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Competing Interests: The authors have no funding or conflicts of interest to disclose.

Aim: To evaluate the efficacy of initial pharmacotherapy for infantile epileptic spasm syndrome (IESS) with electro-clinical outcome characteristics., Method: A retrospective comparative cohort study with 280 IESS patients was designed; I. vigabatrin monotherapy (n = 129, 46 %); II. hormonotherapy (ACTH/oral prednisolone) (n = 73, 26 %); and III. vigabatrin plus early initiation of hormonotherapy in the first 14 days (n = 78, 28 %). Two types of outcomes were defined: (1) short-term outcome with spasm cessation time ≤42 days and resolution of hypsarrhythmia on the EEG on ≤3 months and (2) long-term outcome with spasm relapse rate or evolution to a new epileptic syndrome., Results: The etiology-specific diagnoses of the IESS cohort were defined according to the ILAE classification: structural (n = 131, 46.8 %), genetic (n = 28, 10 %), metabolic (n = 13, 4.6 %), immune-infectious (n = 10, 3.6 %), and unknown (n = 98, 35 %). Each treatment modalities had similar short- and long-term outcome characteristics. However, hormonotherapy with steroids (ACTH/oral prednisolone) provided "early IESS resolution" with spasm cessation and resolution of hypsarrhythmia (p = 0.042). The relapse rates of IESS were significantly higher in the etiology well-defined group compared to the unknown group (p = 0.005). The genetic-etiology specific group was more likely to have evolved to a new electro-clinical syndrome with a rate of 83.3 % than the others (p = 0.039)., Conclusion: We observed that the early initiation of hormonotherapy with VGB (sequential therapy) should be investigated in etiology well-defined subgroup with short- and long-term outcome characteristics., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to disclose., (Copyright © 2025. Published by Elsevier Ltd.)

Objective: To evaluate the etiology-specific diagnosis of early-onset developmental epileptic encephalopathies (EO-DEEs) in a nationwide Turkish cohort to determine the implications for therapeutic management., Methods: The cohort comprised 1450 patients who underwent EO-DEE. The utility of genetic testing was assessed with respect to the initial phases of next generation sequencing (NGS) (2005-2013) and the current NGS era (2014-2022). A predefined four-stepwise diagnostic model was evaluated using cost-effectiveness analysis. The diagnostic and potential therapeutic yields of the genetic tests were subsequently determined., Results: Gene-related EO-DEEs were identified in 48.3 % (n = 701) of the cohort: non-structural genetic (62.6 %), metabolic genetic (15.1 %), and structural genetic (14.1 %). The most common nonstructural genetic variants were SCN1A (n = 132, 18.8 %), CDKL5 (n = 30, 4.2 %), STXBP1 (n = 21, 2.9 %), KCNQ2 (n = 21, 2.9 %), and PCDH19 (n = 17, 2.4 %). The rate of ultra-rare variants (< 0.5 %) was higher in the NGS era (52 %) than that in the initial phase (36 %). The potential therapeutic yields with precision therapy and antiseizure drug modification were defined in 34.5 % and 56.2 % in genetic-EO-DEEs, respectively. The diagnostic model provided an etiology-specific diagnosis at a rate of 78.7 %: structural (nongenetic) (31.4 %), genetic (38.5 %), metabolic (6.1 %), and immune-infectious (2.8 %). Based on a cost-effectiveness analysis, the presented diagnostic model indicated the early implementation of whole-exome sequencing for EO-DEEs., Significance: In the present cohort, the higher rate (48.3 %) of gene-related EO-DEE diagnoses in the NGS era provides a potential therapeutic management plan for more patients., Competing Interests: Declaration of competing interest There are no conflicts of interest that require disclosure by any of the authors. This article does not contain any pertinent financial information that the authors are required to disclose. This manuscript does not receive any external funding., (Copyright © 2024 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Next-generation sequencing (NGS) coupled with bioinformatic tools has revolutionized the detection of copy number variations (CNVs), which are implicated in the emergence of Mendelian disorders. In this study, we evaluated the diagnostic yield of exome sequencing-based CNV analysis in 449 patients with suspected Mendelian disorders. We aimed to assess the diagnostic yield of this recently utilized method and expand the clinical spectrum of intragenic CNVs. The cohort underwent whole exome sequencing (WES) and clinical exome sequencing (CES). Using GATK-gCNV, we identified 12 pathogenic CNVs that correlated with their clinical findings and resulting in a diagnostic yield of 2.67%. Importantly, the study emphasizes the role of CNVs in the etiology of Mendelian disorders and highlights the value of exome sequencing-based CNV analysis in routine diagnostic processes., (© 2024. The Author(s).)

