What Is the Treatment for Refractory Epilepsy?

Epilepsy is a group of neurons in the brain that are highly synchronized due to different causes and often caused by self-limiting abnormal discharges. The epileptic, transient, repetitive and usually stereotypical central nervous system dysfunction Is characterized by a syndrome. Although the seizures of most patients with epilepsy can be controlled by drug treatment at present, some patients have poor response to antiepileptic drugs and the seizures are difficult to control. They are called intractable epilepsy and also called refractory epilepsy. Intractable epilepsy has not reached a consensus because scholars of various countries have not reached consensus on the type of antiepileptic drugs, treatment time, efficacy judgment, single or combined drugs, and there are obvious defects. Junl Jensen has identified refractory epilepsy in the literature as those who have received appropriate antiepileptic medication for years without delay. Ohtsuda et al. Considered it to be an ineffective case of all antiepileptic drugs. Chinese scholar Wu Xun and others define refractory epilepsy as frequent seizures, at least 4 times a month, and apply appropriate first-line antiepileptic drugs for regular treatment and the blood concentration of the drug is within the effective range. Still unable to control the onset and affect daily life; no progressive central nervous system disease or occupying lesions. At present, most of the domestic diagnosis of refractory epilepsy is based on this standard. Refractory epilepsy accounts for about 20% to 30% of patients with epilepsy.

Basic Information

Visiting department

Neurology

Common locations

Brain

Common symptoms

Disturbance of consciousness, muscle twitching

Causes of refractory epilepsy

There are reasons for refractory epilepsy. Some scholars in China have proposed risk factors for refractory epilepsy: complex partial epilepsy; there are multiple types of epilepsy at the same time; the status of epilepsy persists; there are falls Authors; cluster seizures; seizures that often cause trauma; mental retardation; abnormal EEG background; family history; certain types of epilepsy in infancy. Japanese scholars have explored its clinical reasons and believe that there are the following points: repeated refractory episodes of anti-treatment; cerebral organic damage; combined with psychiatric problems, intolerance of antiepileptic drugs, social environment, and self-induced When there are other problems, epilepsy treatment is difficult; Inaccurate diagnosis and treatment. In clinical work, structural damage can also be found in the brain of patients with epilepsy, such as nodular sclerosis, perforation of the brain, traumatic brain injury or history of birth trauma, or diffuse slow waves in EEG, non-specific abnormal waves Such changes and those with mental retardation have significantly worse efficacy than those without epilepsy. Foreign studies have shown that organic lesions often exist in the brain tissue of patients with refractory epilepsy.

Intractable epilepsy

Intractable epilepsy can be summarized into three parts: special types of epilepsy syndrome; symptomatic epilepsy caused by special causes; idiopathic or cryptogenic epilepsy.

1. Special type of epilepsy syndrome

Epilepsy syndrome usually has its own special etiology, pathogenesis, clinical manifestations, and disease evolution rules. Our clinically common intractable epilepsy syndromes are Otahara syndrome (early infantile epilepsy encephalopathy), infantile spasms, Lennox-Gastaut syndrome, Rasmussen Syndrome, Sturge-Weber syndrome , Persistent partial epilepsy, severe myoclonic epilepsy in children, refractory myoclonic absence, epilepsy on the inner side of the lobe, etc.

2. Symptomatic epilepsy caused by a specific cause

The proportion of symptomatic epilepsy in refractory epilepsy is significantly higher than that of ordinary epilepsy. Symptomatic epilepsy is an important part of refractory epilepsy. Tumors, trauma, vascular malformations, cerebrovascular diseases, various metabolic diseases, hypoxia, developmental abnormalities, intracranial infections, parasites, nutritional disorders, endocrine disorders and certain drugs can cause seizures and become the cause of epilepsy . Many of these symptomatic epilepsy with a clear cause can develop into refractory epilepsy.

3. Idiopathic or cryptogenic epilepsy

Idiopathic or cryptogenic epilepsy is part of refractory epilepsy. In the diagnosis and treatment of some idiopathic or cryptogenic epilepsy, it is difficult to develop effective seizures for a long time due to misdiagnosis, improper selection of drugs, side effects of drugs, patients' failure to comply with medical orders, economic problems, and social factors. Treatment of epilepsy. Therefore, we must pay attention to the initial diagnosis and treatment of epilepsy.

