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Seizures

Updated : May 15, 2024





Background

Seizures are electrical disruptions in the nervous system that cause altered mental phenomena, dislocation, motor action, and consciousness in some frightened patients. 

Abnormal and excessive electrical signals in brain neurons cause a short-term disorder in brain activity due to abnormal electrical signals. 

Partial seizures are common in adults which is characterized by initial activation in a specific area of the cortex. 

 They often present with symptoms like motor or sensory phenomena. 

 Generalized seizures occur from widespread cortical activation at onset of partial seizures. 

 This discourse discusses the assessment and treatment of seizures emphasizing the interprofessional team role in improving patient outcomes. 

 It also discusses the timing for differential diagnosis and evaluation methods. 

 

Epidemiology

Epilepsy incidence in North America ranges from 16 to 51 cases per 100,000 person-years with prevalence rate ranging from 2.2 to 41 cases per 1000.

Partial epilepsy accounts for up to two-thirds of new cases with higher incidence in socioeconomically disadvantaged populations. 

 25% to 30% of new-onset seizures are provoked and secondary to another cause. 

 Epilepsy incidence peaks in younger and older age brackets with cerebrovascular disease leading to cause among older individuals. 

Anatomy

Pathophysiology

Excitatory and inhibitory neurons in the brain control the generation of signals and suppression of activity otherwise. 

A balance between these two forces is present in a healthy brain, but it may be disturbed by depression of inhibitory system or exaggeration of excitation. 

The reduction of hyperexcitability may be associated with reduced GABA function or increased glutamate sensitivity of the receptors. 

However, when a group of neurons is in the hyperexcitable condition, they become persistently overexcited and, as a result, they spark multiple high-frequency action potentials. 

Those axons increase the likelihood of repetitive electrical discharges by the neurons, triggering a seizure in non-related areas of the brain. 

Etiology

Epilepsy is a neurological disorder, which leads to irregular electrical impulses in the brain. 

 

It can be triggered by different life events, such as head injury, stroke, brain tumors, heredity, metabolic syndrome, or drug withdrawal. 

The seizures result with the traumatic brain injuries, strokes, and brain tumors because of their irregular electrical activity. 

Since hypoglycemia, electrolyte imbalances, or kidney or liver failure, can be involved in the case then genetic factors are needed, as well. 

For instance, abrupt termination of certain subsidence substances and medications is among. 

Lastly, the withdrawal of medications or drugs, sudden discontinuation or change of medication or substance, can also cause seizures as well. 

Genetics

Prognostic Factors

The prognosis of persons with epilepsy is determined by several factors such as the type of epilepsy, its frequency, the age when seizures develop and the genetic factors. 

In children, the first onset is associated with a good prognosis, which means that their epilepsy may not be as severe as in adults. 

More frequent seizures make the patient’s prognosis grimmer. 

Epilepsy that begins in the early phase of life is generally considered to have a better prognosis than those which begin in adult life. 

These biological factors induced, such as in turn, may elevate this risk of drug-resistant epilepsies and other propositions should occur. 

Clinical History

Early childhood (0-5 years old): At this stage of developmeny from birth to 5 years, 30-40% of all seizures are febrile seizures, the episode of which is initiated when there is a rapid rise in temperature, at times accompanied by other alarming clinical signs. 

Older adults (above 60 years): The incidence of epilepsy in this category also trend upward, as notable cases such as the occurrence of a stroke, a primary brain tumor, or Alzheimer’s disease tend to happen more frequent. 

Physical Examination

A seizure refers to a sequence of tests to evaluate the neurological state of the person. 

These tests encompass the neurological assessment, which measures the consciousness of individuals, responsiveness, muscle tone, reflexes, coordination, and sensation. 

The examiner checks the head and neck for trauma; on the other hand, a cardiac exam specifically checks for abnormalities or arrhythmias. 

A respiratory assessment performed, for dealing with breathing patterns and lung sounds, is used to identify any compromised state during the seizure. 

Skin inspections are done to find out any skin injuries during a seizure. 

