Overview
Persistent status epilepticus is a condition in which epilepsy is characterized by persistent, frequent seizures that do not end spontaneously.
Common causes include inappropriate discontinuation of antiepileptic drugs, brain tumors, and strokes.
Seizures require emergency treatment and are mainly treated with medication.
High lethality and disability, but seizures can be effectively controlled with regular treatment.
What is status epilepticus?
Definition
Status epilepticus is a disease state characterized by persistent seizures.
Clinically, generalized tonic clonic seizures lasting more than 5 minutes, other types of seizures lasting more than 30 minutes or intermittent seizures, and interictal intervals in which the patient does not fully regain consciousness are all considered to be status epilepticus.
The most common type is generalized tonic clonic seizure duration, which is also the most harmful.
Typing
By duration and response to treatment
Early status epilepticus: seizures >5 minutes.
Definitive status epilepticus: seizures >30 minutes.
Refractory status epilepticus: seizures >60 minutes, not responding to conventional treatment, requiring general anesthesia.
Ultra-refractory status epilepticus: failure to terminate seizures after 24 hours of general anesthesia or recurrence during medication reduction or withdrawal.
Types of seizures
Generalized status epilepticus: abnormal brain discharges affect both hemispheres at the same time.
Partial status epilepticus: The onset of abnormal brain discharges is confined to a part of one hemisphere.
Morbidity
It can occur in people of all ages, but is more prevalent in children under 1 year of age and older people over 60 years of age.
Persistent status epilepticus occurs in 10 to 41 per 100,000 people each year, with an overall morbidity and mortality rate of about 20%.
Questions you may be concerned about
How long is a seizure considered a persistent status epilepticus?
The duration of persistent status epilepticus is defined in relation to the type of seizure.
Generalized tonic clonic seizures last greater than 5 minutes.
Other types of seizures last greater than 30 minutes, or are intermittent, but the patient fails to be fully awake between seizures.
Of these, generalized tonic clonic seizures are the most common. The patient manifests paroxysmal, recurrent generalized convulsions, which may be accompanied by loss of consciousness, dilated pupils, cyanosis of the face and lips, and foaming at the mouth.
How to give first aid at home in case of sustained seizure?
First aid for a sustained seizure is similar to that for a single seizure, but it is important to get the patient to a doctor for medical treatment as soon as possible.
First, immediately turn the patient’s head to the side, preferably lying on the patient’s side.
Uncollar the patient’s shirt, clear the patient’s mouth of foreign objects and keep the airway open.
Do not put anything into the patient’s mouth, including dental pads, and do not force-feed medication.
Do not forcefully wrench or press on a twitching limb to avoid fracture.
First aid also call 120 to get professional help as fast as possible.
How are sustained seizures treated?
Treatment for sustained seizures includes stabilizing vital signs, terminating the seizure in time, and dealing with seizure triggers and primary causes.
Stabilize vital signs by preventing hypoxia, dehydration, and electrolyte disorders through oxygen or mechanical ventilation and establishing intravenous access.
Use diazepam, midazolam, phenobarbital, phenytoin sodium and other drugs to terminate seizures.
Targeted treatment of triggers and primary illnesses, such as anti-infective treatment for those due to infection, and resumption of medication for those induced by drug withdrawal.
Causes
Causes
Persistent status epilepticus generally has a clear etiology, as follows.
Intracranial infection.
Cerebrovascular disease.
Cranial trauma.
Intracranial tumors.
Metabolic encephalopathy.
Drug poisoning.
Neurodegenerative diseases.
Predisposing factors
Unstandardized antiepileptic drug therapy: abrupt discontinuation, change of drugs and drug reduction or omission.
Discontinuation of other tranquilizers, administration of isoniazid, tricyclic or tetracyclic antidepressants, etc. can also be induced.
Infection.
Psychiatric factors.
Excessive fatigue.
Pregnancy, childbirth.
