David A. Hsu

The Neuropsychological and Academic Substrate of New/Recent-Onset Epilepsies

OBJECTIVE To characterize neuropsychological and academic status in children, ages 8-18 years, with new-/recent-onset idiopathic generalized epilepsy (IGE) and idiopathic localization-related epilepsy (ILRE) compared with healthy controls. STUDY DESIGN Participants underwent neuropsychological assessment, and parents were interviewed regarding their childs academic history. Cognitive scores for children with epilepsy were age- and sex-adjusted and compared with controls across both broad-band (IGE n = 41 and ILRE n = 53) and narrow-band (childhood/juvenile absence, juvenile myoclonic, benign epilepsy with centro-temporal spikes, and focal [temporal/frontal/not otherwise specified]) syndromes. Academic histories were examined, including problems antecedent to epilepsy onset and diagnosis. RESULTS Children with new/recent-onset epilepsies exhibit considerable cognitive abnormality at baseline, including patterns of shared abnormalities across syndromes (eg, psychomotor slowing) as well as unique syndrome-specific cognitive effects (eg, executive function in IGE and language/verbal memory in ILRE) that are observed and sometimes exacerbated in specific IGE and ILRE syndromes. Academic difficulties are evident in approximately 50% of the children with epilepsy, affecting all syndrome groups to an equal degree. DISCUSSION Patterns of shared and syndrome-specific cognitive abnormalities and academic problems are present early in the course of virtually all epilepsy syndromes examined here, including syndromes classically viewed as benign. This is the base upon which the effects of recurrent seizures, treatment, and psychosocial effects will be added over time.

Neurodegenerative central nervous system Langerhans cell histiocytosis and coincident hydrocephalus treated with vincristine/cytosine arabinoside.

Central nervous system (CNS) complications of Langerhans cell histiocytosis (LCH) include mass lesions and a neurodegenerative (ND) syndrome with ataxia, dysarthria, dysmetria, learning and behavior difficulties and/or characteristic changes on brain MRIs. Hydrocephalus has rarely been reported in LCH. LCH lesions of the orbit, mastoid and temporal bones (“CNS‐Risk” lesions) and diabetes insipidus predispose patients to ND‐CNS‐LCH. Treatment options have been limited and only a case series using trans‐retinoic acid (ATRA) and intravenous immunoglobulin (IVIG) have been published.

Cognitive development in children with new onset epilepsy

To characterize the prospective trajectory of cognitive development in children with new or recent onset epilepsy from baseline to 5 to 6 years after diagnosis.

Striatal Hypertrophy and Its Cognitive Effects in New Onset Benign Epilepsy with Centrotemporal Spikes

Purpose:  Benign epilepsy with centrotemporal spikes (BECTS), the most common childhood epilepsy syndrome, is a neurodevelopmental disorder with a genetic influence. Despite its signature electroencephalographic pattern and distinct focal motor seizure semiology, little is known about the underlying brain anatomic alteration and the corresponding cognitive consequences. Given the motor manifestations of seizures in BECTS, we hypothesize that anatomic networks in BECTS involve a distributed corticostriatal circuit.

Cognition and brain development in children with benign epilepsy with centrotemporal spikes.

Benign epilepsy with centrotemporal spikes (BECTS), the most common focal childhood epilepsy, is associated with subtle abnormalities in cognition and possible developmental alterations in brain structure when compared to healthy participants, as indicated by previous cross‐sectional studies. To examine the natural history of BECTS, we investigated cognition, cortical thickness, and subcortical volumes in children with new/recent onset BECTS and healthy controls (HC).

Neuronal avalanches and criticality: A dynamical model for homeostasis

The dynamics of microelectrode local field potentials from cortical slice cultures shows critical behavior. A desirable feature of criticality is that information transmission is optimal in this state. We explore a biologically plausible neural net model that can dynamically converge on criticality and that can return to criticality if perturbed away from it. Our model assumes the presence of a preferred target firing rate, with dynamical adjustments of internodal connection strengths to approach this firing rate. We suggest that mechanisms for maintaining firing rate homeostasis may also maintain a neural system at criticality.

Neurodevelopmental alterations of large-scale structural networks in children with new-onset epilepsy.

Recent neuroimaging and behavioral studies have revealed that children with new onset epilepsy already exhibit brain structural abnormalities and cognitive impairment. How the organization of large‐scale brain structural networks is altered near the time of seizure onset and whether network changes are related to cognitive performances remain unclear. Recent studies also suggest that regional brain volume covariance reflects synchronized brain developmental changes. Here, we test the hypothesis that epilepsy during early‐life is associated with abnormalities in brain network organization and cognition. We used graph theory to study structural brain networks based on regional volume covariance in 39 children with new‐onset seizures and 28 healthy controls. Children with new‐onset epilepsy showed a suboptimal topological structural organization with enhanced network segregation and reduced global integration compared with controls. At the regional level, structural reorganization was evident with redistributed nodes from the posterior to more anterior head regions. The epileptic brain network was more vulnerable to targeted but not random attacks. Finally, a subgroup of children with epilepsy, namely those with lower IQ and poorer executive function, had a reduced balance between network segregation and integration. Taken together, the findings suggest that the neurodevelopmental impact of new onset childhood epilepsies alters large‐scale brain networks, resulting in greater vulnerability to network failure and cognitive impairment. Hum Brain Mapp 35:3661–3672, 2014.

Neurodevelopment in new-onset juvenile myoclonic epilepsy over the first 2 years

Adults with juvenile myoclonic epilepsy (JME) have subtle brain structural abnormalities in the frontothalamocortical network, poorer cognitive function, and worse long‐term social outcomes, even when their seizures are controlled and/or remitted. The natural history of JME and development of abnormalities in brain structure and cognition from epilepsy onset has not been studied.

An open hypothesis: is epilepsy learned, and can it be unlearned?

Plasticity is central to the ability of a neural system to learn and also to its ability to develop spontaneous seizures. What is the connection between the two? Learning itself is known to be a destabilizing process at the algorithmic level. We have investigated necessary constraints on a spontaneously active Hebbian learning system and find that the ability to learn appears to confer an intrinsic vulnerability to epileptogenesis on that system. We hypothesize that epilepsy arises as an abnormal learned response of such a system to certain repeated provocations. This response is a network-level effect. If epilepsy really is a learned response, then it should be possible to reverse it, that is, to unlearn epilepsy. Unlearning epilepsy may then provide a new approach to its treatment.

Ventricular enlargement in new‐onset pediatric epilepsies

Purpose:  To examine baseline and prospective (2‐year) changes in third, fourth, and lateral ventricle volumes in children with new‐onset idiopathic epilepsies and controls (age 8–18 years).