Teriflunomide in pediatric patients with relapsing multiple sclerosis: Open-label extension of TERIKIDS.

BACKGROUND: The double-blind TERIKIDS study demonstrated the efficacy and safety of teriflunomide. OBJECTIVE: To evaluate the efficacy, safety, and tolerability of continuous teriflunomide treatment in the TERIKIDS open-label extension. METHODS: In the double-blind period, children with relapsing MS were randomized to placebo or teriflunomide (14 mg adult-equivalent dose) for ⩽ 96 weeks. Participants received teriflunomide for ⩽ 192 weeks post-randomization in the open-label extension. RESULTS: The mean age at screening was 14.6 years. For teriflunomide/teriflunomide versus placebo/teriflunomide, estimated clinical relapse risk was reduced by 38% (hazard ratio (HR) 0.62; 95% confidence interval (CI) 0.39-0.98; p = 0.11) and numbers of gadolinium-enhancing T1 and new/enlarging T2 lesions were reduced by 43% (relative risk (RR) 0.570; 95% CI 0.33-0.98; p = 0.043) and 49% (RR 0.511; 95% CI 0.34-0.76; p = 0.001), respectively, in the combined double-blind and open-label periods. There was a trend toward reduced risk of 24-week sustained disability progression for teriflunomide/teriflunomide versus placebo/teriflunomide (HR 0.47; 95% CI 0.23-0.96). During the open-label extension, incidences of safety-related discontinuations were 4.0% (teriflunomide/teriflunomide) and 13.5% (placebo/teriflunomide), including two children who developed pancreatitis in the teriflunomide/teriflunomide group. CONCLUSION: Teriflunomide reduced the long-term risk of focal inflammatory activity, with generally manageable tolerability and no new safety signals. Further evidence would strengthen clinical efficacy findings.ClinicalTrials.gov: NCT02201108.

Evaluation of neurocognitive and social developments after craniosynostosis surgery.

OBJECTIVE: The study focused on assessing the potential neurocognitive and social developmental issues in children with non-syndromic craniosynostosis (NSC) who received optimal surgical treatment. The primary objective was to determine whether NSC, even after optimal surgical treatment, could have negative effects on brain development. METHODS: The study included a total of 73 pediatric patients aged between 2 and 6 years who had previously undergone surgery for NSC at the Gazi University Faculty of Medicine, Department of Neurosurgery. These patients were carefully matched with 107 healthy children who visited the outpatient clinic of the same department in terms of sociodemographic characteristics such as age, gender, and social status. To assess the neurocognitive and social development of the participants, the child psychologist administered a developmental scale to the child and his/her family via video conference. This scale was adapted from the Bayley-III Infant and Child Development Scale by the Gazi University Faculty of Medicine, Division of Pediatric Neurology. RESULTS: The study found no social or gross motor developmental issues in patients who had undergone optimal surgical treatment for NSC. However, the risk of fine motor developmental deficiencies was 4.79 times higher than that of the normal population, and the risk of language developmental deficiencies was 5.75 times higher than that of the normal population. CONCLUSIONS: Despite timely treatment of NSC, long-term neurocognitive and social development issues may arise in affected children. Therefore, it is crucial to monitor these patients after completing surgical treatment and thoroughly examine their development using a multidisciplinary approach.

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.

Using the center of pressure movement analysis in evaluating spontaneous movements in infants: a comparative study with general movements assessment.

