Sleep in children triggers rapid reorganization of memory-related brain processes.

Behavioral evidence shows that sleep is crucial for the consolidation of declarative memories in children as in adults. However, the underlying cerebral mechanisms remain virtually unexplored. Using magnetoencephalography, we investigated in children (8.0-12.5years) the impact of sleep (90-minute nap) on the neurophysiological processes underlying the creation and consolidation of novel associations between unknown objects and their functions. Learning-dependent changes in brain activity were observed within hippocampal and parahippocampal regions, followed by sleep-dependent changes in the prefrontal cortex, whereas no equivalent change was observed after a similar period of wakeful rest. Hence, our results show that in school-age children a 90-minute daytime nap after learning is sufficient to trigger the reorganization of memory-related brain activity toward prefrontal areas, where it incorporates into pre-existing semantic knowledge. This functional reorganization process in children is similar to that observed in adults but occurs at a much faster rate, which may contribute to the development of the impressive learning skills that characterize childhood.

Cognitive Improvement of Attention and Inhibition in the Late Afternoon in Children With Attention-Deficit Hyperactivity Disorder (ADHD) Treated With Osmotic-Release Oral System Methylphenidate.

Long-acting medications have been developed and approved for use in the treatment of attention-deficit hyperactivity disorder (ADHD). These compounds are intended to optimize and maintain symptoms control throughout the day. We tested prolonged effects of osmotic-release oral system methylphenidate on both attention and inhibition, in the late afternoon. A double-blind, randomized, placebo-controlled study was conducted in 36 boys (7-12 years) with ADHD and 40 typically developing children. The ADHD children received an individualized dose of placebo or osmotic-release oral system methylphenidate. They were tested about 8 hours after taking with 2 continuous performance tests (continuous performance test-X [CPT-X] and continuous performance test-AX [CPT-AX]) and a counting Stroop. A positive effect of osmotic-release oral system methylphenidate was present in CPT-AX with faster and less variable reaction times under osmotic-release oral system methylphenidate than under placebo, and no difference with typically developing children. In the counting Stroop, we found a decreased interference with osmotic-release oral system methylphenidate but no difference between children with ADHD under placebo and typically developing children.

Sleep spindle detection through amplitude-frequency normal modelling.

Manual scoring of sleep spindles can be very time-consuming, and achieving accurate manual scoring on a long-term recording requires high and sustained levels of vigilance, which makes it a highly demanding task with the associated risk of decreased diagnosis accuracy. Although automatic spindle detection would be attractive, most available algorithms are sensitive to variations in spindle amplitude and frequency that occur between both subjects and derivations, reducing their effectiveness. We propose here an algorithm that models the amplitude-frequency spindle distribution with a bivariate normal distribution (one normal model per derivation). Subsequently, spindles are detected when their amplitude-frequency characteristics are included within a given tolerance interval of the corresponding model. As a consequence, spindle detection is not directly based on amplitude and frequency thresholds, but instead on a spindle distribution model that is automatically adapted to each individual subject and derivation. The algorithm was first assessed against the scoring of one sleep scoring expert on EEG samples from seven healthy children. Afterward, a second study compared performance of two additional experts versus the algorithm on a dataset of six EEG samples from adult patients suffering from different pathologies, to submit the method to more challenging and clinically realistic conditions. Smaller and shorter spindles were more difficult to evaluate, as false positives and false negatives showed lower amplitude and smaller length than true positives. In both studies, normal modelling enhanced performance compared to fixed amplitude and frequency thresholds. Normal modelling is therefore attractive, as it enhances spindle detection quality.

Cluster-based spike detection algorithm adapts to interpatient and intrapatient variation in spike morphology.

Visual quantification of interictal epileptiform activity is time consuming and requires a high level of expert's vigilance. This is especially true for overnight recordings of patient suffering from epileptic encephalopathy with continuous spike and waves during slow-wave sleep (CSWS) as they can show tens of thousands of spikes. Automatic spike detection would be attractive for this condition, but available algorithms have methodological limitations related to variation in spike morphology both between patients and within a single recording. We propose a fully automated method of interictal spike detection that adapts to interpatient and intrapatient variation in spike morphology. The algorithm works in five steps. (1) Spikes are detected using parameters suitable for highly sensitive detection. (2) Detected spikes are separated into clusters. (3) The number of clusters is automatically adjusted. (4) Centroids are used as templates for more specific spike detections, therefore adapting to the types of spike morphology. (5) Detected spikes are summed. The algorithm was evaluated on EEG samples from 20 children suffering from epilepsy with CSWS. When compared to the manual scoring of 3 EEG experts (3 records), the algorithm demonstrated similar performance since sensitivity and selectivity were 0.3% higher and 0.4% lower, respectively. The algorithm showed little difference compared to the manual scoring of another expert for the spike-and-wave index evaluation in 17 additional records (the mean absolute difference was 3.8%). This algorithm is therefore efficient for the count of interictal spikes and determination of a spike-and-wave index.

Acquired cognitive dysfunction with focal sleep spiking activity.

