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.

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.

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.

Pediatric multiple sclerosis - current status of epidemiology, diagnosis and treatment.

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system that mostly affects younger adults. However, the first symptoms of MS can appear in children and adolescents before the age of 18, and we call this paediatric MS (PMS). It is estimated that paediatric MS accounts for 3-5% of the general population of patients with MS. Despite the fundamental si-milarities to adult MS, PMS has many distinctive features. Paediatric MS has a milder course compared to adults, but leads to sig-nificant disability at an early age. PMS is relapsing-remitting in 95-98% of cases; the primary progressive manifestation is much less common than in adults. The differential diagnosis of MS in children should include other childhood demyelinating diseases, mitochondrial and metabolic diseases, connective tissue diseases, and neuroborreliosis. Differentiating acute disseminated en-cephalomyelitis (ADEM) from the first onset of MS remains the biggest challenge. Over the past 10 years, understanding of the epidemiology, pathophysiology, diagnosis, and treatment of MS in children has significantly expanded. The diagnostic criteria leading to earlier diagnosis and initiation of disease-modifying therapy (DMT) have changed, and the number of drugs used in children has increased. However, many important issues require further research. This review discusses the current state of knowledge regarding the epidemiology, diagnosis, and treatment of multiple sclerosis in children.

Recommendations of the Polish Medical Society of Radiology and the Polish Society of Neurology for a protocol concerning routinely used magnetic resonance imaging in patients with multiple sclerosis.

Magnetic resonance imaging (MRI) is a widely used method for the diagnosis of multiple sclerosis that is essential for the detection and follow-up of the disease. OBJECTIVE: The Polish Medical Society of Radiology (PLTR) and the Polish Society of Neurology (PTN) present the second version of their recommendations for investigations routinely conducted in magnetic resonance imaging departments in patients with multiple sclerosis. This version includes new data and practical comments for electroradiology technologists and radiologists. The recommended protocol aims to improve the MRI procedure and, most importantly, to standardise the method of conducting scans in all MRI departments. This is crucial for the initial diagnostics necessary for establishing a diagnosis, as well as for MS patient monitoring, which directly translates into significant clinical decisions. INTRODUCTION: Multiple sclerosis (MS) is a chronic immune mediated inflammatory demyelinating disease of the central nervous system (CNS), the aetiology of which is still unknown. The nature of the disease lies in a CNS destruction process disseminated in time (DIT) and space (DIS). MRI detects focal lesions in the white and grey matter with high sensitivity (although with significantly lower specificity in the latter). It is also the best tool to assess brain atrophy in patients with MS in terms of grey matter volume (GMV) and white matter volume (WMV) as well as local atrophy (by measuring the volume of thalamus, corpus callosum, subcortical nuclei, and hippocampus) as parameters that correlate with disability progression and cognitive dysfunctions. Progress in MR techniques, as well as advances in postprocessing the obtained data, has driven the dynamic development of computer programs that allow for a more repeatable assessment of brain atrophy in both cross-sectional and longitudinal studies. MR imaging is unquestionably the best diagnostic tool available to follow up the course of the disease and support clinicians in choosing the most appropriate treatment strategy for their MS patient. However, to diagnose and follow up MS patients on the basis of MRI in accordance with the latest standards, the MRI study must adhere to certain quality criteria. Such criteria are the subject of this paper.

Recommendations of the Polish Medical Society of Radiology and the Polish Society of Neurology for the routinely used magnetic resonance imaging protocol in patients with multiple sclerosis.

Magnetic resonance imaging (MRI) is a widely used method for the diagnosis of multiple sclerosis (MS) that is essential for the detection and follow-up of the disease. The Polish Medical Society of Radiology (PLTR) and the Polish Society of Neurology (PTN) present the second version of the recommendations for examinations routinely conducted in magnetic resonance imaging departments in patients with MS, which include new data and practical comments for electroradiology technicians and radiologists. The recommended protocol aims to improve the MRI procedure and, most importantly, to standardise the method of conducting scans in all MRI departments. This is crucial for the initial diagnostics that are necessary to establish a diagnosis as well as monitor patients with MS, which directly translates into significant clinical decisions. MS is a chronic idiopathic inflammatory demyelinating disease of the central nervous system (CNS), the aetiology of which is still unknown. The nature of the disease lies in the CNS destruction process disseminated in time and space. MRI detects focal lesions in the white and grey matter with high sensitivity (with significantly less specificity in the latter). It is also the best tool to assess brain atrophy in patients with MS in terms of grey matter volume and white matter volume as well as local atrophy (by measuring the volume of thalamus, corpus callosum, subcortical nuclei, hippocampus) as parameters that correlate with disability progression and cognitive dysfunctions. Progress in magnetic resonance techniques, as well as the abilities of postprocessing the obtained data, has become the basis for the dynamic development of computer programs that allow for a more repeatable assessment of brain atrophy in both cross-sectional and longitudinal studies. MRI is unquestionably the best diagnostic tool used to follow up the course of the disease and to treat patients with MS. However, to diagnose and follow up the patients with MS on the basis of MRI in accordance with the latest standards, an MRI study must meet certain quality criteria, which are the subject of this paper.

