Evaluating the efficacy of a ketogenic diet in managing drug resistant paediatric DEDPC5-related epilepsy.

AIM: To evaluate the effectiveness of the ketogenic diet treatment in a cohort of patients with drug-resistant epilepsy with a mutation in the DEPDC5 gene. MATERIALS AND METHODS: We followed four paediatric patients with drug resistant DEPDC5-related epilepsy through a ketogenic diet (KD) treatment course. We analyzed the following parameters of their clinical profiles: past medical history, clinical characteristics of seizure morphology, EEG records pre- and post-KD treatment, the results of MRI head and neurological and psychological examinations (pre-treatment and throughout treatment course). We evaluated the effectiveness of previous therapeutic approaches and the current treatment with ketogenic diet alongside results of neuroimaging studies. Effect of KD on co-morbid behavioural and psychiatric symptoms, as well as adverse effects from KD were also assessed. RESULTS: In three patients, the introduction of the ketogenic diet resulted in the cessation of seizures, while in 1 patient with co-morbid cortical dysplasia, epileptic seizures of lesser severity returned after an initial seizure-free period of several weeks. Further, 1 patient was able to transition to a KD-only treatment regimen. The remaining patients were able to reduce the number of antiseizure medicine (ASM) to a monotherapy. In all cases we observed improvements in EEG results. Our cohort included one patient whose MRI head showed cortical dysplasia. However, no patients demonstrated any neurological signs in neurological examination. Psychological examination showed normal intellectual development in all patients, although behavioral disorders and difficulties at school were observed. The introduction of KD treatment correlated with improvement in school performance and improved behavioral regulation. No clinically significant adverse events were observed. CONCLUSIONS: KD seems to be both effective and well tolerated in young patients with DEPDC5-related epilepsy, both as a monotherapy and as an adjunct to ASM. We recommend an early adoption of this therapeutic approach in this patient demographic. Our results demonstrate that the positive effects of KD treatment encompass improvements in general functioning, particularly in the context of school performance and behavior, in addition to the achievement of good seizure control.

A suggestive seizure induction technique protocol in a short EEG in children and adolescents.

The use of a suggestive seizure induction procedure (SSI) in medicine, particularly in the differential diagnosis of psychogenic nonepileptic epileptic seizures (PNES), is well documented. However, there is no description of standardized suggestion procedures used in children and adolescents. The research presents a standardized method of SSI with a cotton swab soaked in water. The protocol was developed based on of 544 placebo trials over ten years in a center for the differential diagnosis of children and adolescents. The protocol is a safe tool that allows inducing specific behavior in children and adolescents in whom there is a well-founded suspicion of PNES.

Validation of targeted next-generation sequencing panels in a cohort of Polish patients with epilepsy: assessing variable performance across clinical endophenotypes and uncovering novel genetic variants.

Introduction: Targeted Next-Generation Sequencing Panels (TNGSP) have become a standard in global clinical practice. Instead of questioning the necessity of next-generation sequencing in epilepsy patients, contemporary large-scale research focuses on factors such as the size of TNGSP, the comparative advantages of exome or genome-wide sequencing over TNGSP, and the impact of clinical, electrophysiological, and demographic variables on genetic test performance. This study aims to elucidate the demographic and clinical factors influencing the performance of TNGSP in 138 Polish patients with epilepsy, recognizing the pivotal role of genetic testing in guiding patient management and therapy. Methods: A retrospective analysis was conducted on patients from a genetic clinic in Poznan, Poland, who underwent commercial gene panel studies at Invitae Corporation (USA) between 2020 and 2022. Patient groups were defined based on the age of onset of the first epileptic seizures, seizure type, gender, fever dependence of seizures, presence of intellectual disability or developmental delay, abnormalities in MRI, and the presence of dysmorphic features or congenital malformations. Seizure classification followed the 2017 ILAE criteria. Results: Among the 138 patients, 30 (21.7%) exhibited a pathogenic or likely pathogenic variant, with a distribution of 20.7% in males and 22.5% in females. Diagnostic performance correlated with the patient's age at the onset of the first seizure and the type of seizure. Predominant variants were identified in the SCN1A, PRRT2, CDKL5, DEPDC5, TSC2, and SLC2A1 genes. Additionally, 12 genes (CACNA1A, SCN2A, GRIN2A, KCNQ2, CHD2, DYNC1H1, NEXMIF, SCN1B, DDX3X, EEF1A2, NPRL3, UBE3A) exhibited single instances of damage. Notably, novel variants were discovered in DEPDC5, SCN1A, TSC2, CDKL5, NPRL3, DYNC1H1, CHD2, and DDX3X. Discussion: Identified variants were present in genes previously recognized in both European and non-European populations. A thorough examination of Variants of Uncertain Significance (VUSs), specifically focusing on gene copy number changes, may unveil more extensive chromosomal aberrations. The relatively frequent occurrence of pathological variants in X chromosome-linked genes in girls warrants further investigation, challenging the prevailing notion of male predominance in X-linked epilepsy.

