Pediatric-Onset Chronic Inflammatory Demyelinating Polyneuropathy: A Multicenter Study.

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.

Shared Biological Pathways and Processes in Patients with Intellectual Disability: A Multicenter Study.

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.

TARC and Septin 7 can be better monitoring biomarkers than CX3CL1, sICAM5, and IRF5 in children with seizure-free epilepsy with monotherapy and drug-resistant epilepsy.

Aim: To evaluate i) the relationship between epilepsy and inflammation by analyzing the levels of thymus activation-regulated chemokine (TARC), and interferon regulatory factor 5 (IRF5) in healthy controls, patients with epilepsy on monotherapy and polytherapy, ii) the levels of sICAM5, chemokine (c-x3-c motif) ligand 1 (CX3CL1), and septin 7 (SEPT7) which are important in both inflammation and synaptic formation.Methods: Patients who were seizure-free with monotherapy (epilepsy group-1), patients with drug-resistant epilepsy (epilepsy group-2), and healthy controls were included. Demographical data, disease durations, and medications were noted. Measurements were made by commercial ELISA kits.Results: The numbers of epilepsy group-1, epilepsy group-2, and healthy controls were 23, 20, and 21, respectively. TARC levels were significantly lower in healthy controls than in both epilepsy groups. Higher TARC levels than 0.58 pg/ml indicated epilepsy with a sensitivity of 81.8% and specificity of 84.0%. SEPT7 levels were significantly higher in epilepsy group-1 than in those epilepsy group-2. A negative correlation was found between SEPT7 levels and disease duration as is the case for the correlation between SEPT7 and average seizure duration. A positive correlation was found between IRF5 and CX3CL1 levels, SEPT7 and IRF5 levels, and IRF5 and sICAM5 levels.Conclusions: We suggest that TARC is a promising biomarker, even in a heterogeneous epilepsy group not only for drug-resistance epilepsy but also for seizure-free epilepsy with monotherapy. Additionally, drug resistance, longer disease, and longer seizure durations are related to lower levels of SEPT7, which has an essential role in immunological functions and dendritic morphology.

Clinical predictors of drug-resistant epilepsy in children

Background/aim: In up to 20% of epilepsy patients, seizures may not be controlled despite the use of antiepileptic drugs, either alone or in combination. These individuals are considered to have drug-resistant epilepsy. Drug-resistant epilepsy is usually associated with intellectual disability, psychiatric comorbidity, physical injury, sudden unexpected death, and low quality of life. Early detection and prediction of drug-resistant epilepsy are essential in determining the patient's most appropriate treatment option. This retrospective study aimed to determine the clinical, electroencephalographic, and radiological factors associated with medically intractable childhood seizures. Materials and methods: Data regarding 177 patients diagnosed with drug-resistant epilepsy were compared with 281 patients with drug-responsive epilepsy. Results: Univariate analysis showed that age at seizure onset, having mixed seizure types, history of status epilepticus, history of neonatal seizures, history of both having febrile and afebrile seizures, daily seizures at the onset, abnormality on the first electroencephalogram, generalized epileptic abnormality on electroencephalogram, abnormal neurodevelopmental status, abnormal neuroimaging, and having symptomatic etiology were significant risk factors for the development of drug-resistant epilepsy (p < 0.05). In multivariable analysis, having mixed seizure types, history of status epilepticus, having multiple seizures in a day, intellectual disability, symptomatic etiology, and neuroimaging abnormality remained significant predictors for developing drug-resistant epilepsy. Conclusions: In the course of childhood epilepsy, some clinical features may predict the outcome. Early identification of patients with high risk for drug-resistant epilepsy will help plan the appropriate treatment option. Further prospective studies should confirm these findings.

Risk Factors of Post-Stroke Epilepsy in Children; Experience from a Tertiary Center and a Brief Review of the Literature.

OBJECTIVES: Acute seizures and post-stroke epilepsy have been reported more frequently in patients with pediatric stroke than adults. Acute seizures in the first days of a stroke may deteriorate stroke and ischemia-related neurodegeneration and contribute to the development of post-stroke epilepsy. In this study, we aimed to investigate risk factors for the development of post-stroke epilepsy in children with arterial ischemic stroke. MATERIALS AND METHODS: We recruited 86 children with arterial ischemic stroke. We analyzed variables, including age at admission, gender, complaints at presentation, focal or diffuse neurologic signs, neurologic examination findings, laboratory investigations that were conducted at admission with stroke (complete blood cell count, biochemical-infectious-metabolic-immunological investigations, vitamin B12 levels, vitamin D levels), neuroimaging results, etiologies, time of the first seizure, time of remote seizures, and development of neurologic deficit retrospectively. Seizures during the first six hours after stroke onset were defined as 'very early seizures'. 'Early seizures' were referred to seizures during the first 48 h. Patients who experienced two or more seizures that occurred after the acute phase of seizures were classified as 'epileptic.' A binary logistic regression analysis was used to estimate risk factors. RESULTS: An acute seizure was detected in 59% and post-stroke epilepsy developed in 41% of our cohort. Binary logistic regression analysis demonstrated that 'very early seizures' increased epilepsy risk six-fold. Epilepsy was 16 times higher in patients with 'early seizures'. Low vitamin D levels were defined as a risk factor for post-stroke epilepsy. CONCLUSION: Seizures in the very early period (within the first six hours) are the most significant risk factors for the development of post-stroke epilepsy Further studies regarding seizure prevention and neuroprotective therapies are needed because post-stroke epilepsy will affect long term prognosis in patients with pediatric stroke.

