Posts Tagged seizures

[Abstract + References] The impact of maternal epilepsy on delivery and neonatal outcomes

Abstract

Purpose

Epilepsy is a common neurological disorder that may complicate reproductive health. Our aim in this study was to provide prospective ascertainment of obstetric and neonatal outcomes in women with epilepsy and investigate whether the risk of pregnancy, delivery, and neonatal complications differed between women with epilepsy and women without epilepsy.

Methods

Pregnant women with epilepsy and women without epilepsy (control group) were prospectively evaluated during the years 2013–2018. They were regularly followed by a neurologist and obstetrician until the end of pregnancy.

Results

Delivery and perinatal outcomes were compared between 112 women diagnosed with epilepsy and 277 women without epilepsy. Epilepsy was a significant risk factor for preterm delivery, cesarean section, fetal hypoxia, and Apgar score ≤ 7 at 5 min in offspring (odds ratio (OR) = 2.83, 95% confidence interval (CI) 1.03–7.76; OR = 5.61, 95% CI 3.44–9.14; OR = 1.81, 95% CI 1.08–3.04; OR = 8.12, 95% CI 4.04–16.35, respectively). Seizures during pregnancy had influence on the preference of cesarean section as a mode of delivery (ОR = 3.39; 95% CI 1.40–8.17). The rate of perinatal hypoxia was significantly higher in children born by cesarean section (ОR = 2.84; 95% CI 1.04–7.76). There was no significant difference between women with epilepsy and controls in malformation rate.

Conclusions

Women with epilepsy had an increased risk of pregnancy and delivery complications. Cesarean section was associated with an increased risk of complications in offspring.

 

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via The impact of maternal epilepsy on delivery and neonatal outcomes | SpringerLink

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[Review] Ketogenic Diet and Epilepsy – Full Text PDF

Abstract

Currently available pharmacological treatment of epilepsy has limited effectiveness.
In epileptic patients, pharmacological treatment with available anticonvulsants leads to seizure control in <70% of cases. Surgical intervention can lead to control in a selected subset of patients, but still leaves a significant number of patients with uncontrolled seizures. Therefore, in drug-resistant epilepsy, the ketogenic diet proves to be useful. The purpose of this review was to provide a comprehensive overview of what was published about the benefits of ketogenic diet treatment in patients with epilepsy. Clinical data on the benefits of ketogenic diet treatment in terms of clinical symptoms and adverse reactions in patients with epilepsy have been reviewed. Variables that could have influenced the interpretation of the data were also discussed (e.g., gut microbiota). The data in this review contributes to a better understanding of the potential benefits of a ketogenic diet in the treatment of epilepsy and informs scientists, clinicians, and patients—as well as their families and caregivers—about the possibilities of such treatment. Since 1990, the number of publications on attempts to treat drug-resistant epilepsy with a ketogenic diet has grown so rapidly that it has become a challenge to see the overall trajectory and major milestones achieved in this field. In this review, we hope to provide the latest data from randomized clinical trials, practice guidelines, and new research areas over the past 2 years.

[…]

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[Abstract] Vagus Nerve Stimulation for the Treatment of Epilepsy

First page of article

Vagus nerve stimulation (VNS) was the first neuromodulation device approved for treatment of epilepsy. In more than 20 years of study, VNS has consistently demonstrated efficacy in treating epilepsy. After 2 years, approximately 50% of patients experience at least 50% reduced seizure frequency. Adverse events with VNS treatment are rare and include surgical adverse events (including infection, vocal cord paresis, and so forth) and stimulation side effects (hoarseness, voice change, and cough). Future developments in VNS, including closed-loop and noninvasive stimulation, may reduce side effects or increase efficacy of VNS.

via Vagus Nerve Stimulation for the Treatment of Epilepsy – Neurosurgery Clinics

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[Infographic] First Seizure Management

 

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[Infographic] Operational Classification of Seizure Types

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[WEB SITE] Stem cell-derived neurons stop seizures and improve cognitive function

People with untreatable epilepsy may one day have a treatment: ‘Convincing’ their own cells to become the neurons they need

IMAGE

IMAGE: THIS IS ASHOK K. SHETTY. 
CREDIT: TEXAS A&M UNIVERSITY HEALTH SCIENCE CENTER.