Pharmacoeconomics Aspects of Antiepileptic Drugs in Pediatric Patients with Epilepsy.

OBJECTIVE: This study assessed the differentiation of treatment costs with newer and older antiepileptic drugs (AEDs) through its correlation with treatment effectiveness and an adverse event (AE) in pediatric patients with epilepsy (PPE). METHODS: PPE on monotherapy of AEDs for the last 6 months were screened for this study. Seizure frequency during the study was compared with that within 6 months before the study. The following parameters were also assessed: quality of life in epilepsy, Pittsburgh Sleep Quality Index, and Liverpool AEs Profile. An incremental cost-effectiveness ratio (ICER) analysis based on the costs of pharmacotherapy was also performed. RESULTS: Out of 80 PPE, 67 completed the study, and 13 PPE were lost after failing to meet the inclusion criteria. A total of 56.71% of PPE were on newer AEDs, and 43.28% were on older AEDs. Newer and older AEDs did not differ significantly in seizure frequency reduction and quality of life parameters, although these were improved significantly during the study period. As per ICER, newer AEDs need an additional EUR 36.82 per unit reduction in seizure frequency. CONCLUSION: Newer AEDs have comparatively better efficacy, although not significantly better than older AEDs. However, the additional cost per unit improvement is quite high with newer AEDs, necessitating pharmacoeconomic consideration in pediatric epilepsy treatment.

Pharmacovigilance in Pediatric Patients with Epilepsy Using Antiepileptic Drugs.

OBJECTIVE: To investigate the occurrence of adverse effects of antiepileptic drugs (AEDs) in pediatric epileptic patients on mono- or polytherapy. METHOD: We evaluated eighty consecutive patients that met the following inclusion criteria: aged ≤18 years; diagnosed with epilepsy for at least one year; a stable dose of AED for at least three months; verbal consent to participation in the study. Patients were asked if they had experienced any adverse drug reaction (ADR) related to the AED. Afterward, regardless of the answer, they were interviewed based on a detailed semi-structured questionnaire about the presence of ADRs associated with the AED. The data were analyzed regarding the use of monotherapy or polytherapy. RESULTS: Ninety-seven percent of the patients reported having experienced ADRs related to AEDs. The greatest number of seizures affected the group of patients treated with monotherapy (both at baseline and at followup), but the greatest number of ADRs were observed among patients treated with polytherapy. In patients on monotherapy, the most frequent ADRs reported at baseline included fatigue and somnolence, and among patients with polytherapy, it was fatigue and hair loss. CONCLUSION: Children on polytherapy were significantly more likely to develop ADRs compared to those on monotherapy, but a statistically significant improvement in seizure frequency was also observed in the group of patients on polytherapy. Pharmacovigilance is very important in children with AEDs, so that ADRs can be identified early and managed appropriately.

Analysis of Factors That May Affect the Effectiveness of Ketogenic Diet Treatment in Pediatric and Adolescent Patients.

PURPOSE: The aim was to find predictors for ketogenic diet (KD) treatment effectiveness. In addition, recognized factors influencing the efficacy of KD were analyzed based on the ILAE (International League Against Epilepsy) proposed Classification and Definition of the Epilepsy Syndromes. METHODS: A sample of 42 patients treated with KD were analyzed. The effectiveness of KD was assessed according to the type of diet, the type of seizures, and the known (KE) or undetermined genetic etiology (UNKE). The group of KE consisted of patients with CACNA1S, CHD2, DEPDC5, KIF1A, PIGN, SCN1A, SCN8A, SLC2A1, SYNGAP1 pathogenic variants. The usefulness of the new Classification and Definition of Epilepsy Syndromes proposed by the ILAE was evaluated. RESULTS: KD therapy was effective in 69.05% of cases. No significant correlation was observed with the type of diet used. KE was related to greater effectiveness after KD treatment. KD treatment was most effective in the reduction of non-focal seizures. Considering the ILAE proposed classification, it was found that KD efficacy was higher in patients with simultaneous focal and tonic-clonic seizures compared to patients with only tonic-clonic or focal seizures. CONCLUSION: The occurrence of focal seizures does not determine the potential ineffectiveness of treatment with a ketogenic diet. A significant efficacy of ketogenic diet treatment was observed in the group of patients with focal and generalized seizures, as well as epileptic and developmental encephalopathies. The etiology of epileptic seizures plays a more significant role. The new classification will make it easier to select patients who can benefit from this form of treatment.