BACKGROUND: Researchers have attempted to automate the spontaneous movement assessment and have sought quantitative and objective methods over the past decade. The purpose of the study was to present a quantitative assessment method of spontaneous movement using center-of-pressure (COP) movement analysis. METHODS: A total of 101 infants were included in the study. The infants were placed in the supine position on the force plate with the cranial-caudal orientation. In this position, the recording of video and COP movement data were made simultaneously for 3 min. Video recordings were used to observe global and detailed general movement assessment (GMA), and COP time series data were used to obtain quantitative movement parameters. RESULTS: According to the global GMA, 13 infants displayed absent fidgety movements (FMs) and 88 infants displayed normal FMs. The binary logistic regression model indicated significant association between global GMA and COP movement parameters (chi-square = 20.817, p < 0.001). The sensitivity, specificity, and overall accuracy of this model were 85% (95% CI: 55-98), 83% (95% CI: 73-90), and 83% (95% CI: 74-90), respectively. The multiple linear regression model showed a significant association between detailed GMA (motor optimality score-revised/MOS-R) and COP movement parameters (F = 10.349, p < 0.001). The MOS-R total score was predicted with a standard error of approximately 1.8 points (6%). CONCLUSIONS: The present study demonstrated the possible avenues for using COP movement analysis to objectively detect the absent FMs and MOS-R total score in clinical settings. Although the method presented in this study requires further validation, it may complement observational GMA and be clinically useful for infant screening purposes, particularly in clinical settings where access to expertise in observational GMA is not available.

Effects of caffeine therapy for apnea of prematurity on sleep and neurodevelopment of preterm infants at 6 months of corrected age.

STUDY OBJECTIVES: To determine the differences in sleep patterns between preterm infants who received caffeine and those who did not and to evaluate the effects of caffeine therapy on early neurodevelopment. Secondarily, actigraphy and polysomnography were compared to evaluate the sleep of preterm infants. METHODS: Twenty-eight preterm infants ages 28-34 weeks admitted to a single-center Level III neonatal intensive care unit between May 2020 and May 2021 were included. Sleep was assessed by actigraphy for 72 hours with Respironics Mini-Mitter® Actiwatch-2 and Brief Infant Sleep Questionnaire at 6 months corrected age. On the first day of actigraphy, infants underwent polysomnography between 10:00 am and 3:00 pm. Neurodevelopment was evaluated by the Bayley Scales of Infant and Toddler Development-III, the Ages & Stages Questionnaire, and the Hammersmith Infant Neurological Examination. RESULTS: There were no significant differences in sleep parameters measured by actigraphy, the Brief Infant Sleep Questionnaire, and polysomnography between infants in the caffeine group (n = 12) and no-caffeine group (n = 16). Sensitivity (91.07%) and agreement rate (77.21%) for the actigraphy against polysomnography were highest at the automatic threshold. No significant differences were observed in the neurodevelopment of infants in the caffeine group compared to the no-caffeine group. CONCLUSIONS: Sleep parameters and neurodevelopmental outcomes were not different in infants at 6 months of corrected age with regard to caffeine therapy. Actigraphy at the automatic threshold can be used in infants for sleep pattern assessment. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Influence of Caffeine Therapy in Preterm Infants; URL: https://www.clinicaltrials.gov/ct2/show/NCT04376749; Identifier: NCT04376749. CITATION: Atalah YEY, Baris HE, Akdere SK, et al. Effects of caffeine therapy for apnea of prematurity on sleep and neurodevelopment of preterm infants at 6 months of corrected age. J Clin Sleep Med. 2023;19(12):2075-2085.

Short-term effects of SAFE early intervention approach in infants born preterm: A randomized controlled single-blinded study.

OBJECTIVE: Recent literature suggests that goal-oriented and family-based interventions in enriched environment have a beneficial effect on neuromotor and cognitive development. We aimed to examine the short-term effects of SAFE (Sensory strategies, Activity-based motor training, Family collaboration, and Environmental Enrichment) early intervention approach on motor, cognitive, speech and language, and sensory development in preterm infants. METHODS: The study's sample population consisted of 24 preterm infants with corrected ages between 9 and 10 months. Infants in the control group participated in the family training program in accordance with the neurodevelopmental therapy principles (NDT). Infants in the treatment group were included in the family training program according to the principles of the SAFE Early Intervention Approach. Affordances in the Home Environment for Motor Development-Infant Scale (AHEMD-IS), Test of Sensory Functions in Infants (TSFI), Canadian Occupational Performance Measure (COPM), and Bayley Scales of Infant and Toddler Development III (Bayley III) were used to evaluate infants in both groups before and after 10 weeks of treatment (AHEMD-IS). The Depression, Anxiety, Stress Scale Short Form was used to assess the parents' mental health (DASS-SF). RESULTS: The interaction effects (time × group) revealed significant differences for Bayley-III cognitive and language scores, TSFI total score, and AHEMD-IS total score in favor of the SAFE group (p < .05). However, there were no differences in Bayley-III motor composite score, COPM Performance score, and COPM Satisfaction score between the interaction effects (time × group) of the groups (p > .05). CONCLUSIONS: SAFE early intervention approach improved cognitive, speech and language, sensory outcomes and provide enriched home environment in all domains when compared to NDT-based home program. SAFE is a promising novel early intervention approach for preterm infants.

