Outcomes following exposure to lacosamide monotherapy during pregnancy and breastfeeding - a prospective case series.

AIM OF THE STUDY: To evaluate the safety of lacosamide (LCM) monotherapy during pregnancy and breastfeeding. MATERIAL AND METHODS: Patients taking LCM monotherapy treated at the university epilepsy clinic were prospectively followed up during pregnancy, delivery, and breastfeeding. Data on seizure frequency, LCM dosage, pregnancy course, delivery and breastfeeding, birth outcome, congenital malformation, and development of newborns was collected. RESULTS: Four pregnancies in three patients with refractory focal epilepsy treated with LCM monotherapy were reported. One of these pregnancies ended in a miscarriage during the seventh week of gestation. The average daily LCM dose at the time of conception was 300 mg. Treatment with LCM was continued throughout pregnancy and breastfeeding. The dose of LCM was increased in two pregnancies: in one case following a seizure relapse, and in the other case as a preventive measure to avoid an increase in seizure frequency. Seizure frequency remained stable during pregnancy in two cases. All deliveries were carried out via caesarean section, with an average gestational age at birth of 37.6 weeks. The Apgar score was 10 in all newborns, and no congenital malformations were detected. At the age of 12 months, normal developmental milestones were reached. Infants were breastfed without any complications. CONCLUSIONS AND CLINICAL IMPLICATIONS: This case series adds to a growing body of evidence suggesting the relative safety of LCM monotherapy throughout pregnancy and breastfeeding.

Treatment patterns in women of childbearing age and pregnant women with epilepsy in Poland between the years 2019 and 2022-A nationwide population-based cohort study.

AIM: To describe the antiseizure medications (ASMs) prescription pattern in women of childbearing age (WOCA) and pregnant women with epilepsy in the 2019-2022 period in Poland MATERIALS AND METHODS: The National Health Fund (NHF) databases were analyzed. Women aged 15-49 years were considered as being of childbearing age, while exposure during pregnancy was estimated taking into account 15 months before delivery. ASMs belonging to the N03A subgroup of the Anatomical Therapeutic Chemical Classification System, reimbursed by NHF were analyzed. RESULTS: During 2019, 36 784 WOCA and 921 pregnant women filled at least 1 ASM prescription. In 2022, these numbers were 32 304 and 594, respectively. Valproate was the most widely used ASM in WOCA (38.4 %) in 2019, followed by levetiracetam (35.6 %), lamotrigine (30.1 %), and carbamazepine (20.0 %). The percentage of ASM users decreased in 2022 for valproate (32.1 %; p < 0.001) and carbamazepine (17 %; p < 0.001) and increased for levetiracetam (40.8 %; p < 0.001) and lamotrigine (32.7 %; p < 0.001). In 2019 lamotrigine (42.1 %) and levetiracetam (41.5 %) were the most frequently prescribed ASMs to pregnant women. During the study period, a significant increase in prescriptions for levetiracetam was observed (49.5 %; p = 0.003). The proportion of ASMs exposed pregnancies declined for valproate (from 24.7 to 16 %; p < 0.001) and topiramate (from 6.6 to 3.2 %; p = 0.005). The percentage of polytherapy regimens remained stable over the years, both for WOCA (39 %) and pregnant women (32 %). CONCLUSION: Despite the decline in valproate usage, the drug was still among the most commonly prescribed ASMs in women of childbearing age and pregnant women with epilepsy. The awareness of teratogenic risks and new treatment guidelines should be improved in Poland.

Long-term cenobamate retention, efficacy, and safety: outcomes from Expanded Access Programme.

AIM OF THE STUDY: To evaluate the long-term retention rate, efficacy, and tolerability of adjunctive cenobamate (CNB) in patients with drug-resistant epilepsy within the Polish Expanded Access Programme (EAP). CLINICAL RATIONALE FOR THE STUDY: Long-term retention rate is a useful measure of effectiveness including efficacy, safety, and tolerability of antiseizure medications. MATERIAL AND METHODS: We conducted a multicentre retrospective analysis of consecutive patients with focal epilepsy treated with CNB in the EAP between January 2020 and May 2023. All patients who completed the open-label extension phases of the YKP3089C013 and YKP3089C017 trials were offered the opportunity to continue CNB treatment within the EAP. We analysed cenobamate retention, seizure outcomes, and adverse events. RESULTS: 38 patients (18 females; 47.3%) continued CNB treatment within the Expanded Access Programme for 41 months. The mean baseline age of patients was 39.3 years (range: 18-57). All patients were on polytherapy, with the most commonly used antiseizure medications being valproate, levetiracetam, and carbamazepine. Adjunctive CNB treatment resulted in a reduced mean seizure frequency from 8.1 seizures (range: 4-20) per month to 3 seizures (range: 0-8) per month. At the final follow-up, the median CNB dose was 200 mg/day (range: 50-350). Among the patients, 24 (63.1%) achieved ≥ 50% seizure reduction, and eight (21%) remained seizure-free for at least 12 months. One in three patients experienced adverse events, which resolved in half of the subjects. The most frequent adverse events were dizziness, somnolence, and headache. The retention rate after completing the open-label extension phase was 100%. CONCLUSIONS AND CLINICAL IMPLICATIONS: Long-term effectiveness, including ≥ 50% seizure reduction and a 100% retention rate, was sustained over 41 months of CNB treatment within the Expanded Access Programme. No new safety issues were identified. These results provide support for the potential long-term clinical benefits of cenobamate.

