- Clinical science
A seizure is irregular electrical activity in the brain caused by the hyperexcitability of neurons, especially in cortical areas. Hyperexcitability, in turn, is the result of altered cellular electrochemical properties, which may be caused, for example, by electrolyte imbalances. The etiology varies according to age. Seizures may be provoked by acute conditions (e.g., stroke, traumatic brain injury, alcohol withdrawal) or unprovoked, in which case they are indicative of epilepsy. The lifetime risk for experiencing at least one seizure is approx. 3% in the general population. Individuals who experience a single seizure do not necessarily have epilepsy. Seizures may be classified as generalized or focal. Generalized seizures arise from discharges in both hemispheres, whereas focal seizures begin with discharges in one hemisphere. Depending on the origin of the epileptiform discharge and the type of the seizure, various temporary motor, sensory, autonomic, or psychological symptoms may occur. However, the most frequent clinical presentation involves rhythmic twitching and loss of consciousness (tonic-clonic seizure). After a first seizure occurs, the likely cause must be determined based on medical history (evaluation of provocative factors and seizure type), laboratory tests, and imaging (to detect or rule out structural or metabolic causes). Electroencephalography (EEG) is used to establish the diagnosis. Important antiepileptic drugs are lamotrigine (first-line treatment in focal seizures), valproate (first-line treatment in generalized seizures) and ethosuximide (first-line treatment in typical absence seizures). With appropriate pharmacotherapy, the majority of patients remain seizure‑free in the long term. Epileptic seizures can evolve into ongoing seizure activity (status epilepticus), which is a potentially life‑threatening event and must be addressed as soon as possible (pharmacologic interruption of seizures with a benzodiazepine).
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- Seizure: abnormal, unregulated electrical activity of cortical neurons that results in transient changes in behavior and/or EEG findings
- Epilepsy: a chronic neurologic disorder characterized by any of the following:
- Symptomatic epilepsy: : epilepsy due to an identifiable condition (e.g., brain tumor, structural abnormalities of the brain) that causes an increased predisposition to seizures
- Cryptogenic epilepsy: epilepsy due to an unknown cause (genetic association suspected)
- Nonepileptic seizure: seizures that are provoked by acute conditions (e.g., intoxication, metabolic disturbances). See for details.
- Epilepsy syndromes: epileptic disorders defined by a collection of characteristic clinical manifestations and other features (e.g., age of onset, brain lesions)
Unprovoked seizure (epileptic seizure): due to a general increase in neuronal hyperexcitability
- Genetic: genetic mutations of ion channels or transmitter receptors, chromosomal abnormalities
- Cryptogenic (idiopathic): genetic association suspected
- Structural/metabolic: preexisting, chronic cerebral lesion of CNS abnormality; (e.g., hypoxic-ischemic injury; , PKU; , tuberous sclerosis, congenital cerebral malformations)
Although these seizures are referred to as unprovoked, they may be triggered by certain provocative factors!
Situational factors that can trigger epileptic seizures in epilepsy patients:
- Excessive physical exertion
- Sleep deprivation
- Strobe light flashing
- Loud music
Acute symptomatic seizures that are secondary to acute conditions:
- Metabolic and electrolyte disturbances: hypoglycemia and hyperglycemia, hyponatremia and hypernatremia, hypocalcemia, uremia, thyroid storm, hyperthermia, water intoxication
- Mass: : brain tumors and metastases, hippocampal sclerosis
- Infections: encephalitis, brain abscess, meningitis, septic shock
- Ischemia: : , perinatal injuries
- Trauma: traumatic brain injury
- Increased ICP and cerebral edema: eclampsia, hypertensive encephalopathy, cerebrovascular malformation
- Fever: in infants and children (see )
Common causes according to age group
|Neonates||Infants and children||Adolescents||Younger adults||Older adults (> 35 years)|
Etiological classification (ILAE 2010)
- Genetic: without a discernible structural or metabolic cause
- Structural or metabolic: with a discernible structural or metabolic cause
- Unknown: no tangible cause (the cause is inferred from the clinical presentation and history)
- Classification according to anatomical origin and clinical features
- Sudden onset
- Rapid progression of symptoms
- Duration usually 1–3 minutes
- Varying degree of confusion, impaired alertness
- Residual neurologic symptoms (e.g., Todd's paralysis)
- Duration usually minutes or hours
- Symptoms of, e.g., CNS infection, stroke, intoxication, hypoglycemia, electrolyte disturbances → indicative of acute symptomatic seizure
Focal seizures are more likely to be caused by focal structural abnormalities. Symptoms depend on the anatomical location of the lesion or disturbance within the brain.
