Author(s): Rani Haley Gardner, MD, Sarah Hunton, MD, Lindsay Mohney, DO, Josh Estes, MD, Neil Simmons, MD
Originally published: August 7, 2012 Last updated: June 19, 2024
Jump to:

Disease/Disorder

A seizure is the transient onset of paroxysmal events due to abnormal electrical activity within the brain as a result of excessive or synchronous neuronal activity.1,2

Seizures-and-Epilepsy-Table-1
Seizures-and-Epilepsy-Table-2

Epilepsy is a brain disorder in which there is a chronic underlying CNS disorder resulting in unprovoked, recurring seizures. The International League Against Epilepsy further defines epilepsy as a disease of the brain defined by any of the following: at least two unprovoked seizures greater than 24 hours apart, one unprovoked seizure and a high probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures occurring over the next 10 years, and/or diagnosis of an epilepsy syndrome.1,3

As we are unable to cover the expansive breadth of information related to seizures and epilepsy, this text will focus on general recommendations for evaluation and treatment with a focus on provoked seizures due to acquired brain injury.

Etiology

Seizure precipitants include but are not limited to the following:

Seizures-and-Epilepsy-Table-3

In the case of unprovoked and provoked seizures, events may be triggered by factors such as fatigue, sleep deprivation, or flickering lights.1

Epidemiology including risk factors and primary prevention

Epilepsy

According to the first global report on epilepsy produced in 2019 by the World Health Organization and partners, there are approximately 50 million people worldwide living with epilepsy: a prevalence of 4 to10 per 1000 people.3 Globally, an estimated 5 million people will be diagnosed with epilepsy each year. Close to 80% of people with epilepsy live in low- and middle-income countries. This discrepancy is thought to be secondary to the increased risk of endemic conditions (i.e., malaria, neurocysticercosis), higher incidence of traffic related injuries, birth-related injuries, differences in medical infrastructure, and access to medical care in general.

Up to 10% of the population will have at least 1 seizure within their lifetime. The highest incidence of epilepsy occurs at the extremes of life. The incidence of neonatal seizures is about 1 to 5.5 per 1000 term live births, with estimates for preterm or low birth weight infants having an order of 10 times more common than term infants.4 The occurrence of epilepsy is significantly higher in the elderly population (age 65 or higher) than in any other age cohort, with an estimated prevalence of 1.5%.5

Younger children are at a higher risk if they have congenital, genetic, or developmental conditions; in adults, neoplastic, vascular, and degenerative etiologies are more common. Men are at higher risk than women for epilepsy. Focal seizures are the most common seizure type, yet generalized seizures are more common in children. In critically ill patients with TBI, up to half of reported seizures are subclinical.6,7

Brain tumor related seizures

Seizures are a common occurrence in brain tumor patients. Brain tumor related epilepsy (BTRE) presents in over 80% of cases with patients with diffuse low–grade gliomas, 62-68% of patients with glioblastomas, and 40-47% of patients with meningiomas.8 The frequency of BTRE in patients with brain metastases is 10-15%. Higher risk of seizure potential occurs with tumors that are located in the frontal, parietal, and temporal areas of the brain compared to occipital localization.

Post-stroke seizures

Seizures following a stroke are more likely to occur during the first 24 hours after stroke onset and are more common with hemorrhagic than ischemic etiology. Incidence of early seizure following stroke varies in literature but is estimated to occur in less than 10% of patients with ischemic stroke and approximately 15% of patients with hemorrhagic stroke. Incidence in the literature for late seizures varies significantly, with some studies reporting seizures in up to 2/3 of patients.6,9

Post Traumatic Seizure (PTS) and Post Traumatic Epilepsy (PTE)

Seizures can occur at any time following traumatic brain injury and are categorized based on time frame:

Seizures-and-Epilepsy-Table-4

Cumulative incidence varies widely; over 50% of TBI survivors may report seizure at some point following injury. Incidence varies by severity and intracranial pathology with the highest noted in penetrating injuries. Need for neurosurgical procedures also increases the risk of subsequent seizure.10

Post traumatic epilepsy (PTE) accounts for 5% of all epilepsy cases and accounts for 20% of all symptomatic epilepsy.11 Incidence of new onset seizure is highest in the first year after injury. 82% of individuals who develop late posttraumatic seizures do so within the first 2-years post-injury with an incidence of 8% in patients with mild TBI (GCS 13-15) and 16.8% in patients with severe TBI (GCS 3-8).10 Furthermore, PTE has been shown to develop in 10-20% of all severe TBI patients.11

Patho-anatomy/physiology

An impairment of the biochemical processes at the neurotransmitter and ion channel level causes hyperexcitability and neuronal hypersynchrony. Seizures are a result of this abnormal and excessive neuronal activity because of an imbalance between excitatory and inhibitory forces within the brain.

