Clinical and genetic delineation of autosomal recessive and dominant ACTL6B-related developmental brain disorders.

PURPOSE: This study aims to comprehensively delineate the phenotypic spectrum of ACTL6B-related disorders, previously associated with both autosomal recessive and autosomal dominant neurodevelopmental disorders. Molecularly, the role of the nucleolar protein ACTL6B in contributing to the disease has remained unclear. METHODS: We identified 105 affected individuals, including 39 previously reported cases, and systematically analysed detailed clinical and genetic data for all individuals. Additionally, we conducted knockdown experiments in neuronal cells to investigate the role of ACTL6B in ribosome biogenesis. RESULTS: Biallelic variants in ACTL6B are associated with severe-to-profound global developmental delay/intellectual disability (GDD/ID), infantile intractable seizures, absent speech, autistic features, dystonia, and increased lethality. De novo monoallelic variants result in moderate-to-severe GDD/ID, absent speech, and autistic features, while seizures and dystonia were less frequently observed. Dysmorphic facial features and brain abnormalities, including hypoplastic corpus callosum, parenchymal volume loss/atrophy, are common findings in both groups. We reveal that in the nucleolus, ACTL6B plays a crucial role in ribosome biogenesis, in particular in pre-rRNA processing. CONCLUSION: This study provides a comprehensive characterization of the clinical spectrum of both autosomal recessive and dominant forms of ACTL6B-associated disorders. It offers a comparative analysis of their respective phenotypes provides a plausible molecular explanation and suggests their inclusion within the expanding category of 'ribosomopathies'.

The impact of initial hematocrit values after birth on peri-/intraventricular hemorrhage in extremely low birth weight neonates.

AIM: Peri-/intaventricular hemorrhage (P/IVH) is a common condition in preterm neonates and is responsible for substantial adverse neurological outcome especially in extremely low birth weight infants. As hematocrit after birth is a surrogate marker for blood volume, this study aimed to evaluate the effect of initial hematocrit values after birth on P/IVH development in extreme low birth weight (ELBW) neonates. PATIENTS AND METHODS: A prospective cohort analysis of 92 eligible ELBW neonates was performed. The relationship between initial hematocrit values in ELBW neonates after birth and subsequent development of P/IVH was examined. RESULTS: Twenty-nine of 92 infants developed P/IVH. There were significant differences in initial Hct and maximum carbon dioxide (max PCO2) in the first 3 days levels in the P/IVH group compared with no P/IVH group. Initial Hct level at birth in the P/IVH group were significantly lower than the no P/IVH group while max PCO2 in the first 3 days were found to be significantly high in the P/IVH group. There were no significant differences in other baseline demographic, perinatal, and neonatal characteristics while in univariate analysis, higher gestational age and initial Hct were associated with decreased likelihood of P/IVH. In multiple regression analysis after adjustment, only initial Hct remained significantly associated with P/IVH. There was no difference between the population by subgroups of IVH (IVH I-II and IVH III-IV) according to hematocrit and the severity of IVH. CONCLUSION: Higher initial Hct at birth is associated with decreased P/IVH in ELBW infants. We hypothesized the argument that ELBW infants who have lower initial Hct at birth have less suboptimal volume status that predisposing lower cerebral blood flow and the resultant decrease in cerebral blood flow precede the development of P/IVH.

Evaluation of micronutrient levels in children with cerebral palsy.

BACKGROUND: Many studies evaluating the nutritional status of children with cerebral palsy (CP) have focused on energy requirements and protein intake. The present work aimed to assess nutritional status and micronutrient levels of children with (CP). METHODS: This multicenter, cross-sectional and observational study was conducted in 10 different cities in Turkey. Data were available for 398 participants. Anthropometric measurements, feeding mode, nutritional status, and micronutrient levels were evaluated. RESULTS: The study was conducted with 398 participants (303 patients and 95 healthy controls). Statistical analysis showed that according to the Gomez Classification, weight-for-age (WFA) revealed malnutrition in 92.6% of children with CP, based on Centers for Disease Control and Prevention percentiles. Measurements of micronutrient levels showed that zinc levels were low in patients, whereas vitamin A levels were low in controls. Phosphorous and manganese levels were significantly lower in malnourished children than in typical children. The results revealed that children consuming enteral nutrition solutions had higher selenium and lower zinc levels than non-consumers. CONCLUSIONS: Malnutrition is not only a protein- or calorie-based problem; micronutrient deficiencies might cause severe health problems. Children with chronic neurological disabilities must be carefully evaluated for these issues. Therefore, nutritional interventions should be adapted to nutrition.

