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Seizure disorders

Last updated: November 16, 2018

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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).

Also see the article on generalized epilepsy in childhood.

  • 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:
    • Two or more unprovoked seizures separated by more than 24 hours
    • One unprovoked seizure with an underlying predisposition to seizures (recurrence risk over the next 10 years that is similar to the recurrence risk after two unprovoked seizures)
    • Diagnosis of an epilepsy syndrome
  • 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 provoked seizure for details.
  • Epilepsy syndromes: epileptic disorders defined by a collection of characteristic clinical manifestations and other features (e.g., age of onset, brain lesions)

References:[1][2][3][4][5]

  • Prevalence:
    • Infants: ∼ 100/100,000
    • Adults : ∼ 40/100,000
    • The elderly : ∼ 140/100,000
  • Risk of experiencing at least one seizure up to the age of 75 (in the general population): ∼ 3%

References:[6]

Epidemiological data refers to the US, unless otherwise specified.

Epilepsy

Although these seizures are referred to as unprovoked, they may be triggered by certain provocative factors!

Provocative factors for epilepsy

Situational factors that can trigger epileptic seizures in epilepsy patients:

  • Excessive physical exertion
  • Sleep deprivation
  • Strobe light flashing
  • Loud music

Provoked seizures

Acute symptomatic seizures that are secondary to acute conditions:

Withdrawal from ABBA (alcohol, benzodiazepines, barbiturates, antiseizure drugs) can cause seizures!

Common causes according to age group

References:[7][8][9][10]

Neonates Infants and children Adolescents Younger adults Older adults (> 35 years)

References:[6][7][11][12][13][14][15]

  1. 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)
  2. Classification according to anatomical origin and clinical features

References:[16]

Focal seizures

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 cerebral regions (confined to one hemisphere)
  • Prodromal symptoms: auras
  • Intact consciousness
  • Motor symptoms
  • Sensory and psychiatric symptoms
    • Visual (e.g., hallucinations, micropsia, macropsia)
    • Somatic (e.g., paresthesias)
    • Position (e.g., vertigo)
    • Hearing (e.g., hearing complex sounds)
    • Olfactory (e.g., unusual or intense smells)
  • Autonomic symptoms (e.g. flushing, sweating)
  • Residual neurologic deficits depending on the affected cerebral region
  • Todd's paralysis: Postictal weakness or paralysis of the affected limb or facial muscles (for minutes or up to hours)
Focal seizure with impaired consciousness (complex partial seizures)
Focal seizures may evolve to generalized convulsive seizure (formerly secondarily generalized tonic-clonic)

Primarily generalized seizures

Symptoms are produced by bilateral cerebral cortex disturbances.

Ictal phase Post-ictal phase

Generalized motor seizure

Tonic-clonic seizure
  • Prodromal symptoms may occur hours before seizure onset (e.g., sleep disturbances, lightheadedness, mood changes, anxiety/irritability, impaired concentration)
  • Loss of consciousness (sudden, often without any warning)
  • Motor symptoms:
    1. Tonic phase:
    2. Clonic phase (rhythmic muscle twitching)
  • Bladder or bowel incontinence
  • Tongue bite lacerations
Clonic seizure
  • Loss of consciousness
  • Rhythmic jerking motor movements (of the entire body or only a part)
  • None
Tonic seizure
  • Loss of consciousness (often occur when the patient is drowsy, asleep, or after waking)
  • Muscle contractions (extension or flexion of the head, trunk, and/or extremities)
  • None
Myoclonic seizure (associated with epilepsy syndromes)
  • Brief loss of consciousness
  • Myoclonic: sudden jerky muscle twitching (of the entire body or only a part)
  • None
Atonic seizure (also known as drop attacks; associated with epilepsy syndromes)
  • Brief loss of consciousness
  • Sudden loss of muscle tone: sudden head drop or collapse (lasts ∼ 2 seconds)
  • None
Non-motor (absence) seizure (common type of generalized epilepsy in childhood.)
  • Brief loss of consciousness
  • Interrupted motion or activity, blank stare, unresponsiveness
  • Can occur several hundred times a day and usually ceases after 5–20 seconds
  • Very subtle automatisms (often go unnoticed!): lip smacking, eye fluttering, or head nodding are common
  • None
  • Consciousness returns rapidly, without any impairment
  • Patient often unaware of interruption

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!

References:[1][11][15][17][18]

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 )
  • EEG
    • 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)

Exclude an underlying condition

The first focal seizure or the first focal seizure evolving into a generalized seizure in adults indicates a seizure of structural or metabolic origin and requires further evaluation!

References:[4][7][11][12][15]

Postictal disorientation is key to differentiating between seizures and syncope. Syncope may be accompanied by twitches; however, patients become completely reoriented after a few seconds!

References:[11]

The differential diagnoses listed here are not exhaustive.

Acute management

First seizure

  • 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).

Recurrent seizures

Medical therapy

  • 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
  • Indications
    • Recurrent seizures (2 seizures/6 months) of unknown cause or with a cause that can not be eliminated
    • After the first seizure → only if neuroimaging or EEG show specific findings (e.g., hippocampal sclerosis, characteristic spike‑wave patterns)
  • Treatment options
Focal seizures
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.

Nonpharmacological therapy

  • Indications: pharmacoresistance
  • Surgery
    • Prerequisite: epilepsy that does not respond to medications → often epilepsies with structural origin (most commonly temporal lobe epilepsy)
    • Procedures
      • 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!

References:[7][11][12][19][20][21][22]

Status epilepticus

Criteria

  • ≥ 5 min of continuous seizures
  • OR ≥ 2 seizures with consciousness not being fully regained in the interictal period

Etiology

Treatment

  1. Initial assessment and supportive treatment:
  2. Pharmacological interruption of seizures: initial treatment
  3. Nonbenzodiazepine therapy (to prevent recurrence): fosphenytoin or valproate

Prognosis

  • Mortality of ∼ 20% (in adults with first occurrence of GCSE)

Status epilepticus is a life‑threatening event! If not interrupted, it can lead to cerebral edema, a dangerous rise in body temperature, rhabdomyolysis, and cerebral cardiovascular failure!

General complications of seizures and epilepsy

References:[11][12][20][23][24][25]

We list the most important complications. The selection is not exhaustive.

Risk of seizure recurrence

  • Overall risk of recurrence
    • After the first unprovoked seizure (within 2 years): ∼ 40%
    • After the second unprovoked seizure (within 1 year): ∼ 60%
  • 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).

References:[12][26][27][28][29]

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  2. About Epilepsy: The Basics. http://www.epilepsy.com/learn/about-epilepsy-basics. Updated: March 1, 2014. Accessed: March 31, 2017.
  3. A Revised Definition of Epilepsy. http://www.epilepsy.com/article/2014/4/revised-definition-epilepsy. Updated: April 1, 2014. Accessed: March 31, 2017.
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  5. Types of Epilepsy Syndromes. http://www.epilepsy.com/learn/types-epilepsy-syndromes. Updated: September 1, 2013. Accessed: March 31, 2017.
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  9. Korff CM, Wirrell E. ILAE classification of seizures and epilepsy. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/ilae-classification-of-seizures-and-epilepsy?source=see_link.Last updated: October 20, 2015. Accessed: March 29, 2017.
  10. Millichap JJ. Clinical Features and Evaluation of Febrile Seizures. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/clinical-features-and-evaluation-of-febrile-seizures.Last updated: March 3, 2017. Accessed: March 29, 2017.
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