Epileptic Seizures, Syndromes, and Classifications. Heidi Currier, MD Minnesota Epilepsy Group, PA St. Paul, MN
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2 Epileptic Seizures, Syndromes, and Classifications Heidi Currier, MD Minnesota Epilepsy Group, PA St. Paul, MN
3 Definitions
4 Diagnosis of Seizures A seizure is a sudden surge of electrical activity in the brain that usually affects how a person feels or acts for a short time.
5 Diagnosis of Seizures Potential Diagnosis of Seizures Seizures Reject (syncope, breath holding, loss of consciousness [LOC]) Acute cause? Yes Acute symptomatic No Unprovoked Febrile convulsions Only one Solitary seizure More than one Epilepsy Annegers
6 Diagnosis of Epilepsy After two unprovoked seizures (>24 hours apart), the chance of having another is 73% at four years, versus 40-52% after a single unprovoked seizure. Seizures clustering within 24 hours confer approximately the same risk for later seizures as does a single seizure Hauser WA, et al. NEJM Neligan A, et al. Handb Clin Neurol
7 Diagnosis of Epilepsy A single unprovoked seizure after a remote brain insult: stroke, CNS infection or trauma A single seizure in a patient with a cortical malformation A patient with a seizure and an epilepsy syndrome with a high risk of seizure recurrence A patient with photosensitive epilepsy: seizures are provoked by lights?? Risk of a second unprovoked seizure is comparable to the risk for further seizures after two unprovoked seizures Hauser WA, et al. N Engl J Med Hesdorffer DC, et al. Epilepsia
8 New Changes An Operational Clinical Definition of Epilepsy: At least two unprovoked (or reflex) seizures occurring more than 24 hours apart; One unprovoked (or reflex) seizure and a probability of recurrence risk approximately 60% or more; Diagnosis of an epilepsy syndrome. International League Against Epilepsy. Available at
9 New Changes Advantages: Patient education and access to resources Could improve outcomes by sensitizing clinicians about the risk of recurrence after a single unprovoked seizure Comfort initiating treatment after one unprovoked seizure Physical injuries or social consequences Expand the opportunity for disease modifying interventions that prevent the progression of epilepsy and onset of comorbidities
10 New Changes Disadvantages: Insurability National health programs Stigma to a larger number of people Driving in certain countries, participation in sports
11 Why Classify? Understanding the classification of seizures/epilepsy is the first step towards the correct diagnosis Investigations pursued may be different depending on seizure types Specific seizure types or epilepsy syndromes respond better to specific medications or surgical approaches Prognosis differs; early knowledge of this allows focused treatment and lifestyle modifications for patients and families
12 Who Classifies International League Against Epilepsy (ILAE): The authoritative source of current and emerging knowledge, serving as a leading information resource in optimal clinical care and for finding innovative approaches to addressing the many issues that are encountered in assuring that no one s life is limited by epilepsy
13 Classification 1960: ILAE first published a classification system 1981: The last official update for seizures 1989: The last official update for the epilepsies 2010: A report by the ILAE Commission on Classification and Terminology recommended that changes be made in the current conceptualization, terminology, and definitions of seizures and epilepsy 2016: Proposal for seizure classification and Road Map for Classification of the Epilepsies 2017: Two position papers published (Operational Classification of Seizure Types and Classification of Epilepsies)
14 Classification In between, there were many commissions, unsolicited advice, criticisms, invited critiques, etc Not a single classification system was felt to address the issues and concerns