Objectives: This study aimed to evaluate seizure semiology, electroencephalogram (EEG), magnetic resonance imaging (MRI), and genetic findings, as well as treatment choices in Rett syndrome (RTT)., Methods: A retrospective analysis was conducted on one hundred and twenty cases diagnosed with RTT with a genetic mutation. Data were obtained from nine participating centers., Results: In this study, 93.3 % of patients were female, with typical RTT found in 70 % of cases. Genetic etiology revealed MECP2, FoxG1, and CDKL5 in 93.8 %, 2.7 %, and 1.8 % of cases, respectively. Atypical RTT clinics were observed in 50 % of male cases, with the first EEG being normal in atypical RTT cases (p = 0.01). Generalized tonic-clonic and myoclonic epilepsy were the most common seizure semiologies, while absence and focal epilepsy were less prevalent. Valproate, levetiracetam, lamotrigine, and clobazam were the most commonly used antiepileptic drugs, affecting the severity and frequency of seizures (p = 0.015, p=<0.001, p = 0.022, and p=<0.001, respectively). No significant differences were observed in EEG findings. The initiation of anti-seizure medications significantly altered seizure characteristics (Table 4). A ketogenic diet and vagal nerve stimulation (VNS) correlated with a 50 % improvement in cognitive function, while steroid treatment showed a 60 % improvement. Remarkably, seizures were substantially reduced after VNS application., Conclusion: This study underscores the importance of genetic diagnosis in RTT cases with a clinical diagnosis. These preliminary results will be further validated with the inclusion of clinically diagnosed RTT cases in our ongoing study., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: To compare the amplitude-integrated electroencephalography (aEEG) monitoring (short-term versus prolonged-period) for neonatal seizure detection and outcome., Methods: The aEEG monitoring in a historical cohort (n = 88, preterm:42, and term:46) with neonatal encephalopathy between 2010-2022 was re-evaluated for neonatal seizures (electrographic, electro-clinical, and clinical seizures) and EEG background scoring. The cohort was dichotomized: group I (short-period with 6-12 h, n = 36) and group II (prolonged-period with 24-48 h, n = 52). Both monitoring types were evaluated for the diagnostic accuracy of the "patients with seizures" and for outcome characteristics (early death as well as adverse outcomes at 12 months of age)., Results: A total of 67 (76 %) neonates of the cohort were diagnosed as "patients with seizures": electrographic-only seizures in 10 (15 %), electro-clinical seizures in 22 (33 %), and clinical-only seizures in 35 (52 %). The aEEG provides the "patients with seizures" in neonates with a 36.5 % rate with both types of monitoring: 17/36 (47.2 %) with short-term and 15/52 (28.8 %) with prolonged-period monitoring. The prolonged period aEEG had higher diagnostic values for seizure detection (sensitivity = 0.73 and negative predictivity value = 0.81). However, the aEEG background scores were similar for both types of aEEG monitoring, respectively (the mean ± SD: 4.73 ± 2.9 versus 4.4 ± 4. p = 0.837). The aEEG scoring was correlated with the magnitude of brain injury documented with MRI, the early death, and the adverse outcome at 12 months of age., Conclusions: Both aEEG types are valuable for monitoring the "patients with seizures" and outcome characteristics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: To evaluate the utility of genetic testing for etiology-specific diagnosis (ESD) in infantile epileptic spasms syndrome (IESS) with a step-based diagnostic approach in the next-generation sequencing (NGS) era., Methods: The study cohort consisted of 314 patients with IESS, followed by the Pediatric Neurology Division of Ege University Hospital between 2005 and 2021. The ESD was evaluated using a step-based approach: step I (clinical phenomenology), step II (neuroimaging), step III (metabolic screening), and step IV (genetic testing). The diagnostic utility of genetic testing was evaluated to compare the early-NGS period (2005 to 2013, n = 183) and the NGS era (2014 to 2021, n = 131)., Results: An ESD was established in 221 of 314 (70.4%) infants with IESS: structural, 40.8%; genetic, 17.2%; metabolic, 8.3%; immune-infectious, 4.1%. The diagnostic yield of genetic testing increased from 8.9% to 41.7% in the cohort during the four follow-up periods. The rate of unknown etiology decreased from 34.9% to 22.1% during the follow-up periods. The genetic ESD was established as 27.4% with genetic testing in the NGS era. The genetic testing in the NGS era increased dramatically in subgroups with unknown and structural etiologies. The diagnostic yields of the epilepsy panels increased from 7.6% to 19.2%. However, the diagnostic yield of whole exome sequencing remained at similar levels during the early-NGS period at 54.5% and in the NGS era at 59%., Conclusions: The more genetic ESD (27.4%) was defined for IESS in the NGS era with the implication of precision therapy (37.7%)., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work., (Copyright © 2024. Published by Elsevier Inc.)