Central Apneas Due to the CLIFAHDD Syndrome Successfully Treated with Pyridostigmine.

NALCN mutations lead to complex neurodevelopmental syndromes, including infantile hypotonia with psychomotor retardation and characteristic facies (IHPRF) and congenital contractures of limbs and face, hypotonia, and developmental delay (CLIFAHDD), which are recessively and dominantly inherited, respectively. We present a patient in whom congenital myasthenic syndrome (CMS) was suspected due to the occurrence of hypotonia and apnea episodes requiring resuscitation. For this reason, treatment with pyridostigmine was introduced. After starting the treatment, a significant improvement was observed in reducing the apnea episodes and slight psychomotor progress. In the course of further diagnostics, CMS was excluded, and CLIFAHDD syndrome was confirmed. Thus, we try to explain a possible mechanism of clinical improvement after the introduction of treatment with pyridostigmine in a patient with a mutation in the NALCN gene.

First case series of Polish patients with cerebrotendinous xanthomatosis and systematic review of cases from the 21st century.

Cerebrotendinous xanthomatosis (CTX) is an inborn error of metabolism caused by recessive variants in the cytochrome P450 CYP27A1 gene. CTX is said to manifest with childhood-onset chronic diarrhea and the classic triad of juvenile-onset cataracts, Achilles tendons xanthomas, and progressive ataxia. It is currently one of the few inherited neurometabolic disorders amenable to a specific treatment. The diagnosis may be significantly delayed resulting in permanent neurological impairment. A retrospective review of the clinical characteristics and diagnostic findings in case series of six Polish patients with CTX. Additional retrospective review of symptoms and pathogenic variants of 568 CTX available cases and case series from the past 20 years. To the best of our knowledge, this is the widest review of CTX cases reported in years 2000-2021. We report the largest cohort of Polish patients ever published, with the identification of two hot-spot mutations. During the review of available 568 cases, we found significant differences in the clinical phenotypes and the localization of variants within the gene between Asian and non-Asian populations. These findings may facilitate molecular testing in the Polish and Asian populations. Invariably better screening for CTX and wider awareness is needed.

The PURPLE N study: objective and perceived nutritional status in children and adolescents with cerebral palsy.

PURPOSE: To obtain information on characteristics, management, current objective nutritional status and perception of nutritional status of children with cerebral palsy (CP) from healthcare professionals (HCPs) and caregivers. MATERIALS AND METHODS: A detailed survey of several items on eight main topics (general characteristics, motor function, comorbidities, therapies, anthropometry, feeding mode and problems and perceived nutritional status) was developed and tested for the study. Correlation between nutritional status and Gross Motor Function Classification System (GMFCS) levels was assessed using continuous variables (Z-scores for weight-for-age, height-for-age, weight-for-height, and body mass index-for-age), and categorical variables (being malnourished, stunted, or wasted). HCP and caregiver perceptions of the child's nutritional status as well as agreement between perceived and objective nutritional status and agreement between perceived nutritional status and concerns about the nutritional status were analyzed. RESULTS: Data were available for 497 participants from eight European countries. Poorer nutritional status was associated with higher (more severe) GMFCS levels. There was minimal agreement between perceived and objective nutritional status, both for HCPs and caregivers. Agreement between HCP and caregiver perceptions of the child's nutritional status was weak (weighted kappa 0.56). However, the concerns about the nutritional status of the child were in line with the perceived nutritional status. CONCLUSIONS: The risk of poor nutritional status is associated with more severe disability in children and adolescents with CP. There is a mismatch between HCP and caregiver perceptions of participants' nutritional status as well as between subjective and objective nutritional status. Our data warrant the use of a simple and objective screening tool in daily practice to determine nutritional status in children and adolescents with CP. Clinical trial registration: ClinicalTrials.gov Identifier: NCT03499288 (https://clinicaltrials.gov/ct2/show/NCT03499288). IMPLICATIONS FOR REHABILITATIONUse of the ESPGHAN recommendations and simple screening tools in daily practice is needed to improve nutritional care for individuals with CP.Attention should be paid to the differences in the perception of nutritional status of individuals with CP between professionals and caregivers to improve appropriate referral for nutritional support.Objective measures rather than the professional's perception need to be used to define the nutritional status of individuals with CP.

