University of Lynchburg DMSc Doctoral Project Assignment Repository

University of Lynchburg DMSc Doctoral Project Assignment Repository


Oncology or Neurology


Dr. Thomas Colletti


Approximately 40% of newly diagnosed epilepsy patients will continue to experience resistant breakthrough seizures despite stable antiepileptic drug regimens. Rescue treatments have demonstrated efficacy and safety for select seizure emergencies. There are three regulatory approved and commercially available outpatient, nasally inhaled or rectally administered medications for acute repetitive seizures (ARS), and two injectable benzodiazepine formulations are indicated for parenteral treatment of established status epilepticus. Despite these advances in acute seizure control, no studies have been shown to abort an ongoing seizure following home administration of rescue therapy by the patient or a caregiver at the first clinical sign of seizure onset. Such treatment would require rapid systemic absorption without intravenous access, and clinical trial evidence of seizure cessation within minutes of administration that is superior to placebo (eg, seizure self-regulation). Rapid epileptic seizure termination (REST) therapy may be applicable to multiple types of seizure emergencies beyond ARS. Focal or generalized seizures preceded by an aura, flurries of absence of myoclonic seizures, or prolonged focal and generalized seizures present an increased risk for morbidity and/or progression to status epilepticus and may be responsive to REST therapy. Novel investigational drug-device combination therapies have demonstrated feasibility of intraictal delivery and cessation of epileptiform activity within two minutes. Randomized, placebo-controlled trials of REST treatment for diverse seizure emergencies are ongoing, and if positive, hold the potential to decrease bouts of mental and physical incapacitation in patients with refractory epilepsy.


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