Usage and impact of patient-reported outcomes in epilepsy.

BACKGROUND: The use of patient-reported outcomes (PRO) in clinical practice is gaining increasing attention. This study aimed to provide a critical assessment of the current state-of-the-art and beliefs about the use of PRO in the management of people with epilepsy across some European countries. METHODS: Structured interviews were conducted with European experts to collect insights about (I) the personal experience with PRO; (II) the value and impact of PRO in the decision-making process at the national level; and (III) the interest for and use of PRO by national health authorities. RESULTS: Nine neurologists (Austria, Belgium, Czechia, Denmark, France, Greece, Italy, Poland, and United Kingdom), three health economists (Portugal, Romania, and Sweden), and one epidemiologist (Slovakia) participated. They all stated that PRO are collected at their own countries in the context of clinical trials and/or specific projects. During everyday clinical practice, PRO are collected routinely/almost routinely in Austria and Sweden and only at the discretion of the treating physicians in Czechia, Denmark, France, Greece, and Portugal. There was complete consensus about the favorable impact that the PRO can have in terms of clinical outcomes, healthcare resources utilization, and general patient satisfaction. Only participants from Portugal and Sweden answered that the PRO are perceived as very important by the National Health Authorities of their respective countries. CONCLUSIONS: Differences exist in attitudes and perspectives about PRO in epilepsy across Europe. An active plan is warranted to harmonize the measurement of PRO and ensure they can be relevant to people with epilepsy and health services.

Safety of brand name to generic substitution of lacosamide in patients with epilepsy - A prospective single-center observational study.

PURPOSE: Lacosamide is a widely used third-generation antiseizure medication. However, there is a lack of evidence regarding the safety of substituting brand-name lacosamide with its generic version. This study aimed to determine the clinical outcomes associated with switching from the brand-name to the generic form of lacosamide (LCM) in patients with epilepsy. METHODS: This prospective observational study involved patients undergoing treatment with LCM at the university epilepsy clinic. In 2018, the price of the brand-name LCM in Poland increased up to 110-fold compared to generic products. Anticipating that most patients would opt to switch to the generic formulations due to financial constraints, we chose to follow up them prospectively to assess the safety of transitioning from the brand-name to the generic form of LCM. RESULTS: A total of 81 patients, aged 18-62 years, diagnosed with focal epilepsy and undergoing LCM treatment at our institution, decided to switch from the brand-name (Vimpat) to generic variations (Lacosamide TEVA, Lacosamide Glenmark, and Lacosamide Accord). Following the switch, no significant difference was observed in terms of seizure frequency before and after (p = 0.55, Wilcoxon signed-rank test). Subsequently, adverse events were recorded in four patients (4.9%) during the initial follow-up visit post-switch, including somnolence (2 patients) and dizziness (2 patients). Notably, all adverse events resolved by the second follow-up visit without necessitating treatment modification. Importantly, no patient switched back to brand-name medication CONCLUSION: The generic substitution of lacosamide was found to be generally safe in our study. Nonetheless, to confirm our findings, larger prospective studies are required.

Deep Brain Stimulation of the Anterior Nucleus of the Thalamus in Drug-Resistant Epilepsy in the MORE Multicenter Patient Registry.

