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BioMed Research International 2023L. and are two traditional herbs with probable antiseizure effects. This study evaluated the effects of these two herbal extracts on pentylenetetrazol- (PTZ-) induced...
L. and are two traditional herbs with probable antiseizure effects. This study evaluated the effects of these two herbal extracts on pentylenetetrazol- (PTZ-) induced seizures in mice. We prepared hydroalcoholic extracts using seeds and the aerial parts of and then randomly divided 190 mice into 19 groups. Normal saline (10 mg/kg), diazepam (2 mg/kg), (2.5, 5, 10, 15, 30, 45, and 60 mg/kg), and (200, 400, 600, and 800 mg/kg) were intraperitoneally (IP) administrated 30 min before an IP administration of PTZ (90 mg/kg). Animals were observed for behavioral changes for one hour. In addition, the effects of flumazenil and naloxone on the antiseizure activity of and were assessed. showed antiseizure activity at the dose of 10 mg/kg; it prolonged the seizure latency and decreased the seizure duration. The mortality protection rate was 90% for this herbal extract. (600 mg/kg) prolonged the seizure latency and decreased both seizure duration and mortality. Neither flumazenil nor naloxone significantly reversed the antiseizure activities of and In mice, the hydroalcoholic extracts of and showed antiseizure activity against PTZ-induced seizures. We could not delineate the exact antiseizure mechanisms of these extracts in the current study.
Topics: Mice; Animals; Plant Extracts; Peganum; Lavandula; Flumazenil; Seizures; Naloxone
PubMed: 38089644
DOI: 10.1155/2023/4121998 -
Journal of Veterinary Internal Medicine 2023The long-term effect of implantable vagus nerve stimulators (VNS) on seizures has not been evaluated in epileptic dogs.
BACKGROUND
The long-term effect of implantable vagus nerve stimulators (VNS) on seizures has not been evaluated in epileptic dogs.
OBJECTIVES
Report seizure frequency in medication-resistant epileptic dogs before and after VNS implantation.
ANIMALS
Twelve client-owned dogs with idiopathic epilepsy and >1 seizure day per 3 weeks despite 3 months of appropriate use of 2 antiseizure medications and seizure diaries maintained 6 months before and >12 months after VNS implantation.
METHODS
Uncontrolled, open-label, before and after study. Mean monthly seizures and inter-seizure periods obtained from contemporaneous seizure diaries in the 6 months before implantation were compared with 0 to 6 months, 7 to 12 months, and subsequent 12-month periods after implantation. The number of dogs with >50% decrease in seizure frequency, >3 times increase in inter-ictal period interval, and seizure freedom for >3 months at the time of death or last follow-up were recorded.
RESULTS
Five of 12 dogs were euthanized <12 months after implantation. All 7 remaining dogs showed >50% decrease in seizure frequency until last follow-up, starting at a median of 37 to 48 months after implantation (range, 0-6 to 61-72 months) and a >3-fold increase in mean inter-seizure interval starting a median of 25 to 36 months after implantation (range, 0-6 months to 49-60 months), 3/7 dogs were seizure-free at death or last follow-up.
CONCLUSIONS AND CLINICAL IMPORTANCE
Monthly seizure frequencies decreased and inter-seizure intervals increased in all dogs 2 to 3 years after VNS implantation, but a high proportion were euthanized before this time point. Prospective clinical trials are required to establish causality and the magnitude of this association.
Topics: Humans; Dogs; Animals; Prospective Studies; Treatment Outcome; Epilepsy; Seizures; Vagus Nerve; Vagus Nerve Stimulation; Retrospective Studies; Dog Diseases
PubMed: 37864369
DOI: 10.1111/jvim.16908 -
Seizure Aug 2023This retrospective chart review study (GWEP20052) evaluated plant-derived highly purified cannabidiol (CBD; Epidyolex®; 100 mg/mL oral solution) use without clobazam...
PURPOSE
This retrospective chart review study (GWEP20052) evaluated plant-derived highly purified cannabidiol (CBD; Epidyolex®; 100 mg/mL oral solution) use without clobazam as add-on therapy in patients aged ≥2 years with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) enrolled in a European Early Access Program.
METHODS
Data were extracted from patient charts covering a period starting 3 months before CBD treatment and concluding after 12 months of CBD treatment, or sooner if a patient discontinued CBD or started clobazam.