Celiac disease and catatonia: more than a coincidence?

BACKGROUND: Catatonia is a complex neuropsychiatric disorder involving stupor, waxy flexibility, and mutism lasting more than 1 hour. It has arisen mostly from mental and neurologic disorders. Organic causes are more prominent in children. CASE: A 15-year-old female who had refused to eat and drink for 3 days, had not talked, and had stood in a fixed position for long periods was admitted to the inpatient clinic, and she was diagnosed with catatonia. Her maximum score on the Bush-Francis Catatonia Rating Scale (BFCRS) was 15/69 on day 2 of her stay. On neurologic examination, the patient`s cooperation was limited, and she was apathetic to her surroundings and stimuli and inactive. Other neurologic examination findings were normal. To investigate catatonia etiology, her biochemical parameters, thyroid hormone panel, and toxicology screening were conducted but all parameters were normal. Cerebrospinal fluid examination and autoimmune antibodies were negative. Sleep electroencephalography showed diffuse slow background activity, and brain magnetic resonance imaging was normal. As a first-line treatment for catatonia, diazepam was started. With her poor response to diazepam, we continued to evaluate the cause and found the transglutaminase levels were 153 U/mL (normal values, < 10 U/mL). The patient`s duodenal biopsies showed changes consistent with Celiac disease (CD). Catatonic symptoms did not benefit from a gluten-free diet or oral diazepam for 3 weeks. Then, diazepam was replaced with amantadine. With amantadine, the patient recovered within 48 hours, and her BFCRS retreated to 8/69. CONCLUSIONS: Even without gastrointestinal manifestations, CD may present with neuropsychiatric symptoms. According to this case report, CD should be investigated in patients with unexplained catatonia, and that CD may only present with neuropsychiatric symptoms.

ALG11-CDG: novel variant and review of the literature.

OBJECTIVES: Asparagine-dependent glycosylation 11-congenital disorders of glycosylation (ALG11-CDG) is a rare autosomal recessive N-glycosylation defect with multisystem involvement particularly neurological symptoms such as epilepsy and neuromotor developmental delay. CASE PRESENTATION: A 31-month-old male patient admitted to our center with complaints of axial hypotonia, drug-resistant myoclonic seizures, microcephaly and deafness. The electroencephalography (EEG) showed a burst-suppression pattern without hypsarrhythmia. Basal metabolic investigations were unremarkable. Progressive cerebral atrophy, hypomyelination and corpus callosum hypoplasia were striking features in brain MRI images taken during our follow-up. Compound heterozygous mutations of the ALG11 gene were found by whole exome sequencing (WES) analysis. It was determined that the c.476T>C mutation is a novel mutation. CDG type 1 pattern was detected with the examination of carbohydrate-deficient transferrin (CDT) by capillary zone electrophoresis. CONCLUSIONS: In patients with a possible congenital defect of glycosylation, a screening test such as CDT analysis is suggested. To discover novel mutations in this rare disease group, expanded genetic analysis should be performed.

Sleep assessment in preterm infants: Use of actigraphy and aEEG.

