Exploring the efficacy and safety of oral minocycline combined with antiepileptic drugs in the treatment of drug-resistant epilepsy in NORSE patients, obtaining preliminary research data, and providing evidence and data support for the next large-scale randomized controlled clinical study.

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.

Inclusion Criteria:

1. Age ≥ 8 years old;
2. It meets the NORSE diagnostic criteria: (1) newly emerging intractable status epilepticus, (2) no previous epilepsy or other related nervous system disease, (3) no clear acute structural, toxic and metabolic factors leading to intractable status epilepticus;
3. NORSE medical history ≥ 6 months, with a frequency of ≥ 4 episodes per month;
4. Take two or more antiepileptic drugs;
5. The patient and their family members are aware of this study and sign an informed consent form.

Exclusion Criteria:

1. Patients who are allergic to any component of tetracycline or product formulation;
2. Persistent state of epilepsy;
3. Adjustment of antiepileptic drugs during the trial period;
4. Immunotherapy, ketogenic diet and other added treatments were not stable or other treatments were started during the trial;
5. Epilepsy surgery;
6. In the treatment of vagus nerve stimulation and transcranial magnetic stimulation;
7. Patients with severe infection, cerebrovascular disease, malignant tumor and other nervous system disease, and patients with severe dysfunction of heart, liver, kidney and other organs;
8. Non epileptic seizures such as syncope and hysteria;
9. Participating in clinical trials of other drugs;
10. Women during lactation or pregnancy;
11. Incomplete clinical data;
12. The patient or family member withdraws the informed consent form.