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Journal of Epilepsy Research Dec 2020The definition of status epilepticus (SE) was revised recently in accordance with the various evidences of neuronal injury and changes in clinical settings. Currently,... (Review)
Review
The definition of status epilepticus (SE) was revised recently in accordance with the various evidences of neuronal injury and changes in clinical settings. Currently, the most acceptable duration of continuous seizure activity is 5 minutes. In 2015, the International League Against Epilepsy Task Force, which was convened to develop a definition and classification of SE, presented a new classification based on four axes: 1) semiology, 2) etiology, 3) electroencephalogram (EEG) correlates, and 4) age. The essential element of nonconvulsive SE (NCSE) is the presence of neurological abnormalities induced by a prolonged epileptic process. The definition of refractory SE involves either clinical or electrographic seizures that persist after adequate doses of an initial benzodiazepine and acceptable second-line antiseizure drugs. The use of EEG is critical in the diagnosis and treatment of NCSE. However, there are a wide range of EEG abnormalities in NCSE. Both the Neurocritical Care Society and the American Epilepsy Society have suggested a paradigm for treating convulsive SE (CSE). The first-line treatment of CSE with benzodiazepine is well-established. The second-line treatment comprises intravenous (IV) doses of fosphenytoin (phenytoin), valproate, phenobarbital, levetiracetam, or midazolam. Although fosphenytoin (phenytoin) and valproate are commonly used in NCSE, the effectiveness of antiepileptic drugs (AEDs) on NCSE has not been well studied. New AEDs such as IV levetiracetam and lacosamide can also be used to treat NCSE with fewer side effects and drug-drug interactions. For refractory SE, general anesthesia with IV midazolam, propofol, pentobarbital, or thiopental could be applied. Use of ketamine, megadose phenobarbital therapy, and multiple combinations of various AEDs including high doses of oral AEDs can also be considered. New-onset refractory status epilepticus (NORSE) and its subcategory, febrile infection-related epilepsy syndrome, involve autoimmune processes. AEDs alone are poorly effective in the treatment of SE in autoimmune encephalitis. Immunotherapy such as steroids, immunoglobulin, rituximab, or tocilizumab can be effective.
PubMed: 33659195
DOI: 10.14581/jer.20008 -
Indian Pediatrics Mar 2020Refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE) are neurological emergencies with considerable mortality and morbidity. In this paper,... (Review)
Review
CONTEXT
Refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE) are neurological emergencies with considerable mortality and morbidity. In this paper, we provide an overview of causes, evaluation, treatment, and consequences of RSE and SRSE, reflecting the lack of high-quality evidence to inform therapeutic approach.
SOURCES
This is a narrative review based on personal practice and experience. Nevertheless, we searched MEDLINE (using PubMed and OvidSP vendors) and Cochrane central register of controlled trials, using appropriate keywords to incorporate recent evidence.
RESULTS
Refractory status epilepticus is commonly defined as an acute convulsive seizure that fails to respond to two or more anti-seizure medications including at least one non-benzodiazepine drug. Super-refractory status epilepticus is a status epilepticus that continues for ≥24 hours despite anesthetic treatment, or recurs on an attempted wean of the anesthetic regimen. Both can occur in patients known to have epilepsy or de novo, with increasing recognition of autoimmune and genetic causes. Electroencephalography monitoring is essential to monitor treatment response in refractory/super-refractory status epilepticus, and to diagnose non-convulsive status epilepticus. The mainstay of treatment for these disorders includes anesthetic infusions, primarily midazolam, ketamine, and pentobarbital. Dietary, immunological, and surgical treatments are viable in selected patients. Management is challenging due to multiple acute complications and long-term adverse consequences.
CONCLUSIONS
We have provided a synopsis of best practices for diagnosis and management of refractory/super-refractory status epilepticus and highlighted the lack of sufficient high-quality evidence to drive decision making, ending with a brief foray into avenues for future research.
