Stress-Reducing Techniques Lead to Fewer Seizures

Stress-reducing techniques may help medication-resistant epilepsy patients experience fewer seizures, a randomized, controlled, double-blind study found.

Patients who performed muscle-relaxing exercises had 29% fewer seizures, while patients who engaged in focused-attention activity reduced seizures by 25%, reported Sheryl R. Haut, MD, of Montefiore Medical Center and the Albert Einstein College of Medicine in the Bronx, N.Y., and colleagues in Neurology.

“Despite all the advances we have made with new drugs for epilepsy, at least one-third of people continue to have seizures, so new options are greatly needed,” Haut said in a statement. “Since stress is the most common seizure trigger reported by patients, research into reducing stress could be valuable.”

Congenica and FutureNeuro unite to deliver more accurate diagnoses for genetic epilepsy

New software to deliver faster and more accurate diagnoses in genetic epilepsies is the ambition of a ground-breaking partnership between Congenica, a global provider of clinical genomics interpretation software, and FutureNeuro, the SFI Research Centre for Chronic and Rare Neurological Diseases, supported by Science Foundation Ireland. The software will be designed to work with electronic health record (EHR) systems, including the Irish electronic health record for Epilepsy, so that the entire diagnostic process, from initial DNA sequencing to determining treatment options, is available to clinicians and patients through their electronic records.

The partnership, operating out of the FutureNeuro Human Genetics lab of Professor Gianpiero Cavalleri in RCSI, Dublin, will build on Congenica’s clinical genomics analysis software, Sapientia™, to assist clinicians in making more tailored treatment decisions for certain types of genetic epilepsy. At the moment, epilepsy is diagnosed using EEGs, CT scans or MRIs, which only provide a limited picture of a person’s epilepsy. Genomics, which focuses on the structure, function, mapping, and editing of genomes, is a new and powerful tool for reaching a molecular diagnosis, which in turn can inform and improve treatment options.

“Genomics is changing clinical medicine,” said Dr Norman Delanty, Clinical Neurologist with FutureNeuro, “neurologists need to embrace it as a new powerful diagnostic tool to allow us to understand the many challenging faces of epilepsy, and lead us to individualising treatment and prognosis in the clinic.”

Study shows levetiracetam outweighs common therapies for nonsyndromic pediatric epilepsy

A comparison of 2 drugs commonly prescribed for infants with nonsyndromic epilepsy (NSE) found that oral anticonvulsant therapy levetiracetam significantly reduces treatment regiment and seizure rates when compared to phenobarbital.

multicenter cohort study of 155 infants with NSE provided the first evidence that one common initial pediatric therapy for non-conforming epilepsy is significantly more beneficial than the other.

Anne T. Berg, PhD, from Stanley Manne Children’s Research Institute at Ann & Robert H. Lurie Children’s Hospital of Chicago, told MD Magazine that although levetiracetam is already far and away the preferred initial therapy for children suffering from NSE, this is substantial analysis showing that it is superior to the next-prescribed therapy in managing short-term seizures.

The study compared the 2 therapies as initial monotherapies in 155 children with NSE with seizure onset at 1 month to 1 year of age. Researchers administered levetiracetam to 117 patients, and phenobarbital to 38 patients for 6 months.

About 40% of infants receiving levetiracetam did not require an additional anti-epileptic therapy to help control seizures, and became seizure-free within 3 months of initial of initial therapy. Just 16% of the patients treated with phenobarbital reached the same outcome.

The true value of the study may come from its network building. The involved 17 medical centers, all from the US  Pediatric Epilepsy Research Consortium, have been conglomerated since 2012, and is looking to emulate the extensive research found in other cooperative groups such as the Children’s Oncology Group, Berg said.

Diazepam Buccal Soluble Film Clinical Trial: Safety and Tolerability Study

This Phase 3, multicenter, open-label study of chronic, intermittent use of study drug (DBSF) is designed to evaluate the safety and tolerability of the buccal formulation of diazepam in children, adolescents and adults with acute repetitive seizures.

Detailed Description:

The Primary objective of the study is to assess the safety and tolerability of DBSF (study drug) administered to subjects with epilepsy for the treatment of seizures over a minimum 12-month period.