The primary excitatory neurotransmitter in the brain is glutamate, and the primary inhibitory neurotransmitter is gamma-aminobutyric acid (GABA). Antiepileptic drugs (AEDs) facilitate neuronal inhibition and/or reduce excitation.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Individuals in whom the sole cause of a seizure is a correctable condition, for example a metabolic disturbance without an underlying structural lesion, are rarely at risk for future epilepsy or recurrent seizures in the absence of recurrence of the condition.

The risk of seizure recurrence after a first unprovoked seizure has been estimated to be 40-50% within the first two years.12 Treatment may reduce this risk by as much as 50%. Abnormal neurologic exam, postictal paralysis, abnormal electroencephalogram (EEG), and strong family history of seizures increase the risk of seizure recurrence.

Approximately 60-70% of individuals whose seizures are completely controlled can eventually discontinue antiepileptic therapy.13

Specific secondary or associated conditions and complications

Increasing evidence shows a link between epilepsy and psychiatric conditions, especially depression and anxiety.3

Consequences and complications associated with seizures and epilepsy include but are not limited to:

  • Impairment of consciousness
  • Physical injuries during the event
  • Anoxic injury to the brain
  • Learning disabilities
  • Memory loss
  • Language deficits
  • Impaired self-esteem
  • Fatigue
  • Mood disorders (e.g., anxiety, depression, adjustment disorders)
  • Loss of independence and limitations in participation, including specific work activities and driving.
  • Sudden unexpected death in epilepsy (SUDEP)

Side effects of AEDs are common and include blood dyscrasias, osteoporosis, weight gain, negative cognitive impairments, nausea, sedation, and/or ataxia.

Essentials of Assessment

History

A comprehensive history is necessary to confirm seizure activity, characterize the seizure, and identify risk factors for seizure. An accurate description of surrounding events, including witness interview, helps identify sources that elicit seizures, the presence of any aura, and ictal/postictal behaviors.2

  • Aura may include abnormal smell or taste, déjà vu feeling, or an intense feeling that a seizure is imminent.
  • Patients or witnesses may report generalized convulsions, repetitive movements, staring spells, visual or auditory disturbances, or dysesthesias
  • To better categorize seizure, information should be gathered on focal versus generalized onset; awareness versus unawareness during episode; motor versus nonmotor manifestations

History should also include a comprehensive review of medications, alcohol or drug use/abuse, family history, and thorough medical history, including history of head trauma, stroke, neurodegenerative diseases, and intracranial infections. In patients with confirmed epilepsy, history should assess seizure control and the functional/social impact of seizures.

Differential diagnosis includes but is not limited to transient ischemic attacks, vaso-vagal/syncopal episodes, delirium, migraine headaches, movement disorders, and psychological factors.

Physical examination

A careful neurologic examination in the interictal period, including assessment of cortical function and mental status, is essential. The presence of TBI or other premorbid neurological disorder can mask signs and symptoms of seizure.  Thus, observation for subtle clues and symptoms is essential to seizure diagnosis.

The physical manifestation of a seizure is dependent on its classification2,3

  • Generalized tonic-clonic seizures: Abrupt onset with loss of consciousness; generalized muscle rigidity, followed by jerking/twitching movements. Often followed by a postictal phase characterized by deep sleep with deep respirations and gradual awakening accompanied by a headache.
  • Focal seizures with dyscognitive features (complex partial seizures): altered consciousness without loss of consciousness often associated with repetitive behaviors or automatisms (lip smacking, snapping fingers, facial grimacing). The postictal phase includes confusion, somnolence, and headaches.
  • Focal seizures without dyscognitive features (simple partial seizures): person is aware of self and environment during the seizure, even if immobile
  • Absence seizures (typically occurs during childhood):  staring spell with impaired consciousness; duration is typically 5-10 seconds.
  • Subclinical seizures: abnormal electroencephalographic activity without physical symptoms or signs.
  • Physical exam findings of seizure associated trauma or pathology: evidence of head trauma/healed trauma, tongue/mouth lacerations or bite injuries, meningeal signs, papilledema, etc.