Background: There is no certain validated electroencephalographic (EEG) parameters for outcome prediction in children with self-limited epilepsy with centrotemporal spikes. To assess the effectiveness of antiseizure medication (ASM) for seizure outcome with respect to the spike-wave index (SWI) on serial EEG recordings., Methods: In this multicenter study, the study cohort consisted of 604 children with self-limited epilepsy with centrotemporal spikes. A data set of epilepsy centers follow-up between 2010 and 2022. The cohort was divided into 4 groups as those receiving 3 different monotherapy (carbamazepine [CBZ]/valproic acid [VPA]/levetiracetam [LEV]) and dual therapy. SWI analysis was performed with the percent of spikes in the 2-minute epoch in the 5th 6th minutes of the nonrapid eye movement sleep EEG record. The study group were also categorized according to seizure burden with seizure frequency (I) >2 seizures and (II) >5 seizures. Seizure outcome was evaluated based on the reduction in seizure frequency over 6-month periods: (1) 50% reduction and (2) seizure-free (complete response)., Results: ASM monotherapy was achieved in 74.5% children with VPA, CBZ, and LEV with similar rates of 85.8%, 85.7%, and 77.9%. Dual therapy was need in the 25.5% of children with SeLECT. More dual therapy was administered in children aged below 5 years with a rate of 46.2%. Earlier seizure-free achievement time was seen in children with LEV monotherapy with more complete-response rate (86.7%) compared the VPA and CBZ., Conclusions: We also determined that the children on dual therapy had more SWI clearance in the subsequent EEG recordings. The ROC curve analyses were performed to predict initial drug selection with using the SWI% might be used for the prediction of ASM type and drug selection in children., Competing Interests: Declaration of competing interest All authors have declared that they have no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Various etiologies may underlie optic neuritis, including autoantibody-mediated disorders described in the last decade. We re-examined demographic, clinical, laboratory features and prognostic factors in pediatric patients with autoimmune optic neuritis according to current knowledge., Methods: Cases of pediatric ON from 27 centers in Türkiye diagnosed between 2009 and 2022 were included for retrospective evaluation., Results: The study included 279 patients, 174 females and 105 males, with a female-to-male ratio of 1.65. The average age at onset was 12.8 ± 3.4 years, and mean follow-up, 2.1 years (range: 1-12.1 years). Patients <10 years old were grouped as "prepubertal" and those ≥10 years old as "others". The diagnoses made at the end of follow-up were multiple sclerosis associated optic neuritis (n = 90, 32.3 %), single isolated optic neuritis (n = 86, 31 %), clinically isolated syndrome (n = 41, 14.7 %), myelin oligodendrocyte glycoprotein antibody associated optic neuritis (n = 22, 7.9 %), and relapsing isolated optic neuritis (n = 18, 6.5 %). Predominant diagnoses were myelin oligodendrocyte glycoprotein antibody associated optic neuritis and acute disseminated encephalomyelitis associated optic neuritis in the prepubertal group and multiple sclerosis associated optic neuritis in the older group. Recurrences were observed in 67 (24 %) patients, including 28 with multiple sclerosis associated optic neuritis, 18 with relapsing isolated optic neuritis, 11 with myelin oligodendrocyte glycoprotein antibody associated optic neuritis, 8 with aquaporin-4 antibody related optic neuritis, and 2 with chronic relapsing inflammatory optic neuropathy. Recurrences were more common among female patients. Findings supporting the diagnosis of multiple sclerosis included age of onset ≥ 10 years (OR=1.24, p = 0.027), the presence of cranial MRI lesions (OR=26.92, p<0.001), and oligoclonal bands (OR=9.7, p = 0.001). Treatment in the acute phase consisted of intravenous pulse methylprednisolone (n = 46, 16.5 %), pulse methylprednisolone with an oral taper (n = 212, 76 %), and combinations of pulse methylprednisolone, plasmapheresis, or intravenous immunoglobulin (n = 21, 7.5 %). Outcome at 12 months was satisfactory, with 247 out of 279 patients (88.5 %) demonstrating complete recovery. Thirty-two patients exhibited incomplete recovery and further combination treatments were applied. Specifically, patients with relapsing isolated optic neuritis and aquaporin-4 antibody related optic neuritis displayed a less favorable prognosis., Conclusion: Our results suggest optic neuritis is frequently bilateral in prepubertal and unilateral in peri‑ or postpubertal patients. Age of onset 10 or older, presence of oligoclonal bands, and brain MRI findings reliably predict the development of multiple sclerosis. The risk of developing multiple sclerosis increases mostly during the second and third years of follow-up. Relapsing isolated optic neuritis remains a separate group where the pathogenesis and outcome remain unclear. Investigation of predisposing and diagnostic biomarkers and long follow-up could help to define this group., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

We evaluated clinical parameters distinguishing cognitive disengagement syndrome (CDS) and childhood absence epilepsy (CAE). 40 children with CDS, 27 with CAE, and 41 controls aged 7-12 were compared regarding sleep problems, CDS, and ADHD symptoms. CDS-sluggishness symptoms, but not CDS-daydreaming symptoms, were significantly higher in CDS group than CAE group. CDS scale provided a weak discrimination value between CDS and CAE. Sleep problems and ADHD symptoms were similar between the two clinical entities. These findings highlight that CDS and CAE might have overlapping symptoms. 'Daydreaming' symptoms but not 'sluggishness' symptoms seem to be main overlapping manifestations between CDS and CAE.

Objectives: To evaluate clinical characteristics, imaging features and etiological profile of Radiologically Isolated Syndrome (RIS) along with clinical and radiological follow-up., Methods: Demographic, clinical and radiological data of patients younger than 18 years fulfilling the criteria for RIS were retrospectively analyzed. RIS was defined by the detection of lesions meeting the revised 2010 McDonald Criteria for dissemination in space on magnetic resonance imaging (MRI) in the absence of any symptoms of demyelinating disease or an alternative cause for the MRI findings., Results: There were total 69 patients (38 girls, 31 boys). The median age at index MRI was 15.7 years, and median follow-up time was 28 months. The most common reason for neuroimaging was headache (60.9%). A first clinical event occurred with median 11 months in 14/69 (20%) of cases. Those with oligoclonal bands (OCB) in cerebrospinal fluid (CSF) and follow-up longer than 3 years were more likely to experience a clinical event (p<0.05): 25% of those with OCB manifested clinical symptoms within the first year and 33.3% within the first two years compared to 6.3% and 9.4%, respectively in those without OCB. Radiological evolution was not associated with any variables: age, sex, reason for neuroimaging, serum 25-hydroxyvitamin D level, elevated IgG index, OCB positivity, total number and localization of lesions, presence of gadolinium enhancement, achievement of 2005 criteria for DIS and duration of follow-up., Conclusion: Children and adolescents with RIS and CSF OCB should be followed-up for at least 3 years in order to detect any clinical symptoms suggestive of a demyelinating event. Because disease-modifying treatments are not approved in RIS and no consensus report justifies their use especially in pediatric RIS, close follow-up of OCB-positive patients is needed for early recognition of any clinical event and timely initiation of specific treatment., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to evaluate the adaptability of pediatric residents to the current seizure classification of the International League Against Epilepsy-2017 (ILAE-2017) using a modular education program (MEP)., Materials and Methods: The MEP design consisted of 8 modules, including 5 modules for the current version of the ILAE-2017 seizure classification and 3 modules for the older ILAE-1981 version. The MEP was implemented with a group of pediatric residents, and it comprised 50 illustrative pediatric seizure videos along with an instruction manual kit that included a seizure determinator. Following a 3-month follow-up period, a posttest was conducted using 58 new videos in the MEP., Results: The overall success rates of the participants were similar both ILAE-2017 (41%) and ILAE-1981 (38.5%) seizure classifications in the post-MEP test. Regarding the ILAE-2017 mod- ules, the participants demonstrated a higher proficiency in classifying focal nonmotor seizures (56.3%) compared to focal motor seizures (34.9%). However, when it came to generalized seizures, the participants had significantly lower accuracy rates for generalized nonmotor seizures (26%) compared to generalized motor seizures (46%) with the ILAE-2017 classifica- tion. The seizure types that were most commonly misclassified, with an error rate exceeding 50%, were automatisms and myoclonic seizures within the focal seizure modules and atypical absences in generalized seizure modules of ILAE-2017., Conclusion: The single-day MEP yielded modest results, with a success rate of 41% in terms of the initial adaptability of pediatric residents to the ILAE-2017 seizure classification. However, to ensure successful implementation of the ILAE-2017 classification in clinical practice, additional booster applications of the MEP are required.

