Evaluating the Credibility and Reliability of Online Information on Cannabidiol (CBD) for Epilepsy Treatment in Poland.

The interest in the potential therapeutic use of cannabis, especially cannabidiol (CBD), has increased significantly in recent years. On the Internet, users can find lots of articles devoted to its medical features such as reducing seizure activity in epilepsy. The aim of our work was to evaluate the information contained on the websites, including social media, in terms of the credibility and the reliability of current knowledge about the usage of products containing cannabidiol in epilepsy treatment. We used online available links found using the Newspointtool. The initial database included 38,367 texts, but after applying the inclusion and exclusion criteria, 314 texts were taken into consideration. Analysis was performed using the DISCERN scale and the set of questions created by the authors. In the final assessment, we observed that most of the texts (58.9%) were characterized by a very poor level of reliability and the average DISCERN score was 26.97 points. Additionally, considering the form of the text, the highest average score (35.73) came from entries on blog portals, whereas the lowest average score (18.33) came from comments and online discussion forums. Moreover, most of the texts do not contain key information regarding the indications, safety, desired effects, and side effects of CBD therapy. The study highlights the need for healthcare professionals to guide patients towards reliable sources of information and cautions against the use of unverified online materials, especially as the only FDA-approved CBD medication, Epidiolex, differs significantly from over-the-counter CBD products.

Hydrophilic interaction liquid chromatography with mass spectrometry for the separation and identification of antisense oligonucleotides impurities and nusinersen metabolites.

With the development of therapeutic oligonucleotides for antisense and gene therapies, the demand for analytical methods also increases. For the analysis of complex samples, for example plasma samples, where the use of mass detection is essential, hydrophilic interaction liquid chromatography is a suitable choice. The aim of the present work was to develop a method for separation and identification of the oligonucleotide impurities and metabolites by hydrophilic interaction liquid chromatography. First of all, the effects of different chromatographic conditions (e.g. pH of the aqueous part of the mobile phase, buffer concentration, column temperature) on the retention and separation of phosphorothioate oligonucleotides standards on the amide stationary phase were investigated. A set of model oligonucleotides containing a fully modified 21mer and its typical impurities (shortmers and oligonucleotides with different number of thiophosphate modifications) was used. The results showed that the concentration of the salt in the mobile phase as well as its pH, are the most influential parameters with regard to peak shape and separation. The knowledge gained was applied to the analysis of an unpurified 18mer oligonucleotides, analogues of the drug nusinersen used for the treatment of spinal muscular atrophy. The successful separation and identification of twenty-six and twenty-eight impurities was performed with the developed HILIC method. The method was applied to analysis of nusinersen metabolites of serum samples of patients treated with Spinraza.

Comparison of knowledge and awareness of epilepsy between medical students of two universities in Poland.

BACKGROUND: Epilepsy is one of the most common neurological disorders. As a chronic disease, associated with long-term treatment with antiseizure medication, it can have a negative impact on patients' quality of life. Moreover, patients are faced with a significant psychosocial burden associated with the stigma surrounding epilepsy. Medical professionals should be well educated and free of prejudices in order to provide adequate care for patients with epilepsy. The aim of the study was to evaluate the knowledge and awareness of epilepsy among medical students of years 1-6 in Poland and examine if certain personality traits influence students' view of epilepsy. METHODS: The study was conducted using snowball sampling of 166 Polish medical students from Medical University of Gdansk and Medical University of Warsaw. Participants completed a survey which consisted of their subjective assessment of knowledge of epileptology, actual knowledge of epileptology, and their view of stereotypes about epilepsy. In addition, students completed the IPIP-BFM-20 personality questionnaire. RESULTS: Polish medical students have sufficient basic knowledge about epilepsy (mean scores of students from both universities is 14 out of 25 points). There is still room for improvement, especially in the field of epidemiology, semiology, factors provoking seizures, antiseizure medications, and most importantly about first aid during seizure (e.g., 7% of respondents believed it is necessary to put something between teeth of a patient during seizure). Age and the year of study were well correlated with knowledge score (p = 0.008) and level of awareness of the stereotypes. We found that most personality traits do not have a strong impact on the level of knowledge about epilepsy. CONCLUSIONS: Most students have a satisfying level of knowledge about epilepsy. Academic teachers should put more emphasis on first aid during seizures and awareness of psychosocial challenges associated with the disease. It is crucial for future physicians to not only possess sufficient theoretical knowledge, but also establish an empathetic doctor-patient relationship in order to provide better care for patients with epilepsy and other chronic diseases.