The physical exam should be comprehensive to assist in searching for an underlying cause of seizure, such as infection or a systemic disorder.

Functional assessment

Depending on the cause and duration of the seizure, there can be subsequent impairments in mobility, self-care, behavior, cognition, mood, self-esteem, learning abilities, and speech/language. In mesial temporal sclerosis (also commonly referred to as hippocampal sclerosis), the most commonly diagnosed focal structural abnormality in patients with epilepsy, associated neuropsychiatric impairments may include decreased memory, cognition, depression, anxiety, and psychiatric comorbidities.14

Laboratory studies

Laboratory tests include

  • Comprehensive metabolic panel including sodium, glucose, calcium, magnesium, renal and liver function levels
  • Hematology studies
  • Toxicology screens
  • Serum prolactin level (elevated post seizure, must be drawn within 1 hour of the event)
  • Lumbar puncture is indicated if there is suspicion of a central neurologic infectious process

Imaging

Non contrast head CT in emergent setting is   recommended for patients presenting with their first seizure and/or those with risk factors such as fever, trauma, malignancy, focal seizure, or immunosuppression. Head CT may not be warranted in already established seizure patients.15

While CT Head imaging is most sensitive for hemorrhage, Magnetic resonance imaging (MRI) facilitates better identification of structural causes of epilepsy, such as mesial temporal sclerosis, cortical dysplasia, brain tumors, vascular malformations, TBI, cerebral infarction and infectious processes.

An epilepsy protocol for the MRI should be performed; specific sequences can be institute dependent but should include the following16-18

  • Standard T1-weighted sagittal/Coronal images.
  • T2-weighted axial/Coronal fast spin-echo sequences.
  • Gradient echo (T2) sequences.
  • Fluid-attenuated inversion recovery (FLAIR) sequences.
  • Three-dimensional (3D) volume acquisition sequences with high definition of the gray-white junction; 3D fast spoiled gradient recalled echo acquisition at the steady state.

Functional imaging techniques such as Double inversion recovery (DIR), fluid and white matter suppression (FLAWS), edge-enhancing gradient echo (EDGE), positron emission tomography (PET), single-photon emission computerized tomography (SPECT), functional magnetic resonance imaging (fMRI), and magnetic resonance spectroscopy (MRS) are helpful in localizing/mapping epileptic foci and can aide in surgical management of epilepsy.18-20

Supplemental assessment tools

The primary use of EEG is to support clinical suspicion for diagnosis and classification of suspected epilepsy. EEG can help classify seizure type and choice of anti-seizure medication if epileptiform discharges are captured during monitoring. Patients with EEG abnormalities after first seizure have 21-45% increased risk for recurrent seizure.21 EEG has low sensitivity for seizures; thus, a normal EEG does not rule out epilepsy. Sensitivity is improved with long-term video EEGs which may be helpful in recording multiple seizures.  Epileptiform discharges are associated with epilepsy, while non epileptiform abnormalities are nonspecific EEG abnormalities that do not support the diagnosis of epilepsy.

Neuropsychological testing can be used in nonoperative or postoperative epilepsy patients to assess level of cognitive functioning. Results can assist with recommendations for vocational and cognitive rehabilitation.

Early predictions of outcomes

Epilepsy usually requires lifelong treatment. One third of patients with epilepsy continue to have seizures despite anti-seizure medication. This has stayed true despite advancements in antiepileptic medications.Refractory epilepsy requiring multiple medications is more likely in those with seizures due to underlying structural abnormalities, multiple seizure types, or comorbid developmental delays.21

Regarding post-traumatic seizures, immediate (within 24 hours post-injury) seizures are considered transient and do not contribute to risk of post-traumatic epilepsy. A seizure occurring after the 24-hour mark following injury increases risk of developing late post-traumatic seizures.5,8,22 Prophylactic treatment of seizures may reduce the incidence of early post-traumatic seizures (occurring 24 hours to 7 days post-injury) but has no impact on late seizures (occurring > 1 week following injury) or on mortality following traumatic brain injury.

