Tag: epilepsy

Categories : NeurologyTags :

What Happens When the Brain Loses a Hub?

On By ModernMedia
Photo by Jafar Ahmed on Unsplash

A University of Iowa-led team of international neuroscientists have obtained the first direct recordings of the human brain in the minutes before and after a brain hub crucial for language meaning was surgically disconnected. The results reveal the importance of brain hubs in neural networks and the remarkable way in which the human brain attempts to compensate when a hub is lost, with immediacy not previously observed. The findings were reported recently in the journal Nature Communications.

Hubs are critical for connectivity

The human brain has hubs – the intersection of many neuronal pathways that help coordinate brain activity required for complex functions like understanding and responding to speech. But debate has reigned as to whether highly interconnected brain hubs are irreplaceable for certain brain functions. By some accounts the brain, as an already highly interconnected neural network, can in principle immediately compensate for the loss of a hub, in the same way that traffic can be redirected around a blocked-off city centre.

With a rare experimental opportunity, the UI neurosurgical and research teams led by Matthew Howard III, MD, professor and DEO of neurosurgery, and Christopher Petkov, PhD, professor and vice chair for research in neurosurgery, have achieved a breakthrough in understanding the necessity of a single hub. By obtaining evidence for what happens when a hub required for language meaning is lost, the researchers showed both the intrinsic importance of the hub as well as the remarkable and rapid ability of the brain to adapt and at least partially attempt to immediately compensate for its loss.

Evaluating the impact of losing a brain hub

The study was conducted during surgical treatment of two patients with epilepsy. Both patients were undergoing procedures that required surgical removal of the anterior temporal lobe – a brain hub for language meaning – to allow the neurosurgeons access to a deeper brain area causing the patients’ debilitating epileptic seizures. Before this type of surgery, neurosurgery teams often ask the patients to conduct speech and language tasks in the operating room as the team uses implanted electrodes to record activity from parts of the brain close to and distant from the planned surgery area. These recordings help the clinical team effectively treat the seizures while limiting the impact of the surgery on the patient’s speech and language abilities.

Typically, the recording electrodes are not needed after the surgical resection procedure and are removed. The innovation in this study was that the neurosurgery team was able to safely complete the procedure with the recording electrodes left in place or replaced to the same location after the procedure. This made it possible to obtain rare pre- and post-operative recordings allowing the researchers to evaluate signals from brain areas far away from the hub, including speech and language areas distant from the surgery site. Analysis of the change in responses to speech sounds before and after the loss of the hub revealed a rapid disruption of signaling and subsequent partial compensation of the broader brain network.

“The rapid impact on the speech and language processing regions well removed from the surgical treatment site was surprising, but what was even more surprising was how the brain was working to compensate, albeit incompletely within this short timeframe,” says Petkov, who also holds an appointment at Newcastle University Medical School in the UK.

The findings disprove theories challenging the necessity of specific brain hubs by showing that the hub was important to maintain normal brain processing in language.

“Neurosurgical treatment and new technologies continue to improve the treatment options provided to patients,” says Howard, who also is a member of the Iowa Neuroscience Institute.

“Research such as this underscores the importance of safely obtaining and comparing electrical recordings pre and post operatively, particularly when a brain hub might be affected.”

According to the researchers, the observation on the nature of the immediate impact on a neural network and its rapid attempt to compensate provides evidence in support of a brain theory proposed by Professor Karl Friston at University College London, which posits that any self-organising system at equilibrium works towards orderliness by minimising its free energy, a resistance of the universal tendency towards disorder.

These neurobiological results following human brain hub disconnection were consistent with several predictions of this and related neurobiological theories, showing how the brain works to try to regain order after the loss of one of its hubs.

Source: University of Iowa Health Care

Categories : Neurology New Compounds and TreatmentsTags :

A New Drug Could Provide Hope in Treatment-resistant Epilepsy

On By ModernMedia
Photo by Towfiqu Barbhuiya on Unsplash

In cases where standard therapies fail, an in-development drug called XEN1101 reduces seizure frequency by more than 50% in some patients and in some cases eliminates them, according to a new study published in JAMA Neurology. Unlike several treatments that must be started at low doses and slowly ramped up, the new drug can safety be taken at its most effective dose from the start, the authors say.

Focal seizures, the most common type seen in epilepsy, occur when nerve cells in a particular brain region send out a sudden, excessive burst of electrical signals. Along with seizures, this uncontrolled activity can lead to abnormal behaviour, periods of lost awareness, and mood changes. While many available therapies control or reduce seizures, they fail to stop seizures in about one-third of patients and may cause harsh side effects, experts say.

Led by researchers at NYU Grossman School of Medicine, a new clinical trial found that patients who added XEN1101 to their current antiseizure treatments saw a 33% to 53% drop in monthly seizures, depending on their dose. By contrast, those given a placebo had on average 18% fewer seizures during the treatment phase of the trial, which lasted eight weeks. Most patients then volunteered to extend the trial, with about 18% of those treated with the new drug remaining entirely seizure free after six months, and about 11% having no seizures after a year or longer.

