Autoimmune encephalitis is the most commonly identified cause of new-onset refractory status epilepticus, but half remain cryptogenic. Outcome at discharge is poor but improves during follow-up. Epilepsy develops in most cases. The role of anesthetics and immune therapies warrants further investigation.

The major pathological lesion of Parkinson's disease (PD) is the selective cell death of dopaminergic (DA) neurons in substantia nigra (SN). Although the initial cause and subsequent molecular signaling mechanisms leading to DA cell death underlying the PD process remain elusive, brain-derived neurotrophic factor (BDNF) is thought to exert neuroprotective as well as neurotrophic roles for the survival and differentiation of DA neurons in SN. Addressing molecular mechanisms of BDNF action in both primary embryonic mesencephalic cultures and in vivo animal models has been technically difficult because DA neurons in SN are relatively rare and present with many heterogeneous cell populations in midbrain. We have developed and characterized a DA neuronal cell line of embryonic SN origin that is more accessible to molecular analysis and can be used as an in vitro model system for studying SN DA neurons. A clonal SN DA neuronal progenitor cell line SN4741, arrested at an early DA developmental stage, was established from transgenic mouse embryos containing the targeted expression of the thermolabile SV40Tag in SN DA neurons. The phenotypic and morphological differentiation of the SN4741 cells could be manipulated by environmental cues in vitro. Exogenous BDNF treatment produced significant neuroprotection against 1-methyl-4-phenylpyridinium, glutamate, and nitric oxide-induced neurotoxicity in the SN4741 cells. Simultaneous phosphorylation of receptor tyrosine kinase B accompanied the neuroprotection. This SN DA neuronal cell line provides a unique model system to circumvent the limitations associated with primary mesencephalic cultures for the elucidation of molecular mechanisms of BDNF action on DA neurons of the SN. Key words: neuroprotection; BDNF; substantia nigra; dopaminergic neuron; Parkinson's disease; transgenic mice; neuronal differentiation; conditional immortalizationThe neuropathological symptoms of Parkinson's disease (PD) result from the greater than normal selective degeneration of substantia nigra (SN) dopaminergic (DA) neurons during aging. In PD the initial cause or causes and molecular mechanisms leading to the DA cell death are unknown. Treatment to prevent DA cell loss in PD is not available. Because of the paucity of DA neurons and the presence of numerous other cell populations in SN, it has not been possible to definitively address the molecular mechanisms of both DA neuronal survival and differentiation. Thus, it is crucial to acquire an abundant source of homogeneous DA neurons in vitro for the molecular dissection of SN DA neurons. To generate a consistent and abundant source of SN DA neurons in vitro, several approaches, using developmental, anatomical, somatic, or genetic manipulations, have been investigated. First, Hynes et al. (1995) tried to recapitulate the ontogeny of SN DA neuronal differentiation in explant cultures. Sonic hedgehog can induce effectively DA neurons in rat embryonic forebrain /midbrain explant. But, to practically manipulate the DA neuronal differentiation in vitro...

Why seizures spontaneously terminate remains an unanswered fundamental question of epileptology. Here we present evidence that seizures self-terminate via a discontinuous critical transition or bifurcation. We show that human brain electrical activity at various spatial scales exhibits common dynamical signatures of an impending critical transition-slowing, increased correlation, and flickering-in the approach to seizure termination. In contrast, prolonged seizures (status epilepticus) repeatedly approach, but do not cross, the critical transition. To support these results, we implement a computational model that demonstrates that alternative stable attractors, representing the ictal and postictal states, emulate the observed dynamics. These results suggest that self-terminating seizures end through a common dynamical mechanism. This description constrains the specific biophysical mechanisms underlying seizure termination, suggests a dynamical understanding of status epilepticus, and demonstrates an accessible system for studying critical transitions in nature.critical slowing down | epilepsy | electrocorticogram | local field potential A lthough extensive observations and research have elucidated some mechanism of seizure initiation and maintenance, how seizures spontaneously terminate remains one of the most important, but still unanswered, questions in epileptology (1). Some of the potential mechanisms of seizure termination (2) include glutamate depletion (3), dynamic changes in ion concentrations (4-6), persistent activation of a hyperpolarization-activated cation conductance (7), changing synaptic effectiveness (5, 8), modulatory effects from subcortical structures and the cerebellum (9), and reduced pH (10). Together, these studies suggest distinct pathways to seizure termination through specific biophysical mechanisms.We propose here a dynamical understanding of seizure termination that encompasses and constrains these and other hypothesized biophysical mechanisms. Specifically, we propose that focal seizures with secondary generalization terminate in a manner consistent with crossing a critical transition or bifurcation in which the system traverses a critical threshold and shifts suddenly to an alternative, attracting dynamical regime (11). Such regime shifts between alternative stable states have been described in many real-world systems (12-14) and exhibit a repertoire of early warning indicators (15-17). The seizing brain provides a unique living system for studying the signatures of an impending critical transition as well as one in which interventions can have profound practical import.We characterize the features of seizure termination in both multiscale in vivo data from patients with epilepsy and a computational model of cortical field activity. We show that population electrical activity-observed at macroscopic spatial scales-exhibits numerous signatures of an impending critical transition, whereas spatially localized recordings of neural spiking activity possess different dynamics. These insi...

This study provides Class II evidence that QEEG + raw interpreted by experts identifies seizures in patients in the ICU with a sensitivity of 63%-68% and FPR of 0.5 seizures per hour.