15 Classification of Seizures Classified according to their: Clinical features Ictal EEG manifestation Interictal EEG features Commission on Classification and Terminology of the ILAE. Epilepsia
16 ILAE Seizure Classification : Generalized Partial Simple Complex Unclassified Other Status Epilepticus Post-1997: Self-limiting Generalized Focal Continuous Generalized Focal Precipitating Stimuli for Reflex Seizures Commission on Classification and Terminology of the ILAE. Epilepsia. 1981; Engel J Jr. Epilepsia
17 ILAE Classification of Epileptic Seizures PARTIAL SEIZURES Seizure Types SIMPLE PARTIAL SEIZURES Features EEG findings suggest focal onset Consciousness not impaired 1. With motor symptoms: Vocalization arrest of speech a. Focal motor b. Focal motor march (Jacksonian) c. Versive d. Postural e. Phonatory 2. With somatosensory or special sensory symptoms Simple hallucinations a. Somatosensory b. Visual c. Auditory d. Olfactory e. Gustatory f. Vertiginous 3. With autonomic symptoms or signs Epigastric sensations, pallor, sweating, flushing, piloerection, pupillary dilation 4. With psychic symptoms Disturbance of higher cortical function COMPLEX PARTIAL SEIZURES Consciousness impaired ABSENCE SEIZURES Typical absence Atypical absence MYOCLONIC SEIZURES CLONIC SEIZURES TONIC SEIZURES TONIC-CLONIC SEIZURES ATONIC SEIZURES *SWC = spike-wave complex Regular and symmetric 3-Hz *SWC on EEG Irregular slow SWC on EEG, abn Bkgrnd Polyspike or slow SWC on EEG Fast activity or slow SWC on EEG Low-voltage fast EEG Rhythm of less than 10 Hz on EEG Poly SWC or low-voltage fast Commission on Classification and Terminology of the ILAE. Epilepsia
18 Classification Why change? Previous classifications are based on concepts that predate modern neuroimaging, genomic technologies and concepts in molecular biology Provide a common international terminology and classification New classification should reflect best knowledge but will not be arbitrary and should ultimately serve the purpose of improving clinical practice and research
19 ILAE Proposal for Revised Terminology for Organization of Seizures and Epilepsies 2010 *No NN sz International League Against Epilepsy. ILAE Proposal for Revised Terminology for Organization of Seizures and Epilepsies Available at:
20 ILAE Proposal for Seizure Classification 2016 Fisher RS, et al. Operational classification of seizure types by the International League Against Epilepsy Available at:
21 ILAE Proposal for Seizure Classification 2017 Fisher RS, et al. Operational classification of seizure types by the International League Against Epilepsy Available at:
22 Focal - Reconceptualized For seizures: Focal epileptic seizures are conceptualized as originating within networks limited to one hemisphere. These may be discretely localized or more widely distributed. Ictal onset is consistent from one seizure to the other with preferential propagation patterns Berg AT, et al. Epilepsia
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24 Generalized - Reconceptualized For seizures Generalized epileptic seizures are conceptualized as originating at some point within, and rapidly engaging, bilaterally distributed networks. can include cortical and subcortical structures, but not necessarily include the entire cortex Although the onset may appear localized, the location and lateralization are not consistent from one seizure to the other Berg AT, et al. Epilepsia
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26 Focal Seizures Aware (knowledge of self or environment) Previous term: Simple partial Awareness: recall, responsiveness and consciousness maintained Fisher, et al Berg AT, et al. Epilepsia
27 Focal Seizures Impaired Awareness/Unaware Previous term: complex partial Dyscognitive Fisher, et al
28 Focal Seizures Evolving to bilateral, tonic clonic seizure Previous terms: partial seizure secondarily generalized; secondarily generalized tonic-clonic seizure With tonic, clonic, or tonic and clonic components Fisher, et al Berg AT, et al. Epilepsia
