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Advances in the pathophysiology of status epilepticus

Authors

  • J. W. Y. Chen,

    1. Department of Neurology and Brain Research Institute, Geffen School of Medicine at UCLA, and VA Greater Los Angeles Health Care System, Los Angeles, CA, USA
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  • D. E. Naylor,

    1. Department of Neurology and Brain Research Institute, Geffen School of Medicine at UCLA, and VA Greater Los Angeles Health Care System, Los Angeles, CA, USA
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  • C. G. Wasterlain

    1. Department of Neurology and Brain Research Institute, Geffen School of Medicine at UCLA, and VA Greater Los Angeles Health Care System, Los Angeles, CA, USA
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  • All authors declare no conflict of interests

Claude G. Wasterlain, Department of Neurology, Geffen School of Medicine at UCLA, and VA Greater Los Angeles Health Care System, West L.A. VA Medical Center (127), 11301 Wilshire Boulevard, West Los Angeles, CA 90073, USA
Tel.: +1 310 268 3595
Fax: +1 310 268 4611
e-mail: wasterla@ucla.edu

Abstract

Status epilepticus (SE) describes an enduring epileptic state during which seizures are unremitting and tend to be self-perpetuating. We describe the clinical phases of generalized convulsive SE, impending SE, established SE, and subtle SE. We discuss the physiological and biochemical cascades which characterize self-sustaining SE (SSSE) in animal models. At the transition from single seizures to SSSE, GABAA (gamma-aminobutyric acid) receptors move from the synaptic membrane to the cytoplasm, where they are functionally inactive. This reduces the number of GABAA receptors available for binding GABA or GABAergic drugs, and may in part explain the development of time-dependent pharmacoresistance to benzodiazepines and the tendency of seizures to become self-sustaining. At the same time, ‘spare’ subunits of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-D-aspartic acid) receptors move from subsynaptic sites to the synaptic membrane, causing further hyperexcitability and possibly explaining the preserved sensitivity to NMDA blockers late in the course of SE. Maladaptive changes in neuropeptide expression occur on a slower time course, with depletion of the inhibitory peptides dynorphin, galanin, somatostatin and neuropeptide Y, and with an increased expression of the proconvulsant tachykinins, substance P and neurokinin B. Finally, SE-induced neuronal injury and epileptogenesis are briefly discussed.

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