Aetiology

Generalised tonic-clonic seizures (GTCSs)

  • Aetiology depends directly on the epilepsy syndrome or provoking element that initiated the epileptiform activity.

  • GTCSs associated with any epilepsy syndrome are termed unprovoked, while GTCSs caused by a reversible stimulus are termed provoked.

  • Provoked seizures can be caused by toxins, illicit substances, medications that lower seizure thresholds, or metabolic derangements.

Generalised-onset epilepsies

  • Aetiology is presumed to be genetic in most cases.

  • Characteristic electroencephalogram (EEG) findings of generalised epileptiform activity, normal brain imaging, and a positive family history are often classic features, suggesting a hereditary abnormality on a molecular level.

  • A number of causal molecular abnormalities have been discovered; mutations in genes that code for sodium, potassium, chloride, and calcium ion channels have all been linked with generalised epilepsy syndromes.[4][5][12][13]​​​​​ However, in many cases the underlying genes are not known, and inheritance is often polygenic/epigenetic.[2]

Focal-onset epilepsies

  • There is often an identifiable or presumed structural cause underlying the development of seizures. This can include cortical malformations, dysplasias, neoplasms, infarcts, vascular malformations, or areas of damage from prior trauma.

  • Occasionally, focal-onset epilepsies occur with no identifiable lesion on imaging.

Pathophysiology

The true mechanism of epileptogenesis remains an intensely studied and somewhat controversial topic. In general, seizures are caused by properties of neurons that lead to inappropriate hyperexcitability and hypersynchrony. Some research suggests that groups of neurons must have the abnormal capability to generate intrinsic discharge bursts, coupled with decreased gamma-aminobutyric acid inhibition and the activation of local recurrent excitatory currents.[14] A variety of genetic and structural abnormalities can contribute to clusters of neurons (or all neurons) developing this state.[15]

For GTCSs, the nature of this hyperexcitability and hypersynchrony depends on the underlying aetiology of the epilepsy.

  • Generalised-onset epilepsy: the GTCS begins immediately with bihemispheric electrical discharges; some work suggests that a thalamic generator is the source of, or a pacemaker for, this seizure type, with thalamocortical circuitry facilitating the engagement of broader synaptic connections.[16]

  • Focal-onset epilepsy: the seizure initiates as a focal seizure, and then evolves through the ipsilateral hemisphere as the normal inhibitory forces begin to break down. In a focal to bilateral tonic-clonic seizure, the ictal activity crosses to the contralateral hemisphere (most often via the corpus callosum), and then continues the pattern of hyperexcitability and hypersynchrony in the contralateral hemisphere (in addition to the ipsilateral hemisphere).

Classification

International League Against Epilepsy (ILAE) classification of the epilepsies[1][2]

Classification of the epilepsies was updated by the ILAE in 2017.[1][2] Three levels are presented:

  • Seizure type

  • Epilepsy type (focal; generalised; combined generalised and focal; and unknown)

  • Epilepsy syndrome.

Seizure types are classified as follows:

1. Generalised-onset seizures

  • Motor

    • Tonic-clonic

    • Other motor.

  • Non-motor (absence)

2. Focal-onset seizures

  • Motor onset

  • Non-motor onset.

The term 'focal to bilateral tonic-clonic seizure' is a description of a focal-onset seizure that propagates to engage bilateral networks.

3. Unknown-onset seizures

  • Motor

    • Tonic-clonic

    • Other motor.

  • Non-motor

The 2017 ILAE guidelines for seizure classification included the following changes:[1]

  • 'Partial' becomes 'focal'

  • Awareness is used as a classifier of focal seizures

  • The terms dyscognitive, simple partial, complex partial, psychic, and secondarily generalised are eliminated

  • New focal seizure types include automatisms, behaviour arrest, hyperkinetic, autonomic, cognitive, and emotional

  • Atonic, clonic, epileptic spasms, myoclonic, and tonic seizures can be of either focal or generalised onset

  • Focal to bilateral tonic-clonic seizure replaces secondarily generalised seizure

  • New generalised seizure types are absence with eyelid myoclonia, myoclonic absence, myoclonic-atonic, myoclonic-tonic-clonic

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

In 2022 the ILAE published a new classification and definition of epilepsy syndromes that classifies epilepsy for patients of different age groups.[3]​ Those relevant to the current topic are idiopathic generalised epilepsy syndromes and epilepsy syndromes with onset at a variable age.[4][5]

Use of this content is subject to our disclaimer