Tag: epilepsy

Categories : Diseases, Syndromes and ConditionsTags :

Guidelines for Cannabinoid Treatments in Drug Resistant Epilepsy

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Due to the sizeable interest in the use of cannabis-based medications in treating drug resistant epilepsy and comparative lack of clinical guidance on prescription, an expert working group in Australia recently developed an interim “consensus advice” for prescribers and published it in the British Journal of Clinical Pharmacology.

The working group was made up of paediatric and adult epilepsy specialists, clinical pharmacists, pharmacologists, and cannabis researchers. Epilepsy occurs in 1–2% of the population, and about one in three people with epilepsy are considered drug resistant to standard antiseizure medications.

Since there are few clinical data available on comparative efficacy of cannabinoids with registered epilepsy treatments, the authors recommend cannabinoids only in drug resistant epilepsy, in carefully selected compliant patients with specific epilepsy phenotypes.

The document provides an overview of the different cannabis medicines currently available for treating epilepsy in children and adults, with information on dose, drug interactions, toxicity, and type and frequency of symptom and seizure relief. The consensus advice will be updated as new evidence emerges and will provide the structure for a more definitive guideline in the future.

“In the absence of a registration dossier, scientific experiments and case reports are helpful to provide some guidance to optimised dosing. However as in this guidance, observational data obtained from clinical practice – which often includes information not included in scientific experiments or even early clinical trial data, such as treating patients with other comorbidities, taking multiple medications, and patient diversity – can be very helpful to clinical practice,” said senior author Jennifer H. Martin, MBChB, MA, PhD, FRACP, a researcher at the University of Newcastle and the Director of the Australian Centre for Cannabis Clinical and Research Excellence.

Source: Wiley

Categories : Neurology Obstetrics & GynaecologyTags :

Reduced Antiepileptic Drug Effectiveness in Pregnancy Uncovered

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Blood levels of many commonly used antiepileptic drugs drop dramatically with the onset of pregnancy, which can result in ‘breakthrough seizures’ according to a study published in JAMA Neurology.

The findings, collected as part of the multicentre study Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD), explain why many people with epilepsy start experiencing breakthrough seizures after conception, underscoring the need to increase antiseizure medication doses and closely monitor blood levels over the course of pregnancy.

A fine-tuned medication regime is critical in epilepsy. “Some people mistakenly believe that changes in the drugs’ blood concentration won’t occur until after 20 weeks of pregnancy, but our study shows how important it is to start monitoring and adjusting patients’ medication dosages early on,” said lead author Dr Page Pennelll. “Nearly half of all pregnancies in the United States are unplanned, so it is important to ensure that doctors have a clear picture of each patient’s baseline drug level even if they are not trying to conceive.”

A life-altering neurological condition, two-thirds of epilepsy cases do not have a known cause. In people with epilepsy, nerve cells in the brain are hyper-reactive, causing them to change the pattern of their electrical activity and become spontaneously active. That synchronous activation is manifested in seizures.

Epilepsy has a fraught history of diagnosis and management; people with epilepsy go undiagnosed or under-treated. First-generation drugs to control it had many dangerous side effects and were contraindicated for people who are trying to conceive.

Since then, safer medications have entered the U.S. market and become widely available, but clinicians started noticing a new problem – patients whose epilepsy was successfully managed with medications started having seizures soon after becoming pregnant.

“Identifying which antiseizure medications may have changes in concentrations and at what point in pregnancy those changes occur is important for determining which patients may need to be monitored more closely during pregnancy and after delivery,” said senior author Professor Angela Birnbaum at the University of Minnesota.

To solve the mystery, the researchers embarked on a study to analyse blood concentrations of 10 commonly used antiseizure drugs and compare them across different stages of pregnancy and after childbirth.

The study found that blood levels of seven out of 10 of the medications they examined dropped dramatically — from 29.7% for lacosamide, a commonly prescribed anticonvulsant, and up to 56.4% for lamotrigine.

In addition, the researchers noted that the drop in drug levels occurred mere days after conception.

