Denis Verheulpen

Regional cerebral glucose metabolism in epilepsies with continuous spikes and waves during sleep.

Background: Epileptic syndromes with continuous spikes and waves during sleep (CSWS) represent a wide spectrum of epileptic conditions associated with cognitive dysfunctions that have the EEG pattern of CSWS as a common feature. Reported are the results of voxel-based analyses of brain glucose metabolism performed in a group of 18 children with CSWS. Methods: Voxel-based analyses of cerebral glucose metabolism were performed using statistical parametric mapping (SPM). First, each patient was compared with a control group and the influence of age, epileptic activity, and corticosteroid treatment on metabolic abnormalities was studied. Also, disease-related changes in the contribution of a brain area to the level of metabolic activity in another brain area were investigated using pathophysiologic interactions in groups of patients compared with the control group. Results: Individual SPM analyses identified three metabolic patterns: association of hypermetabolic and hypometabolic areas, hypometabolic areas only, and normal pattern. Age and intensity of awake interictal spiking did not significantly differ in patients showing focal hypermetabolism compared with the other ones. Treatment with corticosteroids was associated with absence of focal hypermetabolism. In the group of patients with hypermetabolic areas, analyses of pathophysiologic interactions showed disease-related altered functional connectivity between the parietal and frontal cortices. Conclusions: Cerebral metabolic patterns are heterogeneous among patients with CSWS. This metabolic heterogeneity could be related to the use of corticosteroid treatment before PET. The parietofrontal altered connectivity observed in patients with hypermetabolism is interpreted as a phenomenon of remote inhibition of the frontal lobes induced by highly epileptogenic and hypermetabolic posterior cortex.

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.

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 (Abs) to the etiology and/or pathology of some human epilepsies. Methods: Six epilepsy patients with Rasmussens encephalitis (RE) and 71 patients with other epilepsies were tested for Abs 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 Abs 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 Abs 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 Abs, the hallmark of systemic-lupus-erythematosus. The sera (but not the CSF) of some RE patients contained also clinically elevated levels of –classical— autoimmune Abs to glutamic-acid-decarboxylase, cardiolipin, β2-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 Abs to GluR3 and dsDNA on both sides of the blood-brain barrier, and additional autoimmune Abs only in serum. Since all these Abs 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.

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.

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

Case reportTwo patients with a posterior fossa arachnoid cyst responsible for isolated facial nerve palsy are reported.DiscussionThe 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.

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.