Crawl Position Depends on Specific Earlier Motor Skills.

Early assessment of motor performance should allow not only the detection of disturbances but also create a starting point for the therapy. Unfortunately, a commonly recognised method that should combine these two aspects is still missing. The aim of the study is to analyse the relationship between the qualitative assessment of motor development at the age of 3 months and the acquisition of the crawl position in the 7th month of life. A total of 135 children were enrolled (66 females). The analysis was based on physiotherapeutic and neurological assessment and was performed in the 3rd, 7th and 9th months of life in children, who were classified according to whether they attained the crawl position or not in the 7th month. Children who did not attain the crawl position in the 7th month did not show distal elements of motor performance at the age of 3 months and thus achieved a lower sum in the qualitative assessment. Proper position of the pelvis at the age of 3 months proved to be very important for the achievement of the proper crawl position at the 7th month. Failure to attain the crawl position in the 7th month delays further motor development. The proximal-distal development must be achieved before a child is able to assume the crawl position. Supine position in the 3rd month seemed more strongly related to achieving the crawl position than assessment in the prone position.

CLN8 Mutations Presenting with a Phenotypic Continuum of Neuronal Ceroid Lipofuscinosis-Literature Review and Case Report.

CLN8 is a ubiquitously expressed membrane-spanning protein that localizes primarily in the ER, with partial localization in the ER-Golgi intermediate compartment. Mutations in CLN8 cause late-infantile neuronal ceroid lipofuscinosis (LINCL). We describe a female pediatric patient with LINCL. She exhibited a typical phenotype associated with LINCL, except she did not present spontaneous myoclonus, her symptoms occurrence was slower and developed focal sensory visual seizures. In addition, whole-exome sequencing identified a novel homozygous variant in CLN8, c.531G>T, resulting in p.Trp177Cys. Ultrastructural examination featured abundant lipofuscin deposits within mucosal cells, macrophages, and monocytes. We report a novel CLN8 mutation as a cause for NCL8 in a girl with developmental delay and epilepsy, cerebellar syndrome, visual loss, and progressive cognitive and motor regression. This case, together with an analysis of the available literature, emphasizes the existence of a continuous spectrum of CLN8-associated phenotypes rather than a sharp distinction between them.

Variety of symptoms of GLUT1 deficiency syndrome in three-generation family.

OBJECTIVE: Glucose transporter type 1 deficiency (G1D) syndrome is generally a genetic disorder because of a mutation of the SLC2A1 gene. The clinical picture of G1D is heterogeneous. The aim of this paper was to present the case of G1D, recognized in a three-generation family, caused by missense mutation p.Arg92Trp in SLC2A1 gene, and showing high clinical heterogeneity and evolution of symptoms over time. METHODS: Three-generation family members, showing symptoms suggesting G1D, have been characterized in terms of the clinical picture, electroencephalogram (EEG) recordings, brain neuroimaging, and the psychological assessment data. All subjects were offered genetic testing of the SLC2A1 gene. RESULTS: We sequenced the SLC2A1 gene in the proband of the family and identified the c.274C > T variant (p.Arg92Trp). The presence of the same mutation was confirmed in all affected family members; however, significant variations in the clinical picture among them were observed. In addition to the typical symptoms for G1D (e.g., epilepsy, intellectual disability), patients presented movement disorders, stiffness, and dysarthria, as well as psychiatric symptoms. After using the ketogenic diet, epileptic seizures disappeared, but the rest of the symptoms were resistant to treatment. CONCLUSIONS: Despite the same underlying mutation, clinical symptoms may vary among members of one family. Different clinical symptoms are observed depending on the patient's age. Not all symptoms occur in all patients within one family despite the same genetic background. However, the importance of early therapy for the clinical course of the disease requires further study.

EXOME REPORT: Novel mutation in ATP6V1B2 segregating with autosomal dominant epilepsy, intellectual disability and mild gingival and nail abnormalities.