Alcohol consumption.
Pathogenesis
Seizures in status epilepticus require a group of neurons to initiate and sustain abnormal discharges, which may be the result of impaired or impaired endogenous inhibitory mechanisms or increased excitability of the neurons due to a variety of causes.
Symptoms
Any of the seizure types can produce a status epilepticus. Different types of persistent status epilepticus have different manifestations.
The main manifestations
Generalized status epilepticus
Generalized Tonic-Clonic Seizure Persistency
During a seizure, the patient may experience loss of consciousness, dilated pupils, apnea, cyanosis, foaming at the mouth, and bilateral tonic clonic seizures.
Afterwards, the patient may fall asleep and wake up with headache, generalized muscle pain, fatigue, and no memory of the seizure.
Continuous state of tonic seizure
Continuous contraction of bilateral limbs or whole body muscles, muscle rigidity, no clonus.
Accompanied by varying degrees of impaired consciousness.
Occasional tonic seizures or other types of seizures, such as myoclonus, atypical agnosia and atonic seizures.
Clonic seizure persistence
Rhythmic jerking of bilateral limbs.
Blurred consciousness or even coma may occur if it lasts for a long time.
Myoclonic seizure persistence
Sudden, transient, rapid, electric shock-like twitching of muscles, which may be limited to a single muscle or group of muscles in the face, trunk, limbs, or all over the body.
Less frequently, there is an impairment of consciousness.
Loss-of-consciousness seizure persistence
It is mainly characterized by a reduced level of consciousness, or even just a decrease in reactivity and academic performance.
Partial Seizure Duration
Simple Partial Seizure Syndrome
Characterized by recurrent localized sustained facial or somatic convulsions, or persistent somatic localized sensory abnormalities, with clear consciousness during the seizure.
Limbic lobe status epilepticus
Often manifested with impaired consciousness and psychiatric symptoms, also known as psychomotor status epilepticus, commonly seen in temporal lobe epilepsy.
Lateralized convulsive status with hemiplegia
Mostly occurs in young children, manifested by one-sided convulsions, accompanied by postictal transient or permanent paralysis of the same side of the limb.
Complications
Metabolic disorders: Acidosis may be characterized by weakness of the limbs and deep, long breaths. There is a significant decrease in blood pH.
Cerebral edema: manifested by headache, nausea, vomiting, impaired consciousness, etc. In severe cases, cerebral hernia may occur, even leading to death.
Pulmonary edema: manifested by cough, pink foamy sputum, dyspnea, and even sudden death.
Consultation
Department of Medicine
Emergency Department
In the following cases, it is recommended to go to the emergency department as soon as possible or call 120 emergency.
Symptoms such as limb twitching and involuntary movements are not relieved for more than 5 minutes.
The patient has apnea and loss of consciousness after the seizure stops.
Seizures in pregnant women.
Fever accompanied by convulsions.
Seizure stops and is followed by a second seizure.
Neurology
After stabilization by the Emergency Department, treatment and follow-up usually require a visit to the Department of Neurology.
Preparation
Preparing for your visit: registering, preparing your documents, and frequently asked questions.
Tips for medical treatment
The patient or his/her family members should try to record the symptoms, duration and frequency of seizures, etc., so as to provide more reference for the doctor.
If the patient is convulsing all over the body, remove dangerous objects from the surrounding area and do not forcefully pry open the mouth or stuff towels or chopsticks in the patient’s mouth.
Special Note: Family members are recommended to accompany the patient to the doctor in case the patient falls or has an accident.
Preparation Checklist
症状清单
What are the symptoms before, during and after the seizure?
Is this the first seizure?
How long does each seizure last?
Was there high fever during the seizure?
病史清单
Is there a family history of epilepsy?
Any previous encephalitis, meningitis, or trauma to the brain?
