Introduction

A common well-accepted clinical axiom in neurology is "seizures beget seizures." Therefore, seizure prevention, vigorous follow-up, and early therapy are key to success. More important, early treatment is not only more effective, but it also stops progression to status epilepticus. Every time seizures occur, it causes neurological dysfunction despite adequate oxygenation. Thus, it is vital to establish seizure precautions daily.[1][2][3][4]  

One factor when considering seizure precautions is knowledge of triggers and precipitating factors. Even though non-compliance with medications is one of the most common causes of breakthrough seizures, all caregivers and healthcare workers should examine these individuals for any underlying metabolic or infectious triggers.[5][6][7][8] In patients with therapeutic drug levels, one should consider fever or any abnormal laboratory parameter as a cause. Substance abuse screening is important in the youth. Imaging studies and electroencephalogram (EEG) are important to establish the risk of seizure recurrence.  In almost all cases, the prehospital care of seizure patients is supportive. Most seizures only last a few seconds or minutes, especially the simple febrile seizures in children.

Initial considerations for patients with an ongoing seizure:

• If the individual continues to have seizures in the emergency room, the one should follow the ABCs (airway, breathing, circulation)
• Administer oxygen if the individual is in status epilepticus, is cyanotic or is in respiratory distress. Some individuals may require rapid sequence intubation, but one should only use a short-acting neuromuscular blocker to avoid masking of the seizure activity
• Check finger stick blood glucose and replace if <50 mg/dl[8]
• Obtain a toxicology screen and anti-convulsant drug levels (if appropriate).
• If the patient is intubated and paralyzed, consider EEG monitoring to determine if there is still ongoing seizure activity
• All patients with an active seizure should have two large-bore intravenous lines. Administer intravenous glucose and thiamine promptly. If the patient has signs of an infection, get cultures and consider the use of antibiotics

The key aim of treatment is to control the seizure before any significant neuronal damage occurs, which usually occurs between 20 to 60 minutes. Anoxia and central nervous system (CNS) infections correlate with a high mortality rate in status epilepticus.

Function

Ensuring Safety Precautions

Both the caregiver and the healthcare provider have an important duty in ensuring the safety of the patient with seizures. It is important to understand that although lifestyle changes and safety precautions are needed, one should avoid becoming too controlling and rigid. People with epilepsy also need to live a good-quality life that offers independence.[9][10][11][12]

During the Seizure

1. First, ensure adequate ventilation and place patients on the floor on their left side 
2. Loosen clothing around the neck and ensure the airway is patent. If the patient is clenching the teeth, do not force the mouth open with any object as this can cause severe damage
3. Remove all items from the surrounding that can be hazardous. The patient may be oblivious to what's happening and may not even know what he or she is doing.
4. If the patient is confused and wandering, either gently guide him/her away and block access to outside areas
5. Reassure the individual and be comforting
6. Call 911. In most cases, the seizure ends before EMS arrives. However, there are cases when seizures may last over 3 to 5 minutes. Or the individual may have developed breathing difficulties or severe injuries. If a pregnant patient or a person with diabetes develops a seizure, it is prudent to call an ambulance.
7. Finally, if the patient does not regain full consciousness, then call EMS. Most patients will remain confused for about 45 to 90 minutes after a seizure, so you must use judgment in calling for help.
8. Avoid restraints but make sure the patient is in a bed with padded side rails
9. Place the individual in a lateral position with the neck slightly flexed; this will help the saliva drain from the mouth and prevent the tongue from falling backward
10. Remove all nearby furniture and other hazards from the area
11. Provide verbal assurance as the individual is regaining consciousness
12. Provide the patient with privacy if possible
13. Call for help and start treatment as ordered by the caregiver

When a seizure occurs, it is important to note:

1. Date, time, and duration of the seizures
2. Level of activity at the time of the seizure
3. Level of mental status (confused, excited, dazzled, unresponsive or conscious)
4. Presence of aura
5. What type of body movements, which part?
6. How did the seizure progress? Symmetrical, unilateral or bilateral?
7. What type of motor activity? Myoclonic, clonic, tonic, posturing, dystonic
8. Eye movements, deviation, open/closed, flickering of eyelids, nystagmus
9. Twitching
10. Head-turning
11. Respiratory, rate rhythm
12. Heart rate and rhythm
13. Skin temperature: cold, warm, cyanosis
14. Diaphoresis
15. Gastrointestinal (GI) vomiting, nausea, diarrhea
16. Eyes pupillary size, symmetry, reaction to light
17. Sensation, hallucinations
18. Any other unusual behavior

After the Seizure (Postictal Stage)

After a seizure, most patients experience confusion, fatigue, muscle pain and/or a headache. Thus, one should permit the individual to sleep. For the next few days, reassurance is essential. Being calm and helping reorient the person is also of importance.

Most seizures are painless and end spontaneously. Seizures are not harmful to others but can lead to complications such as stress on the lungs, brain and the heart. Individuals with prior lung problems may develop labored breathing and respiratory distress. Thus, one may need to administer oxygen.