|Focal seizures||Origin||Ictal phase||Post-ictal phase|
|Focal seizure with intact consciousness (simple partial seizures)|| || || |
|Focal seizure with impaired consciousness (complex partial seizures)|| |
|Focal seizures may evolve to generalized convulsive seizure (formerly secondarily generalized tonic-clonic)|
Symptoms are produced by bilateral cerebral cortex disturbances.
|Ictal phase||Post-ictal phase|
Generalized motor seizure
|Tonic-clonic seizure|| |
|Clonic seizure|| || |
|Tonic seizure|| || |
|Myoclonic seizure (associated with epilepsy syndromes)|| || |
|Atonic seizure (also known as drop attacks; associated with epilepsy syndromes)|| || |
|Non-motor (absence) seizure (common type of .)|| || |
Focal seizures may eventually involve both cerebral hemispheres, thereby evolving into a generalized seizure (typically focal frontal lobe seizures!). Distinguishing between pure focal, focal → generalized, and purely generalized seizures is crucial!
Confirm a seizure
- Patient history: (from patient or witnesses): e.g., evidence of an aura, observation of typical symptoms (e.g., twitching), identification of provocative factors (e.g., sleep deprivation or unreliable intake of antiseizure medication )
- During the seizure (ictal)
- Epileptiform discharges (e.g., spikes, sharp waves, spike waves, and hypsarrhythmia) are usually detected.
- If no epileptiform discharges are detected, diagnosis of pseudoseizures should be considered.
Between seizures (interictal)
- Often normal findings (even after provocation via sleep deprivation, hyperventilation, or visual stimuli)
- Possibly showing epileptiform activity (bursts of abnormal discharges featuring spikes and/or sharp waves)
EEG criteria for epileptic seizures:
- Well‑defined beginning and end
- Progressive increase in amplitude
- Frequency changes during the course of the seizure
- During the seizure (ictal)
Exclude an underlying condition
- ECG: In every patient with loss of consciousness during an ictal event, cardiogenic causes (e.g., cardiac arrhythmias resulting in cerebral hypoxia) should be ruled out.
- CT/MRI (with and without contrast): structural lesions (e.g., brain tumors) should be ruled out after a first seizure.
- Laboratory tests
- Lumbar puncture: cerebrospinal fluid analysis (e.g., if CNS infection is suspected)
Levels of diagnostic specificity
- Electroclinical syndrome: combination of clinical signs and symptoms that defines a distinctive, identifiable clinical disorder
Constellation: groups of clinical entities with common or similar underlying causes
- Less specific than electroclinical syndromes, but often involving a specific abnormality that can be treated surgically
- Example: temporal lobe epilepsy (as a result of hippocampal sclerosis)
Structural and metabolic epilepsies:
- Epilepsies of structural or metabolic origin that do not fit the more precise categories of “electroclinical syndrome” and “constellation” should be described according to their etiology
- Example: “epilepsy with primarily generalized seizures as a result of bilateral degeneration of the frontal lobes”
- Epilepsies of unknown cause: heterogenous group of epilepsies that require extensive additional information from medical history, neurological exam, and instrumental diagnostics (e.g., electroencephalography)
- Stroke (including transient ischemic attack )
- Sleep disorders
Breath-holding spell (benign condition)
- Occurs in children (6 months–6 years )
- Strong association with iron deficiency anemia
- Clinical features
- Triggers: distress, strong emotions (e.g., anger, frustration) due to tantrums or injury
- Diagnosis: based on typical presentation of BHS (no confirmatory test exists)
- Treatment: reassurance
The differential diagnoses listed here are not exhaustive.
- Avoid hazards
- Monitor vital signs (especially oxygenation via pulse oximetry)
- Long-term medical therapy is usually not required, unless there are abnormalities seen on EEG or MRI (or the patient is in status epilepticus).
- Remove cause or provoking factors (e.g., stop illicit drug abuse, treat underlying disorders).
Principles of treatment
- In epilepsy, the seizure threshold is pathologically lowered → Antiepileptic drugs work by raising this lowered threshold and thus protecting against future seizures.
- Criteria for the choice of antiepileptic drugs
- Type of epilepsy (as per clinical evaluation or instrumental findings)
- Patient age
- Comorbidities and contraindications
- Treatment options
|Primary generalized seizures|| |
- Combination therapy
- If possible, monotherapy should be maintained → increase dosage before initiating combination therapy
- If combination therapy is administered, drugs from different classes and/or with different pharmacologic modes of action should be tried.
- Termination of treatment
- To be evaluated on a case‑by‑case basis
- May be considered if the patient has < 2 seizures/year, an inconspicuous provocation EEG, normal psychological findings, and no hereditary predisposition
- Generally possible after 2–5 seizure‑free years with normal EEG results
- Medications must be tapered cautiously.
