Is the Antiparasitic Drug Ivermectin a Suitable Candidate for the Treatment of Epilepsy?

Abstract found on PubMed

There are only a few drugs that can seriously lay claim to the title of “wonder drug” and ivermectin, the world’s first endectocide and forerunner of a completely new class of antiparasitic agents, is among them. Ivermectin, a mixture of two macrolytic lactone derivatives (avermectin B1a and B1b in a ratio of 80:20), exerts its highly potent antiparasitic effect by activating the glutamate-gated chloride channel that is absent in vertebrate species. However, in mammals, ivermectin activates several other Cys-loop receptors, including the inhibitory GABAA and glycine receptors and the excitatory nicotinic acetylcholine receptor of brain neurons. Based on these effects on vertebrate receptors, ivermectin has recently been proposed to constitute a multifaceted wonder drug for various novel neurological indications, including alcohol use disorders, motor neuron diseases, and epilepsy. This review critically discusses the preclinical and clinical evidence of anti-seizure effects of ivermectin and provides several arguments why ivermectin is not a suitable candidate drug for the treatment of epilepsy. First, ivermectin penetrates the mammalian brain poorly, so it does not exert any pharmacological effects via mammalian ligand-gated ion channels in the brain unless it is used in high, potentially toxic doses or the blood-brain barrier is functionally impaired. Second, ivermectin is not selective but activates numerous inhibitory and excitatory receptors. Third, the preclinical evidence for anti-seizure effects of ivermectin is equivocal and, at least in part, ED50 s in seizure models are in the range of the LD50 . Fourth, the only robust clinical evidence of anti-seizure effects stems from the treatment of patients with onchocerciasis in which the reduction of seizures is due to a reduction in microfilariae densities but not a direct anti-seizure effect of ivermectin. We hope that this critical analysis of available data will avert that the unjustified hype associated with the recent use of ivermectin to control COVID-19 recurs also in neurological diseases such as epilepsy.

“Untold Distress” – How Did the COVID-19 Pandemic Affect Those Who Had Previously Experienced an Epilepsy-Related Bereavement?

Abstract found on PubMed

Purpose: This study explores the impact of the COVID-19 pandemic and lockdown on people with lived experience of sudden bereavement as a consequence of an epilepsy-related death.

Method: We developed an online survey with fixed-choice and open-ended response formats to collect data on grief symptoms and well-being during the pandemic. A total of 275 people bereaved by epilepsy-related deaths between 1980-2020 participated in this study: with 79 participants providing free-text responses for inductive thematic analysis.

Results: In total, 84% of participants reported a bereavement following a sudden death of a person aged under 40, with 22% aged 19 and under. The majority (77% of participants) reported they had been thinking more about the person who died compared to before the COVID-19 outbreak and 54% had experienced more distressing flashbacks to the time of death. Additionally, 61% reported more difficulties falling asleep and staying asleep and 88% of participants reported that the outbreak and response measures had negatively impacted upon their mental health. Medication was being taken for a diagnosed mental health condition by 33% of participants at the time of the study. We categorized these negative experiences during COVID in to four main themes – ‘Family’, ‘Lifestyle’, ‘Personal Well-being’ and ‘Health Services and Shielding Populations’. The ‘Personal Well-being’ theme was inextricably linked to grief symptoms including ‘reflection on the death’, ‘re-exposure to feeling’, ‘grief’, ‘salience of sudden deaths in the media’ and ‘inability to commemorate anniversaries and rituals’. These findings were consistent for bereaved people irrespective of the recency of the death.

Conclusion: This study highlights the impact of the disruption caused by the pandemic on the grief management of those bereaved by epilepsy-related death. Grief is not static and its management is connected to the psychosocial and formal support structures that were disrupted during the pandemic. The removal of these supports had an adverse effect upon the mental health and well-being of many bereaved. There is an urgent need for a system-wide transformation of epilepsy and mental health services to be inclusive of the needs and experiences of people impacted by sudden deaths in epilepsy and the contribution of the specialist service developed by families and clinicians to meet this gap.

