The 2017 ILAE Classification of Seizures Robert S. Fisher, MD,

The 2017 ILAE Classification of Seizures Robert S. Fisher, MD, PhD Maslah Saul MD Professor of Neurology Director, Stanford Epilepsy Center In 2017, the ILAE released a new classification of seizure types, largely based upon the existing classification formulated in 1981. Primary differences include specific listing of certain new focal seizure types that may previously only have been in the generalized category, use of awareness as a surrogate for consciousness, emphasis on classifying focal seizures by the first clinical manifestation (except for altered awareness), a few new generalized seizure types, ability to classify some seizures when onset is unknown, and renaming of certain terms to improve clarity of meaning. The attached PowerPoint slide set may be used without need to request permission for any non-commercial educational purpose meeting the usual "fair use" requirements. Permission from [email protected] is however required to use any of the slides in a publication or for commercial use. When using the slides, please attribute them to Fisher et al. Instruction manual for the ILAE 2017 operational classification of seizure types. Epilepsia doi: 10.1111/epi.13671.

ILAE 2017 Classification of Seizure Types Basic Version 1 Focal Onset Aware Impaired Awareness Motor Non-Motor Generalized Onset Motor Tonic-clonic Other motor Non-Motor (Absence) focal to bilateral tonic-clonic Unknown Onset Motor Tonic-clonic Other motor Non-Motor Unclassified 2 1 Definitions, other seizure types and descriptors are listed in the accompanying paper & glossary of terms 2 Due to inadequate information or inability to place in other categories From Fisher et al. Instruction manual for the ILAE 2017 operational classification of seizure types. Epilepsia doi: 10.1111/epi.13671

ILAE 2017 Classification of Seizure Types Expanded Version1 Generalized Onset Focal Onset Impaired Awareness Aware Motor tonic-clonic clonic tonic myoclonic myoclonic-tonic-clonic myoclonic-atonic atonic epileptic spasms2 Motor Onset automatisms 2 atonic clonic epileptic spasms2 hyperkinetic myoclonic tonic Non-Motor (absence) focal to bilateral tonic-clonic Motor tonic-clonic epileptic spasms Non-Motor behavior arrest Unclassified3 typical atypical myoclonic eyelid myoclonia Non-Motor Onset autonomic behavior arrest cognitive emotional sensory Unknown Onset 1 Definitions, other seizure types and descriptors are listed in the accompanying paper and glossary of terms. 2 These could be focal or generalized, with or without alteration of awareness 3 Due to inadequate information or inability to place in other categories From Fisher et al. Instruction manual for the ILAE 2017 operational classification of seizure types. Epilepsia doi: 10.1111/epi.13671

INTERNATIONAL CLASSIFICATION OF SEIZURES 1981 Partial Seizures (start in one place) Simple (no loss of consciousness of memory) Sensory Motor Sensory-Motor Psychic (abnormal thoughts or perceptions) Autonomic (heat, nausea, flushing, etc.) Complex (consciousness or memory impaired) With or without aura (warning) With or without automatisms Secondarily generalized Generalized Seizures (apparent start over wide areas of brain) Absence (petit mal) Tonic-clonic (grand mal) Atonic (drop seizures) Dreifuss et al. Proposal for revised clinical and Myoclonic electroencephalographic classification of epileptic seizures. From the Commission on Other Classification and Terminology of the Unclassifiable seizures International League Against Epilepsy. Epilepsia. 1981;22:489-501.

Motivation for Revision Some seizure types, for example tonic seizures or epileptic spasms, can have either a focal or generalized onset. Lack of knowledge about the onset makes a seizure unclassifiable and difficult to discuss with the 1981 system. Retrospective seizure descriptions often do not specify a level of consciousness, and altered consciousness, while central to many seizures, is a confusing concept. Some terms in current use do not have high levels of community acceptance or public understanding, such as “psychic,” “partial,” “simple partial,” “complex partial”, and “dyscognitive.” Some important seizure types are not included.

