William D. Gaillard

Infantile spasms: A U.S. consensus report

The diagnosis, evaluation, and management of infantile spasms (IS) continue to pose significant challenges to the treating physician. Although an evidence‐based practice guideline with full literature review was published in 2004, diversity in IS evaluation and treatment remains and highlights the need for further consensus to optimize outcomes in IS. For this purpose, a working group committed to the diagnosis, treatment, and establishment of a continuum of care for patients with IS and their families—the Infantile Spasms Working Group (ISWG)—was convened. The ISWG participated in a workshop for which the key objectives were to review the state of our understanding of IS, assess the scientific evidence regarding efficacy of currently available therapeutic options, and arrive at a consensus on protocols for diagnostic workup and management of IS that can serve as a guide to help specialists and general pediatricians optimally manage infants with IS. The overall goal of the workshop was to improve IS outcomes by assisting treating physicians with early recognition and diagnosis of IS, initiation of short duration therapy with a first‐line treatment, timely electroencephalography (EEG) evaluation of treatment to evaluate effectiveness, and, if indicated, prompt treatment modification. Differences of opinion among ISWG members occurred in areas where data were lacking; however, this article represents a consensus of the U.S. approach to the diagnostic evaluation and treatment of IS.

Brain Hyperconnectivity in Children with Autism and its Links to Social Deficits

Autism spectrum disorder (ASD), a neurodevelopmental disorder affecting nearly 1 in 88 children, is thought to result from aberrant brain connectivity. Remarkably, there have been no systematic attempts to characterize whole-brain connectivity in children with ASD. Here, we use neuroimaging to show that there are more instances of greater functional connectivity in the brains of children with ASD in comparison to those of typically developing children. Hyperconnectivity in ASD was observed at the whole-brain and subsystems levels, across long- and short-range connections, and was associated with higher levels of fluctuations in regional brain signals. Brain hyperconnectivity predicted symptom severity in ASD, such that children with greater functional connectivity exhibited more severe social deficits. We replicated these findings in two additional independent cohorts, demonstrating again that at earlier ages, the brain of children with ASD is largely functionally hyperconnected in ways that contribute to social dysfunction. Our findings provide unique insights into brain mechanisms underlying childhood autism.

Developmental aspects of language processing: fMRI of verbal fluency in children and adults†

We examined developmental differences, in location and extent of fMRI language activation maps, between adults and children while performing a semantic fluency task. We studied 29 adults and 16 children with echo planar imaging BOLD fMRI at 1.5 T using covert semantic verbal fluency (generation of words to categories compared to rest) using a block design. Post task testing was administered to assess performance. Individual data were analyzed with an a priori region of interest approach from t maps (t = 4) and asymmetry indices (AI). Group studies were analyzed using SPM 99 (Wellcome, UK; fixed effect, corrected P < 0.0001). We found no significant differences in location or laterality of activation between adults and children for a semantic verbal fluency task. Adults activated more pixels than children in left inferior frontal gyrus and left middle frontal gyrus, but AIs were the similar across ages (r2 < 0.09). Extent or laterality of activation was not affected by performance (r2 < 0.15). The brain areas that process semantic verbal fluency are similar in children and adults. The laterality of activation does not change appreciably with age and appears to be strongly lateralized by age 7 years. Hum. Brain Mapping 18:176–185, 2003.

Measurement of whole temporal lobe and hippocampus for MR volumetry Normative data

We measured the volumes of the entire length of temporal lobe and hippocampal formation from coronal images in 29 healthy young adults to take into account normal side-to-side variation. Although whole-brain, temporal lobe, and left hippocampal volumes were significantly smaller in women, normalizing measurements for the whole brain eliminated intersex temporal lobe and hippocampal differences. There was a weak but significant inverse correlation between age and normalized hippocampal, but not temporal lobe or whole-brain, volume. In contrast to previous studies, we found no significant side-to-side differences in the sizes of temporal lobes or hippocampi. When performing MR volumetry, it is important to include the entire length of the hippocampal formation.