RESULTS
Of 114 enrolled patients, data were available for 107 (92 LGS, 15 DS) who received CBD without clobazam for ≥3 months. Mean age: 14.5 (LGS) and 10.5 (DS) years; female: 44% (LGS) and 67% (DS). Mean time-averaged CBD dose: 13.54 (LGS) and 11.56 (DS) mg/kg/day. Median change from baseline in seizure frequency per 28 days over 3-month intervals varied from -6.2% to -20.9% for LGS and 0% to -16.7% for DS. Achievement of ≥50% reduction in drop (LGS) or convulsive (DS) seizures at 3 and 12 months: LGS, 19% (n = 69) and 30% (n = 53); DS, 21% (n = 14) and 13% (n = 8). Retention on CBD without clobazam (enrolled set): 94%, 80%, 69%, and 63% at 3, 6, 9, and 12 months. Adverse event (AE) incidence was 31%, most commonly somnolence, seizure, diarrhea, and decreased appetite. Two patients discontinued CBD owing to AEs, and four patients with LGS experienced elevated liver enzymes.
CONCLUSION
Results support favorable effectiveness and retention of CBD without concomitant clobazam for up to 12 months in clinical practice.
Topics: Humans; Adolescent; Cannabidiol; Lennox Gastaut Syndrome; Clobazam; Retrospective Studies; Anticonvulsants; Epilepsies, Myoclonic; Seizures; Treatment Outcome
PubMed: 37331197
DOI: 10.1016/j.seizure.2023.05.003 -
Epilepsia Open Dec 2023Sex differences in epilepsy appear driven in part due to effects of gonadal steroids, with varying results in experimental models based on species, strain, and method of...
OBJECTIVE
Sex differences in epilepsy appear driven in part due to effects of gonadal steroids, with varying results in experimental models based on species, strain, and method of seizure induction. Furthermore, removing the main source of these steroids via gonadectomy may impact seizure characteristics differently in males and females. Repeated low-dose kainic acid (RLDKA) systemic injection paradigms were recently shown to reliably induce status epilepticus (SE) and hippocampal histopathology in C57BL/6J mice. Here, we investigated whether seizure susceptibility in a RLDKA injection protocol exhibits a sex difference and whether gonadectomy differentially influences response to this seizure induction paradigm in males and females.
METHODS
Adult C57BL/6J mice were left gonad-intact as controls or gonadectomized (females: ovariectomized, OVX; males: orchidectomized, ORX). At least 2 weeks later, KA was injected ip, every 30 minutes at 7.5 mg/kg or less until the animal reached SE, defined by at least 5 generalized seizures (GS, Racine stage 3 or higher). Parameters of susceptibility to GS induction, SE development, and mortality rates were quantified.
RESULTS
No differences in seizure susceptibility or mortality were observed between control males and control females. Gonadectomized mice exhibited increased susceptibility and reduced latency to both GS and SE in comparison to corresponding controls of the same sex, but the effects were stronger in males. In addition, ORX males, but not OVX females, exhibited strongly increased seizure-induced mortality.
SIGNIFICANCE
The RLDKA protocol is notable for its efficacy in inducing SE and seizure-induced histopathology in C57BL/6J mice, the background for many transgenic strains in current use in epilepsy research. The present results indicate that this protocol may be beneficial for investigating the effects of gonadal hormone replacement on seizure susceptibility, mortality, and seizure-induced histopathology, and that gonadectomy unmasks sex differences in susceptibility to seizures and mortality not observed in gonad-intact controls.
Topics: Female; Mice; Animals; Male; Kainic Acid; Mice, Inbred C57BL; Seizures; Status Epilepticus; Epilepsy; Castration; Steroids
PubMed: 37715318
DOI: 10.1002/epi4.12828 -
Medicina Sep 2023Status epilepticus (SE) is the most frequent neurological emergency in neuropediatrics. It is the result of the failure of the mechanisms responsible for terminating an... (Review)
Review
Status epilepticus (SE) is the most frequent neurological emergency in neuropediatrics. It is the result of the failure of the mechanisms responsible for terminating an epileptic seizure or its onset, which leads to a prolonged epileptic seizure. The estimated incidence between 3-42 cases per 100,000 people per year. It has a bimodal distribution, affecting children and the elderly at the extremes of life. Mortality estimates are variable depending on age and etiology. Mortality in children could be lower than in adults, but it reaches a high morbidity of up to 66%. The definition has changed over the years in order to specify the start of treatment and to complement it with the scientific data, a time t1 and a t2 have been established. The time (t1) is the moment when treatment should begin, which varies depending on the semiology, at 5 minutes for a generalized tonicclonic seizure and at 10 minutes for a focal seizure. The second time (t2) refers to neuronal damage. Prompt and effective treatment decreases the risks of cardiac and respiratory complications, admission to intensive care units, and death.