Possible Seizure Classifications Could be Based On: Pathophysiology Anatomy Networks Practical, by: Modify Existing But this is currently impossible with our limited understanding Temporal Frontal Parietal Occipital Diencephalic Brainstem Neocortical Limbic Thalamo-Cortical Brainstem AED response Surgical target Disabling EEG pattern Many others 1981 ILAE System 2010 ILAE update In the absence of fundamental knowledge, ILAE chose to extend the existing classification The is an operational (practical) system, not a true scientific classification Others might devise special operational classifications for specific use, e.g., neonatal, ICU This classification is predominantly for clinicians

How Do Clinicians Classify Seizures ? Elicit symptoms and signs of event (semiology) Look for familiar patterns in symptoms and signs Sometimes use ancillary data, e.g., EEG, MRI, genes, antibodies, etc. one-to many Symptoms Signs Seizure Type many-to-one examples automatisms focal impaired awareness seizure absence seizure automatisms autonomic focal impaired awareness seizure

Key Seizure Signs and Symptoms? Symptoms Medical Term automatic behaviors automatisms emotions or appearance of emotions emotions extension or flexion postures tonic flushing/sweating/piloerection autonomic jerking arrhythmically myoclonus jerking rhythmically clonus language or thinking problems, deja vu cognitive lid jerks eyelid myoclonia limp atonic numb/tingling, sounds, smells, tastes visions, vertigo sensations pausing, freezing, activity arrest behavior arrest thrashing/pedaling hyperkinetic trunk flexion spasm

The Elements of Change Allow some seizures to be either focal or generalized onset Classify seizures of unknown onset Clarify “impairment of consciousness” Include a few previously unclassified types Update word usage for greater public clarity Validate use of supportive information, e.g. EEG Conform with ICD 11 and 12 Update the 2001 glossary of seizure terms Standardize common descriptors to describe seizures Map old to new terms

The Elements of Change Allow some seizures to be either focal or generalized onset Classify seizures of unknown onset Clarify “impairment of consciousness” Include a few previously unclassified types Update word usage for greater public clarity Validate use of supportive information, e.g. EEG Conform with ICD 11 and 12 Update the 2001 glossary of seizure terms Standardize common descriptors to describe seizures Map old to new terms

Some Seizure Onsets can be Focal or Generalized Focal Onset Generalized Onset atonic atonic clonic clonic epileptic spasms epileptic spasms myoclonic myoclonic tonic tonic tonic-clonic tonic-clonic

The Elements of Change Allow some seizures to be either focal or generalized onset Classify seizures of unknown onset Clarify “impairment of consciousness” Include a few previously unclassified types Update word usage for greater public clarity Validate use of supportive information, e.g. EEG Conform with ICD 11 and 12 Update the 2001 glossary of seizure terms Standardize common descriptors to describe seizures Map old to new terms

Seizures of Unknown Onset Hypothetical case: You hear a noise and enter the video-EEG room to find the patient in bed, grunting, eyes rolled up, all limbs stiff, then rhythmically jerking for a minute. He was offcamera at the start. What seizure type is this? Some seizure types are worth describing even if onset is unknown: tonic-clonic epileptic spasms behavior arrest

The Elements of Change Allow some seizures to be either focal or generalized onset Classify seizures of unknown onset Clarify “impairment of consciousness” Include a few previously unclassified types Update word usage for greater public clarity Validate use of supportive information, e.g. EEG Conform with ICD 11 and 12 Update the 2001 glossary of seizure terms Standardize common descriptors to describe seizures Map old to new terms

Key Role of Impaired Consciousness Among many possible behaviors during a seizure, impairment of consciousness has always had a key role in classifying the seizure, because of practical importance for: Driving Safety during seizures Employability Interference with schooling and learning

Loss (or Impairment) of Consciousness Two types of seizures with loss of consciousness How well does the public understand LOC during a complex partial seizure?

Loss (or Impairment) of Consciousness Elements of consciousness Awareness of ongoing activities Memory for time during the event Responsiveness to verbal or nonverbal stimuli Sense of self as being distinct from others Which would be the best surrogate marker ? The 2017 Classification chooses awareness Consciousness remains in the classification but “awareness” is in the seizure name In several languages, these words are the same Awareness is not used to classify generalized onset seizures

The Elements of Change Allow some seizures to be either focal or generalized onset Classify seizures of unknown onset Clarify “impairment of consciousness” Include a few previously unclassified types Update word usage for greater public clarity Validate use of supportive information, e.g. EEG Conform with ICD 11 and 12 Update the 2001 glossary of seizure terms Standardize common descriptors to describe seizures Map old to new terms