Background: Although the underlying genetic causes of intellectual disability (ID) continue to be rapidly identified, the biological pathways and processes that could be targets for a potential molecular therapy are not yet known. This study aimed to identify ID-related shared pathways and processes utilizing enrichment analyses., Methods: In this multicenter study, causative genes of patients with ID were used as input for Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes enrichment analysis., Results: Genetic test results of 720 patients from 27 centers were obtained. Patients with chromosomal deletion/duplication, non-ID genes, novel genes, and results with changes in more than one gene were excluded. A total of 558 patients with 341 different causative genes were included in the study. Pathway-based enrichment analysis of the ID-related genes via ClusterProfiler revealed 18 shared pathways, with lysine degradation and nicotine addiction being the most common. The most common of the 25 overrepresented DO terms was ID. The most frequently overrepresented GO biological process, cellular component, and molecular function terms were regulation of membrane potential, ion channel complex, and voltage-gated ion channel activity/voltage-gated channel activity, respectively., Conclusion: Lysine degradation, nicotine addiction, and thyroid hormone signaling pathways are well-suited to be research areas for the discovery of new targeted therapies in ID patients., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: To evaluate the clinical features, demographic features, and treatment modalities of pediatric-onset chronic inflammatory demyelinating polyneuropathy (CIDP) in Turkey., Methods: The clinical data of patients between January 2010 and December 2021 were reviewed retrospectively. The patients were evaluated according to the Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society Guideline on the management of CIDP (2021). In addition, patients with typical CIDP were divided into two groups according to the first-line treatment modalities (group 1: IVIg only, group 2: IVIg + steroid). The patients were further divided into two separate groups based on their magnetic resonance imaging (MRI) characteristics., Results: A total of 43 patients, 22 (51.2%) males and 21 (48.8%) females, were included in the study. There was a significant difference between pretreatment and post-treatment modified Rankin scale (mRS) scores (P < 0.05) of all patients. First-line treatments include intravenous immunoglobulin (IVIg) (n = 19, 44.2%), IVIg + steroids (n = 20, 46.5%), steroids (n = 1, 2.3%), IVIg + steroids + plasmapheresis (n = 1, 2.3%), and IVIg + plasmapheresis (n = 1, 2.3%). Alternative agent therapy consisted of azathioprine (n = 5), rituximab (n = 1), and azathioprine + mycophenolate mofetil + methotrexate (n = 1). There was no difference between the pretreatment and post-treatment mRS scores of groups 1 and 2 (P > 0.05); however, a significant decrease was found in the mRS scores of both groups with treatment (P < 0.05). The patients with abnormal MRI had significantly higher pretreatment mRS scores compared with the group with normal MRI (P < 0.05)., Conclusions: This multicenter study demonstrated that first-line immunotherapy modalities (IVIg vs IVIg + steroids) had equal efficacy for the treatment of patients with CIDP. We also determined that MRI features might be associated with profound clinical features, but did not affect treatment response., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: The aim of the study was to identify the predominant predictors of seizure relapse following discontinuation of ASM in epileptic children., Methods: The study cohort consisted of 403 epileptic children who had a withdrawal process of ASM (monotherapy: 344; dual therapy or polytherapy: 59) after at least a 2-year seizure-free period. Patients were categorized if they had a well-defined epileptic syndrome. Epileptic children with ongoing ketogenic diet, vagal nerve stimulation, or surgery were excluded from the cohort due to the additional withdrawal process related to other therapy modalities., Results: The cohort's seizure relapse rate was 12.7% (51/403). The highest rates of seizure relapse were defined for genetic etiology at 25% and structural etiology at 14.9%. An epilepsy syndrome was defined in 183 of 403 children (45.4%). There was no difference in the seizure relapse rate between the subgroups of well-defined epileptic syndromes; 13.8% for self-limited focal epileptic syndromes, 11.7% for developmental and epileptic encephalopathies, and 7.1% for generalized epileptic syndromes. Five predictors were defined as the most powerful predictors of seizure relapse in univariate analysis: age at epilepsy diagnosis >2 years (hazard ratio [HR]: 1.480; 95% confidence interval [CI]: 1.134-1.933), defined etiology (HR: 1.304; 95% CI: 1.003-1.696), focal seizure (HR: 1.499; 95% CI: 1.209-1.859), ≤3 months duration of the withdrawal process (HR: 1.654; 95% CI: 1.322-2.070), and a history of neonatal encephalopathy with or without seizures (HR: 3.140; 95% CI: 2.393-4.122). In multivariate analysis, the main predictor of seizure relapse was a history of neonatal encephalopathy with or without seizures (HR: 2.823; 95% CI: 2.067-3.854)., Significance: The duration of seizure freedom before discontinuation of ASM was not a predominant risk factor for seizure relapse: 2-3 years versus >3 years. The predictive values of five predictors of seizure relapse rate should be evaluated for patients with different epilepsy subgroups., (© 2023 International League Against Epilepsy.)