检查清单
Imaging tests: cranial CT, cranial MRI
Laboratory tests: blood test, urine test
Other tests: electroencephalography, electrocardiography, cerebrospinal fluid, genetic testing
用药清单
Midazolam, Diazepam, Phenytoin Sodium, Lorazepam, Phenobarbital, Propofol, Isobarbital
Diagnosis
Disease diagnosis
Medical History
A complete and thorough medical history will help the physician in making a diagnosis and differential diagnosis, and the family will need to provide the physician with the following information.
History of present illness
Information such as age of onset, detailed course of seizures, progression of the disease, seizure triggers, duration of seizures, frequency of seizures and treatment.
Past history
Any past illnesses related to seizures, such as craniocerebral trauma, encephalitis, meningitis.
Any other underlying medical conditions, such as heart disease or liver or kidney disease.
Any previous treatment and adherence to medication.
Family history
It is also important to inform the physician whether there are relatives at all levels of the patient’s life who have had seizures or disorders that may be associated with them (e.g., migraines).
Clinical manifestations
Symptoms
Uncontrollable jerking of the whole body or parts of the body, prolonged or recurrent seizures.
Physical signs
The doctor will focus on the patient’s state of consciousness, mental status, limb strength, various reflexes and pathological signs. The patient will also be observed for the shape and size of the head, external appearance, the presence of physical deformities, and to screen for certain neurocutaneous syndromes.
Patients may present with dysfunctions of the conscious, mental, motor, sensory or autonomic nerves, such as disorientation, disorders of consciousness, mental disorders, and so on.
Laboratory Tests
Blood tests
Including routine blood tests, blood glucose, electrolytes, liver and kidney function, blood gases, pyruvic acid, lactic acid, etc., can help to understand the patient’s state of health and help to identify with other causes of loss of consciousness.
Regular checkups of blood counts, liver and kidney function, and drug concentrations can also assist in monitoring adverse reactions to the use of epilepsy medications.
Those who are already taking antiepileptic drugs should be monitored for drug concentration.
Urine examination
Including urine routine and screening for inherited metabolic diseases, which can help to find the cause of the disease.
Cerebrospinal fluid examination
Mainly used to rule out intracranial infectious diseases and is also useful in the diagnosis of certain inherited metabolic diseases. It helps to diagnose the cause of the disease.
Imaging
Magnetic Resonance Imaging (MRI) is highly valuable in detecting structural abnormalities in the brain. Routine cranial MRI is recommended. It helps in etiologic diagnosis.
CT of the head has an advantage over MRI in showing calcific or hemorrhagic lesions.
Electroencephalography.
The most essential feature of epileptic seizure is the abnormal over-discharge of neurons in the brain, and EEG is the most intuitive and convenient examination that can reflect the electrical activity of the brain, and it is the most important auxiliary means of diagnosing epileptic seizure and determining the type of epileptic seizure, and it is a routine and necessary examination for epileptic patients.
Electrocardiogram
For patients with suspected or newly diagnosed epilepsy, electrocardiography (ECG) is routinely performed to help detect certain cardiac seizures (e.g. syncope due to arrhythmia) that are easily misdiagnosed as epileptic seizures, as well as early detection of certain cardiac arrhythmias (e.g. Long Q-T Syndrome, Brugada Syndrome, and conduction block, etc.), so that misdiagnosis can be avoided.
Genetic testing
It has become an important diagnostic aid.
It is not used as a routine etiologic screening tool and is usually performed when there is already a high clinical suspicion of a disease.
Differential Diagnosis
Syncope
Similarity: both have episodes of loss of consciousness.
Differences: There are more differences between the two, as follows.
Compared with status epilepticus, syncope has clear triggers, such as nervousness, emotional excitement, standing for a long time, coughing, laughing, urination, defecation and so on.
It can often be characterized by pallor, sweating, sometimes irregular pulse, occasionally accompanied by twitching and urinary incontinence.