Impairment of cognitive functions in children and adolescents with focal epilepsy.

Introduction: Frontal Lobe Epilepsy (FLE) and Temporal Lobe Epilepsy (TLE) are the two most frequent types of focal epilepsies and they are connected with difficulties in cognitive functioning. Despite multiple trials to systematize profile of cognitive functioning among children with epilepsy by researchers, the available data are ambiguous. The aim of our study was to compare the cognitive function of children upon diagnosis of TLE and FLE and during follow-up and to compare with a control group of healthy children. Material and methods: Study included 39 patients with newly diagnosed TLE, 24 patients with FLE whose first epileptic seizure occurred between their 6th and 12th year of life and 24 healthy children matched by age, sex and IQ level. Neuropsychological examination was performed the moment of diagnosis and 2-3 years later using diagnostic tools validated and standardized to the patient's age. Intergroup comparison was conducted in both stages of study. Also, correlation between localization of epileptic focus and cognitive difficulties was analysed. Results: Children with FLE and TLE accomplished worse results in most of the cognitive tasks compared to the control group already in the initial examination. Patients with FLE presented difficulties in memorizing verbal and visual material, attention and in learning new information. Patients with TLE had difficulties in tasks engaging verbal and non-verbal memory and attention. In the follow-up, patients with FLE presented more severe cognitive impairment compared with the other groups. Despite similar tendencies among children with TLE significantly worse results in tasks engaging verbal memory and attention were observed among patients with FLE. It is noteworthy that patients suffering from FLE and TLE present deficits in many aspects of cognitive functioning already at the time of diagnosis. Conclusion: Children and adolescents suffering from epilepsy are at risk of psychosocial difficulties, emotional disorders and mental illnesses. Thus, full assessment of cognitive function is essential in this patient group not only at the moment of diagnosis but also during follow-up in order to quickly introduce an individual support system.

A novel de novo FEM1C variant is linked to neurodevelopmental disorder with absent speech, pyramidal signs and limb ataxia.

The principal component of the protein homeostasis network is the ubiquitin-proteasome system. Ubiquitination is mediated by an enzymatic cascade involving, i.e. E3 ubiquitin ligases, many of which belong to the cullin-RING ligases family. Genetic defects in the ubiquitin-proteasome system components, including cullin-RING ligases, are known causes of neurodevelopmental disorders. Using exome sequencing to diagnose a pediatric patient with developmental delay, pyramidal signs and limb ataxia, we identified a de novo missense variant c.376G>C; p.(Asp126His) in the FEM1C gene encoding a cullin-RING ligase substrate receptor. This variant alters a conserved amino acid located within a highly constrained coding region and is predicted as pathogenic by most in silico tools. In addition, a de novo FEM1C mutation of the same residue p.(Asp126Val) was associated with an undiagnosed developmental disorder, and the relevant variant (FEM1CAsp126Ala) was found to be functionally compromised in vitro. Our computational analysis showed that FEM1CAsp126His hampers protein substrate binding. To further assess its pathogenicity, we used the nematode Caenorhabditis elegans. We found that the FEM-1Asp133His animals (expressing variant homologous to the FEM1C p.(Asp126Val)) had normal muscle architecture yet impaired mobility. Mutant worms were sensitive to the acetylcholinesterase inhibitor aldicarb but not levamisole (acetylcholine receptor agonist), showing that their disabled locomotion is caused by synaptic abnormalities and not muscle dysfunction. In conclusion, we provide the first evidence from an animal model suggesting that a mutation in the evolutionarily conserved FEM1C Asp126 position causes a neurodevelopmental disorder in humans.

Next-generation sequencing testing in children with epilepsy reveals novel clinical, diagnostic and therapeutic implications.

