AIM: This exploratory study evaluates rating scale usage by experts from the European Reference Network for Rare Neurological Diseases (ERN-RND) for paediatric MD, considering factors like diagnosis, intellectual disability, age, and transition to adult care. The aim is to propose a preliminary framework for consistent application. METHODS: A multicentre survey among 25 ERN-RND experts from 10 European countries examined rating scale usage in paediatric MD, categorizing MD into acute, non-progressive, and neurodegenerative types. Factors influencing scale choice and the transition to adult care practices were analysed. A comprehensive literature search was conducted to identify the earliest age of application of these scales in paediatric patients. RESULTS: The study identifies various rating scales and establishes their usage frequencies for different MDs. Experts highlighted the need for standardized scales and proposed preliminary evaluation strategies based on clinical contexts. Challenges in applying scales to young, non-cooperative patients were acknowledged. INTERPRETATION: The study recommends developing standardized rating scales for paediatric MDs to improve evaluations and data collection. It suggests potential scales for specific clinical scenarios to better evaluate disease progression. Comprehensive, patient-centred care remains crucial during the transition to adult care, despite the identified challenges. This exploratory approach aims to enhance patient outcomes and care.

• Keywords
• Ataxia, Dystonia, Movement disorders, Myoclonus, Paediatrics, Rating scales,
• MeSH
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Pediatrics standards   methods   MeSH
• Movement Disorders * therapy   diagnosis   MeSH
• Transition to Adult Care standards   MeSH
• Severity of Illness Index MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Geographicals
• Europe MeSH

Spinal muscular atrophy (SMA) is one of the most common genetic diseases and was, until recently, a leading genetic cause of infant mortality. Three disease-modifying treatments have dramatically changed the disease trajectories and outcome for severely affected infants (SMA type 1), especially when initiated in the presymptomatic phase. One of these treatments is the adeno-associated viral vector 9 (AAV9) based gene therapy onasemnogene abeparvovec (Zolgensma®), which is delivered systemically and has been approved by the European Medicine Agency for SMA patients with up to three copies of the SMN2 gene or with the clinical presentation of SMA type 1. While this broad indication provides flexibility in patient selection, it also raises concerns about the risk-benefit ratio for patients with limited or no evidence supporting treatment. In 2020, we convened a European neuromuscular expert working group to support the rational use of onasemnogene abeparvovec, employing a modified Delphi methodology. After three years, we have assembled a similar yet larger group of European experts who assessed the emerging evidence of onasemnogene abeparvovec's role in treating older and heavier SMA patients, integrating insights from recent clinical trials and real-world evidence. This effort resulted in 12 consensus statements, with strong consensus achieved on 9 and consensus on the remaining 3, reflecting the evolving role of onasemnogene abeparvovec in treating SMA.

• Keywords
• Adeno-associated viral vector, Disease modifying treatment, Effectiveness, Gene therapy, Newborn screening, Onasemnogene abeparvovec, Safety, Spinal muscular atrophy, Survival motor neuron gene, Zolgensma®,
• MeSH
• Biological Products therapeutic use   MeSH
• Genetic Therapy * methods   MeSH
• Consensus MeSH
• Humans MeSH
• Recombinant Fusion Proteins MeSH
• Muscular Atrophy, Spinal * therapy   genetics   MeSH
• Spinal Muscular Atrophies of Childhood therapy   genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Europe MeSH
• Names of Substances
• Biological Products MeSH
• Recombinant Fusion Proteins MeSH
• Zolgensma MeSH Browser

BACKGROUND: The central vein sign (CVS) has been proposed as a novel MRI biomarker to improve diagnosis of pediatric-onset MS (POMS). However, the role of CVS in POMS progression has yet to be discovered. OBJECTIVES: To investigate the appearance of CVS and its correlation with POMS disease progression. METHODS: One hundred fifty-six POMS from two MS centers in Israel and Czech Republic MS centers were followed for five years. Patient assessment was performed by the Expanded Disability Status Scale (EDSS) and Annual Relapse Rate (ARR). Patients in whom at least 40 % of brain MRI lesions had CVS ("rule of 40") were determined as CVS-positive. RESULTS: The total group of POMS consisted of 96 CVS-negative (61.5 %), aged 14.6 ± 1.9 years, EDSS 2.0, 75 % Interquartile Range (IQR) 1.0-3.0, disease duration (DD) 6.28 ± 0.38 years, and 60 CVS-positive (38.5 %), aged 15.1 ± 0.3 years, EDSS 2.0, IQR 1.5-3.0, DD 5.62 ± 0.13 years, were analyzed. After a three and five-year follow-up, the CVS-positive patients had higher EDSS scores than those who were CVS-negative, 2.0, IQR 1.0-2.5, vs 1.0, IQR 1.0-2.0, (p = 0.009) and 2.0, IQR 1.0-3.25 vs 1.0, IQR 1.0-2.0, (p = 0.0003), respectively. Patients with CVS-positive POMS were characterized by a significantly higher ARR (0.78 ± 0.08 vs 0.57 ± 0.04, p = 0.002). These results were confirmed in subgroups of Disease Modifying Treatments (DMT) untreated and treated patients. CONCLUSION: CVS-positive POMS is characterized by higher disability progression than CVS-negative, indicating the importance of CVS in disease pathogenesis.