New Seizure Types New Focal Seizures Motor Non-Motor atonic automatisms clonic epileptic spasms hyperkinetic myoclonic tonic behavior arrest (autonomic) (cognitive) emotional (sensory) New generalized seizures absence with eyelid myoclonia epileptic spasms (infantile spasms) myoclonic-atonic (e.g., Doose) myoclonic-tonic-clonic (e.g., JME) New combined seizures (focal to bilateral tonic-clonic) (parentheses) indicates prior existence, but renaming

The Elements of Change Allow some seizures to be either focal or generalized onset Classify seizures of unknown onset Clarify “impairment of consciousness” Include a few previously unclassified types Update word usage for greater public clarity Validate use of supportive information, e.g. EEG Conform with ICD 11 and 12 Update the 2001 glossary of seizure terms Standardize common descriptors to describe seizures Map old to new terms

Wording Changes OLD TERM NEW TERM Unconscious (still used, not in name) Partial Impaired awareness (surrogate) Simple partial Focal aware Complex partial Focal impaired awareness Dyscognitive (word discontinued) Focal impaired awareness Psychic Cognitive Focal Secondarily generalized tonic-clonic Focal to bilateral tonic-clonic Arrest, freeze, pause, interruption Behavior arrest

The Elements of Change Allow some seizures to be either focal or generalized onset Classify seizures of unknown onset Clarify “impairment of consciousness” Include a few previously unclassified types Update word usage for greater public clarity Validate use of supportive information, e.g. EEG Conform with ICD 11 and 12 Update the 2001 glossary of seizure terms Standardize common descriptors to describe seizures Map old to new terms

Supportive Information Seizures are usually classified by symptoms and signs But supportive information may be helpful, when available: Videos brought in by family EEG patterns Lesions detected by neuroimaging Laboratory results such as detection of anti-neuronal antibodies Gene mutations Diagnosis of an epilepsy syndrome diagnosis

The Elements of Change Allow some seizures to be either focal or generalized onset Classify seizures of unknown onset Clarify “impairment of consciousness” Include a few previously unclassified types Update word usage for greater public clarity Validate use of supportive information, e.g. EEG Conform with ICD 11 and 12 Update the 2001 glossary of seizure terms Standardize common descriptors to describe seizures Map old to new terms

ICD9, 10, 11, 12 ICD 9 & 10 are in use now with old terminology: petit mal, grand mal ICD 11 does not name seizure types, but ILAE syndromes and etiologies ICD 12 should conform to the new ILAE seizure type classification

The Elements of Change Allow some seizures to be either focal or generalized onset Classify seizures of unknown onset Clarify “impairment of consciousness” Include a few previously unclassified types Update word usage for greater public clarity Validate use of supportive information, e.g. EEG Conform with ICD 11 and 12 Update the 2001 glossary of seizure terms Standardize common descriptors to describe seizures Map old to new terms

Glossary: Full list in Epilepsia Paper WORD DEFINITION SOURCE absence, typical a sudden onset, interruption of ongoing activities, a blank stare, possibly a brief up- ward deviation of the eyes. Usually the patient will be unresponsive when spoken to. Duration is a few seconds to half a minute with very rapid recovery. Although not always available, an EEG would show generalized epileptiform discharges during the event. An absence seizure is by definition a seizure of generalized onset. The word is not synonymous with a blank stare, which also can be encountered with focal onset seizures. Adapted from 11 absence, atypical an absence seizure with changes in tone that are more pronounced Adapted from Dreifuss 1 than in typical absence or the onset and/or cessation is not abrupt, often associated with slow, irregular, generalized spike-wave activity arrest see behavioral arrest new atonic sudden loss or diminution of muscle tone without apparent preceding myoclonic or tonic event lasting 1 to 2 s, involving head, trunk, jaw, or limb musculature. 11 automatism a more or less coordinated motor activity usually occurring when cognition is impaired and for which the subject is usually (but not always) amnesic afterward. This often resembles a voluntary movement and may consist of an inappropriate continuation of preictal motor activity. 11

The Elements of Change Allow some seizures to be either focal or generalized onset Classify seizures of unknown onset Clarify “impairment of consciousness” Include a few previously unclassified types Update word usage for greater public clarity Validate use of supportive information, e.g. EEG Conform with ICD 11 and 12 Update the 2001 glossary of seizure terms Standardize common descriptors to describe seizures Map old to new terms

Common Descriptors of other symptoms and signs during seizures. These are not seizure types, just suggested descriptive words. A free text description is also highly encouraged.