Intractable epilepsy

1. Routine and special inspections

Routine examination of blood, urine, stool and determination of blood glucose, electrolytes (calcium, phosphorus).

2. Cerebrospinal fluid examination

Central nervous system infections, such as viral encephalitis, increase stress, increase white blood cell counts, increase protein, and reduce sugars and chlorides during bacterial infections. Cerebral parasites can have eosinophilia. In the case of central nervous system syphilis, Treponema pallidum antibody test was positive. Intracranial tumors can have increased intracranial pressure and increased protein.

3. Serum or cerebrospinal fluid amino acid analysis

Possible abnormalities in amino acid metabolism can be found.

4. Neurophysiological examination

(1) Traditional EEG recording, including scalp electrodes and special electrodes, such as sphenoid electrodes, nasopharyngeal electrodes, oval hole electrodes, and intracranial electrodes.

(2) Event-related evoked potentials.

5. Neuroimaging

CT and MRI have greatly improved the diagnosis of epilepsy focal structure abnormalities. Most symptomatic epilepsy can see pathological changes on CT or MRI.

6. Neurochemical examination

Ion-specific electrodes and microdialysis probes that have been applied can be placed in the epilepsy area of the brain to measure certain biochemical changes between, during and after seizures.

7. Neuropathological examination

It is a pathological examination of surgical removal of epilepsy lesions. It can be determined that the cause of epilepsy is caused by brain tumors, scars, vascular malformations, sclerosis, inflammation, abnormal development or other abnormalities.

8. Cognitive and emotional function tests

(1) Scale test: divided into children and adults. Children's examinations mainly include: assessment of children's learning, life, and emotions through semi-quantitative assessment methods. The main tools are the Children's Sleep Disorders Scale, the Children's Social Function Evaluation Scale, the Cornell Children's Behavior Questionnaire, the Children's Adapted Behavior Assessment, Emotional assessment. Examinations for adults: Cornell Health Index, Pittsburgh Sleep Index, Self-Rating Anxiety Scale and Self-Rating Depression Scale.

(2) Cognitive function check: The main tools are Das-Naglieri cognitive assessment system, Webster intelligence scale, continuous processing test.

Diagnosis of refractory epilepsy

At present, there is no unified diagnostic standard for refractory epilepsy. Schmidt proposed the score for children with refractory epilepsy:

(1) Grade 0 uses a non-first-line antiepileptic drug (AEDs), regardless of dose.

(2) Grade I use first-line AEDs below the recommended dose.

(3) Grade II first - line AEDs are in the recommended dose range.

(4) Grade III first - line AEDs with plasma concentrations in the therapeutic range.

(5) Grade IV first - line AEDs, maximum tolerated dose.

(6) Level V more than one first-line AEDs, the maximum tolerated dose.

(7) Level VI more than one first-line AEDs, maximum tolerated dose and several second-line AEDs.

Grades 0 to are iatrogenic refractory epilepsy, and grades to are truly refractory epilepsy. Domestic Huang Yuangui and others believe that the necessary conditions for the diagnosis of refractory epilepsy are: the diagnosis of epilepsy is correct and the typing is correct; the first-line AEDs are used as single or multiple drugs in combination with regular treatment; the dose reaches the maximum tolerated dose, and the blood concentration is within the therapeutic range; Seizures cannot be controlled after the above treatment for more than 2 years; those who affect daily life are affected.

There is a lack of standards to determine the frequency of attacks after refractory epilepsy. Systemic tonic-clonic seizures are more than 4 times a month. It is usually more complex, partial seizures, absence seizures, and myoclonic seizures. Seizures affect daily life as a standard.

Differential diagnosis of refractory epilepsy

Incorrect diagnosis, improper drug selection, insufficient dosage, and poor patient compliance can lead to iatrogenic refractory epilepsy. For children with benign partial epilepsy, valproic acid should be preferred. If AEDs are used to reduce the child's wakefulness, Phenobarbital can increase seizures, carbamazepine is ineffective or increase seizures in myoclonic epilepsy, and myoclonic epilepsy is preferred for diazepam, nitrazepam, and clonazepam. Reduced drugs are prone to relapse, and the side effects of lowering the level of wakefulness are large, which is not suitable for children. Failure to take medication on time, alcoholism, lack of sleep, and excessive fatigue can make clinical episodes last forever, and those with poor clinical efficacy should not be classified as refractory. Pseudoseizures must be ruled out, which can coexist with epilepsy. At this time, more attention must be paid to identification. Video EEG is important for identification. Prolactin levels rise after seizures, and there is no change in pseudoepileptic seizures.

