Annual Fundamentals Symposium

Annual Fundamentals Symposium
The
New Definition and Classification of Epilepsy
Symposium Chair:
Robert Fisher, M.D., Ph.D.
Friday, December 2, 2016

Convention Center – General Assembly
12:30 – 3:00 p.m.

EDUCATION CREDITS
Accreditation Claiming CME Credit and CME Certificates

The American Epilepsy Society is accredited Attendees who registered in the following categories may claim
by the Accreditation Council for Continuing CME or CE for the meeting: physician, health care provider,
Medical Education (ACCME) to provide trainee, one-day and two-day. Meeting registration includes
continuing medical education for physicians. credit claiming: there is no separate fee to claim CME/CE.
Attendees will receive an emailed notification to access the
AMA Credit Designation Statement online evaluation and credit claim system.
The American Epilepsy Society designates this live activity for a The evaluation and credit claim system will remain open
maximum of 29.50 AMA PRA Category 1 Credits™. Physicians through Tuesday, February 28, 2017. Evaluations and credit
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determined that non-U.S. licensed physicians who participate in
A meeting attendance certificate will be available at the
this CME activity are eligible for a maximum of 29.50 AMA PRA
registration desk for international meeting attendees on
Category 1 Credits™.
Tuesday, December 6.
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for educational activities certified for AMA PRA Category 1 Resolution of Conflicts of Interest
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recognized state medical society. Physician assistants may balance, independence, objectivity and scientific rigor. All
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apparent conflicts of interest. In accordance with the ACCME
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23
American Epilepsy Society | www.AESnet.org | Houston, Texas 70th Annual Meeting | 6th Biennial North American Regional Epilepsy Congress
OVERVIEW
This session will review the 2014 new definition of epilepsy, the new International League Against Epilepsy
(ILAE) classification of seizures and epilepsy (these are official ILAE positions), the presentation and prognosis of
acute symptomatic seizures and possible scientific underpinnings of the definition and classification of seizures.
Participants will become familiar with application of the definition of epilepsy and new classification system for
seizures. Familiarity with these areas will allow better determination in practice of who has epilepsy, who has
outgrown it, what type of seizures they have and when seizures are “reactive.”
LEARNING OBJECTIVES
Following participation in this symposium, learners should be able to:
• Review and discuss the ILAE definition of epilepsy and how it impacts clinical practice
• Differentiate between epilepsy and an epilepsy syndrome
• Recognize when a seizure is precipitated by an antecedent event rather than being an unprovoked seizure.
• Classify seizures according to the ILAE Operational
• Classification of Seizure Types system.
TARGET AUDIENCE
Intermediate: Epilepsy fellows, epileptologists, epilepsy neurosurgeons, and other providers with experience in
epilepsy care (e.g., advanced practice nurses, nurses, physician assistants), neuropsychologists, psychiatrists,
basic and translational researchers.
PROGRAM
Chair: Robert Fisher, M.D., Ph.D.
Introduction
New Definition of Epilepsy

Jacqueline French, M.D.
New Classification of Seizure Types

Robert Fisher, MD, Ph.D.
New Roadmap for Epilepsy

Ingrid Scheffer, M.D., Ph.D.
New Insights about Acute Symptomatic Seizures

Dale Hesdorffer, Ph.D.
Towards a Scientific Basis for Definition and Classification of Epilepsy

Ivan Soltesz, Ph.D.
Conclusions
Education Credit
2.5 CME Credits
Nurses may claim up to 2.5 contact hours for this session.

Pharmacy Credit
AKH Inc., Advancing Knowledge in Healthcare approves this knowledge-based activity for 2.5 contact
hours (0.25 CEUs). UAN 0077-9999-16-083-L01-P. Initial Release Date: 12/2/16.
Commercial Support Acknowledgement

Supported in part by an educational grants from Eisai Inc., Lundbeck, and Supernus Pharmaceuticals, Inc.
FACULTY/PLANNER DISCLOSURES
It is the policy of the AES to make disclosures of financial relationships of faculty, planners and staff involved in
the development of educational content transparent to learners. All faculty participating in continuing medical
education activities are expected to disclose to the program audience (1) any real or apparent conflict(s) of
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disclosure by faculty of commercial relationships, if any, and discussions of unlabeled or unapproved uses will
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FACULTY / PLANNER BIO AND DISCLOSURES

