Treatment Of Epilepsy In Children Research Articles

(360) Can CBD Reduce the Use of Pain Medication? Lessons from a Survey in a Pain Clinic Environment

During the past decade, Cannabis derivatives in pain medicine have been of increasing interest. Specifically, the non-psychoactive Cannabidiol (CBD) has received recent attention. CBD has been used as a treatment for childhood epilepsy, chronic pain, and anxiety disorders, and presents a unique situation in healthcare: patients may be more familiar with it than their physician. We asked patients and staff in the environment of seven pain clinics in Southern California about their knowledge, beliefs, and personal experience surrounding CBD products. After IRB review (exempt status) we utilized the internet survey platform SurveyMonkey to administer the survey online. Our participants were 45.26±14.02 (Mean±SD) years old, the majority identified as white, has an annual household income of less than $20,000, and is insured by Medicare or Medicaid. Among our participants, 63% report to have tried a CBD product (including products containing THC) and 37.30% of these answered that the used CBD product did not contain THC. Of these, the majority responded that CBD products have helped their condition (57.45%) and reduced their pain medication (61.7%), including opioids (44.68%). Among the pain conditions patients reported relieve were back pain (63.83%), nerve pain (38.30%), neck pain (38.30%), migraines (29.79%), limb pain (19.15%), fibromyalgia (19.15%), and other (19.15%). Overall, participants familiarity with the dosing of their CBD product varied. Generally, participants believe CBD is a good treatment option, and not harmful. The overall attitude and experience of participants regarding CBD products was positive and CBD only was reported to reduce pain medication, including opioids. With the voluntary nature of a survey design come some study limitations that warrant attention. However, studies like this can help identify areas of interest for future research and more controlled research has to follow. Supported by a grant from Versea Pharmaceuticals During the past decade, Cannabis derivatives in pain medicine have been of increasing interest. Specifically, the non-psychoactive Cannabidiol (CBD) has received recent attention. CBD has been used as a treatment for childhood epilepsy, chronic pain, and anxiety disorders, and presents a unique situation in healthcare: patients may be more familiar with it than their physician. We asked patients and staff in the environment of seven pain clinics in Southern California about their knowledge, beliefs, and personal experience surrounding CBD products. After IRB review (exempt status) we utilized the internet survey platform SurveyMonkey to administer the survey online. Our participants were 45.26±14.02 (Mean±SD) years old, the majority identified as white, has an annual household income of less than $20,000, and is insured by Medicare or Medicaid. Among our participants, 63% report to have tried a CBD product (including products containing THC) and 37.30% of these answered that the used CBD product did not contain THC. Of these, the majority responded that CBD products have helped their condition (57.45%) and reduced their pain medication (61.7%), including opioids (44.68%). Among the pain conditions patients reported relieve were back pain (63.83%), nerve pain (38.30%), neck pain (38.30%), migraines (29.79%), limb pain (19.15%), fibromyalgia (19.15%), and other (19.15%). Overall, participants familiarity with the dosing of their CBD product varied. Generally, participants believe CBD is a good treatment option, and not harmful. The overall attitude and experience of participants regarding CBD products was positive and CBD only was reported to reduce pain medication, including opioids. With the voluntary nature of a survey design come some study limitations that warrant attention. However, studies like this can help identify areas of interest for future research and more controlled research has to follow. Supported by a grant from Versea Pharmaceuticals

Clinical analysis of levetiracetam in the treatment of children and adolescents with epilepsy

Objective To explore and compare the clinical efficacy of levetiracetam tablets and compound sodium valproate sustained release tablets in the treatment of children and adolescents with epilepsy. Methods From April 2017 to April 2018, 80 children and adolescents with epilepsy treated in Chaonan Minsheng Hospital of Shantou were selected as study objects, and they were randomly divided into two groups by drawing lots, with 40 cases in each group.The observation group was given levetiracetam tablets, and the control group was treated with valproate.The improvement of EEG after therapy, the total effective rate, and the incidence of adverse reactions were observed and evaluated. Results The EEG improvement rates after treatment for 6 months in the observation group and control group were 41.17%, 45.71%, respectively, the difference was not statistically significant(χ2=0.508, P>0.05). The EEG improvement rates after treatment for 9 months in the observation group and control group were 70.58%, 74.28%, respectively, the difference was not statistically significant(χ2=0.225, P>0.05). The total effective rate in the observation group was 92.50%, which was 95.00% in the control group, the difference was not statistically significant between the two groups(χ2=0.354, P>0.05). However, the incidence rate of adverse reactions of the observation group(22.50%) was significantly lower than that of the control group(45.00%)(χ2=6.864, P<0.05). Conclusion Both levetiracetam tablets and compound sodium valproate sustained release tablets have appreciable efficacy and safety in the treatment of epilepsy in children and adolescents, but levetiracetam therapy has less adverse reactions, which deserves further promotion in monotherapy of epilepsy in children and adolescents. Key words: Epilepsy; Electroencephalography; Treatment outcome; Adverse drug reaction reporting systems; Sodium valproate; Levetiracetam; Child; Adolescent

