Super-refractory status epilepticus (SRSE) is a critical condition in which seizures persist despite anesthetic use for 24 h or longer. High mortality has been reported in patients with SRSE, but the cause of death remains unclear. We investigated the factors associated with mortality, including clinical characteristics, SE etiologies and severities, treatments, and responses in patients with SRSE in a 13-year tertiary hospital-based retrospective cohort study comparing these parameters between deceased and surviving patients. SRSE accounted for 14.2% of patients with status epilepticus, and 28.6% of SRSE patients died. Deceased patients were mostly young or middle-aged without known systemic diseases or epilepsy. All deceased patients experienced generalized convulsive status epilepticus and failure of anesthetic tapering-off, significantly higher than survivors. An increased number of second-line anesthetics besides midazolam was observed in the deceased (median, 3, interquartile range 2–3) compared to surviving (1, 1–1; p = 0.0006) patients with prolonged use durations (p = 0.047). For mortality, the cut-off number of second-line anesthetics was 1.5 (AUC = 0.906, p = 0.004). Deceased patients had significantly higher renal and cardiac complications and metabolic acidosis than survivors. In SRSE management, multi-anesthetic use should be carefully controlled to avoid systemic complications and mortality.
Transcranial direct current stimulation (tDCS) is a promising noninvasive neuromodulatory treatment option for multiple neurologic and psychiatric disorders, but its mechanism of action is still poorly understood. Adult hippocampal neurogenesis (AHN) continues throughout life and is crucial for preserving several aspects of hippocampal-dependent cognitive functions. Nevertheless, the contribution of AHN in the neuromodulatory effects of tDCS remains unexplored. Here, we sought to investigate whether multisession anodal tDCS may modulate AHN and its associated cognitive functions. Multisession anodal tDCS were applied on the skull over the hippocampus of adult male mice for 20 min at 0.25 mA once daily for 10 d totally. We found that multisession anodal tDCS enhances AHN by increasing the proliferation, differentiation and survival of neural stem/progenitor cells (NSPCs). In addition, tDCS treatment increased cell cycle reentry and reduced cell cycle exit of NSPCs. The tDCS-treated mice exhibited a reduced GABAergic inhibitory tone in the dentate gyrus compared with sham-treated mice. The effect of tDCS on the proliferation of NSPCs was blocked by pharmacological restoration of GABABreceptor-mediated inhibition. Functionally, multisession anodal tDCS enhances performance on a contextual fear discrimination task, and this enhancement was prevented by blocking AHN using the DNA alkylating agent temozolomide (TMZ). Our results emphasize an important role for AHN in mediating the beneficial effects of tDCS on cognitive functions that substantially broadens the mechanistic understanding of tDCS beyond its well-described in hippocampal synaptic plasticity.SIGNIFICANCE STATEMENTTranscranial direct current stimulation (tDCS) has been shown to effectively enhance cognitive functions in healthy and pathologic conditions. However, the mechanisms underlying its effects are largely unknown and need to be better understood to enable its optimal clinical use. This study shows that multisession anodal tDCS enhances adult hippocampal neurogenesis (AHN) and therefore contributes to enhance context discrimination in mice. Our results also show that the effect of tDCS on AHN is associated with reduced GABAergic inhibition in the dentate gyrus. Our study uncovers a novel mechanism of anodal tDCS to elicit cognitive-enhancing effects and may have the potential to improve cognitive decline associated with normal aging and neurodegenerative disorders.
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