Multiple sclerosis (MS) is a chronic immune-mediated inflammatory demyelinating disease of the central nervous system (CNS), the exact etiology of which remains unknown. The pathological hallmark of MS involves CNS tissue damage characterized by dissemination in space (DIS) and dissemination in time (DIT). Magnetic resonance imaging (MRI) represents the most sensitive paraclinical tool for detection, diagnosis, and longitudinal monitoring of MS, playing a crucial role in treatment decision-making. The recently published 2024 McDonald criteria, incorporating advances in MR acquisition and post-processing techniques, necessitate revision of current MRI protocols used in routine clinical practice. These updated criteria expand the definition of typical MS lesion locations to include the optic nerves and introduce novel MRI biomarkers - the central vein sign (CVS) and paramagnetic rim lesions (PRLs) - which enhance diagnostic specificity and differential diagnosis. This manuscript presents the third version of recommendations developed by the Polish Medical Society of Radiology and the Polish Neurological Society for standardized MRI examination protocols in patients with MS. These evidence-based recommendations incorporate contemporary technical advances, provide practical guidance for radiographers and radiologists, and aim to standardize imaging procedures across all MRI departments in Poland. Implementation of this protocol is essential for establishing reliable diagnoses, ensuring adequate disease monitoring, and supporting critical clinical decisions regarding treatment initiation and modification.

Nesfatin-1 and ghrelin O-acyltransferase (GOAT) have established roles in metabolic regulation and neuronal excitability, yet their relationship in epilepsy remains conflicted. This cross-sectional study compared 22 adolescent epilepsy patients (13.1 ± 2.0 years; 11 women/11 men) with 20 age-matched healthy controls (HCs) (12.3 ± 2.2 years; 8 women/12 men). Serum and salivary nesfatin-1 and GOAT levels were measured by enzyme-linked immunosorbent assay; Spearman's rank correlation assessed inter-neuropeptide relationships. Serum nesfatin-1 was markedly elevated in patients with epilepsy compared to HCs (44.04 (interquartile range 38.19-76.72) vs. 8.65 (interquartile range 7.82-9.01) ng/mL, p < 0.001; ~5-fold). Serum GOAT was similarly elevated (4.90 (interquartile range 4.17-6.66) vs. 1.41 (interquartile range 1.21-1.79) ng/mL, p < 0.001; 3.5-fold). A significant inverse correlation between serum nesfatin-1 and GOAT levels was identified in patients with epilepsy (rho = -0.68, 95% CI [-0.86, -0.36], p < 0.001) but not in HCs (p = 0.53) and remained independent of age, sex, body mass index and epilepsy type. This inverse correlation was significant in women (rho = -0.68, p = 0.021) with a similar trend in men (rho = -0.53, p = 0.096). Salivary nesfatin-1 mirrored serum patterns (2.3-fold increase; p < 0.001), while salivary GOAT showed a 9-fold reduction (p < 0.001). This study provides the first evidence of an inverse nesfatin-1/GOAT correlation in adolescent epilepsy, suggesting disease-specific neuroendocrine dysregulation. These exploratory findings support the potential of these neuropeptides as candidate biomarkers warranting further validation and offer new insights into the metabolic-excitability axis in epilepsy.

Spinal muscular atrophy mainly affects motor neurons in the spinal cord, leading to progressive muscular atrophy and weakness. This study aims to carefully analyse the effect of body parameters on motor function and fine motor skills, measured at one-year intervals, in patients with spinal muscular atrophy. The study included 38 participants diagnosed with SMA. Patients were divided into three groups based on their level of motor function: non-sitters (n = 9), sitters (n = 23), and walkers (n = 6). Anthropometric measurements (weight, height/length) were taken in all participants, and BMI and BMI-z-score were calculated. The motor function was assessed using validated scales: CHOP-INTEND for the non-sitters group and HFMSE scale for the sitters and walkers group. The RULM scale assessed fine motor skills for the sitters and walkers group. At the 12-month follow-up, the CHOP-INTEND scale showed improvement in most non-sitter patients (6/9). The sitter’s group was more heterogeneous on the HFMSE scale, with 10 out of 23 patients showing deterioration in function, 8 showing improvement, while the walker’s group showed the least variability. In the non-sitters group, the dominant category of BMI z-score was underweight, while half of the sitters in the group were underweight, although there were just as many healthy weights. The strongest group, the walkers, was mostly healthy. We have observed a certain tendency that as BMI increases, motor function increases in all groups, while fine motor skill decreases in the most varied sitters group. As BMI increases in SMA patients, motor function improves. Fine motor skill deteriorates as BMI increases in the sitter’s group. The assessment of individual components of motor function and fine motor skills reveals the actual changes that occur over time in patients with SMA.

