Epihunter Classroom Makes Silent Epileptic Seizures Visible

Epihunter, the revolutionary new digital solution that makes silent epileptic seizures visible, is live on global crowdfunding platform Indiegogo. It is raising funds to bring the project to life.

Motor seizures are very visible by their muscle and body movements. Absence seizures – also called non-motor seizures or “petits-mals” – are much more difficult to notice for the outside observer. The person involved will simply stare, react in slow motion and stop movements. Seizures can last from a few seconds to several minutes. This makes it challenging for parents to report seizure frequency to medical professionals. Moreover, it can be especially tough in the classroom, both for the child and teacher.

Epihunter meets this challenge. Utilizing consumer EEG headsets and a proprietary app, Epihunter alerts teachers of epileptic absence seizures in the classroom. This way, Epihunter builds digital solutions to help normalize the daily life of people with epilepsy. It aims to facilitate observers to note exactly what is happening and hence hopes to avoid misunderstandings for those that don’t fully understand what is happening.

A Deep Brain Stimulation System in Epilepsy Clinical Trial: Tracking Neural Excitability

Brief Summary: The main purpose of this research project is to evaluate the safety and effectiveness of a surgically implanted device called the Medtronic Activa PC+S System in patients with medically refractory epilepsy (people who have seizures that are not completely controlled by medical therapy). The system sends small electrical pulses into a part of the brain called the thalamus to help control seizures. It sends this signal in regularly, regardless of if a seizure is occurring. A different version of this device is already approved for the treatment of epilepsy in Australia. This study aims to use the brain’s responses to single pulse electrical stimulation to measure the level of seizure susceptibility. The investigators would like to show that this measure can be used to provide more effective deep brain stimulation therapies, to stop seizures.

Anticipated Study Start Date: March 27, 2018
Estimated Primary Completion Date: December 2020
Estimated Study Completion Date: December 2020

Eligibility Criteria

Inclusion Criteria:

Patients with epilepsy with non-resectable pathologies, or clearly defined focal seizures without a defined structural pathology.

Patients will be required to have a seizure diary (of up to 3 months) recording at least five seizures per month that are well separated in time (at least 8 hours apart).

Exclusion Criteria:

Previous diagnosis of psychogenic/non-epileptic seizures.

New Direction For Precision Medicine In Epilepsy

In a new approach to precision medicine research, scientists used bioinformatics tools to identify common features of genes associated with infantile spasms compared to other forms of early life epilepsy. Their analysis, published in PLOS ONE, reveals that infantile spasms are not only unique clinically, but also biologically. Focus on specific biological mechanisms underlying the genes that cause infantile spasms could help find new targets for treatment.

‘Our novel approach marks a paradigm shift in precision medicine from single gene discovery to grouping genes by their underlying biology,’ says lead author Anne Berg, PhD, epilepsy specialist at Ann & Robert H. Lurie Children’s Hospital of Chicago and Research Professor in Pediatrics at Northwestern University Feinberg School of Medicine. ‘To develop new treatments, we can start looking at mechanisms common to many associated genes, instead of trying to therapeutically target one gene at a time. With this approach, we are starting to ask why certain genes are involved, which might help us understand why some treatments are effective and others are not. Such an approach could ultimately help us choose the treatment that mostly precisely matches the genetic signature and biology of the child’s epilepsy.’

‘We used bioinformatics tools to perform what is called gene set enrichment analysis, which means that we looked at common molecular properties of genes that lead to infantile spasms and other types of seizures,’ says Dr. Berg. ‘We examined how these genes function in the cell, in what processes they are involved, where in the cell they are expressed. We found that the genes associated with infantile spasms are uniquely involved in developmental functions within the cell body, which might be linked to why spasms tend to start at the same time in an infant’s development.’

Variants in one gene account for 7% of juvenile myoclonic epilepsy cases

An extremely rare genetic variant that affects the maturation, migration, and death of neurons appears to be responsible for about 7% of cases of juvenile myoclonic epilepsy.

Variants of the intestinal-cell kinase gene (ICK) occurred in 12 members of a family affected by the disorder and were confirmed in 22 of 310 additional patients, Julia N. Bailey, PhD , of the University of California, Los Angeles, and her colleagues reported in the March 15 issue of the New England Journal of Medicine .

But among these 34 patients, the variant manifested as different epileptic phenotypes, suggesting genetic pleiotropism, the investigators said.

The investigators drew data from the GENESS (Genetic Epilepsies Studies) consortium, which has study sites in the United States, Mexico, Honduras, Brazil, and Japan. The current study from the databank analyzed information from 334 families with genetic generalized epilepsies. Among these, 310 patients had adolescent-onset myoclonic seizures and polyspike waves, or had a diagnosis of JME.

