Effect of meteorological factors and lunar phases on occurrence of psychogenic nonepileptic seizures.

BACKGROUND: Psychogenicnonepilepticseizures (PNES) lack the abnormal electrographical discharges in electroencephalogram seen in epileptic seizures. The notion of the effects of meteorological factors and lunar phases onoccurrence of seizures in patients with PNES has been the subject of very few research studies and the available evidence in the literature is equivocal. In this study, we aimed to study the influence oflunarphases and meteorological factors on the frequency of PNES and its semiological categories. METHODS: We retrospectively reviewed the medical records of patients discharged with a diagnosis of PNES from our epilepsy monitoring unit in a 3-year period. The 119 patients who met the inclusion criteria were categorized into hypermotor, hypomotor, or intact sensorium based on semiology of their seizures. The occurrence of PNES, in total and in each semiological category, was correlated with the daily average temperature, atmospheric pressure, and the 4 lunar phases. RESULTS: There were 31.8% and 11.1% more-than-expected captured seizures when the average daily atmospheric pressure was lower or higher, respectively, of what is generally considered a comfortable atmospheric pressure. No consistent relation was found between the full moon phases and occurrence of PNES. CONCLUSION: A significant association between atmospheric pressure and the occurrence of nonepileptic seizures was found, whereas no consistent increase in PNES was observed during the full moon phases. There is still an open debate about the effect of the lunar phases on human behavior and neurological disorders such as PNES.

Recycling drug screen repurposes hydroxyurea as a sensitizer of glioblastomas to temozolomide targeting de novo DNA synthesis, irrespective of molecular subtype.

Background: Glioblastoma (GBM) is the most common and most aggressive primary malignant brain tumor. Standard-of-care treatment involves maximal surgical resection of the tumor followed by radiation and chemotherapy (temozolomide [TMZ]). The 5-year survival rate of patients with GBM is <10%, a colossal failure that has been partially attributed to intrinsic and/or acquired resistance to TMZ through O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status in the tumor. Methods: A drug screening aimed at evaluating the potential recycling and repurposing of known drugs was conducted in TMZ-resistant GBM cell lines and primary cultures of newly diagnosed GBM with different MGMT promoter methylation status, phenotypic/genotypic background and subtype, and validated with sphere formation, cell migration assays, and quantitative invasive orthotopic in vivo models. Results: We identified hydroxyurea (HU) to synergize with TMZ in GBM cells in culture and in vivo, irrespective of MGMT promoter methylation status, subtype, and/or stemness. HU acts specifically on the S-phase of the cell cycle by inhibiting the M2 unit of enzyme ribonucleotide reductase. Knockdown of this enzyme using RNA interference and other known chemical inhibitors exerted a similar effect to HU in combination with TMZ both in culture and in vivo. Conclusions: We demonstrate preclinical efficacy of repurposing hydroxyurea in combination with TMZ for adjuvant GBM therapy. This combination benefit is of direct clinical interest given the extensive use of TMZ and the associated problems with TMZ-related resistance and treatment failure.

Alexia Without Agraphia: A Rare Entity.

Pure alexia refers to an acquired disorder associated with the damage to medial occipitotemporal gyrus in the dominant hemisphere, which is also known as visual word form area (VWFA). VWFA is involved in rapid word recognition and fluent reading. Alexia without agraphia is a disconnection syndrome that occurs when the splenium is also damaged with the occipital lobe on a dominant side. We report a case of a 72-year-old right-handed male who presented with alexia without agraphia accompanied by right homonymous hemianopia resulting from acute infarct of the left occipital lobe, the splenium of the corpus callosum and posterior thalamus that probably occurred on the previous day. During the evaluation, he exhibited marked impairment in the ability to read with the vision being grossly normal. Magnetic resonant imaging (MRI) revealed an acute infarct of the left occipital lobe, the splenium of the corpus callosum and posterior thalamus. A computerized tomography angiogram (CTA) revealed left posterior cerebral artery (PCA) territory infarct without any evidence of hemorrhagic conversion. Infarction of the occipital lobe on the dominant side (left) in a right-handed individual may cause a disruption in the visual word form area and is manifested by an inability to read with no abnormalities in visual acuity.

Systemic anticancer neural stem cells in combination with a cardiac glycoside for glioblastoma therapy.

The tumor-tropic properties of neural stem cells (NSCs) have been shown to serve as a novel strategy to deliver therapeutic genes to tumors. Recently, we have reported that the cardiac glycoside lanatoside C (Lan C) sensitizes glioma cells to the anticancer agent tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Here, we engineered an FDA-approved human NSC line to synthesize and secrete TRAIL and the Gaussia luciferase (Gluc) blood reporter. We showed that upon systemic injection, these cells selectively migrate toward tumors in the mice brain across the blood-brain barrier, target invasive glioma stem-like cells, and induce tumor regression when combined with Lan C. Gluc blood assay revealed that 30% of NSCs survived 1 day postsystemic injection and around 0.5% of these cells remained viable after 5 weeks in glioma-bearing mice. This study demonstrates the potential of systemic injection of NSCs to deliver anticancer agents, such as TRAIL, which yields glioma regression when combined with Lan C.

Multiplex blood reporters for simultaneous monitoring of cellular processes.

Reporters secreted into the conditioned medium of cells in culture or into blood in vivo have shown to be useful tools for simple and noninvasive monitoring of biological processes in real-time. Here, we characterize the naturally secreted Vargula luciferase as a secreted blood reporter and show that this reporter can be multiplexed with the secreted Gaussia luciferase and alkaline phosphatase for simultaneous monitoring of three different cellular processes in the same biological system. We applied this system to monitor the response of three different subsets of glioma cells to a clinically relevant chemotherapeutic agent in the same well in culture or animal in vivo. This system could be extended to any field to detect multiple processes in the same biological system and is amenable for high-throughput screening to find drugs that affect multiple cellular populations/phenomena simultaneously.