“Our findings show that XEN1101 may offer a swift, safe, and effective way to treat focal epilepsy,” said study lead author, neurologist Jacqueline French, MD. “These promising results offer hope for those who have struggled for decades to get their symptoms under control.”

French, a professor in the Department of Neurology at NYU Langone Health, notes that XEN1101 was well tolerated by the study participants, who reported side effects similar to other antiseizure treatments, including dizziness, nausea, and fatigue, and the majority felt well enough to continue the regimen. Another benefit of the drug, she adds, is that it takes more than a week to break down, so levels in the brain remain consistent over time. This steadiness allows the treatment to be started at full strength and helps to avoid dramatic spikes that worsen side effects, and dips that allow seizures to return. This lengthy breakdown time also allows for a “grace period” if a dose is accidently skipped or taken late.

XEN1101 is part of a class of chemicals called potassium-channel openers, which avert seizures by boosting the flow of potassium out of nerves, stopping them from firing. French notes that while other drugs of this kind have been explored for epilepsy patients in the past, such treatments were taken out of use because the compounds were later found to gradually build up in the skin and eyes, prompting safety concerns, the researchers say.

Meanwhile, XEN1101 combines the effectiveness of potassium-channel openers with the safety of more traditional drugs, says French, who is also a member of NYU Langone’s Comprehensive Epilepsy Center.

For the study, which included 285 men and women with epilepsy and ran from January 2019 to September 2021, the research team recruited adults with epilepsy who had already tried and stopped taking an average of six drugs that failed to treat their focal seizures. Patients in the trial had to have experienced at least four episodes a month despite ongoing treatment to qualify. The patients were randomly provided either a daily oral capsule of XEN1101 (in 10mg, 20mg, or 25mg doses) or placebo.

Among the results, the trial revealed no signs of dangerous side effects such as heart problems, allergic reactions, or concerning skin discolourations. However, French says that the research team plans to expand the number of patients exposed to the drug and monitor for potential issues that could arise in the long term, or include specific groups of people, such as pregnant women. In addition, the team also intends to explore XEN1101 for other types of seizures, including those that broadly affect the brain at the same time (generalised seizures).

“Our study highlights the importance of finding as many therapeutic options as possible for those who suffer from seizures,” says French. “Since everyone responds differently, treating epilepsy cannot be a one-size-fits-all approach.”

Source: NYU Langone Health / NYU Grossman School of Medicine

Categories : General Interest NeurologyTags :

Inspiring, but not Therapeutic: Study Finally Silences The ‘Mozart Effect’

On By ModernMedia
Photo by Sergio Capuzzimati on Unsplash

Over the past fifty years, there have been remarkable claims about the effects of Wolfgang Amadeus Mozart’s music. Reports about alleged symptom-alleviating effects of listening to Mozart’s Sonata KV448 in epilepsy attracted a lot of public attention. However, the empirical validity of the underlying scientific evidence has remained unclear. Now, University of Vienna psychologists Sandra Oberleiter and Jakob Pietschnig show in a new study published in the journal Nature Scientific Reports that there is no evidence for a positive effect of Mozart’s melody on epilepsy.

In the past, Mozart’s music has been associated with numerous ostensibly positive effects on humans, animals, and even microorganisms. For instance, listening to his sonata has been said to increase the intelligence of adults, children, or foetuses in the womb. Even cows were said to produce more milk, and bacteria in sewage treatment plants were said to work better when they heard Mozart’s composition.

However, most of these alleged effects have no scientific basis. The origin of these ideas can be traced back to the long-disproven observation of a temporary increase in spatial reasoning test performance among students after listening to the first movement allegro con spirito of Mozart’s sonata KV448 in D major.

More recently, the Mozart effect experienced a further variation: Some studies reported symptom relief in epilepsy patients after they had listened to KV448. However, a new comprehensive research synthesis by Sandra Oberleiter and Jakob Pietschnig from the University of Vienna, based on all available scientific literature on this topic, showed that there is no reliable evidence for such a beneficial effect of Mozart’s music on epilepsy. They found that this alleged Mozart effect can be mainly attributed to selective reporting, small sample sizes, and inadequate research practices in this corpus of literature. “Mozart’s music is beautiful, but unfortunately, we cannot expect relief from epilepsy symptoms from it” conclude the researchers.

Source: University of Vienna

Categories : Obstetrics & GynaecologyTags :

No Added Seizure Risk from Antidepressant Use in Pregnancy

On By ModernMedia
Pregnant with ultrasound image
Source: Pixabay

A large Swedish study in the journal Neurology found that pregnant women taking selective serotonin reuptake inhibitors (SSRIs) or selective norepinephrine reuptake inhibitors (SNRIs) during the first trimester of was not linked to an increased risk for neonatal seizures and epilepsy in childhood.

Any increase in seizures or epilepsy is likely due to other factors, the researchers said.