Objective: The aim of this study is to evaluate the prognostic factors in a single-center pediatric cohort with autoimmune encephalitis., Materials and Methods: The study group consisted of 23 pediatric autoimmune encephalitis patients (seropositive autoimmune encephalitis: 15, seronegative autoimmune encephalitis: 8). Five group prognostic parameters were evaluated: clinical manifestations, elect roenc ephal ograp hy features, magnetic resonance imaging characteristics, biomarkers, and treatment modalities. Three scoring models were applied: the Antibody Prevalence in Epilepsy and Response to Immunotherapy in Epilepsy for predicting autoimmune-related epilepsy in the whole cohort and the anti-N-methyl-d-aspartate receptor Encephalitis 1-Year Functional Status score for overall outcome in patients with anti-N-methyl-d-aspartate receptor encephalitis., Results: The initial clinical spectrum of the disease was similar in the seronegative and seropositive groups. Almost half of the patients (48%) recovered without any complications with first-line immunotherapy. The patients with movement disorders in the acute phase of the disease needed more likely second-line immunotherapy (P = .039). The presence of status epilepticus at admission was significantly associated with adverse outcomes and the development of autoimmune-related epilepsy (P = .019). Autoimmune-related epilepsy was defined in an equal proportion of patients (91.5%) with 2 immune epilepsy scores (Antibody Prevalence in Epilepsy and Response to Immunotherapy in Epilepsy). The N-methyl-d-aspartate receptor Encephalitis 1-Year Functional Status score and the modified Rankin score assessed for the first-year prognosis were strongly correlated among the patients with anti-N-methyl-d-aspartate receptor encephalitis (P = .03, Spearmen's rho = 0.751)., Conclusions: The presence of status epilepticus was the most important prognostic factor in the patients with the adverse outcome. The studied scoring models (Anti-N-methyl-d-aspartate receptor Encephalitis 1-Year Functional Status, Antibody Prevalence in Epilepsy, and Response to Immunotherapy in Epilepsy) have also been proven to be applicable to the pediatric age group for predicting overall outcome and autoimmune-related epilepsy.

Cerebral folate deficiency (CFD) syndrome is a rare treatable neurometabolic disorder with low levels of the active form of folaten in cerebrospinal fluid (CSF) arising from different causes such as FOLR1 gene mutations or autoantibodies against the folate receptor-alpha (FR) protein that can block folate transport across the choroid plexus. It is characterized by late infantile onset refractory seizures, ataxia, movement disorder, and unexplained global developmental delay. Here, we report a patient diagnosed with autistic spectrum disorder, followed by refractory myoclonic-atonic seizures, ataxia, and loss of motor skills over time. A homozygous missense (c.665A > G) mutation in FOLR1 gene and extremely low CSF 5-methyltetrahydrofolate level led to the diagnosis of CFD. Although she was initiated on combined oral and intravenous high doses of folinic acid treatment at 6 years of age, mild improvement was achieved in terms of epileptic seizures and motor skills. It is important that CFD should be kept in mind in cases with refractory myoclonic-atonic seizure and folinic acid treatment should be started as soon as possible., (© 2021. Belgian Neurological Society.)