Environmental

While uncommon (4-7% of all epilepsy diagnoses), seizures can be reflexive and triggered by environmental factors such as loud noises and flashing lights More commonly, environmental stress, sleep deprivation, alcohol, or hormonal fluctuations associated with menstrual cycles can also trigger a seizure.17Environmental safety considerations include avoiding heights/climbing activities, scuba diving, and swimming alone.

Social role and social support system

Seizures and epilepsy can significantly impact functional independence, learning abilities, employability, insurability/financial resources, self-esteem, mood, ability to drive or operate heavy equipment, and vocational skills.

Support systems should provide resources within the home and the community to provide these patients, families, and support network with education, and counseling about seizure triggers, physical and psychosocial consequences of seizures, and coping with seizure/epilepsy diagnosis.

Professional issues

States differ in their requirements for reporting seizure/epilepsy diagnoses to the Office of Driver Services. Physicians should be knowledgeable of their local state law and regulations regarding drivers with an active history of epilepsy.24

Rehabilitation Management and Treatments

Available or current treatment guidelines

Choice of AED should take into consideration drug effectiveness for the seizure type, potential adverse effects including neurological/cognitive impairments, medication interactions, comorbid medical conditions, age and sex (pregnancy risk), lifestyle, cost, and patient preferences. 5

Monotherapy is preferred. 10-15% of people need two AEDs to control seizure activity.

First-line antiepileptic drugs include25-29

  • Generalized tonic-clonic seizures: Levetiracetam, Valproate, Lamotrigine
  • Focal seizures: Carbamazepine, Oxcarbazepine, Lamotrigine, Lacosamide
  • Absence seizures: Ethosuximide, Valproate

Status epilepticus: Benzodiazepines such as buccal midazolam, rectal diazepam, or IV lorazepam are the first line of treatment followed by phenytoin, valproate, or levetiracetam. If second line does not work then consider barbiturates or anesthesia medications such as propofol.25-29

Routine follow up of patients on AEDs should include AED serum level, blood counts, albumin level (for phenytoin), and hepatic and renal function monitoring.

Treatment for seizures resistant to AEDs include Responsive neurostimulation, deep brain stimulation, vagal nerve stimulation or surgical procedure31 such as laser ablation, anteromedial temporal resection, corpus callosotomy, functional hemispherectomy (hemispherotomy), and multiple subpial transection.

The following are recommendations for prophylaxis/treatment of seizures in commonly encountered diagnoses in the rehabilitation setting:

  • TBI:5,32
    • Patients with severe injury should be placed on seizure prophylaxis for 7 days following injury.
    • Medications options for prophylaxis include Levetiracetam, Phenytoin, and Valproate. Phenytoin has been shown helpful in reducing early seizures but no evidence to support protective effect for late post traumatic seizures. Levetiracetam is increasingly being used for seizure prophylaxis post trauma due to its favorable side effect profile. 33
    • Immediate seizures (within first 24 hours) post-TBI do not require any additional prophylaxis after 7 days. 34
    • Early seizures (between days 1 and 7) post-TBI should be treated for at least 24 months with AEDs, unless there was a casual time-limited intracranial abnormality. 34 (hydrocephalus, active hemorrhage, or infectious process). Early seizures are associated with a higher incidence of intracranial bleeding. Incidence of early seizures post-TBI decreases significantly with seizure prophylaxis the first 7 days post-TBI.
    • Late seizures (after 7 days) post TBI should be treated for at least 24 months.35
    • Any seizure post-TBI that is considered status epilepticus, requires treatment with AEDs for at least 12-24 months.6
    • Individuals with frequent seizures during the first year post-trauma are less likely to have seizure remission.23
  • Brain tumors6,36
    • Anticonvulsant medications are not proven effective in preventing initial seizures, thus prophylactic use should not be routinely used in patients with newly diagnosed brain tumors. If an AED has been started, taper and discontinue anticonvulsants after the first postoperative week, particularly in those patients who are medically stable and who are experiencing anticonvulsant-related side effects.
    • Anticonvulsant medications are indicated for brain tumor patients who have had at least one seizure. There is no current consensus on length of treatment, though AEDs can be considered for taper once seizure-free for 12-24 months and/or following tumor removal.
  • Stroke4,7,37
    • Current guidelines from the American heart association, recommend against the use of prophylactic antiseizure medication in both ischemic and hemorrhagic stroke. Despite this, AED use has increased during the acute hospital course likely due to limited large scale randomized controlled trials and concern for increased seizure risk among specific subgroups of hemorrhagic stroke patients, such as those with subarachnoid hemorrhage.

