Epilepsy patients who have not responded to standard drug treatments may benefit from a new therapy that delivers high frequency bursts of electrical stimulation, called microbursts, to the brain. Rush University Medical Center in Chicago is the first health care provider in the world to provide this treatment, known as microburst vagus nerve stimulation.

The treatment is akin to a heart pacemaker. A surgeon places an electronic pulse generator under the skin in the chest and attaches it to the left vagus nerve, which runs down the side of the body from the stem of the brain through the neck and chest to the abdomen.

The device sends regular electrical pulses through the vagus nerve to the brain to prevent epileptic seizures from occurring. The stimulator’s settings can be changed according to each patient’s needs using a special programming wand, with no additional surgery needed.

The study consists of two groups of patients with epilepsy, enrolling up to 40 patients in total at approximately 15 sites in the United States. The first group will include 20 patients with primary generalized tonic-clonic seizures. The second group will consist of 20 patients with partial onset seizures, including complex partial seizures with or without secondary generalization.

Each patient will participate in the study for a minimum of 15 months. The study will measure the percent change in seizure frequency and occurrence of stimulation-related adverse events in comparison to a patient’s baseline. Activation of various areas of the brain in response to stimulation will be assessed using functional magnetic resonance imaging or fMRI. Patients also will be evaluated to assess changes from baseline in seizure severity, quality of life, antiepileptic drug use, suicidality and adverse events.

PURPOSE: To establish if listening to Mozart’s Sonata for two pianos in D major (K448) has an anti-epileptic effect on the EEGs (electroencephalograms) of children.

METHODS: Forty five children (2-18 years; mean 7 years 10 months) who had epileptiform activity on EEG were recruited from those attending for scheduled EEG investigations. Mozart’s Sonata for two pianos in D major (K448) and an age-appropriate control music were played during the EEG. There were five consecutive states during the record, each lasting 5?min; before Mozart music (baseline), during Mozart music, after Mozart music/before control music, during control music and after control music. Epileptic discharges were counted manually and the mean frequency of epileptic discharges calculated in each state.

RESULTS: A significant reduction (p?<?0.0005) in the frequency of epileptic discharges was found during listening to the Mozart music compared to the baseline. No evidence of a difference in mean epileptic discharges was found between the baseline and the other three states or between listening to the Mozart music and control music.

CONCLUSION: This study confirms an anti-epileptic effect of Mozart music on the EEG in children, which is not present with control music. The role of ‘Mozart therapy’ as a treatment for drug-resistant epilepsy warrants further investigation.

Engage Therapeutics, Inc. announced May 4th the dosing of the first patient in its multi-center, double-blind, randomized Phase 2b StATES (Staccato®AlprazolamTerminatesEpilepticSeizures) trial to investigate the safety and efficacy of Staccatoalprazolam in subjects with epilepsy that have a predictable seizure pattern.

The StATES trial (NCT03478982) will enroll 108 patients across 40 U.S.-based clinical sites. The primary endpoint is the cessation of seizure activity. Seizure episode severity, as well as the incidence of adverse events, will also be evaluated. Topline data is expected in the second half of 2019.Staccatoalprazolam, a single use, investigational epileptic seizure rescue therapy, combines the Staccato delivery technology, which is currently used in a U.S. Food and Drug Administration (FDA)-approved product, with alprazolam, an FDA-approved benzodiazepine. Together, this combination is novel for an epilepsy application in a patient population in need of innovative rescue options.

Greg Mayes, president, CEO and founder of Engage Therapeutics, said, “For individuals with epilepsy that have a predictable seizure pattern, currently available rescue treatments can only address the prevention of seizure activity once the first seizure ends, but Staccato alprazolam has the potential to be the first and only product that can abort an active seizure. We are excited by the enthusiastic response that this study has received from the epilepsy community and how quickly we have been able to advance this promising candidate to this point in development.”

Medtronic plc, the global leader in medical technology, announced on April 30, 2018 that the U.S. Food and Drug Administration (FDA) has granted premarket approval for Medtronic’s Deep Brain Stimulation (DBS) therapy as adjunctive treatment for reducing the frequency of partial-onset seizures, in individuals 18 years of age or older who are refractory, or drug-resistant, to three or more antiepileptic medications. DBS therapy for epilepsy delivers controlled electrical pulses to a target in the brain called the anterior nucleus of the thalamus (ANT), which is part of a network involved in seizures.