Anxiety and Depression in Epilepsy Clinical Trial: A Treatment Study

Brief Summary: As a potential solution to address high rates of depression and anxiety seen in epilepsy patients and poor mental health care access, this randomized trial aims to study treatment for anxiety and depression in epilepsy taking place directly within the epilepsy clinic vs. psychiatry referral (typical care). Patients that meet eligibility criteria, including significant symptoms of depression and/or anxiety, will be randomized to the either the intervention group or the control group. The intervention will consist of an initial prescription for an FDA-approved medication to treat depression/anxiety and telephone-based chronic care management plan for repeated symptom measurement and side effect surveillance. The control group will receive usual care, which is a referral order to psychiatry placed by their treating neurologist.

Anticipated Study Start Date: April 2018
Estimated Primary Completion Date: March 2019
Estimated Study Completion Date: March 2019

Eligibility Criteria

Ages Eligible for Study: 18 Years and older (Adult, Senior)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No

Inclusion Criteria

  • Provision of signed and dated informed consent form
  • Stated willingness to comply with all study procedures and availability for the duration of the study
  • Age 18 or older
  • Ability to take oral medication and the willing to adhere to the intervention regimen
  • Minimum of 1 prior clinic visit at the Comprehensive Epilepsy Center
  • Adequate cognition (Montreal Cognitive Assessment, MoCA score of 20 or greater)
  • Diagnosis of epilepsy: EEG with documented seizure or epileptiform discharges OR non-epileptiform EEG and seizure remission with antiseizure drug OR treating epileptologist’s leading clinical impression is epilepsy
  • (Neurological Disorders Depression Inventory for epilepsy, NDDI-E score greater than 15 and/or Generalized Anxiety Disorder-7, GAD-7 score greater than or equal to 10

 

Exclusion Criteria

  • Pregnancy or lactation
  • Known allergic reactions to escitalopram or venlafaxine
  • Comorbid psychogenic nonepileptic seizures
  • Prior psychiatric hospitalization
  • Prior suicide attempt
  • History of manic or psychotic symptoms (past manic episode (SCID-I), or psychotic symptom screen positive)
  • Current treatment by a psychiatrist or counselor/therapist
  • Active suicidality at the time of screening
  • Current treatment with buspirone or an SSRI/SNRI/atypical antidepressant (specifically bupropion, fluoxetine, levomilnacipran, citalopram, milnacipran, desvenlafaxine, mirtazapine, duloxetine, paroxetine, escitalopram, sertraline, fluvoxamine, venlafaxine, vilazodone, vortioxetine)

Study: De Novo Hotspot Variants in CYFIP2 Cause Early-Onset Epileptic Encephalopathy

Study findings suggest that de novo Arg87 variants in CYFIP2 are associated with severe neurological disorders.

OBJECTIVE: The cytoplasmic fragile X mental retardation 1 interacting proteins 2 (CYFIP2) is a component of the WAVE regulatory complex, which is involved in actin dynamics. An obvious association of CYFIP2 variants with human neurological disorders has never been reported. Here, we identified de novo hotspot CYFIP2 variants in neurodevelopmental disorders and explore the possible involvement of the CYFIP2 mutants in the WAVE signaling pathway.

METHODS: We performed trio-based whole exome sequencing (WES) in 210 families and case-only WES in 489 individuals with epileptic encephalopathies. The functional effect of CYFIP2 variants on WAVE signaling was evaluated by computational structural analysis and in vitro transfection experiments.

RESULTS: We identified three de novo CYFIP2 variants at the Arg87 residue in four unrelated individuals with early-onset epileptic encephalopathy. Structural analysis indicated that the Arg87 residue is buried at an interface between CYFIP2 and WAVE1, and the Arg87 variant may disrupt hydrogen bonding, leading to structural instability and aberrant activation of the WAVE regulatory complex. All mutant CYFIP2 showed comparatively weaker interactions to the VCA domain than wild type CYFIP2. Immunofluorescence revealed that ectopic speckled accumulation of actin and CYFIP2 was significantly increased in cells transfected with mutant CYFIP2.

INTERPRETATION: Our findings suggest that de novo Arg87 variants in CYFIP2 have gain-of-function effects on the WAVE signaling pathway, and are associated with severe neurological disorders

Study: KEAP1 inhibition is neuroprotective and suppresses the development of epilepsy

Hippocampal sclerosis is a common acquired disease that is a major cause of drug-resistant epilepsy. A mechanism that has been proposed to lead from brain insult to hippocampal sclerosis is the excessive generation of reactive oxygen species, and consequent mitochondrial failure. Here we use a novel strategy to increase endogenous antioxidant defences using RTA 408, which we show activates nuclear factor erythroid 2-related factor 2 (Nrf2, encoded by NFE2L2) through inhibition of kelch like ECH associated protein 1 (KEAP1) through its primary sensor C151.

Activation of Nrf2 with RTA 408 inhibited reactive oxygen species production, mitochondrial depolarization and cell death in an in vitro model of seizure-like activity. RTA 408 given after status epilepticus in vivo increased ATP, prevented neuronal death, and dramatically reduced (by 94%) the frequency of late spontaneous seizures for at least 4 months following status epilepticus.