• MeSH
• Child MeSH
• Humans MeSH
• Magnetic Resonance Imaging * MeSH
• Adolescent MeSH
• Brain diagnostic imaging   pathology   MeSH
• Cerebral Veins diagnostic imaging   physiopathology   MeSH
• Follow-Up Studies MeSH
• Disability Evaluation MeSH
• Disease Progression * MeSH
• Multiple Sclerosis diagnostic imaging   physiopathology   MeSH
• Age of Onset MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Geographicals
• Czech Republic MeSH
• Israel MeSH

• Publication type
• Editorial MeSH

OBJECTIVE: Developmental and epileptic encephalopathies (DEEs) are a group of severe, early-onset epilepsies characterised by refractory seizures, developmental delay, or regression and generally poor prognosis. DEE are now known to have an identifiable molecular genetic basis and are usually examined using a gene panel. However, for many patients, the genetic cause has still not been identified. The aims of this study were to identify causal variants for DEE in patients for whom the previous examination with a gene panel did not determine their genetic diagnosis. It also aims for a detailed description and broadening of the phenotypic spectrum of several rare DEEs. METHODS: In the last five years (2015-2020), 141 patients from all over the Czech Republic were referred to our department for genetic testing in association with their diagnosis of epilepsy. All patients underwent custom-designed gene panel testing prior to enrolment into the study, and their results were inconclusive. We opted for whole exome sequencing (WES) to identify the cause of their disorder. If a causal or potentially causal variant was identified, we performed a detailed clinical evaluation and phenotype-genotype correlation study to better describe the specific rare subtypes. RESULTS: Explanatory causative variants were detected in 20 patients (14%), likely pathogenic variants that explain the epilepsy in 5 patients (3.5%) and likely pathogenic variants that do not fully explain the epilepsy in 11 patients (7.5%), and variants in candidate genes in 4 patients (3%). Variants were mostly de novo 29/40 (72.5%). SIGNIFICANCE: WES enables us to identify the cause of the disease in additional patients, even after gene panel testing. It is very important to perform a WES in DEE patients as soon as possible, since it will spare the patients and their families many years of a diagnostic odyssey. In particular, patients with rare epilepsies might significantly benefit from this approach, and we propose using WES as a new standard in the diagnosis of DEE instead of targeted gene panel testing.

• Keywords
• Developmental and epileptic encephalopathies (DEE), Exome sequencing, Gene panel,
• MeSH
• Epilepsy, Generalized * genetics   MeSH
• Epilepsy * diagnosis   genetics   MeSH
• Phenotype MeSH
• Genetic Association Studies MeSH
• Genetic Testing MeSH
• Humans MeSH
• Exome Sequencing MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

OBJECTIVE: Although genetic causes of drug-resistant focal epilepsy and selected focal malformations of cortical development (MCD) have been described, a limited number of studies comprehensively analysed genetic diagnoses in patients undergoing pre-surgical evaluation, their outcomes and the effect of genetic diagnosis on surgical strategy. METHODS: We analysed a prospective cohort of children enrolled in epilepsy surgery program over January 2018-July 2022. The majority of patients underwent germline and/or somatic genetic testing. We searched for predictors of surgical outcome and positive result of germline genetic testing. RESULTS: Ninety-five patients were enrolled in epilepsy surgery program and 64 underwent resective epilepsy surgery. We ascertained germline genetic diagnosis in 13/74 patients having underwent germline gene testing (pathogenic or likely pathogenic variants in CHRNA4, NPRL3, DEPDC5, FGF12, GRIA2, SZT2, STXBP1) and identified three copy number variants. Thirty-five patients underwent somatic gene testing; we detected 10 pathogenic or likely pathogenic variants in genes SLC35A2, PTEN, MTOR, DEPDC5, NPRL3. Germline genetic diagnosis was significantly associated with the diagnosis of focal epilepsy with unknown seizure onset. SIGNIFICANCE: Germline and somatic gene testing can ascertain a definite genetic diagnosis in a significant subgroup of patients in epilepsy surgery programs. Diagnosis of focal genetic epilepsy may tip the scales against the decision to proceed with invasive EEG study or surgical resection; however, selected patients with genetic focal epilepsies associated with MCD may benefit from resective epilepsy surgery and therefore, a genetic diagnosis does not disqualify patients from presurgical evaluation and epilepsy surgery.