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.

Children with epilepsy against their healthy peers and those with headaches: Differences-similarities.

INTRODUCTION: Epilepsy, like most chronic diseases, affects bio-psycho-social functioning of children and adolescents. The aim of this work was to assess functioning of children with epilepsy compared with the group of healthy children and those with headaches carried out by children themselves and their mothers. MATERIAL AND METHODS: The study included 209 children with epilepsy and 173 children with headaches and 182 healthy students and their mothers. The research tool was Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL™ 4.0) questionnaire. RESULTS: Quality of life of healthy children was rated the highest in all areas by both children and mothers. In younger and older children, difference was demonstrated between the assessment of the quality of life of healthy children and the ones with epilepsy or healthy children and the ones with and headaches in all areas of the PedsQL™ 4.0 questionnaire (p<0.05). Children with epilepsy had the most difficulties in subscale School Functioning in their own and their mothers' opinion. Healthy children and their mothers rated the subscale Emotional Functioning lowest. CONCLUSIONS: The functioning of children with epilepsy in the assessment of children and their mothers was the closest to the functioning of children with headaches. Quality of children's life assessment by children with epilepsy and by healthy children differed between the group of girls and boys and between older and younger children in all PedsQLTM 4.0 questionnaire areas. A medium response compatibility between children with epilepsy and their mothers was shown in individual questions.

The assessment of risk factors for febrile seizures in children.

OBJECTIVE: The aim of the paper was to assess the risk factors of febrile seizures in children. METHODS: The paper presents an analysis of a group of 176 children aged 6 months to 5 years who were admitted to A&E because of febrile seizures. RESULTS: The analysed group of 176 children comprised 61.96% boys and 38.07% girls, and the average age equalled 23 months. Family history was significant in 9.66% of patients. A statistically significant difference was noticed between insignificant family history and the incidence of febrile seizures. In all the studied groups of children the factor that determined the incidence of febrile seizures was a sudden increase in the body temperature with an infection of the upper respiratory tract of several day's duration as another cause. Febrile seizure incident was most frequently associated with a sudden increase in the body temperature in 53.40% children. A statistically significant difference was observed between persisting fever and an increase thereof during the day. Yet another factor predisposing for febrile seizures incidence was an infection of the upper respiratory system that could be observed in 32.95% patients. The mean body temperature when the seizures occurred was 38.9°C. CONCLUSIONS: A sudden increase in the body temperature within the first day of pyrexia predisposes for the incidence of febrile seizures and it was proved that it depends on how long fever persists during the day. The other factor triggering the seizures was an infection of the upper respiratory tract of several days' duration.

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.

Genotype-phenotype correlations in Polish patients with SCN8A-related epilepsy: A multicentre observational study.

BACKGROUND: Voltage-gated sodium channels are involved in the initial depolarisation of neurones. As such, they play important roles in neurotransmission. Variants in the genes encoding these channels may lead to altered functionality and neurodevelopmental disorders. Pathogenic variants of SCN8A, which encodes the voltage-gated Na+ channel Nav1.6, have been associated with various encephalopathies characterised by developmental delay and epileptic seizures. Herein, we discuss the genotype-phenotype associations in a group of 17 novel Polish patients with SCN8A mutations, further expanding the molecular and phenotypic spectrum of SCN8A-related diseases. METHODS: The participants were recruited from five clinical centres in Poland. Pathogenic and likely pathogenic SCN8A variants were identified using a next-generation sequencing (NGS) panel and exome sequencing, respectively. Magnetic resonance imaging (MRI) and electroencephalography (EEG) recordings were performed to obtain relevant clinical data on brain malformations and epileptic seizures. RESULTS: Three phenotypes were observed in the study group: developmental and epileptic encephalopathy, early onset epileptic encephalopathy, and neurodevelopmental disorders without epilepsy. Patients in the first two phenotypic subgroups presented with epileptic seizures within the first few months of life. Their semiology evolved with age, comprising mostly tonic, clonic, and tonic-clonic seizures, with eyelid myoclonia, myoclonic seizures, and epileptic spasms. The most prevalent neurological feature was developmental delay. Alterations in muscle tone were more frequent than in previous reports. CONCLUSIONS: Seventeen patients with 11 novel mutations in SCN8A had alterations in muscular tone accompanied by typical features of SCN8A-related encephalopathies (i.e., developmental delay and a wide range of seizures).