Subclinical Hypothyroidism During Valproic Acid Therapy in Children with Epilepsy

Background : Valproic Acid (VPA) is an effective anticonvulsant widely used for the treatment of epilepsy in children, but there are pitfalls in VPA therapy, especially in case of various endocrine organs like thyroid. So the aim of this study was to evaluate the thyroid dysfunction in terms of subclinical hypothyroidism during Valproic Acid (VPA) therapy in children with epilepsy.&#x0D; Methods: The study was conducted in the Department of Paediatrics, and Shishu Bikas Kendra, Chittagong Medical College Hospital (CMCH) over one year duration on 50 newly diagnosed idiopathic epileptic children who were decided to start Valproate at the dose of 20mg/kg/day. At the same time similar number (n=50) of age and sex matched children visited the paediatric OPD for other health events(e.g. acute upper respiratory infection, Influenza like illness and Acute watery diarrhoea) other than epilepsy were included in the study as control group. Thyroid function status like serum levels of Thyroid-Stimulating Hormone (TSH) Free Triiodothyronine (FT3) and Free Thyroxin (FT4) were evaluated at baseline and after six months. Moreover, serum VPA level was also measured in children receiving valproate at follow up visit. Anti thyroid peroxidise antibody (Anti TPO ab) was checked at follow up visit in those having TSH level beyond normal reference range. After collecting all data it was analyzed by SPSS-19.&#x0D; Results: In the current study, cases consisted of 30(60%) male and 20(40%) female children. Male to female ratio was 1.5:1. Gender and age were matched in cases and control group (p&gt;0.05). Most of the population in the cases were from rural areas 29(58%) and most of them 40(80%) belonged to middle class family. The mean±SD of TSH level significantly increased after six months in comparison with base line values (1.76±0.57μIU/ml vs. 2.70±1.50μIU/ml, p&lt;0.05) and with control group at follow up visit (1.74±0.73μIU/ml vs 2.70±1.50μIU, p&lt;0.05). On the other hand, in the control group there were no significant changes of TSH level in comparison with base line (1.82±0.55μIU vs 1.74±0.73μIU/ml, p=0.16). The mean±SD of FT4 value decreased significantly in the cases after six months though remained within normal reference range (1.24±0.27ng/dl vs1.11±0.13ng/dl, p&lt;0.05) FT3 level remained unchanged. Five (10%) epileptic children in the cases were found to have subclinical hypothyroidism at follow up who had TSH level beyond the normal reference range. Anti thyroid peroxidase antibody was negative among them. In contrast, no one in control group was found to have TSH level beyond the normal limit. All cases were clinically euthyroid. No significant correlations were found between TSH level and serum VPA level (r2 = 0.035 p= 0.193).&#x0D; Conclusion: Subclinical hypothyroidism develops in children with epilepsy during VPA therapy. Proper attention should be given so that development of overt hypothyroidism can be avoided.&#x0D; Chatt Maa Shi Hosp Med Coll J; Vol.17 (2); Jul 2018; Page 14-20

