Epileptic Seizures, Syndromes and Classifications Seizures, Syndromes and Classifications Randa...

Epileptic Seizures, Syndromesand Classifications

Randa Jarrar, MDChild Neurologist

Phoenix Children's HospitalClinical Assistant Professor, Department of Pediatrics

University of ArizonaAssistant Professor, Department of Neurology

Mayo Graduate School of MedicinePhoenix, Arizona

Definitions

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.

Annegers. 1997.

Potential Diagnosis of Seizures

Reject (syncope, breath holding, loss of consciousness [LOC])

Acute cause?

Yes No

Acute symptomatic

Febrile convulsions

Unprovoked

Only one

Solitary seizure

More than one

Epilepsy

Seizures

Diagnosis of Seizures

• 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. 1998.Neligan A, et al. Handb Clin Neurol. 2012.

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. 1998.Hesdorffer DC, et al. Epilepsia. 2009.

Diagnosis of Epilepsy

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: http://www.ilae.org/visitors/centre/Definition-2014.cfm.

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

New Changes

• Disadvantages:– Insurability– National health programs– Stigma to a larger number of people– Driving in certain countries, participation in sports

Status Epilepticus

• A condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms, which lead to abnormally, prolonged seizures (after time point t1).

• It is a condition, which can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures.

Trinka E, et al. Epilepsia. 2015.

Back to Classification

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

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

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

http://www.ilae.org/visitors/centre/Class-Roadmap.cfm

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

Classification

• One has to be familiar with the old, the new, and the ugly

Classification of Seizures - 1981

• Classified according to their:– Clinical features– Ictal EEG manifestation– Interictal EEG features

Commission on Classification and Terminology of the ILAE. Epilepsia. 1981.

ILAE Seizure Classification 1981

1981: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. 2001.

ILAE Classification of Epileptic SeizuresSeizure Types Features

PARTIAL SEIZURES EEG findings suggest focal onset

SIMPLE PARTIAL SEIZURES Consciousness not impaired1. With motor symptoms: Vocalization arrest of speech

a. Focal motorb. Focal motor march

(Jacksonian)

c. Versived. Posturale. Phonatory

2. With somatosensory or special sensory symptoms Simple hallucinationsa. Somatosensoryb. Visualc. Auditory

d. Olfactorye. Gustatoryf. Vertiginous

3. With autonomic symptoms or signs Epigastric sensations, pallor, sweating, flushing, piloerection, pupillary dilation

4. With psychic symptoms Disturbance of higher cortical functionCOMPLEX PARTIAL SEIZURES Consciousness impaired

ABSENCE SEIZURESTypical absence Regular and symmetric 3-Hz *SWC on EEGAtypical absence Irregular slow SWC on EEG, abn Bkgrnd

MYOCLONIC SEIZURES Polyspike or slow SWC on EEG

CLONIC SEIZURES Fast activity or slow SWC on EEG

TONIC SEIZURES Low-voltage fast EEG

TONIC-CLONIC SEIZURES Rhythm of less than 10 Hz on EEG

ATONIC SEIZURES Poly SWC or low-voltage fast*SWC = spike-wave complex Commission on Classification and Terminology of the ILAE. Epilepsia. 1981.

ILAE Seizure Classification

1981: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. 2001.

Issues with 1981 Classification• Some seizure types (tonic or epileptic spasms) can have

either a focal or generalized onset• Lack of knowledge about the onset makes a seizure

unclassifiable with the 1981 system• A need to move away from preservation or alteration of

awareness, responsiveness or consciousness as the only descriptor of a focal seizure (although it remains an important classifier)

• 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 (myoclonic absence)

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

International League Against Epilepsy. ILAE Proposal for Revised Terminology for Organization of Seizures and Epilepsies 2010. Available at:

http://www.ilae.org/commission/class/documents/ILAE%20HandoutV10.pdf

ILAE Proposal for Revised Terminology for Organization of Seizures and Epilepsies 2010

*No NN sz

Fisher RS, et al. Operational classification of seizure types by the International League Against Epilepsy. 2016. Available at: http://www.ilae.org. 2016

ILAE Proposal for Seizure Classification 2016

Major Changes in Classification, Terminology, and Concepts: For Seizures

OLD TERMINOLOGY & CONCEPTS

• Partial: The first clinical and EEG changes indicate initial activation of a system of neurons limited to a part of one cerebral hemisphere

• Generalized: The first clinical changes indicate initial involvement of both hemispheres

NEW TERMINOLOGY & CONCEPTS

• Focal seizures are conceptualized as originating at some point within networks limited to one hemisphere

• Generalized seizures are conceptualized as originating at some point within and rapidly engaging bilaterally distributed networks

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.

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. 2010.