About 3.4 million Americans, or 1.2 percent of the population, have active epilepsy. Although the majority respond to medication, between 20 and 40 percent of patients with epilepsy continue to have seizures even after trying multiple anti-seizure drugs. Even when the drugs do work, people may develop cognitive and memory problems and depression, likely from the combination of the underlying seizure disorder and the drugs to treat it.

A team led by Ashok K. Shetty, PhD, a professor in the Department of Molecular and Cellular Medicine at the Texas A&M College of Medicine, associate director of the Institute for Regenerative Medicine and a research career scientist at the Olin E. Teague Veterans’ Medical Center, part of the Central Texas Veterans Health Care System, is working on a better and permanent treatment for epilepsy. Their results published this week in the Proceedings of the National Academy of Sciences (PNAS).

Seizures are caused when the excitatory neurons in the brain fire too much and inhibitory neurons–the ones that tell the excitatory neurons to stop firing–aren’t as abundant or aren’t operating at their optimal level. The main inhibitory neurotransmitter in the brain is called GABA, short for gamma-Aminobutyric acid.

Over the last decade, scientists have learned how to create induced pluripotent stem cells from ordinary adult cells, like a skin cell. These stem cells can then be coaxed to become virtually any type of cells in the body, including neurons that use GABA, called GABAergic interneurons.

“What we did is transplant human induced pluripotent stem cell-derived GABAergic progenitor cells into the hippocampus in an animal model of early temporal lobe epilepsy,” Shetty said. The hippocampus is a region in the brain where seizures originate in temporal lobe epilepsy, which is also important for learning, memory and mood. “It worked very well to suppress seizures and even to improve cognitive and mood function in the chronic phase of epilepsy.”

Further testing showed that these transplanted human neurons formed synapses, or connections, with the host excitatory neurons. “They were also positive for GABA and other markers of specialized subclasses of inhibitory interneurons, which was the goal,” Shetty said. “Another fascinating aspect of this study is that transplanted human GABAergic neurons were found to be directly involved in controlling seizures, as silencing the transplanted GABAergic neurons resulted in an increased number of seizures.”

“This publication by Dr. Shetty and his colleagues is a major step forward in treating otherwise incurable diseases of the brain,” said Darwin J. Prockop, MD, PhD, the Stearman Chair in Genomic Medicine, director of the Texas A&M Institute for Regenerative Medicine and professor at the Texas A&M College of Medicine. “One important aspect of the work is that the same cells can be obtained from a patient.” This type of process, called autologous transplant, is patient specific, meaning that there would be no risk of rejection of the new neurons, and the person wouldn’t need anti-rejection medication.

“We will need to make sure that we’re doing more good than harm,” Shetty said. “Going forward, we need to make sure that all of the cells transplanted have turned into neurons, because putting undifferentiated pluripotent stem cells into the body could lead to tumors and other problems.”

The development of epilepsy often happens after a head injury, which is why the Department of Defense is interested in funding the development of better treatment and prevention options.

“A great deal of research is required before patients can be safely treated,” Prockop said. “But this publication shows a way in which patients can someday be treated with their own cells for the devastating effects of epilepsy but perhaps also other diseases such as Parkinsonism and Alzheimer’s disease.”

Shetty cautioned that these tests were early interventions after the initial brain injury induced by status epilepticus, which is a state of continuous seizures lasting more than five minutes in humans. The next step is to see if similar transplants would work for cases of chronic epilepsy, particularly drug-resistant epilepsy. “Currently, there is no effective treatment for drug-resistant epilepsy accompanying with depression, memory problems, and a death rate five to 10 times that of the general population,” he said. “Our results suggest that induced pluripotent stem cell-derived GABAergic cell therapy has the promise for providing a long-lasting seizure control and relieving co-morbidities associated with epilepsy.”

 

via Stem cell-derived neurons stop seizures and improve cognitive function | EurekAlert! Science News

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[Editorial] New Directions in the Management of Status Epilepticus – Neurology

Status Epilepticus (SE) is a neurological emergency and has high morbidity and mortality. The International League Against Epilepsy (ILAE) recently updated their definition to specify that, “SE is a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms, which lead to abnormally, prolonged seizures.” Such phenomena can lead to long-term neurological complications due to neuronal death, glia, neurological injury, aberrant neuroplasticity, oxidative stress and inflammation, and alteration of neuronal networks. Depending upon the type and duration of SE, these mechanisms are quite variable. Therefore, in response to the updated definition of SE, novel avenues of research are required to address the specified involvement of the underlying mechanisms and pathophysiology resulting in the development of and outcomes from SE.