Robert S. Fisher, MD, PhD, Chair and Faculty
Professor of neurology
Stanford University School of Medicine
Dr. Fisher is Maslah Saul MD Professor and Director of the Stanford Epilepsy Center and EEG lab. He received
awards from the Klingenstein Foundation, Epilepsy Foundation, CURE and NIH. He has published about 220
peer-reviewed articles and 3 books. He was named from 1996 to 2016 in Best Doctors in America. He received
the Ambassador Award from ILAE, the 2005 American Epilepsy Society Service Award and the 2006 Annual
Clinical Research Award. Dr. Fisher is Past-President of the American Epilepsy Society, and has served on the
Board of the ILAE and as Editor-in-Chief of the Journal, Epilepsia. He is past Editor-in-Chief of epilepsy.com. Dr.
Fisher led the project to develop a formal definition of who has epilepsy and an update of seizure type
classification. His recent research is on new devices to detect and treat seizures.
Dr. Fisher discloses receiving support for Stockholder/Ownership Interest (excluding diversified mutual funds):
Applied Neurometrics, Avails Medical, Cerebral Therapeutics, Smart-Monitor, Zeto, Inc.
Jacqueline A. French, MD, Faculty

Professor
New York University School of Medicine
Dr Jacqueline French is a Professor of Neurology at NYU. She has served as President of the American Epilepsy
Society, Chair of the ILAE North American Commission, Secretary of the American Society of Experimental
Neurotherapeutics, and is currently serving as Chief Scientific Officer of the Epilepsy Foundation.
Dr French’s career has focused on development of new therapies for epilepsy. She created and serves as the
president of the Epilepsy Study Consortium, a non-profit devoted to speeding new therapies to people who
need them. She has been the principle investigator on studies for many new AEDs that have recently been
approved. She recieved the AES Service award, and the Epilepsy Foundation’s Hero award. She is the author of
over 200 articles and book chapters and lectures internationally on her work.
Dr. French discloses receiving support for Consulting Fees (e.g., advisory boards): Adamas, Anavex; Contracted
Research: Acorda, Adamas, Alexza, Eisai, Epilepsy Foundation, Epilepsy Study Consortium, Neurelis, Novartis
Pharmaceuticals, Pfizer, SK LifeScience, Sunovion, Takeda, UCB Pharma; Salary: Ep
Dale C. Hesdorffer, MPH, MPhil, PhD, Faculty
Professor of Epidemiology
GH Serviesy Center and Department of Epidemiology, Columbia University
Dr. Dale Hesdorffer, PhD is a Professor of Epidemiology at the Gertrude H Sergievsky Center and Department of
Epidemiology. She has written on a broad range of topics of interest in the epidemiology of epilepsy. Papers
include risk factors for developing epilepsy, consequences of prolonged febrile seizures, epilepsy comorbidities,
and mortality in epilepsy including SUDEP. She has also written on diuretics as prevention of epilepsy in the
elderly. Her studies of incidence include epilepsy and single unprovoked seizure, acute symptomatic seizures,
the effect of status epilepticus on incident epilepsy and subsequent mortality. She has been a member of the
Commission on Epidemiology of the International League Against Epilepsy (ILAE) and co-chairs the Comorbidity
Task Force.
Dr. Hesdorffer discloses receiving support for Consulting Fees (e.g., advisory boards): Cyberonics, Upsher-Smith
Laboratories
Ingrid E. Scheffer, MBBS PHD FRACP FAA, Faculty

Professor
Epilepsy Research Center, Department of Medicine
University of Melbourne, Austin Health, Heidelberg, Victoria Australia
Professor Ingrid Scheffer
AO MBBS PhD FRACP FAHMS FAA Chair of Paediatric Neurology Research
University of Melbourne; Director of Paediatrics, Austin Health.
Professor Scheffer’s work has led the field of epilepsy genetics over 25 years. She has led the first
reclassification of the epilepsies in two decades as Chair of the ILAE Commission for Classification. Her awards
include AES Clinical Research Award, L’Oréal-UNESCO Women in Science Laureate (Asia-Pacific), co-recipient of
the Prime Minister’s Prize for Science and received an Order of Australia. She is a Fellow of the Australian
Academy of Science and the Australian Academy of Health and Medical Sciences.
Dr. Scheffer discloses she has no financial relationships to disclose relevant to this activity.
Ivan Soltesz, PhD, Faculty