29 Issues with the New ILAE Report on Seizures Not a real change but some conceptual changes Definitions are not given for the different seizures types, so what they are and what they need to include is not clear Changed complex to dyscognitive because they felt the term was misused or misunderstood when they could have emphasized its meaning Free text description of types of focal seizures may be fine in clinical practice but problematic for research, epidemiology
30 Issues with the New ILAE Report on Seizures NN seizures are still difficult to categorize Spasms were included but with no definition of their features No reflex epilepsy category No status epilepticus category
31 Epilepsy Classification
32 ILAE 1989 Classification of Epilepsies and Epilepsy Syndromes Localization-related: Idiopathic, symptomatic, cryptogenic Generalized: Idiopathic, symptomatic, cryptogenic Epilepsies and syndromes undetermined whether focal or generalized With both generalized and focal: LKS, NNsz, SMEI, CSW Not clear if focal or generalized seizures Special syndromes: Situation related seizures isolated SE and febrile sz LKS=Landau-Kleffner Syndrome; NNsz=Neonatal Seizures; SMEI=Severe Myoclonic Epilepsy in Infancy; CSW=Continuous Spike Waves Commission on Classification and Terminology of the ILAE. Epilepsia
33 ILAE 1989 Classification of Epilepsies and Epilepsy Syndromes Idiopathic presumed genetic with an age-related onset, clinical and EEG characteristics Symptomatic known or suspected disorder Cryptogenic unknown but presumed symptomatic Commission on Classification and Terminology of the ILAE. Epilepsia
34 ILAE 1989 Classification of Epilepsies and Epilepsy Syndromes Localization related (focal, partial) Generalized Undetermined Idiopathic BECTS Childhood epilepsy with occipital spikes Primary reading epilepsy Symptomatic EPC Temporal epilepsy Frontal epilepsy Parietal epilepsy Occipital epilepsy Commission on Classification and Terminology of the ILAE. Epilepsia Cryptogenic Idiopathic Symptomatic Cryptogenic NN familial convulsion B NN convulsions B myoclonic epilepsy of infancy CAE JAE JME GTC upon awakening Other generalized idiopathic epilepsies With activation LGS West Myoclonic astatic Epilepsy with myoclonic absences EME EIEE With specific etiology: Aicardi
35 ILAE 1989 Classification of Epilepsies and Epilepsy Syndromes Defined each of these epilepsy syndromes: Age of onset, clinical features, EEG features, and prognosis Commission on Classification and Terminology of the ILAE. Epilepsia
36 Issues with the 1989 Classification Cannot be used by pediatricians or internists as classification requires EEG, video EEG Appeared better for pediatric epilepsies Some NN epilepsy syndromes were placed under generalized (benign familial NN convulsions) when they might include partial seizures
37 Issues with the 1989 Classification West syndrome/lgs was placed under generalized Idiopathic seemed to imply benign Symptomatic contrasts with subclinical
38 Major Changes in Classification, Terminology, and Concepts of Etiology 1989 Idiopathic: There is no underlying cause other than a possible hereditary predisposition Symptomatic: The epilepsy is the consequence of a known or suspected disorder of the CNS Cryptogenic: This refers to a disorder whose cause is hidden or occult. Cryptogenic epilepsies are presumed to be symptomatic 2010 Genetic: The epilepsy is the direct result of a known or presumed genetic defect in which seizures are the core symptom Structural/metabolic: There is a structural or metabolic condition that is associated with a substantially increased risk of developing epilepsy Unknown: The nature of the underlying cause is unknown; it may be due to an unidentified genetic, structural, or metabolic disorder Commission on Classification and Terminology of the ILAE. Epilepsia. 1981; Commission on Classification and Terminology of the ILAE. Epilepsia. 1989; Berg AT, et al. Epilepsia. 2010; Berg AT, et al. Epilepsia. 