A new collaboration between researchers at the Drexel University College of Medicine and Temple University, led by research coordinator Vernon Kalugdan and Dr. Ralph J. Riviello, will be focusing on a condition called status epilepticus — named for patients who remain in a prolonged, often life threatening, state of seizure. The prolonged state transforms into a condition called Established Status Epilepticus if symptoms are resistant to typical seizure medications. Status epilepticus is also unique in that only 7-10 percent of these patients suffer from epilepsy, but it has been known to affect both the very young and very old.
“The symptoms of [status epilepticus] are like those of a normal seizure: involuntary convulsions involving one or both sides of the body, incontinence of bowel and/or bladder, and so on. This is typically an unconscious state where the brain’s signals are firing off all at once with no direct purpose,” Riviello described in an email interview.
“A seizure itself is actually a symptom of many possible disorders [or] causes that can range from chemical imbalances, malignancy such as tumors or cancers, traumatic injuries to the brain, bleeding in the brain, etc. While the brain’s signals are being mixed up, the signals to control the breathing and protection of the airway are included. There is also a significant surge of electricity going through the brain during a seizure. These are among a number of issues that can lead to permanent disability or even death,” he continued.
Riviello acts as a professor of emergency medicine at DUCOM and also works in the emergency department of Hahnemann University Hospital. Practicing for 18 years, Riviello has also conducted investigative trials on other issues including strokes, congestive heart failure, musculoskeletal injuries, sexual assault and neurological emergencies. His current study, named the Established Status Epilepticus Treatment Trial is being conducted through the Neurological Emergencies Treatment Trials lead by Temple University.
There are several options for treatment of these conditions, but according to Riviello the research into which is most effective and for what reasons is not well established.
“The ESETT study is looking to answer what is the best and/or worst of 3 medicines for ESE. That is, when first line agents (like benzodiazepines) fail, what is the best second line agent in stopping the seizure activity,” Riviello said.
Because of the impaired state that comes with the onset of a seizure, consent to this study comes with some complications and employs FDA Guidelines 21 CFR 50.24.
“This guideline speaks specifically about Exception From Informed Consent, or EFIC. That is, if a research study holds the potential to save a life and a traditional consent cannot be otherwise obtained, it is possible to be done with a waiver of consent at that time. In the case of ESE, a true life-threatening emergency, the above FDA guideline applies,” he explained.
The study includes participants aged two and up and will involve the administration of one of three randomized FDA-approved antiepileptic drugs: valproic acid, levetiracetam or fosphenytoin. According to Riviello, there is no placebo.
“As the study moves along, if one drug is proven to be dangerous or beneficial, it will be given less frequently or more often respectively, again, through the randomization process,” Riviello said.
“It is believed that with 795 enrollments the answer to the question should be found. It is possible that the answer be found before 795 enrollments. If one drug is found to be so efficacious, the study will stop enrolling as it will then become unethical to keep testing when we have found the answer,” he continued.
According to Riviello, studies such as this have had success in the past. One study found that 10 mg of Midazolam administered through intramuscular injections was more effective than 2 mg of Lorazepam given intravenously. The results of this study, according to Riviello, “rewrote the books for the pre-hospital treatment of seizures in Pennsylvania.”
Although Riviello’s study is no longer looking for participants, the study is seeking preliminary opinions from the community before beginning. An online survey can be taken at www.pnett.org/seizure.html.