The person might stay for a while in a postictal stage characterized by confusion, drowsiness, weakness, or other neurological signs. 

Age group

Associated comorbidity

  1. Epilepsy 
  2. Neurodevelopmental disorders
  3. Brain injury
  4. Febrile seizures
  5. Hypogylcemia

Associated activity

Acuity of presentation

Seizures can have different kinds of beginning, i.e., sharp, slow, abrupt, and latent. 

Seizures that begin suddenly can make one lose consciousness or begin having convulsions with no warning. 

Gradual seizures usually start with mild feelings until it becomes obvious. 

Certain people can experience “aura” symptoms or “warning signs” such as sensory disturbances in the brain or mood changes before a seizure develops. 

The postictal period includes confusion and tiredness after a seizure, and some with gradual resolution and some with quicker recovery. 

Due to the urgency of seizure presentations, an immediate hyperbaric medical rescue is necessary to avoid complications and minimize the damage in the brain. 

Differential Diagnoses

Epilepsy 

Febrile seizures 

Syncope 

Metabolic disturbances 

Structural brain abnormalities 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Patients with reversible seizures may be discharged after appropriate interventions with adjustments to medication and follow-ups. 

Noncompliant patients may need restarting antiepileptic drug regimens. 

Alcohol withdrawal seizures patients can be discharged after appropriate treatment and observation with lorazepam administration reducing recurrence risk. 

Adults experiencing first unprovoked seizure and returning to normal neurological function may not require immediate medical treatment but caution should be exercised until follow-up, testing, and reassessment occur. 

Chronic seizure disorders can be treated with various medications including sodium channel blockers, GABA receptor agonists, GABA reuptake inhibitors, and glutamate antagonists. 

For generalized convulsive status epilepticus the immediate seizure treatment should begin alongside stabilization and diagnostic procedures. 

Benzodiazepines like diazepam are recommended as first-line medications but respiratory depression is a common side effect requiring careful monitoring for appropriate dosing. 

Consultation with a neurologist is essential for effective treatment. 

The Established Status Epilepticus Treatment Trial (ESETT) has concluded but the optimal second-line medication for benzodiazepine-refractory status epilepticus remains uncertain. 

Second-line medications include valproate, fosphenytoin, and levetiracetam. 

Advanced airway management and blood pressure support may be necessary in cases, where generalized convulsive status epilepticus persists. 

The optimal treatment for refractory status epilepticus remains unknown but propofol or continuous benzodiazepine infusion in combination with other anesthetic medications. 

ICU admission is typically necessary and accompanied by continuous EEG monitoring. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Lifestyle modifications in treating seizures

One of the most crucial triggering consequences of seizures is bright lights, tension, sleeplessness, and some drugs. 

Managing mealtimes, sleep patterns, and medication schedules is very important. 

Removing all potentially dangerous objects from the area and obstructions is essential. 

Ensure the possibility of developing a new approach to combine the aftereffects and stave off any pain that can result from injuries. 

Medical alert wristbands containing already-installed data and a GPS locator can also be installed for extra safety. 

An example of this would be if someone is timely crushed by the person delivering the seizure, especially if this is occurring in dangerous environments such as stairs or swimming pools. 

Role of benzodiazepines

Carbamazepine:It is used in the therapy of neuropathic pain, in addition to stabilizing the neuronal membranes,as a result of the inhibition of voltage-gated sodium channels. 

Oxcarbazepine: It works like carbamazepine in treating foval and generalized tonic-clonic seizures. 

Use of GABA inhibitor

Phenytoin: It works primarily by stabilizing the inactive state of voltage-gated sodium channels in the brain reducing the incidence of seizures. 

Use of barbiturates

Phenobarbital: It enhances the activity of gamma-aminobutyric acid, in the brain by binding to GABA-A receptors, which are ligand-gated chloride channels, thereby increasing the duration of chloride channel opening. 

Use of carboxylic acid

Valproate: Sodium valproate is an anticonvulsant medication used in the treatment of various types of seizures, both focal and generalized. 

It increases the concentration of GABA in the brain, by inhibiting degradation. 