Association of nerve conduction impairment and insulin resistance in children with obesity.

AIM: The objective of our study was to investigate nerve conduction in normoglycemic obese children. METHODS: A total of 60 children with obesity (30 female and 30 male) and 30 healthy children (15 female and 15 male) were enrolled in the study. Insulin resistance (IR) and other metabolic disturbances were investigated and nerve conduction was measured in all participants. Obese children were divided into groups according to the presence of IR. All results were compared between these subgroups. RESULTS: The nerve conduction velocity (NCV) of motor median nerves in the IR+ group was significantly higher than that in the IR- group and lower than that in the control group. The NCV of the motor peroneal nerve in the IR+ group was significantly lower than that in the IR- group. The sensory nerve action potential (SNAP) of the sensory median nerve was significantly lower in the IR+ group compared to that in the IR- group. The sensory sural nerve's SNAP was significantly lower in the IR+ group than that in the control group. CONCLUSION: Nerve conduction tests may help to detect early pathologies in peripheral nerves and to decrease morbidities in obese children.

Association Between Vitamin D Levels and COVID-19 Infection in Children: A Case-Control Study.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) infection is seen in all age groups, and its symptoms are very variable. The course of the disease can be asymptomatic or mortal. In pediatric patients, vitamin D is thought to be protective against (COVID-19) with its immunomodulator, antiviral, anti-inflammatory, and epithelial integrity properties. Our aim is to investigate the relationship between (COVID-19) infection and vitamin D level. MATERIALS AND METHODS: We included (COVID-19) patients between 1 month and 18 years of age and healthy control groups. We compared epidemiological, clinical, laboratory, and imaging findings in patients. RESULTS: One hundred forty-nine patients were evaluated in our study. Seventy-three (49%) of them were (COVID-19)-positive patients and 76 (51%) of them were healthy control group. The mean 25(OH)-D vitamin level was 15.80 ng/mL (5-41.56) in (COVID-19) patients and 21.51 ng/mL (5-69.80) in the control group. Vitamin D level was shown to be statistically significantly lower in coronavirus disease 2019 patients (P < .001). It was observed that myalgia was more common in patients with low 25(OH)-D levels (P < .048). CONCLUSION: Our study is one of the rare studies examining the relationship between (COVID19) and 25(OH)-D vitamins in the pediatric age group. Children with (COVID-19) have a lower 25(OH)-D vitamin level than the control group.

The significance of MUAC z-scores in diagnosing pediatric malnutrition: A scoping review with special emphasis on neurologically disabled children.

This review by a panel of pediatric gastroenterology-hepatology-nutrition and pediatric neurology experts aimed to address the significance of mid-upper arm circumference (MUAC) assessment in diagnosis of pediatric malnutrition. Specifically, the potential utility of recently developed MUAC z-score tape in clinical practice for larger patient populations was addressed including the neurologically disabled children. In accordance with the evidence-based data, four statements were identified by the participating experts on the utility of MUAC z-score tape, including (1) MUAC z-scores correlate with body mass index (BMI) and weight for height/length (WFH/l) z-scores in diagnosing malnutrition; (2) MUAC z-score tape offers a higher sensitivity to diagnose the mild and moderate malnutrition and better ability to track the changes in nutritional status over time than the other single datapoint measurements; (3) Using single-step MUAC z-score tape in children with cerebral palsy (CP) seems to provide more reliable data on anthropometry; and (4) The clinical value of the tool in classifying secondary malnutrition in CP should be investigated in large-scale populations. In conclusion, enabling single-step estimation of nutritional status in a large-scale pediatric population regardless of age and within a wide range of weight, without formal training or the need for ancillary reference charts and calculators, MUAC z-tape offers a favorable tool for easier and earlier diagnosis of pediatric malnutrition. Nonetheless, further implementation of MUAC z-score screening in larger-scale and/or special populations is necessary to justify its utility in relation to other primary anthropometric indicators in diagnosis of malnutrition as well as in treatment monitoring in the community and hospital setting.

Retracted: Clinical and genetic evaluations of rare childhood epilepsies in Turkey's national cohort.