Mutations in ATP6V1B2, which encodes the B2 subunit of the vacuolar H + ATPase have previously been associated with Zimmermann-Laband syndrome 2 (ZLS2) and deafness-onychodystrophy (DDOD) syndrome. Recently epilepsy has also been described as a potentially associated phenotype. Here we further uncover the role of ATP61VB2 in epilepsy and report autosomal dominant inheritance of a novel missense variant in ATP6V1B2 in a large Polish family with relatively mild gingival and nail problems, no phalangeal hypoplasia and with generalized epilepsy. In light of our findings and review of the literature, we propose that the ATP6V1B2 gene should be considered in families with autosomal dominant epilepsy both with or without intellectual disability, and that presence of subtle gingival and nail problems may be another characteristic calling card of affected individuals with ATP6V1B2 mutations.

Economic and clinical evaluation of vagus nerve stimulation therapy.

OBJECTIVES: The medical and social care of drug-resistant epilepsy (DRE) entails significant costs. Approximately 30 to 40 percent of patients with DRE who underwent vagus nerve stimulator (VNS) implantation achieve an above 50 percent reduction in seizure frequency. The study objective was to analyze the effect of VNS on clinical effects improvement and therapy cost reduction in patients with DRE over a 2-year follow-up period. The second purpose of the study was to compare average costs of VNS treatment of patients with DRE in selected countries, taking into account the purchasing power parity. MATERIALS AND METHODS: The study included all the patients who had VNS implanted at our department between 2014 and 2018. Data on clinical events and medical costs were collected prospectively and obtained from medical documentation. We also reviewed relevant literature on costs of VNS therapy in patients with DRE from the last 18 years. RESULTS: Resource utilization and epilepsy-related events were reduced during the follow-up period compared to the baseline. Average total cost was estimated at EUR 7703.59 in year 1 and at EUR 7108.38 in year 2 following VNS implantation. Average direct costs of VNS treatment of patients with DRE over the last 18 years varied between the countries and ranged from EUR 24 790.43 in the United States to EUR 64.84 in the United Kingdom. CONCLUSION: Vagus nerve stimulator is a cost-effective therapy yielding measurable clinical and therapeutic outcomes over the long term. Moreover, the analysis contained in this review highlights the poor consensus of methodological approaches.

A de novo CTNNB1 nonsense mutation associated with syndromic atypical hyperekplexia, microcephaly and intellectual disability: a case report.

BACKGROUND: In addition to its role in cell adhesion and gene expression in the canonical Wingless/integrated Wnt signaling pathway, ß-catenin also regulates genes that underlie the transmission of nerve impulses. Mutations of CTNNB1 (ß-catenin) have recently been described in patients with a wide range of neurodevelopmental disorders (intellectual disability, microcephaly and other syndromic features). We for the first time associate CTNNB1 mutation with hyperekplexia identifying it as an additional candidate for consideration in patients with startle syndrome. CASE PRESENTATION: We describe an 11 year old male Polish patient with a de novo nonsense mutation in CTNNB1 who in addition to the major features of CTNNB1-related syndrome including intellectual disability and microcephaly, exhibited hyperekplexia and apraxia of upward gaze. The patient became symptomatic at the age of 20 months exhibiting delayed speech and psychomotor development. Social and emotional development was normal but mild hyperactivity was noted. Episodic falls when startled by noise or touch were observed from the age of 8.5 years, progressively increasing but never with loss of consciousness. Targeted gene panel next generation sequencing (NGS) and patient-parents trio analysis revealed a heterozygous de novo nonsense mutation in exon 3 of CTNNB1 identifying a novel association of ß-catenin with hyperekplexia. CONCLUSION: We report for the first time a clear association of mutation in CTNNB1 with an atypical syndromic heperekplexia expanding the phenotype of CTNNB1-related syndrome. Consequently CTNNB1 should be added to the growing list of genes to be considered as a cause of startle disease or syndromic hyperekplexia.

Red ear syndrome - case report and review of literature.

Red ear syndrome is characterized by: paroxysmal, unilateral, recurrent pain, redness and discomfort of the ear lobe accompanied by a burning sensation. The duration and frequency of red ear syndrome attacks is very various and the episodes, usually occur spontaneously. The pathophysiology is still unknown and also there are no medications with approved efficacy. The goal of this brief report is to present a 11-year old girls whose symptoms of red ear syndrome preceded migraine without aura and the signs of redness of the ear occurred in clusters. The occurrence of symptoms of our case may have confirmed the observation that red ear syndrome is associated with primary headaches particularly migraine and cluster headaches. The literature on this case report of pediatric idiopathic red ear syndrome has been reviewed.

Concentration of Il-1ß, Il-2, Il-6, TNFα in the blood serum in children with generalized epilepsy treated by valproate.