Once the seizure has stopped, record the following:

• Vital signs
• Presence of gag reflex
• Presence of a headache, character, location duration and severity
• Bowel or bladder incontinence
• Any visible injury to the skin, joints or face
• Any residual neurological deficits
• Change in behavior
• Mental status, confused, anxious
• Disturbance in speech
• Coordination of movements
• Weakness
• Level of consciousness

Conduct a Postictal Exam

• Ask what the individual was doing before the seizure
• Was this the first seizure
• Ask for the presence of any other illness
• Determine any trigger factors
• Ask if the patient had an excess consumption of coffee, alcohol
• Excessive hydration
• Fever
• Any recent head trauma
• Concurrent infection
• Overexertion
• Sleep deprivation
• Mood alterations (anger, anxiety, depression, stress)

Check Blood Work for the Following Triggers

• Hypoglycemia
• Hyponatremia
• Hypocalcemia
• Hypomagnesemia
• Dehydration

Medication-Related Triggers

• A recent change in dose, the frequency of anti-seizure medication
• Alcohol or sedative withdrawal
• Use of CNS stimulants including caffeine 
• Use of antidopaminergic agents
• Use of atypical antipsychotics like clozapine
• Use of antidepressants like bupropion
• Use of cyclosporine
• Use of quinolone or imipenem/cilastatin
• Exposure to any toxins

Environmental and Hormonal Triggers

• Exposure to loud music
• Flashing lights
• Pregnancy (more likely to be protective)
• Menstruation
• Olfactory stimuli: Specific odors
• Ovulation

Changes in Activity, Lifestyle, and Restrictions

One of the major problems with recommending seizure precautions is the unpredictability of the seizure recurrence. The onus is on the healthcare provider to discuss the following seizure precautions in patients diagnosed with seizures:

• Working at heights
• Climbing tall structures
• Driving
• Cooking using the oven or a fire
• Using heavy machinery and other power tools
• Taking a bath unsupervised
• Swimming unattended

Providers must discuss and document these seizure precautions to prevent any issues including future litigation by the family members. The problem with seizure precautions is that not all seizure patients are alike. Some may only have nocturnal epilepsy, and thus one needs to use judgment in recommending safety maneuvers. For example, patients who practice certain sports like biking and skiing among others should wear a helmet to prevent head traumas.

Issues of Concern

Drug management of Patients with Active Seizures

The drugs of choice for patient management of active seizures are the benzodiazepines. One may administer intravenous lorazepam or diazepam. If the patient has no intravenous access, then intramuscular midazolam, buccal/nasal midazolam, or rectal diazepam are other options. Intravenous lorazepam is more effective than intravenous diazepam in inducing cessation of the seizure and preventing recurrent seizures.[13]

Doses of 0.1 to 0.2 mg/kg of lorazepam administered over several minutes usually work well, and sometimes higher doses are required to stop the seizure. If the seizure persists, there is no upper limit to the dose of the benzodiazepine (despite a decreased effectiveness over time), but, it is vital to monitor the patient for hypotension and/or respiratory depression.

The current American Epilepsy Society Guidelines published 2016 show three choices for second-line therapy including fosphenytoin, levetiracetam, and valproic acid. There is no evidence that one is superior to the others; however, valproic acid has the highest level of evidence (Level B).[8]

Phenytoin is one of the most widely used anti-seizure medications, classically used as the drug of second choice to end an active seizure. Its use is typically when high doses of benzodiazepines have failed to stop the seizure activity. The initial recommended dose is 20 mg/kg intravenously. However, great caution is required when administering intravenous phenytoin as it can cause arrhythmias, hypotension and even cardiac arrest if the dose is greater than 50 mg per minute. The patient must be monitored during the intravenous infusion. Purple glove syndrome is a rare side effect and can be avoided by limiting infusion rates to less than 25 mg per minute.[14]

Fosphenytoin is a precursor of phenytoin and is safer than phenytoin as it does not contain the diluent propylene glycol. However, fosphenytoin is more expensive than phenytoin. Additionally, fosphenytoin can be administered intramuscularly which is an advantage over phenytoin in patients without intravenous access.

Valproic acid is a weak acid with high serum protein binding. Caution is important with a patient with liver and pancreatic disease. Contraindications include pregnant women with known teratogenic risk of spina bifida, low intelligence quotient, and autism in neonates.[15]

Levetiracetam has the safest side effect profile and least number of drug-drug interactions compared to the three above. It is bioavailable equally in oral and parenteral formulations. It is excreted in urine mostly unchanged; thus, it requires dose adjustment in those with renal disease.

Management Following the End of the Seizures 

For those individuals who had a witnessed seizure and now are in the post-ictal phase, supportive care, and seizure precautions are necessary. If the individual had low therapeutic levels of the seizure medications, then it may be appropriate to administer a loading dose in the emergency room before discharge. Reliability of anticonvulsant drug levels varies.[16] The next step following seizure cessation is to look for seizure triggers including toxic/metabolic, stroke, brain mass, iatrogenic, or newly diagnosed epilepsy. Routine blood count, basic metabolic panel, urine drug screen, and urine pregnancy test (when indicated) are considerations for screening. Cranial imaging is indispensable in identifying focal brain abnormalities. Magnetic resonance imaging is superior to conventional computerized tomography scans.[17] Routine EEG has a high diagnostic value in the first 12 to 48 hours following seizure approaching 53.1% versus 23.9%.[18][19][20]. Sleep deprivation increases the yield of routine EEG by about 10%.[20] Lumbar puncture should be a diagnostic option in those with suspected meningoencephalitis.[21] However, discharge is only recommended if there are no other issues on clinical presentation.