Aycan Ünalp, Yigithan Güzin, Bülent Ünay, Ayse Tosun, Dilek Çavusoglu, Hande Gazeteci Tekin, Semra Hiz Kurul, Ebru Arhan, Selvinaz Edizer, Gülten Öztürk, Uluç Yis, Ünsal Yilmaz, Turkish Rare Epilepsies Study Group, Clinical and genetic evaluations of rare childhood epilepsies in Turkey's national cohort, Epileptic Disorders, 2023, (https://doi.org/10.1002/epd2.20150) The above article, published online on 16 August 2023 on Wiley Online Library (www.onlinelibrary.wiley.com), has been retracted by agreement between the authors, the Editor-in-Chief, Sándor Beniczky, and John Wiley & Sons Ltd. The authors asked for a retraction based on an experimental error which would alter the results of the study if corrected.

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.

Acquired epileptiform opercular syndrome: F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) findings and efficacy of levetiracetam therapy.

We report a five-year-old girl presenting with dysphagia, dysarthria, drooling, and generalized tonic convulsions in whom the final diagnosis was acquired epileptiform opercular syndrome. Levetiracetam monotherapy at a dosage of 40 mg/kg/day improved the clinical findings, and seizures were controlled at the end of the first month of treatment. Six months after the initial diagnosis, she presented with speech deterioration and dysarthria. At this time, although sleep and awake electroencephalography (EEG) were normal, FDG-PET showed hypometabolic and hypermetabolic regions in the anterior/inferior and anterior regions of the right frontal lobe, respectively. By increasing before levetiracetam dosage to 50 mg/kg/day, the clinical findings resolved and the patient is still seizure free. Acquired epileptiform opercular syndrome is a rare epileptic disorder in which the seizures are resistant to conventional antiepileptic drugs. Levetiracetam may be an effective antiepileptic drug in controlling seizures and other clinical findings in acquired opercular epileptiform syndrome. Hypometabolic and hypermetabolic regions in FDG-PET study may be due to ongoing seizure activity or impaired glucose metabolism in this disorder.

Osteopenia in children with cerebral palsy can be treated with oral alendronate.

PURPOSE: Cerebral palsy is one of the most common reasons of osteopenia in childhood. Patients have a significantly decreased bone mineral density, and painful fractures with minor traumas are common. Biphosphonates in the treatment of childhood osteoporosis are increasingly being used. This study aimed to evaluate the efficacy of oral alendronate treatment in children with cerebral palsy. METHODS: Twenty-six children (16 boys and 10 girls) aged 3 to 17 years who had quadriplegic cerebral palsy and osteopenia were included in the study. The patients received alendronate (1 mg/kg/week), calcium (600 mg/day), and vitamin D(3) (400 U/day) over a year. A complete blood count, kidney and liver functional tests, plasma calcium, phosphate and alkaline phosphatase levels, and lumbar vertebral bone mineral density were measured before and after treatment. RESULTS: Compared with pretreatment values, bone mineral density, serum calcium, and phosphate levels of the patients statistically increased and alkaline phosphatase levels decreased after treatment. No patient needed to interrupt treatment because of side effects. CONCLUSIONS: Oral alendronate at a dose of 1 mg/kg/week for the treatment of osteopenia in children with cerebral palsy was found to be safe and effective.

Valproic acid-induced DRESS in a child responding to cyclosporine with HLA analysis. / Síndrome DRESS inducido por ácido valproico en una niña que respondió a la ciclosporina con análisis de HLA.

Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome, is a potentially life-threatening rare reaction that causes a severe rash and can lead to multiorgan failure. As in other severe drug eruptions, drug-specific T lymphocytes play a crucial role in DRESS. The hapten/pro-hapten model, pharmacological interaction model, and altered peptide repertoire model are three different models developed to describe the relationship/interaction between a medication or its metabolites and the immune system. We discuss our experience with cyclosporine treatment in a steroid-resistant DRESS syndrome caused by valproic acid in a girl, as well as her clinical, laboratory, and human leukocyte antigens (HLA) study results.

El síndrome de erupción medicamentosa con eosinofilia y síntomas sistémicos (drug reaction with eosinophilia and systemic symptoms, DRESS), también conocido como síndrome de hipersensibilidad inducida por medicamentos, es una reacción rara potencialmente mortal que causa una erupción grave y que puede provocar insuficiencia multiorgánica. Como con otras erupciones medicamentosas graves, los linfocitos T específicos para un medicamento tienen una función crucial en el síndrome DRESS. El modelo de hapteno/pro-hapteno, el modelo de interacción farmacológica y el modelo alterado de repertorio de péptidos son tres modelos diferentes desarrollados para describir la relación/interacción entre un medicamento o sus metabolitos y el sistema inmunitario. Analizamos nuestra experiencia con el tratamiento con ciclosporina en un caso de síndrome DRESS resistente a esteroides causado por ácido valproico en una niña y sus resultados clínicos, de laboratorio y de antígeno leucocitario humano (HLA).