Introduction: Epilepsy is one of the commonest diseases in children, characterized by extensive phenotypic and genetic heterogeneity. This study was conducted to determine the diagnostic utility and to identify novel clinical and therapeutic implications of genetic testing in pediatric patients with epilepsy. Methods: Large multigene panel and/or exome sequencing was performed in 127 unrelated Polish and Ukrainian patients with suspected monogenic epilepsy. Diagnostic yields were presented for five phenotypic subgroups, distinguished by seizure type, electroencephalographic abnormalities, anti-seizure treatment response, and neurodevelopmental deficits. Results: A definite molecular diagnosis was established in 46 out of 127 cases (36%). Alterations in six genes were detected in more than one patient: SCN1A, MECP2, KCNT1, KCNA2, PCDH19, SLC6A1, STXBP1, and TPP1, accounting for 48% of positive cases. 4/46 cases (8.7%) were mosaic for the variant. Although the highest rates of positive diagnoses were identified in children with developmental delay and generalized seizures (17/41, 41%) and in developmental end epileptic encephalopathies (16/40, 40%), a monogenic etiology was also frequently detected in patients with solely focal seizures (10/28, 36%). Molecular diagnosis directly influenced anti-seizure management in 15/46 cases. Conclusion: This study demonstrates the high diagnostic and therapeutic utility of large panel testing in childhood epilepsies irrespective of seizure types. Copy number variations and somatic mosaic variants are important disease-causing factors, pointing the need for comprehensive genetic testing in all unexplained cases. Pleiotropy is a common phenomenon contributing to the growing phenotypic complexity of single-gene epilepsies.

Social Media as a Source of Knowledge about Gene Therapy for Spinal Muscular Atrophy.

Social media is one of the most common sources of medical information. We aimed to evaluate the information contained on websites, including social media and descriptions of fundraisers, in terms of the reliability of knowledge about SMA and gene therapy with onasemnogen abeparvovec. We used a set of available online links found using the Newspointtool. Initially, 1525 texts were included in the study, and after applying the inclusion and exclusion criteria, 112 texts were qualified for analysis using the DISCERN scale and the set of questions prepared by the authors. We observed that most of the texts had poor (48.65%) and medium (27.03%) reliability in the final reliability assessment. All the texts selected for the study were related to gene therapy, although few contained key information about it. In addition, the authors of the entries used various words and phrases that influenced the readers' perceptions of the text. Of the analyzed sources, 68.8% had an emotional component. Social media is a poor source of information about gene therapy for SMA in Poland. The analyzed texts do not provide a full and complete description of the SMA problem. However, it is important to remember that the Internet is a changing source of information and will hopefully contain more relevant entries in the future.

The Clinical and Epidemiological Profile of Paediatric-Onset Multiple Sclerosis in Poland.

Background. Paediatric-onset MS (POMS) has a unique clinical profile compared to the more prevalent adult-onset MS. For this study, we aimed to determine the demographic and clinical characteristics of POMS in Poland as well as addressing some of its epidemiological aspects. Methods. A retrospective study was conducted based on the Polish Multiple Sclerosis Registry, considering a population of children and adolescents with MS (age ≤ 18 years). Data were collected by all 13 centres across Poland specializing in diagnosing and treating POMS. The actual course of the disease and its clinical properties were compared between child (≤12 years) and juvenile (>12 years) patients. MS onset and its prevalence were assessed at the end of 2019, stratified by age range. Results. A total of 329 paediatric or juvenile patients (228 girls, 101 boys) with a clinically definite diagnosis of MS, in conformity with the 2017 McDonald Criteria, were enrolled. For 71 children (21.6%), the first symptoms appeared before the age of 12. The female: male ratio increased with age, amounting to 1:1 in the ≤12 years group and to 2.9:1 in the >12 years group. In most cases, the disease had multi-symptomatic onset (31.3%), and its course was mostly of a relapsing−remitting character (95.7%). The initial Expanded Disability Status Score for both groups was 1.63 ± 1.1, whereas the annual relapse rate was 0.84 during the first 2 years. The time between the onset of symptoms and diagnosis was longer in the younger patients (8.2 ± 4.2 vs. 4.6 ± 3.6 months; p < 0.005). On 31 December 2019, the age-adjusted prevalence standardized to the European standard population was 5.19/100,000 (95% CI, 4.64−5.78). Significantly higher prevalence was noted in the 13−18 years group (7.12; 95% CI, 6.64−7.86) than in the 9−12 years group (3.41; 95% CI, 2.98−3.86) and the <9 years group (0.56; 95% CI, 0.46−0.64; p < 0.001). Conclusion. POMS commencing at the age of ≤12 years is rare, differing significantly from the juvenile-onset and adult MS in terms of clinical characteristics, course, and incidence, as stratified by gender.