Loss of consciousness caused by syncope rarely exceeds 15 seconds and is characterized by rapid return of consciousness and full wakefulness, without postictal confusion.
The interictal EEG is usually not abnormal.
Pseudoseizures
Similarity: both may have blurred consciousness and limb twitching.
Differences: There are more differences between the two, as follows.
Pseudoepileptic seizures often occur after mental stimulation or in the presence of other people.
Seizures are varied, the patient keeps shouting and jerking, there is strong self-expression, exaggerated movements, often with eyes closed tightly, pale/red face, no tongue bite and urinary incontinence, no fall.
Patients with pseudoseizures may respond to external stimuli.
Seizures can last for several hours and the patient needs to be relieved by reassurance or suggestion.
Tourette’s syndrome
Similarities: Tics, sudden, repetitive and stereotyped involuntary twitching of one or more groups of muscles.
Differences: Tourette’s syndrome occurs in children between the ages of 5 and 10. Attacks are characterized by clear consciousness. It is often accompanied by attention deficit, learning difficulties, obsessive-compulsive behavior or obscene language.
Hypoglycemia
Similarity: Tics or tetany of the limbs, accompanied by loss of consciousness.
Differences: Commonly seen in patients with pancreatic β-cell tumors or type 2 diabetes mellitus on long-term hypoglycemic medication. Ineffective on conventional antiepileptic drugs, blood glucose testing can clarify the diagnosis.
Treatment
Aims of treatment
Maintain stable vital signs and provide cardiopulmonary support.
Terminate seizures that are persistent and minimize damage to neurons in the brain.
To find and, if possible, eliminate the causes and triggers of the disease.
Treatment: mainly with medication.
First aid treatment for seizures
The patient’s head should be turned to the side immediately, and if possible, the patient should be kept in the side-lying position.
Uncollar the patient’s shirt to keep the airway open, and quickly clean up any foreign objects in the patient’s mouth to prevent choking or asphyxiation.
Do not put anything into the patient’s mouth and do not force-feed the medicine.
If the patient’s limbs are convulsing violently, do not forcefully pull or press the limbs, or it is likely to lead to fractures.
If the seizures are continuous or frequent, call 120 in time to get the fastest assistance from medical personnel.
General treatment
Keep the airway open, inhale oxygen, and do tracheal intubation or incision if necessary.
Carry out monitoring of cardiac, blood pressure, respiration and EEG, and carry out blood gas analysis and full blood biochemistry examination regularly.
Find out the cause of induced persistent status epilepticus and treat it.
Establish intravenous access.
Medication
Initial treatment is initiated when a generalized tonic clonic seizure lasts more than 5 minutes, and no later than 20 minutes after the seizure to assess whether there is a significant response to treatment.
Second-line therapy was initiated 20 to 40 minutes after the seizure.
Seizure duration greater than 40 minutes was defined as refractory status epilepticus with third-line treatment.
Initial and second-line treatment of status epilepticus
Initial treatment
Overall, initial treatment for status epilepticus includes intramuscular midazolam, intravenous benzodiazepines (with or without subsequent phenytoin sodium), and intravenous phenobarbital, all of which are effective in terminating seizures.
Midazolam.
It has anxiolytic, hypnotic, anticonvulsant, and muscle relaxant properties.
Adverse effects: decreased respiratory capacity and respiratory rate.
Contraindicated in pregnant women in the third trimester of pregnancy, in severe depressive states, severe cardiac, hepatic and pulmonary insufficiency, hypersensitivity to benzodiazepines, and in children.
Intramuscular midazolam is more effective than intravenous lorazepam in the absence of established intravenous access.
Diazepam
It is the most effective drug for the treatment of status epilepticus, with a rapid onset of action, but the short half-life of intravenous diazepam makes it prone to relapse after discontinuation.
Adverse effects: drowsiness, dizziness, fatigue, etc. are common, and ataxia and tremor can be seen in high doses.