James R. Doty Professor of Neurosurgery and Neurosciences
Stanford University
Ivan Soltesz Ph.D. is currently the James R. Doty Professor of Neurosurgery and Neurosciences in the School of
Medicine at Stanford University. His major research interest is focused on neuronal microcircuits, network
oscillations, cannabinoid signaling and the mechanistic bases of circuit dysfunction in epilepsy. He was the
recipient of the NIH Javits Neuroscience Investigator Award, the American Epilepsy Society’s Research
Recognition Award and the international Michael Prize for basic research in epilepsy.
Dr. Soltesz discloses he has no financial relationships to disclose relevant to this activity.
CME REVIEWERS
Juliann Paolicchi, MD, MA, Reviewer
Juliann M Paolicchi, MA, MD, FANA is the Director of Pediatric Epilepsy for New York for the Northeast Regional
Epilepsy Group, a multi-disciplinary both private and academic based epilepsy group. She is a Clinical Professor
of Pediatric Neurology at Rutgers University Medical Center. Dr. Paolicchi is boarded by the ABPN in Neurology
with Special Qualifications in Child Neurology, Epiilepsy, and Clinical Neurophysiology. She has published
extensively in research focusing on outcomes in clinical pharmacology, clinical neurogenetics, and surgical
outcomes in pediatric epilepsy. She has served as the Director of several academic Pediatric Epilepsy Programs
at Ohio State, Vanderbilt, and Weill Cornell Universities, and is a regular faculty speaker at the Kiffen Penry
Epilepsy Program at Wake Forest University.
Dr. Paolicchi discloses receiving support for Contracted Research: GW Pharma, Zogenix; Honoraria: LivaNova,
Lundbeck
John Pollard, MD, Reviewer

University of Pennsylvania
John Pollard, MD is an Adjunct Associate Professor of Clinical Neurology at the University of Pennsylvania. While
he mainly focuses on the clinical care of adult epilepsy patients, he also helps lead efforts to improve clinical
trials and to develop novel seizure biomarkers.
Dr. Pollard discloses receiving support for Other Financial or Material Support: Cognizance Biomarkers, LLC; Own
1.5% of company with no current value: Cognizance Biomarkers, LLC
PHARMACY/NURSE PLANNERS
Gigi Smith, PhD, RN, CPNP-PC: No financial relationships to disclose relevant to this activity.
Dorothy Duffy, PharmD: No financial relationships to disclose relevant to this activity.
AKH STAFF / AES STAFF

AKH staff and planners: No financial relationships to disclose relevant to this activity.
AES staff and planners: No financial relationships to disclose relevant to this activity.
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DISCLAIMER
Opinions expressed with regard to unapproved uses of products are solely those of the faculty and are not
endorsed by the American Epilepsy Society or any manufacturers of pharmaceuticals.
11/28/2016
Disclosure
New Definition of Epilepsy
I am President of the Epilepsy Study Consortium. All consulting is done on behalf
of the consortium, and fees are paid to the consortium. The NYU Comprehensive
Epilepsy Center receives salary support from the consortium;
I have acted as a consultant for Acorda, Biotie, Brabant Pharma, Eisai Medical
Research, Glaxo Smith‐Kline, GW Pharma, Impax, Johnson and Johnson, Marathon
Jacqueline A French, MD Pharmaceuticals, Marinus, Neusentis, Novartis, Pfizer, Sage, Sunovion, SK life
NYU School of Medicine sciences, Supernus Pharmaceuticals, Takeda, UCB, Upsher‐Smith, Ultragenyx,
Vertex, Zynerba, grants and research from Acorda, Alexza, LCGH, Eisai Medical
Research, Lundbeck, Pfizer, SK life sciences, UCB, Upsher‐Smith, Vertex,
I have received grants from NINDS, Epilepsy Therapy Project, Epilepsy Research
Foundation, Epilepsy Study Consortium;
I am on the editorial board of Lancet Neurology, Neurology Today and Epileptic
disorders, and is an associate editor of Epilepsia.
Learning Objectives What’s new?
• Describe the difference between the old and new
definitions of epilepsy
• When you can diagnose epilepsy
• Explain the new concepts of when epilepsy is no – Handling of reflex epilepsy
longer present • Ability to determine that epilepsy has resolved
“Epilepsy” as a concept Seizure vs Epilepsy