Safety and efficacy of risdiplam in patients with type 1 spinal muscular atrophy (FIREFISH part 2): secondary analyses from an open-label trial.

BACKGROUND: Risdiplam is an orally administered therapy that modifies pre-mRNA splicing of the survival of motor neuron 2 (SMN2) gene and is approved for the treatment of spinal muscular atrophy. The FIREFISH study is investigating the safety and efficacy of risdiplam in treated infants with type 1 spinal muscular atrophy versus historical controls. The primary endpoint of part 2 of the FIREFISH study showed that infants with type 1 spinal muscular atrophy attained the ability to sit without support for at least 5 s after 12 months of treatment. Here, we report on the safety and efficacy of risdiplam in FIREFISH part 2 over 24 months of treatment. METHODS: FIREFISH is an ongoing, multicentre, open-label, two-part study. In FIREFISH part 2, eligible infants (aged 1-7 months at enrolment, with a genetically confirmed diagnosis of spinal muscular atrophy, and two SMN2 gene copies) were enrolled in 14 hospitals in ten countries across Europe, North America, South America, and Asia. Risdiplam was orally administered once daily at 0·2 mg/kg for infants between 5 months and 2 years of age; once an infant reached 2 years of age, the dose was increased to 0·25 mg/kg. Infants younger than 5 months started at 0·04 mg/kg (infants between 1 month and 3 months old) or 0·08 mg/kg (infants between 3 months and 5 months old), and this starting dose was adjusted to 0·2 mg/kg once pharmacokinetic data were available for each infant. The primary and secondary endpoints included in the statistical hierarchy and assessed at month 12 have been reported previously. Here we present the remainder of the secondary efficacy endpoints that were included in the statistical hierarchy at month 24: the ability to sit without support for at least 30 s, to stand alone, and to walk alone, as assessed by the Bayley Scales of Infant and Toddler Development, third edition gross motor subscale. These three endpoints were compared with a performance criterion of 5% that was defined based on the natural history of type 1 spinal muscular atrophy; the results were considered statistically significant if the lower limit of the two-sided 90% CI was above the 5% threshold. FIREFISH is registered with ClinicalTrials.gov, NCT02913482. Recruitment is closed; the 36-month extension period of the study is ongoing. FINDINGS: Between March 13 and Nov 19, 2018, 41 infants were enrolled in FIREFISH part 2. After 24 months of treatment, 38 infants were ongoing in the study and 18 infants (44% [90% CI 31-58]) were able to sit without support for at least 30 s (p<0·0001 compared with the performance criterion derived from the natural history of untreated infants with type 1 spinal muscular atrophy). No infants could stand alone (0 [90% CI 0-7]) or walk alone (0 [0-7]) after 24 months of treatment. The most frequently reported adverse event was upper respiratory tract infection, in 22 infants (54%); the most common serious adverse events were pneumonia in 16 infants (39%) and respiratory distress in three infants (7%). INTERPRETATION: Treatment with risdiplam over 24 months resulted in continual improvements in motor function and achievement of developmental motor milestones. The FIREFISH open-label extension phase will provide additional evidence regarding long-term safety and efficacy of risdiplam. FUNDING: F Hoffmann-La Roche.

Development of the Method for Nusinersen and Its Metabolites Identification in the Serum Samples of Children Treated with Spinraza for Spinal Muscular Atrophy.

The application of oligonucleotides as drugs for different genetic diseases is increasing rapidly. Since 2016 they are used during spinal muscular atrophy treatment with the use of nusinersen oligonucleotide. The purpose of this study was to improve methods for the analysis of serum samples of patients treated with nusinersen. The results showed that liquid-liquid extraction (with phenol/chloroform) is insufficient and an additional purification step using solid-phase extraction is necessary. The best results were obtained for microextraction by packed sorbents. Important parameters in the optimization of the method were mainly the type of amine in the mobile phase and the stationary phase. Both influenced the selectivity of metabolite separation and thus their correct identification; while amine type impacted also the intensity of signals. Finally, the highest resolution of separation and the highest peak areas were obtained for N,N-dimethylbutylamine or N,N-diisopropylthylamine with an octadecyl column with a terminal aryl group. Over a dozen of metabolites were successfully identified with the use of methods developed during the study. The 3' exonucleases and 5' exonucleases were mainly responsible for nusinersen metabolism, consequently, 3'end shortmers, and 5'end shortmers were observed, as well as metabolites with simultaneous loss of bases at both ends of the sequence. However, some depurination and depyrimidination products were also identified. To the best of our knowledge, this is the first report on nusinersen and its metabolite identification in serum samples by liquid chromatography and mass spectrometry.

