Personalized at-home neurofeedback compared to long-acting methylphenidate in children with ADHD: NEWROFEED, a European randomized noninferiority trial.

BACKGROUND: Neurofeedback is considered a promising intervention for the treatment of attention-deficit hyperactivity disorder (ADHD). NEWROFEED is a prospective, multicentre, randomized (3:2), reference drug-controlled trial in children with ADHD aged between 7 and 13 years. The main objective of NEWROFEED was to demonstrate the noninferiority of personalized at-home neurofeedback (NF) training versus methylphenidate in the treatment of children with ADHD. METHODS: The NF group (n = 111) underwent eight visits and two treatment phases of 16 to 20 at-home sessions with down-training of the theta/beta ratio (TBR) for children with high TBR and enhancing the sensorimotor rhythm (SMR) for the others. The control group (n = 67) received optimally titrated long-acting methylphenidate. The primary endpoint was the change between baseline and endpoint in the Clinician ADHD-RS-IV total score in the per-protocol population (90 NF/59 controls). TRIAL REGISTRATION: US National Institute of Health, ClinicalTrials.gov #NCT02778360. RESULTS: Our study failed to demonstrate noninferiority of NF versus methylphenidate (mean between-group difference 8.09 90% CI [8.09; 10.56]). However, both treatment groups showed significant pre-post improvements in core ADHD symptoms and in a broader range of problems. Reduction in the Clinician ADHD-RS-IV total score between baseline and final visit (D90) was 26.7% (SMD = 0.89) in the NF and 46.9% (SMD = 2.03) in the control group. NF effects increased whereas those of methylphenidate were stable between intermediate and final visit. CONCLUSIONS: Based on clinicians' reports, the effects of at-home NF were inferior to those of methylphenidate as a stand-alone treatment.

Early Brain Activity Relates to Subsequent Brain Growth in Premature Infants.

Recent experimental studies have shown that early brain activity is crucial for neuronal survival and the development of brain networks; however, it has been challenging to assess its role in the developing human brain. We employed serial quantitative magnetic resonance imaging to measure the rate of growth in circumscribed brain tissues from preterm to term age, and compared it with measures of electroencephalographic (EEG) activity during the first postnatal days by 2 different methods. EEG metrics of functional activity were computed: EEG signal peak-to-peak amplitude and the occurrence of developmentally important spontaneous activity transients (SATs). We found that an increased brain activity in the first postnatal days correlates with a faster growth of brain structures during subsequent months until term age. Total brain volume, and in particular subcortical gray matter volume, grew faster in babies with less cortical electrical quiescence and with more SAT events. The present findings are compatible with the idea that (1) early cortical network activity is important for brain growth, and that (2) objective measures may be devised to follow early human brain activity in a biologically reasoned way in future research as well as during intensive care treatment.

Limited usefulness of neurocognitive functioning indices as predictive markers for treatment response to methylphenidate or neurofeedback@home in children and adolescents with ADHD.

Introduction: Earlier studies exploring the value of executive functioning (EF) indices for assessing treatment effectiveness and predicting treatment response in attention-deficit/hyperactivity disorder (ADHD) mainly focused on pharmacological treatment options and revealed rather heterogeneous results. Envisioning the long-term goal of personalized treatment selection and intervention planning, this study comparing methylphenidate treatment (MPH) and a home-based neurofeedback intervention (NF@Home) aimed to expand previous findings by assessing objective as well as subjectively reported EF indices and by analyzing their value as treatment and predictive markers. Methods: Children and adolescents (n = 146 in the per protocol sample) aged 7-13 years with a formal diagnosis of an inattentive or combined presentation of ADHD were examined. We explored the EF performance profile using the Conners Continuous Performance Task (CPT) and the BRIEF self-report questionnaire within our prospective, multicenter, randomized, reference drug-controlled NEWROFEED study with sites in five European countries (France, Spain, Switzerland, Germany, and Belgium). As primary outcome for treatment response, the clinician-rated ADHD Rating Scale-IV was used. Patients participating in this non-inferiority trial were randomized to either NF@home (34-40 sessions of TBR or SMR NF depending on the pre-assessed individual alpha peak frequency) or MPH treatment (ratio: 3:2). Within a mixed-effects model framework, analyses of change were calculated to explore the predictive value of neurocognitive indices for ADHD symptom-related treatment response. Results: For a variety of neurocognitive indices, we found a significant pre-post change during treatment, mainly in the MPH group. However, the results of the current study reveal a rather limited prognostic value of neurocognitive indices for treatment response to either NF@Home or MPH treatment. Some significant effects emerged for parent-ratings only. Discussion: Current findings indicate a potential value of self-report (BRIEF global score) and some objectively measured neurocognitive indices (CPT commission errors and hit reaction time variability) as treatment markers (of change) for MPH. However, we found a rather limited prognostic value with regard to predicting treatment response not (yet) allowing recommendation for clinical use. Baseline symptom severity was revealed as the most relevant predictor, replicating robust findings from previous studies.