• The “disease” known as epilepsy does not mean • Epileptic seizures are defined as “a transient
the presence of seizures.
occurrence of signs and/or symptoms due to
• Rather, it means that the brain has, for whatever
reason, developed a state in which a seizure could abnormal excessive or synchronous neuronal
happen at a future time. activity in the brain” 1
• A person can be at no immediate risk of a seizure • Until recently, epilepsy was defined as the
and still suffer from epilepsy
– For example a person who is on an effective occurrence of 2 or more unprovoked epileptic
antiepileptic drug seizures
• In other words, epilepsy is brain hyperexcitability,
with or without seizures
1. Fisher et al, Epilepsia 46(4): 470‐472, 2005
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Does this make sense? Epilepsy diagnosis
• The occurrence of 2 unprovoked seizures is a fast • How do you diagnose a brain “state”?
and easy rule to determine the presence of • Is it necessary to wait for 2 seizures ? Is that
epilepsy, and this definition was in existence for appropriate?
decades
• Why wait for the second seizure if we already
• Why? Because the occurrence of two unprovoked
have sufficient evidence that epilepsy has
seizures suggests that the brain has an “enduring
predisposition to generate epileptic seizures” developed?
• We used this as a “surrogate marker ” for the • Should we consider treating as soon as we
presence of the disease know epilepsy is present?
ILAE OFFICIAL
Epilepsy REPORT
Seizure
Threshold really
starts
here!
Seizure
Epilepsy
Epilepsy is a disease of the brain defined by any of the following

conditions
1. A least two unprovoked (or reflex) seizures occurring >24 h apart

2. One unprovoked (or reflex) seizure and a probability of further
seizures similar to the general recurrence risk (at least 60%) after
two unprovoked seizures, occurring over the next 10 years
3. Diagnosis of an epilepsy syndrome
Simonato et al, Lancet Neurol 2014; 13: 949–60
Diagnosis of an epilepsy syndrome How do we know that someone has…
• Presence of an epilepsy syndrome implies a • … a probability of further seizures similar to
chronically reduced seizure threshold the general recurrence risk (at least 60%) after
• Therefore, once sufficient information is two unprovoked seizures, occurring over the
available to determine this, epilepsy can be next 10 years
said to be present • The new definition does not indicate how we
• EG: know that any individual has a “greater
– Single GTCC and generalized polyspike‐wave on likelihood than not” of having another
EEG (idiopathic generalized epilepsy) seizure. This is left up to the clinician to
– Single seizure and centrotempotal spikes (BECTS) determine
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• “The revised definition places no burden on the
Does the new definition impact
treating physician to specify recurrence risk in a treatment decisions?
particular circumstance.
• If epilepsy may be diagnosed after a single
• In the absence of clear information about
recurrence risk, or even knowledge of such seizure, does that mean that it should be
information, the default definition of epilepsy treated at that stage?
originates at the second unprovoked seizure. • The issue is the degree of uncertainty after a
• On the other hand, if information is available to single seizure
indicate that risk for a second seizure exceeds – Until we invent the “epilepsy thermometer” to tell
that which is usually considered to be epilepsy us when the threshold is too low, we can rarely
(about 60%), then epilepsy can be considered to
have 100% certainty that a second seizure will
be present”
occur
Fisher et al, Epilepsia 55 (4): 475‐482, 2014
AAN Guideline
Conclusion:
• Adults with an unprovoked first seizure should
be informed that sz recurrence risk is greatest
early within the first 2 years (21%–45%) (Level
A), and clinical variables associated with
increased risk may include:
– a prior brain insult (Level A),
– an epileptiform EEG (Level A),
– An abnormal CT/MRI(Level B)
– a nocturnal seizure (Level B).
Provoked Seizures
Seizure
AAN Guideline Threshold
Seizures
• Immediate antiepileptic drug (AED) therapy,
as compared with delay of treatment pending
a second seizure, is likely to reduce recurrence Epilepsy
risk within the first 2 years (Level B)
• Clinicians’ recommendations whether to
initiate immediate AED treatment after a first Precipitating Factor
seizure should be based on individualized
assessments that weigh the risk of recurrence
against the AEs of AED therapy.
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These are not Epilepsy because there is no risk of a

