Focal CA3 hippocampal subfield atrophy following LGI1 VGKC-complex antibody limbic encephalitis

Magnetic resonance imaging has linked chronic voltage-gated potassium channel (VGKC) complex antibody-mediated limbic encephalitis with generalized hippocampal atrophy. However, autoantibodies bind to specific rodent hippocampal subfields. Here, human hippocampal subfield (subiculum, cornu ammonis 1-3, and dentate gyrus) targets of immunomodulation-treated LGI1 VGKC-complex antibody-mediated limbic encephalitis were investigated using in vivo ultra-high resolution (0.39 0.39 1.0 mm3 ) 7.0 T magnetic resonance imaging [n = 18 patients, 17 patients (94%) positive for LGI1 antibody and one patient negative for LGI1/CASPR2 but positive for VGKC-complex antibodies, mean age: 64.0 2.55 years, median 4 years post-limbic encephalitis onset; n = 18 controls]. First, hippocampal subfield quantitative morphometry indicated significant volume loss confined to bilateral CA3 [F(1,34) = 16.87, P 5 0.0001], despite hyperintense signal evident in 5 of 18 patients on presentation. Second, early and later intervention (53 versus 43 months from symptom onset) were associated with CA3 atrophy. Third, whole-brain voxel-by-voxel morphometry revealed no significant grey matter loss. Fourth, CA3 subfield atrophy was associated with severe episodic but not semantic amnesia for postmorbid autobiographical events that was predicted by variability in CA3 volume. The results raise important questions about the links with histopathology, the impact of the observed focal atrophy on other CA3-mediated reconstructive and episodic mechanisms, and the role of potential antibody-mediated pathogenicity as part of the pathophysiology cascade in humans.The work was supported by the Medical Research Council (UK) and Engineering and Physical Sciences Research Council (P.A.G.), National Institute for Health Research (T.W.C.N.), National Institute for Health Research (NIHR) Oxford Biomedical Research Centre based at Oxford University Hospitals NHS Trust and University of Oxford (C.R.R., A.MA.D., C.K., & A.V.), John Fell OUP Fund (C.R.R, C.K.), Clinical Training Fellowship from the Guarantors of Brain (T.D.M.), the Patrick Berthoud Charitable Trust (T.D.M), the Encephalitis Society (T.D.M), and the Wellcome Trust (M.H.

Focal CA3 hippocampal subfield atrophy following LGI1 VGKC-complex antibody limbic encephalitis

Magnetic resonance imaging has linked chronic voltage-gated potassium channel (VGKC) complex antibody-mediated limbic encephalitis with generalized hippocampal atrophy. However, autoantibodies bind to specific rodent hippocampal subfields. Here, human hippocampal subfield (subiculum, cornu ammonis 1-3, and dentate gyrus) targets of immunomodulation-treated LGI1 VGKC-complex antibody-mediated limbic encephalitis were investigated using in vivo ultra-high resolution (0.39 x 0.39 x 1.0 mm³) 7.0T magnetic resonance imaging [n = 18 patients, 17 patients (94%) positive for LGI1 antibody and one patient negative for LGI1/CASPR2 but positive for VGKC-complex antibodies, mean age: 64.0 ± 2.55 years, median 4 years post-limbic encephalitis onset; n = 18 controls]. First, hippocampal subfield quantitative morphometry indicated significant volume loss confined to bilateral CA3 [F(1,34) = 16.87, P 3 months from symptom onset) were associated with CA3 atrophy. Third, whole-brain voxel-by-voxel morphometry revealed no significant grey matter loss. Fourth, CA3 subfield atrophy was associated with severe episodic but not semantic amnesia for postmorbid autobiographical events that was predicted by variability in CA3 volume. The results raise important questions about the links with histopathology, the impact of the observed focal atrophy on other CA3-mediated reconstructive and episodic mechanisms, and the role of potential antibody-mediated pathogenicity as part of the pathophysiology cascade in humans

Metal Chelation Versus Internal Hydrogen Bonding of The α-hydroxy Carboxylate Group

This study analyzes metal chelation of the α-hydroxy carboxylate group and the effect of the replacement of the hydroxyl group by fluorine in some alkali-metal citrate salts. The structure of potassium citrate monohydrate shows that, unlike the case for sodium or many other salts of citrate, the metal ion does not span the α-hydroxy carboxylate group. In this case, as for free citric acid, the hydrogen atom from the hydroxyl group forms a hydrogen bond to an oxygen atom of the central carboxylate group. When no such hydroxyl hydrogen atom is available for hydrogen bonding, as in potassium 3-fluorodeoxycitrate, where the hydroxyl group is replaced by fluorine, the metal spans the α-fluoro carboxylate group so that the carbon-bound fluorine is part of the coordination sphere of the metal ion. This analysis involved crystal structure analyses by X-ray and neutron diffraction of tripotassium citrate monohydrate with unit cell dimensions a ═ 13.795 (1), b ═ 11.772 (1), c ═ 7.092 (2) Å; β ═ 112.57 (2)°; space group P2/a. In addition, X-ray diffraction studies were done on potassium 3-fluoro-3-deoxycitrate monohydrate, unit cell dimensions a ═ 8.062 (2), b ═ 10.215 (1), c ═ 6.832 (1) Å; α ═ 96.27 (1), β ═ 93.66 (1), γ ═ 69.00 (1)°; space group P1

Rarefied Pure Gas Transport in Non-Isothermal Porous Media: Effective Transport properties from Homogenization of the Kinetic Equation

Viscous flow, effusion, and thermal transpiration are the main gas transport modalities for a rarefied gas in a macro-porous medium. They have been well quantified only in the case of simple geometries. This paper develops a model based on the homogenization of kinetic equations producing effective transport properties (permeability, Knudsen diffusivity, thermal transpiration ratio) in any porous medium sample, as described e. g. by a digitized 3D image. The homogenization procedure -- neglecting the effect of gas density gradients on heat transfer through the solid -- leads to macroscopic transfer relations, and to closure problems in R^6 for the obtention of effective properties. Coherence of the approach with previous literature on the subject is discussed. The asymptotic limits of the model (rarefied and continuum regimes) are also studied. One of the main results is that the effect of the geometry on thermal transpiration has to be described by a tensor which is distinct from the permeability and Knudsen diffusion tensors