Major Changes in Classification, Terminology, and Concepts: For Seizures

• Partial: The first clinical and EEG changes indicate initial activation of a system of neurons limited to a part of one cerebral hemisphere

• Generalized: The first clinical changes indicate initial involvement of both hemispheres

• Focal seizures are conceptualized as originating at some point within networks limited to one hemisphere

• Generalized seizures are conceptualized as originating at some point within and rapidly engaging bilaterally distributed networks

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

Major Changes in Classification of Focal Seizure Types

• Complex Partial: With impairment of consciousness

• Simple Partial: Consciousness not impaired

• Secondarily Generalized: Note that this was not the terminology used in the 1981 document but has come into common use

• No specific classification is recommended – Seizures should be described

accurately according to their semiologic features without trying to fit them into artificial categories

Focal Seizures

• Aware (without impairment of consciousness or awareness)– Previous term: Simple partial– With observable motor or autonomic components

• Eg, focal clonic, autonomic, hemiconvulsive– With subjective sensory or psychic phenomena

• Aura - specific types

– Awareness: recall, responsiveness and consciousness maintained

Berg AT, et al. Epilepsia. 2010.Fisher, et al. www.ilae.org. 2016.

• Unaware (where alteration of cognition is major feature)– Previous term: complex partial– Dyscognitive

Focal Seizures

Fisher, et al. www.ilae.org. 2016.

• Evolving to bilateral, tonic clonic (convulsive) seizure– Previous terms: partial seizure secondarily

generalized; secondarily generalized tonic-clonicseizure

– With tonic, clonic, or tonic and clonic components

Focal Seizures

Fisher, et al. www.ilae.org. 2016.

Focal Seizures

• Without impairment of consciousness or awareness– Previous term: Simple partial– With observable motor or autonomic components

• Eg, focal clonic, autonomic, hemiconvulsive– With subjective sensory or psychic phenomena

• Aura - specific types

• Where alteration of cognition is major feature– Previous term: complex partial– Dyscognitive

Focal Seizures

• Evolving to bilateral, convulsive seizure– Previous terms: partial seizure secondarily

generalized;secondarily generalized tonic-clonic seizure

– With tonic, clonic or tonic and clonic components

Focal Seizures

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

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

ILAE 1989 Classification of Epilepsies and Epilepsy Syndromes

• Two criteria utilized: Topography (generalized or localization-related) and etiology (idiopathic, symptomatic, cryptogenic)

• 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

• Idiopathic presumed genetic with an age-related onset, clinical and EEG characteristics

• Symptomatic known or suspected disorder• Cryptogenic unknown but presumed symptomatic

Localization related (focal, partial)

Idiopathic Symptomatic

• BECTS• Childhood

epilepsy with occipital spikes

• Primary reading epilepsy

• EPC• Temporal

epilepsy• Frontal epilepsy• Parietal epilepsy• Occipital

epilepsy

Cryptogenic

Generalized

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…

Undetermined

• Defined each of these epilepsy syndromes: Age of onset, clinical features, EEG features, and prognosis

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

Issues with the 1989 Classification

• West syndrome/LGS was placed under generalized

• Idiopathic seemed to imply benign• Secondarily generalized• Symptomatic contrasts with subclinical• MTS

2010 Major Changes in Classification, Terminology, and Concepts of Etiology

• 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 central nervous system

• Cryptogenic: This refers to a disorder whose cause is hidden or occult. Cryptogenic epilepsies are presumed to be symptomatic

• 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

2010 Recommended Terminology for Etiology

Use terms which mean what they say:

• Genetic• Structural/Metabolic • Unknown

Genetic

• Concept: The epilepsy is the direct result of a known or inferred genetic defect(s). Seizures are the core symptom of the disorder

• Evidence: Specific molecular genetic studies (well replicated) or evidence from appropriately designed family studies

• Genetic does not exclude the possibility of environmental factors contributing

Structural/Metabolic

• Concept: There is a distinct other structural or metabolic condition or disease present – Eg, Tuberous sclerosis

• Evidence: Must have demonstrated a substantially increased risk of developing epilepsy in association with the condition

Unknown

• Concept: The nature of the underlying cause is as yet unknown

Classification: Old vs. New Organizational Structure for Epilepsies

• Localization-related (focal, partial): Epilepsies with focal seizures

• Generalized: Epilepsies with generalized seizures

• These terms were abandoned as overreaching categories for classifying epilepsies per se, as many syndromes include both seizure types; they may still apply in some, but not all instances (Dravet and West)

Classification: Old vs. New Organizational Structure for Epilepsies

• Hierarchically organized by localization-related, generalized, and undetermined

• Within those groups, by etiology (idiopathic, symptomatic, cryptogenic)

• No specific organization is proposed. Instead a flexible approach depending on needs is advocated

Classification of Epilepsy

• Syndromes• Constellations• Epilepsies associated with a

structural/metabolic condition• Epilepsies of an unknown cause

International League Against Epilepsy. Available at: http://www.ilae.org/commission/class/documents

/ILAE%20HandoutV10.pdf. Accessed July 2016.