seizure in the absence of a precipitating factor Reflex Epilepsies
• Despite the fact that seizures are “provoked”
• Febrile seizures in children age 0.5 – 6 years old
in reflex epilepsies, these are considered
• Alcohol-withdrawal seizures epilepsy, because…
• Metabolic seizures (sodium, calcium, magnesium, glucose, oxygen) • If the seizure threshold were not altered,
• Toxic seizures (drug reactions or withdrawal, renal failure) these precipitants would typically not cause
• Convulsive syncope seizures
• Acute concussive convulsion – Eg photosensitive epilepsy, eating epilepsy
• Seizures within first week after brain trauma, infection or stroke
How do
Seizure
Threshold
we know Epilepsy Resolved
when
epilepsy is
Seizures gone? • Epilepsy is now considered to be resolved
for individuals who had an age-dependent
epilepsy syndrome but are now past the
applicable age or those who have
remained seizure-free for the last 10
years, with no seizure medicines for the
last 5 years.
Fisher et al, Epilepsia 55 (4): 475‐482, 2014
Conclusion: How will the new
Impact on Clinical Care and Practice
definition(s) change our practice?
• Determine whether antiepileptic drugs should be
• Our definition of epilepsy will be more aligned initiated
with our treatment strategies, both in regards
to starting and stopping treatment • Determine which seizures may not be epilepsy
• The new definition should allow us to have a
dialogue with patients
• Maybe in the future we will discover an even
better surrogate marker for the presence of
epilepsy
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Disclosure
The 2017 ILAE Seizure Classification
Stock or options:
• Smart‐Monitor (seizure‐detector watch)
• Cerebral Therapeutics (CSF AED delivery)
Robert S. Fisher, MD, PhD
• Zeto (dry, wireless EEG)
Stanford Neurology
• Applied Neurometrics (dry, wireless EEG)
• Avails Medical (AED and sample analysis)
None are relevant to the subject of this talk
Impact on Clinical Care and Practice Learning Objectives
• Participants will have a better understanding of when • Clarify the new definition of epilepsy
a patient is considered to have epilepsy • Review acute symptomatic seizures
• First showing of the new classification of seizures
• Participants will learn how to apply the new • Discuss the scientific basis for classifying seizures
classification of seizure types and epilepsy
The 2017 ILAE Seizure Classification International Classification of Seizures 1981
Partial Seizures
Simple Dreifuss et al. Proposal for revised
Seizure Classification Task Force: Robert S. Fisher (Chair), J. Helen Cross, Carol D’Souza, Sensory clinical and electroencephalographic
Jacqueline A. French, Norimichi Higurashi, Edouard Hirsch, Floor E. Jansen, Lieven Lagae, Motor classification of epileptic seizures. From
Sensory-Motor the Commission on Classification and
Solomon L. Moshé, Jukka Peltola, Eliane Roulet Perez, Ingrid E. Scheffer, Sameer M. Zuberi.
Psychic Terminology of the International
Revision Task Force: Robert S. Fisher (Chair), Sheryl Haut, Andreas Schulze‐Bonhage, Autonomic League Against Epilepsy. Epilepsia.
1981;22:489-501.
Ernest Somerville, Michael Sperling, Elza Marcia Yacubian. Complex
with or without aura
with or without automatisms
Secondarily generalized
Generalized Seizures
Absence, typical and atypical
Tonic-clonic
Atonic
Tonic
Myoclonic
Other
Unclassifiable seizures
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Motivation for Revision Possible Seizure Classifications Could be Based On:
• Some seizure types, for example tonic seizures or epileptic spasms, can Pathophysiology Anatomy Networks Practical, by: Modify Existing

have either a focal or generalized onset.
But this is Temporal Neocortical AED response 1981 ILAE System
• Lack of knowledge about the onset makes a seizure unclassifiable and currently Frontal Limbic Surgical target 2010 ILAE update
difficult to discuss with the 1981 system. impossible with Parietal Thalamo‐Cortical Disabling
our limited Occipital Brainstem EEG pattern
understanding Diencephalic Many others
• Retrospective seizure descriptions often do not specify a level of Brainstem
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 • In the absence of fundamental knowledge, we chose to extend the existing classification
acceptance or public understanding, such as “psychic,” “partial,” “simple • The is an operational (practical) system, not a true scientific classification
partial,” “complex partial”, and “dyscognitive.” • Others might devise special operational classifications for specific use, e.g., neonatal, ICU
• Some important seizure types are not included. • This classification is predominantly for clinicians
How Do Clinicians Classify Seizures ? Key Seizure Signs and Symptoms?
Symptoms Medical Term
• Elicit symptoms and signs of event (semiology)
• Look for familiar patterns in symptoms and signs automatic behaviors automatisms
• Sometimes use ancillary data, e.g., EEG, MRI, genes, antibodies, etc. emotions or appearance of emotions emotions
one‐to many extension or flexion postures tonic
Symptoms + Signs Seizure Type flushing/sweating/piloerection autonomic
many‐to‐one jerking arrhythmically myoclonus

