SUMMARY Introduction The potential for prenatal exposure to antiseizure medications to increase the risk of congenital malformations has been a concern for decades. This study fills an information gap regarding congenital malformations and related factors in the offspring of mothers with epilepsy in Poland. Materials and methods The study uses prospectively collected data from an institutional database of a tertiary epilepsy centre between 2000 and 2024, including data from 1,467 pregnancies (mean maternal age = 29.02). Results These pregnancies resulted in live births (83.9%), miscarriages (15.4%), and perinatal deaths (0.7%). Major congenital malformations (MCM), identified at birth, were observed in 6.4% of children, most commonly affecting the cardiovascular system (33.0%), urogenital system (21.3%), and involving multiple defects (13.8%). Mothers of children with MCM were older than those of children without MCM, p = 0.026. No statistically significant associations were found between the occurrence of MCMs and the type of epilepsy, folic acid intake prior pregnancy, seizures in the first trimester, type of treatment (mono-vs polytherapy), or treatment versus no treatment. Among all medications, only valproate use was associated with a higher risk of MCM – 30.9% versus 20.5%, χ 2 = 5.60, p = 0.026, ϕ = 0.06. Conclusions The use of valproate by women with epilepsy during pregnancy increases the risk of birth defects in the child. These findings support efforts to reduce VPA use during pregnancy and to encourage pregnancy planning. Mothers of children with major congenital malformations were statistically older – a weak but potentially clinically significant risk factor. Aside from maternal age, no other analysed factors were linked to a higher risk of malformations.

Summary Background Seizure resolution is often difficult to attain promptly in status epilepticus (SE). Clobazam (CLB) is structurally different from typical benzodiazepines with an affinity to the α2 subunit of GABA-A receptors, rendering unique efficacy in seizure termination. Aim To assess the response of clobazam in refractory status epilepticus (RSE) and to correlate this response with EEG patterns. Materials and Methods This was a single-center retrospective study conducted at a neurocritical care unit between January 2018 and June 2023. The study included fifty consecutive patients with RSE, out of which sixteen adult patients had continuous EEG monitoring both before and during treatment with clobazam until the resolution of RSE. Patients for whom clobazam was the last anti-seizure medication (ASM) used were included in the study. Thirty-four patients were excluded for various reasons, like lack of continuous EEG monitoring (cEEG), status post cardiac arrest, exclusion of clobazam due to medical issues or adverse events, or admission to the hospice floor. Results Out of the sixteen patients included in the study, twelve (75%) had focal nonconvulsive RSE on cEEG and four had focal convulsive RSE when clobazam was administered. Thirteen out of sixteen patients (81.25%) responded successfully to clobazam, with an average time of 23.5 hours since starting the medication. On average, three other ASMs were tried before clobazam, initiated at a mean time of 27 hours since SE onset. The study identified EEG patterns correlated with the use of clobazam :1) lateralised periodic discharges that evolved from 1–1.5 Hz to 2–3 Hz, then evolved to rhythmic theta/delta activity with embedded LPDs; 2) repetitive spikes that evolved to theta and delta frequencies (good responders to CLB), and iii) low voltage faster frequencies and evolved to theta delta frequencies (less responders to CLB). Conclusion Rapid pharmacoresistance to first-line benzodiazepines and ASM occurs as seizures persist during SE. Our study provides EEG correlates to the successful use of CLB in RSE based on its unique targeting of the GABA-A subtype receptors involved in postsynaptic phasic inhibition.