At different disease stages

New onset/acute

  • Initial seizure: Treat acute underlying cause (metabolic derangements, alcohol and drug withdrawal, intracranial hemorrhages, infectious process, hypoxic events, drug toxicity). If there is strong evidence of an epileptogenic focus, AED treatment should be initiated.
  • Initiate an AED after 2 or more unprovoked seizures.

Chronic/following prolonged treatment

  • After a seizure-free period of 2-4 years, it is reasonable to consider discontinuation of AEDs. Tapering should be performed slowly; there is no well-defined accepted tapering schedule. It should be done over a 2-3 month period at minimum.35

Coordination of care

Support patients to participate more actively in managing their care. Medical care should be coordinated with measures to address psychosocial consequences. Treatment team should include primary care physician, neurologist, physiatrist, neurosurgeon, psychiatry/psychology, physical therapy, occupation therapy, speech therapy, and vocational therapist.

Emerging/unique interventions

Deep brain stimulation (DBS) is useful in treating pharmacologically refractory epilepsy. Stimulation of the anterior nuclei of the thalamus (ANT) has been shown to be useful in adjunctive treatment of refractory epilepsy; the FDA approved DBS in the ANT as treatment for severe and refractory partial-onset seizures.38-40 Other deep brain areas, such as the hippocampus, subthalamic nucleus, caudate nucleus, and cerebellum, are being studied as potential DBS targets.38Transcranial magnetic stimulation (TMS) is another option for treatment in refractory cases of epilepsy. Low-frequency high intensity repetitive TMS has a significant antiepileptic effect when delivered to epileptogenic areas of the brain and can also reduce interictal epileptic discharges thus improving psychological conditions in patients. Further studies are needed to develop a standard protocol including frequency of dosing.41

Cutting Edge/Emerging and Unique Concepts and Practice

Trend toward alternative and complimentary medicine including medical marijuana, essential oils, and cannabidiol. Limited literature has suggested benefits especially in refractory seizures or for patients in which titration of AEDs is limited due to adverse effects. However, there is currently a paucity of randomized control trials and limited federal regulation. Some compounds have the potential to lower seizure threshold and potentiate seizure, thus routine use for seizure treatment cannot be recommended at this time.3,42,43

Clobazam is a benzodiazepine which is used for treatment of various types of epilepsy, though only approved for Lennox-Gastuat syndrome in the United States. It has less sedating effects that other benzodiazepines and has high safety profile and efficacy in refractory epilepsy.44

Responsive neurostimulator (RNS) is a device that when implanted in the cortical or subcortical epileptogenic areas of the brain detects abnormal activity and delivers electrical stimulation to inhibit seizures prior to the onset of symptoms. Clinical trials are ongoing currently, but data supports the RNS device as a therapy option for refractory partial seizures.45-47

Other treatment options that are being explored include Synchrotron radiation and lactate dehydrogenase inhibition.30,45

With recent popularity of artificial intelligence (AI), there are emerging studies investigating incorporation of AI and machine learning (ML) into clinical practice to assist with detecting and monitoring seizures, differentiating epilepsy from mimics, to improve neuroanatomic localization and lateralization, and predicting response to treatments. This application is still in its infancy with limited randomized control trials and uncertain medicolegal ramifications of ML/AI.48,49

Gaps in the Evidence-Based Knowledge

Although there are multiple resources providing recommendations regarding prophylaxis for seizures/epilepsy in high risk populations such as patients with CNS pathology, there are limited references providing a consensus to develop evidence-based guidelines for prevention and treatment. Global initiatives aim to provide more information about prevention as well as novel targets for treatment of epilepsy.

