SUMMARYObjective: To determine the clinical characteristics, surgical challenges, and outcome in children younger than 3 years of age undergoing epilepsy surgery in Canada. Methods: Retrospective data on patients younger than age 3 years who underwent epilepsy surgery at multiple centers across Canada from January 1987 to September 2005 were collected and analyzed. Results: There were 116 patients from eight centers. Seizure onset was in the first year of life in 82% %, and mean age at first surgery was 15.8 months (1-35 months). Second surgeries were done in 27 patients, and a third surgery in 6. Etiologies were malformations of cortical development (57), tumor (22), Sturge-Weber syndrome (19), infarct (8), and other (10). Surgeries comprised 40 hemispheric operations, 33 cortical resections, 35 lesionectomies, 7 temporal lobectomies, and one callosotomy. There was one surgical mortality. The most common surgical complications (151 operations in 116 patients) were infection (17) and aseptic meningitis in 13. Of 107 patients with seizure outcome assessed more than one year postoperatively, 72 (67.3%) were seizure free (Engel I), 15(14%) had >90% improvement (Engel II), 12 had >50% improvement (Engel III), and 8 did not benefit from surgery (Engel IV). Development improved in 55.3% after surgery. Conclusion: Epilepsy surgery in children younger than 3 years of age is relatively safe and is effective in controlling seizures. Very young age is not a contraindication to surgery in children with refractory epilepsy, and early surgery may impact development positively.

The mechanisms underlying memory formation in the hippocampal network remain a major unanswered aspect of neuroscience. Although high-frequency activity appears essential for plasticity, salience for memory formation is also provided by activity in ventral tegmental area (VTA) dopamine projections. Here, we report that activation of dopamine D1 receptors in dentate granule cells (DGCs) can preferentially increase dendritic excitability to both highfrequency afferent activity and high-frequency trains of backpropagating action potentials. Using whole-cell patch clamp recordings, calcium imaging, and neuropeptide Y to inhibit postsynaptic calcium influx, we found that activation of dendritic voltagedependent calcium channels (VDCCs) is essential for dopamineinduced long-term potentiation (LTP), both in rat and human dentate gyrus (DG). Moreover, we demonstrate previously unreported spike-timing-dependent plasticity in the human hippocampus. These results suggest that when dopamine is released in the dentate gyrus with concurrent high-frequency activity there is an increased probability that synapses will be strengthened and reward-associated spatial memories will be formed.A s an animal explores a specific location, place cells in the dentate gyrus (DG) of the hippocampus fire bursts of action potentials (APs) (1) that can result in the formation of a new, long-term contextual memory (2). This is part of the "pattern separation" mechanism, whereby only a small population of dentate granule cells (DGCs) become very active and pass on the incoming cortical input to be later represented or "completed," in the downstream CA3 network (3). Memory formation related to a specific place can be enhanced by an associated salience, such as reward (4). Recent work suggests that disruption of mesocorticolimbic dopamine responses blocks conditioned place preference (CPP), a reward-driven form of spatial memory (5, 6). Furthermore, nicotine-induced CPP requires dopamine D1 receptor (D1R) activation in the DG (7). The medial perforant pathway (MPP) carries spatial information to the middle third of the molecular layer (8). In DGCs, D1Rs are concentrated throughout the dendritic tree (9). This suggests that bursting activity in DGCs, coincident with local dopamine release, may enhance formation of salient memories, but a mechanism remains unknown.One potential mechanism mediating plasticity is the coincidence of backpropagating dendritic APs with appropriately timed synaptic input (10); this mechanism requires postsynaptic Ca 2+ influx (11). Ca 2+ channels have been implicated in nonlinear, frequency-dependent responses in dendrites (12) and D1Rs can potentiate dendritic excitability in hippocampal area CA1 (13). Because the molecular layer of the DG is innervated by dopaminergic terminals from the ventral tegmental area (VTA) (14) we examined the possibility that interactions at the level of DGC dendrites between firing frequency, dendritic Ca 2+ responses, and D1Rs, may mediate plasticity in medial perforant path synaptic inputs....

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BackgroundRasmussen’s encephalitis (RE) is an inflammatory encephalopathy of unknown cause defined by seizures with progressive neurological disabilities. Herein, the pathogenesis of RE was investigated focusing on inflammasome activation in the brain.MethodsPatients with RE at the University of Alberta, Edmonton, AB, Canada, were identified and analyzed by neuroimaging, neuropsychological, molecular, and pathological tools. Primary human microglia, astrocytes, and neurons were examined using RT-PCR, enzyme-linked immunosorbent assay (ELISA), and western blotting.ResultsFour patients with RE were identified at the University of Alberta. Magnetic resonance imaging (MRI) disclosed increased signal intensities in cerebral white matter adjacent to cortical lesions of RE patients, accompanied by a decline in neurocognitive processing speed (P <0.05). CD3ϵ, HLA-DRA, and TNFα together with several inflammasome-associated genes (IL-1β, IL-18, NLRP1, NLRP3, and CASP1) showed increased transcript levels in RE brains compared to non-RE controls (n = 6; P <0.05). Cultured human microglia displayed expression of inflammasome-associated genes and responded to inflammasome activators by releasing IL-1β, which was inhibited by the caspase inhibitor, zVAD-fmk. Major histocompatibility complex (MHC) class II, IL-1β, caspase-1, and alanine/serine/cysteine (ASC) immunoreactivity were increased in RE brain tissues, especially in white matter myeloid cells, in conjunction with mononuclear cell infiltration and gliosis. Neuroinflammation in RE brains was present in both white matter and adjacent cortex with associated induction of inflammasome components, which was correlated with neuroimaging and neuropsychological deficits.ConclusionInflammasome activation likely contributes to the disease process underlying RE and offers a mechanistic target for future therapeutic interventions.

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