Summary Background Epileptic seizure is a transient period of signs and symptoms resulting from the abnormal excessive and synchronous neuronal activity in the brain, resulting in brain damage. To prevent complications, the antiseizure medication is needed. Several agents have a potency of anti-seizure effect, including ibuprofen. Unfortunately, there are few studies regarding the anti-seizure effect of ibuprofen. Aim To determine the anti-seizure effect of ibuprofen to reduce the symptoms of epileptic seizures. Materials and Methods A systematic review using the databases ScienceDirect, SpringerLink, Nature, and Pubmed. The article was obtained using the keywords “ibuprofen” and (“epilepsy” or “anticonvulsant” or “antiseizure” or “epileptic” or “neuroinflammation”) in the period 2012 to 2022 and screened with inclusion and exclusion criteria. Out of the 1376 articles screened, there are three studies included in this review. The SYRCLE Risk of Bias Tool was used to assess the risk of bias, and the data was synthesised using SWiM guidelines. Results Ibuprofen affects seizures by reducing the number, grade, and duration of seizure intensity in the PTZ-induced rats. Despite the risk of bias assessment revealing some potential bias in the studies, our study shows that ibuprofen has potency as an additional agent for epileptic seizures among febrile convulsive patients. Conclusion In animal models of seizures, ibuprofen has an antiseizure effect by reducing the number, grade, and duration of seizures.

Summary Introduction In patients suspected of epilepsy, electroencephalography (EEG) is an essential tool in the diagnostic workup. Currently, visual analysis of interictal epileptiform discharges by experts is the gold standard. Neurophysiologists perform an analysis of EEG through visual inspection. This is very time-consuming and inefficient. There is an increasing need to develop reliable and validated automated EEG analysis methods. Methods based on artificial intelligence can potentially help achieve this task. Aim The present review paper aims to present the current state of knowledge regarding the ability of artificial intelligence to distinguish abnormal from normal EEG in patients suspected of epilepsy. Material and methods This review covers the most relevant and recent papers identified using the PubMed database. Results and discussion Artificial intelligence (AI) has the potential to improve the management of epilepsy. It was shown that AI could distinguish normal from abnormal recordings, detect seizures, or detect interictal epileptiform discharges. The AI model (SCORE-AI) was developed and validated to assess routine clinical EEGs comprehensively. The sensitivity of SCORE-AI (86.7%) was lower than the sensitivity of the human experts (93.3%) and two models, Encevis (96.7%) and Persyst (100%) but higher than the sensitivity of SpikeNet (66.7%). The accuracy of SCORE-AI was similar to that of human experts and higher than that of the three previously published AI models. SCORE-AI achieves high specificity similar to the human raters and significantly higher accuracy than the three previously published AI models. Conclusion Methods based on artificial intelligence can potentially be helpful in EEG analysis. SCORE-AI may reduce excessive workloads for experts who interpret high volumes of EEG recordings. The SCORE-AI is the first model capable of completing a fully automated and comprehensive clinically relevant assessment of routine EEGs.

SUMMARY Background Between 14% and 20% of cases of drug-resistant epilepsy may be attributed to an impaired cellular or humoral immune response. Aim Our study aimed to assess disorders of the immune response of the humoral or cellular type and their impact on the course of the disease, factors suggesting the diagnosis of an autoimmune etiology. We wanted to analyse these factors, looking for correlations with a history of status epilepticus. Materials and methods This study prospectively analysed 30 patients who were diagnosed with drug-resistant epilepsy. The patients were divided into two groups: those who had previously experienced status epilepticus and those who had not. The study collected and analysed detailed information about the patient’s medical history, routine blood laboratory tests, albumin and immunoglobulin (IgG) levels, neuropsychological evaluations, electroencephalography tests (EEG), general cerebrospinal fluid (CSF) examinations, tests for the presence of oligoclonal bands, IgG index determination, MRZ-reaction (MRZR), chitotriosidase activity, and the presence of anti-herpes type 1 (anti-HSV-1) antibodies and neural autoantibodies. Each patient underwent magnetic resonance imaging (MRI) of the head with intravenous contrast administration using the epileptic protocol. Results There was no statistically significant difference in age, gender, onset and disease duration up to the time of our study. None of the patients showed the presence of the tested antibodies against neuronal surface antigens and oligoclonal bands in the CSF. Conclusion Lack of antibodies against neuronal antigens does not necessarily rule out autoimmune epilepsy. The exact diagnostic criteria are still a subject of debate. A history of SE increases the risk of autoimmune epilepsy.