References

  1. Fisher RS, Acevedo C, Arzimanoglou A, et al. ILAE Official Report: A practical clinical definition of epilepsy. Epilepsia. 2014;55(4):475-482. doi:10.1111/epi.12550
  2. Fisher RS, Cross JH, French JA, et al. Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58(4):522-530. doi:10.1111/epi.13670
  3. Epilepsy: A Public Health Imperative.; 2019. Accessed March 24th, 2024.. https://www.who.int/mental_health/neurology/epilepsy/report_2019/en/
  4.  Krawiec, Conrad, and Maria Rosaria Muzio. “Neonatal Seizure.” StatPearls [Internet]., U.S. National Library of Medicine, 2 Jan. 2023, www.ncbi.nlm.nih.gov/books/NBK554535/.
  5.  Acharya, Jayant N, and Vinita J Acharya. “Epilepsy in the Elderly: Special Considerations and Challenges.” Annals of Indian Academy of Neurology, U.S. National Library of Medicine, Mar. 2014, www.ncbi.nlm.nih.gov/pmc/articles/PMC4001216/.
  6. Winstein CJ, Stein J, Arena R, et al. Guidelines for Adult Stroke Rehabilitation and Recovery: A Guideline for Healthcare Professionals from the American Heart Association/American Stroke Association. Stroke. 2016;47(6). doi:10.1161/STR.0000000000000098
  7. Fordington S, Manford M. A review of seizures and epilepsy following traumatic brain injury. J Neurol. 2020;267(10):3105-3111. doi:10.1007/s00415-020-09926-w
  8. Seidel, Sabine, et al. “Brain Tumor Related Epilepsy: Pathophysiological Approaches and Rational Management of Antiseizure Medication.” Neurological Research and Practice, 4 Sept. 2022, www.ncbi.nlm.nih.gov/pmc/articles/PMC9442934/.
  9. Zelano J, Holtkamp M, Agarwal N, Lattanzi S, Trinka E, Brigo F. How to diagnose and treat post-stroke seizures and epilepsy. Epileptic Disord. 2020;22(3):252-263. doi:10.1684/epd.2020.1159
  10. Ritter AC, Wagner AK, Fabio A, et al. Incidence and risk factors of posttraumatic seizures following traumatic brain injury: A Traumatic Brain Injury Model Systems Study. Epilepsia. 2016;57(12):1968-1977. doi:10.1111/epi.13582
  11. Pease, Matthew, et al. “Risk Factors and Incidence of Epilepsy after Severe Traumatic Brain Injury.” Annals of Neurology, U.S. National Library of Medicine, Oct. 2022, www.ncbi.nlm.nih.gov/pmc/articles/PMC9489614/.
  12. Berg, Anne. “Risk of Recurrence after a First Unprovoked Seizure – Berg – 2008 …” Epilepsia, Wiley Online Library, Jan. 2008, onlinelibrary.wiley.com/doi/full/10.1111/j.1528-1167.2008.01444.x.
  13. Kilinc, S., and C. Campbell. “The Experience of Discontinuing Antiepileptic Drug Treatment: An Exploratory Investigation.” Science Direct, W.B. Saunders, 10 Mar. 2008, www.sciencedirect.com/science/article/pii/S1059131108000344.
  14. Adamcyzk, Bozena, et al. “The Most Common Lesions Detected by Neuroimaging as Causes of Epilepsy.” Medicina (Kaunas, Lithuania), 22 Mar. 2021, www.ncbi.nlm.nih.gov/pmc/articles/PMC8004256/.
  15. Mitchell JW, Kallis C, Dixon PA, Grainger R, Marson AG. Computed tomography in patients with epileptic seizures admitted acutely to hospital: A population level analysis of routinely collected healthcare data. Clin Med (Lond). 2020 Mar;20(2):178-182. doi: 10.7861/clinmed.2019-0303. PMID: 32188655; PMCID: PMC7081820.
  16. Bernasconi A, Cendes F, Theodore WH, et al. Recommendations for the use of structural magnetic resonance imaging in the care of patients with epilepsy: A consensus report from the International League Against Epilepsy Neuroimaging Task Force. Epilepsia. 2019;60(6):1054-1068. doi:10.1111/epi.15612
  17. Salmenpera TM. Imaging in epilepsy. J Neurol Neurosurg Psychiatry. 2005;76(suppl_3):iii2-iii10. doi:10.1136/jnnp.2005.075135