Youth suicide and hospital-presenting suicide attempts: Examination of risk factors for multiple suicide attempts in adolescence.

BACKGROUND: The suicide rate among adolescents around the world has increased rapidly. There are many risk factors for attempting suicide, but not all have been clarified yet. Therefore, it is very important to identify risk factors. This study evaluated adolescents with a history of suicide attempts and their association with chronic diseases. Besides, to check whether they attempted suicide multiple times. Other clinical features related to multiple suicide attempts were investigated. METHOD: This study used a multicentre, retrospective cross-sectional design; 253 adolescents admitted to emergency departments in 2019 for suicide attempts were evaluated. RESULTS: Adolescents with chronic disease were at greater risk for both single and multiple suicide attempts and patients had a 6.14 times higher risk of multiple attempts (p = .013). The likelihood of multiple attempts did not differ according to the presence of somatic or psychiatric disease. Multiple attempters were more likely to poison themselves with their therapeutic drugs (p = .002). CONCLUSION: When adolescents with a chronic disease present to the emergency services after a single suicide attempt using their therapeutic drugs, families should be informed regarding the potential for further attempts.

A Rare Cause of Hyperinsulinemic Hypoglycemia: Kabuki Syndrome

Kabuki syndrome (KS) is a disease characterized by distinctive facial features, skeletal anomalies and delay in neuromotor development. KS 1 is an autosomal dominant condition caused by mutations in the KMT2D gene, whereas KS 2 is an X-linked disorder caused by mutations in the KDM6A gene. In the majority of KS patients who present with hypoglycemia, KDM6A is the defective gene. A 9-month old girl was admitted to our emergency department due to a seizure. On physical examination, hypotonia, mild facial dysmorphism, brachydactyly of the 5th finger, prominent finger pads and pansystolic murmur were detected. A fasting glucose tolerance test was performed the next day due to her history of hypoglycemia, but she had convulsions at the fifth hour of the test. Her serum glucose was 24 mg/dL, insulin 1.94 mIU/L, C-peptide 0.94 ng/mL, growth hormone 11 ng/mL, anti-insulin antibody 4.2 IU/mL, cortisol 19.8 µg/dL, and adrenocorticotropic hormone 9.3 pg/mL. A diagnosis of hyperinsulinemic hypoglycemia was considered. Given the abnormalities, genetic analysis for congenital hyperinsulinism, including the genes causing KS was performed. A heterozygous frameshift mutation (c.2579del, p.Leu860Argfs*70) was detected in the KMT2D gene. Epilepsy and other neurological symptoms may be seen in KS patients and in some of these the neurological symptoms are the result of hypoglycemia. In such cases, the detection and prevention of hypoglycemia can help prevent the progression of neurological symptoms. We suggest considering the diagnosis of KS for patients with hypoglycemia and dysmorphic features, even if the patient does not manifest all features of KS.

Type 4 hypersensitivity development in a case due to mifamurtide.

BACKGROUND: This report aims to discuss the mechanism of pleural and pericardial effusion related to mifamurtide which is an immunological agent used as adjuvant chemotherapy in osteosarcoma. CASE: Mifamurtide (2 mg/m < sup > 2 < /sup > ) and European and American Osteosarcoma Studies (EURAMOS) protocol were used together intravenously after complete surgical resection. No side effects occurred except for fever after the first dose. However, pleural, pericardial effusion, and splenic nodule formation began 11 months after discontinuation of mifamurtide treatment. Pleural biopsy revealed a type 4 hypersensitivity reaction. We treated the patient with 1,5 mg per day colchicine. Pericardial effusion attacks and nodules in the spleen disappeared. The patient had a mild pleural effusion attack which has not yet repeated. CONCLUSION: Mifamurtide, which activates macrophages, can also activate immunity with a stand by effect and cause a hypersensitivity reaction.

Neuroleptic malignant syndrome due to risperidone treatment in a child with Joubert syndrome.