Purpose: Brain monoamine vesicular transport disease is an infantile-onset movement disorder that mimics cerebral palsy. In 2013, the homozygous SLC18A2 variant, p.Pro387Leu, was first reported as a cause of this rare disorder, and dopamine agonists were efficient for treating affected individuals from a single large family. To date, only 6 variants have been reported. In this study, we evaluated genotype-phenotype correlations in individuals with biallelic SLC18A2 variants., Methods: A total of 42 affected individuals with homozygous SLC18A2 variant alleles were identified. We evaluated genotype-phenotype correlations and the missense variants in the affected individuals based on the structural modeling of rat VMAT2 encoded by Slc18a2, with cytoplasm- and lumen-facing conformations. A Caenorhabditis elegans model was created for functional studies., Results: A total of 19 homozygous SLC18A2 variants, including 3 recurrent variants, were identified using exome sequencing. The affected individuals typically showed global developmental delay, hypotonia, dystonia, oculogyric crisis, and autonomic nervous system involvement (temperature dysregulation/sweating, hypersalivation, and gastrointestinal dysmotility). Among the 58 affected individuals described to date, 16 (28%) died before the age of 13 years. Of the 17 patients with p.Pro237His, 9 died, whereas all 14 patients with p.Pro387Leu survived. Although a dopamine agonist mildly improved the disease symptoms in 18 of 21 patients (86%), some affected individuals with p.Ile43Phe and p.Pro387Leu showed milder phenotypes and presented prolonged survival even without treatment. The C. elegans model showed behavioral abnormalities., Conclusion: These data expand the phenotypic and genotypic spectra of SLC18A2-related disorders., (Copyright © 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this study was to investigate the frequency of sleep problems in adolescents with epilepsy and their caregivers. We also examined the behavioural difficulties in adolescents with epilepsy and compared these behaviors with healthy controls., Methods: This observational case-control study included 37 adolescents with epilepsy and their caregivers, and 43 healthy age-matched adolescents and their caregivers. The Children`s Sleep Habits Questionnaire (CSHQ), DSM-5 Level 2 Sleep Disorders Scale for Children, and Strengths & Difficulties Questionnaire (SDQ) were used to evaluate sleep habits, sleep problems, and behavioural difficulties in adolescents. The DSM-5 sleep disorder scale for adults was used to evaluate the caregivers` sleep problems., Results: Adolescents with epilepsy had higher sleep problem scores such as daytime sleepiness and overall sleep problems compared with healthy controls. The psychopathological symptoms such as conduct problems, hyperactivity/inattention, and total behavior were also more frequent in adolescents with epilepsy. There was a nonsignificant increase in DSM-5 sleep disturbance score in caregivers of adolescents with epilepsy. Sleep onset delay had a significant negative correlation with total behavioral difficulties (r = -0.44, p < 0.01), and emotional problems (r = -0.47, p < 0.05) in adolescents with epilepsy. Sleep duration was negatively correlated with conduct problems (r = -0.33, p < 0.05), but positively correlated with prosocial score (r = 0.46, p < 0.01) in adolescents with epilepsy. Night waking was positively correlated with total behavioral difficulties (r = 0.35, p < 0.05) and hyperactivity score (r = 0.38, p < 0.05) in adolescents with epilepsy., Conclusions: Adolescents with epilepsy have more frequent sleep disturbances and maladaptive behaviors such as hyperactivity/inattention, and conduct problems compared with healthy controls, and their caregivers are more vulnerable to sleep problems. Moreover, we also demonstrated a strong association between sleep disturbances and behavioral problems in adolescents with epilepsy.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a rare autoimmune entity in psychiatry literature that occurs when antibodies attack NMDA-type glutamate receptors in the brain. Principle clinical features include a neurological domain such as seizure, orofacial dyskinesia, dystonia, and choreic-like movements of extremities. Also the psychiatric manifestations of this form of encephalitis may vary from psychotic-like symptoms to mood symptoms like depression or mania. Herein we report on five female child cases diagnosed with anti-NMDAR encephalitis, presented with both neurological and psychiatric clinical picture, and highlight the trajectory of disorder from a psychiatric perspective.

Appropriate treatment of neonatal seizures with an effective therapy is important in reducing long-term neurologic disabilities. Sixty-seven neonates, who received intravenous (IV) levetiracetam (LEV) as first-line therapy for treating seizures between 2013 and 2017 were evaluated retrospectively to investigate the efficacy of LEV and its neurodevelopmental outcome at 12 months of age. Of the 67 neonates (44 preterm and 23 term babies) evaluated for seizures, 55 (82%) had a defined etiology. EEG confirmation was obtained in 36 (57.1%) of the neonates with clinical seizures. On the 7th day of the treatment (mean seizure control time 7.4 ± 15.1 days), LEV was effective as monotherapy in 43 (64%), whereas add-on therapy was required in 24 (36%) neonates. At the 1-year follow-up, 76% of infants achieved drug-free state, nine (18%) infants remained on LEV monotherapy and three (6%) needed add-on therapy. Neurodevelopmental outcome of the infants was assessed with Ankara Development Screening Inventory and results suggested favorable neurodevelopmental outcome in 69.7% of the infants with at the end of the 1-year follow-up with LEV monotherapy. In conclusion, this retrospective cross-sectional study demonstrated that IV LEV is an effective first-line therapy for treating neonatal clinical seizures and LEV monotherapy effect was sustained during the first year follow-up., (© 2020. Belgian Neurological Society.)

Multisystem inflammatory syndrome in children (MIS-C) is a rare but life-threatening inflammatory immune response associated with severe acute respiratory syndrome coronavirus 2 infection. The majority of patients have been presented with hypotension, shock, gastrointestinal, cardiovascular and mucocutaneous symptoms. The incidence of neurologic symptoms in MIS-C is of rising concern as they are not well described and reported in fewer patients. An 8-year-old boy was admitted to the hospital with headache, fever, conjunctivitis, and hyperinflammatory findings diagnosed as MIS-C. Fundus examination performed with complaints of headache, vomiting, and conjunctivitis showed bilateral papilledema. Pseudotumor cerebri is a rare manifestation of MIS-C that can lead to vision loss and may not only be resolved with the standard treatment for MIS-C. We report a case of MIS-C presented with neurologic symptoms due to pseudotumor cerebri and successfully treated with intravenous immunoglobulin and acetazolamide., Competing Interests: The author has no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The study aimed to evaluate the patients with a diagnosis of cerebral sinovenous thrombosis in terms of clinical findings, etiology and underlying risk factors, imaging findings, treatment, and prognosis in the long term., Materials and Methods: Medical records of 19 patients whose ages ranged between 0 days and 17 years with clinical and radiological cerebral sinovenous thrombosis in Ege University Department of Child Neurology were retrospectively evaluated., Results: Nine of nineteen cases were female (47.3%). The median age was 84 months (0-201 months). The most common complaint at the presentation was headache (n=12) and the most common physical examination finding was papilledema (n=11). In etiology, otitis/mastoiditis in three cases, iron deficiency anemia in three cases, sinusitis in two cases, catheter use in four cases, Behçet's disease in three cases were determined. The most common observed genetic factors causing thrombosis was methylenetetrahydrofolate reductase mutation. The transverse sinus (68.4%) is the sinus where thrombosis is most frequently observed. As a result of an average follow-up of 12 months (2-72 months), hemiparesis (n=3/19, 15.7%) and epilepsy (n=5/19, 26.3%) were recorded as sequelae findings, and no mortality was observed., Conclusion: In cases presenting with headache, evaluation of papilledema on funduscopic examination should not be skipped. Neurological imaging should be performed in the change of consciousness of poor feeding infants and children with infections in the head and neck area or underlying chronic diseases. When cerebral sinovenous thrombosis is detected, anticoagulant therapy should be started immediately., Competing Interests: Conflict of interest: The authors have no conflicts of interest to declare., (Copyright © 2021 Turkish Pediatric Association.)