Topics: Anesthetics; Anticonvulsants; Combined Modality Therapy; Diagnosis, Differential; Diet Therapy; Electroencephalography; Humans; Risk Factors; Status Epilepticus; Treatment Failure
PubMed: 32198865
DOI: 10.1007/s13312-020-1759-0 -
Pharmaceutical Biology Dec 2019γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter and it is well established that activation of GABA receptors favours sleep. l-Theanine, a naturally...
CONTEXT
γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter and it is well established that activation of GABA receptors favours sleep. l-Theanine, a naturally occurring amino acid first discovered in green tea, is a well-known anti-anxiety supplement with proven relaxation benefits.
OBJECTIVE
This study investigated the potential synergistic sleep enhancement effect of GABA/l-theanine mixture.
MATERIALS AND METHODS
Pentobarbital-induced sleep test was applied to find proper concentration for sleep-promoting effect in ICR mice. Electroencephalogram (EEG) analysis was performed to investigate total sleeping time and sleep quality in normal SD rats and caffeine-induced awareness model. Real-time polymerase chain reaction (RT-PCR) was applied to investigate whether the sleep-promoting mechanism of GABA/l-theanine mixture involved transcriptional processes.
RESULTS
GABA/l-theanine mixture (100/20 mg/kg) showed a decrease in sleep latency (20.7 and 14.9%) and an increase in sleep duration (87.3 and 26.8%) compared to GABA or theanine alone. GABA/l-theanine mixture led to a significant increase in rapid eye movement (REM) (99.6%) and non-REM (NREM) (20.6%) compared to controls. The use of GABA/l-theanine mixture rather than GABA or l-theanine alone restored to normal levels sleep time and quality in the arousal animal model. The administration of GABA/l-theanine led to increased expression of GABA and the glutamate GluN1 receptor subunit.
CONCLUSIONS
GABA/l-theanine mixture has a positive synergistic effect on sleep quality and duration as compared to the GABA or l-theanine alone. The increase in GABA receptor and GluN1 expression is attributed to the potential neuromodulatory properties of GABA/l-theanine combination, which seems to affect sleep behaviour.
Topics: Animals; Drug Synergism; Drug Therapy, Combination; Glutamates; Mice; Mice, Inbred ICR; Random Allocation; Rats; Rats, Sprague-Dawley; Receptors, Glutamate; Sleep Latency; Sleep, Slow-Wave; gamma-Aminobutyric Acid
PubMed: 30707852
DOI: 10.1080/13880209.2018.1557698 -
Cell Metabolism Mar 2023Animals that consume fermenting fruit and nectar are at risk of exposure to ethanol and the detrimental effects of inebriation. In this report, we show that the hormone...
Animals that consume fermenting fruit and nectar are at risk of exposure to ethanol and the detrimental effects of inebriation. In this report, we show that the hormone FGF21, which is strongly induced by ethanol in murine and human liver, stimulates arousal from intoxication without changing ethanol catabolism. Mice lacking FGF21 take longer than wild-type littermates to recover their righting reflex and balance following ethanol exposure. Conversely, pharmacologic FGF21 administration reduces the time needed for mice to recover from ethanol-induced unconsciousness and ataxia. FGF21 did not counteract sedation caused by ketamine, diazepam, or pentobarbital, indicating specificity for ethanol. FGF21 mediates its anti-intoxicant effects by directly activating noradrenergic neurons in the locus coeruleus region, which regulates arousal and alertness. These results suggest that this FGF21 liver-brain pathway evolved to protect against ethanol-induced intoxication and that it might be targeted pharmaceutically for treating acute alcohol poisoning.
Topics: Humans; Animals; Mice; Alcoholic Intoxication; Ethanol; Fibroblast Growth Factors; Brain
PubMed: 36889282
DOI: 10.1016/j.cmet.2023.02.005 -
Frontiers in Nutrition 2022L-Theanine is commonly used to improve sleep quality through inhibitory neurotransmitters. On the other hand, Mg, a natural NMDA antagonist and GABA agonist, has a...
