First-Drug Efficacy and Drug-Resistant Epilepsy Rates in Children With New-Onset Epilepsies: A Multicenter Large Cohort Study.

Objective: This study aimed to assess the first-drug efficacy rate in newly diagnosed children with epilepsies treated with antiseizure medications. Methods: This retrospective study was conducted on 1003 children (age range: 3-10 years, and the mean duration of follow-up: 22 ± 13 months) with newly diagnosed epilepsy. The following parameters were evaluated: first-drug efficacy rate, first-drug-failure rate, and drug resistance rate in the cohort. Results: The first-drug-failure rate was defined in 335/1003 (33%) of the patients, no seizure control in 315 (31%), and drug withdrawal in 20 (2%). There was no significant difference between the group with focal-onset seizures and the group with generalized onset seizures. The first-drug efficacy rate was 67% in children with focal-onset seizures and 66% in children with generalized-onset seizures. Adjunctive antiseizure medication therapy was initiated in 335 patients-dual therapy with 180 patients (18%) and polytherapy with 155 (15%). Drug-resistant epilepsy was defined as 15% in the follow-up period. Etiology-specific diagnoses of the cohort were structural (n = 165, 17%), genetic (n = 25, 3%), metabolic (n = 15%), immune-infectious (n = 17 (2%), and unknown (n = 781, 77%). With a comparison of the 2 most common etiology subgroups (structural versus unknown), a first-drug efficacy rate of 53% and a higher prevalence of drug-resistant epilepsy at 30% were observed in children with structural etiology. First-drug efficacy was statistically lower in children without well-defined epilepsy syndromes (65%) compared with the rate of those with well-defined epilepsy syndrome (79%). Conclusion: This study revealed a first-drug failure rate (33%) in the presented cohort with a drug-resistance epilepsy rate (15%).

Optic neuritis in Turkish children and adolescents: A multicenter retrospective study.

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.

Short-Term and Long-Term Effects of Levetiracetam Monotherapy On Hematological Parameters in Children with Idiopathic Epilepsy.

Objectives: Levetiracetam (LEV) is a broad-spectrum anti-seizure drug (ASD) that has been widely used in recent years. It is thought to have an effect on the release of neurotransmitters that occur as a result of vesicle fusion and exocytosis by binding to synaptic vesicle glycoprotein 2A. Methods: The study enrolled patients diagnosed in the Pediatric Neurology Outpatient Clinic who were being followed with the diagnosis of childhood idiopathic epilepsy and were receiving LEV as ASD monotherapy. Sixty-four patients with complete blood count data from the pretreatment (Pre-T) period, the short-term period of 3 to 6 months after treatment (Post-TS), and the long-term period after 12 months (Post-TL) were included in the study. The demographic data of the patients included in the study were retrospectively analyzed for seizure frequency, seizure type, initial and subsequent EEG results, starting date of the treatment, and complete blood count data. Results: Of 64 patients, 36 were male and 28 were female. The mean age of patients was 8.7±3.8 (2.5-16) years. In the whole population, post-TL lymphocyte counts were found to be decreased compared to pre-TL lymphocyte counts. This decrease was statistically significant for patients over 6 years of age (n=46) (p<0.075). In the post-TL period, hematocrit, hemoglobin, mean corpuscular volume, and mean platelet (PLT) volume increased, while white blood cell, PLT, neutrophil, and monocyte counts decreased (p<0.05). Seizure-free status was achieved in 92.2% of cases. Frequent seizures were observed only in five patients who were older than 6 years. Pre-treatment EEG findings were normal for 15 (23.4%) patients, generalized for 8 (12.5%) patients, and focal for 41 (64.1%) patients. According to the pretreatment EEG findings, all of the patients with improvement in EEG were those whose findings were focal (p<0.001). Conclusion: In children with idiopathic epilepsy, long-term LEV monotherapy may cause significant changes in hematological parameters. LEV seems to have effects on the counts and perhaps functions of PLTs, lymphocytes, monocytes, and neutrophils, particularly in the long-term.

Acute necrotizing encephalopathy associated with RANBP2 mutation: value of MRI findings for diagnosis and intervention.