Introduction. Nesfatin-1 and Ghrelin O-acetyltransferase (GOAT) are peptide hormones involved in stress response and pain modulation beyond their metabolic functions. This study investigated whether these biomarkers differ between adolescents with headaches and healthy controls and examined their relationship with temporomandibular disorders (TMD). Material and methods. This cross-sectional study measured Nesfatin-1 and Ghrelin/GOAT levels in the serum and saliva of 44 adolescents with headaches (aged 10-17 years, diagnosed per ICHD-3 beta criteria) and 20 age-matched healthy controls. TMD was assessed using the Diagnostic Criteria for TMD (DC/TMD). Statistical comparisons were performed using non-parametric tests, with significance set at p < 0.05. Results. Nesfatin-1 was elevated in all headache patients compared to controls in both blood (patient median range: 39.5-45.0 ng/mL vs. control median range: 8.1-9.0 ng/mL, p<0.001) and saliva (patient median range: 6.6-8.2 ng/mL vs. control median range: 1.8-2.3 ng/mL, p<0.001) regardless of headache type (migraine vs. tension-type) or TMD status. Ghrelin/GOAT showed opposite patterns in blood versus saliva: serum levels were higher in patients (median range: 5.9-6.6 ng/mL vs. 1.4 ng/mL in controls, p<0.001), while salivary levels were lower (median range: 0.2 ng/mL vs. 1.4 ng/mL in controls, p<0.001). Gender differences emerged in clinical manifestations: females had more muscle pain (74% vs 38%, p = 0.016), while males reported more psychological distress (90% vs 48%, p = 0.003). Conclusions. This study reveals altered Nesfatin-1 and Ghrelin/GOAT levels in adolescents with headaches, independent of headache type or TMD status. These findings suggest potential utility as pain-related biomarkers, though validation studies with larger sample sizes and receiver operating characteristic analyses are needed before clinical implementation. Gender specific clinical patterns underscore the importance of sex-stratified approaches in adolescent pain management.

MOGAD is a demyelinating syndrome with the presence of antibodies against myelin oligodendrocyte glycoprotein, which is, next to multiple sclerosis and the neuromyelitis optica spectrum, one of the manifestations of the demyelinating process, more common in the pediatric population. MOGAD can take a variety of clinical forms: acute disseminated encephalomyelitis (ADEM), retrobulbar optic neuritis, often binocular (ON), transverse myelitis (TM), or NMOSD-like course (neuromyelitis optica spectrum disorders), less often encephalopathy. The course may be monophasic (40–50%) or polyphasic (50–60%), especially with persistently positive anti-MOG antibodies. Very rarely, the first manifestation of the disease, preceding the typical symptoms of MOGAD by 8 to 48 months, is focal seizures with secondary generalization, without typical demyelinating changes on MRI of the head. The paper presents a case of a 17-year-old patient whose first symptoms of MOGAD were focal epileptic seizures in the form of turning the head to the right with the elevation of the left upper limb and salivation. Seizures occurred after surgical excision of a tumor of the right adrenal gland (ganglioneuroblastoma). Then, despite a normal MRI of the head and the exclusion of onconeural antibodies in the serum and cerebrospinal fluid after intravenous treatment, a paraneoplastic syndrome was suspected. After intravenous steroid treatment and immunoglobulins, eight plasmapheresis treatments, and the initiation of antiepileptic treatment, the seizures disappeared, and no other neurological symptoms occurred for nine months. Only subsequent relapses of the disease with typical radiological and clinical picture (ADEM, MDEM, recurrent ON) allowed for proper diagnosis and treatment of the patient both during relapses and by initiating supportive treatment. The patient’s case allows us to analyze the multi-phase, clinically diverse course of MOGAD and, above all, indicates the need to expand the diagnosis of epilepsy towards demyelinating diseases: determination of anti-MOG and anti-AQP4 antibodies.