The Elements of Change Allow some seizures to be either focal or generalized onset Classify seizures of unknown onset Clarify “impairment of consciousness” Include a few previously unclassified types Update word usage for greater public clarity Validate use of supportive information, e.g. EEG Conform with ICD 11 and 12 Update the 2001 glossary of seizure terms Standardize common descriptors to describe seizures Map old to new terms

Examples of Mapping Old to New Terms Full List in Epilepsia paper

Rules for Classifying Seizures (1 of 2) Onset: Decide whether seizure onset is focal or generalized, using an 80% confidence level. Awareness: For focal seizures, decide whether to classify by degree of awareness or to omit awareness as a classifier. Impaired awareness at any point: A focal seizure is a focal impaired awareness seizure if awareness is impaired at any point during the seizure. Onset predominates: Classify a focal seizure by its first prominent sign or symptom. Do not count transient behavior arrest. Behavior arrest: A focal behavior arrest seizure shows arrest of behavior as the prominent feature of the entire seizure. Motor/Non-motor: A focal aware or impaired awareness seizure maybe further sub-classified by motor or nonmotor characteristics. Alternatively, a focal seizure can be characterized by motor or non-motor characteristics, without specifying level of awareness. Example, a focal tonic seizure.

Rules for Classifying Seizures (2 of 2) Optional terms: Terms such as motor or non-motor may be omitted when the seizure type is otherwise unambiguous. Additional descriptors: It is encouraged to add descriptions of other signs and symptoms, suggested descriptors or free text. These do not alter the seizure type. Example: focal emotional seizure with tonic right arm activity and hyperventilation. Bilateral vs. generalized: Use the term “bilateral” for tonic-clonic seizures that propagate to both hemispheres and “generalized” for seizures that apparently originate simultaneously in both. Atypical absence: Absence is atypical if it has slow onset or offset, marked changes in tone or EEG spike-waves at less than 3 per second. Clonic vs. myoclonic: Clonic refers to sustain rhythmical jerking and myoclonic to a regular unsustained jerking. Eyelid myoclonia: Absence with eyelid myoclonia refers to forced upward jerking of the eyelids during an absence seizure.

The Net Effect The net effect of updating the Classification of Seizures should be the following: 1. Render the choice of a seizure type easier for seizures that did not fit into any prior categories; 2. Clarify what is meant when a seizure is said to be of a particular type; 3. Provide more transparency of terminology to the nonmedical community.

Examples 1. A woman awakens to find her husband having a seizure in bed. The onset is not witnessed, but she is able to describe bilateral stiffening followed by bilateral shaking. EEG and MRI are normal.

Examples Old unclassified New unknown onset tonic-clonic 1. A woman awakens to find her husband having a seizure in bed. The onset is not witnessed, but she is able to describe bilateral stiffening followed by bilateral shaking. EEG and MRI are normal. This seizure is classified as onset unknown tonic-clonic. There is no supplementary information to determine if the onset was focal or generalized. In the old classification, this seizure would have been unclassifiable.

Examples 2. In an alternate scenario of case #1, the EEG shows a clear right parietal slow wave focus. The MRI shows a right parietal region of cortical dysplasia.

Examples Old partial onset, secondarily generalized seizure New focal to bilateral tonic-clonic seizure 2. In an alternate scenario of case #1, the EEG shows a clear right parietal slow wave focus. The MRI shows a right parietal region of cortical dysplasia. In this circumstance, the seizure can be classified as focal to bilateral tonic-clonic, despite the lack of an observed onset, because a focal etiology has been identified, and the overwhelming likelihood is that the seizure had a focal onset. The old classification would have classified this seizure as partial onset, secondarily generalized seizure.

Examples 3. A child is diagnosed with Lennox-Gastaut syndrome of unknown etiology. EEG shows runs of slow spike-wave. Seizure types include absence and others.

