A grid of nine brains wit different portions highlighted in red, yellow, and green.

New Noninvasive Approach Maps Seizure-Generating Brain Areas

A new noninvasive method can effectively map the source and scale of seizure activity in people with epilepsy, according to a recent study. The tool could lower the number of surgeries needed to treat epilepsy. Clinicians often rely on an invasive technique to try to find the area responsible for someone’s seizures by implanting electrodes deep into the the outer layer of the brain, in one surgery before removing brain tissue in a second surgery. But these methods can lead to bleeding and infection.

The new approach couples machine learning, a type of artificial intelligence (AI), with electroencephalography (EEG) recordings from 76 electrodes placed on the scalp, to localize seizure activity in the brain. Unlike previous EEG techniques, it can also show how much brain tissue is involved. However, noninvasive imaging techniques come with trade-offs. While EEG is adept at recording activity during a seizure, it cannot always home in on a seizure’s source with precision. The layers of fluid, skull and brain tissue that lie between the electrodes and the underlying brain activity can distort the signal. And reverse-engineering the source location from that distorted signal is mathematically difficult.

Previous EEG methods could “pinpoint the center of gravity” of the recorded seizure activity, says lead investigator Bin He, professor of biomedical engineering at Carnegie Mellon University in Pittsburgh, Pennsylvania. But knowing where seizure activity is centered is not enough for surgical treatment of epilepsy.

To circumvent this problem, Bin Hee and his colleagues developed a new algorithm, called “fast spatio-temporal iteratively reweighted edge sparsity (FAST-IRES)”. Rather than just localizing the source, their algorithm provides information about the extent of the brain network that gives rise to the EEG signal. FAST-IRES also uses machine learning to calculate the thresholds at which signals are deemed significant. As a proof of concept, Hee and his colleagues tested FAST-IRES on EEG recordings from 36 people with epilepsy who were pursuing surgery as treatment. The researchers found that their method was as successful as implanted electrodes at finding the location and extent of the seizure source and would have produced similar surgical outcomes.

Efficacy and Tolerability of Intravenous Brivaracetam (Briviact®) for Status Epilepticus: A Systematic Review

Abstract, published in Journal of the Neurological Sciences

Background & Objectives: Status epilepticus (SE) is an emergent neurologic condition that carries a high risk of morbidity and mortality. Intravenous brivaracetam (IV BRV) may be an alternative anticonvulsant against SE, although the sparseness of controlled studies on the topic limits its recommendation for this indication. This systematic review aimed to determine the efficacy and safety of IV BRV in the treatment of SE.

Results: From a total of 34 studies identified in a comprehensive literature search, 5 uncontrolled studies with 77 patients were included in this review. Thirty-seven out of 77 patients (48%) with SE responded to IV BRV. Reported time to seizure cessation may be immediate from a few minutes to several hours after IV BRV treatment.

Conclusions: Limited evidence from 5 uncontrolled studies involving a limited number of patients suggests that IV BRV may be efficacious and safe in terminating seizures among patients with SE or refractory SE. Further studies employing either prospective, controlled trials or registry-based study designs are essential to determine the definitive role of IV BRV in patients with status epilepticus.

A black and white digital rendering of a brain with colorful dots showing seizure localization and spread.

Novel Approach is Helping to Explain Epileptic Seizures

Many patients with treatment-resistant epilepsy seek surgical resection, a procedure that removes part of the brain where seizures begin. Although resection can greatly reduce the number of seizures a person experiences, and in some cases, can eliminate seizures completely, the surgery is most successful when a surgeon can first pinpoint the exact spot in the brain where seizures begin, a challenging feat that has not yet been perfected in the clinic. New research from Boston University (BU) neuroscientists and statisticians, published in the journal Nature Communications, could someday improve the success of resections and, therefore, the quality of life for people with epilepsy.