According to the Epilepsy Foundation, 3.4 million individuals in the United States have epilepsy. Antiepileptic drug (AED) medication is the primary treatment to control seizures; however, up to one third of individuals with epilepsy have seizures that do not successfully respond to AEDs.

“Many patients in the United States with severe epilepsy are not able to control their seizures with currently-available drugs and are not candidates for potentially curative surgery,” said Dr. Robert Fisher, director of the Stanford Epilepsy Center, Stanford University, and lead principal investigator of the SANTE trial. “Epilepsy that is refractory to AED treatment is an unsolved problem, and DBS therapy will now serve as an important new treatment option, including for people with poorly localized or multiple regions of seizure origin.”

The FDA approval is based on both the blinded phase and the 7-year follow-up data collected in Medtronic’s clinical trial called SANTE (Stimulation of the Anterior Nucleus of the Thalamus in Epilepsy). The SANTE trial was a prospective, randomized, double-blind pivotal study to evaluate the use of DBS therapy for patients with medically refractory epilepsy with partial-onset seizures, with or without secondary generalization, that were drug-resistant to three or more antiepileptic medications. The trial collected data from 110 patients who were implanted with a Medtronic DBS system at 17 centers located in the US.

PURPOSE: The paper presents a long-term follow-up study of VNS patients, analyzing seizure outcome, medication changes, and surgical problems.

METHOD: 74 adults with VNS for 10 to 17 years were evaluated yearly as: non-responder – NR (seizure frequency reduction <50%), responder – R (reduction???50% and <90%), and 90% responder – 90R (reduction???90%). Delayed R or 90R (??4?years after surgery), patients with antiepileptic medication changes and battery or complete system replacement were identified. Statistical analysis of potential outcome predictors (age, seizure duration, MRI, seizure type) was performed.

RESULTS: The rates of R and 90R related to the patients with outcome data available for the study years 1, 2, 10, and 17 were for R 38.4%, 51.4%, 63.6%, and 77.8%, and for 90R 1.4%, 5.6%, 15.1%, and 11.1%. The absolute numbers of R and 90R increased until years 2 and 6. Antiepileptic therapy was changed in 62 patients (87.9%). There were 11 delayed R and four delayed 90R, with medication changes in the majority. At least one battery replacement was performed in 51 patients (68.9%), 49 of whom R or 90R. VNS system was completely replaced in 7 patients (9.5%) and explanted in 7 NR (9.5%). No significant predictor of VNS outcome was found.

CONCLUSIONS: After an initial increase, the rate of R (seizure reduction ??50% and <90%) and 90R (seizure reduction???90%) remains stable in long-term follow-up. The changes of antiepileptic treatment in most patients potentially influence the outcome. Battery replacements or malfunctioning system exchange reflect the patient’s satisfaction and correlate with good outcomes.

Zogenix, Inc., a pharmaceutical company developing therapies for the treatment of rare central nervous system (CNS) disorders, today announced additional data from analyses of its first Phase 3 trial (Study 1) of the company’s investigational drug, ZX008 (low-dose fenfluramine hydrochloride), for the adjunctive treatment of seizures associated with Dravet syndrome. Top-line results from Study 1 were previously reported in September 2017. The additional Study 1 results were presented in two late-breaker poster presentations at the Emerging Science session at the 2018 American Academy of Neurology (AAN) Annual Meeting being held April 21-27 in Los Angeles, California (see study data here and here).

As previously reported, Study 1 met its primary objective of demonstrating that ZX008, at a dose of 0.8 mg/kg/day, is superior to placebo as an adjunctive therapy in the treatment of Dravet syndrome in children and young adults based on change in the frequency of convulsive seizures between the 6-week baseline observation period and the 14-week treatment period (p<0.001).

“It is highly encouraging to see that the efficacy and tolerability in this subgroup of patients who had previously failed treatment with stiripentol was comparable to the full Study 1 population,” said Rima Nabbout, M.D., Ph.D., Department of Pediatric Neurology, Reference Center for Rare Epilepsies, and one of the poster’s authors. “As stiripentol is a commonly used antiepileptic drug, it is important to understand how tolerable and effective ZX008 is in this subgroup of patients.”