Improving the basic science understanding of SE will facilitate essential clinical trials. One can envision such experiments to include device and compound-based technological interventions directed at aborting the seizure activity and improving clinical outcomes. Benzodiazepines remain one of the cornerstones of treatment, and studies are underway to study new delivery options, including intranasal, buccal, and intramuscular midazolam, in addition to rectal diazepam, with the goal of aborting the seizure activity outside the hospitals, as rapidly as possible. Approved and off-label anticonvulsants, such as phenytoin, phenobarbital, valproate, topiramate, levetiracetam, lacosamide, steroids, immunosuppressants, and neuroprotective compounds, have also shown some efficacy at treating SE. However, substantial challenges remain in optimally managing SE and minimizing the short- and long-term complications. Such difficulties can be overcome by innovative approaches targeting the underlying mechanisms of neuronal excitability, glia, neuronal death, neuroplasticity, oxidative stress, inflammation, and neuroinflammation.

The book comprises six original research articles and four reviews. Collectively, the materials provide insights into the pathophysiology, clinical presentation, treatment, recent advances and future directions in the management of SE, with the goal of providing an in-depth view and advancing the field to improve management of SE.

The book opens with an original research article by Kristin Phillips et al. which showed the role of hypothermia as a neuroprotective agent for preventing the development of calcium plateau against SE-induced delayed hippocampal injury. Hypothermia-mediated neuroprotection after pilocarpine-induced SE was evident from decreased Fluoro-Jade C+ neurons in the hippocampus. The second original article by Matos et al. described SE-induced changes in spontaneous locomotor activity and the temporal expression of genes related to circadian rhythms (Clock, Bmal1, Cry1, Cry2, Per1, Per2, and Per3) in the hippocampus at both early post-SE and chronic epilepsy phases. Authors propose that seizures can act as a non-photic cue and altered temporal expression of clock genes likely contributes to the pathogenesis of mesial temporal lobe epilepsy. The third original article by Hutson et al. presented an interesting case study which showed evidence of brain dynamics resetting after successful anticonvulsant treatment following SE utilizing stereo encephalography (SEEG) data.

A review by Kirmani et al. conferred the current literature about autoimmune SE including therapeutic options and future directions. An original research article by Wyatt-Johnson et al. reported that SE-induced morphological alterations in microglia at different time-points and discussed the role of such changes on epileptogenesis. Another research article by Kortland et al. addressed the socioeconomic outcome and quality of life outcome in adults after status epilepticus in their original article. The authors conducted a multicenter, longitudinal, matched case-control analysis and concluded that relatively favorable outcomes seen in patients with refractory and super refractory SE as compared to non-refractory SE cases underlying the need of effective therapeutic choices.

An original research article by Bertoglio et al. compared the effects of two different protocols of kainate-induced SE in two strains of rats on neurodegeneration and chronic epilepsy development. The findings revealed that severe neuron loss after SE does not necessarily correlate with a higher seizure rate in the chronic phase after SE. In a review article, Castro et al. discussed the efficacy and promise of resveratrol, a phytoalexin found in the skin of red grapes, for easing SE-induced neurodegeneration, neuroinflammation, aberrant neurogenesis and for restraining the evolution of SE-induced brain injury into a chronic epileptic state. Sharma et al. by reviewing methods of induction and characterization of behavioral SE and EEG correlates in mice and rats, highlighted the advantages of a repeated low dose of kainate protocol for minimizing the variability in the initial SE severity and reducing the mortality rate. The last original article by Lucchi et al. described the role peroxisome proliferator-activated receptor gamma in the anticonvulsant properties of EP-80317, a Ghrelin receptor antagonist in pilocarpine-induced SE rat model and repeated 6 Hz corneal stimulation model in mice.

via Frontiers | Editorial: New Directions in the Management of Status Epilepticus | Neurology

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[Abstract] Antiepileptic drug treatment during pregnancy and delivery in women with epilepsy – A retrospective single center study

Highlights

Pregnancies in women with epilepsy (WWE) increased significantly during our 11-year study period (41% increase).