Epilepsy Research News: December 2022

This issue of Epilepsy Research News includes summaries of articles on:

 

Increased Seizures After COVID Compared to the Flu

Researchers have found that the risk of seizures or epilepsy following a COVID infection is significantly higher than after being infected with the flu. The team looked at the health records of people who had been infected with COVID and matched them (so that they were similar in characteristics such as age, sex, and medical conditions) with a group of people who had been infected with the flu. The team then compared the incidence of epilepsy and seizures between the two groups over a six-month period following the initial infection. The rate of new cases of epilepsy or seizures was 0.94% in the people who had COVID, compared with 0.6% in those who had the flu. The team indicated that while the overall risk of seizures was very low, people who had COVID were 55% more likely to develop epilepsy or seizures over the next six months than people who had the flu.

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New Statistical Tool to Understand Seizures

A new study seeks to understand how some people’s seizures change over time in what is known as a seizure ‘cycle’ and understand how certain triggers might increase or decrease seizure risk, perhaps giving people with epilepsy a better idea of how and why their seizures happen, and to better recognize the early warning signs. The study found that aging itself, as well as common triggers, may be contributing factors to how the medical condition affects those prone to seizures. The researchers studied the seizure diaries of more than 1,000 patients ages 2 months to 80 years and developed a new statistical model to explicitly capture the effect of factors that may drive transitions in seizure risk, looking at factors like antiseizure medications, illness, and menstrual cycles. In examining the way seizure cycles vary in people with epilepsy, the researchers found that individuals in older age groups had shorter “calm” stretches between seizures, while younger age groups had longer stretches. This work paves the way for future studies to further examine seizure cycles.

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Identification of a Possible Molecule to Treat Temporal Lobe Epilepsy (TLE)

Researchers have recently identified and developed a small molecule called D4 with the potential to treat TLE by suppressing neuroinflammation. The findings suggest that D4 strongly suppresses TLE-induced neuroinflammation, curbs TLE seizures, and increases survival rate in an animal model of TLE. D4 works by blocking “hemichannels” in the brain, which are channels that act as pathways for neuroinflammatory molecules. The researchers note that their findings bring forward a possible new pathway for drug development for epilepsy and also highlight the involvement of neuroinflammation in epilepsy.

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Pinpointing Brain Areas Involved in GLUT1 Deficiency Syndrome Seizures

A small group of brain cells linked to a circuit in the brain is responsible for setting off whole-brain seizures in a rare form of epilepsy affected by blood sugar levels, a new study suggests. This rare genetic disorder is known as GLUT1 deficiency syndrome. Researchers used a combination of electroencephalography (EEG) as well as brain imaging in humans to show that the seizures started from brain areas called the thalamus and somatosensory cortex. When blood sugar levels dipped, abnormal electrical activity in the circuit formed by these areas spread throughout the brain. The researchers also used an animal model of GLUT1 deficiency syndrome to further investigate this circuit and pinpoint the cell types important in causing an imbalance in inhibitory brain activity compared to excitatory brain activity (which can lead to seizures). The researchers suggested these results could point to a mechanism for seizures in GLUT1 deficiency syndrome that might be targeted as a potential treatment for seizures related to GLUT1 Deficiency syndrome.

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The Unforeseen Future: Impacts of the Covid-19 Pandemic on Home Video-EEG Telemetry

Abstract found on PubMed

The COVID-19 pandemic had widespread impact on healthcare systems globally – particularly services arranged around elective admission and attendance such as epilepsy monitoring units and Home Video-EEG Telemetry (HVET). Here, we review the ongoing impacts of the pandemic on HVET services amongst several different providers who used different initial models of HVET. We discuss the features of HVET which led to success in being able to provide continued diagnostic services to patients with epilepsy and related disorders and through retrospective audit of our services demonstrate the high diagnostic yield of HVET. We reflect on this unforeseen future and its implications for other diagnostic techniques and approaches.

The Risk of Seizures and Epilepsy is Higher After COVID Than After the Flu – New Research

Article published by The Conversation

Epilepsy is more common as we get older, and the main risk factor for the condition in later life is stroke. Given that COVID affects older adults most severely and can result in stroke, some might speculate that COVID could see more people develop epilepsy. Whether this is actually the case, though, has been difficult to prove.

In a new study, we’ve found that the risk of seizures or epilepsy following a COVID infection is significantly higher than after an influenza infection.