Topics: Adult; Aged; Child; Humans; Status Epilepticus; Seizures; Heart; Hospitalization; Intensive Care Units
PubMed: 37714128
DOI: No ID Found -
Experimental Neurology Dec 2023Dravet syndrome is a rare form of severe genetic epilepsy characterized by recurrent and long-lasting seizures. It appears around the first year of life, with a quick...
Dravet syndrome is a rare form of severe genetic epilepsy characterized by recurrent and long-lasting seizures. It appears around the first year of life, with a quick evolution toward an increase in the frequency of the seizures, accompanied by a delay in motor and cognitive development, and does not respond well to antiepileptic medication. Most patients carry a mutation in the gene SCN1A encoding the α subunit of the voltage-gated sodium channel Nav1.1, resulting in hyperexcitability of neural circuits and seizure onset. In this work, we applied transcranial static magnetic stimulation (tSMS), a non-invasive, safe, easy-to-use and affordable neuromodulatory tool that reduces neural excitability in a mouse model of Dravet syndrome. We demonstrate that tSMS dramatically reduced the number of crises. Furthermore, crises recorded in the presence of the tSMS were shorter and less intense than in the sham condition. Since tSMS has demonstrated its efficacy at reducing cortical excitability in humans without showing unwanted side effects, in an attempt to anticipate a possible use of tSMS for Dravet Syndrome patients, we performed a numerical simulation in which the magnetic field generated by the magnet was modeled to estimate the magnetic field intensity reached in the cerebral cortex, which could help to design stimulation strategies in these patients. Our results provide a proof of concept for nonpharmacological treatment of Dravet syndrome, which opens the door to the design of new protocols for treatment.
Topics: Animals; Mice; Humans; NAV1.1 Voltage-Gated Sodium Channel; Epilepsies, Myoclonic; Seizures; Transcranial Magnetic Stimulation; Disease Models, Animal; Magnetic Phenomena
PubMed: 37884190
DOI: 10.1016/j.expneurol.2023.114581 -
Annals of Clinical and Translational... Oct 2023Circadian and multidien cycles of seizure occurrence are increasingly discussed as to their biological underpinnings and in the context of seizure forecasting. This...
OBJECTIVE
Circadian and multidien cycles of seizure occurrence are increasingly discussed as to their biological underpinnings and in the context of seizure forecasting. This study analyzes if patient reported seizures provide valid data on such cyclical occurrence.
METHODS
We retrospectively studied if circadian cycles derived from patient-based reporting reflect the objective seizure documentation in 2003 patients undergoing in-patient video-EEG monitoring.
RESULTS
Only 24.1% of more than 29000 seizures documented were accompanied by patient notifications. There was cyclical underreporting of seizures with a maximum during nighttime, leading to significant deviations in the circadian distribution of seizures. Significant cyclical deviations were found for focal epilepsies originating from both, frontal and temporal lobes, and for different seizure types (in particular, focal unaware and focal to bilateral tonic-clonic seizures).
INTERPRETATION
Patient seizure diaries may reflect a cyclical reporting bias rather than the true circadian seizure distributions. Cyclical underreporting of seizures derived from patient-based reports alone may lead to suboptimal treatment schemes, to an underestimation of seizure-associated risks, and may pose problems for valid seizure forecasting. This finding strongly supports the use of objective measures to monitor cyclical distributions of seizures and for studies and treatment decisions based thereon.
Topics: Humans; Retrospective Studies; Seizures; Epilepsies, Partial; Electroencephalography; Documentation
PubMed: 37608738
DOI: 10.1002/acn3.51880 -
Neurocritical Care Dec 2023Critically ill children with acute neurologic dysfunction are at risk for a variety of complications that can be detected by noninvasive bedside neuromonitoring.... (Review)
Review
Critically ill children with acute neurologic dysfunction are at risk for a variety of complications that can be detected by noninvasive bedside neuromonitoring. Continuous electroencephalography (cEEG) is the most widely available and utilized form of neuromonitoring in the pediatric intensive care unit. In this article, we review the role of cEEG and the emerging role of quantitative EEG (qEEG) in this patient population. cEEG has long been established as the gold standard for detecting seizures in critically ill children and assessing treatment response, and its role in background assessment and neuroprognostication after brain injury is also discussed. We explore the emerging utility of both cEEG and qEEG as biomarkers of degree of cerebral dysfunction after specific injuries and their ability to detect both neurologic deterioration and improvement.