Twelve different AEDs were prescribed to WWE during pregnancies in the 11-year period investigated (2005-2015) with Lamotrigine (36.1%), Carbamazepine (25.0%), and Valproic Acid (13.5%) most commonly used.

Valproic acid use was markedly reduced comparing the years 2005-2010 (18.4%) and 2011-2015 (9.4%), a reduction of 48%.

Unfortunately, a trend towards an increase in treating WWE with more than one AED was observed.

Cover image Epilepsy ResearchAbstract

Purpose

Antiepileptic drugs (AED) are among the most common teratogenic drugs prescribed to women of childbearing age. During pregnancy, the risk of seizures has to be weight against the use of AED treatment. Primary goal was to observe and describe AED treatment policy and its changes during an eleven-year period at our third referral center.

Methods

We scrutinized the medical health records for all cases of female epileptic patients admitted for labor at the Rabin Medical Center during the years 2005 – 2015.

Results

A total of 296 deliveries were recorded with 136 labors occurring in the period 2005-2010 (22.7/y) and 160 in 2011-2015 (32.0/y; increase of 41%). Twelve different AEDs were prescribed to WWE during pregnancies in the 11-year period investigated (2005-2015). Most commonly used AEDs during pregnancy were Lamotrigine (36.1%), Carbamazepine (25.0%), and Valproic Acid (13.5%). Comparing their use during the years 2005-2010 and 2011-2015, Lamotrigine (35.3% vs. 36.9%) and Carbamazepine use (23.5% vs. 26.0%) increased slightly. Valproic acid use was markedly reduced in the second period: 18.4% in the years 2005-2010 lowered to 9.4% during 2011-2015, a reduction of 48%. Unfortunately, a trend towards an increase in treating WWE with more than one AED was observed.

Conclusions

The proportion of WWE treated with VPA during pregnancy was significantly reduced in the observed period (2005-2015). Change in fetal outcome during this period for WWE could not be detected.

via Antiepileptic drug treatment during pregnancy and delivery in women with epilepsy—A retrospective single center study – ScienceDirect

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[Abstract + References] Efficacy and Safety of Cannabidiol in Epilepsy: A Systematic Review and Meta-Analysis

Abstract

Background

Approximately one-third of patients with epilepsy presents seizures despite adequate treatment. Hence, there is the need to search for new therapeutic options. Cannabidiol (CBD) is a major chemical component of the resin of Cannabis sativa plant, most commonly known as marijuana. The anti-seizure properties of CBD do not relate to the direct action on cannabinoid receptors, but are mediated by a multitude of mechanisms that include the agonist and antagonist effects on ionic channels, neurotransmitter transporters, and multiple 7-transmembrane receptors. In contrast to tetra-hydrocannabinol, CBD lacks psychoactive properties, does not produce euphoric or intrusive side effects, and is largely devoid of abuse liability.

Objective

The aim of the study was to estimate the efficacy and safety of CBD as adjunctive treatment in patients with epilepsy using meta-analytical techniques.

Methods

Randomized, placebo-controlled, single- or double-blinded add-on trials of oral CBD in patients with uncontrolled epilepsy were identified. Main outcomes included the percentage change and the proportion of patients with ≥ 50% reduction in monthly seizure frequency during the treatment period and the incidence of treatment withdrawal and adverse events (AEs).

Results

Four trials involving 550 patients with Lennox–Gastaut syndrome (LGS) and Dravet syndrome (DS) were included. The pooled average difference in change in seizure frequency during the treatment period resulted 19.5 [95% confidence interval (CI) 8.1–31.0; p = 0.001] percentage points between the CBD 10 mg and placebo groups and 19.9 (95% CI 11.8–28.1; p < 0.001) percentage points between the CBD 20 mg and placebo arms, in favor of CBD. The reduction in all-types seizure frequency by at least 50% occurred in 37.2% of the patients in the CBD 20 mg group and 21.2% of the placebo-treated participants [risk ratio (RR) 1.76, 95% CI 1.07–2.88; p = 0.025]. Across the trials, drug withdrawal for any reason occurred in 11.1% and 2.6% of participants receiving CBD and placebo, respectively (RR 3.54, 95% CI 1.55–8.12; p = 0.003) [Chi squared = 2.53, degrees of freedom (df) = 3, p = 0.506; I2 = 0.0%]. The RRs to discontinue treatment were 1.45 (95% CI 0.28–7.41; p = 0.657) and 4.20 (95% CI 1.82–9.68; p = 0.001) for CBD at the doses of 10 and 20 mg/kg/day, respectively, in comparison to placebo. Treatment was discontinued due to AEs in 8.9% and 1.8% of patients in the active and control arms, respectively (RR 5.59, 95% CI 1.87–16.73; p = 0.002). The corresponding RRs for CBD at the doses of 10 and 20 mg/kg/day were 1.66 (95% CI 0.22–12.86; p = 0.626) and 6.89 (95% CI 2.28–20.80; p = 0.001). AEs occurred in 87.9% and 72.2% of patients treated with CBD and placebo (RR 1.22, 95% CI 1.11–1.33; p < 0.001). AEs significantly associated with CBD were somnolence, decreased appetite, diarrhea, and increased serum aminotransferases.