Purpose: To assess the spike characteristics and temporal spike evolution on serial EEG of children with childhood epilepsy with centrotemporal spikes (CECTS) treated with anti-seizure medication., Methods: The study cohort consisted of 127 children with CECTS divided into three groups based on anti-seizure medication responsiveness: group I: seizure-free with monotherapy (n: 61, 48%), group II: seizure-controlled with monotherapy (n: 52, 41%) and group III: seizure-controlled with dual therapy (n: 14, 11%). The clinical profiles and sequential four-year follow-up visual EEG recordings of the children were evaluated. Each EEG was reanalyzed with three spike characteristics on the epochs: (1) spike-wave rate, (2) spike topography, and (3) spike localization. We calculated the spike clearance velocity, which is defined as a decrease in the spike-wave rate over time in four-year sequential follow-up EEGs., Results: There was no statistical significance across the study groups with respect to initial EEG spike characteristics (spike-wave rate, spike localization, and spike topography). Seizure recurrence occurred in 15 patients (12.8%) who discontinued anti-seizure medication. There was no statistically significant difference between the spike characteristics on EEG just before the discontinuation of anti-seizure medication and seizure recurrence. However, the spike clearance velocity was significantly slower in group III than in group I in four-year sequential follow-up EEGs (p = 0.002). A statistically significant decrease in the mean spike-wave rate was observed in group I in the first year of anti-seizure medication (p<0.001). The spike clearance velocity was also more prominent during the second year of treatment in group II and the third year of treatment in group III. However, the spike clearance velocity was not different across the anti-seizure medication groups (oxcarbazepine, valproic acid, and levetiracetam)., Conclusion: Spike clearance velocity might be a valuable EEG marker to guide anti-seizure medication in children with CECTS., (Copyright © 2021. Published by Elsevier Ltd.)

Anti-myelin oligodendrocyte glycoprotein antibodies have been associated with a wide range of clinical presentations including monophasic and relapsing disease courses. Lack of a definitive marker for predicting further relapses and the final diagnoses complicates the clinical follow-up and treatment decisions for patients with the first episode. This study retrospectively analyzed the clinical spectrum, treatment protocols and outcome of nine children with MOG antibody-associated demyelinating disease. Diagnoses at first presentation were acute disseminated encephalomyelitis (ADEM) in six cases (67%), optic neuritis in two cases (22%), and clinically isolated syndrome in one case (11%). The disease remained monophasic in five (56%) cases. All cases with a monophasic disease course were negative for anti-MOG antibody titers in the third month. The initial diagnosis of all relapsing cases was ADEM. Three of the four cases with a relapsing disease course were available for anti-MOG antibody testing at the third month and all were positive, however, antibody titers at the sixth month were inconsistent. Cases with a relapsing disease course had no further attacks after monthly intravenous immunoglobulin treatment. Relapsing disease course is not rare in childhood MOG-antibody associated demyelinating disease. Monthly IVIG treatment may be a good alternative for the long-term treatment of relapsing cases with a low side effect profile. Anti-MOG antibody serostatus at remission periods should be interpreted cautiously. Further studies are needed to better understand and predict the clinical course of pediatric patients with MOG-antibody associated diseases.

Purpose: Sulthiame (STM) has been recommended as an effective antiepileptic drug (AED) in children with epileptic encephalopathy with status epilepticus in sleep (ESES). The aim of this study is to evaluate the efficacy of STM add-on treatment in children with pattern of ESES with respect to the etiologic subgroup., Methods: Twenty-nine children with ESES pattern with three different etiologic subgroups (epileptic syndromes: 14, structural/infectious: 9, unknown: 6) who were given STM as add-on treatment were included into the study. The efficacy of STM was evaluated in terms of seizure control, electroencephalography (EEG) findings, need of the new AEDs after add-on STM, and behavioral and cognitive improvement., Results: The range of the follow-up duration after add-on STM treatment was between 5 and 51 months. At the end of 1 year of STM treatment, the most successful electrophysiologic improvement was identified in the well-defined epileptic syndrome group; epileptic syndrome, 71.4% (10/14); structural/infectious, 33.3% (3/9); and unknown, 0% (0/6). Patients who had complete response or persistent ESES pattern at the 3rd month were still in the same condition at the 6th and 12th months. However, the ESES pattern reappeared in 35.2% of the patients who had partial electrophysiological improvement at the 3rd month. In the epilepsy syndrome group, eight out of ten patients who had either complete or partial EEG response after 1 year of STM treatment displayed behavioral and cognitive improvement., Conclusion: Sulthiame might be a valid add-on treatment of ESES especially in children with epilepsy syndromes.

