Idiopathic (Genetic) Generalized Epilepsy

The definition of a seizure is an abnormal, hypersynchronous discharge of cortical neurons causing transient signs and symptoms. Epilepsy is brain disorder "characterized by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychological, and social consequences of this condition. The definition of epilepsy requires the occurrence of at least one epileptic seizure." A diagnosis of epilepsy is considered in the following circumstances:

1. Two unprovoked seizures more than 24 hours apart

2. One unprovoked seizure but with a high recurrence risk (such as abnormal baseline EEG)

3. A diagnosis of an epilepsy syndrome

The terminology and classification of epilepsy have undergone significant change in recent years with the revised International League Against Epilepsy (ILAE) classification of epilepsies in 2017, replacing the 1989 classification. This update encompasses scientific advancement and establishes a viable clinical tool for the practicing clinician while remaining applicable for research and development of anti-epileptic therapies.

The new classification defined by the 2017 ILAE Seizure Classification operates on a three-tier system. The first tier is the location within the brain of the epileptogenic focus.

Focal Seizures have origins “within networks limited to one hemisphere. They may be discretely localized or more widely distributed. Focal seizures may originate in subcortical structures.” Focal seizures can be further subclassified according to the following:

1. Motor onset or non-motor onset

1. Motor:(with subgroups of automatisms, atonic, clonic, myoclonic, epileptic spasms, hyperkinetic, tonic)

   1. automatism: coordinated, purposeful, repetitive motor activity. A common example is lip-smacking.

   2. atonic: focal loss of tone

   3. clonic: focal rhythmic jerking

   4. myoclonic: irregular brief focal jerking

   5. epileptic spasms: focal flexion or extension of arms with flexion of trunk,

   6. hyperkinetic: activities such as pedaling or thrashing

   7. tonic: sustained focal stiffening

2. Non-motor (with subgroups autonomic, behavior arrest, cognitive, emotional, sensory).

   1. autonomic: a sense of heat or cold, flushing, gastrointestinal sensations, a sense of heat or cold, piloerection (goosebumps), palpitations, sexual arousal, respiratory changes, or other autonomic effects.

   2. behavior arrest: behavioral arrest as the predominant aspect of the entire seizure.

   3. cognitive: the patient reports or exhibits deficits in language, thinking or associated higher cortical functions. Examples can also be a feeling of deja vu, jamais vu, hallucinations, or illusions.

   4. emotional: emotional changes, such as fear, anxiety, agitation, anger, paranoia, pleasure, joy, laughing (gelastic seizure), or crying (dacrystic seizure). These are often subjective.

   5. sensory: somatosensory sensations, such as olfactory, visual, auditory, hot or cold feeling, taste, or vestibular sensations.

2. Intact or non-intact awareness (a surrogate marker for consciousness). Awareness means consciousness during the seizure, not being aware that a seizure has occurred. Impairment of awareness at any point constitutes non-intact awareness. Responsiveness is not a classification criterion by ILAE as focal impaired consciousness seizures can be associated with alertness and responsiveness to commands.

3. Focal to bilateral tonic-clonic. This replaces the term "secondarily generalized tonic-clonic." "Bilateral" describes how the seizure propagates as opposed to "generalized" which describes generalized onset of the seizure location.

Generalized onset seizures have origins “originating at some point within, and rapidly engaging, bilaterally distributed networks." Most generalized seizures are associated with impaired consciousness, so this is a descriptive criterion. They are classified as motor or non-motor. As many seizures evolve into tonic-clonic, it is important to characterize the beginning of a seizure in detail. If a certain type of seizure only occurs when generalized (such as absence seizures), the "generalized" may be omitted.