jerking rhythmically clonus
examples language or thinking problems, deja vu cognitive
complex partial seizure lid jerks eyelid myoclonia
automatisms absence seizure limp atonic
numb/tingling, sounds, smells, tastes visions, vertigo sensations
automatisms pausing, freezing, activity arrest behavior arrest
autonomic complex partial seizure thrashing/pedaling hyperkinetic
trunk flexion spasm
The Elements of Change The Elements of Change
• Allow some seizures to be either focal or generalized onset • Allow some seizures to be either focal or generalized onset
• Classify seizures of unknown onset • Classify seizures of unknown onset
• Clarify “impairment of consciousness” • Clarify “impairment of consciousness”
• Include a few previously unclassified types • Include a few previously unclassified types
• Update word usage for greater public clarity • Update word usage for greater public clarity
• Validate use of supportive information, e.g. EEG • Validate use of supportive information, e.g. EEG
• Conform with ICD 11 and 12 • Conform with ICD 11 and 12
• Update the 2001 glossary of seizure terms • Update the 2001 glossary of seizure terms
• Standardize common descriptors to describe seizures • Standardize common descriptors to describe seizures
• Map old to new terms • Map old to new terms
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11/28/2016
Some Seizure Onsets can be Focal or Generalized The Elements of Change
• Allow some seizures to be either focal or generalized onset
• Classify seizures of unknown onset
Focal Onset Generalized Onset
• Clarify “impairment of consciousness”
atonic atonic
• Include a few previously unclassified types
clonic clonic
epileptic spasms
• Update word usage for greater public clarity
epileptic spasms
myoclonic myoclonic • Validate use of supportive information, e.g. EEG
tonic tonic • Conform with ICD 11 and 12
tonic‐clonic tonic‐clonic
• Update the 2001 glossary of seizure terms
• Standardize common descriptors to describe seizures
• Map old to new terms
Seizures of Unknown Onset The Elements of Change
Hypothetical case: You hear a noise and enter the video‐EEG • Allow some seizures to be either focal or generalized onset
room to find the patient in bed, grunting, eyes rolled up, all limbs
stiff, then rhythmically jerking for a minute. He was off‐camera at
the start. What seizure type is this? • Clarify “impairment of consciousness”
Some seizure types are • Include a few previously unclassified types
worth describing even if • Update word usage for greater public clarity
onset is unknown:
• tonic‐clonic • Validate use of supportive information, e.g. EEG
• epileptic spasms
• behavior arrest • Conform with ICD 11 and 12
Key Role of Impaired Consciousness Loss (or Impairment) of Consciousness
Among many possible behaviors during a seizure, Two types of seizures with loss of consciousness
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
How well does the public understand LOC during a complex partial seizure?
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Loss (or Impairment) of Consciousness The Elements of Change
Elements of consciousness
• Awareness of ongoing activities • Classify seizures of unknown onset
• Memory for time during the event • Clarify “impairment of consciousness”
• Responsiveness to verbal or nonverbal stimuli
• Sense of self as being distinct from others • Include a few previously unclassified types
Which would be the best surrogate marker ?
• Validate use of supportive information, e.g. EEG
• The 2017 Classification chooses awareness
• Conform with ICD 11 and 12
• Consciousness remains in the classification
but “awareness” is in the seizure name • Update the 2001 glossary of seizure terms
• In several languages, these words are the same • Standardize common descriptors to describe seizures
• Awareness is not used to classify generalized onset seizures • Map old to new terms
New Seizure Types The Elements of Change
New Focal Seizures New generalized seizures • Classify seizures of unknown onset
Motor Non‐Motor absence with eyelid myoclonia
atonic behavior arrest epileptic spasms (infantile spasms) • Clarify “impairment of consciousness”
(autonomic) myoclonic‐atonic (e.g., Doose)
automatisms
clonic (cognitive) myoclonic‐tonic‐clonic (e.g., JME) • Include a few previously unclassified types
epileptic spasms emotional
hyperkinetic (sensory) • Update word usage for greater public clarity
myoclonic
tonic New combined seizures • Validate use of supportive information, e.g. EEG
(focal to bilateral tonic‐clonic)
(parentheses) indicates prior existence, but renaming
Wording Changes The Elements of Change
O L D T E R M N E W T E R M
Unconscious (still used, not in name) Impaired awareness (surrogate) • Clarify “impairment of consciousness”
Partial Focal • Include a few previously unclassified types
Simple partial Focal aware • Update word usage for greater public clarity
Complex partial Focal impaired awareness
Dyscognitive (word discontinued) Focal impaired awareness
Psychic Cognitive
Secondarily generalized tonic‐clonic Focal to bilateral tonic‐clonic • Update the 2001 glossary of seizure terms
Arrest, freeze, pause, interruption Behavior arrest • Standardize common descriptors to describe seizures
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Supportive Information The Elements of Change
Seizures are usually classified by symptoms and signs • Allow some seizures to be either focal or generalized onset
But supportive information may be helpful, when available: • Classify seizures of unknown onset
• Videos brought in by family
• EEG patterns • Clarify “impairment of consciousness”
• Lesions detected by neuroimaging
• Laboratory results such as detection of anti‐neuronal antibodies • Include a few previously unclassified types
• Gene mutations
• Diagnosis of an epilepsy syndrome diagnosis
ICD9, 10, 11, 12 The Elements of Change
• 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 • Clarify “impairment of consciousness”
Glossary The Elements of Change
WORD DEFINITION SOURCE • Allow some seizures to be either focal or generalized onset
absence, typical a sudden onset, interruption of ongoing activities, a blank stare, possibly a Adapted from 11
brief up‐ ward deviation of the eyes. Usually the patient will be unresponsive • Classify seizures of unknown onset
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.
absence, atypical an absence seizure with changes in tone that are more pronounced Adapted from
Dreifuss 1 • Update word usage for greater public clarity
than in typical absence or the onset and/or cessation is not abrupt, often
associated with slow, irregular, generalized spike‐wave activity
see behavioral arrest new
arrest
atonic sudden loss or diminution of muscle tone without apparent preceding 11
myoclonic or tonic event lasting ~1 to 2 s, involving head, trunk, jaw, or limb
musculature. • Update the 2001 glossary of seizure terms
a more or less coordinated motor activity usually occurring when cognition is 11
automatism
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.
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Common Descriptors The Elements of Change
of other symptoms
and signs during
seizures. • Allow some seizures to be either focal or generalized onset
These are not seizure • Classify seizures of unknown onset
types, just suggested
descriptive words.
A free text description
is also highly encouraged. • Update word usage for greater public clarity
Examples of Mapping Old to New Terms
ILAE 2017 Classification of Seizure Types Basic Version 1
Focal Onset Generalized Onset Unknown Onset
Aware
Impaired Motor Motor
Awareness Tonic‐clonic Tonic‐clonic
Other motor
Other motor
Motor Non‐Motor (Absence) Non‐Motor
Non‐Motor
Unclassified 2
focal to bilateral tonic‐clonic
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
ILAE 2017 Classification of Seizure Types Expanded Version1 Rules for Classifying Seizures (1 of 2)
Focal Onset Generalized Onset Unknown Onset
Impaired Motor Onset: Decide whether seizure onset is focal or

