Epilepsy is a chronic brain disorder marked by recurrent and unprovoked seizures. These seizures can be classified as focal or generalized and idiopathic or secondary to another condition. Clinical presentation correlates to the classification of the epileptic disorder. Diagnosis is confirmed with EEG. While some epileptic disorders resolve over time, many require lifelong antiepileptic medication for management or, in some refractory cases, surgical procedures.

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Epilepsy is a chronic brain disorder marked by recurrent and unprovoked seizures.

  • Seizures are episodes of neurologic dysfunction caused by abnormal excitatory activities of neurons and are characterized by sudden changes in senses, perception, motor activity, or behavior. 
  • Seizures triggered by reversible or avoidable causes do not classify as epilepsy and do not require treatment with antiepileptic medications.


  • Prevalence: approximately 65 million people worldwide  
    • Lifetime prevalence in the United States: 7.6 per 1000 individuals
    • In older adults: 2%–5% in adults > 60 years of age (3–4 times higher than for younger adults)
  • Incidence: bimodal distribution with peaks in the young and old (< 1 year and > 70 years) 
    • In children: 0.5%–8% per 1000 person-years
    • New-onset epilepsy in older adults: 1–3 per 1000 person-years


Several features may be used to classify epilepsy, which is useful in considering management options. 

  • Features:
    • Seizure types
    • EEG findings: 
      • Generalized onset
      • Local or focal onset 
    • Age at onset
    • Course 
    • Associated clinical features
  • Underlying pathophysiology 
    • Idiopathic (primary):
      • Presumed to be genetic
    • Symptomatic (secondary):
      • Due to structural changes in the brain
      • Described by location of the lesion (e.g., temporal lobe epilepsy)
  • Most common epilepsy syndromes:
    • Idiopathic/generalized onset:
      • Childhood absence epilepsy
      • Juvenile absence epilepsy
      • Juvenile myoclonic epilepsy 
    • Idiopathic/focal onset: benign childhood epilepsy with centrotemporal spikes (BECTS) 
    • Symptomatic/generalized onset
      • Infantile spasms (West syndrome)
      • Lennox-Gastaut syndrome epilepsy
    • Symptomatic/focal onset: temporal lobe epilepsy

Clinical Presentation

Epilepsy syndromes relate to seizure types and are classified primarily using the clinical history; classification requires input from a family member or witness to the seizure in addition to history from the affected individual.

Focal epilepsies

  • Specific epileptogenic origin in a certain region of the brain limited to 1 hemisphere
  • Most common type of epilepsy in all age groups
  • Presents with a set of symptoms related to the region of origin
  • Can become generalized secondarily
  • Can be caused by any local structural alteration (e.g., scars due to ischemia, vessel malformations)
  • Types of focal epilepsies:
    • BECTS: 
      • Idiopathic
      • Also called rolandic epilepsy
      • Age at onset: 1–16 years (mean, 7–9 years)
      • 1-sided clonic seizure with strong salivation, especially at night
      • Often involves the face
      • Upper extremity motor activity is common
      • No altered consciousness
      • Associated with language function problems
      • Seizures stop before adolescence.
    • Temporal lobe epilepsy: 
      • Age at onset: 10–30 years (80% present before age 16)
      • Most common type of focal epilepsy
      • Seizures start with temporal lobe aura (déjà vu) and progress to altered awareness with automatisms.  
      • Causes include hippocampal sclerosis, encephalitis, head trauma, hamartomas, glial tumors, vascular and congenital malformations, and perinatal injury.
      • Most common cause of refractory focal epilepsy in adults: temporal lobe epilepsy associated with hippocampal sclerosis
    • Focal seizures with impaired awareness (previously known as complex partial seizures):
      • Focal motor seizures
      • Focal sensory seizures
      • Autonomic seizures
    • Focal seizures without impaired awareness

Generalized epilepsies

  • Assume a widespread pathology (affect the whole brain)
  • Idiopathic generalized epilepsies account for the greatest number of occurrences:
    • Childhood absence epilepsy (also known as petit mal epilepsy or pyknolepsy):
      • Age at onset: 3–10 years
      • Characterized by brief staring episodes with behavioral arrest 
      • May occur tens to hundreds of times per day 
      • May be provoked by hyperventilation 
      • Strong family history
      • Remission in 2–6 years
    • Juvenile absence epilepsy:
      • Similar to childhood absence epilepsy but with a later onset (ages 10–16)
      • About 40% of individuals are not permanently free of seizures.
      • Lifelong antiepileptic medication may be required.  
    • Juvenile myoclonic epilepsy: 
      • Age at onset: 12–20 years
      • Myoclonus is always present.
      • Generalized tonic-clonic seizures 
      • Absence seizures may also be seen. 
      • May be provoked by sleep deprivation and photic stimulation
      • Requires lifelong epileptic therapy.
    • Generalized motor seizures (grand mal epilepsy): generalized tonic-clonic seizures with great irregularity
  • Symptomatic generalized epilepsies:
    • Most often caused by early childhood brain damage due to hypoxia or metabolic diseases. 
    • Infantile spasms (West syndrome): 
      • Occurs in the 1st year of life 
      • Triad of infantile spasm, hypsarrhythmia (EEG pattern), and psychomotor delay
      • Epileptic spasms occur in clusters during sleep transition. 
      • Etiologies: perinatal hypoxic injury, brain malformations, tuberous sclerosis, Down syndrome, metabolic disorders 
      • Poor prognosis with likely neurodevelopmental delay
    • Lennox-Gastaut syndrome:
      • Age at onset: 2–8 years 
      • Seizures are generally astatic (falling), absence, and/or generalized tonic-clonic.
      • Can develop from West syndrome or late generalized brain damage
      • Poor prognosis with severe developmental delay and medically nonrefractory seizures 