To try to more definitively answer whether COVID is associated with epilepsy or seizures, we looked at the health records of people who had been infected with COVID. We then carefully matched them (so that they were similar in characteristics like age, sex and medical conditions) with a group of people who had been infected with influenza.

Each group consisted of 152,754 people, none of whom had previously been diagnosed with epilepsy or recurrent seizures. We compared the incidence of epilepsy and seizures between the two groups over a six month period following the initial infection.

The rate of new cases of epilepsy or seizures was 0.94% in the people who had COVID, compared with 0.6% in those who had influenza. While the overall risk of seizures is therefore small, these cases show that people who had COVID were 55% more likely to develop epilepsy or seizures over the next six months than people who had influenza.

We then looked to see if certain groups were particularly susceptible to seizures or epilepsy after COVID. We found that, compared to influenza, children aged under 16 and people who were not hospitalized were more likely to develop epilepsy or seizures.

Epilepsy Research News: September 2022

This issue of Epilepsy Research News includes summaries of articles on:

 

Recent Advances in Precision Medicine for Genetic Epilepsy

The genetic basis of many epilepsies is increasingly understood. This gives rise to the possibility of precision treatments that can be tailored to a person’s specific genetic epilepsy. CURE Epilepsy Taking Flight grantee Juliet Knowles, MD, PhD, led a collection of prominent stakeholders within the epilepsy community, including CURE Epilepsy’s Dr. Laura Lubbers, in authoring a critical review that describes recent progress, new or persistent challenges, and future directions of precision medicine for genetic epilepsies, among other things. The article states that though current medical therapy for most epilepsies remains imprecise, the epilepsy community is ready to make big steps forward in precision therapy tailored to a person’s specific genetic epilepsy because of increased access to genetic testing and counseling and advances in the ability to diagnose genetic epilepsies. The authors conclude that the future of precision medicine for genetic epilepsy looks bright if progress in this area continues in a strategic and coordinated manner.
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Mortality Rates are Higher Among Veterans with Drug Resistant Epilepsy, Prompting Need for Improved Management

According to data from an observational cohort study, US veterans with drug-resistant epilepsy have higher rates of mortality than the general population, suggesting a critical need for appropriate management of epilepsy in this population. The findings showed that lower mortality was associated with increased utilization of medical care, especially when utilizing a Veterans Affairs Epilepsy Center of Excellence compared to a neurology clinic alone. The study authors noted that the higher mortality risk might be lowered by appropriate referrals for comprehensive evaluation, adequate diagnostic testing, and optimal medication management and that adequate resources should be allocated to care for this patient group.
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Seizures and Epilepsy Risk Still High Two Years After Delta, Omicron Infections

A recent study found an increased risk among adults for epilepsy or seizures two years after COVID-19 infection. Researchers used data collected as part of a two-year retrospective cohort study to investigate the neurological and psychiatric impact of SARS-CoV-2 infections. The researchers discovered that participants who had been infected with the Delta COVID-19 variant had an increased risk for epilepsy or seizures (amongst other risks) when compared to participants who had been infected with the Alpha variant. They also found that while the death rate decreased after the emergence of the Omicron variant, the virus still carried about the same risks for psychiatric or neurological problems, including epilepsy or seizures, compared to the Delta variant. The authors note that these findings emphasize there is a need for further research into the long-term impact of COVID-19.
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Study of Potassium Channels Reveals Novel Mechanism Behind Epilepsy

Epilepsy can have a variety of causes, including genetic variants in a family of proteins that regulate potassium ions in the brain. A research team is examining the mechanisms behind the function and dysfunction of two of these proteins, the potassium ion channels KCNQ2 and KCNQ3, as well as their interactions with an antiseizure medication, to develop a new strategy to treat epilepsy. The team identified a set of mutations in these ion channels associated with early infantile epileptic encephalopathy, a severe form of childhood epilepsy, that specifically disrupts the function of these channels. The researchers took advantage of the antiseizure drug retigabine, given its mechanism of action on neuronal KCNQ channels, and demonstrated that the function of these mutated KCNQ channels can be restored. Their studies suggest that targeting the function of KCNQ channels may be an effective strategy for developing more effective therapies for epilepsy.
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Brain Abnormalities in Epilepsy Detected by New AI Algorithm