“It’s not likely the medications themselves that are causing the seizures and epilepsy in children, but rather the reasons why these women are taking the medication,” according to Kelsey Kathleen Wiggs, a PhD candidate at Indiana University in Bloomington. There are also the other background factors that differ between women who do and do not use SSRI/SNRIs.

“When it rains, it pours,” Wiggs said. “Women who are taking antidepressants in pregnancy are doing that for lots of different reasons, and they might be at risk for different things than women who aren’t taking those medications in pregnancy.”

The study found an elevated risk for neonatal seizures (risk ratio [RR] 1.41) and epilepsy in early childhood (HR 1.21) among offspring of mothers who used antidepressants in pregnancy.

Adjustment for maternal indications for SSRI/SNRI use and background factors like smoking during pregnancy revealed that they were drivers for both associations: neonatal seizures (RR 1.10); epilepsy diagnosis at 5 years (HR 0.96). Parental history of epilepsy was not found to affect the association.

The findings provide a “conclusive answer” to these concerns with using SSRI/SNRIs during pregnancy, according to Anne Berg, PhD, and Torin Glass, BM, Bch, BAO.

“[SSRI/SNRIs] have been demonstrated to have serotonergic central nervous system effects and are associated with an observable withdrawal syndrome which may be seen in the neonate following in utero exposure,” noted Drs Berg and Glass, in an accompanying editorial.

“The authors understood that with a population-based data registry and huge sample size, they had more than sufficient statistical power to detect even a modest increase in risk,” the editorialists wrote. “They tested this hypothesis and were able to reject it, definitively!”

In order to determine whether antidepressants had a causal association with infant seizures and childhood epilepsy, the researchers analysed data from national Swedish healthcare registries on a total of 1 721 274 children in Sweden born between 1996 and 2011.

Participants were divided into two groups: one group of mothers who reported use of an SSRI (fluoxetine, citalopram, paroxetine, sertraline, fluvoxamine, escitalopram) or SNRI (venlafaxine, duloxetine) during the first trimester of pregnancy (n = 24 308), and another group with no reported antidepressant use (n = 1 696 966).

Source: MedPage Today

Categories : NeurologyTags :

People with Epilepsy Live Significantly Shorter Lives

On By ModernMedia
Depiction of a human brain
Image by Fakurian Design on Unsplash

A Danish cohort study published in Brain shows that people with epilepsy live 10-12 years fewer than those without the condition, with a slightly greater reduction for men than women. The study researchers also found that excess mortality is particularly pronounced among people with epilepsy and mental disorders.

One of the most frequently occurring neurological diseases, epilepsy affects 50 million people worldwide, and is known to increase the risk of early death by three times.

“The significantly reduced life expectancy is found both in people who develop epilepsy as a result of an underlying condition, such as brain cancer or stroke, and in those who develop epilepsy without an obvious underlying cause,” explained Julie Werenberg Dreier, one of the researchers behind the study.

The average reduction in life expectancy was 12 years for men with epilepsy and 11 years for women. Among people with epilepsy and mental disorders life expectancy was on average reduced by up to 16 years.

“We discovered that the reduced life expectancy for people with epilepsy was related to a wide range of causes of death which don’t just include the neurological, but also cardiovascular diseases, psychiatric disorders, alcohol related conditions, accidents and suicide,” said Jakob Christensen, one of the researchers behind the study.

Researchers used Danish healthcare register to follow almost six million Danes, including more than 130 000 people with epilepsy.

“The large study has enabled detailed analyses of a range of different causes of death and, for the first time, we’ve been able to estimate the number of years lost due to individual causes of death in people with epilepsy. This is important information as it can be used to target preventive efforts in order to reduce the mortality gap that we currently see in people with epilepsy,” said Julie Werenberg Dreier.

The mortality rate among people with epilepsy is due to a wide range of different conditions that cut across virtually all medical specialities, the researchers said. There is therefore a need for a collective effort to reduce mortality.

“The alarming results provide important knowledge for all healthcare professionals who, in one way or another, come into contact with people with epilepsy — also when prioritising and allocating resources in the healthcare system. The results clearly show how serious a disease epilepsy can be, and the findings of the study should be used in the prioritisation and planning of preventive measures,” said Jakob Christensen, emphasising that the results confirm the tendencies that have been shown in a few smaller studies which have estimated reduction in life expectancy in people with epilepsy.

“The study should be followed up by additional research, for example into the questions of how medical treatment and recurring seizures affect life expectancy.”

Source: Aarhus University

Categories : Diseases, Syndromes and ConditionsTags :

Guidelines for Cannabinoid Treatments in Drug Resistant Epilepsy

On By ModernMedia
Cannabis plants
Photo by Harrison Haines on Pexels

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

On By ModernMedia
Photo by Shvets Productions on Pexels

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

On By ModernMedia
Photo by Pavel Danilyuk on Pexels

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

On By ModernMedia
Photo by Ben Wicks on Unsplash

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

On By ModernMedia
Photo by Hush Naidoo on Unsplash

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