• Keywords
• Focal drug-resistant epilepsy, Genetic testing, Malformations of cortical development, Paediatric epilepsy surgery, mTOR,
• MeSH
• Child MeSH
• Epilepsies, Partial * complications   MeSH
• Epilepsy * genetics   surgery   complications   MeSH
• Fibroblast Growth Factors genetics   MeSH
• Genetic Testing MeSH
• Humans MeSH
• Malformations of Cortical Development * genetics   MeSH
• Prospective Studies MeSH
• GTPase-Activating Proteins genetics   MeSH
• Nerve Tissue Proteins genetics   MeSH
• Drug Resistant Epilepsy * diagnosis   genetics   surgery   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• FGF12 protein, human MeSH Browser
• Fibroblast Growth Factors MeSH
• NPRL3 protein, human MeSH Browser
• GTPase-Activating Proteins MeSH
• Nerve Tissue Proteins MeSH
• SZT2 protein, human MeSH Browser

OBJECTIVE: The pathophysiological processes leading to epileptogenesis and pharmacoresistance in epilepsy have been the subject of extensive preclinical and clinical research. The main impact on clinical practice is the development of new targeted therapies for epilepsy. We studied the importance of neuroinflammation in the development of epileptogenesis and pharmacoresistance in childhood epilepsy patients. METHODS: A cross-sectional study conducted at two epilepsy centers in the Czech Republic compared 22 pharmacoresistant patients and 4 pharmacodependent patients to 9 controls. We analyzed the ProcartaPlex™ 9-Plex immunoassay panel consisting of interleukin (IL)-6, IL-8, IL-10, IL-18, CXCL10/IP-10, monocyte chemoattractant protein 1 (CCL2/MCP-1), B lymphocyte chemoattractant (BLC), tumor necrosis factor-alpha (TNF-α), and chemokine (C-X3-X motif) ligand 1 (fractalkine/CXC3CL1) to determine their alterations in cerebrospinal fluid (CSF) and blood plasma, concurrently. RESULTS: The analysis of 21 paired CSF and plasma samples in pharmacoresistant patients compared to controls revealed a significant elevation of CCL2/MCP-1 in CSF (p < 0.000512) and plasma (p < 0.00.017). Higher levels of fractalkine/CXC3CL1 were revealed in the plasma of pharmacoresistant patients than in controls (p < 0.0704), and we determined an upward trend in CSF IL-8 levels (p < 0.08). No significant differences in CSF and plasma levels were detected between pharmacodependent patients and controls. CONCLUSION: Elevated CCL2/MCP-1 in CSF and plasma, elevated levels of fractalkine/CXC3CL1 in CSF, and a trend toward elevated IL-8 in the CSF of patients with pharmacoresistant epilepsy indicate these cytokines as potential biomarkers of epileptogenesis and pharmacoresistance. CCL2/MCP-1was detected in blood plasma; this assessment may be easily achieved in clinical practice without the invasiveness of a spinal tap. However, due to the complexity of neuroinflammation in epilepsy, further studies are warranted to confirm our findings.

• Keywords
• Chemokine, Cytokine, Epileptogenesis, Interleukin, Pharmacodependent, Pharmacoresistant,
• MeSH
• Biomarkers cerebrospinal fluid   MeSH
• Chemokine CCL2 * cerebrospinal fluid   MeSH
• Chemokine CX3CL1 MeSH
• Epilepsy * diagnosis   drug therapy   MeSH
• Interleukin-8 cerebrospinal fluid   MeSH
• Humans MeSH
• Neuroinflammatory Diseases MeSH
• Cross-Sectional Studies MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Biomarkers MeSH
• CCL2 protein, human MeSH Browser
• Chemokine CCL2 * MeSH
• Chemokine CX3CL1 MeSH
• Interleukin-8 MeSH

This review focused on vaccination in children with movement disorders, including cerebral palsy and the movement disorders triggered by vaccination in children with and without neurological disabilities. The following clinical questions were addressed: 1) Can children with movement disorders be vaccinated? 2) Can vaccination trigger movement disorders in children without neurological disabilities? 3) Can vaccination trigger movement disorders in children with neurological disabilities? and 4) Is there any consensus of care concerning vaccination in children with movement disorders? Following the PRISMA reporting guidelines, 1096 records were identified and 34 relevant papers were included. No evidence that vaccinations are contraindicated for children with movement disorders was noticed. Several reports of neurological adverse events, including movement disorders in children without neurological disabilities after various types of vaccination, were found. The reporting rates were low, the causality was controversial, and patient outcomes were mostly favourable. There was limited (if any) evidence in our search that any vaccination leads to any movement disorder exacerbation. Finally, no generally accepted consensus or standards of care concerning vaccination in patients with movement disorders were found. In summary, we found few precautions for vaccination in this group of patients and concluded that general best practice guidelines for immunization should be followed. In addition, influenza and pneumococcal vaccines are recommended because they can reduce morbidity and mortality in individuals severely affected by movement restrictions.