INTRODUCTION: Acute necrotizing encephalopathy (ANEC) is a rare entity characterized by encephalopathy following a febrile illness. Most patients are sporadic; however, recurrent and familial cases have been associated with RAN-binding protein 2 (RANBP2) mutation. Well-defined MRI findings can even be life-saving with early diagnosis and treatment. METHODS: In this article, nine pediatric cases diagnosed with ANEC1 both clinically and radiologically, and with least one variation in the RANBP2 gene, are presented. RESULTS: All patients were previously healthy and presented with encephalopathy after an acute febrile infection. The patients of 44% had a similar attack history in their family. Influenza A/B was detected in 7 patients (78%). One patient was admitted at age 32 years old. The first clinical findings of patients were encephalopathy (100%), seizure (44%), vision problems (33%), ataxia (11%), and monoplegia (11%). Recurrent attacks were seen in two (22%) patients. Brain MRI findings including bilateral thalamus, external capsules, and brainstem involvements were highly suggestive for RANBP2 mutation. Based on MRI findings, genetic analyses were quickly performed and confirmed. All of the patients were treated with empirical encephalitis treatment, oseltamivir, intravenous immunoglobulin (IVIG), high-dose steroid and, if necessary, plasmapheresis, but three (33%) patients died despite treatment. CONCLUSION: ANEC associated with RANBP2 mutation may occur early or late-onset and can be recurrent and fatal. Therefore, early diagnosis and treatment have the potential to modify the severity of this encephalopathy. Well-defined MRI findings are highly instructive for early diagnosis.

A rare cause of microcephaly, thin corpus callosum and refractory epilepsy due to a novel SLC1A4 gene mutation.

L-serine is an important amino acid that ensures neuronal differentiation and development. The SLC1A4 gene encodes proteins that transport amino acids such as serine, alanine, threonine and glutamate into neurons. Pathogenic variants in SLC1A4 gene interneuron transport of L-serine impaired and a severe global developmental delay occurs, characterized by microcephaly and refractory seizures. In this article, we would like to describe the demographic, clinical, electroencephalography (EEG) and magnetic resonance imaging (MRI) features of a patient with a novel pathogenic variant in the 6th exon of the SLC1A4 gene (p.Gly374Arg) detected by whole-exome sequencing, which is extremely rare (there have been twenty patients reported in the literature). It is emphasized that SLC1A4 gene variants should be kept in mind if the patients have microcephaly, global developmental delay, refractory seizures, and there are no abnormalities in basal metabolic investigations, and the thin corpus callosum and myelination delay is seen on the MRI.

Optic nerve ultrasonography in the evaluation of the relationship between arachnoid cyst and headache.

AIM: This study is aimed to show the difference between optic nerve sheath diameter (ONSD) values in migraine patients with and without arachnoid cysts from migraine patients and control groups, and to evaluate the relationship with the arachnoid cyst size on magnetic resonance imaging (MRI) and their clinical severity. METHODS: This cross-sectional study included pediatric patients who were previously diagnosed with migraine and the control group. The patients consist of 3 groups. The first group was 24 patients with arachnoid cysts on brain magnetic resonance imaging (MRI) who met the diagnostic criteria for migraine (group 1); the second group was 20 patients with only headache without arachnoid cysts or other findings on brain magnetic resonance imaging (MRI) (group 2); the third group was completely healthy 20 control group. Demographic data of the patients, the onset of headache time, clinical severity, electroencephalography (EEG) findings, optic nerve sheath diameter (ONSD) measurements by ultrasonography, and the volume of arachnoid cyst on brain MRI were determined and compared. RESULTS: The optic nerve sheath diameter (ONSD) value was the highest in group 1 and the lowest in the control group (p: 0.001). The clinical severity was statistically different between the groups (p: 0.038). Accordingly, the majority of the clinical severity of group 1 was determined in grades 3 and 4. A weak positive correlation was found between the arachnoid cyst size on MRI and the ONSD measurement (r = 0.410, p = 0.047). The ONSD value statistically significantly increased with clinical severity in group 1 (p: 0.003). CONCLUSION: The reliability of the optic nerve sheath diameter (ONSD) measurements in determining the increase of the intracranial pressure was shown in previous studies. This is the first study in the literature presenting that the intracranial pressure effects of arachnoid cysts can be demonstrated by ONSD. We have considered that arachnoid cysts detected in headaches can create a compression effect and cause the pain to intensify.

