Authors :
Presenting Author: Jesus Pina-Garza, MD – TriStar Centennial Children’s Hospital
Tracy Glauser, MD – Comprehensive Epilepsy Center
Eric Segal, MD – Hackensack University Medical Center and Northeast Regional Epilepsy Group and Hackensack Meridian School of Medicine
James Wheless, BScPharm, MD, FAAP, FACP, FAAN, FAES, FCNS – University of Tennessee Health Science Center and Le Bonheur Children's Hospital
Randa Jarrar, MD – Phoenix Children’s Hospital
Jurriaan Peters, MD PhD – Boston Children's Hospital
Muhammad Zafar, MD – Duke University School of Medicine
Steven M Wolf, MD – Westchester Medical Center, Hawthorne, NY, United States
Genei Bougher, MSN, APRN – Northwest Florida Clinical Research Group
Charles Davis, PhD – CSD Biostatistics, Inc.
Leock Ngo, PhD – Neurelis, Inc.
Miguel Lopez-Toledano, PhD – Neurelis, Inc.
Adrian Rabinowicz, MD – Neurelis, Inc., Center for Molecular Biology and Biotechnology (CMBB) in the Charles E. Schmidt Collage of Science at Florida Atlantic University
Enrique Carrazana, MD – Neurelis, Inc., John A. Burns School of Medicine; University of Hawaii, Honolulu, HI
Rationale:
Seizure clusters (SCs), prolonged seizures, and status epilepticus (SE), although differentiated clinically, can be seen as overlapping concepts in a spectrum of seizure emergencies. Diazepam nasal spray, approved by the US Food and Drug Administration for treating SCs in patients with epilepsy aged ≥2 years, has been shown to lead to rapid termination of prolonged seizures within SCs that were treated 5-15 min after seizure start in pediatric and adult patients. This preliminary analysis assessed treatment of impending SE with diazepam nasal spray (recommended as first-line treatment of SE in the prehospital setting) in patients with focal or generalized epilepsy with motor seizures or seizures with alterations of awareness aged 2-17 and ≥18 years.Methods:
Data were collected and pooled from the patient diaries of 2 studies (total 199 patients; 4080 seizure episodes) evaluating diazepam nasal spray with dosing based on age and weight (pooled age range: 2-65 years). The International League Against Epilepsy defines tonic-clonic SE and focal SE with impaired consciousness using timepoints t1, when seizures are considered abnormally prolonged, and t2, when long-term consequences may occur. For this analysis, seizures were categorized as generalized, focal, or unclassified based on each patient’s epilepsy diagnosis and medical history. SE events were defined by t1 (treatment >5 min after onset for generalized and >10 min for focal and unclassified seizures); t2 was 30 min for generalized and 60 min for focal and unclassified seizures. Treated SE episodes were analyzed by seizure type, time from seizure onset to dose, time from dose to seizure termination, and total seizure duration, and responder and recurrence analyses were performed. Second-dose use was a proxy for effectiveness. Hospitalization data were summarized.Results:
Of 97 patients with ≥1 episode treated after t1, 53 were aged 2-17 years, and 44 were aged ≥18 years. Among pediatric patients, seizure type was generalized in 39 patients (253 episodes), focal in 11 (26 episodes), and unclassified in 6 (31 episodes); 2 patients had >1 category. Among adult patients, seizure type was generalized in 13 patients (63 episodes), focal in 20 (219 episodes), and unclassified in 11 (79 episodes). The median total seizure durations were ≤t2 for most pediatric and adult categories (Figure 1). High proportions of individual patients and events had SE termination by or before t2 (Figure 2), and low proportions (≤9%) of events had seizure recurrence (96.7% of these >t1) within 24 h of SE termination after treatment. For each seizure type, second-dose rates were < 20% for pediatric and < 8% for adults. There were a total of 7 hospitalizations for SE among 4 patients included in the current analysis; all were generalized in type in pediatric patients.
Conclusions:
This pooled cohort analysis demonstrates that treatment with diazepam nasal spray provides consistent and rapid control of impending SE episodes treated in the prehospital setting in patients with epilepsy aged 2-17 and ≥18 yearsFunding: Neurelis, Inc.