Expanding the phenotype of DNAJC30-associated Leigh syndrome.

Leigh syndrome (LS) is a progressive neurodegenerative disease, characterized by extensive clinical, biochemical, and genetic heterogeneity. Recently, biallelic variants in DNAJC30 gene, encoding a protein crucial for the repair of mitochondrial complex I subunits, have been associated with Leber hereditary optic neuropathy and LS. It was suggested that clinical heterogeneity of DNAJC30-associated mitochondrial disease may be attributed to digenic inheritance. We describe three Polish patients, a 9-year-old boy, and female and male siblings, aged 17 and 11 years, with clinical and biochemical manifestations of LS. Exome sequencing (ES) identified a homozygous pathogenic variant in DNAJC30 c.152A>G, p.(Tyr51Cys) in the 9-year-old boy. In the siblings, ES identified two DNAJC30 variants: c.152A>G, p.(Tyr51Cys) and c.130_131del, p.(Ser44ValfsTer8) in a compound heterozygous state. In addition, both siblings carried a novel heterozygous c.484G>T, p.(Val162Leu) variant in NDUFS8 gene. This report provides further evidence for the association of DNAJC30 variants with LS. DNAJC30-associated LS is characterized by variable age at onset, movement disorder phenotype and normal or moderately elevated blood lactate level. Identification of a candidate heterozygous variant in NDUFS8 supports the hypothesis of digenic inheritance. Importantly, DNAJC30 pathogenic variants should be suspected in patients with LS irrespective of optic nerve involvement.

Recommendations for treatment strategies in people with epilepsy during times of shortage of antiseizure medications

In times of severe antiseizure medication (ASM) shortage due to emergency situations (e.g., disasters, conflicts, sudden disruption to international supply chains), management of people with epilepsy with available ASMs can be difficult. A group of experts was brought together by the International League Against Epilepsy (ILAE) to formulate recommendations for such circumstances. Every effort was made to base these recommendations on direct published literature or extrapolations from basic information available about ASMs. Actual published literature in this area is, however, limited, and at times, assumptions were made by the experts to generate these recommendations. During times of shortage of ASMs, switching between different ASMs (e.g., oxcarbazepine and carbamazepine) can occasionally be considered as a mitigation procedure. However, for many ASMs, the option of an overnight switch to another drug does not exist. Switching from brand to generic or between generic products has often been shown to be safe, if required. Finally, when supplies of benzodiazepines or equipment to administer medications intravenously are not available, rectal administration of some ASMs may be an emergency alternative route for treating serial seizures and status epilepticus. Decision-making with regard to treatment and possible options should be driven by what is best for the patient.

Natural history of Type 1 spinal muscular atrophy: a retrospective, global, multicenter study.

BACKGROUND: ANCHOVY was a global, multicenter, chart-review study that aimed to describe the natural history of Type 1 spinal muscular atrophy (SMA) from a broad geographical area and provide further contextualization of results from the FIREFISH (NCT02913482) interventional study of risdiplam treatment in Type 1 SMA. METHODS: Data were extracted from medical records of patients with first symptoms attributable to Type 1 SMA between 28 days and 3 months of age, genetic confirmation of SMA, and confirmed survival of motor neuron 2 copy number of two or unknown. The study period started on 1 January 2008 for all sites; study end dates were site-specific due to local treatment availabilities. Primary endpoints were time to death and/or permanent ventilation and proportion of patients achieving motor milestones. Secondary endpoints included time to initiation of respiratory and feeding support. RESULTS: Data for 60 patients from nine countries across Asia, Europe and North and South America were analyzed. The median age (interquartile range [IQR]) for reaching death or permanent ventilation was ~ 7.3 (5.9-10.5) months. The median age (IQR) at permanent ventilation was ~ 12.7 (6.9-16.4) months and at death was ~ 41.2 (7.3-not applicable) months. No patients were able to sit without support or achieved any level of crawling, standing or walking. INTERPRETATION: Findings from ANCHOVY were consistent with published natural history data on Type 1 SMA demonstrating the disease's devastating course, which markedly differed from risdiplam-treated infants (FIREFISH Part 2). The results provide meaningful additions to the literature, including a broader geographical representation.