Source: University of Pittsburgh

Categories : NeurologyTags :

An Updated Look at the Link Between Alcohol and Epilepsy

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A new meta-analysis has established an association between alcohol and epilepsy, in contrast to previous studies which reported conflicting results on the relationship.

Epilepsy is one of the most common neurological conditions, with an annual incidence of 40–70 per 100 000 people in industrialised countries. It is also a  disease that is highly stigmatised.

A number of studies have focused on how alcohol consumption leads to provoked seizures, commonly resulting from alcohol withdrawal, or heavy intoxication. Very few of these however focused on the link between alcohol consumption and unprovoked seizures. A 2010 meta-analysis found that alcohol users were more prone to developing unprovoked seizures – but data from recent cohort studies contradict these findings. A 2018 meta-analysis suggested that the relationship may only hold true for heavy drinkers.

Now, using more accurate diagnostic methods and recent data, a team of scientists from Pusan National University, South Korea, conducted an updated meta-analysis to conclusively clarify the relationship between alcohol consumption and unprovoked seizures and epilepsy.

For this meta-analysis, appearing in Drug and Alcohol Dependence, the researchers included a total of eight studies, of which five were case-control studies and three were cohort studies. They analysed the data to assess the dose-response relationship between alcohol intake and epilepsy. The results suggested that overall, compared to non-drinkers, alcohol drinkers were at a significantly higher risk of developing epilepsy, which increased with alcohol intake. These findings are consistent with previous meta-analyses.

An important finding was that cohort studies did not show a positive association between alcohol intake and epilepsy. In fact, 2 out of 3 cohort studies suggested that alcohol intake reduces the risk of epilepsy.

More large cohort studies are needed to prove a causal relationship between alcohol drinking and epilepsy, as well as a threshold of onset, said second author Professor Yun Hak Kim.

Source: EurekAlert!

Categories : Neurology PaediatricsTags :

Scientists Find Epilepsy Biomarker in Autistic Children

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Scientists have discovered that an important brain protein that quiets overactive brain cells and is abnormally low in children with autism, which may explain why so many children with autism also have epilepsy. The findings were published in Neuron.

This protein can be detected in the cerebrospinal fluid, making it a promising marker to diagnose autism and potentially treat the epilepsy that accompanies the disorder.

Mutated versions of this gene were known to cause autism combined with epilepsy, and epilepsy appears in 30% to 50% of children with autism. Autism, which is 90% genetic, affects 1/58 children in the US.

Appropriately nicknamed ‘catnap2’, the protein, CNTNAP2, is produced by the brain cells when they become overactive. Because the brains of children with autism and epilepsy lack sufficient CNTNAP2, scientists found, their brains become overactive, leading to seizures.

For the study, the researchers analysed the cerebrospinal fluid in individuals with autism and epilepsy, and in mouse models. Though, cerebrospinal fluid has been used in researching disorders such as Parkinson’s, this is the first study showing it is an important biomarker in autism.

The new finding about CNTNAP2’s role in calming the brain in autism and epilepsy may lead to new treatments.

“We can replace CNTNAP2,” said lead study author Peter Penzes, the director of the Center for Autism and Neurodevelopment at Northwestern University Feinberg School of Medicine. “We can make it in a test tube and should be able to inject it into children’s spinal fluid, which will go back into their brain.”

Penzes’ lab is currently working on this technique in preclinical research.

The level in the spinal cord is proxy for the level in the brain, explained Penzes. When brain cells are too active because of overstimulation, they produce more CNTNAP2, which floats away and binds to other brain cells to calm them. The protein also leaks into the cerebrospinal fluid, where scientists were able to measure it, giving them a clue for how much is produced in the brain.

Source: EurekAlert!

Categories : Cardiovascular Disease NeurologyTags :

Hypertension Doubles Epilepsy Risk

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A new study has found that hypertension may double an adult’s risk of developing epilepsy, according to a new study published in Epilepsia.

The study recruited 2986 US participants with an average age of 58 years, 55 new cases of epilepsy were identified during an average follow-up of 19 years. Hypertension, defined as presence of elevated blood pressure or use of antihypertensive medications, was linked to a nearly 2-fold higher risk of epilepsy. After excluding participants with normal blood pressure who were taking antihypertensive medications, hypertension was linked to a 2.44-times higher risk of epilepsy.