Neuroprotective Effects of Lacosamide and Memantine on Hyperoxic Brain Injury in Rats.

In neonates supraphysiological oxygen therapy has been demonstrated to cause neuronal death in hippocampus, prefrontal cortex, parietal cortex, and retrosplenial cortex. There is a need for the detection of novel neuroprotective drugs. Neuroprotective effects of lacosamide or memantine have been demonstrated in adult patients with ischemia, trauma and status epilepticus. The effects in immature brains may be different. This study aimed to evaluate neuroprotective effects of lacosamide and memantine treatment in a hyperoxia-induced brain injury model in immature rats. This study was performed in the Animal Experiments Laboratory of Dokuz Eylul University Faculty of Medicine. Neonatal Wistar strain rat pups were exposed to hyperoxia (80% oxygen + 20% nitrogen) for five days postnatally. They were divided into five groups; hyperoxia + lacosamide, hyperoxia + memantine, hyperoxia + lacosamide and memantine, hyperoxia + saline, control groups. After termination of the experiment, brain tissues were examined. Neuron counting in examined regions were found to be higher in hyperoxia + memantine and hyperoxia + lacosamide and memantine groups than hyperoxia + saline group. The presence of apoptotic cells evaluated with TUNEL and active Caspase-3 in hyperoxia + memantine and hyperoxia + lacosamide and memantine groups were found to be lower compared to hyperoxia + saline group. This study demonstrates that neuron death and apoptosis in newborn rat brains after hyperoxia is reduced upon memantine treatment. This is the first study to show the effects of memantine and lacosamide on hyperoxia-induced damage in neonatal rat brains.

Intravenous Levetiracetam for Treatment of Seizures in Term and Preterm Neonates.

CONTEXT: Seizures are the most frequent neurological disturbance in the neonatal period, and there are no evidence-based guidelines for the treatment of neonatal seizures. Here we report a study on the use of levetiracetam as second-line therapy in the treatment of seizures in term and preterm neonates. AIM: The aim of this study was to assess the efficacy and safety of levetiracetam for seizures of term and preterm neonates. SETTINGS AND DESIGN: We retrospectively analyzed data of the patients who had seizures and who were treated with levetiracetam as an add-on therapy to phenobarbital during the neonatal period. STATISTICAL ANALYSIS: The Statistical Package for the Social Sciences (SPSS) software, version 15.0 (SPSS, Chicago, Illinois), was used for statistical analysis. Continuous variables were expressed as mean values and standard deviations. RESULTS: Thirty-six patients (8 term and 28 preterm) received levetiracetam. Mean dose of levetiracetam was 31.67 ± 14.83mg/kg/day. Twenty-five of the patients (69.4%) were seizure free with levetiracetam treatment. Electroencephalography recordings improved in 28 (77.8%) of the patients after levetiracetam. No severe adverse effects were observed. CONCLUSION: Our data suggest that levetiracetam may be a safe and effective treatment for neonatal seizures, which are unresponsive to phenobarbital.

Coexistence of guanidinoacetate methyltransferase (GAMT) deficiency and neuroleptic malignant syndrome without creatine kinase elevation.

We describe the first child with guanidinoacetate methyltransferase (GAMT) deficiency who developed neuroleptic malignant syndrome (NMS) after the treatment of risperidone without elevated creatine kinase (CK) levels. The patient presented with lethargy, hyperthermia, generalized tremor and rigidity with normal serum CK levels. After cessation of risperidone and adding clonezepam to the supportive treatment, symptoms of NMS were ameliorated. We conclude that although serum CK elevation is a useful indicator for the early detection of NMS, normal serum CK levels may be seen during the NMS course in the presence of GAMT deficiency.

Genetic Landscape of Congenital Myasthenic Syndromes From Turkey: Novel Mutations and Clinical Insights.