Conclusions

Adjunctive CBD in patients with LGS or DS experiencing seizures uncontrolled by concomitant anti-epileptic treatment regimens is associated with a greater reduction in seizure frequency and a higher rate of AEs than placebo.

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via Efficacy and Safety of Cannabidiol in Epilepsy: A Systematic Review and Meta-Analysis | SpringerLink

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[WEB SITE] New epilepsy warning device could save thousands of lives — ScienceDaily

Nightwatch bracelet on the arm of a young epilepsy patient.
Credit: LivAssured

A new high-tech bracelet, developed by scientists from the Netherlands detects 85 percent of all severe night-time epilepsy seizures. That is a much better score than any other technology currently available. The researchers involved think that this bracelet, called Nightwatch, can reduce the worldwide number of unexpected night-time fatalities in epilepsy patients. They published the results of a prospective trial in the scientific journal Neurology.

SUDEP, sudden unexpected death in epilepsy, is a major cause of mortality in epilepsy patients. People with an intellectual disability and severe therapy resistant epilepsy, may even have a 20% lifetime risk of dying from epilepsy. Although there are several techniques for monitoring patients at night, many attacks are still being missed.

Consortium researchers have therefore developed a bracelet that recognizes two essential characteristics of severe attacks: an abnormally fast heartbeat, and rhythmic jolting movements. In such cases, the bracelet will send a wireless alert to carers or nurses.

The research team prospectively tested the bracelet, known as Nightwatch, in 28 intellectually handicapped epilepsy patients over an average of 65 nights per patient. The bracelet was restricted to sounding an alarm in the event of a severe seizure. The patients were also filmed to check if there were any false alarms or attacks that the Nightwatch might have missed. This comparison shows that the bracelet detected 85 percent of all serious attacks and 96% of the most severe ones (tonic-clonic seizures), which is a particularly high score.

For the sake of comparison, the current detection standard, a bed sensor that reacts to vibrations due to rhythmic jerks, was tested at the same time. This signalled only 21% of serious attacks. On average, the bed sensor therefore remained unduly silent once every 4 nights per patient. The Nightwatch, on the other hand, only missed a serious attack per patient once every 25 nights on average. Furthermore, the patients did not experience much discomfort from the bracelet and the care staff were also positive about the use of the bracelet.

These results show that the bracelet works well, says neurologist and research leader Prof. Dr. Johan Arends. The Nightwatch can now be widely used among adults, both in institutions and at home. Arends expects that this may reduce the number of cases of SUDEP by two-thirds, although this also depends on how quickly and adequately care providers or informal carers respond to the alerts. If applied globally, it can save thousands of lives.

Watch the video here: https://youtu.be/0G_BQK4LK88

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Materials provided by Eindhoven University of TechnologyNote: Content may be edited for style and length.


Journal Reference:

  1. Johan Arends, Roland D. Thijs, Thea Gutter, Constantin Ungureanu, Pierre Cluitmans, Johannes Van Dijk, Judith van Andel, Francis Tan, Al de Weerd, Ben Vledder, Wytske Hofstra, Richard Lazeron, Ghislaine van Thiel, Kit C.B. Roes, Frans Leijten. Multimodal nocturnal seizure detection in a residential care settingNeurology, 2018; 10.1212/WNL.0000000000006545 DOI: 10.1212/WNL.0000000000006545

via New epilepsy warning device could save thousands of lives — ScienceDaily

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