  18. Duncan JS, Winston GP, Koepp MJ, Ourselin S. Brain imaging in the assessment for epilepsy surgery. Lancet Neurol. 2016;15(4):420-433. doi:10.1016/S1474-4422(15)00383-X
  19. Sada N, Lee S, Katsu T, Otsuki T, Inoue T. Epilepsy treatment. Targeting LDH enzymes with a stiripentol analog to treat epilepsy. Science. 2015;347(6228):1362-1367. doi:10.1126/science.aaa1299
  20. Rugg-Gunn FJ, Boulby PA, Symms MR, Barker GJ, Duncan JS. Imaging the neocortex in epilepsy with double inversion recovery imaging. Neuroimage. 2006 May 15;31(1):39-50. doi: 10.1016/j.neuroimage.2005.11.034. Epub 2006 Feb 7. PMID: 16460962.
  21.  Emilio Perucca, Piero Perucca, H Steve White, Elaine C Wirrell. Drug resistance in epilepsy. The Lancet Neurology. Volume 22, Issue 8, 2023, Pages 723-734, ISSN 1474-4422, https://doi.org/10.1016/S1474-4422 (23)00151-5.
  22. Haltiner AM, Temkin NR, Dikmen SS. Risk of seizure recurrence after the first late posttraumatic seizure. Arch Phys Med Rehabil. 1997;78(8):835-840. doi:10.1016/S0003-9993(97)90196-9
  23. Okudan ZV, Ozkara C. Reflex epilepsy: triggers and management strategies. Neuropsychiatr Dis Treat. 2018;Volume 14:327-337. doi:10.2147/NDT.S107669
  24. Kass JS, Rose RV. Driving and Epilepsy: Ethical, Legal, and Health Care Policy Challenges. Contin Minneap Minn. 2019;25(2):537-542. doi:10.1212/CON.0000000000000714
  25. Chen Z, Brodie MJ, Liew D, Kwan P. Treatment Outcomes in Patients With Newly Diagnosed Epilepsy Treated With Established and New Antiepileptic Drugs: A 30-Year Longitudinal Cohort Study. JAMA Neurol. 2018;75(3):279–286. doi:10.1001/jamaneurol.2017.3949
  26. Smith PEM. Initial management of seizure in adults. The New England journal of medicine. 2021;385(3):251-263. https://nejm.org/doi/full/10.1056/NEJMcp2024526. doi: 10.1056/NEJMcp2024526.
  27. Abou-Khalil BW. Update on Antiepileptic Drugs 2019: Contin Lifelong Learn Neurol. 2019;25(2):508-536. doi:10.1212/CON.0000000000000715
  28. Kapur J, Elm J, Chamberlain JM, et al. Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus. N Engl J Med. 2019;381(22):2103-2113. doi:10.1056/NEJMoa1905795
  29. Rho JM. Inhibition of Lactate Dehydrogenase to Treat Epilepsy. N Engl J Med. 2015;373(2):187-189. doi:10.1056/NEJMcibr1503558
  30. West S, Nevitt SJ, Cotton J, et al. Surgery for epilepsy. Cochrane Database Syst Rev. 2019;6:CD010541. doi:10.1002/14651858.CD010541.pub3
  31. Kwon SJ, Barletta JF, Hall ST, et al. Lacosamide versus phenytoin for the prevention of early post traumatic seizures. J Crit Care. 2019; 50:50-53. doi:10.1016/j.jcrc.2018.11.010
  32. Szaflarski JP, Sangha KS, Lindsell CJ, Shutter LA. Prospective, Randomized, Single-Blinded Comparative Trial of Intravenous Levetiracetam Versus Phenytoin for Seizure Prophylaxis. Neurocrit Care. 2010;12(2):165-172. doi:10.1007/s12028-009-9304-y
  33. Randomised study of antiepileptic drug withdrawal in patients in remission. Medical Research Council Antiepileptic Drug Withdrawal Study Group. Lancet Lond Engl. 1991;337(8751):1175-1180.
  34. Fordington S, Manford M. A review of seizures and epilepsy following traumatic brain injury. J Neurol. 2020 Oct;267(10):3105-3111. doi: 10.1007/s00415-020-09926-w. Epub 2020 May 22. PMID: 32444981; PMCID: PMC7501105.
  35. Glantz MJ, Cole BF, Forsyth PA, et al. Practice parameter: Anticonvulsant prophylaxis in patients with newly diagnosed brain tumors: Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2000;54(10):1886-1893. doi:10.1212/WNL.54.10.1886