Thus, acute KEAP1 inhibition following status epilepticus exerts a neuroprotective and disease-modifying effect, supporting the hypothesis that reactive oxygen species generation is a key event in the development of epilepsy.

Study: Pharmacological characterization of the cannabinoid receptor 2 agonist, ?-caryophyllene on seizure models in mice

A study finds Cannabinoid receptor 2 agonist ?-caryophyllene may be clinically relevant as treatment against seizure spread.

PURPOSE: Activation of CB1 receptors, produces anticonvulsant effect accompanied by memory disturbance both in animal seizure tests and in patients with epilepsy. Few reports considered the role of CB2 receptor on seizure susceptibility and cognitive functions. The aim of the present study was to explore the effect of a selective CB2 receptor agonist ?-caryophyllene (BCP) in models of seizures and cognition in mice.

METHODS: Dose-dependent effects of BCP was studied in maximal electroshock seizure (MES) test, subcutaneous pentylenetetrazole (scPTZ) test and Morris water maze test. Phenytoin and diazepam were used as reference drugs in seizure tests. The effect of sub-chronic treatment with BCP for 7?days (50 and 100?mg?kg-1) was assessed on status epilepticus (SE) induced by kainic acid (KA) model and oxidative stress through measurement of malondialdehyde (MDA) level in the hippocampus. The acute neurotoxicity was determined by a rotarod test.

RESULTS: The BCP exerted a protection in the MES test at the lowest dose of 30?mg?kg-1 at the 4-h interval tested comparable to that of the referent drug phenytoin. The CB2 agonist was ineffective in the scPTZ test. The BCP displayed no neurotoxicity in the rotarod test. The BCP decreased the seizure scores in the KA-induced SE, which effect correlated with a diminished lipid peroxidation. The CB2 agonist exerted a dose-dependent decrease of latency to cross the target area during the three days of testing in the Morris water maze test.

CONCLUSION: [The] results suggest that the CB2 receptor agonists might be clinically useful as an adjunct treatment against seizure spread and status epilepticus and concomitant oxidative stress, neurotoxicity and cognitive impairments.

Improved method for mesial temporal lobe epilepsy surgery: Automated trajectory planning for laser interstitial thermal therapy

Following laser interstitial thermal therapy for mesial temporal lobe epilepsy, computer-assisted planning provides a better safety profile, with potentially improved seizure-free outcome and reduced neuropsychological deficits, according to an Epilepsia study.

Objective: Surgical resection of the mesial temporal structures brings seizure remission in 65% of individuals with drug-resistant mesial temporal lobe epilepsy (MTLE). Laser interstitial thermal therapy (LiTT) is a novel therapy that may provide a minimally invasive means of ablating the mesial temporal structures with similar outcomes, while minimizing damage to the neocortex. Systematic trajectory planning helps ensure safety and optimal seizure freedom through adequate ablation of the amygdalohippocampal complex (AHC). Previous studies have highlighted the relationship between the residual unablated mesial hippocampal head and failure to achieve seizure freedom. We aim to implement computer-assisted planning (CAP) to improve the ablation volume and safety of LiTT trajectories.

Methods: Twenty-five patients who had previously undergone LiTT for MTLE were studied retrospectively. The EpiNav platform was used to automatically generate an optimal ablation trajectory, which was compared with the previous manually planned and implemented trajectory. Expected ablation volumes and safety profiles of each trajectory were modeled. The implemented laser trajectory and achieved ablation of mesial temporal lobe structures were quantified and correlated with seizure outcome.

Results: CAP automatically generated feasible trajectories with reduced overall risk metrics (P< .001) and intracerebral length (P = .007). There was a significant correlation between the actual and retrospective CAP-anticipated ablation volumes, supporting a 15 mm diameter ablation zone model (P < .001). CAP trajectories would have provided significantly greater ablation of the amygdala (P = .0004) and AHC (P = .008), resulting in less residual unablated mesial hippocampal head (P = .001), and reduced ablation of the parahippocampal gyrus (P = .02).

Significance: Compared to manually planned trajectories CAP provides a better safety profile, with potentially improved seizure-free outcome and reduced neuropsychological deficits, following LiTT for MTLE.

Mayo project receives grant for collaborative epilepsy project

The Minnesota Partnership for Biotechnology and Medical Genomics awarded five grants to Mayo Clinic collaborative projects in 2018.

Five teams at the clinic will begin two-year projects to work on treatment options for the following diseases: epilepsy, Alzheimer’s disease, osteoporosis, colorectal cancer and bacterial infections.

Those teams, and their projects, include: Lynne Bemis, Ph.D., University of Minnesota Medical School, Duluth Campus, and Gregory Worrell, M.D., Ph.D., Mayo Clinic, who will research training vesicles in the brain to help with epilepsy treatment.