Expanding Phenotype of Poirier-Bienvenu Syndrome: New Evidence from an Italian Multicentrical Cohort of Patients.

BACKGROUND: Poirier-Bienvenu Neurodevelopmental Syndrome (POBINDS) is a rare disease linked to mutations of the CSNK2B gene, which encodes for a subunit of caseinkinase CK2 involved in neuronal growth and synaptic transmission. Its main features include early-onset epilepsy and intellectual disability. Despite the lack of cases described, it appears that POBINDS could manifest with a wide range of phenotypes, possibly related to the different mutations of CSNK2B. METHODS: Our multicentric, retrospective study recruited nine patients with POBINDS, detected using next-generation sequencing panels and whole-exome sequencing. Clinical, laboratory, and neuroimaging data were reported for each patient in order to assess the severity of phenotype, and eventually, a correlation with the type of CSNK2B mutation. RESULTS: We reported nine unrelated patients with heterozygous de novo mutations of the CSNK2B gene. All cases presented epilepsy, and eight patients were associated with a different degree of intellectual disability. Other features detected included endocrinological and vascular abnormalities and dysmorphisms. Genetic analysis revealed six new variants of CSNK2B that have not been reported previously. CONCLUSION: Although it was not possible to assess a genotype-phenotype correlation in our patients, our research further expands the phenotype spectrum of POBINDS patients, identifying new mutations occurring in the CSNK2B gene.

Pediatric anti-NMDA receptor encephalitis associated with COVID-19.

Anti-N-methyl-D-aspartate receptor encephalitis is a clinical condition characterized by acute behavioral and mood changes, abnormal movements, autonomic instability, seizures, and encephalopathy. We describe a 7-year-old boy diagnosed with autoimmune encephalitis due to NMDAR antibody in association with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019) (COVID-19), without pulmonary involvement or fever. The patient presented with acute ataxia, rapidly developed encephalopathy, and autoimmune encephalitis was suspected. Steroid treatment was withheld because of lymphopenia and intravenous immunoglobulin was started. The absence of clinical response prompted plasmapheresis and, when lymphocyte counts improved, pulse steroid treatment was applied. The latter was followed by significant improvement and the patient was discharged in a conscious and ambulatory state. Autoimmune encephalitis should be considered in the presence of neurological symptoms accompanying SARS-CoV-2 infection and steroid treatment should be preferred unless limited by contraindications.

Neurodevelopmental risk evaluation of premature closure of the anterior fontanelle.

PURPOSE: To evaluate neurological development of completely healthy children with anterior fontanelle premature closure via Denver Developmental Screening Test II and to compare the results with control group. METHOD AND RESULTS: The records of 140 patients applied to Mersin University Pediatric Neurology Outpatient Clinic between 2011 and 2019 with the complaint of premature closure of the anterior fontanelle were retrospectively reviewed. Patients with microcephaly, craniosynostosis, infection, sequelae of hypoxia-ischemia, metabolic disorders, intracranial hemorrhage, epilepsy, endocrine problems, and dysmorphic features were excluded from the study. Sixty-six completely healthy children with anterior fontanelle premature closure were included in the study. Denver Developmental Screening Test II was performed by the same developmental specialist to the children with premature closure of the anterior fontanelle as well as to the healthy control group. For each child included in the case and the control group, 90% of the values for each development area were calculated and recorded. Then, the results were compared. Denver II Developmental Screening Test (p < 0.001) and gross motor subtest (p < 0.001) results showed statistically significant retardation in the case group compared with the control group. CONCLUSIONS: The study was the first study in the literature on the gross motor development of children with premature closure of anterior fontanelle, and it has been found significantly undeveloped compared with the control group, and it has been concluded that similar patients should be evaluated from this view point in pediatric neurology department.