Pregnant women, lactating women, neonates, patients with glaucoma, patients with myasthenia gravis are prohibited. Severe acute alcoholism, hypoproteinemia and other patients, as well as long-term bedridden patients should be used with caution.
Diazepam plus phenytoin sodium: slow down the rate of sedation or stop the drug if there is a decrease in blood pressure or cardiac arrhythmia during administration.
Lorazepam.
Its effect is similar to diazepam. It has central sedative, anticonvulsant and muscle relaxant effects.
Adverse effects: depression, dizziness, weakness, and unsteady gait; may cause malaise or hepatic or renal impairment.
Contraindicated in patients with acute narrow-angle glaucoma, pregnant women, and patients <18 years of age. This product should not be used by lactating women. Use with caution in the elderly and patients with pulmonary insufficiency.
Intravenous lorazepam is more effective than intravenous phenytoin sodium when the duration of the attack is greater than 10 minutes.
Phenobarbital.
Slow-acting, mainly used as a long-acting antiepileptic after diazepam controls seizures.
Adverse effects: can suppress respiration at too high a dose and may have effects on liver and kidney function.
Second-line therapy
When the above medications fail, second-line treatment is an option: combination therapy with additional antiepileptic drugs.
Treatment of refractory status epilepticus
In about one-third of patients who are not controlled with the above treatments, a third-line treatment regimen is used. This stage requires treatment under intensive care, and some patients even need to go to the ICU. The main treatments in this stage are intravenous midazolam, propofol, and isobarbital.
Midazolam
Fast onset of action, easy to use, less inhibitory effect on blood pressure and respiration than traditional drugs.
In recent years, it has widely replaced isobarbital, and has a tendency to become the standard treatment for refractory status epilepticus.
Propofol
is a non-barbiturate, short-acting anesthetic for intravenous use that terminates seizures and epileptiform discharges on the EEG within seconds.
Adverse effects include central nervous system excitatory symptoms such as myotonia, corns, and choreoathetosis. Adverse reactions such as rhabdomyolysis, refractory hypoxemia, acidosis, and cardiac failure may occur in children when the recommended intravenous dose is administered over 24 hours.
Isoamylbarbitone
is the standard therapy for refractory status epilepticus persistence and is almost always effective.
Common adverse effects include hypotension, respiratory depression, and delayed resuscitation.
Treatment of Super-Refractory Persistent Status Epilepticus
Super-refractory status epilepticus is defined as persistent status epilepticus when clinical seizures or EEG epileptiform discharges fail to terminate or recur after more than 24 hours of anesthetic medication.
Treatment for this stage is still in the clinical research phase. Treatment with ketamine anesthesia and inhalational anesthetics may be effective.
Prevention and treatment of complications
Cerebral edema occurs and can be treated with a rapid IV drip of 20% mannitol 125-250 mL.
Prophylactic application of antibiotics can control the infection.
When high fever occurs, physical hypothermia can be performed.
Correct metabolic disorders in time, such as hypoglycemia, hyponatremia, hypocalcemia, hyperosmolar state. Correct acidosis.
Other treatments
For super-refractory persistent status epilepticus, electroconvulsive shock, immunomodulation, hypothermia, surgery, transcranial magnetic stimulation, and the ketogenic diet may also be effective.
The details of the ketogenic diet are described below.
The ketogenic diet is a high-fat, moderate-protein, low-carbohydrate dietary regimen used primarily to treat refractory epilepsy. It needs to be used under the supervision of a dietitian.
Food ratios
The weight ratio of fat to protein + carbohydrate combination in ketogenic diet is 4:1.
The diet needs to avoid high carbohydrate foods such as starchy fruits and vegetables, bread, pasta, cereals, sugar, and beer.
Increase the intake of high-fat foods such as meats (salmon, lamb, beef, chicken thighs, etc.), nuts (walnuts, almonds, pine nuts, etc.), avocado, butter and cooking oils (olive oil, coconut oil).
