are needed in order to better characterize the etiologies of sleepless pediatric sleep-deprived EEG recordings.

The Role of Prematurity in Patients With Hemiplegic Cerebral Palsy.

A multicenter retrospective study was conducted to investigate the perinatal factors, imaging findings and clinical characteristics of hemiplegic cerebral palsy with a particular focus on children born prematurely. Our cohort included 135 patients of whom 42% were born prematurely; 16% were extreme premature infants who were born at 30 weeks or earlier. Nineteen (14%) were twins. Right hemiplegia was slightly more common and accounted for 59% of the patients. Imaging findings of intraventricular hemorrhage and periventricular leukomalacia were more prevalent in premature children whereas stroke, porencephaly, cerebral hemorrhage and cerebral atrophy were more evenly distributed in both term-born and prematurely-born children (p< 0.01). The overall prevalence of epilepsy in the cohort was 26% with no differences in full-term compared to prematurely-born children. Regardless of the gestational birth age, intellectual deficits were more common in the presence of comorbidity of both hemiplegia and epilepsy (p< 0.05).

Correlation between efficacy of levetiracetam and serum levels among children with refractory epilepsy.

BACKGROUND: Levetiracetam is used as adjunctive therapy in various types of seizures. Studies evaluating the effect of levetiracetam on children with refractory epilepsy are scarce. The aim of this study was to evaluate the correlation between serum concentration of levetiracetam and either efficacy or tolerability in children with refractory epilepsy, and to determine the value of levetiracetam blood level monitoring. METHODS: Medical records of 50 children with refractory epilepsy treated with levetiracetam and regularly followed at Assaf Harofeh Medical Center were retrospectively reviewed. Trough serum levetiracetam concentration was determined using high-performance liquid chromatography and correlated with the administered dose and clinical report. RESULTS: No correlation between levetiracetam serum levels and clinical efficacy, tolerability or administered dosage was found. The average dose of levetiracetam was 43.7 ± 20.0 (range 14-100) mg/kg/day and the average serum concentration was 16.0 ± 9.5 (range 2.5-38.5) µg/mL. Forty-five patients (95%) had more than a 50% reduction of seizure frequency, with 22 (44%) patients becoming seizure-free for at least 6 months. Adverse events related to levetiracetam were reported in 15 (30%) patients. No correlation between serum concentrations and adverse events was found. These results were not affected by gender, age, type of seizure, and other drugs. CONCLUSIONS: Determination of serum concentration is not needed in all children treated with levetiracetam. Serum concentrations may be valuable either in patients with refractory epilepsy for compliance evaluation or in patients with satisfactory control of seizures for determination of their therapeutic baseline.

Seizure occurrence during pediatric short-term EEG.

AIM: To identify the patients who are more likely to experience a seizure during short-term EEG recording. METHODS: We retrospectively reviewed the EEG recordings and medical records of 294 patients, who were admitted to the Pediatric Departments in Assaf Harofeh Medical Center, and referred for a short-term EEG during a 5-years period following a seizure. RESULTS: Fifteen (5.1%) patients had seizures during short-term EEG. The likelihood of seizure occurrence was increased by history of seizures (odds ratio 11.86, 95% confidence interval 2.54-55.37), abnormal neurological examination (odds ratio 3.33, 95% confidence interval 1.05-10.55), and the presence of interictal epileptiform discharges (odds ratio 10.07, 95% confidence interval 1.26-80.42). Treatment with antiepileptic drugs and mental retardation were significantly more common among patients with seizures. CONCLUSIONS: Children with a higher likelihood of a seizure during short-term EEG can be identified using data mainly obtained by history and neurological examination.