Neuroimaging in childhood arterial ischaemic stroke: evaluation of imaging modalities and aetiologies.

AIM: The aim of this study was to describe neuroimaging patterns associated with arterial ischaemic stroke (AIS) in childhood and to differentiate them according to stroke aetiology. METHOD: Clinical and neuroimaging (acute and follow-up) findings were analysed prospectively in 79 children (48 males, 31 females) aged 2 months to 15 years 8 months (median 5 y 3 mo) at the time of stroke by the Swiss Neuropaediatric Stroke Registry from 2000 to 2006. RESULTS: Stroke was confirmed in the acute period in 36 out of 41 children who underwent computed tomography, in 53 of 57 who underwent T2-weighted magnetic resonance imaging (MRI) and in all 48 children who underwent diffusion-weighted MRI. AIS occurred in the anterior cerebral artery (ACA) in 63 participants and in all cases was associated with lesions of the middle cerebral artery (MCA). The lesion was cortical-subcortical in 30 out of 63 children, cortical in 25 out of 63, and subcortical in 8 of 63 children. Among participants with AIS in the posterior circulation territory, the stroke was cortical-subcortical in 8 out of 16, cortical in 5 of 16, and thalamic in 3 out of 16 children. INTERPRETATION: AIS mainly involves the anterior circulation territory, with both the ACA and the MCA being affected. The classification of Ganesan is an appropriate population-based classification for our Swiss cohort, but the neuroimaging pattern alone is insufficient to determine the aetiology of stroke in a paediatric population. The results show a poor correlation between lesion pattern and aetiology.

Current incidence of acute neurologic complications after open-heart operations in children.

BACKGROUND: Previously, neurologic dysfunction was estimated to complicate 25% or less of pediatric open-heart operations. We sought to determine the current incidence and spectrum of early postoperative neurologic complications. METHODS: We undertook a retrospective review of all patients undergoing open heart operations in 1 year at our institution with the goal to identify all neurologic complications occurring in the early postoperative period. RESULTS: Open-heart operations were performed in 706 children. Sixteen children (2.3%) had neurologic complications develop, including 9 (1.3%) with definite clinical seizures, 1 with suspected seizures and bilateral subdural hemorrhage, 2 with coma after cardiac arrest, 2 with transient mild choreoathetosis, 1 with facial palsy, and 1 with persistent irritability. Causes of seizure were cyclosporin A toxicity posttransplant (4), cerebral ischemia post cardiac arrest (3), and unknown (2). In infants less than 1 year of age, the incidence of seizures was 1.2%. CONCLUSIONS: This review suggests a decrease in acute neurologic morbidity after pediatric open heart operation. Clinical seizures remain the most common complication. Posttransplant, cyclosporin-associated seizures have emerged as an important etiologic category, coincident with an increase in cardiac transplantation in children.

Prognostic value of neonatal discontinuous EEG.

The burst suppression pattern on the neonatal electroencephalogram (EEG) is associated with a poor outcome. However, this serious abnormality constitutes only a small proportion of discontinuous neonatal EEGs. We sought to establish whether any easily measurable parameters among the broad range of excessively discontinuous neonatal EEGs are predictive of outcome. We retrospectively reviewed the EEGs and medical records of 43 term infants with excessively discontinuous EEGs. We quantitated 10 parameters in the bursts and interburst intervals, among them the predominant interburst interval duration (defined as the duration of more than 50% of all interburst intervals of an EEG). Univariate and multivariate analyses were performed on the 10 EEG variables in relation to neurologic outcome and subsequent epilepsy. Based on multivariate analysis, a single easily measurable EEG parameter related significantly to outcome. A predominant interburst interval duration of more than 30 seconds correlated with the occurrence of both unfavorable neurologic outcome and subsequent epilepsy (P = 0.040 and P = 0.033, respectively). In conclusion, a infant whose EEG contains a predominant interburst interval duration of more than 30 seconds has a 100% probability of experiencing severe neurologic disabilities or death and an 86% chance of developing subsequent epilepsy. This easily quantitated EEG parameter could be valuable for the early estimation of neurologic prognosis.

Anesthesia management in a young child with aromatic l-amino acid decarboxylase deficiency.

Aromatic l-amino acid decarboxylase (AADC) deficiency is characterized by an almost complete absence of sympathetic autoregulation, because of very low levels of circulating catecholamines. Here, we report the successful management of four consecutive anesthesia procedures in a young child presenting with AADC deficiency. Our experience suggests that, with appropriate anticipation of the potential autonomic disturbances, anesthesia, at least for minor surgical and diagnostic procedures, can be conducted safely in patients with AADC deficiency.

Prolonged treatment for acute symptomatic refractory status epilepticus: outcome in children.

High-dose suppressive therapy (HDST) is used to treat refractory status epilepticus (RSE). Prolonged therapy is required in some cases, and prognosis is important in making therapeutic decisions. The authors therefore studied the long-term outcome in previously normal children who survived prolonged HDST for acute symptomatic RSE. All have intractable epilepsy, and none returned to baseline.