  36. Angriman F, Tirupakuzhi Vijayaraghavan BK, Dragoi L, Lopez Soto C, Chapman M, Scales DC. Antiepileptic Drugs to Prevent Seizures After Spontaneous Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis. Stroke. 2019;50(5):1095-1099. doi:10.1161/STROKEAHA.118.024380
  37. Klinger N, Mittal S. Deep brain stimulation for seizure control in drug-resistant epilepsy. Neurosurg Focus. 2018; 45(2):E4. doi:10.3171/2018.4.FOCUS1872
  38. Kim SH, Lim SC, Kim J, Son B-C, Lee KJ, Shon Y-M. Long-term follow-up of anterior thalamic deep brain stimulation in epilepsy: A 11-year, single center experience. Seizure. 2017;52:154-161. doi:10.1016/j.seizure.2017.10.009
  39. Fisher R, Salanova V, Witt T, et al. Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy: Deep Brain Stimulation of Anterior Thalamus for Epilepsy. Epilepsia. 2010;51(5):899-908. doi:10.1111/j.1528-1167.2010.02536.x
  40. Mishra A, Maiti R, Mishra BR, Jena M, Srinivasan A. Effect of Repetitive Transcranial Magnetic Stimulation on Seizure Frequency and Epileptiform Discharges in Drug-Resistant Epilepsy: A Meta-Analysis. J Clin Neurol Seoul Korea. 2020;16(1):9-18. doi:10.3988/jcn.2020.16.1.9
  41. Bahr TA, Rodriguez D, Beaumont C, Allred K. The Effects of Various Essential Oils on Epilepsy and Acute Seizure: A Systematic Review. Evid-Based Complement Altern Med ECAM. 2019;2019: 6216745. doi:10.1155/2019/6216745
  42. Alexis Arzimanoglou, Ulrich Brandl, J Helen Cross, et al. Epilepsy and Cannabidiol: A guide to treatment. Epileptic Disord. 2020;22(1). doi:10.1684/epd.2020.1141
  43. Gauthier AC, Mattson RH. Clobazam: A Safe, Efficacious, and Newly Rediscovered Therapeutic for Epilepsy. CNS Neurosci Ther. 2015;21(7):543-548. doi:10.1111/cns.12399
  44. Bergey GK, Morrell MJ, Mizrahi EM, et al. Long-term treatment with responsive brain stimulation in adults with refractory partial seizures. Neurology. 2015;84(8):810-817. doi:10.1212/WNL.0000000000001280
  45. Kanner AM, Bicchi MM. Antiseizure Medications for Adults With Epilepsy: A Review. JAMA. 2022;327(13):1269–1281. doi:10.1001/jama.2022.3880
  46. Fordington S, Manford M. A review of seizures and epilepsy following traumatic brain injury. J Neurol. 2020 Oct;267(10):3105-3111. doi: 10.1007/s00415-020-09926-w. Epub 2020 May 22. PMID: 32444981; PMCID: PMC7501105.
  47. Hartshorn A, Jobst B. Responsive brain stimulation in epilepsy. Ther Adv Chronic Dis. 2018 Jul;9(7):135-142. doi: 10.1177/2040622318774173. Epub 2018 May 7. PMID: 29963302; PMCID: PMC6009082.
  48. Kerr, W.T., McFarlane, K.N. Machine Learning and Artificial Intelligence Applications to Epilepsy: a Review for the Practicing Epileptologist. Curr Neurol Neurosci Rep 23, 869–879 (2023). https://doi.org/10.1007/s11910-023-01318-7
  49. Robert P. McInnis, Muhammad Abubakar Ayub, Jin Jing, Jonathan J. Halford, Farrah J. Mateen, M. Brandon Westover. Epilepsy diagnosis using a clinical decision tool and artificially intelligent electroencephalography. Epilepsy & Behavior. Volume 141, 2023, 109135, ISSN 1525-5050. https://doi.org/10.1016/j.yebeh.2023.109135.

Original Version of the Topic:

Tamara Zagustin, MD. Seizures and epilepsy. 8/7/2012

Previous Revision(s) of the Topic

Rani Haley Lindberg, Devin Wells MD. Seizures and epilepsy. 4/5/2016

Rani Haley Lindberg, Lindsay Mohney, DO. Seizures and Epilepsy. 3/11/2021

Author Disclosures

Rani Haley Gardner, MD
Nothing to Disclose

Sarah Hunton, MD
Nothing to Disclose

Lindsay Mohney, DO
Nothing to Disclose

Josh Estes, MD
Nothing to Disclose

Neil Simmons, MD
Nothing to Disclose