SUMMARY Introduction Cenobamate (CNB) is a newly approved antiseizure medication in Europe. It is used as an add-on treatment for focal-onset seizures in adult patients with epilepsy that is not responding to other medications. Aim This report discusses the practical aspects of using cenobamate to treat adult patients with epilepsy based on current experiences. Discussion and conclusions Studies have shown that cenobamate is effective in reducing seizure frequency in adult patients with drug-resistant focal onset epilepsy when used as add-on therapy. It also has a high seizure freedom rate, a good treatment retention rate, and a favorable safety profile. The aspects discussed include using cenobamate in special populations and potential interactions with other drugs, management strategies to mitigate the risk of adverse reactions illustrated by a specific clinical case. Further studies involving larger patient groups are necessary to assess the drug’s efficacy and safety profile, particularly in special populations and patients with other types of epileptic seizures.

Summary Introduction Acute Ischemic Stroke (AIS) is a medical emergency with focal neurological deficits. Todd’s paralysis (TP) is defined as a transient loss of motor ability and weakness that lasts hours to days and typically occurs after a focal seizure. Given the high prevalence of stroke and the rising availability of reperfusion therapies, timely detection of eligible patients is critical. Pre- and early-hospital differential diagnosis of various conditions with comparable clinical presentations is still difficult. Aim This review discusses Todd’s post-epileptic paralysis, one of the most common stroke mimics (SM), in pre- and early-hospital settings. Discussion and Conclusions The review covers the most critical findings on the TP and its emergency care as a common stroke mimic. Because TP is an excluding diagnosis, the most severe and curable illnesses must be recognised. Since thrombolysis is safe in SM, delaying or withholding medication may be improper when the advantages of treating a stroke mimic outweigh the dangers of treating a stroke mimic.

Summary Introduction Beta-propeller protein-associated neurodegeneration (BPAN) is a neurodegenerative disorder; its estimated prevalence is 2 to 3 per million individuals. All published cases of BPAN have been sporadic, with a clear female predominance and mutations in various exons of the WDR45 gene. Case presentation The study aimed to confirm the diagnosis of BPAN in a 9-year-old girl with a developmental delay since early childhood complicated with intellectual disability, lack of speech and febrile and non-febrile tonic-clonic seizures. The patient also had autistic symptoms as well as some Rett-like symptoms: stereotypical movements of the hands–twisting objects, putting hands in the mouth. Discussion Clinical exome analysis and Sanger sequencing of the proband have been performed to confirm the diagnosis. The novel heterozygous missense mutation c.755T>C of the WDR45 «autophagy» gene was revealed. Sanger sequencing of the trio (proband and parents) proved the de novo nature of mutation; its clinical significance has been defined as probably pathogenic. Thus, we report a new missense variant of the WDR45 gene in a girl with a clinical picture of BPAN. The use of NGS made it possible to get a correct diagnosis during rather a short period before the second debilitating phase of the disease started so that the physicians and the family would have time to prepare and hopefully choose the way to resist.

Summary Introduction Succinic semialdehyde dehydrogenase deficiency (SSADH), also known as 4-hydroxybutyric aciduria (OMIM #271980, 610045), is an ultra-rare neurometabolic disorder inherited in an autosomal recessive pattern. It is usually characterised by a relatively nonprogressive encephalopathy in the first two years of life with hypotonia and developmental delay, associated with mild ataxia and hyporeflexia, as well as delays in language and speech development. Case report We report on a case of a four-year-old girl with SSADH deficiency who presented, at the age of 11 months old, with marked hypotonia, global neurodevelopmental delay and epilepsy. The diagnosis of “Succinic semialdehyde dehydrogenase deficiency” was indicated as there was a marked elevation of the levels of 4-hydroxy-butyric and 3,4-dihydroxybutyric acid caused by mutation at the gene ALDH5A1 in the homozygous state, identified with WES technique. Currently, she is four years old and has a severe global psychomotor delay, excessive hypotonia, hyperextensibility, and ataxia and is free of seizures. Conclusion At the early stage of clinical presentation, the condition is difficult to differentiate from other encephalopathies. This case report suggests that analysis of urinary organic acids should be performed in all patients at risk to allow early diagnosis. DNA analysis with the WES technique can confirm the diagnosis.