BACKGROUND AND OBJECTIVES: The efficacy of deep brain stimulation of the anterior nucleus of the thalamus (ANT DBS) in patients with drug-resistant epilepsy (DRE) was demonstrated in the double-blind Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy randomized controlled trial. The Medtronic Registry for Epilepsy (MORE) aims to understand the safety and longer-term effectiveness of ANT DBS therapy in routine clinical practice. METHODS: MORE is an observational registry collecting prospective and retrospective clinical data. Participants were at least 18 years old, with focal DRE recruited across 25 centers from 13 countries. They were followed for at least 2 years in terms of seizure frequency (SF), responder rate (RR), health-related quality of life (Quality of Life in Epilepsy Inventory 31), depression, and safety outcomes. RESULTS: Of the 191 patients recruited, 170 (mean [SD] age of 35.6 [10.7] years, 43% female) were implanted with DBS therapy and met all eligibility criteria. At baseline, 38% of patients reported cognitive impairment. The median monthly SF decreased by 33.1% from 15.8 at baseline to 8.8 at 2 years (p < 0.0001) with 32.3% RR. In the subgroup of 47 patients who completed 5 years of follow-up, the median monthly SF decreased by 55.1% from 16 at baseline to 7.9 at 5 years (p < 0.0001) with 53.2% RR. High-volume centers (>10 implantations) had 42.8% reduction in median monthly SF by 2 years in comparison with 25.8% in low-volume center. In patients with cognitive impairment, the reduction in median monthly SF was 26.0% by 2 years compared with 36.1% in patients without cognitive impairment. The most frequently reported adverse events were changes (e.g., increased frequency/severity) in seizure (16%), memory impairment (patient-reported complaint, 15%), depressive mood (patient-reported complaint, 13%), and epilepsy (12%). One definite sudden unexpected death in epilepsy case was reported. DISCUSSION: The MORE registry supports the effectiveness and safety of ANT DBS therapy in a real-world setting in the 2 years following implantation. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that ANT DBS reduces the frequency of seizures in patients with drug-resistant focal epilepsy. TRIAL REGISTRATION INFORMATION: MORE ClinicalTrials.gov Identifier: NCT01521754, first posted on January 31, 2012.

Epileptiform activity in the acute phase of stroke predicts the outcomes in patients without seizures.

Background and purpose: The abnormalities in EEG of stroke-patients increase the risk of epilepsy but their significancy for poststroke outcome is unclear. This presented study was aimed at determining the prevalence and nature of changes in EEG recordings from the stroke hemisphere and from the contralateral hemisphere. Another objective was to determine the significance of abnormalities in EEG in the first days of stroke for the post-stroke functional status on the acute and chronic phase of disease. Methods: In all qualified stroke-patients, EEG was performed during the first 3 days of hospitalization and at discharge. The correlation between EEG abnormalities both in the stroke hemisphere and in the collateral hemisphere with the neurological and functional state in various time points was performed. Results: One hundred thirty-one patients were enrolled to this study. Fifty-eight patients (44.27%) had abnormal EEG. The sporadic discharges and generalized rhythmic delta activity were the most common abnormalities in the EEG. The neurological status on the first day and the absence of changes in the EEG in the hemisphere without stroke were the independent factors for good neurological state (0-2 mRS) at discharge. The age-based analysis model (OR 0.981 CI 95% 0.959-1.001, p = 0.047), neurological status on day 1 (OR 0.884 CI 95% 0.82-0.942, p < 0.0001) and EEG recording above the healthy hemisphere (OR 0.607 CI 95% 0.37-0.917, p = 0.028) had the highest prognostic value in terms of achieving good status 90 days after stroke. Conclusions: Abnormalities in EEG without clinical manifestation are present in 40% of patients with acute stroke. Changes in EEG in acute stroke are associated with a poor neurological status in the first days and poor functional status in the chronic period of stroke.

Trends in antiseizure medications utilization among women of childbearing age with epilepsy in Poland between 2015 and 2019.

PURPOSE: To determine trends in the use of antiseizure medications (ASMs) among women of childbearing age (WOCA) and girls aged 12-14 years with epilepsy between 2015 and 2019 in Poland. METHODS: The study used data from the Pex database, which captures information on prescriptions dispensed from 85% of community pharmacies in Poland. The prescriptions issued by neurologists who provide epilepsy care in Poland were studied. Six of the most commonly prescribed ASMs were analyzed: carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, topiramate, and valproate. RESULTS: The use of valproate and carbamazepine decreased in all age groups. Among the newer ASMs, the use of lamotrigine, levetiracetam, and topiramate increased and oxcarbazepine decreased significantly in WOCA. The only subgroup with statistically significant changes in all ASMs prescriptions were women aged 19-34 years. For girls aged 12-14 years, significant changes were found only for valproate and carbamazepine. In the last year of observation (2019) valproate and lamotrigine accounted for two-thirds of ASMs units prescribed to WOCA. Valproate accounted for half of the prescribed drug units in girls aged 12-14 years. The lowest rates of VPA prescriptions were found in women aged 19-34 years. CONCLUSIONS: There is a change in prescribing habits in WOCA with epilepsy in Poland with trends toward using less teratogenic ASMs. However, many WOCAs are treated with valproate and topiramate despite their known teratogenicity risk. Valproate is still the most commonly prescribed ASM in WOCA and girls aged 12-14 years. Educational interventions for healthcare professionals are needed to improve prescribing practices in WOCA with epilepsy in Poland.