Guidelines for imaging infants and children with recent-onset epilepsy

The International League Against Epilepsy (ILAE) Subcommittee for Pediatric Neuroimaging examined the usefulness of, and indications for, neuroimaging in the evaluation of children with newly diagnosed epilepsy. The retrospective and prospective published series with n ≥30 utilizing computed tomography (CT) and magnetic resonance imaging (MRI) (1.5 T) that evaluated children with new‐onset seizure(s) were reviewed. Nearly 50% of individual imaging studies in children with localization‐related new‐onset seizure(s) were reported to be abnormal; 15–20% of imaging studies provided useful information on etiology or and seizure focus, and 2–4% provided information that potentially altered immediate medical management. A significant imaging abnormality in the absence of a history of a localization‐related seizure, abnormal neurologic examination, or focal electroencephalography (EEG) is rare. Imaging studies in childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, and benign childhood epilepsy with centrotemporal spikes (BECTS) do not identify significant structural abnormalities. Imaging provides important contributions to establishing etiology, providing prognostic information, and directing treatment in children with recently diagnosed epilepsy. Imaging is recommended when localization‐related epilepsy is known or suspected, when the epilepsy classification is in doubt, or when an epilepsy syndrome with remote symptomatic cause is suspected. When available, MRI is preferred to CT because of its superior resolution, versatility, and lack of radiation.

Dysmaturation of the default mode network in autism.

Two hypotheses of autism spectrum disorder (ASD) propose that this condition is characterized by deficits in Theory of Mind and by hypoconnectivity between remote cortical regions with hyperconnectivity locally. The default mode network (DMN) is a set of remote, functionally connected cortical nodes less active during executive tasks than at rest and is implicated in Theory of Mind, episodic memory, and other self‐reflective processes. We show that children with ASD have reduced connectivity between DMN nodes and increased local connectivity within DMN nodes and the visual and motor resting‐state networks. We show that, like the trajectory of synaptogenesis, internodal DMN functional connectivity increased as a quadratic function of age in typically developing children, peaking between, 11 and 13 years. In children with ASD, these long‐distance connections fail to develop during adolescence. These findings support the “developmental disconnection model” of ASD, provide a possible mechanistic explanation for the Theory‐of‐Mind hypothesis of ASD, and show that the window for effectively treating ASD could be wider than previously thought. Hum Brain Mapp 35:1284–1296, 2014.

FDG-Positron Emission Tomography and Invasive EEG: Seizure Focus Detection and Surgical Outcome

Summary: Purpose: To study the value of [18F]2‐deoxyglucose (FDG)‐positron emission tomography when surface ictal EEG is nonlocalizing.

Effect of Valproate on Cerebral Metabolism and Blood Flow: An 18F-2-Deoxyglusose and 15O Water Positron Emission Tomography Study

Summary: We compared the effect of valproate (VPA) on cerebral metabolic rate for glucose (CMRGlc) and cerebral blood flow (CBF), measured with 18F‐2–deoxyglucose (I8FDG) and 15O water positron emission tomography (PET), in 10 normal volunteers. Mean VPA dose was 17.7 mg/kg, and mean VPA level was 82.1 mg/L (±16.5) for 4 weeks. VPA reduced global CMRGlc by 9.4% (9.60 2 0.76 vs. 8.59 ± 1.02 mg Glc/min/100 g, p < 0.05) and regionally in all anatomic areas (p < 0.05 for 11 of 26 areas). VPA diminished global CBF by 14.9% (56.55 ± 6.70 vs. 47.48 ± 4.42 ml/min/100 g, p < 0.002) and regionally in all anatomic areas (p < 0.05 for 12 of 26 areas). No significant correlation was noted between VPA level and either global CMRGlc or CBF. The effect of VPA on global CMRGlc is similar to that of carbamazepine (CBZ) and phenytoin but less than that of phenobarbital, Valium, or combination therapy with VPA and CBZ. VPA reduced regional CBF (rCBF) but not CMRGlc in the thalamus, an effect that may be associated with VPAs mechanism of action against generalized seizures.

Intact Implicit Learning of Spatial Context and Temporal Sequences in Childhood Autism Spectrum Disorder

Autism spectrum disorder (ASD) is defined by atypicalities in domains that are posited to rely on implicit learning processes such as social communication, language, and motor behavior. The authors examined 2 forms of implicit learning in 14 children with high-functioning ASD (10 of whom were diagnosed with Aspergers syndrome) and 14 control children, learning of spatial context known to be mediated by the medial temporal lobes (using the contextual cueing task) and of sequences known to be mediated by frontal-striatal and frontal-cerebellar circuits (using the alternating serial reaction time task). Both forms of learning were unimpaired in ASD. Spatial contextual implicit learning was spared in ASD despite slower visual search of spatial displays. The present findings provide evidence for the integrity of learning processes dependent on integration of spatial and sequential contextual information in high-functioning children with ASD.

Cerebral MRI abnormalities associated with vigabatrin therapy.

Purpose:  Investigate whether patients on vigabatrin demonstrated new‐onset and reversible T2‐weighted magnetic resonance imaging (MRI) abnormalities.