The syndrome of continuous spike-waves during slow sleep (CSWS) is considered an epileptic encephalopathy in which the epileptiform abnormalities may contribute to progressive cognitive dysfunction. The characteristic electroencephalographic feature of the syndrome occurs during non-REM sleep, and takes the form of continuous bilateral and diffuse slow spike-waves that persist through all slow sleep stages. Using a case study design including clinical, neuropsychological, electroencephalographic, and positron emission tomography with 18F-fluorodeoxyglucose (PET-FDG) investigations, we describe the clinical and electroencephalographic findings in two patients who presented with nonsymptomatic epilepsy with unilateral spike-waves during sleep. Both patients presented with a left unilateral motor neglect of the upper limb that was associated with unilateral CSWS activity over the right hemisphere, predominantly in the centrotemporal region. PET-FDG studies during the active phase of CSWS showed right centrotemporal hypermetabolism in both cases. After treatment, a regression of the CSWS activity and an improvement of the cerebral FDG pattern were paralleled by a remission of the motor neglect. These cases demonstrate that the electroencephalographic pattern of CSWS in nonsymptomatic epilepsies is not necessarily diffuse and bilateral, and that focal unilateral CSWS activity can be associated with focal neuropsychological deficits. These findings add further evidence that the spectrum of clinical conditions associated with the electroencephalographic pattern of CSWS can include different forms of acquired cognitive disturbances that may be focal in nature.

Coexistence of idiopathic rolandic epilepsy and CSWS in two families.

PURPOSE: To report two families combining benign childhood epilepsy with centrotemporal spikes (BCECS) and cryptogenic epilepsy with continuous spike-waves during sleep (CSWS) in first-degree relatives. METHODS: Clinical, EEG, and cerebral imaging data are described. RESULTS: FAMILY 1: The proband was 3 years old at epilepsy onset. First seizures were convulsive, with centrotemporal spikes on EEG. At age 5 years, he had complex partial seizures, psychomotor regression, and centrotemporal CSWS. [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) showed left parietal hypermetabolism. After several antiepileptic drug (AED) trials, valproate (VPA) and ethosuximide (ESM) induced seizure remission, CSWS disappearance, and psychomotor improvement. Learning disabilities, however, persisted. Family history was remarkable for BCECS in his father. FAMILY 2: The proband was 2 years old at epilepsy onset. First seizures were convulsive, with centrotemporal CSWS on EEG. Despite several AED trials including corticosteroids, focal negative myoclonia, atypical absences, and psychomotor regression occurred, leading to severe mental retardation. FDG-PET showed bilateral parietal hypermetabolism. Vagus nerve stimulator was implanted. Her family history was remarkable for BCECS in her father and febrile convulsions in infancy in her mother. CONCLUSIONS: These data suggest the existence of a common genetic basis between BCECS and cryptogenic epilepsies with CSWS. The higher expression in patients with CSWS could be related to other genetic or acquired factors. These data suggest that these epileptic syndromes constitute edges of a continuum.

Levetiracetam efficacy in epileptic syndromes with continuous spikes and waves during slow sleep: experience in 12 cases.

PURPOSE: To assess the add-on efficacy of levetiracetam on the EEG, behavior, and cognition of children with continuous spikes and waves during slow sleep (CSWS). METHODS: Charts of children with behavioral and/or cognitive deterioration associated with CSWS who received levetiracetam at 50 mg/kg/day as add-on treatment were retrospectively reviewed. Awake and sleep EEG recordings and detailed neuropsychological and behavioral assessments were available at baseline and 2 months after levetiracetam initiation. In children showing clinical and/or electrophysiological improvement after 2 months, levetiracetam was continued with a new evaluation at 1 year. RESULTS: Twelve patients were included (9 cryptogenic and 3 symptomatic cases). Seven patients (58.3%) showed improvement of EEG record. Among these seven patients, neuropsychological evaluation was improved in three, and in the other four patients, not testable because of severe cognitive impairment, behavior was improved. Two patients improved in neuropsychological evaluation despite the lack of EEG improvement. Eight patients (66.6%) continued levetiracetam treatment after 2 months. After 1 year, four patients were still on levetiracetam, two because sustained effect on EEG and behavior and the two others because improvement in neuropsychological testing despite unchanged EEG. Levetiracetam was discontinued in the other four patients because of neuropsychological or behavioral deterioration associated with CSWS pattern, between 9 and 11 months after treatment initiation. CONCLUSIONS: This retrospective study suggests that levetiracetam has a positive effect on the EEG, the behavior, and the cognition of patients with epilepsy and CSWS. Additional studies are warranted in order to assess the place of this drug in these epileptic conditions.

Facial nerve palsy in posterior fossa arachnoid cysts: report of two cases.

CASE REPORT: Two patients with a posterior fossa arachnoid cyst responsible for isolated facial nerve palsy are reported. DISCUSSION: The relationships between the cyst and the facial nerve and between the facial nerve palsy and the size variation of the cyst are discussed and documented by pre- and postoperative magnetic resonance imaging.