КЛИНИЧЕСКИЕ ПРЕДИКТОРЫ НЕЭФФЕКТИВНОСТИ СТАРТОВОЙ МОНОТЕРАПИИ ЭПИЛЕПСИИ У ДЕТЕЙ

Actuality. Effectiveness of epilepsy treatment in children is determined by the possibility of achieving clinical remission at initial monotherapy. The spectrum of anticonvulsants recommended for initial treatment of epilepsy in children is relatively known, but the analysis of their prescription indicates the influence of other non-pharmacologic factors on the possibility of achieving adequate control over epileptic seizures. Objective of the study: to find the frequency of achieving clinical remission in children with epilepsy while taking initial anticonvulsant and to define a combination of independent clinical factors which determine ineffectiveness of initial anticonvulsant monotherapy. Material and methods. Using the method of target selection there was performed a cohort retrospective-prospective comparative study of 447 children with epilepsy aged from birth to 17 years old. The frequency of clinical remission at initial anticonvulsant therapy was analyzed; a comparative study of clinical parameters was made within the frames of mono-factor analysis in order to find significant differences with consideration of age of epilepsy onset and effectiveness of initial treatment. Results. The study found the influence of a child’s age at epilepsy debut on achieving clinical remission at initial monotherapy: the younger the child, the lower is the possibility of its acheving, pllat<0.001. The highest frequency of absence of remission was noted in children under 1 year (72.5%) and those aged 1-3 years (71.4%) in comparison to children of older age groups (33.0%-59.5%), pFisher<0.001.The factors which define the prognosis of initial treatment of epilepsy in children were determined: in case of chronic somatic comorbidity ineffectiveness of therapy was noted in 69.8% of cases (pFisher<0.001) and chances of remission absence raised by 2.5 times (ОR=2.480; S=0.201; 95% CI [1.672; 3.681]; in case of psychic comorbidity therapy was ineffective in 87.6% of cases (pFisher<0.001) with a 7-fold increase of chances of remission absence (ОR=7.06; S=0.283; 95% CI [4.054; 12.291]; in case of neurologic comorbidity monotherapy was ineffective in 76.3% of cases (pFisher<0.001) and chances of remission absence increased by 3.9 times (ОR=3.925; S=0.206; 95% CI [2.62; 5.88]. For the first time the combination of independent factors in patients with epilepsy was stated – age at disease onset less than 6 years, presence of neurologic disorders, focal or combined types of epilepsy, presence of chronic somatic comorbidity. The set of these factors validly defines prognosis of effectiveness of initial anticonvulsant therapy with precision of 78.5% (AUC = 0.785; 95% CI [0.742; 0.828]) (p<0.001) by the results of ROC-analysis and with precision of 72.5% by the results of logistic regression (0.725 with 95% CI [0.680; 0.765]), which proves the tactics of fast correction of anticonvulsant dosage, its change and using rational polytherapy at initial stage of epilepsy treatment in children. Conclusions. New data regarding prognosis of effectiveness of initial anticonvulsant momotherapy in children were received; they allow defining the possibility of achieving clinical remission at prescribing the first anticonvulsant with a probability of more than 70%.

Ognitive Disorders and Their Correction in Children With Epilepsy

The article is devoted to the analysis of literature data on the study of cognitive disorders in children. The issues of the prevalence of these disorders are considered. Ir was noted the fact that the high prevalence of epilepsy in the population, frequent combination with mental retardation and personality changes and the need for long-term therapy anticonvulsant therapy determine the exceptional importance of this problem in pediatric neurology and psychiatry. The issues under consideration are due to the fact that the presence of cognitive disorder is one of the essential aspects in epileptological practice, as well as the fact that neurologists and psychiatrists involved in the treatment of epilepsy in children and adolescents often underestimate these disorders. The article pays attention to the etiological and pathogenetic aspects of the cognitive disorders formation, the dependence of the occurrence of these disorders on the localization of the epileptic focus, on the nature of the seizures and age-related features of the epilepsy course. It is indicated that cognitive disorders in patients with epilepsy is determined by biological and social factors interaction complex. The main points that can explain the cognitive and behavioral problems in children with epilepsy are underlined. Two mechanisms in the violation of the cognitive activity of patients with epilepsy are identified. It is indicated that psychosocial problems for patients often come to the fore, including cases when control over seizures has not been achieved yet. In particular, depression in patients with difficult to control epilepsy affects quality of life more than frequent suizures. In addition, depression can have a significant impact on cognitive function. Complaints on speech functions, memory, attention, thinking disorders that patients can present at the doctor’s appointment, are in second place after complaints on seizures. It was also given attention to the views on approaches to the treatment of cognitive disorders. It is indicated, that providing assistance to children with cognitive disorders should have a comprehensive and individual approach, combining non-medicament and medication methods.bThe funds belonging to the group of nootropic drugs, and also directed psychological correction, supported by antiepileptic therapy are applied traditionally for the treatment of cognitive disorders.

Effects of personalized continuation nursing mode in pediatric epilepsy

Objective To explore the effects of individualized continuation nursing mode in children with epilepsy. Methods A total of 80 cases of children with epilepsy and their families who received treatment in the Affiliated Children's Hospital of Nanjing Medical University from April 2016 to April 2017 were selected as the research subjects. All the subjects were divided into the control group and the observation group, with 40 cases in each, by random numbering method. Conventional nursing intervention and the individualized continuation nursing mode were applied in the control group and the observation group respectively. The medical compliance after discharge, the cognition of health knowledge, the epilepsy recurrence rate, hospital review rate, treatment efficiency, psychological status and quality of life of the children were compared between the two groups. Results After 1 year intervention, 5 of the indicators of the observation group were better than those of the control group, the medical compliance 70.0%, the cognition of health knowledge 90.0%, the epilepsy recurrence rate 12.5%, hospital review rate 95.5%, and treatment efficiency 75.0%. All the differences were statistically significant (χ2=6.794, 6.063, 5.897, 5.746, 6.906; P<0.05) . The scores of Self-rating Anxiety Scale and Self-rating Depression Scale in the observation group were both lower than in the control group, and the scores of quality of life in the observation group were higher than those in the control group, with statistical significances (P<0.05) . Conclusions The application of individualized continuation nursing mode in epilepsy children can improve the therapeutic effect and medical compliance, effectively improve anxiety and depression of children, and also effectively improve the quality of life of children with epilepsy, which has high practical value for clinical treatment of epilepsy in children. Key words: Children; Epilepsy; Quality of life; Individualized continuation nursing mode; Intervention effect