This paper aims to investigate the possible roles of a set of neurotrophic factors (brain-derived neurotrophic factor-BDNF, nerve growth factor-NGF) and neuropeptides (neuropeptide Y-NPY, and galanin) in children with active epileptogenesis. The cerebrospinal fluid (CSF) levels of BDNF, NPY, NGF and galanin were measured with enzyme-linked immunosorbent assays in epileptic children (n = 73) and controls (n = 64). There were no significant alterations in the CSF levels of BDNF, NPY and NGF in epileptic children with active clinical seizures compared with the levels of controls. However profoundly depressed galanin levels were found in infants with epileptic encephalopathy (mean ± SD:0.63 ± 0.19 pg/ml) and significantly increased galanin levels were measured in children with drug resistant epilepsy during the period of status epilepticus (mean ± SD: 6.92 ± 1.19, pg/ml pg/ml) compared with the levels of controls. Depressed levels of galanin might reflect a defective anti-epileptogenic effect of galanin in infants with epileptic encephalopathy. On the contrary, increased CSF levels of galanin might be a result of anti-epileptogenic effects of this peptide in epileptic children with status epilepticus., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Isaacs syndrome is rare disorder with peripheral nerve hyperexcitability syndromes with acquired neuromyotonia in childhood. We present a 13-year-old girl with muscle stiffness and neuromyotonia diagnosed Isaac syndrome with spontaneous discharge potentials on motor unit in electromyography and the diagnosis supported by the presence of antinuclear antibodies. A successful treatment was obtained using low-dose carbamazepine. Cause of Isaacs syndrome is unknown, generally thought to be an autoimmune etiology with voltage-gated potassium channelopathy; it sometimes occurs as a paraneoplastic syndrome. Early use of electromyography has critical role in the differential diagnosis with certain muscle disorders and peripheral nerve hyperexcitability syndromes., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Pediatric Neurosciences.)

Background and Objectives: Acute disseminated encephalomyelitis (ADEM) is an immune-mediated, inflammatory and demyelinating disorder of the central nervous system. There have been a few studies in recent years on the fact that these cases have neurocognitive impairment. The purpose of this study is to evaluate the neurocognitive outcome and quality of life in cases with ADEM., Methods: Eleven cases who were on follow-up between 2008 and 2017 were included in the study, systemic, neurological and psychiatric examinations were done. All magnetic resonance images were re-evaluated. The neuropsychiatric evaluation was performed by clinical examination and psychometric scales; (1) The Pediatric Quality of Life Inventory 4.0, (2) Child Behavior Checklist, (3) Children`s Depression Inventory, (4) The Wechsler Intelligence Scale for Children-Revised and (5) Continuous Performance Test. The cases in our study underwent neuropsychiatric evaluation 3-42 months after the diagnosis of ADEM had been established., Results: Nine cases (81.8%) fully recovered without neurologic deficit. One case (9.1%) had a psychiatric disorder. During follow-up, cognitive and psychiatric problems were encountered in half of the cases (54.5%). Most of the cases with basal ganglia involvement (80%) displayed attention deficit and cognitive problems., Conclusion: In particular, cases with basal ganglia involvement should be followed carefully in terms of attention and cognitive problems.

Neuralgic amyotrophy is characterized by recurrent, painful, unilateral neuropathy involving mainly the upper brachial plexus followed by muscle weakness and muscle wasting. There are two forms: idiopathic and hereditary. Hereditary neuralgic amyotrophy is an autosomal dominant disease that is often linked to a mutation of SEPT9, a gene of the Septin family. The phenotypic spectrum of the disease may include hypotelorism, cleft palate, and other minor dysmorphisms. The age of onset is from infancy to adulthood. Hereditary neuralgic amyotrophy can be triggered by external stimuli such as infections, vaccinations, cold, stress, surgery, and strenuous exercise. Here, we report a six-year-old girl who was found to have mutation in the SEPT9 gene when she presented with recurrent attacks of painful brachial plexopathy following vaccinations, and was diagnosed as having hereditary neuralgic amyotrophy., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (Copyright: © 2019 Turkish Archives of Pediatrics.)

Introduction: This research was conducted to determine the views and information of the society about smoking cessation services and to find out the smoking status., Materials and Methods: This descriptive study was conducted at Hacettepe University Adult Hospital. The questionnaire was conducted to the participants with face to face interview techniques between the dates 3-8 August 2011 and asked about socio-demographic characteristics, smoking status and the views on smoking cessation methods and services. In the analysis, descriptive statistics, chi-square and Fisher's exact chi-square test was used where necessary. p< 0.05 was accepted for statistical significance., Results: The average age of 599 individuals participated to the research was 36.95 ± 12.80 years and 56.6% were male. The participants declared their smoking status that 48.9% do not smoke, 15.9% quit smoking, 35.2% stated as still smoking. Among current smokers 60.2% thought to quit smoking in the last 12 months. Of the participants 42.1% have tried to quit smoking in the past 12 months. 46% percent of smokers and 56.3% non-smokers stated that they are aware of smoking cessation outpatient clinics (p= 0.033). The percentage of awareness of smoking cessation line was 67.8%, and 46.9% are aware of AMATEMs. Same percentages are as 49.5% and 28.4% for the ones who quit smoking. 59.7% of smokers think that nicotine-free preparates and 17.4% think that nicotine preparates is successful; these percentages are 89.7% and 36.7% for non-smokers., Conclusion: Tendency to cessation among tobacco users and have awareness about the services that support cessation and believe that the law reduces the harms of tobacco use. However, more interventions are needed to reach those who are at low-income level. Also being a role model to the children in the society and to use attitudes and behaviors in smoking cessation campaigns are thought to be effective.