Examples Old atypical absence seizures New atypical absence seizures 3. A child is diagnosed with Lennox-Gastaut syndrome of unknown etiology. EEG shows runs of slow spike-wave. Seizure types with this child include absence, tonic, and focal motor seizures. In this case, the absence seizures are classified as atypical absence (the word “generalized” may be assumed) due to the EEG pattern and underlying syndrome. The absence seizures would have had the same classification in the old system.

Examples 4. The same child as in #3 has seizures with stiffening of the right arm and leg, during which responsiveness and awareness are retained.

Examples Old tonic seizures New focal aware tonic seizures 4. The same child as in #3 has seizures with stiffening of the right arm and leg, during which responsiveness and awareness are retained. This seizure is a focal aware tonic seizures (the word “motor” can be assumed). In the old system, the seizures would have been called tonic seizures, with a perhaps incorrect assumption of generalized onset.

Examples 5: A 25 year old woman describes seizures beginning with 30 seconds of an intense feeling that “familiar music is playing.” She can hear other people talking, but afterwards realizes that she could not determine what they were saying. After an episode, she is mildly confused, and has to “reorient herself.”

Examples Old complex partial seizures New focal seizures with impaired awareness 5: A 25 year old woman describes seizures beginning with 30 seconds of an intense feeling that “familiar music is playing.” She can hear other people talking, but afterwards realizes that she could not determine what they were saying. After an episode, she is mildly confused, and has to “reorient herself.” The seizures would be classified as focal seizures with impaired awareness. Even though the patient is able to interact with her environment, she cannot interpret her environment, and is mildly confused.

Examples 6. A 22 year-old man has seizures during which he remains fully aware, with the “hair on my arms standing on edge” and a feeling of being flushed.

Examples Old simple partial autonomic seizures New focal aware autonomic seizures 6. A 22 year-old man has seizures during which he remains fully aware, with the “hair on my arms standing on edge” and a feeling of being flushed. These are classified as focal aware non-motor autonomic, or more succinctly focal aware autonomic. The old classification would have called them simple partial autonomic seizures.

Examples 7. A 4 year-old boy with myoclonic-atonic epilepsy (Doose syndrome) has seizures with a few arm jerks, then a limp drop to the ground.

Examples Old myoclonic astatic seizures New myoclonic-atonic seizures 7. A 4 year-old boy with myoclonic-atonic epilepsy (Doose syndrome) has seizures with a few arm jerks, then a limp drop to the ground. These are now classified as myoclonic-atonic seizures (the word “generalized” may be assumed). The old classification would have called these unclassified or unofficially, myoclonic-astatic seizures.

Examples 8. A 35 year-old man with juvenile myoclonic epilepsy has seizures beginning with a few bilateral arm jerks, followed by stiffening of all limbs and then rhythmic jerking of all limbs.

Examples Old myoclonic seizures followed by a tonic-clonic seizure New myoclonic-tonic-clonic seizures 8. A 35 year-old man with juvenile myoclonic epilepsy has seizures beginning with a few regularly-spaced jerks, followed by stiffening of all limbs and then rhythmic jerking of all limbs. This would be classified as generalized myoclonic-tonic-clonic seizures. No corresponding single seizure type existed in the old classification, but they might have been called myoclonic seizures followed by a tonic-clonic seizure.

Examples 9. A 14-month old girl has sudden flexion of both arms with head flexing forward for about 2 seconds. These seizures repeat in clusters. EEG shows hypsarrhythmia with bilateral spikes, most prominent over the left parietal region. MRI shows a left parietal dysplasia.

Examples Old infantile spasms (focality not specified) New focal epileptic spasms 9. A 14-month old girl has sudden flexion of both arms with head flexing forward for about 2 seconds. These seizures repeat in clusters. EEG shows hypsarrhythmia with bilateral spikes, most prominent over the left parietal region. MRI shows a left parietal dysplasia. Because of the ancillary information, the seizure type would be considered to be focal epileptic spasms (the term “motor” can be assumed). The previous classification would have called them infantile spasms, with information on focality not included.

Examples 10. A 75 year-old man reports an internal sense of body trembling. No other information is available.

The End “Words, words, words, I’m so sick of words!” Eliza Doolittle, My Fair Lady