BACKGROUND: The aim of the study was the comparison of concentrations of IL-1ß, IL-2, IL-6 and TNFα before and after valproate (VPA) treatment in blood serum in patients with generalized seizures diagnosed and treated in the Department of Developmental Neurology, Poznan University of Medical Sciences from January 2006 to May 2007. METHODS: The analysis was conducted in a group of 21 patients with well controlled, generalized seizures (mean age 7.7±4.7 years) before and after 4-6 months of VPA therapy. Quantitative determination IL-1ß, IL-2, IL-6 and TNFα were performed with method of enzyme-linked immunosorbent assay (ELISA). The serum drug concentration was determined with the use of fluorescence-polarization-immunoassay system (FPIA). RESULTS: The concentration of IL-6 in blood serum of patients decreased significantly (p<0.001) after 4-6 months of VPA therapy, but concentration of IL-1ß (p=0.732), IL-2 (p=0.865), TNFα (p=0.079) did not change significantly. The serum concentration of VPA in all of patients was in therapeutic range (mean 77.53±19.71µg/ml). CONCLUSIONS: The serum level of pro-inflammatory IL-6 in patients with generalized epilepsy decreased in statistically significant way during VPA therapy, so the anti-inflammatory properties of VPA are also important for the effective control of seizure. Due to the incompatibility of reports on the influence of VPA on cytokine system in patients with generalized epilepsy, this problem needs more investigations, especially in the group of children.

Association study of the 2-bp deletion polymorphism in exon 6 of the CHRFAM7A gene with idiopathic generalized epilepsy.

There is evidence of linkage between the 15q13-q14 locus, containing the gene encoding the α7 subunit (CHRNA7) of the neuronal nicotinic acetylcholine receptor (nAChR) and its partially duplicated isoform (CHRFAM7A), and epilepsy. Additionally, a 2-bp deletion polymorphism (c.497-498delTG; rs67158670) in CHRFAM7A, resulting in a frame shift and truncation of the protein product, is associated with some neurological diseases. This study was designed to explore the possibility of an association of the c.497-498delTG polymorphism of CHRFAM7A with idiopathic generalized epilepsies (IGEs) in Polish children and young patients. The study included 197 IGE patients and 258 unrelated healthy individuals. The frequency of the CHRFAM7A c.497-498delTG polymorphism was determined in each group using heteroduplex analysis. An association between the c.497-498delTG polymorphism of CHRFAM7A and IGE was evidenced. It was demonstrated that the frequency of the CHRFAM7A 2-bp deletion carriers was significantly lower in the IGE patients than in the control group. The observed frequency of 2-bp deletion carriers was high in IGE subjects (64%), but significantly higher in control subjects (76%). Carriers of at least one copy of the -2 bp allele had halved their risk of IGE susceptibility (delTG/delTG and delTG/wild-type versus wild-type/wild-type: odds ratio=0.55; 95% confidence intervals=0.365-0.827; p=0.004). Moreover, it has been demonstrated that this polymorphic variant is associated with the c.524-12_524-11insGTT variation (rs10649395) in intron 7 of CHRFAM7A. Our study substantiates the involvement of the α7 subunit of nAChR in the pathophysiology of IGEs and indicates that the CHRFAM7A c.497-498TG deletion or a nearby polymorphism may play a role in the pathogenesis of IGE. Further work should concentrate on ascertaining the exact mechanism of this polymorphism's effect and its relationship with IGE.

[Homocysteine and asymmetric dimethylarginine (ADMA) in epilepsy]. / Homocysteina i asymetryczna dimetyloarginina (ADMA) w padaczce.

Homocysteine (Hcy) is a thyol amino acid resulting from demethylation of methionine. It is metabolized through two pathways: remethylation and trassulfuration, which use as cofactors folate, vitamin B6 and vitamin B12. Hyperhomocysteinemia (hHcy) is a risk factor for cerebrovascular disease, dementia, inborn defects, impaired cognitive function. Several drugs may change metabolic pathways of Hcy, leading to an alteration of plasma Hcy levels. HHcy has been documented in epileptic patients after chronic treatment with antiepileptic drugs (carbamazepine, valproate). HHcy may lead to increase of the level of asymmetric dimethylarginine (ADMA). ADMA has been identified as a potential risk factor for cardiovascular disease and endothelial dysfunction. ADMA is a product of methylation of L-arginine and endogenous nitric oxide (NO) synthase inhibitor, and regulator of NO production. NO plays a role in the convulsant effect. Supplementation of B vitamins, folate and L-arginine is a strategy to reduce Hcy levels in patients with epilepsy treatment antiepileptic drugs.