2011; Scheffer IE, et al. Epilepsa Genetic: Refers to a pathogenic variant (mutation) of significant effect in causing the individual s epilepsy Structural: Refers to abnormalities visible on structural neuroimaging where the electroclinical assessment together with the imaging findings lead to a reasonable inference that the imaging abnormality is the likely cause of the patient s seizures Metabolic: Results directly from a known or presumed metabolic disorder in which seizures are a core symptom of the disorder Immune: Results directly from an immune disorder in which seizures are a core symptom of the disorder Infectious: Results from a known infection in which seizures are a core symptom of the disorder Unknown
39 Genetic Concept: Refers to a pathogenic variant (mutation) of significant effect in causing the individual s epilepsy Genetic Inherited Evidence: Specific molecular genetic studies (well replicated) or evidence from appropriately designed family studies Berg AT, et al. Epilepsia. 2011; Scheffer IE, et al. Epilepsia
40 Structural Concept: Refers to abnormalities visible on structural neuroimaging where the electroclinical assessment together with the imaging findings lead to a reasonable inference that the imaging abnormality is the likely cause of the patient s seizures Eg, Tuberous sclerosis May be caused by genetic or infectious etiologies as well Evidence: Must have demonstrated a substantially increased risk of developing epilepsy in association with the condition Scheffer IE, et al. Epilepsia
41 Metabolic Concept: Results directly from a known or presumed metabolic disorder in which seizures are a core symptom of the disorder May be associated with a genetic defect Evidence: Must have demonstrated a substantially increased risk of developing epilepsy in association with the condition Scheffer IE, et al. Epilepsia
42 Unknown Concept: The nature of the underlying cause is as yet unknown Berg AT, et al. Epilepsia
43 Classification of Epilepsy Syndromes Constellations Epilepsies associated with a structural/metabolic condition Epilepsies of an unknown cause Berg AT, et al. Epilepsia
44 2017 Definition Updates Epileptic encephalopathy Developmental and epileptic encephalopathy Term should be used where appropriate and applied to individuals of any age Developmental: developmental impairment without frequent epileptic activity associated with regression or further slowing of development Epileptic: no preexisting developmental delay and the genetic mutation is not thought to cause slowing in its own right Developmental and epileptic: both factors play a role Benign self-limited or pharmacoresponsive Self-limited: syndrome will likely spontaneously resolve Pharmacoresponsive: the epilepsy syndrome will likely be controlled with appropriate antiepileptic therapy The terms malignant and catastrophic will no longer be used
45 Epilepsy Syndromes
46 Epilepsy Syndromes Why? Patients with epileptic seizures and their families are entitled to diagnosis, prognosis, and management that is specific and precise Medication choices (some AEDs may worsen certain seizure types) Defining the syndrome improves research, and ultimately improves treatment in all aspects
47 Epilepsy Syndromes Seizure type(s) EEG characteristics Age of onset and associated clinical findings Imaging (MRI, CT, etc.) Additional laboratory testing Etiology: Although it may not be uniform
48 Classification of the Epilepsies and Epilepsy Syndromes Epilepsy syndromes: Some syndromes represent a single disease eg, Autosomal dominant nocturnal frontal lobe epilepsy Some syndromes can be result of many diseases eg, West syndrome, Lennox-Gastaut syndrome Some diseases can manifest in different epilepsy syndromes eg, Tuberous Sclerosis Complex Some syndromes may have different outcomes eg, Infantile spasms
49 Childhood Epilepsy Syndromes Juvenile absence GTCS on awakening Childhood absence Rolandic epilepsy Lennox-Gastaut syndrome Simple febrile seizures Benign myoclonic epilepsy Infantile spasms EMEE/EIEE Neonatal seizures JME (13-19) (1-2) (6 mo-1) (0-6 wk) (0-1 mo) (3-7) (6 mo-5) (1-8) (4-13) (10-15) (6-22) Age (y) at Seizure Onset Pellock JM. Neurol Clin