New epilepsy treatment in children: upcoming strategies and rewind to ancient times and concepts

Abstract The epilepsies are the most common chronic neurological disorders in children. Considerable steps towards a better understanding of different aspects of the once considered ‘sacred disease’ have been made over the last two centuries, culminating in the development of new pharmacological and alternative antiepileptic treatments. However, principles of antiepileptic drug therapies have changed little since their breakthrough in the 20th century and the emphasis still lies on treating the symptom by enhancing inhibitory currents and suppressing excitatory networks rather than on addressing underlying neurobiological mechanisms. Around one third of the patients do not respond to the currently available drugs. New therapeutic strategies are on the horizon comprising inflammatory, immune and intracellular pathway targeting, as well as neuromodulation and novel surgical and dietary interventions. Furthermore, the prospect of personalized treatment for epilepsy using epigenetic and genetic techniques is becoming a reality. We discuss current and new concepts and future possibilities in the effort to cure the epilepsies.

Ketogenic diet therapy in infants less than two years of age for medically refractory epilepsy

PurposeThe Ketogenic Diet (KD) is a well-established treatment for epilepsy in children and adults. We describe our 10-year KD experience in children less than two years of age diagnosed with medically refractory epilepsy. MethodsWe conducted a retrospective case-note review of infants managed with KD at our centre between 2006 and 2016. ResultsTwenty-nine children between 2½ weeks and 23 months of age were identified, with mixed epilepsy aetiologies. Ninety-three percent had daily seizures and 82% were on two or more anti-epilepsy drugs (AEDs) at the time of KD commencement. KD was continued for more than four weeks in 86%. Based on a combination of parental reports, hospital observations and seizure diaries, two of 29 became seizure free, seven demonstrated >50% seizure reduction, and eight showed a decrease in seizure intensity/frequency. No adverse effects were observed in 45% patients, and dietary therapy was stopped in only two because of poor tolerability. ConclusionWe conclude that KD can be utilised and is generally well tolerated in infants with severe epilepsies. In addition, our experience suggests efficacy with improved seizure frequency/severity in around 50% without adverse effects on developmental outcome.

Epilepsy in children with cerebral palsy as observed in Nepal

Objective: Epilepsy is a highly treatable condition and is among the few medical interventions available to help children with CP. This study aims to study the situation of epileptic children with CP in Nepal. Methods: This was a retrospective; institution based cross sectional descriptive study. This study included the data of 219 children between 1 and 15 years diagnosed with CP from January 2014 to June 2016, in the clinic of Self-help Group for Cerebral Palsy, Nepal. Kaufman Assessment Battery for Children-II was used to assess their IQ. Severity was classified by Gross Motor Function Classification System and Quality of Life(QoL) as per “Cerebral Palsy-Quality Of Life questionnaire for children” manual. Results: Among 219 CP children 75 children (34%) were found to be suffering from Epilepsy. 12% of dyskinetic and none of ataxic types of CP had epilepsy while 67 children (46%) with spastic CP had Epilepsy. Epilepsy was less prevalent in Unilateral spastic CP compared to bilateral. Epileptic children with similar severity had lesser QoL and IQ while more behaviour problems. Prevalence of epilepsy in CP was found to be independent of the socio-economic status of the parents. It was seen that 29% were not taking Anti Epileptic Drugs (AEDs) due to financial constraints. Only 38% of the children were seizure free. 16% of the parents thought that the seizures were supernatural or paranormal phenomenon, 11% of them believed that epilepsy was contagious and 18% were unsure. 54% of the children were also using non-medical measures for epilepsy as ayurvedic and traditional medicines, religious healing rituals, homeopathy, witch doctors, etc. Conclusion: Epilepsy was most common in children with spastic CP. Treatment of epilepsy in children with CP is essential in promoting the QoL and decreasing co-morbidities. Proper measures should be taken to address this issue, most importantly feasible access to AEDs and awareness.