“Our study shows that hypertension, a common, modifiable, vascular risk factor, is an independent predictor of epilepsy in older age,” said co–lead author Maria Stefanidou, MD, MSc, of Boston University School of Medicine. “Even though epidemiological studies can only show association and not causation, this observation may help identify subgroups of patients who will benefit from targeted, aggressive hypertension management and encourage performance of dedicated clinical studies that will focus on early interventions to reduce the burden of epilepsy in older age.”

Source: Wiley

Categories : NeurologyTags :

Ultrasound Treatment can Target Neural Circuits of Epilepsy

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Image credit: Dr Yu

A pioneering new study from Taiwan showed that focused ultrasound, which can be used to non-invasively target circuits in the brain, may benefit some patients with epilepsy who experience seizures which remain unresponsive to standard anti-seizure medications.

The results showed that of six patients with drug-resistant seizures, two patients had fewer seizures within three days of receiving focused ultrasound; however, one patient showed signs of more frequent subclinical seizures (which are not felt by the individual). The findings from the study were published in the journal Epilepsia.

Imaging tests performed after the treatment show that there were no negative effects on the brain. One patient reported a sensation of heat on the scalp during the treatment, and another patient experienced temporary memory impairment that resolved within three weeks.

“Neuromodulation is an alternative treatment for drug-resistant epilepsy. Compared with the present modalities used in neuromodulation for epilepsy, focused ultrasound can access deeper brain regions and focus on the main target of the epileptic network in a relatively less invasive approach,” explained senior author Hsiang-Yu Yu, MD, of Taipei Veterans General Hospital, in Taiwan. “It gives new hope and sheds new light for patients with drug-resistant epilepsy.”

Source: Wiley

Categories : Diseases, Syndromes and Conditions Medical IndustryTags :

Review Looks at The Evidence for Cannabis in Paediatric Epilepsies

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A review published in Developmental Medicine & Child Neurology investigates the knowledge base of cannabis-based medicinal products in paediatric epilepsies, highlighting areas in need of additional research.

Following reports in the media of children with epilepsies apparently deriving benefits from medical marijuana (or cannabis-based medicinal products) accessed abroad, the UK government allowed clinicians to prescribe these products. A previous review found that there was some benefit in certain drug-resistant epilepsies in children.

In the review, the authors also looked at the prescribing environment surrounding these products. They found that the major obstacle to prescribing is a lack of quality evidence for efficacy and safety.
The authors stress that unlicensed cannabis-based medicinal products should not circumvent the usual regulatory requirements before being prescribed. They are also concerned that children with epilepsy are at risk of being exploited as a “Trojan horse” for the cannabis industry, with widespread acceptance of medicinal cannabis accelerating the wider legalisation of marijuana and opening up a highly lucrative commercial market.

Source: News-Medical.Net

Categories : NeurologyTags :

Neural Connectivity can Predict Epilepsy Outcomes

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Researchers have found that neuron connectivity patterns within brain regions can better indicate disease progression and treatment outcomes for people with brain disorders such as epilepsy.

Many brain diseases lead to cell death and the removal of connections within the brain. A team led by Dr Marcus Kaiser from the School of Medicine at the University of Nottingham looked at epilepsy patients undergoing surgery. Their findings were published in Human Brain Mapping.

They found that changes in the local network within brain regions can predict disease progression, and also whether surgery will be successful or not.

The team found that looking at connectivity within regions of the brain, showed superior results compared to only observing fibre tract connectivity between brain regions, which is the current method. Dividing the surface of the brain into 50 000 network nodes of comparable size, each brain region could be studied as a local network with 100-500 nodes. There were distinct changes seen in these local networks in patients suffering from epileptic seizures.

Employing diffusion tensor imaging, a special measurement protocol for MRI scanners, the team of scientists showed that fibres within and between brain regions are removed for patients.

However, they found that connectivity within regions better predicted whether surgical removal of brain tissue was successful in preventing future seizures.