High prevalence of electroencephalographic frontal intermittent rhythmic delta activity in patients with moderately severe COVID-19.

INTRODUCTION: The aim of our study was to analyse EEG findings in patients with COVID-19 not requiring respiratory support. MATERIAL AND METHODS: We reviewed EEGs performed in patients with COVID-19 between April 2020 and May 2021 at the University Hospital in Kraków, Poland. Demographic and clinical data, including comorbid conditions, discharge disposition, survival, neuroimaging findings, laboratory results, and treatment was collected. RESULTS: The study included 44 EEGs performed in 35 patients (51.4% females), aged 65.5 ± 13.9 years. Almost all patients had at least one comorbidity, and one-third had one or more preexisting neurological conditions. Three quarters of EEGs were abnormal. The most frequent EEG finding was background slowing (16 patients; 45.7%). Frontal findings included frontally predominant rhythmic delta (FIRDA) in 10 (28.6%) patients and focal slowing in the left frontal lobe. Patients with abnormal EEG significantly more often required oxygen supplementation (p = 0.003) and were less likely to recover (p = 0.048). CONCLUSIONS AND CLINICAL IMPLICATIONS: Patients with COVID-19 infection may frequently manifest with an abnormal EEG. FIRDA seems to be a frequent EEG pattern in less severe cases of COVID-19 infection. Future studies are needed to establish whether COVID-19 infection increases the risk for FIRDA, and to investigate its pathogenesis.

Case Report: Vortioxetine in the Treatment of Depressive Symptoms in Patients With Epilepsy-Case Series.

Epilepsy and depression are both serious and potentially disabling conditions which often coexist-bidirectional relationship between the two disorders has been observed. Comorbidity between depression and epilepsy can be attributed to: underlying common pathophysiological mechanisms, psychiatric side effect of antiepileptic medications and psychological response to stress in people with chronic, neurological condition. Despite high prevalence of depressive symptoms in patients with epilepsy, current evidence of the effectiveness of antidepressant therapy in this group of patients is very limited. Vortioxetine is an antidepressant with multimodal activity, very good treatment tolerability, low risk of inducing pharmacokinetic interactions, relative safety of treatment in patients with somatic comorbidities, low risk of causing: sedation, sexual dysfunctions and metabolic side effects. Vortioxetine seems to be a promising treatment option for depressed patients with cognitive dysfunctions, anhedonia and anxiety. In this case series, we report nine cases of patients with epilepsy and depressive symptoms treated with vortioxetine. Seven cases are patients with secondary focal and generalized epilepsy and two with unclassified epilepsy. Three patients presented with depressive episode in the course of bipolar disorder and six patients had depressive symptoms due to organic mood disorder. The dose range of vortioxetine was between 10 and 20 mg. In all of the presented cases effectiveness and tolerability of treatment were very good. Remission of depressive symptoms was achieved in all patients. No epilepsy seizures after switch to vortioxetine were observed in seven cases. In two patients seizures occurred during the first months of vortioxetine treatment but this most probably was due to suboptimal antiepileptic treatment-satisfactory seizure control was achieved after optimization of antiepileptic pharmacotherapy. Vortioxetine was discontinued in two of the presented cases due to pregnancy planning. The duration of observation period during vortioxetine therapy ranged from 2 to 48 months. In conclusion, vortioxetine can be a promising treatment option in patients with epilepsy and comorbid depressive symptoms.

COVID-19 among patients with epilepsy: Risk factors and course of the disease.