Characteristics of symptomatic epilepsy and quality of care in children with neuronal heterotopia

Objective: Study the features of epilepsy in children with heterotopia. Methods: There are 25 patients: 15 boys (60%) and 10 girls (40%). Results: In 24 patients (96%) identified a variety of changes in neurological status. Severe motor impairment with the formation of palsy, a violation of the innervation of the bulbar group cranial nerves – in twelve patients (48%). Muscular hypotonia – 8 patients (32%). Extrapyramidal symptoms lesion as hyperkinesis, ataxia – 6 patients (25%). In 96% of children were noted intellectual-mental disorders in varying degrees of severity. Simple focal seizures were observed in two boys (8%) and one girl (4%), complex focal seizures – in five boys (20%) and three girls (12%). Three boys (12%) and three girls (12%) had focal seizures with secondary generalization. Generalised seizures were observed in four boys (16%) and one girl (4%). Myoclonic-astatic – two girls (8%). Epileptic spasms – two girls (8%). Seizures are not fixed in three boys (12%) and one girl (4%). Three boys and three girls diagnosed focal epilepsy with secondary generalization (24%), including: multifocal – one boy and one girl (8%). The generalized form – in four boys and one girl (20%), epileptic encephalopathy – two girls (8%). Antiepileptic drugs used in the treatment of epilepsy in children with heterotopias in monotherapy and polytherapy. Valproate used in 19 patients (79.17%). Topiramate was used in six patients (25.0%). ACTH is also used in six patients (25.0%). Carboxamide derivatives, phenobarbital, levetiracetam and used to treat epilepsy equally – in five children (20.83%). Benzodiazepines – four patients (17.39%). Vigabatrin – four patients (17.39%). Lamotrigine – one patient (14.29%). Succinimido in therapy have not been applied. Conclusion: Epilepsy is one of the most acute medico-social problems of neurology, have a negative impact on all aspects of the patient's life.

Trends in Antiepileptic Drug Use in Children and Adolescents With Epilepsy

ObjectiveWe describe the trends in antiepileptic drug (AED) use in children and adolescents with epilepsy in the United States. MethodsWe undertook a cross-sectional study based on Medicaid Analytic eXtract data set from 26 US states. Children and adolescents aged three to 18 years with at least one year continuous Medicaid fee-for-service coverage after the second outpatient or the first inpatient diagnosis of epilepsy in each calendar year during 1999 to 2009 were included in the study; therefore, 11 cohorts were established. A patient was defined as being exposed to a specific AED if he or she had at least one-day supply of the AED during the 1-year follow-up period. The annual prevalence of AEDs was reported, stratified by gender and age. The trends in AED use were evaluated through linear regression. ResultsThe sample sizes of the 11 cohorts ranged between 17,304 and 22,672. The annual prevalence of valproic acid use declined from 42.4% in 1999 to 26.5% in 2009, and the prevalence of carbamazepine use declined from 37.1% to 10.2%. Meanwhile, the prevalence of levetiracetam use increased from 5.1% to about 32.0% in 2009, and the prevalence of oxcarbazepine use increased from 1.3% to 19.1%. Since 2008, levetiracetam (29.6%) has replaced valproic acid (27.8%) as the most commonly used AED in children and adolescents with epilepsy. The prevalence of diazepam use increased from 11.6% to 28.1%. SignificanceCompared with first- and second-generation antiepileptic drugs, third-generation AEDs have fewer adverse side effects, resulting in increased patient treatment adherence. Equally important is the economic impact of these newer AEDs. This first-of-its-kind study underscores the need for large database studies that objectively assess the cost-effectiveness of third-generation AEDs versus first- and second-generation AEDs in the treatment of childhood epilepsy.

Ketogenic diet in the treatment of epilepsy in children under the age of 2 years: study protocol for a randomised controlled trial