L-Theanine is commonly used to improve sleep quality through inhibitory neurotransmitters. On the other hand, Mg, a natural NMDA antagonist and GABA agonist, has a critical role in sleep regulation. Using the caffeine-induced brain electrical activity model, here we investigated the potency of L-theanine and two novel Mg-L-theanine compounds with different magnesium concentrations on electrocorticography (ECoG) patterns, GABAergic and serotonergic receptor expressions, dopamine, serotonin, and melatonin levels. Furthermore, we evaluated the sleep latency and duration in the pentobarbital induced sleep model. We herein showed that L-theanine, particularly its various complexes with magnesium increases the expression of GABAergic, serotonergic, and glutamatergic receptors, which were associated with decreased ECoG frequency, increased amplitude, and enhanced delta wave powers. Besides increased dopamine, serotonin, and melatonin; decreased MDA and increased antioxidant enzyme levels were also observed particularly with Mg-complexes. Protein expression analyses also showed that Mg-L-theanine complexes decrease inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) levels significantly. In accordance with these results, Mg complexes improved the sleep latency and duration even after caffeine administration. As a result, our data indicate that Mg-L-theanine compounds potentiate the effect of L-theanine on sleep by boosting slow-brain waves, regulating brain electrical activity, and increasing neurotransmitter and GABA receptor levels.
PubMed: 35449538
DOI: 10.3389/fnut.2022.874254 -
Journal of Clinical Neurophysiology :... May 2022Anesthetic agents have been widely used in the treatment of refractory status epilepticus and the medical management of increased intracranial pressure whenever the goal... (Observational Study)
Observational Study
PURPOSE
Anesthetic agents have been widely used in the treatment of refractory status epilepticus and the medical management of increased intracranial pressure whenever the goal is therapeutic burst suppression. Periodic patterns typically consisting of generalized periodic discharges (GPDs) following emergence from anesthesia have been described in several case reports. However, their clinical significance and in particular whether these patterns are epileptiform remains unclear.
METHODS
This is a single-center, retrospective, observational study examining EEG patterns following emergence from pharmacologically induced burst suppression. Clinical and EEG data were collected. Patients who developed GPDs following anesthetic wean were compared with those who did not.
RESULTS
Over 4.5 years, 14 patients developed GPDs related to anesthetic withdrawal. The GPDs had a frequency between 0.5 and 2.5 Hz. Generalized periodic discharges related to anesthetic withdrawal were transient, with a median duration of 40 hours (interquartile range, 24-48 hours). Notably, in all patients, the pattern was stimulus dependent. When compared with a control group of 19 consecutive patients who did not develop a generalized periodic pattern in the context of the anesthetic wean, there was no significant difference in the status epilepticus relapse between the two groups (29% vs. 44%; P = 0.63). Patients in the GPD group were more likely to be on pentobarbital (93% vs. 58%; P = 0.05) and were more likely to have concomitant systemic infection treated with antibiotics compared with the control group (86% vs. 42%; P = 0.02).
CONCLUSIONS
Generalized periodic patterns are common following the wean of intravenous anesthetics (particularly pentobarbital) and likely represent a transitional encephalopathic state in a subset of patients. Their morphology is distinct and can be differentiated from the reemergence of status epilepticus (if the latter was the indication for anesthetic treatment). Failure to recognize this pattern may lead to prolonged unnecessary treatments if it is mistaken for the emergence of seizure activity. The presence of concomitant systemic infection and associated antibiotic treatment may be risk factors for the development of this pattern.
Topics: Anesthesia; Anesthetics; Electroencephalography; Humans; Patient Discharge; Pentobarbital; Retrospective Studies; Status Epilepticus
PubMed: 33038092
DOI: 10.1097/WNP.0000000000000779