Use of GABA derivative

Vigabatrin: For focal seizures, which originate in a specific area of the brain, vigabatrin can be effective either as monotherapy or as adjunctive therapy. 

 

Role of SV2A ligands in treating myoclonic seizures

Levetiracetam: This drug functions by modulating the release of neurotransmitters, specifically by attaching itself to the synaptic vesicle protein 2A (SV2A) in the brain. 

The dose to treat myoclonic seizures is 500 mg intravenously or orally two times a day and it may be enhanced every two weeks from 500 mg to 1500 mg two times a day. 

Use of dicarboximide in treating absence seizures

Ethosuximide: It is considered as a first-line treatment for for absence seizures which are also known as petit mal seizures. 

Use of phenyltriazines in treating absence seizures

lamotrigine: This can be used as an adjunctive therapy in treating absence seizures. 

Role of surgery in treating seizures

Resective surgery:This involves removing the specific area of the brain where seizures originate. 

This takes place by removing a portion of the temporal lobe, frontal lobe, or other areas depending on the location of the occurrence of seizure. 

Responsive neurostimulation:This considers implanting a device called a neurostimulator, which continuously monitors brain activity and delivers electrical stimulation to interrupt or prevent seizures. 

Corpus callosotomy:In some cases of severe epilepsy, that originates at same time directly from both hemispheres of the brain, the band of nerve fibres that connect the two hemispheres, the corpus callosum may be fragmented in surgical procedures to prevent seizure from spreading between the hemispheres. 

 

Use of phases of management in treating seizures

The stage of assessment and diagnosis is mainly concerned with reviewing medical records in detail, physical examination as well as other diagnostic procedures like electroencephalography, magnetic resonance imaging, or computed tomography to determine the nature and origin of seizure. 

Persons with epilepsy or even other types of chronic seizure disorders are commonly given these kinds of antiepileptic medications. 

More consistency within the lifestyle, for instance, good regular sleep, better control of the stressful environment, and the avoidance of triggering factors are good aids in reducing seizure frequency. 

Regular follow up and monitoring is necessary so that the treatment plan can be maintained on the correct track. 

Medication

 

clorazepate

7.5

mg

Tablet

Orally 

every 8 hrs

increase by <5mg/kg
Maximum 90 mg/kg



clonazepam 

1.5

mg

Tablet

Orally 

every 8 hrs

1

week



diazepam 

2 - 10

mg

Orally 

every 6 hrs



ezogabine 

100

mg

Orally 

every 8 hrs

a day 1 week; titrate and increase for 50 mg orally
Maintenance dose: 200 mg-400 mg orally 8 hours a day
Do not exceed 400 mg a day



ethotoin 

Indicated for Tonic Clonic & Complex Partial Seizures :

1

g/day

Orally 

in 4-6 divided doses; may be increased up to 2-3 g/day



brivaracetam 

50 mg orally/IV 2 times a day; dose can be adjusted b/w 25-100 mg orally/IV
When oral delivery is temporarily unfeasible, patients may use injections;
however, clinical study experience with injection is only available for 4 consecutive days of treatment
Note:
Used to treat partial-onset seizures



carbamazepine 

Maintenance dose: 800 to 1200mg /day
Maximum dose:1600mg/day

Immediate release:
Initial dose:
Tablets: 200mg orally twice a day
Oral suspension: 100mg orally every 6 hours
Increase every week by 200mg/dose divided every 6-8 hours
Maximum dose: 1600mg /day

Extended-release:
Initial dose: 200mg orally twice a day
Increase every week by 200mg/dose divided every 6-8 hours
Maximum dose: 1600mg /day



primidone 

Initially:

100 - 125

mg

Orally 

at bedtime

3

days


then 100-125 mg twice a day for 3 days
following 100-125 mg thrice a day for 3 days, then 250 mg thrice to four times a day; without exceeding 2 g/day