OBJECTIVE: Objective methods to monitor the sleep of preterm infants at the neonatal intensive care unit (NICU) are required to prevent potentially adverse neurodevelopmental outcomes. This study aimed to determine the concordance of actigraphy and amplitude-integrated electroencephalogram (aEEG) against gold standard direct observation (DO) in assessing sleep/wake states of typically developing preterm infants. METHODS: This prospective observational study was conducted in a single center level III NICU. Sleep variables were measured using Philips Respironics Mini-Mitter® Actiwatch-2 for 24 h and compared with 8-h matched data of aEEG and DO. Sensitivity-specificity analysis, Cohen's kappa, prevalence-adjusted and bias-adjusted kappa (PABAK), and Bland Altman plots were generated. RESULTS: Seventeen preterm infants were recruited. A total of 11252 epochs were studied. Sensitivity (86.4%), agreement rate (67.9%), and predictive value for wake (47.9%) for the actigraphy were highest at the automatic activity threshold whereas specificity (54.5%) and predictive value for sleep (75.5%) were highest at low threshold. The sensitivity of aEEG was 79.3% and the specificity was 54.3%. At all thresholds, the agreement was largely equivalent with low kappas (0.14-0.17) and PABAK coefficients (0.22-0.35) for actigraphy and DO. Moderate agreement was observed between aEEG and DO according to the PABAK coefficient (0.44). Mean differences in sleep parameters were not different between DO and aEEG as well as DO/aEEG and actigraphy at medium threshold (p > 0.05). CONCLUSIONS: Actigraphy at medium threshold can be used in depicting sleep in typically developing preterm infants at NICU. aEEG may be an alternative adjunctive method to actigraphy for the evaluation of sleep/wake states in the NICU setting. CLINICAL TRIAL REGISTRATION NUMBER: NCT04145362.

The effect of apoprotein E gene polymorphism on neurocognitive functions of children with CHD.

Studies have demonstrated an association between CHD and neurodevelopmental delay. This delay is associated with many factors like reduced blood flow and oxygen, cardiac catheterisations, and genetic factors. Apo E gene polymorphism is one of these genetic factors. This study aims to show the effect of Apo E gene polymorphism on neurodevelopmental process in children having CHD. A total of 188 children having CHD were admitted to the study. Apo E gene polymorphism of these patients was determined, and psychometric evaluation was performed. The relationship between psychometric test results and gene polymorphism was evaluated. This study shows that, similar to the literature, patients having cyanotic CHD have worse scores than acyanotic patients, and the children with CHD are under risk in terms of neuropsychiatric disorders. Other novel and important findings of this study were the lower verbal scores of ε2 allele carriers than ε4 carriers in Wechsler Intelligence Scale for Children-Revised group and the worse test score of patients having VSD than other acyanotic patients. Besides, some special disorders may be seen in this patient group.

Ultrasensitive Determination of Glial-Fibrillary-Acidic-Protein (GFAP) in Human Serum-Matrix with a Label-Free Impedimetric Immunosensor.

In this work, immobilizing anti-GFAP antibodies via covalent attachment onto L-cysteine/gold nanoparticles that were modified with screen-printed carbon electrodes (Anti-GFAP/L-cys/AuNps/SPCE) resulted in the development of a sensitive label-free impedance immunosensor for the detection of Glial Fibrillary Acidic Protein (GFAP). The immunosensor's stepwise construction was studied using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). L-cysteine was chosen as the linker between GFAP antibodies and Au NPs/SPCE because it enables the guided and stable immobilization of GFAP antibodies, thus resulting in increased immunosensor sensitivity. As a redox probe, 5 mM of [Fe(CN)6]3-/4- was used to measure the electron-transfer resistance (Ret), which was raised by the binding of antigens to the immobilized anti-GFAP on the surface of the modified electrode. A linear correlation between Rct and GFAP concentration was achieved under optimum conditions in the range of 1.0-1000.0 pg/mL, with an extraordinarily low detection limit of 51.0 fg/mL. The suggested immunosensor was successfully used to detect the presence of GFAP in human blood serum samples, yielding good findings. As a result, the proposed platform may be utilized to monitor central nervous system injuries.

Re-examining the characteristics of pediatric multiple sclerosis in the era of antibody-associated demyelinating syndromes.

