PHYSIOLOGICAL ANALYSIS OF RASMUSSENS ENCEPHALITIS - PATCH-CLAMP RECORDINGS OF ALTERED INHIBITORY NEUROTRANSMITTER FUNCTION IN RESECTED FRONTAL CORTICAL TISSUE

Rasmussen's encephalitis (RE) is a progressive, rare childhood disease characterized by severe epilepsy, hemiplegia, dementia, and inflammat ion of the brain. While one mechanism underlying the pathogenesis of R E has been hypothesized to be mediated by production of excitotoxic Gl uR3 autoantibodies to the AMPA receptor, other neuropathological etiol ogies have also been indicated. Whole-cell patch clamp recordings of G ABA(A) receptor mediated responses were conducted in neurons acutely i solated from an RE patient, and compared to properties of non-focal hu man temporal cortical neurons. RE neurons appeared similar anatomicall y to control cortical neurons. Significant differences in GABAergic re sponses were evident between RE and control neurons. GABA was signific antly more potent in RE than in control cortical neurons (EC50 of 13 m u M vs 23 mu M, respectively). In addition, the overall efficacy of GA BA was significantly decreased in RE neurons, associated with a decrea se in postsynaptic GABA current density in RE neurons (5.1 pA/mu m(2)) in comparison to controls (9.2 pA/mu m(2)). Augmentation of GABA resp onses by the benzodiazepine, clonazepam (CNZ), was significantly reduc ed in RE in comparison to control neurons (34% vs 99% augmentation at 100 nM). The RE-associated reduced functional efficacy and altered pha rmacology of neuronal GABA, receptors is consistent with overall disin hibition in RE neurons, and could contribute to the generation of the severe epileptic activity evident in this disorder. (C) 1998 Elsevier Science B.V. All rights reserved.