Achieving motor development milestones at the age of three months may determine, but does not guarantee, proper further development.

Proper motor performance at 3rd month is necessary for further motor development. The paper aims to demonstrate the reliability, sensitivity, and predictive value of an original motor performance assessment tool in comparison with the neurological assessment at 3, 6, and 9 months. Children (n = 123), born at term without pre- or perinatal complications, born at term with pre- or perinatal complications, or born preterm, were assessed at the age of 3, 6, and 9 months, by a neurologist and a physiotherapist. The physiotherapist evaluated 15 qualitative features typical for the age of 3 months in the prone and supine positions. The final neurological assessment determined the degree of developmental disorder. Neurological and global physiotherapeutic assessments showed a statistically significant correlation. Qualitative assessment results were very good in healthy children and decreased with worsening neurological diagnoses. Children diagnosed with cerebral palsy did not show proper qualitative features of 3 months when analyzed at 3, 6, and 9 months. Children with delayed motor development revealed minor qualitative performance impairments as early as 3 months but improved with age. Qualitative assessment at 3 months not only facilitates diagnosis of major developmental disorders but is also a good predictor of delayed motor development in children.

Examination of Upper Limb Function and the Relationship with Gross Motor Functional and Structural Parameters in Patients with Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by the deletion or/and mutation in the survival motor neuron 1 (SMN1) gene on chromosome 5. Until now, only a few articles investigating the relationship between upper limb function and the gross motor function in untreated SMA patients have been published. However, there is still a lack of publications including the relationship between structural changes such as cervical rotation, trunk rotation and side trunk shortening, and upper limb function. The aim of the study was to examine the upper limb function in patients with spinal muscular atrophy and the relationship between the upper limb function, gross motor function, and structural parameters. We present an analysis of 25 SMA patients, divided into sitter and walker groups, undergoing pharmacological treatment (nusinersen or risdiplam), examined twice between the initial examination and evaluation after a 12-month period. The participants were tested using validated scales such as the Revised Upper Limb Module (RULM), the Hammersmith Functional Motor Scale-Extended (HFMSE), and the structural parameters. Our results showed that patients demonstrated greater improvement on the RULM scale than on the HFMSE scale. Moreover, persistent structural changes negatively affected both the upper limb function and gross motor skills.

Broadening the phenotypic spectrum of the presumably epilepsy-related SV2A gene variants.

Missense variants in the synaptic vesicle glycoprotein SV2A gene have been previously found in a few individuals with epilepsy. Adverse reaction to levetiracetam in individuals with various variants of this gene has recently been described. Here, we report on a family with several members affected by epilepsy. In affected members of this family, we identified a variant in the SV2A gene (NM_014849.5: c.1978 G>A, p.(Gly660Arg). This family case further supports the role of the SV2A gene in autosomal dominant epilepsy. It provides new information on the course of epilepsy in people with variants in the SV2A gene who have never been treated with SV2A agonists and specific neurodevelopmental features of this syndrome.

Expanding the Knowledge of KIF1A-Dependent Disorders to a Group of Polish Patients.

BACKGROUND: KIF1A (kinesin family member 1A)-related disorders encompass a variety of diseases. KIF1A variants are responsible for autosomal recessive and dominant spastic paraplegia 30 (SPG, OMIM610357), autosomal recessive hereditary sensory and autonomic neuropathy type 2 (HSN2C, OMIM614213), and autosomal dominant neurodegeneration and spasticity with or without cerebellar atrophy or cortical visual impairment (NESCAV syndrome), formerly named mental retardation type 9 (MRD9) (OMIM614255). KIF1A variants have also been occasionally linked with progressive encephalopathy with brain atrophy, progressive neurodegeneration, PEHO-like syndrome (progressive encephalopathy with edema, hypsarrhythmia, optic atrophy), and Rett-like syndrome. MATERIALS AND METHODS: The first Polish patients with confirmed heterozygous pathogenic and potentially pathogenic KIF1A variants were analyzed. All the patients were of Caucasian origin. Five patients were females, and four were males (female-to-male ratio = 1.25). The age of onset of the disease ranged from 6 weeks to 2 years. RESULTS: Exome sequencing identified three novel variants. Variant c.442G>A was described in the ClinVar database as likely pathogenic. The other two novel variants, c.609G>C; p.(Arg203Ser) and c.218T>G, p.(Val73Gly), were not recorded in ClinVar. CONCLUSIONS: The authors underlined the difficulties in classifying particular syndromes due to non-specific and overlapping signs and symptoms, sometimes observed only temporarily.

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.

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.