BACKGROUND: The discovery of anti-myelin oligodendrocyte glycoprotein (MOG)-IgG and anti-aquaporin 4 (AQP4)-IgG and the observation on certain patients previously diagnosed with multiple sclerosis (MS) actually have an antibody-mediated disease mandated re-evaluation of pediatric MS series. AIM: To describe the characteristics of recent pediatric MS cases by age groups and compare with the cohort established before 2015. METHOD: Data of pediatric MS patients diagnosed between 2015 and 2021 were collected from 44 pediatric neurology centers across Türkiye. Clinical and paraclinical features were compared between patients with disease onset before 12 years (earlier onset) and ≥12 years (later onset) as well as between our current (2015-2021) and previous (<2015) cohorts. RESULTS: A total of 634 children (456 girls) were enrolled, 89 (14%) were of earlier onset. The earlier-onset group had lower female/male ratio, more frequent initial diagnosis of acute disseminated encephalomyelitis (ADEM), more frequent brainstem symptoms, longer interval between the first two attacks, less frequent spinal cord involvement on magnetic resonance imaging (MRI), and lower prevalence of cerebrospinal fluid (CSF)-restricted oligoclonal bands (OCBs). The earlier-onset group was less likely to respond to initial disease-modifying treatments. Compared to our previous cohort, the current series had fewer patients with onset <12 years, initial presentation with ADEM-like features, brainstem or cerebellar symptoms, seizures, and spinal lesions on MRI. The female/male ratio, the frequency of sensorial symptoms, and CSF-restricted OCBs were higher than reported in our previous cohort. CONCLUSION: Pediatric MS starting before 12 years was less common than reported previously, likely due to exclusion of patients with antibody-mediated diseases. The results underline the importance of antibody testing and indicate pediatric MS may be a more homogeneous disorder and more similar to adult-onset MS than previously thought.

Assisting dementia diagnosis through the electrochemical immunosensing of glial fibrillary acidic protein.

Glial fibrillary acidic protein (GFAP) is a member of the intermediate filament family of proteins with increased levels in serum and cerebrospinal fluid of patients with Alzheimer disease (AD) and other neurodegenerative diseases (NDs), such as vascular dementia (VD). This work describes the first magnetic microbeads (MBs)-based electrochemical immunoplatform for GFAP determination. The platform design comprises a sandwich immunoassay implemented on the MBs surface and amperometric transduction at single-use screen-printed carbon electrodes (SPCEs). Micro-sized carboxylic acid magnetic particles (COOH-MBs) were modified with a specific capture antibody (CAb) to selectively link the target protein, which was sandwiched with a biotinylated detector antibody (btn-DAb) further conjugated with a streptavidin-peroxidase (Strep-HRP) conjugate. Amperometric transduction was performed at SPCEs upon capturing the magnetic bioconjugates on their surface and through the hydrogen peroxide/hydroquinone (H2O2/HQ) system. The immunoplatform achieved a limit of detection of 67 pg mL-1 for the amperometric detection of standards and selectivity compatible with clinical applicability to assist in minimally invasive NDs diagnosis and prognosis. The MBs-based immunoplatform was applied with good results to determine the endogenous content of GFAP in protein brain extracts without matrix effect and using just 6.25 ng of sample per determination. Furthermore, the developed methodology was capable of differentiating between healthy subjects and patients diagnosed with VD and AD in only 2 h, providing accurate results in line with those obtained by an ELISA kit that used the same immunoreagents.

Turkish Validity and Reliability of the Hammersmith Infant Neurological Examination (HINE) with High-Risk Infant Group: A Preliminary Study.

OBJECTIVE: The purpose of this study was to establish the reliability of the Turkish translation of the Hammersmith Infant Neurological Examination in infants at 8-12 months corrected age and compare Hammersmith Infant Neurological Examination scores to other predictive assessments. MATERIALS AND METHODS: Perinatal risk factors, term-age magnetic resonance imaging, general movements at 3-month corrected age, and 12-month corrected age The Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) scores were obtained in 35 high-risk infants. The Hammersmith Infant Neurological Examination was evaluated using intra-rater and interrater reliability. Hammersmith Infant Neurological Examination scores were compared to the findings from the three other assessments. RESULTS: Intra-rater and inter-rater reliability was high (intraclass correlation coefficient = 1.00; intraclass correlation coefficient = 0.969, P < .001, 95% CI = 0.939-0.984, respectively). Global Hammersmith Infant Neurological Examination scores were significantly lower in infants with magnetic resonance imaging evidence of brain injury than without (P < .05) and in infants without general movements Fidgety movements (P < .05), than with. There was a significant positive correlation between global Hammersmith Infant Neurological Examination scores and Bayley Scales-III cognitive (P < .001), language (P < .001), and motor composite scores (P < .001). CONCLUSION: This study strongly supports the use of the Turkish translation of the Hammersmith Infant Neurological Examination. Users found it readily understandable and easy to use, and the scores were consistent with 3 different methods of predicting neurodevelopmental outcomes. These findings will aid the early diagnosis, management, and support for children with neurodevelopmental problems.