BackgroundThe incidence of epilepsy is greatest in the first 2 years of life, an age group where there is generally a poor prognosis for both seizure control and neurodevelopmental outcome. Early control of seizures can be associated with better developmental outcome but many of the epilepsies presenting in infancy are poorly responsive to antiepileptic medication. The ketogenic diet (KD) is a high-fat, low-carbohydrate diet designed to mimic the effects of starvation on the body. Dietary fat is converted into ketones in the body and used as an energy source by the brain. The KD has been shown to be successful in controlling seizures in many observational studies, and in two randomised controlled trials (RCTs) in older children. However, little evidence is available in the very young.Methods/designAn open-label RCT where eligible children (age 3 months to 2 years with epilepsy who have failed two antiepileptic drugs (AEDs)) undergo baseline assessment, including medical and seizure history. Participants then start an observation period (7 or 14 days) with documentation of seizure frequency. Randomisation will occur on day 8 or day 15 to receive the KD or a further AED; the allocated treatment will commence on day 15, with instruction and training. A second assessment (4 weeks after start of treatment) will include a clinical review and tolerability questionnaire (modified Hague Scale of Side Effects – for those allocated to the KD group). Assessments will be repeated at 8 weeks after the start of treatment including biochemical investigations, after which, according to patient response, KD (diet group) or AED (standard AED group) will then be continued or changed. Those in the AED group who have failed to achieve seizure control at the 8-week assessment will then be offered KD outside the context of the trial. Those in the KD arm who fail to achieve seizure control will be changed to standard clinical management. All patients will be followed up for 12 months from randomisation for retention, seizure outcome, quality of life and neurodevelopmental status.DiscussionThe slow rate of recruitment is an ongoing practical issue. There is a limitation to the number of eligible patients compared to what was predicted, mainly due to the nature of this patient group. After a substantial amendment to widen inclusion criteria and reduce the baseline period to 7 days for patients with a high seizure burden, the rate of recruitment steadily increased. A number of operational concerns regarding dietetic time were also highlighted impacting on the recruitment rate. However, the combination of a low dropout rate and the opening of further centres, the trial should successfully meet the final recruitment target. All nine centres are now recruiting and we hope to open further centres within the UK.Trial registrationClinicalTrials.gov, identifier: NCT02205931. Registered on 16 December 2013.

Potential risk factors for vitamin D levels in medium- and long-term use of antiepileptic drugs in childhood

Antiepileptic drugs (AED) have potential side effects through vitamin-D. Prevalence of vitamin D insufficiency and potential risk factors for the longitudinal changes of vitamin D levels compared to its baseline levels under AED treatment were investigated in this study. This retrospective study includes patients whose AED therapy were started in only autumn months, between 2000 and 2014. Detailed assessment of neurologic diagnosis and brain MRI findings, ambulatory status, types and durations of AED treatment, and baseline bone health blood tests (vitamin-D, alkaline phosphatase, calcium, and phosphate levels) were obtained on all patients. Vitamin-D deficiency was defined as 25(OH)D <20ng/mL, while vitamin-D insufficiency was defined as 25(OH)D between 21 and 29ng/mL. A total of 172 children (mean age 9.6±4.3years) were followed up 5.3years in average (range 1-14.7). The mean baseline 25(OH)D level was decreased from 24.4±11.6 to 19.6±10.7ng/mL at the last follow up. The mean change in the vitamin-D levels (ΔD-vitamin) was -4.8ng/mL (p=0.003). The rate of vitamin-D deficiency was 54% and insufficiency was 25%. Multivariate logistic regression analysis identified only long-term use of AEDs as a risk factor for the longitudinal decrease. Monotherapy with valproic acid (n=45), carbamazepine (n=20), levetiracetam (n=10) and phenobarbital (n=12) was compared with each other. There was no difference in terms of longitudinal changes in 25(OH)D levels. In the treatment of childhood epilepsy, 25(OH)D levels should be monitored, especially when long-term AED used, in order to prevent D-hypovitaminosis.

Extratemporal disconnective procedures for the treatment of epilepsy in children

Surgical treatment of epilepsy in children often involves brain areas outside the temporal lobe and, therefore, techniques for extratemporal surgery must be included in the armamentarium of epilepsy surgery centers. Nowadays, disconnective procedures are preferable to traditional resective operations because they reduce the rate of complications related to extensive resections while achieving equivalent seizure outcomes. This article describes the practical anatomy and surgical techniques used for temporoparietooccipital (TPO), parietooccipital, and frontal disconnections, as well as the possibility of extending previous lobar disconnections to the whole hemisphere (hemispherotomy).

Behavioral disinhibition and antiepileptic treatment in childhood epilepsy: A retrospective cohort study.

SummaryObjectiveTo test whether specific classes of antiepileptic drugs increase the risk for behavioral disinhibition, a frequent complication of treatment of childhood epilepsy.MethodsIn a sample of children with active epilepsy and antiepileptic drug (AED) treatment (n = 146, age 4–17 years), we performed a retrospective chart analysis of the occurrence of symptoms indicating reduced behavioral disinhibition following AED treatment. We used a risk‐set approach to analyze whether the presence or recent addition of AED categories defined by their mechanism of action were associated with enhanced risk for behavioral disinhibition symptoms.ResultsMean duration of follow‐up was 2,343 days (range 218–6,292, standard deviation [SD] 1,437). Episodes of behavioral disinhibition were reported in 51 (34.9%) children, with variable latencies between latest change and occurrence of behavioral disinhibition symptoms (mean 67 days, range 2–367). Current use of AEDs targeting gamma‐aminobutyric acid (GABA) (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.02–3.29, p = 0.04) and SV2A‐mediated neurotransmitter release (SV2A)‐mediated (2.0, 1.13–3.60, p = 0.02) neurotransmitter release was associated with increased risk for behavioral disinhibition. Restricting the analysis to the 90 days before behavioral disinhibition episode occurrence revealed that only addition of GABAergic AEDs (OR = 26.88, 95% CI = 6.71–107.76, p < 0.001) was associated with behavioral disinhibition. In contrast to our expectations, seizure control was reported to have improved parallel to most behavioral disinhibition episodes.SignificanceThis exploration of behavioral disinhibition in relation to antiepileptic drug treatment indicates that GABA potentiating drugs are specifically associated with behavioral problems during treatment of childhood epilepsy. Behavioral disinhibition episodes often occurred while seizure control improved, which may have reduced alertness for the consequences of AEDs on interictal symptoms. Our findings may be related to the increasing evidence for a role for excitatory actions of GABA in childhood epilepsy.