The presented study identified the appropriate ocrelizumab dosing regimen for patients with pediatric-onset multiple sclerosis (POMS). Patients with POMS aged 10–17 years were enrolled into cohort 1 (body weight [BW] < 40 kg, ocrelizumab 300 mg) and cohort 2 (BW ≥ 40 kg, ocrelizumab 600 mg) during a 24-week dose-exploration period (DEP), followed by an optional ocrelizumab (given every 24 weeks) extension period. Primary endpoints: pharmacokinetics, pharmacodynamics (CD19+ B-cell count); secondary endpoint: safety; exploratory endpoints: MRI activity, protocol-defined relapses, Expanded Disability Status Scale (EDSS) score change. A total of 23 patients (cohort 1: n = 6, age 10–12 years, BW 27.0–39.0 kg; cohort 2: n = 17, age 11–17 years, BW 42.1–108.4 kg) were enrolled. Median treatment duration was 120 (range, 24–193) weeks at the primary analysis cutoff (October 5, 2023). Overall, the pharmacokinetic data were within the range observed at 600 mg in adult patients with MS; however, the exposure at 300 mg in patients < 40 kg was lower than with 600 mg in patients ≥ 40 kg. Shifting the cutoff to 35 kg would provide better exposure to patients with 35–40 kg body weight. Sustained, near-complete B-cell depletion was observed. The safety profile was consistent with that in adults. EDSS scores remained stable; no clinical relapses were observed. A dosing regimen of 300 mg ocrelizumab for patients < 35 kg, and 600 mg for patients ≥ 35 kg (every 24 weeks), was selected for the phase 3 OPERETTA II trial (NCT05123703). ClinicalTrials.gov: NCT04075266.

IntroductionTargeted 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.MethodsA retrospective analysis was conducted on patients from a genetic clinic in Poznań, 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.ResultsAmong 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.DiscussionIdentified 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.

Zespół Phelan-McDermid to rzadka genetycznie uwarunkowana choroba wynikająca z delecji fragmentu 13.3 ramienia q chromosomu 22, którą charakteryzuje występowanie globalnego opóźnienia w rozwoju psychoruchowym, niepełnosprawność intelektualna, opóźnienie lub brak rozwoju mowy oraz cechy autystyczne. Do manifestacji neurologicznych tego zespołu należą napady padaczkowe, które występują u 17-70% pacjentów. Jednak rozpoznanie padaczki u dzieci z delecją 22q13.3 stanowi wyzwanie diagnostyczne co wynika z niewielkiej ilości danych dotycząch charakterystycznego typu napadów padaczkowych oraz wzorców EEG w tym zespole. Dlatego też poniżej przedstawiamy dwoje pacjentów (7,5-letniego chłopca oraz 11-letnią dziewczynkę) z zespołem Phelan-McDermid oraz zbliżoną semiologią napadów padaczkowych. U obojga pacjentów napady występowały rzadko, były prowokowane gorączką, dobrze odpowiadały na leki przeciwnapadowe.

A boy is presented in whom Down Syndrome mosaicism and spinal muscular atrophy by overlapping clinical symptoms delayed the diagnosis and caused complicated motor development. The boy from the first pregnancy was delivered vaginally, week 37, Apgar 10, birth weight 3,650 g. The mother, aged 30, had no family history of Down Syndrome or neuromuscular diseases. Primary diagnosis at the age of 3 weeks: unbalanced male karyotype -mos 47, XY+21 [22]/46, XY. At 20 months, the parents observed the disappearance of the high kneeling function and asked for a neurologist’s consultation. The neurological examination showed symmetrically reduced muscle tone and symmetrically weakened knee and ankle tendon reflexes. The physiotherapeutic assessment revealed a symmetrical weakening of muscle strength and hand tremor (features characteristic of patients with spinal muscular atrophy). The final diagnosis, set at the age of 27 months, was thus the mosaic form of Down Syndrome and spinal muscular atrophy type 2.