Psychosis: a rare onset symptom of pediatric multiple sclerosis.

Neuropsychiatric symptoms are common in multiple sclerosis (MS), but it is rarely associated with psychosis as the initial manifestation. Fourteen-year-old boy admitted with auditory hallucinations. His neurological examination was normal. Brain magnetic resonance imaging (MRI) showed multiple demyelinating lesions in the mesencephalon and periventricular regions. His IgG index was high and the oligoclonal band was positive. MS was diagnosed and pulsed corticosteroids were given and his psychotic symptoms regressed. After 22months, the patient presented with hemi-hypoesthesia, and repeated MRI showed new contrast enhancing lesion detected. His complaints completely resolved with pulse corticosteroid therapy. Increasing morbidity due to delay in MS treatment underlines the need to consider MS in the differential diagnosis of pediatric cases presenting with psychosis.

Safety and efficacy of teriflunomide in paediatric multiple sclerosis (TERIKIDS): a multicentre, double-blind, phase 3, randomised, placebo-controlled trial.

BACKGROUND: Therapeutic options for children with multiple sclerosis are scarce. Teriflunomide is approved in more than 80 countries for the treatment of adults with relapsing multiple sclerosis. The TERIKIDS study examined the safety and efficacy of teriflunomide in children with relapsing multiple sclerosis. METHODS: The TERIKIDS trial was a multicentre, phase 3, double-blind, parallel-group, randomised, placebo-controlled study conducted at 57 clinical centres in 22 countries in Asia, Europe, the Middle East, North Africa, and North America. The trial enrolled patients aged 10-17 years, diagnosed with relapsing multiple sclerosis and with at least one relapse in the year preceding screening or at least two relapses in the 2 years preceding screening. Patients were randomly assigned (2:1) to oral teriflunomide (dosage equivalent to 14 mg in adults) or matching placebo, using an interactive web and voice response system, for up to 96 weeks. Personnel in all sites and all patients were masked to study treatment in the double-blind period. Early entry into a subsequent 96-week open-label extension phase was possible before the end of the double-blind period for patients with confirmed clinical relapse or high MRI activity (at least five new or enlarged T2 lesions at week 24, followed by at least nine new or enlarged T2 lesions at week 36, or at least five new or enlarged T2 lesions at weeks 36 and 48, or at weeks 48 and 72). The primary endpoint was time to first confirmed clinical relapse by the end of the double-blind period. Key secondary imaging endpoints were number of new or enlarged T2 lesions and number of gadolinium-enhancing lesions per MRI scan. Efficacy endpoints were analysed in the intention-to-treat population, and safety was assessed in all patients randomly assigned to treatment and exposed to the double-blind study medication. This study is registered with ClinicalTrials.gov (trial number NCT02201108) and is closed to recruitment, but an additional optional open-label extension is ongoing. FINDINGS: Between July 24, 2014, and the date of last patient visit on Oct 25, 2019, 185 patients were screened for eligibility, 166 (90%) were enrolled, and 109 were randomly assigned teriflunomide and 57 were randomly assigned placebo. 102 (94%) of 109 and 53 (93%) of 57 completed the double-blind period. Switch to the ongoing open-label extension because of high MRI activity was more frequent than anticipated in the placebo group (14 [13%] of 109 patients in the teriflunomide group vs 15 [26%] of 57 in the placebo group), decreasing the power of the study. After 96 weeks, there was no difference in time to first confirmed clinical relapse with teriflunomide compared with placebo (hazard ratio 0·66, 95% CI 0·39-1·11; p=0·29). Teriflunomide reduced the number of new or enlarged T2 lesions versus placebo by 55% (relative risk 0·45, 95% CI 0·29-0·71; p=0·00061), and the number of gadolinium-enhancing lesions by 75% (relative risk 0·25, 0·13-0·51; p<0·0001). Adverse events occurred in 96 (88%) patients in the teriflunomide group and 47 (82%) patients in the placebo group; serious adverse events occurred in 12 (11%) patients in the teriflunomide group and 6 (11%) patients in the placebo group. Nasopharyngitis, upper-respiratory-tract infection, alopecia, paraesthesia, abdominal pain, and increased blood creatine phosphokinase were more frequent with teriflunomide than with placebo. During the double-blind phase, four patients in the teriflunomide group had pancreatic adverse events (two with acute pancreatitis and two with pancreatic enzyme elevation), of which three events led to treatment discontinuation. INTERPRETATION: No significant difference in time to first confirmed clinical relapse was found, possibly because more patients than expected switched from the double-blind to the open-label treatment period because of high MRI activity. Key secondary imaging analyses and a prespecified sensitivity analysis of probability of relapse or high MRI activity suggest that teriflunomide might have beneficial effects in children with relapsing multiple sclerosis by reducing the risk of focal inflammatory activity. FUNDING: Sanofi.