Pharmacokinetics and Pharmacogenetics of Carbamazepine in Children.

Although carbamazepine is one of the oldest anticonvulsant drugs, it is still heavily utilized for treatment of epilepsy in children. The aim of this article was to review the current knowledge about pharmacokinetics and pharmacogenetics of carbamazepine in children. The literature for this review was systematically searched for in the MEDLINE and SCINDEKS databases. Oral bioavailability of carbamazepine in children is about 75-85%, and it is approximately 75-85% bound to plasma proteins. Apparent volume of distribution is 1.2-1.9l/kg and total clearance between 0.05 and 0.1l/h/kg. Pharmacokinetics of carbamazepine in children is age and body weight dependent and highly variable due to influence of dosing regimen and co-medication. The current evidence on the importance of pharmacogenetics for carbamazepine efficacy and safety in children supports the association of PXR*1B, HNF4a rs2071197, CYP1A2*1F, ABCC2 1249G>A, and PRRT2 c.649dupC with either pharmacokinetics or pharmacodynamics of carbamazepine. The importance of human leukocyte antigen (HLA)typing for prediction of adverse drug reactions to carbamazepine in children is also confirmed. Both genetic and environmental factors are responsible for shaping pharmacokinetics and pharmacodynamics of carbamazepine in children. To ensure safe and effective use of carbamazepine in this population, physicians should adjust dosing regimen according to existing pattern of genetic and environmental influences.

Perampanel in the treatment of drug-resistant epilepsy in children

Background. Despite the existing variety of available methods for the treatment of drug-resistant epilepsy in children, there are still many patients that are not suitable for surgical treatment and have no response to alternative therapeutic measures (vagus nerve stimulation and ketogenic diet). In these patients, the problem of searching for new antiepileptic drugs is particularly urgent. The article presents original data on the efficacy and tolerability of perampanel in children with epilepsy. Materials and methods . Our retrospective study included 55 children (33 males and 22 females) under the age of 18 that received perampanel. This study was performed without external sponsor support at the Svt. Luka’s Institute of Child Neurology and Epilepsy during 2015–2017. Results . Perampanel demonstrated high efficiency against generalized (myoclonic and tonic) seizures and moderate efficiency against focal motor seizures. The drug was significantly less effective in patients with atypical absence seizures and ineffective in children with atonic seizures. Perampanel was generally well tolerated by the majority of patients. The most frequent adverse effects that required the drug to be withdrawn (9 out of 55 cases, 16.4 %) were psychic exhaustion and apathy. Less frequent side effects that lead to perampanel cessation included aggravation (4 %), psychotic episode (2 %) and idiosyncrasy (2 %). Such transient states as ataxia (21 %), decreased appetite (13 %) and muscle rela xation (24.5 %) did not require perampanel withdrawal. Our results suggest that the efficacy of perampanel is 58.5 %. Currently, 37.8 % of patients continue receiving the drug, whereas in 20.7 % of children it was withdrawn due to adverse reactions, despite its high efficacy against seizures. In 41.5 % of patients, we observed neither positive effect nor adverse reactions. Conclusions . Further studies on perampanel in children under 12 years old are needed, since our results suggest its efficiency for drug-resistant epilepsy.

