The Efficacy and Safety of Minocycline in the Treatment of Drug-resistant Epilepsy in NORSE Patients

New-onset refractory status epilepticus (NORSE) is a rare but special clinical manifestation with a high mortality rate. Most cases evolve into Super refractory status epilepticus (SRSE), with poor treatment efficacy, short-term mortality rate of 12-27%, and high long-term disability rate. Most survivors eventually develop into Drug resistant epilepsy (DRE) and experience cognitive impairment. Frequent seizures seriously affect patients' daily life and work, Controlling the frequency of seizures is particularly important. At present, the pathogenesis of this disease is still unclear, and the treatment plan is still controversial. In recent years, research has found that inflammatory and immune responses in the body may be involved in the pathogenic process. In response to the current research on the inflammatory immune mechanism and epilepsy, the use of anti-inflammatory drugs and immune modulators may be a new treatment direction. Minocycline is a semi synthetic tetracycline broad-spectrum antibiotic with good blood-brain barrier penetration. Since the end of the 19th century, the efficacy of minocycline has been reported in many models of nervous system disease, including hemorrhagic and ischemic stroke, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, etc. Because of its ability to cross the blood-brain barrier, its detoxification effect on activated microglia and its proven human safety record, it seems to be a promising candidate drug for epilepsy treatment. In summary, minocycline has good blood-brain barrier permeability, as well as anti-inflammatory, immunomodulatory, and potential anti epileptic effects, with good safety. Therefore, this study intends to carry out a randomized controlled, open label, evaluator blind proof of concept study to explore the efficacy and safety of minocycline in the treatment of drug-resistant epilepsy in patients with NORSE.