Topics: Humans; Child; Critical Illness; Seizures; Electroencephalography; Brain Injuries; Intensive Care Units, Pediatric; Monitoring, Physiologic
PubMed: 36949358
DOI: 10.1007/s12028-023-01686-5 -
Journal of Clinical Neurophysiology :... Jan 2024Evaluating the effects of antiseizure medication (ASM) on patients with epilepsy remains a slow and challenging process. Quantifiable noninvasive markers that are...
PURPOSE
Evaluating the effects of antiseizure medication (ASM) on patients with epilepsy remains a slow and challenging process. Quantifiable noninvasive markers that are measurable in real-time and provide objective and useful information could guide clinical decision-making. We examined whether the effect of ASM on patients with epilepsy can be quantitatively measured in real-time from EEGs.
METHODS
This retrospective analysis was conducted on 67 patients in the long-term monitoring unit at Boston Children's Hospital. Two 30-second EEG segments were selected from each patient premedication and postmedication weaning for analysis. Nonlinear measures including entropy and recurrence quantitative analysis values were computed for each segment and compared before and after medication weaning.
RESULTS
Our study found that ASM effects on the brain were measurable by nonlinear recurrence quantitative analysis on EEGs. Highly significant differences ( P < 1e-11) were found in several nonlinear measures within the seizure zone in response to antiseizure medication. Moreover, the size of the medication effect correlated with a patient's seizure frequency, seizure localization, number of medications, and reported seizure frequency reduction on medication.
CONCLUSIONS
Our findings show the promise of digital biomarkers to measure medication effects and epileptogenicity.
Topics: Child; Humans; Retrospective Studies; Seizures; Brain; Electroencephalography; Epilepsy
PubMed: 35583401
DOI: 10.1097/WNP.0000000000000946 -
Brain Stimulation 2023Longitudinal EEG recorded by implanted devices is critical for understanding and managing epilepsy. Recent research reports patient-specific, multi-day cycles in...
BACKGROUND
Longitudinal EEG recorded by implanted devices is critical for understanding and managing epilepsy. Recent research reports patient-specific, multi-day cycles in device-detected epileptiform events that coincide with increased likelihood of clinical seizures. Understanding these cycles could elucidate mechanisms generating seizures and advance drug and neurostimulation therapies.
OBJECTIVE/HYPOTHESIS
We hypothesize that seizure-correlated cycles are present in background neural activity, independent of interictal epileptiform spikes, and that neurostimulation may temporarily interrupt these cycles.
METHODS
We analyzed regularly-recorded seizure-free data epochs from 20 patients implanted with a responsive neurostimulation (RNS) device for at least 1.5 years, to explore the relationship between cycles in device-detected interictal epileptiform activity (dIEA), clinician-validated interictal spikes, background EEG features, and neurostimulation.
RESULTS
Background EEG features tracked the cycle phase of dIEA in all patients (AUC: 0.63 [0.56-0.67]) with a greater effect size compared to clinically annotated spike rate alone (AUC: 0.55 [0.53-0.61], p < 0.01). After accounting for circadian variation and spike rate, we observed significant population trends in elevated theta and beta band power and theta and alpha connectivity features at the cycle peaks (sign test, p < 0.05). In the period directly after stimulation we observe a decreased association between cycle phase and EEG features compared to background recordings (AUC: 0.58 [0.55-0.64]).
CONCLUSIONS
Our findings suggest that seizure-correlated dIEA cycles are not solely due to epileptiform discharges but are associated with background measures of brain state; and that neurostimulation may temporarily interrupt these cycles. These results may help elucidate mechanisms underlying seizure generation, provide new biomarkers for seizure risk, and facilitate monitoring, treating, and managing epilepsy with implantable devices.
Topics: Humans; Electroencephalography; Epilepsy; Seizures; Brain
PubMed: 37979654
DOI: 10.1016/j.brs.2023.11.005