The use of neuroimaging, Prechtl's general movement assessment and the Hammersmith infant neurological examination in determining the prognosis in 2-year-old infants with hypoxic ischemic encephalopathy who were treated with hypothermia.

BACKGROUND: The use of neuroimaging, the General Movement Assessment (GMA), and the Hammersmith Infant Neurological Examination (HINE) to identify the risk of neurodevelopmental delay in early infancy is recommended. AIM: The aim of this study was to examine the predictive power of neuroimaging, GMA and HINE for neurodevelopmental delay and cerebral palsy (CP) in infants with hypoxic ischemic encephalopathy (HIE) who were treated with hypothermia. STUDY DESIGN: Retrospective cohort. SUBJECTS AND OUTCOME MEASURES: This retrospective study included 47 (18 female and 29 male) infants who were treated with hypothermia due to HIE. Neonates with a diagnosis of HIE were followed and assessed using neuroimaging, GMA, HINE and the Bayley Scales of Infant and Toddler Development-II (Bayley II) between 3 m and 2 years of age. RESULTS: Out of the 47 infants with HIE, no fidgety movements were observed in 5 infants. The sensitivity and specificity in determining the psychomotor developmental index (PDI) score were 97% and 100%, respectively, for MRI; 92.9% and 100% for GMA; and 91.9% and 80% for the HINE. The sensitivity and specificity in determining the mental developmental index (MDI) score were 95% and 85.7%, respectively, for MRI; 90.5% and 80% for GMA; and 91.9% and 50% for HINE. The sensitivity and specificity in determining CP diagnosis at the age of 2 years were 83.3% and 95%, respectively, for MRI; 83.3% and 100% for GMA; and 83.3% and 87.8% for HINE. CONCLUSION: The interpretation of MRI, GMA, and HINE that are performed within the early period of life may be the gold standard for the early detection of neurodevelopmental risks in 2-year-old infants with HIE. Clinical implementation of these methods in the early period in the follow-up of these infants offers useful information for the early identification of neurodevelopmental risk and for planning early intervention.

Influence of Intensive Care Unit Enlightenment on Premature Infants on Functional Brain Maturation Assessed by Amplitude-Integrated Electroencephalograph.