Diagnosis is based on history, lab results, and EEG findings.

Initial evaluation

  • History and exam must determine if seizures are provoked or unprovoked.
  • Neuroimaging indicated for initial seizure event: 
    • Noncontrast CT 
    • Brain MRI

Lab testing

  • For a 1st seizure: 
    • Chemistries: electrolytes, glucose, calcium, magnesium, BUN/creatinine, liver function tests
    • CBC
    • Urinalysis
    • Toxicology screen
  • Pregnancy test in women of childbearing years, as pregnancy may affect treatment decisions
  • Serum lactate:
    • If episode was not witnessed 
    • Elevated in the 1st 2 hours after a seizure
    • Differentiates seizures from syncope or psychogenic nonepileptic seizure (PNES)

Electroencephalography (EEG)

EEG is a test to monitor the elctrical sensitivity of the brain.

Types of normal electrical activity on an electroencephalogram

Types of normal electrical activity on an electroencephalogram

Image by Lecturio.
  • Gold standard for diagnosing epilepsy 
  • Indicated for those who do not return to baseline consciousness in the emergent setting
  • Included as part of the workup for new-onset seizures
  • More specific in adults than in children
  • Procedure:
    • Electrodes are placed on the surface of the scalp and connected to a computer, which detects brain electrical activity.
    • Provocation factors can be used to show epileptogenic potentials: photic stimulation, hyperventilation, or sleep deprivation
  • Video-EEG monitoring is the standard test for:
    • Classifying the type of seizure or syndrome
    • Diagnosing PNES or pseudoseizures (psychiatric-related)
Electrical activity of the brain on an EEG during a seizure

Electrical activity of the brain on an EEG during a seizure

Image by Lecturio.
Electrode placement of 21 electrodes of international 10-20 system for EEG

Electrode placements for standard EEG

Image: “21 electrodes of International 10-20 system for EEG” by トマトン124. License: Public Domain

Important EEG findings with respective epilepsy syndromes

  • BECTS: centrotemporal spikes activated by sleep 
  • Temporal lobe epilepsy: temporal lobe spikes or sharp waves 
  • Childhood and juvenile absence epilepsy:
    • Classically 3-Hz (2.5 to 5 Hz) spike-wave complexes
    • Juvenile form can be slightly faster (3–4 Hz)
  • Juvenile myoclonic epilepsy (JME): 
    • 4–6 Hz generalized polyspike and wave discharges
    • Often frontal predominance
  • Infantile spasms (West syndrome): 
    • Hypsarrhythmia (interictal EEG pattern of very-high-amplitude, random, slow waves and spikes in all cortical areas)
    • Chaotic, irregular, disorganized interictal pattern
  • Lennox-Gastaut syndrome: slow spike–wave complexes (< 2.5 Hz)
  • Creutzfeldt-Jakob disease: triphasic waves


The choice of antiseizure medications is based on the type of epilepsy syndrome. Starting treatment after a single unprovoked seizure remains controversial.

Antiepileptic medications

  • Determine whether epilepsy is partial or generalized. 
  • Goals of treatment:
    • Seizure-free status 
    • No adverse effects
Table: Antiepileptic drugs by mechanism of action
NameMechanism of actionIndicationSide effects
PhenobarbitalEnhances GABA-mediated inhibition of synaptic transmissionAll types of epilepsy except absence
  • Sedation
  • Induces cytochrome P450 enzymes for drug interactions
PhenytoinInhibits Na channel activation to inhibit neurotransmissionFocal seizures and generalized tonic-clonic seizures
  • Nausea/vomiting
  • Long-term use associated with osteoporosis, peripheral neuropathy, and gingival hyperplasia
  • Induces CYP450: drug interactions
FosphenytoinSame as phenytoinSame as phenytoinLess risk of hypotension and cardiac dysfunction then with phenytoin
CarbamazepineWorks on voltage-gated Na channels to inhibit synaptic transmissionFocal and secondary generalized seizures
  • Nausea/vomiting
  • Hyponatremia
  • Agranulocytosis
  • Induces CYP450 enzymes
LamotrigineBlocks excitatory Na ion channelsFocal and generalized epilepsy; safest antiepileptic drug during pregnancy
  • Dizziness
  • Drowsiness
  • Rash that can progress to Stevens-Johnson syndrome
EthosuximideWorks on T-type Ca channel to decrease burst firing of thalamocortical neuronsAbsence seizures
  • Nausea/vomiting
  • Blood dyscrasias
GabapentinActs on voltage-gated Ca channels, which increase inhibitory toneFocal seizures
  • Somnolence
  • Weight gain
LevetiracetamModifies synaptic protein SV2AFocal and generalized epilepsy; often used as 1st-line therapy; well tolerated
  • Somnolence
  • Ataxia
  • Irritability
TopiramateBlocks voltage-gated Na channels; also inhibits carbonic anhydrase, causing acidosis in the brain → partial protection against seizuresPrimary generalized onset tonic-clonic seizures
  • Fatigue
  • Cognitive problems
  • Weight loss, appetite suppression
  • Kidney stones
Valproic acidMultipleFocal seizures with impaired awareness, generalized and absence seizures
  • Nausea/vomiting
  • Weight gain
  • Hair loss
  • Hepatotoxic (hepatic inhibitor)
  • Pancreatitis
  • Teratogenic