Joubert syndrome is a rare autosomal recessive disease characterized by hypotonia, ataxia, episodic hyperpnea, psychomotor retardation, abnormal ocular movements, cerebellar vermian hypoplasia, and molar tooth sign on magnetic resonance imaging. Neuroleptic malignant syndrome is an uncommon and potentially fatal idiosynchratic reaction of antipsychotic drugs, in which the clinical scenario encompass muscular rigidity, hyperthermia, autonomic dysfunction, altered consciousness, high creatinine phosphokinase levels, and leukocytosis. This report describes a case of neuroleptic malignant syndrome due to risperidone in a child with Joubert syndrome.

Posterior Reversible Encephalopathy Syndrome in a Normotensive Child after Allogeneic Hematopoietic Stem Cell Transplantation.

Posterior reversible encephalopathy syndrome (PRES) is an uncommon clinicoradiological syndrome that is characterized by acute neurological symptoms such as headache, convulsion, visual disturbance, and altered consciousness. The characteristic magnetic resonance (MR) finding is vasogenic edema, predominantly in the subcortical areas of the posterior parietal and occipital lobes on T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequences. Herein, we described a rare case of PRES induced by cyclosporine (CsA) after an allogeneic hematopoietic stem cell transplantation (HSCT) from a sibling donor.

Latencies to first interictal epileptiform discharges in different seizure types during video-EEG monitoring.

PURPOSE: Interictal epileptiform discharges (IEDs) have high diagnostic value concerning patients with epilepsy and the instances of obtaining IEDs increase with longer recording times. However, the merit of a single, extended electroencephalography (EEG) recording in detecting IEDs has not been substantiated. We aimed to determine the optimal duration of an EEG required to diagnose epilepsy in different seizure types. METHODS: Overall, 84 patients-29 with generalised onset epilepsy and 55 with focal onset epilepsy-were evaluated. Long-term video electroencephalographic monitoring (VEM) was analysed to find the first definite IED besides assessing the first seizure and latency. RESULTS: The median latency of the first IED (12 min, ranging from 1 to 440 min vs. 55 min, ranging from 2 to 7500 min; p = 0.014) and the median duration of a VEM recording (2 d, ranging from 1 to 10 d vs. 3 d, ranging from 1 to 10 d; p = 0.012) were found significantly lower in the generalised epilepsy group compared with that in the focal epilepsy group. CONCLUSIONS: Generalised onset epilepsy showed a significantly shorter latency to IED and VEM duration compared with focal onset epilepsy. In our data set, all the patients with generalised onset epilepsy had interictal IED within 10 h, but the patients with focal onset epilepsy required monitoring for three days to obtain IED.

Evaluation of the relationship between C677T variants of methylenetetrahydrofolate reductase gene and hyperhomocysteinemia in children receiving antiepileptic drug therapy.

Homocysteine (Hcy) is a sulfur-containing amino acid involved in methionine metabolism. Elevated plasma Hcy concentration is a possible risk factor for vascular disease. Folate and vitamin B-12 are vitamins that are necessary for remethylization of Hcy to methionine. The methylenetetrahydrofolate reductase (MTHFR) is the key enzyme in remethylation of Hcy to methionine and supplies the required 5-methyltetrahydrofolate as the methyl donor for this reaction. It is well known that some antiepileptic drugs (AED) can lead to hyperhomocysteinemia by affecting the levels of folate and vitamin B-12. The C677T variant of MTHFR gene can also lead to hyperhomocysteinemia particularly when serum folate level is decreased. In this study, we investigated the levels of serum folate, vitamin B-12 and Hcy in epileptic patients receiving carbamazepine (CBZ) or valproic acid (VPA) as monotherapy, and we also evaluated the probable contribution of the C677T variant of MTHFR gene in hyperhomocysteinemia. A total of 93 patients with idiopathic epilepsy receiving CBZ or VPA as monotherapy were included in this study. CBZ and VPA groups consisted of 29 and 64 patients, respectively. The control group comprised 62 healthy children. We measured serum folate, vitamin B-12 and Hcy levels in each group. We found that mean serum folate level was statistically lower and mean Hcy level was higher in epileptic patients receiving CBZ or VPA when compared with those of controls'. We also determined the C677T variants of MTHFR gene (as normal, heterozygote or homozygote) in epileptic patients. We compared the variant groups for serum folate, vitamin B-12 and Hcy levels and found no significant differences among them. In conclusion, C677T variants of MTHFR gene have no contribution in hyperhomocysteinemia in epileptic patients receiving CBZ or VPA.