INTRODUCTION: The study assessed the prevalence and risk factors for SARS-CoV-2 infection in patients with epilepsy (PWE). Additionally, the course of COVID-19 and its impact on seizure control was investigated. MATERIAL AND METHODS: Subjects with definite (confirmed by positive RT-PCR nasopharyngeal swab or serum anti-SARS-CoV-2 antibodies) and probable COVID-19 were identified via telephone survey among PWE treated at the university epilepsy clinic. RESULTS: Of 252 screened subjects, 17 (6.7%) had definite and 14 (5.5%) probable COVID-19. The percentage of PWE with definite COVID-19 was much higher than the percentage of subjects with confirmed COVID-19 in Polish general population (3.65%). In the heterogenous population of PWE, including patients with drug-resistant epilepsy, physical/intellectual disability, and comorbidities, we were not able to identify any risk factors for contracting COVID-19. The course of infection was mild or moderate in all subjects, not requiring oxygen therapy or respiratory support. The most common symptoms were fever, fatigue, headaches, muscle aches, and loss of smell/taste and continued for approximately 7-21 days, except for loss of smell/taste which lasted usually several weeks. Seizure exacerbation was noted in only one pregnant patient with confirmed COVID-19 and it was likely related to decreased serum level of levetiracetam in the third trimester. CONCLUSION: The study provided reassuring findings related to the low risk of seizure exacerbation in PWE during the course of COVID-19. Patients with epilepsy may be at increased risk of SARS-CoV-2 infection. Epilepsy characteristics are not likely to modify the risk of COVID-19.

Expert opinion: use of valproate in girls and women of childbearing potential with epilepsy: recommendations and alternatives based on a review of the literature and clinical experience-a European perspective.

Valproate is a broad-spectrum antiepileptic drug (AED) of particular interest in pediatric epilepsy syndromes and idiopathic generalized epilepsy, as it is relatively more effective in these syndromes than other AEDs. In 2018, the European Medicines Agency introduced new restrictions on the use of valproate in girls and women of childbearing potential to avoid exposure during pregnancy. The strengthening of existing restrictions sparked controversy and debate among patients and the medical community. The high prevalence of epilepsy syndromes amenable to valproate treatment in women of childbearing age and the little information available on the teratogenic potential of alternative treatments have created uncertainty on how to manage these patients. In this consensus statement, based on a review of the literature and the clinical experience of a panel of European epilepsy experts, we present general recommendations for the optimal clinical management of AED treatment in girls, women of childbearing potential, and pregnant women across the different epilepsy syndromes.

Genetic testing and the phenotype of Polish patients with Unverricht-Lundborg disease (EPM1) - A cohort study.

AIM OF THE STUDY: The aim of this study was to explore genetic findings and the phenotype in Polish patients with Unverricht-Lundborg disease (ULD). MATERIALS AND METHODS: We retrospectively evaluated mutations in the cystatin B (CSTB) gene and clinical presentation in a cohort of patients with ULD. The study population consisted of 19 (14 males) patients with genetically confirmed disease. RESULTS: Sixteen patients were homozygous for the expanded dodecamer repeat mutation alleles, one subject was compound heterozygous for the dodecamer repeat expansion and other mutation, in two, the type of mutation has not yet been established. The numbers of repeats in the CSTB gene varied from 60 to 81. Clinical information was available for 16 subjects. The disease course was progressive in all patients, leading to severe disability, mainly due to myoclonus, in nine. CONCLUSIONS AND CLINICAL IMPLICATIONS: Genetic findings and the clinical picture of our patients with ULD were in accordance with available studies. The most common genetic defect underlying ULD was homozygosity for an unstable expansion of a dodecamer repeat in the CSTB gene. Patients with action or/and stimulus sensitive myoclonus or intractable myoclonus epilepsy, especially with onset in late childhood/adolescence should be screened for ULD.

Predictors of remission in patients with epilepsy.

AIM OF STUDY: To evaluate the rate and factors predicting seizure remission in a large cohort of patients with epilepsy. MATERIALS AND METHODS: Patients with epilepsy treated at a university epilepsy clinic were included in this study. The following information was collected by means of a structured questionnaire: age, sex, age at onset of epilepsy, aetiology of epilepsy, the presence of intellectual disability, duration and type of epilepsy, frequency of seizures, treatment of epilepsy, and mechanism of action of antiepileptic drugs (AEDs). RESULTS: A total of 530 adult patients participated in this study (mean age ± standard deviation: 36.1 ± 12.6 years). Of these, 327 (61.7%) were female, and 364 (68.7%) patients had focal epilepsy. Twelve-month seizure freedom was achieved in 246 (46.4%) patients. Logistic regression revealed several independent predictors of seizure freedom: younger age (odds ratio (OR) = 0.98; p = 0.037), male sex (OR = 1.54; p = 0.050), generalised epilepsy (OR = 1.61; p = 0.052), lower number of prescribed AEDs (OR = 0.22; p = 0.001), and taking a combination of valproate and lamotrigine (OR = 2.51; p = 0.024). CONCLUSIONS: Most patients with epilepsy enter remission on monotherapy with their first or second AED. However, a substantial proportion of patients may benefit from combination therapy including valproate and lamotrigine polytherapy.