- Indications: pharmacoresistance
- Prerequisite: epilepsy that does not respond to medications → often epilepsies with structural origin (most commonly temporal lobe epilepsy)
- Resection (surgical removal of pathological lesions)
- Disconnection (surgical breaking of neuronal circuits)
- Stimulation techniques: vagus nerve stimulation, deep brain stimulation
- Dietary measures: ketogenic diet
It is necessary to distinguish between focal and primary generalized seizures in order to decide on the appropriate therapy!
- ≥ 5 min of continuous seizures
- OR ≥ 2 seizures with consciousness not being fully regained in the interictal period
- Common causes are withdrawal from antiepileptic drugs; , metabolic disturbances; (e.g., hyponatremia), drug toxicity; (e.g., tricyclic antidepressants), structural brain lesions/injury (e.g., tumors, trauma, stroke), and CNS infections.
- Generalized convulsive status epilepticus (GCSE):
- Nonconvulsive status epilepticus (NCSE): generally less serious than GSCE, but should also be treated as soon as possible (same general treatment strategy)
Initial assessment and supportive treatment:
- Place patient in recovery position to prevent injury.
- Quick neurological examination (to determine type and cause of status epilepticus) and general medical evaluation (particularly airway, breathing, and circulation)
- Establish secure IV access (two, if possible), collection of blood for routine blood tests (particularly electrolytes and glucose levels), toxicology screen, antiepileptic drug levels, and arterial blood gas (ABG) analysis
- Supportive therapy as necessary (e.g., oxygen, glucose, thiamine naloxone )
- Monitoring of vital signs: especially oxygen saturation (via pulse oximetry), blood pressure, cardiac action, and breathing
- If patient does not regain consciousness after seizures stop or nonconvulsive status epilepticus is suspected → continuous EEG monitoring
- If acute brain injury (e.g., intracerebral hemorrhage) is suspected → obtain a cranial CT
- If CNS infection is suspected → conduct a lumbar puncture
Pharmacological interruption of seizures: initial treatment
First line: IV lorazepam; second line: IV diazepam or midazolam → if IV access is not possible or drugs are administered by someone who is not a medical professional → select another application form (e.g., rectal diazepam, buccal or intranasal lorazepam/midazolam)
- If the patient does not respond within 1 minute → administer additional lorazepam (or a second-line benzodiazepine)
- If the patient does not respond within another 10–20 minutes → saturation with fosphenytoin via separate access (alternatively: phenobarbital, levetiracetam, or valproate)
- If seizure activity does not stop despite application of a benzodiazepine and a nonbenzodiazepine antiseizure drug → refractory status epilepticus
- No later than 45–60 min after onset: continuous administration of anesthetics with intubation and ICU monitoring; e.g., thiopental, propofol, or midazolam
- First line: IV lorazepam; second line: IV diazepam or midazolam → if IV access is not possible or drugs are administered by someone who is not a medical professional → select another application form (e.g., rectal diazepam, buccal or intranasal lorazepam/midazolam)
- Nonbenzodiazepine therapy (to prevent recurrence): fosphenytoin or valproate
- Mortality of ∼ 20% (in adults with first occurrence of GCSE)
General complications of seizures and epilepsy
- Hyperthermia, cardiorespiratory deficits, excitatory toxicity → potentially irreversible tissue damage; (particularly to the CNS; , for example in the form of cortical laminar necrosis; ), which in turn may also result in further seizures
- Postictal transient anion gap metabolic acidosis with increased lactic acid and reduced serum bicarbonate → usually resolves spontaneously within 60–90 minutes after seizure activity stops
- Physical trauma (e.g., posterior dislocation of the glenohumeral joint)
- Associated psychiatric disorders (e.g., anxiety, depression and risk of suicide, cognitive impairments)
- Psychosocial issues (e.g., problems at the workplace)
We list the most important complications. The selection is not exhaustive.
Risk of seizure recurrence
- Overall risk of recurrence
- After a single tonic‑clonic seizure: ∼ 40%
- In genetic epilepsy: ∼ 25–30% (within 3 months)
- Patients with normal EEG results: ∼ 15% (within 1 year)
- Patients with abnormal EEG results: ∼ 40% (within 1 year)
Impact of medical therapy
- Immediate initiation of pharmacotherapy after a first unprovoked seizure lowers risk of recurrence in the short term (within 2 years) but does not significantly improve long‑term risk.
- Approx. 80% of epilepsy patients who are treated with antiepileptic drugs remain seizure‑free for extended periods (3–5 years).
- State law may require that patients who have had a seizure not be permitted to drive or operate heavy machinery for a certain length of time.