Secondary objectives of the study are;
– To evaluate the usability of study drug as assessed by the ability of caregivers/subjects to administer study drug based on the Instructions for Use (IFU).
– To evaluate the Quality of Life of the subjects during the study drug treatment period as assessed by age appropriate use of epilepsy scales [Pediatric Quality of Life Inventory (PedsQL), Quality of Life in Epilepsy Inventory (QOLIE) 39 and Quality of Life in Epilepsy Inventory (QOLIE) 49] over a minimum 12-month period.

Anticipated Study Start Date: February 28, 2018
Estimated Primary Completion Date: April 30, 2019
Estimated Study Completion Date: June 7, 2019

Eligibility Criteria

Ages Eligible for Study: 2 Years to 65 Years (Child, Adult)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No

Inclusion Criteria:

  1. Female or male subject between the ages of 2 and 65 years of age, inclusive
  2. Written informed consent to participate in the study
  3. Subject has an established diagnosis of epilepsy either partial or generalized epilepsy with motor seizures with clear alteration of awareness, and while on a regimen of anti-epileptic medication(s), still experiences bouts of seizures (frequent break through seizures, e.g. ARS or seizure clusters) and who, in the opinion of the Investigator, may need benzodiazepine intervention for seizure control at least 1 time a month on average.
  4. Caregiver, if needed for subject, provides written informed consent and is able to administer study drug in the event of a seizure.
  5. Female subjects ?12 years of age have a negative serum pregnancy test at screening. Female subjects of childbearing potential, (not surgically sterile or less than 2 years postmenopausal), must have a partner who is sterile, agrees to abstinence, be practicing double barrier contraception or using an FDA approved contraceptive (e.g., licensed hormonal or barrier methods) for greater than 2 months prior to screening visit and commit to an acceptable form of birth control for the duration of the study and for 30 days after the study
  6. No aspects of the medical history and/or the physical-neurological examination that at the judgment of the Investigator, in consultation with the Sponsor, will interfere with administration or absorption of study drug, or could evolve into a safety issue
  7. No clinically significant abnormal findings on the electrocardiogram (QTcF?450 msec for males and QTcF?470 msec for females)
  8. Subject and caregiver must be willing to comply with all study visits and all required study procedures

 

Exclusion Criteria

  1. A history of clinically significant gastrointestinal, renal/genitourinary, hepatic, hematologic, dermatologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, or cardiovascular disease, or any other clinically significant abnormalities, such as physical examination, vital signs, laboratory tests or ECG at Screening or Baseline which in the opinion of the investigator require further investigation or treatment or which may interfere with study procedures or safety or other medical conditions (e.g., cardiac, respiratory, gastrointestinal, psychiatric, renal disease) which are not adequately and stably controlled, or which in the opinion of the investigator(s) could affect the subject’s safety or interfere with the study assessments or any other condition which, in the opinion of the Investigator, would jeopardize the safety of the subject
  2. Subject has had significant traumatic injury, major surgery or open biopsy within 30 days prior to study screening
  3. Subject with an active major depression or a past suicide attempt, or any suicidal ideation of 4, or 5 or any suicidal behavior in lifetime using C-SSRS. The pediatric C-SSRS should be used for subjects 6 to 11 years of age. The adult C-SSRS should be used for subjects ?12 years of age. Note that this exclusion is only applicable to cognitive-appropriate subjects who are able to understand and complete the Suicide Rating Scale
  4. A history of allergic or adverse responses to diazepam or any other benzodiazepine
  5. Participation in a clinical trial other than MonoSol Rx Phase 2 studies 160325 and 160326 within 30 days prior to Day 0. Participation in an observational (non-interventional) study is not an exclusion, provided that there are no scheduling conflicts with this study. Received any other investigational medication (unless it can be documented that the subject received only placebo) or device within 8 weeks or 5 half-lives (whichever is longer) before assignment to study drug treatment
  6. Lactating female or positive serum pregnancy test (ß-hCG) at screening for female subjects ?12 years of age
  7. Positive blood screen for HIV, HbSAg, or Hepatitis C, or a positive urine screen for alcohol or drugs of abuse, except marijuana use for medicinal indications. When marijuana is or was used for medicinal indications in the opinion of the Investigator, it is not considered as drug abuse and the subject can be enrolled in states where medical marijuana use is legal, even if the marijuana metabolites in the urine revealed as positive

FDA grants breakthrough therapy designation for Dravet syndrome treatment

The FDA has granted Zogenix Inc. breakthrough therapy designation for low-dose fenfluramine use to treat seizures related to Dravet syndrome, according to a press release issued by the company.