Refractory epilepsy complications

At present, epilepsy is considered to be a pathological state caused by a single specific cause, not just the type of seizures. Epileptic encephalopathy is a progressive brain dysfunction caused by epilepsy-like discharges themselves. The brain dysfunction caused by different etiology and after the attack is different, and the clinical complications are different, but the common point is that it may cause accidents such as trauma or asphyxia due to the attack.

Refractory epilepsy treatment

At present, the main treatment methods for intractable epilepsy are multiple antiepileptic drugs combined with physical therapy and surgical treatment.

Antiepileptic drug treatment

Although there are many treatments for epilepsy, antiepileptic drugs are still the most important method for treating epilepsy, and it is no exception for refractory epilepsy. With the continuous advent of new AEDS in recent years, it has provided more options for the treatment of refractory epilepsy. The application of drugs must consider the choice of drugs. For the selection of antiepileptic drugs, the factors to be considered in clinical application are: the type of seizures and epilepsy syndrome; the possibility of exacerbation or induction of new types of seizures; gender; age; comorbidities and concomitant medication Titration rate; Adverse reactions; Drug interactions; Whether the composition and dosage scale of the medication are convenient to apply; Cost. Of course, the first issue to consider is the type of seizures and epilepsy syndrome.

2. Physical therapy

With the deepening of the research on refractory epilepsy, some new treatment methods have been gradually discovered. In recent years, the electrical stimulation of epilepsy has become a research hotspot. Epilepsy electrical stimulation treatment can be divided into peripheral nerve electrical stimulation and brain electrical stimulation. Peripheral nerve electrical stimulation mainly refers to vagus nerve stimulation; brain electrical stimulation includes cerebellar electrical stimulation, deep nucleus electrical stimulation of the brain, and stimulation of epileptic foci. The most remarkable is the transcranial magnetic stimulation treatment, which was born at the end of the last century. This technology may become one of the non-invasive epilepsy treatment technologies.

3. Surgical treatment

At present, surgery has become an important treatment method for refractory epilepsy. However, not all patients with refractory epilepsy are suitable for surgery, and surgery has its strict indications and contraindications. The indications are: Frequent epilepsy affects patients' normal life and work, and those who are ineffective or unable to tolerate drug side effects after regular and adequate drug treatment. Regular and adequate medication refers to monitoring the blood concentration of the drug, medication and observation after 2 to 3 years (traumatic epilepsy continued for 5 years) under the guidance of a doctor. Focal epilepsy is confirmed by auxiliary examination to have localized epileptic focus in the brain, which is constant and can be operated on. The lesions of secondary epilepsy can be removed by surgery. Intractable epilepsy without constant epileptic focus, damage to the epilepsy can reduce and reduce seizures. The contraindications are: primary epilepsy does not seriously affect work, study, and life; have serious medical or neurological diseases, and have serious behavioral disorders, such as severe diabetes, heart and kidney disease, brain atrophy, etc. People with severe mental illness or mental retardation with IQ below 70; Memory dysfunction of the cerebral hemisphere on the opposite side of the lesion.

Refractory epilepsy prevention

The prevention of epilepsy is very important. The prevention of epilepsy involves not only the medical field, but also the whole society. The prevention of epilepsy should focus on three levels: one is to focus on the cause and prevent the occurrence of epilepsy; the second is to control the seizures; the third is to reduce the epilepsy to patients Physical, psychological and social adverse effects.

The prevention and early diagnosis of early onset of symptomatic epilepsy syndrome and early treatment are also very important. The importance of genetic counseling should be particularly emphasized for those with genetic factors. A family survey should be conducted in detail to understand the patient's parents, siblings and close relatives. Whether there are epileptic seizures and their seizure characteristics, for some serious genetic diseases that can cause mental retardation and epilepsy, prenatal diagnosis or neonatal screening tests should be performed to decide whether to terminate pregnancy or treat early.