Dose Adjustments

Dosing considerations:
Should not exceed more than 2 g/day
Do not stop abruptly, due to the chances of risk to status epilepticus
Therapeutic efficacy may take several weeks to achieve

phenobarbital 

Initial dosages of 1-3 mg/kg/day either intravenously or orally in 1 to 2 divided doses; modify as necessary to achieve a therapeutic steady-state level of 20 mg/L



phenobarbital 

Indicated for Status Epilepticus:


Administer a loading dose of 15-20 mg/kg intravenous at a rate of 25-100 mg/min; if required, repeat in 10 minutes with an additional 5-10 mg/kg; provide respiratory support once the maximal dosage is given



valproate 

Indicated for Complex Partial Seizures

10-15 mg/kg IV divided 2 times a day infused over 1 hour
May be increased to 60 mg/kg daily
Maximum duration is 14 days (AS soon as possible switch to Oral)



valproic acid 

Complex partial seizures:

10-15 mg/kg orally daily; may increase to 5-10 mg/kg once in a week
Do not exceed 60 mg/kg a day

Conversion to Monotherapy:

Reduce the dosage of a concomitant medication by about 25% every 14 days; this dosage reduction may occur when valproate therapy is started or one to two weeks after the start of valproate therapy

simple and complex absence seizures:

Initial dose: 15 mg/kg orally divided 2-4 times a day; may increase to 5-10 mg/kg
Do not exceed 60 mg/kg a day



cannabidiol 


Indicated for Seizures
Lennox-Gastaut syndrome/Dravet syndrome:
Initial dose: 2.5 mg/kg orally two times a day
Maintenance dose: After one week, may enhance to 5 mg/kg two times a day
If a 5 mg/kg two times a day dose is tolerated, and then seizure diminishment is required. when the maintenance dose is enhanced to 10 mg/kg two times a day (20 mg/kg every day), the patient may benefit, and it may achieve by an enhanced weekly increment of 2.5 mg/kg two times a day as tolerated
If further quick titration from 10 mg/kg every day to 20 mg/kg every day is warranted, the dose might be enhanced no further frequently than the every other day
20 mg/kg every day dosage administration resulted in a somewhat substantial diminishment in rates of seizures than the 10 mg/kg every day maintenance dose, Yet with enhancement in adverse reactions
Tuberous sclerosis complex:
Initial dose: 2.5 mg/kg orally two times a day
Enhanced weekly increment of 2.5 mg/kg two times a day as tolerated to the maintenance dose of 12.5 mg/kg two times a day
If further quick titration is warranted, the dose might be enhanced no further frequently than the every other day
Dose <12.5 mg/kg two times a day, effectiveness is not studied in individuals with Tuberous sclerosis complex



stiripentol 


Indicated for Seizures
stiripentol is indicated for treating seizures related with Dravet syndrome in patients taking clobazam. However, there is no clinical data available to support the use of stiripentol as monotherapy in Dravet syndrome
The recommended dosage for stiripentol is 50 mg/kg daily, to be administered orally in two or three divided doses (16.67 mg/kg three times a day or 25 mg/kg two times a day). The maximum daily dosage should not exceed 3000 mg
If the require dosage is not feasible with the available strengths, it is permissible to the nearest possible dosage (within 50-150 mg of 50 mg/kg daily dosage). Additionally, a mixture of the two available strengths can be used to attain the prescribed dosage



midazolam intranasal 

Indicated to treat stereotypic episodes (intermittent) in patients with seizure activity, which are different from usual episodes of epilepsy
The recommended starting dosage is 5 mg, administered as a single spray into one nostril
Second dose (if necessary)
If the patient does not show any response to the initial dose, an extra 5 mg (1 spray) can be administered in the opposite nostril after a 10-minute interval
However, it is important to refrain from administering a second dose if the patient has trouble breathing or if excessive sedation is unusual throughout a seizure cluster episode
Maximum dose and frequency
don't use more than two doses in each single episode of seizure
dont treat more than an episode after every 3 days and not more than five episodes each month



levetiracetam 

ER: (Only for Partial-Onset Seizures)

1000 mg once daily orally
On the basis of effectiveness and tolerability, increase in 1000 mg increments every two weeks
1000–3000 mg taken orally once day as a maintenance dosage
3000 mg/day is the maximum dosage

