Jacqueline French, MD

“I always talk about the ‘television seizure.’ You never see anybody on TV having a seizure which is not falling to the ground, shaking their arms and legs, frothing at the mouth—and I think if you asked a person on the street, ‘what is a seizure,’ that’s what they would tell you.”

 as part of the Human Epilepsy Project by a group of authors including Jacqueline French, MD, professor of neurology, and director, Translational Research and Clinical Trials in Epilepsy, NYU Grossman School of Medicine, suggests that the early identification of nonmotor seizures may help prevent injury and serious morbidity.

In the study, more patients with new-onset focal disease presented with initial nonmotor seizures than motor seizures (55% vs. 45%, respectively; 

 = .04), and the majority of injuries reported by patients prior to diagnosis for those who presented initially with nonmotor seizures occurred in those who ultimately developed motor seizures (92 of 167 patients; 55.1%). Those who never developed motor seizures were less likely to be injured (8 of 79; 10.1%) by a significant margin (

Part of the challenge in identifying these patients is one of education about seizures, French told 

. Most people, she noted, don’t understand the multiple ways a seizure can present—often without convulsions. She pointed to the successful F.A.S.T. (Face drooping, Arm weakness, Slurred speech, Time to call 9-1-1) campaign that has aided in stroke as a good example of how to push for better understanding. She offered up epilepsy’s own version: S.S.S.S.S—short, sudden, strange, similar spells.

REFERENCE
Pellinen J, Tafuro E, Yang A, et al. Focal nonmotor versus motor seizures: The impact on diagnostic delay in focal epilepsy. 

. Published online October 20, 2020. doi: 10.1111/epi.16707

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The director of Translational Research and Clinical Trials Epilepsy at NYU Grossman School of Medicine discussed the need to improve education about nonmotor seizures.

Jacqueline French, MD: Barriers to Identifying Nonmotor Seizures

“What we started to find out is that these seizures, that [patients] were now getting treated for and diagnosed with, in many cases had been going on for a long time before they came to medical attention.”

Recently, an analysis as part of the larger Human Epilepsy Project suggested that overcoming the obstacles that prevent an earlier diagnosis of focal epilepsy might help prevent the morbidity-related consequences of the delays in identifying new-onset disease, such as motor vehicle accidents.

The project, which includes an international team of over 300 doctors, researchers, healthcare workers, and patients at 27 hospitals, was developed to study the biomarkers of new-onset focal epilepsy. The analysis, published in October 2020, consisted of 246 participants with nonmotor seizures and 201 participants with motor seizures at disease onset, and ultimately showed that those with nonmotor seizures experienced a delay in median time to diagnosis from first seizure tenfold that of those with motor seizures (

To find out more about this work, the findings so far, and how it came to be, 

 reached out to study author Jacqueline French, MD, professor of neurology, and director, Translational Research and Clinical Trials in Epilepsy, NYU Grossman School of Medicine. French shared some insight into the project and what this analysis highlighted.

The director of Translational Research and Clinical Trials Epilepsy at NYU Grossman School of Medicine discussed the groundwork done with the Human Epilepsy Project for a recent analysis.

Jacqueline French, MD: Identifying Focal Epilepsy Seizures

“In the past, [there have been agents] that have burned the inside of the nose, so you lost your sense of smell. To know that it doesn’t happen with this therapy is essential.”

 annual meeting of the American Epilepsy Society (AES)

, December 6-10, 2019, in Baltimore, Maryland, Jacqueline A. French, MD, professor of neurology, NYU Langone Medical Center, and colleagues presented a number of safety findings for intranasal diazepam (Valtoco; Neurelis) in the treatment of epileptic seizures.

All told, the use of the spray as seizure rescue medication was deemed safe with multiple uses over the long-term. The analysis included data from 132 patients and 2485 seizure episodes across a 1-year follow-up period. Patients received either 5, 10, 15, or 20 mg of intranasal diazepam, with a second dose administered 4 to 12 hours later if needed.

, are reassuring at the very most and essential at the very least, as in years past, the use of intranasal delivery systems was not always successful. In addition to noting the importance of these data, French also shared her insight into why comparative data with other rescue medications—which is not yet available&mdash;will be helpful in determining who may benefit.