“We are very pleased that the FDA has granted breakthrough therapy designation based on the efficacy and safety results from Study 1 reported in the fall of 2017,” Gail M. Farfel, PhD, chief development officer of Zogenix, said in the release. “We look forward to working closely with the FDA as we conclude our phase 3 clinical program in Dravet syndrome, a rare and catastrophic form of childhood epilepsy.

ZX008 can also be used for the treatment of Lennox-Gastaut syndrome, according to the release This form of epilepsy is also severe and begins in childhood. Those who have this condition are likely to also have intellectual disability.

Ketogenic Diet Clinical Trial: The Modified Ketogenic Diet for the Treatment of Pharmacoresistant Epilepsy in Adults, an Observational Cohort Study

This study is a prospective observational cohort study for adult patients with drug resistant epilepsy who are not suitable for resective epilepsy surgery. The intervention is a modified ketogenic diet. The carbohydrate load will be between 20-30gm per day. Blood ketones and blood sugars will be monitored. The primary outcome measure is seizure frequency at 12 months. There are a number of secondary outcome measures including tolerability, seizure severity, quality of life, lipid profiles and health care utilization.

Status: Recruiting
Estimated Study Completion date: September 1, 2018

Eligibility Criteria

Ages Eligible for Study: 18 Years to 100 Years (Adult, Senior)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
Sampling Method: Non-Probability Sample

The study will have no formal inclusion/exclusion criteria as it is purely observational and it will be the clinical team’s decision as to whether or not people are seen by the dietary clinic based on established dietary clinic protocols.

UH Engineer Locates Brain’s Seizure Onset Zone in Record Time: Discovery Breakthrough for Epilepsy Patients

A University of Houston biomedical engineer is reporting a dramatic decrease in the time it takes to detect the seizure onset zone (SOZ), the actual part of the brain that causes seizures, in patients with epilepsy.

Using oscillating brain waves, rather than observing seizures as they happen, assistant professor Nuri Ince locates the seizure onset zone in one hour. Current treatment protocols for detecting the zone require prolonged monitoring in the hospital for up to 10 days. Ince’s new method to locate the seizure onset zone, reported in Brain, A Journal of Neurology, could save patients weeks of hospitalization, reduce complications and costs associated with what has traditionally been an arduous, and often painful, procedure.

Ince developed a pipeline of machine learning algorithms to interpret the brain waves, and after two years his algorithm identified the pattern.

“Can you imagine monitoring a patient for just one hour, as compared to before when it takes days or weeks?” Ince said, still marveling at the saving of both time and money this translational project will bring to the patient and their families.

UH Engineer Locates Brain’s Seizure Onset Zone in Record Time: Discovery Breakthrough for Epilepsy Patients

A University of Houston biomedical engineer is reporting a dramatic decrease in the time it takes to detect the seizure onset zone (SOZ), the actual part of the brain that causes seizures, in patients with epilepsy.

Using oscillating brain waves, rather than observing seizures as they happen, assistant professor Nuri Ince locates the seizure onset zone in one hour. Current treatment protocols for detecting the zone require prolonged monitoring in the hospital for up to 10 days. Ince’s new method to locate the seizure onset zone, reported in Brain, A Journal of Neurology, could save patients weeks of hospitalization, reduce complications and costs associated with what has traditionally been an arduous, and often painful, procedure.

Ince developed a pipeline of machine learning algorithms to interpret the brain waves, and after two years his algorithm identified the pattern.

“Can you imagine monitoring a patient for just one hour, as compared to before when it takes days or weeks?” Ince said, still marveling at the saving of both time and money this translational project will bring to the patient and their families.

