I. Definition The ILAE 2010 definition is commonly used: failure to achieve sustained seizure freedom despite the application of two correctly selected and tolerated antiepileptic drugs (alone or in combination). The diagnosis and differential diagnosis of drug-refractory epilepsy Drug-refractory epilepsy accounts for about 20%-40% of the epilepsy population. Patients with drug-refractory epilepsy who cannot effectively control their seizures have a significantly higher risk of accidental death than patients with other epilepsies, and this has a serious impact on the patient’s employment, psychology, life, and growth and development of children. Therefore, a timely and correct diagnosis of drug-refractory epilepsy is beneficial for physicians at different levels and epilepsy specialists to provide more effective treatment and services to patients. The diagnosis of drug-refractory epilepsy has not yet been fully unified, but the diagnosis first emphasizes the “regular” application of “two” drugs. If a patient discontinues a drug before it reaches an effective therapeutic concentration because of intolerable side effects, it cannot be considered a regular application. Secondly, any form of seizure (including aura) that occurs during the course of treatment, or that is triggered by sleep deprivation, menstruation, fever, etc., should be considered “not effectively controlled. There is controversy as to how long after treatment a seizure is considered to be completely controlled, but it is generally accepted that three times the length of the longest interictal period before treatment, or 12 months seizure-free (whichever is longer), is considered to be completely controlled after treatment. In addition, the diagnosis of drug-refractory epilepsy should take into account factors such as drug side effects, the impact of seizures on psychology, life and work, and child development. Before diagnosing drug-refractory epilepsy, a detailed history and medication history must be taken and the EEG must be reinterpreted to rule out pseudo-“refractory epilepsy”. Pseudo-intractable epilepsy may be caused by the following factors: 1. Incorrect diagnosis. 2. 2. Incorrect seizure typing. 3. Improper drug selection. 4. Inadequate medication or drug overdose. 5. Poor patient compliance, etc. Therefore, in patients with frequent clinical seizures and poor drug control, the following questions should be addressed in a stepwise manner: 1. whether the seizure is a seizure, a seizure combined with a pseudo-seizure or a non-seizure event only. Non-epileptic seizure events that may be misdiagnosed as refractory epilepsy include psychogenic seizures, sleep disorders, movement disorders, syncope, transient ischemic attacks, cardiac arrhythmias, and metabolic disturbances. 2. Whether a definite cause and precipitating factors can be found. 3.Redetermination of the type of seizure or epilepsy syndrome. 4. Systematic review of past treatment, including types of AEDs, doses, side effects, and blood levels, and whether inappropriate use of antiepileptic drugs has led to increased seizures, such as carbamazepine, which is ineffective for akathisia and myoclonic seizures, but also increases seizures. 5, to understand the patient’s compliance, whether there is untimely medication, alcohol abuse, staying up late, etc.. The patient’s intelligence, knowledge level and psychological status should be evaluated. Third, early identification of drug-refractory epilepsy After a patient is diagnosed with epilepsy, the time to be diagnosed with drug-refractory epilepsy varies according to different syndromes or causes of seizures: some patients can be diagnosed very early, and some need longer time to confirm complete remission of seizures due to few seizures, and have to be observed and followed for a long time to be diagnosed with drug-refractory epilepsy. Therefore, early identification of drug-refractory epilepsy is beneficial for early referral to a comprehensive epilepsy center for evaluation and selection of appropriate treatment, as well as for early education and preparation of patients and family members on related knowledge, such as possible patient stigma, depression, decreased academic performance, and sudden unexpected death. Improving the prognosis of the patient. Patients diagnosed with temporal lobe epilepsy (especially medial temporal lobe epilepsy with hippocampal sclerosis) have a significantly higher chance of achieving complete seizure remission with surgical treatment than patients on long-term medication, and are considered to have predictable drug-refractory epilepsy with good surgical outcomes, and should be treated surgically as early as possible. Early identification of drug-refractory epilepsy should be considered from two aspects: 1. Early identification of syndromes that are prone to develop into refractory epilepsy. Some patients with clinical epilepsy are likely to have refractory epilepsy from the very beginning of the diagnosis, rather than with the evolution of the condition. This refractory epilepsy mainly includes some specific types of epileptic syndromes: the common ones are Otahara syndrome (early-onset infantile epileptic encephalopathy), infantile spasms, Lennox-Gastaut syndrome, Rasmussen syndrome, medial temporal lobe epilepsy, and laughing seizures from hypothalamic malformations. 2. Early identification of risk factors that predispose to the development of drug-refractory epilepsy. Risk factors that predispose to refractory epilepsy include: (1) Poor initial antiepileptic drug therapy. (2) Age-dependent epileptic encephalopathy. (3) Presence of frequent seizures prior to epilepsy diagnosis and treatment. (4) History of persistent status epilepticus. (5) Prolonged active seizures. (6) Clear etiology such as hippocampal sclerosis, cortical developmental abnormalities, tumors, traumatic softening foci, and dual pathology.