• Keywords
• Adverse events, Cerebral palsy, Immunization, Movement disorders, Vaccination,
• MeSH
• Influenza, Human * MeSH
• Child MeSH
• Humans MeSH
• Cerebral Palsy * complications   MeSH
• Movement Disorders * etiology   MeSH
• Vaccination adverse effects   MeSH
• Influenza Vaccines * MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Influenza Vaccines * MeSH

OBJECT: Epilepsy surgery is an effective treatment for selected patients with focal intractable epilepsy. Complete removal of the epileptogenic zone significantly increases the chances for postoperative seizure-freedom. In complex surgical candidates, delineation of the epileptogenic zone requires a long-term invasive video/EEG from intracranial electrodes. It is especially challenging to achieve a complete resection in deep brain structures such as opercular-insular cortex. We report a novel approach utilizing intraoperative visual detection of stereotactically implanted depth electrodes to inform and guide the extent of surgical resection. METHODS: We retrospectively reviewed data of pediatric patients operated in Motol Epilepsy Center between October 2010 and June 2020 who underwent resections guided by intraoperative visual detection of depth electrodes following SEEG. The outcome in terms of seizure- and AED-freedom was assessed individually in each patient. RESULTS: Nineteen patients (age at surgery 2.9-18.6 years, median 13 years) were included in the study. The epileptogenic zone involved opercular-insular cortex in eighteen patients. The intraoperative detection of the electrodes was successful in seventeen patients and the surgery was regarded complete in sixteen. Thirteen patients were seizure-free at final follow-up including six drug-free cases. The successful intraoperative detection of the electrodes was associated with favorable outcome in terms of achieving complete resection and seizure-freedom in most cases. On the contrary, the patients in whom the procedure failed had poor postsurgical outcome. CONCLUSION: The reported technique helps to achieve the complete resection in challenging patients with the epileptogenic zone in deep brain structures.

• Keywords
• Children, Epilepsy surgery, Opercular-insular region, SEEG,
• MeSH
• Child MeSH
• Electroencephalography MeSH
• Epilepsy * surgery   MeSH
• Electrodes, Implanted MeSH
• Insular Cortex MeSH
• Humans MeSH
• Drug Resistant Epilepsy * surgery   MeSH
• Retrospective Studies MeSH
• Treatment Outcome MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Variants of GATOR1-genes represent a recognised cause of focal cortical dysplasia (FCD), the most common structural aetiology in paediatric drug-resistant focal epilepsy. Reports on familial cases of GATOR1-associated FCD are limited, especially with respect to epilepsy surgery outcomes. METHODS: We present phenotypical manifestations of four unrelated patients with drug-resistant focal epilepsy, FCD and a first-degree relative with epilepsy. All patients underwent targeted gene panel sequencing as a part of the presurgical work up. Literature search was performed to compare our findings to previously published cases. RESULTS: The children (probands) had a more severe phenotype than their parents, including drug-resistant epilepsy and developmental delay, and they failed to achieve seizure freedom post-surgically. All patients had histopathologically confirmed FCD (types IIa, IIb, Ia). In Patient 1 and her affected father, we detected a known pathogenic NPRL2 variant. In patients 2 and 3 and their affected parents, we found novel likely pathogenic germline DEPDC5 variants. In family 4, we detected a novel variant in NPRL3. We identified 15 additional cases who underwent epilepsy surgery for GATOR1-associated FCD, with a positive family history of epilepsy in the literature; in 8/13 tested, the variant was inherited from an asymptomatic parent. CONCLUSION: The presented cases displayed a severity gradient in phenotype with children more severely affected than the parents. Although patients with GATOR1-associated FCD are considered good surgical candidates, post-surgical seizure outcome was poor in our familial cases, suggesting that accurate identification of the epileptogenic zone may be more challenging in this subgroup of patients.

• Keywords
• Epilepsy surgery, Focal cortical dysplasia, Focal epilepsy, GATOR1, Malformations of cortical development, Targeted gene panel sequencing,
• MeSH
• Child MeSH
• Phenotype MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Malformations of Cortical Development genetics   surgery   MeSH
• Adolescent MeSH
• Tumor Suppressor Proteins genetics   MeSH
• GTPase-Activating Proteins genetics   MeSH
• Drug Resistant Epilepsy genetics   MeSH
• Retrospective Studies MeSH
• Germ-Line Mutation MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Names of Substances
• DEPDC5 protein, human MeSH Browser
• Tumor Suppressor Proteins MeSH
• NPRL2 protein, human MeSH Browser
• NPRL3 protein, human MeSH Browser
• GTPase-Activating Proteins MeSH