Clinical Significance

Individuals who have had 2 or more unprovoked seizures over 24 hours apart can be diagnosed with epilepsy. However, the current standard of care for a single unprovoked seizure is avoiding the triggers. Anticonvulsants are usually not recommended unless the individual has risk factors to endure recurrent seizures.[22] Current evidence does not support starting anti-seizure medications following first-time seizure since it does not change the quality of life; although, it lowers risk for recurrence.[23] However, these patients should see a neurologist within 15 days. Following new onset seizure, patients are counseled about the following risk factors to facilitate the decision making about starting anticonvulsants[21]:

1. Differential diagnosis of new-onset, seizure-like event includes migraine, TIA, syncope, and psychogenic events.
2. Ancillary tests: Computed head topography study is less sensitive when compared to magnetic resonance brain imaging with sensitivity reaching 30%. Commonly missed abnormalities include low-grade gliomas and hippocampal sclerosis. About 29% of patients with new-onset epilepsy will have an abnormal electroencephalogram following their first routine (i.e., 20-minute study) study.
3. Discuss seizure triggers: Older data suggest that up to 30% of patients with suspected alcohol withdrawal seizures had a potentially epileptogenic structural abnormality related to a traumatic injury.
4. Prolactin level can conditionally differentiate a convulsive seizure from a nonepileptic event; this requires measuring prolactin level 10 to 20 minutes after a suspected event compared with a baseline prolactin level collected at least 6 hours before the suspected event. Prolactin test cannot distinguish epileptic seizure from syncope

Beside recurrent seizures, consider antiseizure therapy following a single seizure with either abnormal EEG with seizure tendency or abnormal MRI brain.[23] A close follow-up with the primary care provider or the neurologist should be a priority. Before discharge, all patients need to have the drug levels measured to ensure a therapeutic level and compliance. A seizure patient needs indefinite follow up with a primary caregiver or a neurologist.

Other Issues

Outpatient Care

The decision to discharge patients following a seizure requires good clinical judgment.

Prevention

To date, there are no data to suggest that any intervention other than prescribed anti-seizure medications can prevent status epilepticus or recurrent seizures. Thus, the most important thing to emphasize to patients is medication compliance. The anti-seizure medication prescribed depends on the patient's underlying diagnosis, severity, pre-existing medications, other comorbidity and potential for drug interactions. A consultation with a neurologist who will oversee and direct the medication prescribed is necessary. Anytime a medication dose or frequency changes, it should be done in consultation with the neurologist.

Discontinuing Anticonvulsant Agents

To discontinue the anticonvulsant agent, the patient has to be seizure free for about 2 to 5 years. Children usually outgrow their epileptic syndromes, and most do not require the use of antiseizure medications in adult life. The relapse rate in children is about 25%, whereas in adults it varies from 40% to 60%. This difference is most likely due to the different epileptic syndromes present in the two populations. Almost 75% of seizure relapses occur within the first 12 months after discontinuation of the medication. About 50% of patients have a seizure within the first 12 weeks. It is therefore critical to educate patients on seizure precautions during the first 3 months after discontinuation of medications; this means absolutely no driving and the Department of Motor Vehicles (DMV) might need to be informed. There are no formal guidelines for discontinuation of antiseizure drugs and roughly done over 8 to 24 weeks. A slower titration recommended for particular drugs such as carbamazepine, oxcarbazepine, phenobarbital, primidone, and benzodiazepines. Before discontinuing anti-seizure medications, it is important to know the risk factors for seizures. A normal EEG and a brain MRI are indicators of a low-risk of recurrence, but if the EEG shows focal abnormalities or MRI brain reveals focal limbic or cortical abnormalities, then the risk of recurrence is higher. Other factors also associated with a high risk of seizure recurrence after discontinuing medication include:

• Having a history of tonic-clonic or atonic seizures are associated with a much higher risk than absence seizures
• Higher and increased frequency of seizures
• A long duration of epilepsy before seizure control
• A short duration of freedom in between seizures

Enhancing Healthcare Team Outcomes

While most patients in the emergency room are manageable without a neurological consultation, consider neurology consult for the following:

• If the patient meets the definition of status epilepticus: Status epilepticus is defined as 2 or more subsequent seizures without regaining of consciousness or 30 minutes or more of continuous seizure activity.[24]

• Any patient with a known diagnosis of epilepsy who has a breakthrough seizure: Non-adherence with anticonvulsants is a leading cause of the emergence of breakthrough seizures.[25] These patients may need medication change to prevent future seizures.

• Prolonged postictal state: Patients are usually admitted to a telemetry floor with close monitoring and further workup.