Positive Effect of Steroids in Posterior Reversible Encephalopathy Syndrome

We present a case of posterior reversible encephalopathy syndrome with severe clinical manifestation. Apart from initial aphasia, hemiparesis, and a generalized seizure, the patient had a prolonged loss of consciousness. Although blood pressure was normalized, the clinical status deteriorated continuously. After adding steroids to the therapy, the patient recovered rapidly, suggesting that this could have been a useful therapeutic approach. Even the vasogenic edema in the cerebral magnetic resonance imaging disappeared shortly within 6 days

Re-cycling paradigms: cell cycle regulation in adult hippocampal neurogenesis and implications for depression

Since adult neurogenesis became a widely accepted phenomenon, much effort has been put in trying to understand the mechanisms involved in its regulation. In addition, the pathophysiology of several neuropsychiatric disorders, such as depression, has been associated with imbalances in adult hippocampal neurogenesis. These imbalances may ultimately reflect alterations at the cell cycle level, as a common mechanism through which intrinsic and extrinsic stimuli interact with the neurogenic niche properties. Thus, the comprehension of these regulatory mechanisms has become of major importance to disclose novel therapeutic targets. In this review, we first present a comprehensive view on the cell cycle components and mechanisms that were identified in the context of the homeostatic adult hippocampal neurogenic niche. Then, we focus on recent work regarding the cell cycle changes and signaling pathways that are responsible for the neurogenesis imbalances observed in neuropathological conditions, with a particular emphasis on depression

Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation

A functional genetic screen using loss-of-function and gain-of-function alleles was performed to identify modifiers of tau-induced neurotoxicity using the 2N/4R (full-length) isoform of wild-type human tau expressed in the fly retina. We previously reported eye pigment mutations, which create dysfunctional lysosomes, as potent modifiers; here, we report 37 additional genes identified from ∼1900 genes screened, including the kinases shaggy/GSK-3beta, par-1/MARK, CamKI and Mekk1. Tau acts synergistically with Mekk1 and p38 to down-regulate extracellular regulated kinase activity, with a corresponding decrease in AT8 immunoreactivity (pS202/T205), suggesting that tau can participate in signaling pathways to regulate its own kinases. Modifiers showed poor correlation with tau phosphorylation (using the AT8, 12E8 and AT270 epitopes); moreover, tested suppressors of wild-type tau were equally effective in suppressing toxicity of a phosphorylation-resistant S11A tau construct, demonstrating that changes in tau phosphorylation state are not required to suppress or enhance its toxicity. Genes related to autophagy, the cell cycle, RNA-associated proteins and chromatin-binding proteins constitute a large percentage of identified modifiers. Other functional categories identified include mitochondrial proteins, lipid trafficking, Golgi proteins, kinesins and dynein and the Hsp70/Hsp90-organizing protein (Hop). Network analysis uncovered several other genes highly associated with the functional modifiers, including genes related to the PI3K, Notch, BMP/TGF-β and Hedgehog pathways, and nuclear trafficking. Activity of GSK-3β is strongly upregulated due to TDP-43 expression, and reduced GSK-3β dosage is also a common suppressor of Aβ42 and TDP-43 toxicity. These findings suggest therapeutic targets other than mitigation of tau phosphorylation

Electroencephalography Findings in Older Adults Undergoing Geriatric Treatment: A Surrogate for the Outcome?

Background: Comprehensive geriatric care (CGC) is a multidisciplinary approach developed to meet the needs of older patients. Electroencephalography (EEG) provides valuable information for monitoring the cerebral function. As a surrogate, EEG findings may help to estimate the course of diseases as well as the treatment outcomes. Objectives: Therefore, the aim of the present study is to investigate EEG findings in older patients receiving CGC. Methods: Patients with an initial EEG in a geriatric unit between May 2019 and April 2020 and treated using the CGC approach were analyzed. EEG abnormalities were defined as generalized (diffuse) background slowing and/or intermittent/persistent focal slowing and/or epileptiform discharges. Assessment results for the Barthel index (BI), Tinetti Balance and Gait test (TBGT), and Timed Up and Go test (TUG) were analyzed in relation to the presence of EEG abnormalities. Results: The study included 398 patients (mean age: 83.0 ± 6.57 years, 69.3% were female). Abnormal EEG patterns were found in 94 (23.6%) patients. Patients with EEG abnormalities had a mean age of 83.4 years versus a mean of 82.8 years in those without (p = 0.451). Based on all calculated scores, the majority of the patients improved after CGC, with a tendency to higher-grade improvements in those without EEG abnormalities (BI: 86.2% vs. 75.5%, p = 0.024; TUG: 53.3% vs. 31.9%, p p = 0.088). The presence of EEG abnormalities was associated with the parameters dementia (36.2% vs. 22.4%, p = 0.010), known epilepsy/seizure (19.1% vs. 5.9%, p p p = 0.030) during hospitalization. Conclusions: We found EEG abnormalities in almost a quarter of the patients treated in the geriatric unit. In older patients, the presence of EEG abnormalities is associated with lower improvements after CGC