Congenital myasthenic syndromes are clinically and genetically heterogeneous disorders of neuromuscular transmission. Most are treatable, but certain subtypes worsen with cholinesterase inhibitors. This underlines the importance of genetic diagnosis. Here, the authors report on cases with genetically proven congenital myasthenic syndromes from Turkey. The authors retrospectively reviewed their experience of all patients with congenital myasthenic syndromes, referred over a 5-year period (2011-2016) to the Child Neurology Department of Dokuz Eylül University, Izmir, Turkey. In addition, PubMed was searched for published cases of genetically proven congenital myasthenic syndromes originating from Turkey. In total, the authors identified 43 (8 new patients, 35 recently published patients) cases. Defects in the acetylcholine receptor (n = 15; 35%) were the most common type, followed by synaptic basal-lamina associated (n = 14; 33%) and presynaptic syndromes (n = 10; 23%). The authors had only 3 cases (7%) who had defects in endplate development. One patient had mutation GFPT1 gene (n = 1; 2%). Knowledge on congenital myasthenic syndromes and related genes in Turkey will lead to prompt diagnosis and treatment of these rare neuromuscular disorders.

Expanding spectrum of SCN1A-related phenotype with novel mutations.

Mutations in the genes encoding voltage-gated sodium channels cause a variety of epilepsy syndromes, with most of the mutations occurring in SCN1A gene. It is one of the most well-researched epilepsy genes. The SCN1A gene, which seems to be a relevant regulator of excitability of the CNS, is implicated in various epilepsy phenotypes through various genetic mechanisms ranging from common variants to rare monogenic variants. It is known that SCN1A gene is tightly linked to severe myoclonic epilepsy of infancy (SMEI). However, its phenotypic spectrum is expanding. Here, we report clinical and genetic findings of 10 patients with SCN1A mutations where two of them were found to have novel mutations. Our findings support understanding and updating knowledge on the correlation between phenotype distribution and location and type of mutations in SCN1A-related disorders.

Myelin Oligodendrocyte Glycoprotein Antibody Persistency in a Steroid-Dependent ADEM Case.

Myelin oligodendrocyte glycoprotein (MOG) is a candidate target antigen in demyelinating central nervous system diseases, including acute disseminated encephalomyelitis (ADEM), neuromyelitis optica, and multiple sclerosis. It may give prognostic information regarding monophasic or recurrent course of the disease. MOG antibodies have been shown to be positive in high titers during the first episode of ADEM with rapidly decreasing to undetectable limits after recovery. However, persistent MOG antibodies are considered as a predicting factor for multiple sclerosis, optic neuritis relapses, and incomplete recovery of ADEM. Here we report a unique case with persistent MOG antibodies presented with multiphasic ADEM-like attacks. A 6-year-old girl was consulted with encephalopathy, gait disturbance, and oculomotor nerve palsy. Periventricular white matter lesions were seen on cranial magnetic resonance imaging studies. ADEM was diagnosed and treated with steroid. During follow-up, she experienced repeated episodes after steroid therapy termination. We were able to search MOG antibody at the ninth attack. The positivity of this antibody remained. It was thought to be associated with steroid-dependent course, and azathioprine and intravenous human immunoglobulin treatment were added. Patients with persistent MOG antibodies may benefit from addition of immunosuppressant agents, which may decrease the number of attacks.

Importance of acrocyanosis in delayed walking.

We present a four-year-old wth ethylmalonic encephalopathy who presented with delayed walking. She had bilateral hyperintense lesions in the basal ganglia. Molecular analysis revealed a homozygous c.3G>T mutation in the ETHE1 gene. She did not have typical findings of the disease including recurrent petechia, chronic diarrhea and acrocyanosis was very subtle and orthostatic. She benefited from riboflavine and Q10 treatments. We suggest that acrocyanosis should be questioned and examined in patients with motor delay.

Importance of neurologic and cutaneous signs in the diagnosis of Schimke immuno-osseous dysplasia.

Schimke immuno-osseous dysplasia is an autosomal recessive multisystem disorder caused by defects in SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1 gene (SMARCAL1). SMARCAL1 product is a helicase that has role in selective cellular proliferation. The disorder is characterized by spondyloepiphyseal dysplasia with short stature, nephropathy, T cell deficiency, neurologic and cutaneous signs. Patients may have hyperpigmented skin lesions similar to café au lait spots. Symptoms and disease severity in Schimke immuno-osseous dysplasia varies from patient to patient. Genetic, epigenetic and environmental factors play role on the severity of the disease. Here we report on a patient with short stature, steroid resistant nephrotic syndrome and recurrent infections. Cutaneous findings and developmental delay helped us to reach the diagnosis of Schimke immuno-osseous dysplasia. A homozygous missense mutation in SMARCAL1 gene confirmed the clinical diagnosis.