MicroRNAs as Biomarkers Clinical Trial: Circulating microRNAs as Biomarkers of RESPIratory Dysfunction in Patients With Refractory epilePSY (MIRESPILEPSY)

Sudden and unexpected death in epilepsy (SUDEP) has become a major issue for patients with epilepsy and their physicians. SUDEP is a nontraumatic and non-drowning death in patients with epilepsy, unrelated to a documented status epilepticus, in which postmortem examination does not reveal a toxicologic or anatomic cause of death. It primarily affects young adults with drug-resistant epilepsy, with an incidence of about 0.5%/year. A recent study reported that up to 20% of patients with childhood onset drug resistant epilepsy will die of a SUDEP by the age of 45. Apart from optimizing antiepileptic drugs, no preventive treatment is available to prevent SUDEP. As underscored by the World Health Organization (WHO), there is an urgent need to develop specific therapeutic approaches to tackle this issue.

The primary objective of the proposal is to evaluate the diagnostic value of a set of circulating microRNAs pre-selected because of their implication in the regulation of molecular pathways involved in the respiratory regulation to identify patients with seizure-related respiratory dysfunction, as defined by occurrence ictal/peri-ictal pulse oxymetry < 90%.

A total of 50 patients will be included over a period of one year. Patients undergoing long-term video-EEG/SEEG monitoring will be recruited in the epilepsy monitoring unit of the Department of Functional Neurology and Epileptology, Hospices Civils de Lyon, Lyon, France.

It will be a case-control study in a cohort of patients with drug-resistant focal epilepsy undergoing long-term video-EEG monitoring, in which patients who demonstrate ictal/post-ictal hypoxemia (cases) will be compared with those without seizure-related respiratory dysfunction (controls).

Elibibility Criteria

Inclusion Criteria

For the patients:

  • Adult patient (? 18 years) suffering from drug-resistant focal epilepsy or from drug-resistant generalized epilepsy according to ILAE classification
  • Patient undergoing long-term video-EEG monitoring in Epilepsy unit of Lyon to record and characterize her/his seizure
  • Patient who gave her/his written informed consent to participate to the study
  • Patient affiliated to the French health care system

 

For the healthy volunteers:

  • Adult (? 18 years)
  • Without history of neurological disorders and/or psychiatric disorders, and/or general medical disorders
  • Subject who gave her/his written informed consent to participate to the study
  • Subject affiliated to the French health care system

 

Exclusion Criteria

For the patients:

  • Ongoing major depressive episode as defined by a score ? 15 at the French version of the NDDI-E scale*
  • Current panic disorder as defined by a score ? 7 at the French version of the GAD-7 scale*
  • Ongoing treatment with selective serotonin reuptake inhibitor
  • Patient who benefit from a protective measure

 

For the healthy volunteers:

  • Presence of the symptoms of anxiety and/or depression as defined by a score ? 11 at the French version of the Hospital Anxiety and Depression Scale (HADS)
  • Ongoing treatment with selective serotonin reuptake inhibitor
  • Subjects with these psychiatric comorbidities and/or treatment will be excluded in order to limit risk that the relation previously reported between miR-135a, miR-16, miR-1202 and depression and/or panic disorder and/or response to selective serotonin

Second Phase 3 of Dravet Drug Completes Enrollment

Zogenix, Inc. announced on January 31st that the last patient has been randomized into the treatment period of Study 1504, its second Phase 3 clinical trial evaluating ZX008 (low-dose fenfluramine) as an adjunctive treatment for seizures in children and young adults with Dravet syndrome.

At the 71st American Epilepsy Society (AES) Annual Meeting in December, positive safety and efficacy data from the company’s Study 1 trial, exhibiting the drug’s ability to achieve a clinically meaningful benefit in the same indication, were presented.

Dravet syndrome is a pediatric epilepsy disorder in which a wide variety of seizure types plague the patient, and the condition is often associated with a high mortality rate. It typically begins in the first year of life of an otherwise healthy infant, and those affected can also experience developmental delays, and, at present, there aren’t any approved orphan drugs to treat the condition.

“The completion of patient randomization in Study 1504 represents another significant achievement in our ZX008 Phase 3 development program in Dravet syndrome,” said Stephen J. Farr, Ph.D., President and CEO of Zogenix in a press release. “We expect to announce top-line data from this study in the second quarter of this year. The data generated to date from the Phase 3 clinical program have further strengthened our confidence in the potential of ZX008 to become an important treatment option for the control of seizures in patients suffering from Dravet syndrome, a rare and catastrophic form of epilepsy.”