Autoimmune epilepsy: some epilepsy patients harbor autoantibodies to glutamate receptors and dsDNA on both sides of the blood-brain barrier, which may kill neurons and decrease in brain fluids after hemispherotomy.

PURPOSE: Elucidating the potential contribution of specific autoantibodies (Ab's) to the etiology and/or pathology of some human epilepsies. METHODS: Six epilepsy patients with Rasmussen's encephalitis (RE) and 71 patients with other epilepsies were tested for Ab's to the "B" peptide (amino acids 372-395) of the glutamate/AMPA subtype 3 receptor (GluR3B peptide), double-stranded DNA (dsDNA), and additional autoimmune disease-associated autoantigens, and for the ability of their serum and cerebrospinal-fluid (CSF) to kill neurons. RESULTS: Elevated anti-GluR3B Ab' s were found in serum and CSF of most RE patients, and in serum of 17/71 (24%) patients with other epilepsies. In two RE patients, anti-GluR3B Ab's decreased drastically in CSF following functional-hemispherotomy, in association with seizure cessation and neurological improvement. Serum and CSF of two RE patients, and serum of 12/71 (17%) patients with other epilepsies, contained elevated anti-dsDNA Ab's, the hallmark of systemic-lupus-erythematosus. The sera (but not the CSF) of some RE patients contained also clinically elevated levels of "classical" autoimmune Ab's to glutamic-acid-decarboxylase, cardiolipin, beta2-glycoprotein-I and nuclear-antigens SS-A and RNP-70. Sera and CSF of some RE patients caused substantial death of hippocampal neurons. CONCLUSIONS: Some epilepsy patients harbor Ab's to GluR3 and dsDNA on both sides of the blood-brain barrier, and additional autoimmune Ab's only in serum. Since all these Ab's may be detrimental to the nervous system and/or peripheral organs, we recommend testing for their presence in epilepsy, and silencing their activity in Ab-positive patients.

Autonomic responses to sighs in healthy infants and in victims of sudden infant death.

OBJECTIVE: Sigh, defined as an isolated breath with an increased tidal volume, can be associated with abrupt changes in heart rate (HR) or blood oxygenation. Sigh may be followed by a central apnea. As impairment of autonomic control was postulated in future SIDS victims, we hypothesized that their autonomic responses to sighs were different from those of healthy control infants. METHODS: Sighs followed by central apnea were studied in the sleep recordings of 18 infants who eventually died of SIDS and of 18 control infants. The infants of the two groups were matched for sex, gestational age, postnatal age, weight at birth and sleep position during sleep recording. HR autoregressive power spectral analysis was performed on RR intervals preceding and following sighs. RESULTS: In all infants, most sighs followed by an apnea were found in NREM sleep. Compared to the control infants, the future SIDS victims were characterized by a greater sympathovagal balance and a lower parasympathetic tonus before the sighs. Following the sighs, no more differences were found in NREM sleep. CONCLUSION: Based on the present findings, it can be postulated that sighs contribute to reset autonomic tonus during NREM sleep.

Transient cerebral arteriopathy in infancy associated with enteroviral infection.

We report the case of an 18-month-old boy who presented aphasia and right hemiplegia of acute onset. The neurological deficit completely resolved after a few hours, but identical transient neurological deficits and seizures occurred during the following days. Imaging showed proximal stenosis of the medial cerebral artery and deep ischaemic lesions in the territory of this artery. Analysis of the cerebrospinal fluid showed pleocytosis and an active enteroviral infection with positive RNA detection. The evolution was consistent with transient cerebral arteriopathy of childhood as magnetic resonance angiography showed normalization of the arterial lesions. This is the first report of an enteroviral infection associated with this entity. We want to stress the importance of performing a cerebrospinal fluid analysis when an ischaemic stroke of unclear aetiology occurs in a child.

Physiological relationship between autonomic reactions and arousals in infancy.

OBJECTIVE: Changes in blood pressure (BP) were measured following auditory stimuli in the prone and the supine position to study the correlation between arousal from sleep and autonomic responses. METHOD: Two newborns born at term, two infants and four children were recorded polygraphically during one night, while sleeping in the prone and the supine position. They were exposed to white noises of increasing intensities during both rapid eye movement (REM) and non-rapid eye movement (NREM) sleep in each position. BP changes were measured by Finapress in the children and by pulse transient time (PTT) in the infants and newborns. RESULTS: Basal systolic BP pressures were lower (P<0.001) and PTT were higher (P=0.008) in the prone than in the supine position in children and in infants. Following the auditory stimulations, the increases in systolic BP (P=0.024) and the decreases in PTT (P=0.006) were smaller in prone than in supine position. During cortical arousals, the same findings were found, independently of sleep stages. CONCLUSION: Compared with when they are sleeping supine, children and infants sleeping prone had lower basal BP and higher PTT and smaller changes in BP and PTT after auditory stimulation. Reduced BP changes to stimuli could be implicated in the increased arousal thresholds in prone position.