THE FORMATION OF COGNITIVE AND MENTAL DISORDERS IN EPILEPSY: THE ROLE OF VARIOUS FACTORS ASSOCIATED WITH DISEASE AND TREATMENT (A REVIEW OF LITERATURE AND CASE REPORTS)

Cognitive and mental disorders often occur in patients with epilepsy and significantly reduce the quality of life of patients and their families. Approximately in 35 % of patients, despite treatment, various violations of intelligence, behavior, affective sphere of different degree of seve rity are preserved. In general, mental (affective, anxious and psychotic) disorders occur in epilepsy 2–3 times more often than in the general population. The most common is depression: the occurrence of depression and anxiety in epilepsy varies from 20 to 55 % (and more than 50 % of patients with refractory focal epilepsy, especially epilepsy of the temporal lobe of the brain). Children are a particularly vulnerable category of patients: in addition to persistent intellectual disabilities (mental retardation), they may have specific impairments in the form of mental and speech development delay, learning difficulties, attention deficit hyperactivity disorder. Causes of cognitive and mental disorders in epilepsy can directly be the factor underlying epilepsy (genetic disease, structural brain defect, etc.), epileptic seizures, interictal epileptiform activity, side effects of antiepileptic drugs (AED). In many cases, a patient with epilepsy combines several of these causes, and it is often difficult to determine which one cause is leading. The contribution of specific factors is difficult to estimate, because different factors can have an independent different effect on cognitive impairment. Some of causes underlying cognitive and mental disorders in epilepsy can be influenced and thus reduce the existing risk. Such measures include early diagnosis and effective adequate treatment of epileptic encephalopathy, as early as possible control of seizures, justified appointment of AED in children with cognitive impairment of unknown etiology and frequent epileptiform discharges on the electroencephalogram, careful monitoring of cognitive side effects of AED and assessment of benefit–risk ratio, early surgical treatment of patients with resistance to therapy. Of course, the use of AED with the most favorable profile of influence on cognitive functions plays an important role in the treatment of epilepsy. In the treatment of epilepsy in children, it’s especially important to give preference to AED, which doesn’t negatively influence on the cognitive sphere.

Aberrant epilepsy-associated mutant Nav1.6 sodium channel activity can be targeted with cannabidiol.

Mutations in brain isoforms of voltage-gated sodium channels have been identified in patients with distinct epileptic phenotypes. Clinically, these patients often do not respond well to classic anti-epileptics and many remain refractory to treatment. Exogenous as well as endogenous cannabinoids have been shown to target voltage-gated sodium channels and cannabidiol has recently received attention for its potential efficacy in the treatment of childhood epilepsies. In this study, we further investigated the ability of cannabinoids to modulate sodium currents from wild-type and epilepsy-associated mutant voltage-gated sodium channels. We first determined the biophysical consequences of epilepsy-associated missense mutations in both Nav1.1 (arginine 1648 to histidine and asparagine 1788 to lysine) and Nav1.6 (asparagine 1768 to aspartic acid and leucine 1331 to valine) by obtaining whole-cell patch clamp recordings in human embryonic kidney 293T cells with 200 μM Navβ4 peptide in the pipette solution to induce resurgent sodium currents. Resurgent sodium current is an atypical near threshold current predicted to increase neuronal excitability and has been implicated in multiple disorders of excitability. We found that both mutations in Nav1.6 dramatically increased resurgent currents while mutations in Nav1.1 did not. We then examined the effects of anandamide and cannabidiol on peak transient and resurgent currents from wild-type and mutant channels. Interestingly, we found that cannabidiol can preferentially target resurgent sodium currents over peak transient currents generated by wild-type Nav1.6 as well as the aberrant resurgent and persistent current generated by Nav1.6 mutant channels. To further validate our findings, we examined the effects of cannabidiol on endogenous sodium currents from striatal neurons, and similarly we found an inhibition of resurgent and persistent current by cannabidiol. Moreover, current clamp recordings show that cannabidiol reduces overall action potential firing of striatal neurons. These findings suggest that cannabidiol could be exerting its anticonvulsant effects, at least in part, through its actions on voltage-gated sodium channels, and resurgent current may be a promising therapeutic target for the treatment of epilepsy syndromes.

Treatment of epilepsy in children with brain tumors

Symptomatic focal epilepsy is frequently caused by supratentorial brain tumors that may be surgically removed. The authors studied outcomes of surgical treatment depending on the use of electrocorticography c (ECoG). Seventy-five children, aged 5-7 years, with supratentorial brain tumors were examined. Symptomatic epilepsy was found in 52 (69.3%) patients. Dysembryoplastic neuroepithelial tumors (DNET) and fibrillary astrocytomas were the most epileptogenic tumors. The outcomes on the Engel scale were as follows: in 27 patients with surgical intervention without ECoG: class I - 9 patients, class II - 7 patients, class III - 5 patients, class IV - 6 patients and in 25 patients operated with ECoG: class I - 19 patients, class II - 4 patients and class III - 2 patients. The significant difference (p<0.01) between I+II Engel classes in comparison with III+IV Engel classes in operated patients demonstrated the necessity of ECoG during surgery in the resection of supratentorial brain tumors in patients with symptomatic epilepsy.