IR:

500 mg IV/oral 2 times a day
Depending on effectiveness and tolerance, increase dosage twice daily in increments of 500 mg every two weeks
500 to 1500 mg intravenously or orally twice day for maintenance
3000 mg/day is the maximum dosage



trimethadione 

Initial dose-Administer 900 mg orally, three to four times a day, in divided doses.
This dose can be increased by 300 mg weekly until therapeutic effects are noticed or toxic symptoms occur.
Maintenance dose- Administer 900 to 2400mg orally, three to four times daily, in divided doses.



paraldehyde 

Indicated for Seizure associated with status epilepticus poisoning or tetanus
The suggested dose is 5 to 10 ml intramuscularly



pipenzolate methylbromide/phenobarbitone 

Put some drops in mouth daily as per physicians advised



diazepam buccal 

FDA Accepted diazepam buccal (Libervant) Film NDA for treatment of seizure clusters in patients between two and five years of age
Now waiting for approval of Prescription Drug User Fee Act (PDUFA)



thiopental 

Dose of 75 to 125 mg should be administered as soon as possible after the convulsion starts



lorazepam 

Status Epilepticus:

The usual dose is 4 mg per administration, delivered intravenously (IV) at a rate of 2 mg per minute, If the seizure persists for 5-10 minutes, an additional IV dose of 4 mg should be administered



 

clonazepam 

1.5

mg

Tablet

Orally 

every 8 hrs

1

week



ethotoin 

Indicated for Tonic Clonic & Complex Partial Seizures :

750

mg/day

Orally 

in 4-6 divided doses; increased up to 500 mg-1 g/day



brivaracetam 

Age: 1 month-16 years
Wt <11 kg: 0.75-1.5 mg/kg orally every 12 hours; may be increased to 0.75-3 mg/kg
Wt 11-<20 kg: 0.5-1.25 mg/kg orally every 12 hours; may be increased to 0.5 to 2.5 mg/kg
Wt 20-<50 kg: 0.5 to 1 mg/kg orally every 12 hours; may be increased to 0.5 to 2 mg/kg
Wt ≥50 kg: 25-50 mg orally every 12 hours; may be increased to 25 to 100 mg
Age: ≥16 years
50 mg orally every 12 hours; may be increased to 25 mg-100 mg
Note:
Used to treat partial-onset seizures



carbamazepine 

Indicated for epilepsy:

<6 years of age:
Initial dose(Oral suspension):10 to 20mg/kg/day orally every 6 hours
Initial dose(Tablet): 10 to 20mg/kg/day orally every 8-12 hours
Maintenance dose:400 to 800mg/day
Maximum dose: 1000mg/day

6-12 years:
Initial dose(Oral suspension):100mg orally every 6 hours
Initial dose(Tablet): 100mg orally every 12 hours
Maintenance dose:400 to 800mg/day
Maximum dose: 1000mg/day

Over 12 years of age:
Initial dose(Oral suspension):100mg orally every 6 hours
Initial dose(Tablet): 200mg orally every 12 hours
Maintenance dose:800 to 1200mg/day
Maximum dose: 1000mg/day



phenobarbital 

Neonates (<28 days): 3 to 5 mg/kg/day in 1 to 2 divided doses intravenous or orally
Infants: 5 to 6 mg/kg/day in 1 to 2 divided doses intravenous or orally
1-5 years: 6-8 mg/kg/day in 1 to 2 divided doses intravenous or orally
6-12 years: 4-6 mg/kg/day in 1 to 2 divided doses intravenous or orally
>12 years: 1-3 mg/kg/day in 1-2 divided doses intravenous or orally, OR 50-100 mg twice or thrice a day



phenobarbital 

Infants and young children: 15-20 mg/kg intravenous given at a maximum rate of 2 mg/kg/min; Do not exceed 1000 mg/dose
<60 kg: <30 mg/min intravenous rate
When required, repeat with a 5-10 mg/kg bolus dosage after 15-30 minutes; do not exceed a total dose of 40 mg/kg



valproate