Safety, tolerability, and efficacy of a widely available nusinersen program for Polish children with Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is a devastating neuromuscular disorder with limited treatment options. Nusinersen is the first disease-modifying therapy to treat children and adults with SMA. This study aimed to review the safety, tolerability, and efficacy data of a nusinersen treatment program in Polish children. A total of 298 patients aged from 0 to 18 years were included in the nusinersen treatment program in Poland between March 1 and September 20, 2019. All patients were prospectively followed for at least one year. The mean age at treatment onset was 6.9 years. SMA type 1 symptoms were reported in 127 patients (43.5%), SMA type 2 symptoms in 68 cases (23.3%), and SMA type 3 in 93 patients (31.8%). No patient met the inefficiency criteria defined in the program. One year after treatment initiation, all patients assessed by the CHOP-INTEND scale had improved or remained stable. The mean change in CHOP-INTEND score was an increase of 8.9 points between baseline and after one-year treatment (p < 0.001). Except for 2 fatal cases, not related to the treatment, no serious adverse events were reported. The results of our study indicate that treatment with nusinersen is beneficial for children with SMA regardless of their age, baseline functional status, or the number of SMN2 gene copies. Therapy with nusinersen was effective and well tolerated by patients.

Reflex seizures in rare monogenic epilepsies.

Reflex seizures (RSs) are epileptic events consistently induced by specific triggers. They occur in epilepsies of varied etiologies and are often accompanied by spontaneous seizures. The genetic background of RSs is heterogeneous and polygenic or multifactorial inheritance is suspected in the majority of cases. Although causative single-gene variants are rarely identified, the number of genes associated with RSs is gradually increasing. In this article, we describe individuals presenting reflex seizures as predominant epileptic events in whom we identified pathogenic and likely pathogenic variants in CACNA1A, GNAO1, and NOVA2 genes. In addition, we summarize rare monogenic epilepsies associated with RSs. The presence of RSs in our patients expands the phenotypic spectrum of the diseases and contributes to our knowledge of the underlying monogenic defects in reflex seizures.

Pediatric-onset multiple sclerosis in Poland: A registry-based retrospective cohort study.

BACKGROUND: Epidemiologic data on pediatric-onset multiple sclerosis (POMS) in Central and Eastern Europe are limited. The aim of this study was to determine the incidence, prevalence and the clinical features of POMS in Poland. METHODS: Registry-based retrospective study was conducted among Polish children population (age ≤ 18 years), between 1 January 2010 and 31 December 2019. A total of 329 pediatric or juvenile patients fulfilled the International Pediatric MS Study Group (IPMSSG) criteria for MS, reported to the Polish Multiple Sclerosis Registry, were considered for estimation of age- and sex-specific prevalence (per 100,000 persons), and incidence rates (per 100,000 person-years). The demographic data, clinical presentation and treatment strategies also were investigated. RESULTS: On December 31, 2019 in the database were collected data of 329 patients up to 18 years with POMS diagnosis (101 boys and 228 girls; mean age 15.3 ± 3.8 years). The age-adjusted prevalence standardized to the European Standard Population was 5.19/100,000 (95% confidence interval (CI), 4.64-5.78). A significantly higher prevalence was recorded in girls (7.41; 95% CI, 6.48-8.44) than in boys (3.08; 95% CI, 2.50-3.74; P<0.001). The mean annual standardized incidence in Poland between 2015 - 2019 was 0.77 (95%CI, 0.45-1.02) per 100,000 person-years. The highest overall standardized incidence 1.06 (95%CI, 0.82-1.34) was noted in 2018. Most of patients (95.7%) had relapsing-remitting disease with polysymptomatic onset in one-thirds of the cases, and 82.3% were treated with disease-modifying drugs. Family history of MS was reported in 26 cases (7.9%). CONCLUSION: In this first report of registry-based study from Poland an increasing prevalence and incidence of POMS was found during the last years. This temporal trend corroborate the findings of studies conducted elsewhere.