Choose vegetables that are low in sugar, such as squash, winter squash, zucchini, bitter melon, tomatoes, onions and celery.
Prognosis
Cure
With the increased awareness of persistent status epilepticus and advances in its treatment in recent years, its morbidity and mortality have declined significantly.
Hazards
Status epilepticus can be life-threatening, with some studies suggesting that the case fatality rate is as high as 13% to 20%.
Frequent seizures of status epilepticus can cause cognitive impairment, which is manifested as memory impairment, intellectual decline, personality change, etc., and gradual loss of learning ability, working ability and even living ability.
Seizures are prone to falls, burns, drowning, traffic accidents, etc., increasing the risk of accidental injury.
Daily life
Daily life
Adjust dietary structure
Daily diet should be light, avoid overfilling and overstuffing, overcooling and overheating, smoking and alcohol, as well as spicy and stimulating food.
Increase the daily intake of vegetables and fruits, ensure the supply of dietary fiber, minerals (especially calcium, iron, etc.) and vitamins, and ensure smooth bowel movement.
Long-term use of antiepileptic drugs may affect the metabolism and absorption of folic acid, which can seriously lead to megaloblastic anemia. In addition to vegetables and fruits, it is necessary to supplement animal offal, eggs, beans, yeast and nuts.
Drinking alcohol, cola, strong tea and coffee is prohibited.
Rest and keep warm
Life should be regular, avoiding overstress, labor, staying up late, etc.
Winter is the season of high incidence of epilepsy, and cold air stimulation is easy to induce epilepsy, so epileptic patients should pay attention to keep warm.
Daily activities
Maintain adequate sleep.
Epileptic patients should not do dangerous sports, such as swimming, mountaineering, parachuting, skiing, diving and so on.
Try to avoid occupations such as working at heights and driving.
In order to avoid patients from developing bad emotions such as self-isolation, anxiety and depression, they can do appropriate activities such as bowling, ping-pong, jogging, walking, yoga, etc. with someone accompanying them.
Listening to music, playing the piano, painting, calligraphy, doing handicrafts, meditating, conducting psychological counseling, and attending parties can also stabilize the patient’s mood and cultivate his or her emotions to a certain extent.
Adherence to medication
Take medication on time, according to the amount and regularity, avoid missing doses, and do not stop, reduce or change medication without authorization.
If patients have poor adherence to medication, it is mostly because they are afraid of adverse drug reactions, forget to take the medication, or think that they can stop taking the medication if they do not have seizures for a period of time.
The following methods can help improve patients’ medication adherence: strengthening the monitoring of side effects, keeping a medication record, using dated pill boxes, and using reminder notes and alarm clocks.
Keep a record of your condition and review your medication regularly
Patients or their family members can keep accurate records of the form, frequency and duration of seizures by means of taking videos with cell phones and video recording devices, keeping diaries or journals, etc. This will help doctors understand the condition of the patient and the effectiveness of treatment, and can better assist them in formulating and adjusting treatment plans.
Generally, for the first 3 months after taking the medication, the examination is repeated every month; after taking the medication for 3 months, the examination is repeated at regular intervals of 3 to 6 months. If the seizures are well controlled, the EEG is usually rechecked once a year.
Prevention
Regular use of medication
Take antiepileptic drugs strictly according to the doctor’s prescription, and do not change the dosage or medication at will.
Protect yourself and actively treat the primary disease
Actively treat diseases that may cause seizures.
Avoid head trauma.
Avoid stimuli to minimize seizures
Patients who experience seizures in response to specific stimuli should avoid stimulus triggers to help prevent seizures from recurring. For example, avoid eating irritating foods, avoid consuming alcoholic beverages, caffeine, nicotine, etc.; avoid too strenuous exercise, and should try to avoid emotional tension and excessive stress.