50 Childhood Epilepsy Syndromes Childhood absence epilepsy Juvenile absence epilepsy Juvenile myoclonic epilepsy Self-limited epilepsy with centrotemporal spikes Infantile spasms Lennox-Gastaut syndrome
51 Childhood Absence Epilepsy Age of onset: 3-6 years Seizures very frequent Abrupt onset with loss of consciousness Abrupt end with resumption of activity No postictal period, child often unaware of seizure Automatisms, blinking can occur EEG Ictal: 3 Hz spike and wave, symmetric and synchronous Interictal: normal Induced by hyperventilation, occasionally photic stimulation
52 Pediatric Epilepsy Syndromes: Absence Epilepsy
53 Absence Seizure: 3 Hz Spike and Wave
54 Juvenile Absence Epilepsy Age of onset: 7-17 years Lower seizure frequency than CAE; less frequent than every day, may be sporadic Majority (80%) have GTC seizures, upon awakening, which usually precede absences EEG: Ictal: Hz generalized discharges Interictal: normal Typically responsive to therapy;?lifelong
55 Juvenile Myoclonic Epilepsy of Janz (JME) Mixed seizure disorder: Myoclonic Generalized tonic clonic (GTC) Absence seizures Familial disorder Onset usually in the second decade? Lifelong
56 Juvenile Myoclonic Epilepsy: Myoclonic Seizures Usually mild to moderate in intensity, may involve entire extremity rather than isolated muscles, generally bilateral Occur after awakening Aggravated by fatigue, sleep deprivation or EtOH May fall or drop objects Myoclonic status epilepticus can occur
57 Juvenile Myoclonic Epilepsy: Generalized Tonic-Clonic Seizures GTC or clonic-tonic-clonic seizures common 41/43 in series of Delgado-Escueta 83% in series of Asconape and Penry Myoclonic jerks precede GTC in majority, and may evolve into GTC Occur shortly after awakening or during early morning sleep Delgado-Escueta AV, Enrile-Bacsal F. Neurology. 1984; Asconape J, Penry JK. Epilepsia
58 Juvenile Myoclonic Epilepsy: Absence Seizures Occur in a significant number: 40% on the series of Delgado-Escueta Usually occur in association with GTC or CTC seizures Most commonly occur shortly after awakening Delgado-Escueta AV, Enrile-Bacsal F. Neurology
59 Juvenile Myoclonic Epilepsy: The EEG Interictal EEG: 3.5 to 6 Hz spike and wave and multiple spike and wave complexes With myoclonic seizures: Ictal EEG consists of Hz rapid spikes with slow waves Photosensitivity common Abnormality may only appear in sleep
60
61 Self-limited Epilepsy with Centrotemporal Spikes Age of Onset: 3-13 years with peak at 7-8 years Seizure frequency typically low: 13% single seizure 66% infrequent 21% frequent (Lerman and Kivity) Nocturnal seizures only in 50%, both waking and sleep in 15%, waking only in 10%-20% Status epilepticus is rare Lerman P, Kivity S. Arch Neurol. 1975; Scheffer IE, et al. Epilepsia
62 Clinical Characteristics of Self-limited Epilepsy with Centrotemporal Spikes Oral/Buccal/Lingual paresthesias Speech arrest Preservation of consciousness Sialorrhea Tonic or clonic facial movements Lerman P, Kivity S. Arch Neurol. 1975; Scheffer IE, et al. Epilepsia
63 Self-limited Epilepsy with Centrotemporal Spikes: EEG Characteristics Interictal EEG: Distinctive, high amplitude, diphasic spike or sharp wave with prominent slow wave Midtemporal (T3,T4) and Central (C3,C4) Bilateral, independent Marked Sleep-Activation Horizontal Dipole present Lerman P, Kivity S. Arch Neurol. 1975; Scheffer IE, et al. Epilepsia
64
65 Problems with the New ILAE Report Some clear epilepsy syndromes (CAE, etc) are mixed in the same bag as heterogeneous disorders (LGS) Didn t offer any new definitions or even definitions of the syndromes
66 Framework for Epilepsy Classification Scheffer IE, et al. Epilepsia
67 Other Terms Commonly Used Remote symptomatic Lesional/non-lesional Temporal/extratemporal
68 Patients will Forever Divide their Seizures into Two Types Petit mal Grand mal
69 Thank You!
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