Use of cannabidiol in the treatment of epilepsy.

INTRODUCTION: Cannabis sativa has been cultivated for human use for about 5,000 years, and has likewise been used in the treatment of epilepsy for thousands of years. STATE OF THE ART: Cannabidiol (CBD), which was isolated from cannabis sativa in 1940, has an anti-seizure effect and no psychoactive activity. Its effectiveness in reducing various types of seizures has been proven in animal seizure and epilepsy models. Recent randomised, placebo-controlled trials have confirmed its effectiveness in patients with drug-resistant epilepsy. CLINICAL IMPLICATIONS: The aim of this position paper was to present the specific mechanism of CBD's anti-seizure action and current indications for CBD's use in epilepsy. The only cannabis-derived drug that has successfully passed clinical trials and has obtained United States Food and Drug Administration and European Medicines Agency approval for epilepsy is Epidiolex®. This paper presents the outcomes of the completed clinical trials with the use of this drug. FUTURE DIRECTIONS: CBD may be an effective drug in drug-resistant epilepsy, particularly in Dravet Syndrome, Lennox- Gastaut Syndrome and seizures associated with tuberous sclerosis complex. Additional randomised, placebo-controlled studies with CBD are needed.

Epilepsy awareness among school-aged students in Poland.

OBJECTIVE: Epilepsy can be a well-controlled condition with only a slight impact on patients' life. Lack of knowledge within society contributes to children with epilepsy experiencing discrimination and hostility. The aim of this study was to evaluate the awareness of epilepsy and general views on people struggling with this disease among school-aged children. METHODS: The study was conducted on a random sample of Polish school students, in total 472 participants. Participants' knowledge was assessed by a self-completed survey. RESULTS: Students are unaware of the wide range of symptoms occurring during seizures. More than half claimed that people experiencing epilepsy should not perform sports activities. Alarmingly, 30% of participants believe that those patients should not leave the house and they should be excluded from many jobs. Almost all participants would help a person experiencing seizures and remember proper head protection; shockingly, 20% of children would try to put something in the person's mouth. Older students seem to be better educated on epilepsy, but the percentage of incorrect personal beliefs and myths is similar for each age group. SIGNIFICANCE: School-aged students have insufficient knowledge of epilepsy. More emphasis should be put on first aid during seizures and on the spectrum of epilepsy symptoms. Educating society is important for life quality of people experiencing epilepsy.

COVID-19 pandemic influence on epilepsy course in pediatric patients.

INTRODUCTION: In 2020, Coronavirus Disease 2019 (COVID-19) was declared as a global pandemic. Self-reported stress, anxiety, and insomnia, which are believed to be common triggers for epilepsy, are more likely to occur. We aimed to establish the influence of COVID-19 pandemic itself on changes in the daily life routine related to pandemic on epilepsy course in pediatric patients. The unique form of clinical care which is telemedicine was also taken into consideration. We wanted to evaluate patients' satisfaction with telemedicine and if changing stationary visits into telemedicine influenced epilepsy course in our patients. METHODS: Patients, who attended developmental neurology outpatient clinic in the period March-December 2020 were collected. As patients were minors, legal guardians were asked to fill out the questionnaire. Patients were divided according to the outcome into three groups: those with a worsened, stable, or improved course of epilepsy during the pandemic. Appropriate statistical tests for two-group and multi-group comparisons have been implemented. Post hoc p values were also calculated. RESULTS: Four hundred and two questionnaires were collected. Most of the patients had a stable course of epilepsy during the pandemic; in 13% of participants an improvement has been observed, worsening of the disease was seen in 16% of patients. Age, sex, type of epilepsy, number of seizure incidents before pandemic, and duration of the disease had no statistically significant connection with changes in the course of the disease. Behavioral changes and altered sleep patterns were found to be more common in the worsened group. Fifty-eight percent of patients were satisfied with telemedicine. Poorer satisfaction was connected with less frequent visits, cancellation of scheduled appointments, and lack of help in case of need in an emergency situation. CONCLUSION: Epilepsy course in pediatric patients seems to be stable during COVID-19 pandemic. Sleep disturbances and changes in a child's behavior may be related to increase in seizure frequency. Telemedicine is an effective tool for supervising children with epilepsy. Patients should be informed about possible ways of getting help in urgent cases.