Dr Kaiser, Professor of Neuroinformatics at the University of Nottingham, explained: “When someone has an epileptic seizure, it ‘spreads’ through the brain. We found that local network changes occurred for regions along the main spreading pathways for seizures. Importantly, regions far away from the starting point of the seizure, for example in the opposite brain hemisphere, were involved.

“This indicates that the increased brain activity during seizures leads to changes in a wide range of brain regions. Furthermore, the longer patients suffered, the more regions showed local changes and the more severe were these changes.”

The researchers from the involved universities, along with the company Biomax, evaluated the scans of 33 temporal lobe epilepsy patients and 36 control subjects.

Project partners used the NeuroXM™ knowledge management platform to develop a knowledge model for high-resolution connectivity with more than 50 000 cortical nodes and several millions of connections and corresponding automated processing pipelines accessible through Biomax’s neuroimaging product NICARA™.

Project manager Dr Markus Butz-Ostendorf from Biomax said: “Our software can be easily employed at hospitals and can also be combined with other kinds of data from genetics or from other imaging approaches such as PET, CT, or EEG.”

Professor Yanjiang Wang, who is one of the corresponding authors, and Ms Xue Chen, both from China University of Petroleum (East China), commented: “Local connectivity was not only better in overall predictions but particularly successful in identifying patients where surgery did not lead to any improvement, identifying 95% of such cases compared to 90% when used connectivity between regions”.

Source: University of Nottingham

Categories : Mental Health NeurologyTags :

Repurposed Drug Exploits Ion Channel in The Brain To Treat Depression

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Researchers from the Icahn School of Medicine at Mount Sinai Hospital have repurposed a drug to treat depression by using an ion channel that is a completely different mechanism than regular antidepressants.

A study demonstrated that a drug called ezogabine, which opens KCNQ2/3 type of potassium channels in the brain, is linked to significant improvements in depressive symptoms and anhedonia (a lack of ability to feel pleasure) in patients with depression. Anhedonia is a complex, core symptom of depression and is associated with poor outcomes such as increased risk of suicide and reduced responsiveness to antidepressants.
Ezogabine is an anticonvulsant for epilepsy treatment; this novel application in treating depression opens up the investigation of the KCNQ2/3 channel as a potential drug target.

“Our study is the first randomized, placebo-controlled trial to show that a drug affecting this type of ion channel in the brain can improve depression and anhedonia in patients. Targeting this channel represents a completely different mechanism of action than any currently available antidepressant treatment,” said Professor James Murrough, MD, PhD, at the Icahn School of Medicine at Mount Sinai, and senior author of the paper.

The KCNQ2/3 channel belongs to the KCNQ (or Kv7) family of ion channels which are important controllers of brain cell excitability and function in the central nervous system, affecting brain cell function by controlling electrical charge flow across the cell membrane in the form of potassium (K+) ions. Previous research in mice also showed involvement of KCNQ2/3 in depression. Mice that were more resilient to stress had increased KCNQ2/3 channels in their brains.

“We viewed enhanced functioning of the KCNQ channel as a potential molecular mechanism of resilience to stress and depression,” said Ming-Hu-Han, PhD, who also discovered that by increasing the activity of this channel, such as by administering ezogabine, to depressed mice, the drug acted as an antidepressant.

A trial with adult human patients showed that, compared to placebo, those treated with ezogabine showed a large reduction in a number of key measures of depression severity, anhedonia, and overall illness severity.
“The fundamental insight by Dr Han’s group that a drug that essentially mimicked a mechanism of stress resilience in the brain could represent a whole new approach to the treatment of depression was very exciting to us,” said Dr Murrough.

In collaboration with Dr Han, Dr Murrough carried out a series of human studies, with an initial open-label (no placebo) study in patients with depression providing initial evidence that ezogabine could improve symptoms of depression and anhedonia.

“I think it’s fair to say that most of us on the study team were quite surprised at the large size of the beneficial effect of ezogabine on clinical symptoms across multiple measures related to depression. We are greatly encouraged by these findings and the hope they offer for the prospect of developing novel, effective treatments for depression and related disorders. New treatments are urgently needed given that more than one-third of people suffering from depression are inadequately treated with currently approved therapeutics.”

Source: Eureka Alert