Mark Kramer, a BU professor of mathematical neuroscience, says that “seizures evolve within the extraordinarily complicated and three-dimensional network of the brain’s cells and tissues such that the slightest change within that network can lead to sudden explosions or reductions in seizure spread”. But, during a resection, the clinical team which places a grid with individual electrodes directly on the brain’s surface, views each electrode as a separate data point instead of as a network.

Being able to represent the brain’s collective behavior would represent a big step forward. To accomplish this task, the researchers came up with a new way to analyze the brain activity data gathered by the electrodes. Specifically, they developed an algorithm that finds patterns of connectivity in these brain networks that can be traced as they evolve through time before, during, and after a seizure.

Results suggest that patients with fewer, shorter-lasting dynamic communities during seizure have improved surgical outcomes. Importantly, researchers believe that if they can track the seizure back to the point where it ignites, it may be possible to extinguish the seizure before it ever has the opportunity to spread.

Whose Seizures Last Longest? Impact of Clinical and Demographic Factors

Abstract, published in Epilepsia

Objective: To investigate the impact of clinical and demographic parameters on the duration of seizures starting at a single place in the brain (focal onset), with and without secondary spread, using precise duration measurements from intracranial electroencephalographic (iEEG) recordings. These recordings are made with electrodes placed directly on the brain.

Methods: Patients with focal epilepsy syndromes and iEEG recordings were retrospectively identified from the database of the local epilepsy center (2006-2016). Seizure duration was defined as the time between seizure onset and end, according to the iEEG. The specific seizure symptoms were classified based on video recordings. Clinical and demographic data were extracted from patient reports.

Results: In total, 69 adults were included, and 654 focal onset seizures were analyzed. Those that spread throughout the brain and involved violent convulsing (98/654 [~15%]) were significantly longer than without secondary spread (556/654 [~85%]). Most focal seizures (545/654 [83.3%]) ended within 2 minutes. The duration of focal seizures was prolonged with increasing age of the patients and was significantly shortened by secondary spread. Furthermore, seizures with secondary spread that were also preceded by an aura, began at the front of the brain, or occurred during sleep were shorter.

Significance: The identified modifiers of seizure duration are of great relevance for clinical risk evaluation, especially in the aging epilepsy patient suffering from epilepsy with secondary generalized seizures.

Report on a Psychoeducational Intervention for Psychogenic Non-Epileptic Seizures in Argentina

Published in Seizure

Highlights

  • Group psychoeducation in Argentina included patients with PNES and caregivers.
  • Psychoeducation could have a positive impact in patients with PNES in Argentina.
  • Patients who participated in the group reported improved emotional functioning.
  • “Group” and “psychoeducational” modality was rated as positive by most participants.

Abstract

Purpose: To examine the effects of a three-session psychoeducational intervention on patients diagnosed with psychogenic non-epileptic seizures (PNES) in an Argentinian public hospital. PNES are involuntary episodes that look and feel similar to epileptic seizures but have psychological rather than neurological causes. It was hypothesized that patients would experience improvements in their understanding of PNES, illness perception, and affective scores but might not necessarily experience a significant change in post-traumatic and dissociative symptoms and in seizure frequency.

Results: This psychoeducational intervention produced results that were similar to interventions reported in US and European studies with regard to changes on psychological measures. Moreover, many patients also reported (on the final day of the intervention) a decrease in seizure frequency. All patients reported that participating in the intervention was a positive experience. Also, all but one patient referred that the participation in the group would have a positive impact on their quality of life.

Conclusions: Psychoeducational interventions appear to have had positive results in Argentinian patients with PNES. This is initial step in the design of empirically based psychoeducational/supportive initiatives for patients in South America.