OBJECTIVE: Amplitude-integrated electroencephalograph (aEEG) presents a valuable tool for functional brain maturation of preterm infants. However, the effect of enlightenment on functional brain maturation of premature infants has not been investigated. We aimed to do this with aEEG. STUDY DESIGN: A total of 32 infants, 30 to 35 gestational weeks, were involved in the study. They were randomly distributed into three groups in which different lighting protocols were applied. In group 1, the infants' incubators were covered for 24 hours. In group 2, the infants' incubators were open for 24 hours. In group 3, the infants' incubators were covered for 12 hours and open for another 12 hours. The infants are evaluated with aEEG recordings done on the 3rd (first measurement) and 10th days (second measurement) along with the Burdjalov scoring. Analysis of aEEG recordings was performed, based on sleep-wake cycles (SWCs), upper and lower margin amplitudes, narrowband and broadband of SWC, and bandwidth of SWC. RESULTS: At first, the narrowband lower amplitudes in group 1 were higher than those of the other groups (p = 0.042), but the difference was not significant in the second measurement (p = 0.110). The Burdjalov scores were higher in group 1 and group 3 on 10th day, though not statistically significant (p = 0.871). When the infants were re-evaluated according to the gestational weeks, the Burdjalov scores of the two groups less than 34 weeks (30-31 and 32-33 weeks) were similar, whereas 34 to 35 weeks were higher when compared with those of the two groups. CONCLUSION: The difference observed between groups in terms of narrowband lower amplitude in the first measurement may reflect the effect of intrauterine environment rather than enlightenment at the same gestational age because it was made on the third day. However, the fact that all groups have similar results on day 10 suggests that other factors in the intensive care setting may diminish the effect of enlightenment. Burdjalov scores are associated with maturation, and high scores found in the 34- to 35-week group suggest that the 34-week maturation might be a threshold for SWC and development in our group sample.

Evaluation of state and trait anxiety levels of parents and children before electroencephalography procedures: A prospective study from a tertiary epilepsy center.

BACKGROUND: Inadequate or misinformation about electroencephalography (EEG) and epilepsy may lead to anxiety in children and their parents. The purpose of this study was to make a simultaneous evaluation of the anxiety levels of children and parents before EEG procedures and to make a brief assessment of their knowledge about EEG. METHODS AND MATERIALS: Children aged between 8 and 18 years who were referred for EEG tests at Department of Pediatric Neurology, Gazi University Faculty of Medicine, Ankara, Turkey and their parents were included in the study, prospectively. Data were collected through Personal Information Forms; an EEG questionnaire form, which questioned the knowledge of the participants about EEG; the Spielberger's State-Trait Anxiety Inventory (STAI) to determine anxiety levels of the parents; and the State-Trait Anxiety Inventory for Children-State form (STAIC) to determine the anxiety levels of the children. The following parameters were collected in a database: demographic data about children and parents (sex, age), indication of suspected diagnosis on EEG request (i.e., the referral diagnosis), history of epilepsy, number of EEG recordings, and results of previous EEG recordings. The state and trait anxiety test results of the children were compared between the girls and boys, between age groups, and their parents' results in terms of both trait and state anxiety in terms of EEG, sex, ages, educational levels, and working. RESULTS: Eighty-five children (mean age: 13.25 ±â€¯3.02 years) and 85 parents (mean age: 41.16 ±â€¯7.65 years) were included in the study. The children's mean trait anxiety score was 32.51 ±â€¯8.09, and the mean state anxiety score was 34.97 ±â€¯7.62. Half of the children who had a trait anxiety score of ≤30 points had increased state anxiety levels because they received more than 30 points in the state anxiety evaluation score. No significant differences were found between the boys and girls in terms of the state and trait anxiety scores (p > 0.05). The parents' mean trait anxiety score was 39.16 ±â€¯7.74, and the mean state anxiety score was 42.74 ±â€¯6.22. Forty (47%) parents were found to have trait anxiety, and 52 (61.2%) parents had state anxiety before the EEG. The trait anxiety score of the mothers was statistically significantly higher than that of the fathers (p < 0.01). The investigation of the knowledge level of both parents and children about EEG demonstrated some misunderstandings or points of insufficiency. CONCLUSION: The present study revealed that both parents and children had insufficient knowledge about EEG, and the procedure caused anxiety for both the parents and children. When EEG procedures are requested, parents and children should be given brief information about EEG and epilepsy. We think that in this way, the knowledge of both parents and children about this issue may be increased and their anxiety may be decreased.