PURPOSE: The aim of this study was to evaluate the effects of vagus nerve stimulation (VNS) on heart rate variability (HRV) in children with epilepsy.

RESULTS: Increased heart rates (HRs); decreased SDNN, SDANN, RMMSD, and PNN50; and increased LF/HF ratios were identified before VNS therapy (p<0.05). Even though remarkable improvement was seen after 6months of VNS treatment (p<0.05), no further changes were observed in 12-month compared with 6-month levels (p>0.05) in all parameters, still even significantly lower than those of controls (p<0.05). Longer duration of epilepsy and localization of epileptic focus, such as in the temporal lobe, were also found to further contribute to diminished basal HRV levels (p<0.05).

CONCLUSION: The cardiovascular system is under deep sympathetic influence in children with epilepsy. Although VNS seems to provide a substantial improvement by achieving increased parasympathetic effects in short-term therapy, the levels were still lower than those of healthy children after either short- or long-term therapy. Therefore, impaired cardiovascular autonomic regulation may be associated with the epileptic process itself as well as with the contribution of some additional factors. Overall, different aspects such as age, epilepsy duration, epileptic focus, seizure frequency, and AEDs should also be considered for their further possible effects on HRV during VNS therapy.

A batch of new FDA guidance documents for neurology drugs released Thursday February 15 support Commissioner Scott Gottlieb’s oft-stated goal to offer manufacturers more flexibility in how they can win the agency’s approval.

For drugs intended for children age 4 and older with partial onset seizures, the FDA will no longer require that efficacy trials be conducted in children. The agency will now consider efficacy data from adult patients to be sufficient for pediatric approval.

FDA’s reasoning in this instance is that previous trials of seizure drugs conducted in children have shown that their dose-response patterns do not differ from those seen in adult patients. However, formulations of drugs for pediatric patients must still take into consideration the special needs of children, and it’s conceivable that trials will be required to support approval of particular products. “FDA encourages sponsors to explore innovative approaches to pediatric formulation development and testing,” the guidance noted. And the agency will continue to require that clinical trials be conducted in children for safety endpoints.

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.”

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.

A 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.

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

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.

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.

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.

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.