1. Motor (tonic-clonic, clonic, tonic, myoclonic, myoclonic-tonic-clonic, myoclonic-atonic, atonic, epileptic spasms). See above for a description of terms, and the following are identifying characteristics of specific types of generalized onset motor seizures:

1. Tonic-clonic seizure replaces the previous term "grand mal seizure," and is the most recognizable type. If initiated by myoclonic activity, it is classified as myotonic-tonic-clonic. The clonic phase usually decreases over the seizure course. They may be preceded by an "aura" or feeling of impending doom or other autonomic activity, but this does not contribute to focality of the seizure.

2. Generalized clonic seizures begin and end with sustained jerking of the head, neck, face, and trunk. This type is most commonly seen in infants.

3. Tonic seizures involve sustained extension, less commonly flexion, of a muscle group. It should be distinguished from dystonia and athetoid movement caused by antipsychotic medications.

4. Atonic seizures often cause a patient to fall forward or onto the buttocks. In contrast, generalized tonic-clonic seizures generally cause a patient to fall backward.

5. Epileptic spasms cause flexion or extension of proximal muscles and the trunk. They occur most often in clusters and in infants where they are called "infantile spasms."

2. Non-motor or absence (typical, atypical, myoclonic, eyelid myoclonia). The ILAE classification systems retain the distinction between typical and atypical generalized seizures because of different EEG patterns, therapy, and prognosis.

1. Typical generalized seizures with non-motor are commonly referred to as absence seizures. They present with sudden onset of cessation of activity, blank stare, and unresponsiveness. They usually last several seconds to half a minute. If performed during the event, EEG would show generalized epileptiform discharges.

2. Atypical absence seizures are associated with increased muscle tonic behavior and less abrupt beginning and ending of the event. EEG during the event would show slow, irregular spike-and-wave activity at a rate of <3 per second.

3. Myoclonic seizures are characterized by 3-per-second myoclonic jerks ratcheting the arm upwards and correspond to 3-per-second generalized spike-and-wave readings on EEG.

4. Eyelid myoclonia are eyelid myoclonic jerks accompanied by upward eye deviation. If accompanied by EEG abnormalities with eye closure and photosensitivity, this triad is called Jeavons syndrome.

Seizures of unknown onset. If seizures are unwitnessed or unable to be accurately described, they are given this designation. They can be motor, non-motor, or unclassified. Unclassified refers to seizures without enough descriptive information to classify or those that do not fit into other categories. Often, this included tonic-clonic seizures for which the start is unwitnessed

There can be significant overlap between the different classifications and differing bystander opinions about the clinical presentations; therefore, the above classifications are only a framework to define seizure origin and type. The recommended classification system first classifies seizures by location (local, generalized, or unknown); then by type of epilepsy disease (focal, generalized, combined, or unknown); and finally, if the seizure and epilepsy type are part of an overall epilepsy syndrome (eg, JME, CAE, JAE).

The 2017 ILAE terminology introduces new terminology, such as developmental and epileptic encephalopathy. Furthermore, the 2017 Classification also includes the following changes:

1. "Partial" becomes "focal";

2. Awareness is used as a classifier of focal seizures;

3. The terms dyscognitive, simple partial, complex partial, psychic, and secondarily generalized are eliminated;

4. New focal seizure types include automatisms, behavior arrest, hyperkinetic, autonomic, cognitive, and emotional;

5. Atonic, clonic, epileptic spasms, myoclonic, and tonic seizures can be of either focal or generalized onset;

6. Focal to bilateral tonic-clonic seizure replaces secondarily generalized seizure;

7. New generalized seizure types are absence with eyelid myoclonia, myoclonic absence, myoclonic-atonic, myoclonic-tonic-clonic;

8. Seizures of unknown onset may have features that can still be classified.

9. Benign is replaced by the terms self-limited or pharmacoresponsive.

This activity will focus on idiopathic (genetic) generalized epilepsy (IGE), one of the most well-recognized subgroups of generalized epilepsies. Idiopathic generalized epilepsy specifically refers to epilepsy syndromes such as juvenile myoclonic epilepsy (JME), juvenile absence epilepsy (JAE), childhood absence epilepsy (CAE), and generalized tonic-clonic seizures.