An artificial intelligence (AI) algorithm to detect subtle brain abnormalities that cause epileptic seizures has been developed. The abnormalities, known as focal cortical dysplasias (FCDs), can often be treated with surgery but are difficult to visualize on an MRI. The new algorithm is expected to give physicians greater confidence in identifying FCDs in patients with epilepsy. To develop the algorithm, the team quantified features of the brain cortex—such as thickness and folding—in more than 1,000 patient MRI scans from 22 epilepsy centers around the world. They then trained the algorithm on examples labeled by expert radiologists as either being healthy or having FCD. The study’s authors state that the algorithm automatically learns to detect lesions from thousands of MRI scans of patients and can reliably detect lesions of different types, shapes, and sizes. The algorithm can even detect many of those lesions that were previously missed by radiologists. Ultimately, the team would like this AI algorithm to help doctors confidently identify FCDs, and then use surgery to remove them, in hopes of providing a cure for epilepsy.
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Delta, Omicron Infections: Seizures, Brain Fog, Dementia Risk Still High After 2 Years

Article published by Medical News Today

A recent study published in The Lancet sought to examine some long-term psychiatric and neurological problems related to SARS-CoV-2 compared to risks from other respiratory infections.

The researchers first identified nearly 1.2 million patients who had become infected with SARS-CoV-2 between January 20, 2020, and April 13, 2022, and pair matched them with others who had the same vaccination status, age, demographic and risk factors, who had not had COVID-19 but had experienced other respiratory infections.

Next, the authors analyzed the participants’ risk for 14 psychiatric and neurological diagnoses and compared the risk for these disorders to the control cohort. They also looked at how these risks differed before and after waves of infection that were dominated by the Alpha, Delta, and Omicron variants, respectively.

Among adults, there was an increased risk for brain fog, dementia, psychotic disorders, and epilepsy or seizures at the end of the 2-year follow-up.

The researchers further discovered that participants who had been infected with the Delta variant had an increased risk for ischaemic stroke, cognitive deficit, insomnia, anxiety disorders, and epilepsy or seizures when compared to participants who had been infected with the Alpha variant.

These findings emphasize there is a need for further research into the long-term impact of COVID-19.

Epilepsy Research News: August 2022

This issue of Epilepsy Research News includes summaries of articles on:

 

Impact of the COVID-19 Pandemic on People with Epilepsy: Findings From the US Arm of the COV-E Study

A recent survey of people with epilepsy and their caregivers showed that the COVID-19 pandemic has had negative effects on self-management and mental health for those with epilepsy. Some of the topics covered in the study include timeliness of taking medications, mental health, stress, and discussions with a healthcare provider about sleep, antiseizure medications, and potential side effects. The findings highlight the need for healthcare providers to be more aware of the increased emotional distress in people with epilepsy.
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Ketamine: An Effective Treatment for Neonatal, Pediatric Epilepsy

Treatment with a prescription medication called ketamine significantly reduced seizure occurrence related to refractory status epilepticus in neonates and children, according to results of a new study. In the study, researchers sought to determine the safety and efficacy of ketamine in young patients for this difficult to treat form of epilepsy. Results showed that after ketamine infusion, 32 patients experienced seizure cessation, 19 patients experienced seizure reduction, while there was no change in 18 patients. Three patients had adverse events requiring intervention during or within 12 hours of ketamine administration, including hypertension in two patients and delirium in one patient. “Many children with status epilepticus have persistent seizures despite administration of at least two appropriately dosed antiseizure medications,” stated the study authors. “Ketamine… may be a beneficial alternative.”
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Seizures in Young Stroke Survivors Doubles Dementia Risk

For young stroke survivors, the subsequent development of seizures more than doubles their risk of developing dementia, according to a recently published study. Researchers used the IBM Watson Health MarketScan Commercial Claims and Encounters database to identify 23,680 patients (aged 18 to 60 years) with ischemic strokes or hemorrhagic strokes from 2006 through 2009. The researchers found that young patients with stroke who developed seizures had a greater risk for dementia than those without seizures. The authors noted that “since strokes are occurring in younger people and survival rates are increasing, it is important to understand the long-term effects and determine who is at greatest risk for severe complications like dementia.”
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Age at Epilepsy Diagnosis and EEG can Help Predict Returning Seizures After Stopping Antiseizure Medication