Miller I, Wheless JW, Hogan RE, et al. Safety and tolerability of NRL-1, an intranasal formulation of diazepam, in relationship to usage frequency in subjects with epilepsy: interim results from a phase 3, open-label, repeat dose study. Presented at: 2019 American Epilepsy Society Annual Meeting. December 6-10, 2019; Baltimore, Maryland. Abstract 1.22.

The professor of neurology at NYU Langone Medical Center discussed the importance of these safety data for intranasal diazepam, and why future comparative data would be essential.

Jacqueline French, MD: Safety of Intranasal Diazepam As Rescue Medication

“This is one of the potential concerns—that if people don’t ask about these smaller seizures, which many, even neurologists, don’t, they can misdiagnose people…if they have a convulsion, it may be their hundredth seizure instead of their first.”

Although neurologists and epileptologists have learned massive amounts about treating epilepsy in the last 2 decades, so much remains left to understand. Compounding that is the fact that treating epilepsy is complex and complicated. Many patients are refractory, and even the most efficacious antiepileptic drugs can be ineffective.

A less-discussed challenge, however, is that of delayed diagnosis of epilepsy. As Jacqueline French, MD, pointed out in a conversation with 

 at the 2019 American Academy of Neurology (AAN) Annual Meeting in Philadelphia, Pennsylvania, this can cause irreparable damage to patients. Some, she said, may have been experiencing hundreds of subtle, otherwise undetectable seizures for quite some time prior to getting a proper diagnosis.

The director of Translational Research and Epilepsy Clinical Trials at NYU Langone spoke about the nuance involved in diagnosing epilepsy and the misconceptions about how seizures present in the majority of patients.

Jacqueline French, MD: Dangers of Delayed Diagnosis in Epilepsy

“Ten minutes doesn’t sound like a lot, but when you’re about to have a seizure, 10 minutes is an eternity. So what can we do to shorten that time?”

There are a number of available abortive seizure treatments for patients with epilepsy, however, these nasal preparations are accompanied by a number of challenges—the time to effect being chief among them. When patients take an abortive medication in preparation for a seizure event, a window up to 10 minutes for the medication to take effect can present a serious issue.

To help address this, Jacqueline French, MD, and colleagues have been working with an inhaled delivery platform of alprazolam (Staccato Alprazolam, Engage Therapeutics) with the hope of bypassing the challenges of the mucus-membrane based pathway of the nasal delivery. This option offers a route through the lungs, which French told 

 offers “an enormous quantity of space for the drug to be absorbed” into the bloodstream. In just 2 minutes, serum concentrations of the drug in the blood and brain are much higher.

In conducting a phase 2b open-label feasibility study, the professor of neurology and director of translational research and epilepsy clinical trials, NYU Langone, and Chief Medical Innovation Officer, Epilepsy Foundation, and colleagues found that a 1-mg dose was both safe and efficacious in 8 patients with epilepsy and predictable seizure episodes. Overall, 5 patients were considered responders (62.5%), and preliminary safety analysis showed no serious or severe adverse events.

The next phase of the study will be a randomized, double-blind trial including 100 patients who will be assigned to 1 of 2 active treatment arms evaluating 1 mg or 2 mg of Staccato alprazolam compared with placebo. To find out more about the study, 

 spoke with French at the 2019 American Academy of Neurology Annual Meeting in Philadelphia, Pennsylvania.

French J, Liow K, Vazquez B, et al. A two-part, double-blind, placebo-controlled, inpatient, dose-ranging efficacy study of Staccato alprazolam (STAP-001) in patients with epilepsy with a predictable seizure pattern: results from the initial open-label feasibility part. Presented at: 2019 American Academy of Neurology Annual Meeting. May 4-10, 2019; Philadelphia, PA.

The professor of neurology and director of translational research and epilepsy clinical trials at NYU Langone spoke about the results of a phase 2b open-label feasibility study of this novel delivery method for abortive seizure treatment in patients with epilepsy.

Jacqueline French, MD

Articles

Jacqueline French, MD: Barriers to Identifying Nonmotor Seizures

Jacqueline French, MD: Identifying Focal Epilepsy Seizures

Jacqueline French, MD: Safety of Intranasal Diazepam As Rescue Medication

Jacqueline French, MD: Dangers of Delayed Diagnosis in Epilepsy

Jacqueline French, MD: Inhaled Alprazolam for Aborting Predictable Seizure Episodes in Epilepsy

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