ILAE Proposal for Revised Terminology for Organization of Seizures and Epilepsies 2010

* The arrangement of electroclinical syndromes does not reflect etiology,^ Not traditionally diagnosed as epilepsy+ Sometimes referred to as Electrical Status Epilepticus during Slow Sleep (ESES)** Forms of epilepsies not meeting criteria for specific syndromes or constellations

Epilepsy Syndromes

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

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

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

Childhood Epilepsy Syndromes

Neonatal seizuresEMEE/EIEE

Infantile spasmsBenign myoclonic epilepsy

Simple febrile seizuresLennox-Gastaut syndrome

Rolandic epilepsyChildhood absence

GTCS on awakeningJuvenile absence

JME (13-19)(10-15)

(6-22)(3-7)

(4-13)(1-8)

(6 mo-5)(1-2)

(6 mo-1)(0-6 wk)(0-1 mo)

0 5 10 15 20 25

Age (y) at Seizure Onset

Pellock JM. Neurol Clin. 1993.

Benign vs Malignant Epilepsy Syndromes

• Benign: Typically have a good developmental outcomes

• Malignant: Typically have a poor outcomes

• Caveat: • Not every malignant syndrome has a poor

outcomes• Not every benign syndrome has a good outcomes

Benign vs Malignant Epilepsy Syndromes

• Benign Syndromes:• Childhood absence epilepsy• Juvenile absence epilepsy• Juvenile myoclonic epilepsy• Benign childhood epilepsy with centrotemporal spikes

(Rolandic)

• Malignant Syndromes:• Infantile spasms• Lennox-Gastaut syndrome

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

Absence Seizure: 3 Hz Spike and Wave

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: 3.5-4 Hz generalized discharges• Interictal: normal

• Typically responsive to therapy; ?lifelong

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

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

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. 1984.

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. 1984.

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 10-16 Hz rapid spikes with slow waves

• Photosensitivity common• Abnormality may only appear in sleep

• 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

Benign Childhood Epilepsy with Centrotemporal Spikes

Lerman P, Kivity S. Arch Neurol. 1975.

Clinical Characteristics of Benign Epilepsy with Centrotemporal Spikes

• Oral/Buccal/Lingual paresthesias• Speech arrest• Preservation of consciousness• Sialorrhea• Tonic or clonic facial movements

Benign 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

Benign Occipital Epilepsy

• Age of Onset: 15 months to 17 years with peak between 5 and 7 years

• Symptoms and Course: Dependent on time when seizures occur: motor symptoms predominate when nocturnal, visual predominate if diurnal

• Seizure Duration and Frequency: Variable• Headaches and vomiting occur - Migraine in the

differential

• VISUAL: – Amaurosis, elementary

or complex visual hallucinations

• Visual illusions including micropsia, metamorphopsia, or pallinopsia

• Rare in younger children

• MOTOR: – Hemiclonic in 43%; – CPS in 14%– GTC in 13% – Other in 25% (dysphasia,

adversive seizures, dysesthesias)

Clinical Manifestations Benign Occipital Epilepsy

Epilepsy Constellations

• Not exactly electroclinical syndromes• Age of presentation is not a defining feature• Have specific lesions or causes• Have implications on treatment esp surgery• Mesial temporal lobe epilepsy, hypothalamic

hamartoma, Rasmussen

Problems with the New ILAE Report

• There is really no new classification, different organization

• May confuse the wider community• Better to keep idiopathic and add genetic• The category structural and metabolic may

include epilepsies that are neither degenerative or autoimmune

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

Proposed Framework for Epilepsy Classification

http://www.ilae.org/visitors/centre/Class-Roadmap.cfm

Other Terms Commonly Used

• Remote symptomatic• Lesional/non-lesional• Temporal/extratemporal

How Well Do These Systems Work

• Bodensteiner JB, et al. 1988: Classified 2219 descriptions of childhood seizures. Low overall agreement between observers, mainly because of poor details

• Ottman R, et al. 1993: Structured interview. Almost perfect agreement for partial seizures. Moderate to substantial agreement for generalized seizures

Bodensteiner JB, et al. Epilepsia. 1988; Ottman R, et al. Neurology. 1993.

• Senanayke N. 1993: 1250 adult patients, only 5.4% couldn’t be classified (BUT 65% were in undetermined group!!)

• Shah KN, et al. 1992: 483 children, 6% of seizures and 13.5% of epilepsy syndrome could not be classified

• Manford M, et al. 1992: When applied by GPs in England, only 33.6% were given specific diagnosis

Senanayke N. Epilepsia. 1993; Shah KN, et al. Epilepsia. 1992. Manford M, et al. Arch Neurol. 1992.

Several authors found that it works poorly in neonates mainly because consciousness could not be assessed.

Patients will Forever Divide their Seizures into Two Types

• Petit mal• Grand mal

Thank You!

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