Recent research has identified characteristics that can help predict the likelihood of seizures returning in children who have stopped taking antiseizure medication (ASM) after becoming seizure free. Among the characteristics studied, three were associated with a higher chance of having returning seizures after stopping ASM and included adolescent age at diagnosis, unusual EEG findings after the medication was stopped, and having a high number of seizures while taking medication. This information may be useful to doctors as they consider discontinuing antiseizure medication in their patients.
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A New Technique to Understand Temporal Lobe Epilepsy

A team of researchers used a new technique to find a link between a specific protein in the brain and increased vulnerability to neurodegeneration for individuals with temporal lobe epilepsy. The technique used by the researchers made it possible to study small amounts of tissue from hard-to-reach regions within the brain. Using this new technique, the researchers identified changes in a protein called GluN3 that is associated with cellular damage. The technique allowed the researchers to narrow the focus to specific areas of the brain where neurons are dying. The study author has applied to patent the technique, known as ‘area-specific tissue analysis’. This advanced technique may lead to a new understanding of the causes of epilepsy and therapies to help patients, stated the study author.
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Impact of the COVID-19 Pandemic on People with Epilepsy: Findings From the US Arm of the COV-E Study

Abstract found on Wiley Online Library

Objectives: As part of the COVID-19 and Epilepsy (COV-E) global study, we aimed to understand the impact of COVID-19 on the medical care and well-being of people with epilepsy (PWE) in the United States, based on their perspectives and those of their caregivers.

Methods: Separate surveys designed for PWE and their caregivers were circulated from April 2020 to July 2021; modifications in March 2021 included a question about COVID-19 vaccination status.

Results: We received 788 responses, 71% from PWE (n = 559) and 29% (n=229) from caregivers of persons with epilepsy. A third (n = 308) of respondents reported a change in their health or in the health of the person they care for. Twenty-seven percent (n = 210) reported issues related to worsening mental health. Of respondents taking ASMs (n = 769), 10% (n=?78) reported difficulty taking medications on time, mostly due to stress causing forgetfulness. Less than half of respondents received counseling on mental health and stress. Less than half of the PWE reported having discussions with their healthcare providers about sleep, ASMs and potential side effects, while a larger proportion of caregivers (81%) reported having had discussions with their healthcare providers on the same topics. More PWE and caregivers reported that COVID-19 related measures caused adverse impact on their health in the post-vaccine period than during the pre-vaccine period, citing mental health issues as the primary reason.

Significance: Our findings indicate that the impact of the COVID-19 pandemic in the US on people with epilepsy is multifaceted. Apart from the increased risk of poor COVID-19 outcomes, the pandemic has also had negative effects on mental health and self-management. Healthcare providers must be vigilant for increased emotional distress in PWE during the pandemic and consider the importance of effective counseling to diminish risks related to exacerbated treatment gaps.

Epilepsy Management During Difficult Times

Abstract found on John Libbey Eurotext

Major disruption in the delivery of healthcare services can occur in exceptional situations such as natural disasters, conflicts, periods of severe economic hardship, and epidemics. These disruptions typically affect to the greatest extent the most vulnerable segments of the population, including people with epilepsy. Inability to access healthcare services can lead to failure to undergo necessary diagnostic investigations, or to receive needed therapeutic interventions, including epilepsy surgery. Stress and other factors associated with the nature or the cause of the disruption can adversely affect seizure control status, or precipitate the occurrence of psychiatric disorders and other comorbid conditions. Failure to access antiseizure medications is a common occurrence in these situations and can result in loss of seizure control, withdrawal seizures, and status epilepticus. In this article, we provide examples of recent disruptions in healthcare and their implications for people with epilepsy. We discuss the consequences of natural disasters, conflicts, economic sanctions, and focus in greater detail on lessons learnt during the COVID-19 pandemic. We also discuss possible mitigation procedures, focusing in particular on the application of telemedicine to epilepsy care. Finally, we underline the need for governments, healthcare authorities, and international organizations to improve their preparedness to deal with exceptional situations that may arise in the future.