Aware Motor
Awareness generalized, using an 80% confidence level.
tonic‐clonic tonic‐clonic
clonic epileptic spasms Awareness: For focal seizures, decide whether to
Motor Onset tonic Non‐Motor classify by degree of awareness or to omit
automatisms myoclonic
behavior arrest awareness as a classifier.
atonic2 myoclonic‐tonic‐clonic
clonic myoclonic‐atonic
Impaired awareness at any point: A focal seizure is
epileptic spasms2 atonic
a focal impaired awareness seizure if awareness is
hyperkinetic epileptic spasms2
Unclassified3 impaired at any point during the seizure.
myoclonic Non‐Motor (absence)
tonic typical Onset predominates: Classify a focal seizure by its
Non‐Motor Onset atypical first prominent sign or symptom. Do not count
myoclonic transient behavior arrest.
autonomic
eyelid myoclonia
behavior arrest
cognitive Behavior arrest: A focal behavior arrest seizure shows arrest of behavior as the prominent feature of the entire
emotional seizure.
1 Definitions, other seizure types and descriptors are listed in the
sensory accompanying paper and glossary of terms. Motor/Non‐motor: A focal aware or impaired awareness seizure maybe further sub‐classified by motor or non‐
2 These could be focal or generalized, with or without alteration of awareness motor characteristics. Alternatively, a focal seizure can be characterized by motor or non‐motor characteristics,
focal to bilateral tonic‐clonic without specifying level of awareness. Example, a focal tonic seizure.
3 Due to inadequate information or inability to place in other categories
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Rules for Classifying Seizures (2 of 2) The Net Effect
Optional terms: Terms such as motor or non‐motor
may be omitted when the seizure type is otherwise
unambiguous.
The net effect of updating the Classification of Seizures
Additional descriptors: It is encouraged to add should be the following:
descriptions of other signs and symptoms, suggested
descriptors or free text. These do not alter the seizure
1. Render the choice of a seizure type easier for seizures that
type. Example: focal emotional seizure with tonic right
arm activity and hyperventilation. did not fit into any prior categories;
Bilateral vs. generalized: Use the term “bilateral” for 2. Clarify what is meant when a seizure is said to be of a
tonic‐clonic seizures that propagate to both
hemispheres and “generalized” for seizures that particular type;
apparently originate simultaneously in both.
3. Provide more transparency of terminology to the
Atypical absence: Absence is atypical if it has slow onset or offset, marked changes in tone or EEG spike‐waves at nonmedical community.
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.
Examples 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. 1. A woman awakens to find her husband having a seizure
EEG and MRI are normal. 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 Examples
Old = partial onset, secondarily generalized seizure
2. In an alternate scenario of case #1, the EEG shows a New = focal to bilateral tonic‐clonic seizure
clear right parietal slow wave focus. The MRI shows a
2. In an alternate scenario of case #1, the EEG shows a
right parietal region of cortical dysplasia.
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.
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Examples 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.
3. A child is diagnosed with Lennox‐Gastaut syndrome of
Seizure types include absence and others.
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 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. 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 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 5: A 25 year old woman describes seizures beginning with
playing.” She can hear other people talking, but 30 seconds of an intense feeling that “familiar music is
afterwards realizes that she could not determine what playing.” She can hear other people talking, but
they were saying. After an episode, she is mildly afterwards realizes that she could not determine what
confused, and has to “reorient herself.” 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.
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Examples 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. 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 Examples
Old = myoclonic astatic seizures
7. A 4 year‐old boy with myoclonic‐atonic epilepsy New = myoclonic‐atonic seizures
(Doose syndrome) has seizures with a few arm jerks, then
a limp drop to the ground. 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 Examples
Old = myoclonic seizures followed by a tonic‐clonic seizure