Epileptic Spasms in Individuals with Down Syndrome: a Review of the Current Literature

Critical review, published in Epilepsia Open

Epilepsy can occur in individuals with Down syndrome (DS), with epileptic spasms representing the most frequent seizure type in this population. Epileptic spasms are brief seizures characterized by bending of the trunk and bending/extension of the limbs. These types of seizures can have devastating consequences on the development of individuals with the condition. This review sought to explore the lifetime prevalence and underlying mechanism of epileptic spasms in this population. We also aimed to review the response rate to various treatments, the relapse rate, and the development of subsequent epilepsy or autism in this population.

A comprehensive literature search was conducted for articles discussing the lifetime prevalence, diagnosis, treatment, outcomes, or underlying cause of epileptic spasms in animal models or individuals with DS. According to available literature, the global clinic-based lifetime prevalence of epilepsy in individuals with DS ranged from 1.6% to 23.1%, with epileptic spasms representing 6.7% to 66.7% of these cases.

Response rate to treatment with a specific steroid hormone was highest (81%) and has the most literature supporting its use, with other treatments, including vigabatrin (Sabril®) and other antiepileptic drugs, having lower response rates. Epileptic spasms occur more frequently in children with DS than in the general population, though more studies are needed to determine the true lifetime prevalence of epileptic spasms in this population. Generally, children with DS and epileptic spasms tend to be more responsive to treatment and have better outcomes than children with epileptic spasms of unknown cause, in terms of response and relapse rates, as well as the development of intractable epilepsy.

Mutations Linked to Intellectual Disability, Epileptic Seizures Affect Ion Channel’s Function

Summary, originally published on news-medical.net

Two mutations identified in individuals with developmental and epileptic brain disease can be traced back to the same ion channel. Researchers have now elucidated how both independent mutations affect the channel’s function: by making it overly active and highly sensitive to stimulation. The findings are an important step towards unraveling what causes the patients’ symptoms.

Developmental and epileptic encephalopathies are a heterogeneous group of disorders characterized by epilepsy and intellectual disability. Genetic analysis pointed to the involvement of an ion channel called TRPM3. This channel is activated by heat and a variety of chemical ligands. It helps us detect noxious heat, and plays an important role in inflammatory pain.

“Two different mutations in the gene encoding TRPM3 were identified in nine individuals with a diagnosed developmental and epileptic encephalopathy,” explains Thomas Voets (VIB-KU Leuven) whose research is focused on ion channels and their role in pain and heat sensation. “Since the functional consequences of the mutations remained elusive, we set out to understand how disturbances of this particular ion channel can cause intellectual disability and epileptic seizures.”

An overly active channel

Voets, together with his colleague Joris Vriens (KU Leuven) and their team at the Laboratory for Ion Channel Research, could show that both mutations affect TRPM3 channel gating.

Clinical reports pointed out that next to the seizures and intellectual disability, several of the affected patients showed altered sensitivity to heat and pain, which hinted at a modified altered function of TRPM3.”

Joris Vriens, KU Leuven

The team could indeed demonstrate that both mutations lead to a significant gain in channel activity. Not only was basal activity increased, they also observed a higher sensitivity to stimulation by an endogenous neurosteroid and heat. Most strikingly, one of the two mutations resulted in even more pronounced functional alterations, including anomalous activation and reduced sensitivity to an anticonvulsant drug.

“The two mutations identified in the TRPM3 gene give rise to channels with substantially altered functional properties. Whereas the individual effects of both mutations differ, both can be considered as strong gain-of-function mutants, with increased activity, both under basal conditions and when stimulated,” says Voets.

“These two mutations also provide the first genetic evidence that link TRPM3 to a pain phenotype in humans,” adds Vriens. The researchers propose that this increased channel activity may lie at the basis of seizure development and neurodevelopmental symptoms in patients.

Study if US Veterans, Seizure Onset May Signal Dementia in Older Adults

Summary

Older US veterans who developed unprovoked seizures of unknown cause had double the risk of developing dementia over several years of follow-up, according to a study published online in JAMA Neurology.