A rare case of pontine and extrapontine myelinolysis in a pediatric patient with chronic renal failure.

Osmotic demyelination syndrome (ODS) is a very rare condition in childhood occurring usually secondary to the rapid increase of serum sodium levels. This situation occurring secondary to the rapid correction of hyponatremia can be seen more rarely in the form of extrapontine myelinolysis and even the coexistence of these two conditions besides central pontine demyelinolysis. However, osmotic demyelination syndrome due to the rapid correction of hyponatremia in chronic renal failure (CRF) patients is very rare depending on existing uremia. In this article, we present an extremely rare case of pontine and extrapontine myelinolysis, which occurred in a pediatric patient with chronic renal failure, secondary to the rapid correction of hyponatremia. In the diffusion and cranial magnetic resonance imaging (MRI), bilateral symmetrical caudate, putamen, and thalamus involvements and hyperintense linear lesions at the pons, cortical, and subcortical areas were revealed. It was evaluated as pontine and extrapontine myelinolysis. This clinical situation presents that the presence of severe hyponatremia and extremely rapid correction of it can develop pontine and extrapontine myelinolysis even though it is very rare in uremic patients.

Identification of a Novel Mutation in GRIN2A Gene with Global Developmental Delay and Refractory Epilepsy.

We report a 2.5-year-old Turkish boy who first presented with nystagmus, lack of eye contact, and hypotonia at 2 months of age and developed refractory seizures when 6 months old. Extensive metabolic tests and imaging being noncontributory, whole-exome sequencing was carried out which revealed a heterozygote NM_001134407.2:C.3299A>G (p.Glu1100Gly) novel mutation in GRIN2A gene. Topiramate was started and seizures were rapidly brought under control. GRIN2A mutations may result in altered GluN2A membrane trafficking and response to glutamate. This report illustrates the clinical variability of GRIN2A mutations according to the age of onset of symptoms and suggests considering mutations in this gene in cases of global developmental delay, refractory epilepsy, and nystagmus.

A rare concurrence: gelastic seizures in a patient with right temporal nongalenic pial arteriovenous fistula.

INTRODUCTION: Gelastic seizures are the type of seizures that are most commonly seen in childhood and should be excluded definitely in the differential diagnosis of hypothalamic hamartomas. This seizure type may be accompanied by refractory seizures, cognitive decline, and early puberty. However, etiology may also include other causes different than hypothalamic hamartomas. The seizure may also arise from temporal and frontal region, in addition to hypothalamus. Different clinical findings may be observed based on origin and areas of spread. CONCLUSIONS: In this article, we report a case of gelastic seizure that has been observed by a different cause other than hypothalamic hamartoma which was reported for the first time in the literature.

A rare concurrence: Antibodies against Myelin Oligodendrocyte Glycoprotein and N-methyl-d-aspartate receptor in a child.

BACKGROUND: Myelin Oligodendrocyte Glycoprotein antibodies (MOG) may be used as a biomarker for diagnosis of many demyelinating diseases. Especially, patients of acute disseminated encephalomyelitis (ADEM), multiple sclerosis (MS), aquaporin-4 (AQP4) seronegative neuromyelitis optica spectrum disorder (NMOSD), monophasic or recurrent optic neuritis (ON), transverse myelitis and N-methyl-d-aspartate (NMDA) receptor encephalitis (NMDARe) can overlap with Myelin Oligodendrocyte Glycoprotein antibodies. We present a child with autoimmune encephalitis in whom antibodies against Myelin Oligodendrocyte Glycoprotein (MOG) and N-methyl-d-aspartate receptor (NMDAR) were simultaneously detected. The clinical manifestation was characteristic of NMDAR encephalitis, and cranial and spinal magnetic resonance imaging showed no signs of encephalomyelitis. On the other hand, complete recovery within first days of steroid treatment was more compatible with the course of MOG antibody-related disease. CONCLUSIONS: We emphasize the rarity of this antibody combination in children and suggest these patients, although clinically improved, may require longer follow-up due to the risk of recurrence of two autoimmune disorders.