Beware of nonconvulsive seizures in prolonged disorders of consciousness: Long-term EEG monitoring is the key.

OBJECTIVE: Evaluate the prevalence of epileptic seizures (ES) and epileptiform discharges (EDs) in patients with prolonged disorders of consciousness (DOC), and potential influence of amantadine on epilepsy. METHODS: We conducted a retrospective study in 34 patients hospitalized in a DOC care unit for prolonged DOC between 2012 and 2018, who received a long-term EEG monitoring (LTM). We reviewed the prevalence of ES, EDs and nonconvulsive seizures (NCSz), the type of DOC recovery treatment administered, and neurological outcome. RESULTS: LTM was more effective than standard EEGs in detecting EDs (32% vs 21% respectively). Moreover, 12% of the LTM showed NCSz. Among patients with EDs in LTM, 73% showed no EDs in standard EEG recordings, even when performed more than once. The presence of EDs and/or NCSz in LTM was significantly associated with the occurrence of remote clinical epileptic seizures (p = 0.017) but did not influence neurological outcome (p = 1). Amantadine was not associated with higher occurrence of EDs/NCSz or clinical seizures. CONCLUSION: In our prolonged DOC population, LTM showed more pathological results (EDs and NCSz) than standard EEGs, which was significantly associated with remote clinical seizures. SIGNIFICANCE: The use of LTM might be advised to rule out NCSz in patients with prolonged DOC.

Validation of an algorithm of time-dependent electro-clinical risk stratification for electrographic seizures (TERSE) in critically ill patients.

OBJECTIVE: The clinical implementation of continuous electroencephalography (CEEG) monitoring in critically ill patients is hampered by the substantial burden of work that it entails for clinical neurophysiologists. Solutions that might reduce this burden, including by shortening the duration of EEG to be recorded, would help its widespread adoption. Our aim was to validate a recently described algorithm of time-dependent electro-clinical risk stratification for electrographic seizure (ESz) (TERSE) based on simple clinical and EEG features. METHODS: We retrospectively reviewed the medical records and EEG recordings of consecutive patients undergoing CEEG between October 1, 2015 and September, 30 2016 and assessed the sensitivity of TERSE for seizure detection, as well as the reduction in EEG time needed to be reviewed. RESULTS: In a cohort of 407 patients and compared to full CEEG review, the model allowed the detection of 95% of patients with ESz and 97% of those with electrographic status epilepticus. The amount of CEEG to be recorded to detect ESz was reduced by two-thirds, compared to the duration of CEEG taht was actually recorded. CONCLUSIONS: TERSE allowed accurate time-dependent ESz risk stratification with a high sensitivity for ESz detection, which could substantially reduce the amount of CEEG to be recorded and reviewed, if applied prospectively in clinical practice. SIGNIFICANCE: Time-dependent electro-clinical risk stratification, such as TERSE, could allow more efficient practice of CEEG and its more widespread adoption. Future studies should aim to improve risk stratification in the subgroup of patients with acute brain injury and absence of clinical seizures.

Epileptic activity in neurological deterioration after ischemic stroke, a continuous EEG study.

OBJECTIVE: Despite improvement in acute stroke care, almost 40% of patients with ischemic stroke present neurological deterioration. Neurological deterioration is associated with higher death and dependency rates. Neurological deterioration mechanisms are unknown, and half of neurological deterioration remains unexplained. We postulate that a substantial proportion of neurological deterioration in ischemic stroke is associated with periodic discharges/non-convulsive seizures that negatively impact the recovery of ischemic stroke and worsen symptoms. METHODS: Retrospective review of 24 h continuous EEG monitoring (cEEG) performed for neurological deterioration in the stroke unit of a tertiary academic centre. RESULTS: Eighty-one patients were included. cEEG detected epileptic activities in 44% of cases (Non-convulsive seizures/non-convulsive status epilepticus: 10/81 (12%), periodic discharges: 17/81 (21%) and sporadic epileptiform discharges in 14/81 (17%)). The proportion of patients who did not receive recanalization therapy was significantly higher in the NCSE/NCSz/PDs group than in the group devoid of NCSE/NCSz/PDs: 17/22 (77%) vs 13/59 (22%); p < 0,001. Treatment of Non-convulsive seizures /non-convulsive status epilepticus and periodic discharges was followed by EEG improvement in respectively 7/8 and 10/16 of treated patients. CONCLUSIONS: Non-convulsive seizures /non-convulsive status epilepticus /periodic discharges are associated to neurological deterioration after ischemic stroke. SIGNIFICANCE: Treatment of Non-convulsive seizures /non-convulsive status epilepticus and periodic discharges, if such patterns are detected, could help prevent adverse metabolic consequences of epileptic activities on ischemic brain tissue.

