Partial epilepsies have a substantial heritability. However, the actual genetic causes are largely unknown. In contrast to many other common diseases for which genetic association-studies have successfully revealed common variants associated with disease risk, the role of common variation in partial epilepsies has not yet been explored in a well-powered study. We undertook a genome-wide association-study to identify common variants which influence risk for epilepsy shared amongst partial epilepsy syndromes, in 3445 patients and 6935 controls of European ancestry. We did not identify any genome-wide significant association. A few single nucleotide polymorphisms may warrant further investigation. We exclude common genetic variants with effect sizes above a modest 1.3 odds ratio for a single variant as contributors to genetic susceptibility shared across the partial epilepsies. We show that, at best, common genetic variation can only have a modest role in predisposition to the partial epilepsies when considered across syndromes in Europeans. The genetic architecture of the partial epilepsies is likely to be very complex, reflecting genotypic and phenotypic heterogeneity. Larger meta-analyses are required to identify variants of smaller effect sizes (odds ratio <1.3) or syndrome-specific variants. Further, our results suggest research efforts should also be directed towards identifying the multiple rare variants likely to account for at least part of the heritability of the partial epilepsies. Data emerging from genome-wide association-studies will be valuable during the next serious challenge of interpreting all the genetic variation emerging from whole-genome sequencing studies.

Recent experimental data in mice have shown that the inwardly rectifying K+ channel Kir4.1 mediates K+ spatial buffering in the hippocampus. Here we used immunohistochemistry to examine the distribution of Kir4.1 in hippocampi from patients with medication refractory temporal lobe epilepsy. The selectivity of the antibody was confirmed in mice with a glial conditional deletion of the gene encoding Kir4.1. These mice showed a complete loss of labeled cells, indicating that Kir4.1 is restricted to glia. In the human cases, Kir4.1 immunoreactivity observed in cells morphological consistent with astrocytes was significantly reduced in 12 patients with hippocampal sclerosis vs. 11 patients without sclerosis and 4 normal autopsy controls. Loss of astrocytic Kir4.1 immunoreactivity was most pronounced around vessels and was restricted to gliotic areas. Loss of Kir4.1 expression was associated with loss of dystrophin and α-syntrophin, but not with loss of β-dystroglycan, suggesting partial disruption of the dystrophin-associated protein complex. The changes identified in patients with hippocampal sclerosis likely interfere with K+ homeostasis and may contribute to the epileptogenicity of the sclerotic hippocampus.

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The heavy fermion system CeCu 6−x Ag x is studied at its antiferromagnetic quantum critical point, x c = 0.2, by low temperature (T ≥ 50 mK) specific heat, C(T ), and volume thermal expansion, β(T ), measurements. Whereas C/T ∝ log(T 0 /T ) would be compatible with the predictions of the itinerant spin-density-wave (SDW) theory for two-dimensional critical spin fluctuations, β(T )/T and the Grüneisen ratio, Γ(T ) ∝ β/C, diverge much weaker than expected, in strong contrast to this model. Both C and β, plotted as a function of the reduced temperature t = T /T 0 with T 0 = 4.6 K are similar to what was observed for YbRh 2 (Si 0.95 Ge 0.05 ) 2 (T 0 = 23.3 K) indicating a striking discrepancy to the SDW prediction in both systems.