The study included 292,262 veterans, 97% of whom were male, with an average age of 73. During a 5-year baseline period, 2166 veterans developed unprovoked seizures of unknown origin. Veterans who developed seizures were more likely to be younger, black, have lower income, and have higher prevalence of comorbidities, researchers reported.

Over an average 6 years of follow-up, the veterans with late-onset unprovoked seizures had a 2-fold risk of being diagnosed with dementia compared with veterans without seizures, according to the study. When researchers accounted for comorbidities, the effect size and significance of the increased risk were similar. When they added a 2-year lag between seizure onset and dementia diagnose to refute possible reverse causation, the effect sizes and significance remained similar.

“These findings emphasize the need for comprehensive research on late-onset seizures and dementia,” researchers wrote. “Considering the growing elderly population and high incidence of late-onset unprovoked seizures of unknown cause, further studies may have important ramifications for dementia research and clinical practice.”

Clinical Factors Associated with Suicide Risk Independent of Depression in Persons with Epilepsy

Summary, published on MDLinx

In individuals with epilepsy, researchers assessed if epilepsy-related factors are correlated with suicide risk independent of depression. Participants in the cross-sectional study were adults (n = 212; 52.4% men) with epilepsy. Study participants were divided into two age groups (under 40 vs over?40 years). The risk of suicide was reported in 31.6% of candidates, while risk of depression was reported in 22.2% of candidates. Independent of depression and a past or family history of psychiatric disorders, there was a significant link between an antiepileptic drug load greater than one and suicide risk. Independent of current depression, use of pregabalin (Lyrica®) in the younger group and frequent seizures in the older group were associated with a risk of suicide.

The risk of suicide in people with epilepsy may be linked to epilepsy-related factors such as high antiepileptic drug load, frequent seizures (over one per month), and pregabalin use, regardless of depression. Such risk factors can vary according to the patient’s age.

Epilepsy Research News: June 2020

This month’s epilepsy research news includes a study examining the efficacy of cognitive behavioral therapy that is designed specifically to treat individuals with psychogenic nonepileptic seizures (PNES).

In addition, recent research documents the ability of a wearable device called an accelerometer to assess the risk of life-threatening complications associated with seizures, such as Sudden Unexpected Death in Epilepsy (SUDEP). In the same spirit of technological advances, a recently published study discusses assessment of predictive models and underlying factors to assist seizure-free patients and their clinicians in safely withdrawing from antiepileptic drugs (AEDs).

Finally, we spotlight a study suggesting that autism and epilepsy may share neurodevelopmental origins. This work was co-led by Dr. Jamie Capal, who presented a CURE webinar on this work, which you can watch here.

Research News

  • Promising Treatment for PNES: PNES are involuntary episodes that look and feel similar to epileptic seizures but have psychological, not neurological, causes. Researchers have found that adding PNES-specific cognitive behavioral therapy (CBT) to standardized medical care for patients who suffer from these debilitating episodes results in longer periods of seizure freedom and significantly improved quality of life. Learn More
  • Wearable Devices and SUDEP Risk Assessment: An accelerometer (ACC) is a wearable device that measures motion during a convulsive seizure. This study now shows that the “silence” recorded by ACCs after a seizure is a reliable indicator of “post-ictal immobility” (PI) which is the absence of motion following a seizure. PI has been associated with potentially life-threatening complications, including SUDEP. Learn More
  • Antiepileptic Drug (AED) Withdrawal: People with epilepsy who have been seizure-free for 1-2 years and stop taking their AEDs face a risk of recurrent seizures, the likelihood of which is difficult to determine. The authors of this study investigated five risk prediction models and predictive variables to assist in the development of personalized AED withdrawal plans. Learn More
  • Epilepsy and Autism: A study shows that early behavioral signs may predict the development of epilepsy in children with autism, suggesting the two disorders may share common origins. Nevertheless, the authors caution that there are not enough data for clinicians to start using these behavioral indicators as a screening tool. Learn More