Surgical therapies

  • Goals of treatment: 
    • Eliminate the epileptogenic neuronal area. 
    • Minimize neurologic deficit.
    • Increase quality of life. 
  • Presurgery testing to visualize the focus of epileptic activity:
    • High-resolution MRI
    • Video EEG 
    • PET scan 
    • Neuropsychologic testing: to predict cognitive effects after cortical resection
  • Indications for procedures:
    • Refractory seizures despite 1 year of medication therapy with ≥ 2 antiepileptic agents 
    • Well-operable epileptogenic focus 
    • Absence of progressive neuronal disease
  • Types of procedures:
    • Open resective surgery:
      • Disconnects epileptic neural networks (e.g., resection of the corticothalamic tract or medial temporal structures)
      • Palliative surgery: corpus callosotomy and multiple subpial transections
    • Radiosurgery: 
      • Noninvasive resective surgery: Gamma Knife or CyberKnife
      • Availability of this procedure is very limited. 
    • Vagal nerve stimulation:
      • For individuals at too high risk for major surgical procedures 
      • Involves placement of electrodes on the left vagal nerve 
  • Seizure preventive measures: 
    • Education of individuals about avoiding common triggers:
      • Sleep deprivation
      • Alcohol use
      • Certain drug types: opioids, stimulants, other prescription medications
    • In certain countries or states, restraint against operating motor vehicles

Differential Diagnosis

  • Syncope: brief loss of consciousness and muscle tone with spontaneous recovery. Syncope has numerous causes but is usually a result of decreased blood flow to the brain. Individuals with syncope do not have the postictal confusion or prolonged duration of unconsciousness, which are prevalent in those with seizure events. Diagnosis is based on history and appropriate cardiac testing or imaging. Management of syncope includes identifying and treating the secondary cause. 
  • Migraine: primary headache disorder characterized by unilateral headaches associated with photophobia, phonophobia, and nausea. Migraines may be preceded by sensory auras similar to those seen with seizures; however, epilepsy does not present with severe headaches. Diagnosis is based on history, exam, and imaging to rule out other pathology. Management includes decreasing exposure to triggers and medications for acute episodes, as well as migraine prophylaxis.
  • Psychogenic nonepileptic seizure (PNES): resembles epileptic seizures; however, there is no defined cortical EEG activity that would be diagnostic in epileptic seizures. Diagnosis of PNES includes subtle physical exam findings that differentiate it from true seizures, such as closed eyes in a convulsing individual with PNES, and video-EEG monitoring. Management includes psychologic therapy such as CBT and possibly medication for anxiety.
  • Hypoglycemia: emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic individuals. There is no specific or defined limit for normal serum glucose levels in nondiabetic individuals, and hypoglycemia is mainly defined by its clinical features. Hypoglycemia may present with adrenergic symptoms and neuroglycopenic symptoms, including seizures. Diagnosis is based on serum glucose measurement and clinical presentation. Management is with oral glucose, IV dextrose, or IM glucagon.
  • Narcolepsy: neurologic sleep disorder that presents clinically with marked daytime sleepiness and is associated with cataplexy, hypnagogic hallucinations, and sleep paralysis. Diagnostic criteria are found using sleep studies that show a decrease in REM latency. Management includes good sleep hygiene. Medications that act as CNS stimulants and antidepressants are used to target the cataplexy.


  1. Schachter S. (2021). Evaluation and management of the first seizure in adults. UpToDate. Retrieved July 18, 2021, from https://www.uptodate.com/contents/evaluation-and-management-of-the-first-seizure-in-adults 
  2. Drislane F. (2021) Convulsive status epilepticus in adults: treatment and prognosis. UpToDate. Retrieved July 18, 2021, from https://www.uptodate.com/contents/convulsive-status-epilepticus-in-adults-treatment-and-prognosis 
  3. Kapur J, et al. (2019). Randomized trial of three anticonvulsant medications for status epilepticus. New England Journal of Medicine 381:2103–2113. https://doi.org/10.1056/NEJMoa1905795
  4. Munakomi S, Das JM. (2021). Epilepsy surgery. StatPearls. Retrieved August 13, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK562151/
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