Oleate Abrogates Palmitate-Induced Lipotoxicity and Proinflammatory Response in Human Bone Marrow-Derived Mesenchymal Stem Cells and Osteoblastic Cells.

Osteoporosis is a metabolic bone disease associated with unequilibrated bone remodeling resulting from decreased bone formation and/or increased bone resorption, leading to progressive bone loss. In osteoporotic patients, low bone mass is associated with an increase of bone marrow fat resulting from accumulation of adipocytes within the bone marrow. Marrow adipocytes are active secretory cells, releasing cytokines, adipokines and free fatty acids (FA) that influence the bone marrow microenvironment and alter the biology of neighboring cells. Therefore, we examined the effect of palmitate (Palm) and oleate (Ole), 2 highly prevalent FA in human organism and diet, on the function and survival of human mesenchymal stem cells (MSC) and MSC-derived osteoblastic cells. The saturated FA Palm exerted a cytotoxic action via initiation of endoplasmic reticulum stress and activation of the nuclear factor κB (NF-κB) and ERK pathways. In addition, Palm induced a proinflammatory response, as determined by the up-regulation of Toll-like receptor 4 expression as well as the increase of IL-6 and IL-8 expression and secretion. Moreover, we showed that MSC-derived osteoblastic cells were more sensitive to lipotoxicity than undifferentiated MSC. The monounsaturated FA Ole fully neutralized Palm-induced lipotoxicity by impairing activation of the pathways triggered by the saturated FA. Moreover, Ole promoted Palm detoxification by fostering its esterification into triglycerides and storage in lipid droplets. Altogether, our data showed that physiological concentrations of Palm and Ole differently modulated cell death and function in bone cells. We therefore propose that FA could influence skeletal health.

Glycerol metabolism alteration in adipocytes from n3-PUFA-depleted rats, an animal model for metabolic syndrome.

Aquaglyceroporin 7 (AQP7) is a glycerol transporter expressed in adipocytes. Its expression has been shown to be modulated in obesity. Metabolic syndrome is characterized by abdominal obesity, insulin resistance, dyslipidemia, and hypertension. An animal model displaying several features of metabolic syndrome was used to study the AQP7 expression at both mRNA and protein level and glycerol flux in adipocytes. Second generation n3-PUFA depleted female rats is a good animal model for metabolic syndrome as it displays characteristic features such as liver steatosis, visceral obesity, and insulin resistance. Our data show a reduced expression of AQP7 at the protein level in adipose tissue from n3-PUFA-depleted rats, without any changes at the mRNA levels. [U-(14)C]-Glycerol uptake was not modified in adipocytes from n3-PUFA-depleted animals.

Human cystic fibrosis embryonic stem cell lines derived on placental mesenchymal stromal cells.

This study describes the production of two new human embryonic stem cell (hESC) lines affected by cystic fibrosis. These cell lines are heterozygous compounds, each a carrier of the DF508 mutations associated either with E585X or with 3849+10 kb C-->T. The derivation process was performed on irradiated human placental mesenchymal stromal cells and designed to minimize contact with xeno-components. This new source of feeder cells is easy to obtain and devoid of ethical concerns. The cells have a great capacity to proliferate which reduces the need for continuous preparation of new feeder cell lines. In addition, three normal hESC lines were obtained in the same conditions. The five stem cell lines retained hESC-specific features, including an unlimited and undifferentiated proliferation capacity, marker expression and the maintenance of stable karyotype. They also demonstrated pluripotency in vitro, forming cell lineages of the three germ layers, as indicated by immunolocalization of beta-tubulin, alpha-fetoprotein and actin. These new genetic cell lines represent an important in-vitro tool to study the physiological processes underlying this genetic disease, drug screening, and tissue engineering.