The study aimed to analyse the mutual correlations between the metabolic activity of the brain evaluated by the magnetic resonance spectroscopy method (MRS) and intelligence and cognitive functions in adolescents with idiopathic generalised epilepsies (IGE). The focus of the study was placed on the activity of the thalamus and frontal cortex.Twenty newly diagnosed patients with juvenile absence epilepsy (JAE) and juvenile myoclonic epilepsy (JME) were included in the study. Adolescents underwent primary structural neuroimaging (1.5T) and advanced evaluation of the frontal cortex and thalamus by MRS. Concentrations of N-acetyl aspartate (NAA), creatine plus phosphocreatine (Cr) and choline (Cho) were measured and were expressed as ratios of NAA/Cr, NAA/Ch and NAA/Cr+Ch. Patients also completed a panel of IQ and cognitive tests (e.g., FePsy Battery – classification test, verbal fluency test, RAVLT memory test). The correlation between the level of metabolites and the results of intellectual and cognitive tests was examined.Strong correlations were found between IQ and some cognitive functions and metabolic ratios in the IGEs group. Overall the patients whose NAA/Cr, NAA/Ch, NAA/Cr+Ch ratios were lower, obtained worse results in IQ and in some of the neuropsychological tests.The metabolite activity in the thalamus and frontal cortex impacts the results of neuropsychological tests in the group of patients with IGE.

Drooling (sialorrhea) is excessive loss of saliva from the mouth. It is mainly caused by impaired swallowing of saliva. Severe drooling is a common, worrying problem in children and adolescents with neurological disorders, which has negative health and social consequences. The treatment of drooling is a complicated and long-term process that requires the appropriate cooperation of many specialists. The choice of therapy depends on child's intelectual developement, its ability to cooperate and the cause of drooling. The most effective treatment is speech therapy. Pharmacological treatment and surgical interventions should be considered in specific cases in patients with moderate to severe drooling or patients with respiratory complications. Currently, the only registered drug for the treatment of severe sialorrhea in children and adolescents from 3 years of age with chronic neurological disorders is glycopyrronium bromide.

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).

Encefalopatia padaczkowa i rozwojowa związana z genem CDKL5, czyli deficyt kinazy cyklino-zależnej typu 5 (CDD, CDKL5 deficiency disorder), manifestuje się napadami padaczkowymi oraz istotnym opóźnieniem w rozwoju psychoruchowym. Wcześniej uważano CDD za wariant zespołu Retta (wariant Hanefelda), aktualnie jednak jest uznawany jako odrębna jednostka kliniczna. CDD charakteryzuje się wczesnym występowaniem padaczki, zwykle w ciągu pierwszych 3 miesięcy życia. Napady mają charakter polimorficzny. Rozwój psychoruchowy jest znacznie upośledzony; jedynie niewielki odsetek pacjentów potrafi chodzić samodzielnie. Inne istotne cechy kliniczne to korowe upośledzenie widzenia, zaburzenia snu, stereotypowe ruchy rąk, hipotonia, problemy gastroenterologiczne, skolioza oraz infekcje dróg oddechowych. Znaczna lekooporność sprawia, że leczenie jest wyjątkowo wymagające. Wyniki konwencjonalnego leczenia przeciwnapadowego są rozczarowujące, dają jedynie minimalne albo krótkotrwałe rezultaty. Alternatywne metody leczenia, takie jak dieta ketogenna i stymulacja nerwu błędnego, wykazują również ograniczoną skuteczność. Dostępne są jednak nowe możliwości terapeutyczne, takie jak ganaxolone, którego wyniki w zakresie leczenia przeciwnapadowego wydają się obiecujące. Konieczne jest również dalsze badanie potencjału innych leków, takich jak soticlestat, fenfluramina i kannabidiol, zwłaszcza na większych kohortach. Encefalopatia padaczkowa i rozwojowa i związana z genem CDKL5 to złożone zaburzenie o wielu aspektach, a mechanizmy leżące u jego podstaw nie zostały w dalszym ciągu w pełni wyjaśnione. Konieczne jest dalsze badanie procesów patologicznych towarzyszących temu zaburzeniu oraz opracowanie skuteczniejszych metod leczenia. Klinicyści powinni być świadomi objawów chorobowych i wyzwań terapeutycznych, aby zapewnić odpowiednią opiekę i wsparcie osobom dotkniętym tym złożonym schorzeniem.

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.