8. A 35 year‐old man with juvenile myoclonic epilepsy has New = myoclonic‐tonic‐clonic seizures
seizures beginning with a few bilateral arm jerks, followed
by stiffening of all limbs and then rhythmic jerking of all 8. A 35 year‐old man with juvenile myoclonic epilepsy has
limbs. 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.
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Examples 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
9. A 14‐month old girl has sudden flexion of both arms
seizures repeat in clusters. EEG shows hypsarrhythmia
with head flexing forward for about 2 seconds. These
with bilateral spikes, most prominent over the left parietal
seizures repeat in clusters. EEG shows hypsarrhythmia
region. MRI shows a left parietal dysplasia.
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 Examples
Old = unclassified
10. A 75 year‐old man reports an internal sense of body New = unclassified
trembling. No other information is available.
10. A 75 year‐old man reports an internal sense of body
trembling. No other information is available. EEG and
MRI are normal. This event is unclassified and may or
may not even be a seizure.
The End
“Words, words, words, I’m so sick of words!”

Eliza Doolittle, My Fair Lady
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Disclosure
New roadmap for epilepsy Name of Commercial Interest
Honoraria/travel: GSK, Eisai, UCB, Transgenomics
Ingrid E Scheffer AO, MBBS PhD FRACP FAHMS FAA
Chair, ILAE Classification Task Force Scientific advisory board: GSK, UCB, Eisai
University of Melbourne, Austin & Royal Children’s Hospitals
Melbourne, Australia Grants: NHMRC, NIH, HRC, March of Dimes, US DOD, ARC
Learning Objectives Are we there yet?
• Understand the new framework of the epilepsies
• Understand the term “developmental and epileptic
encephalopathy”
• Replace ”benign” with “self‐limited” and “pharmaco
responsive”
Classification of the Epilepsies
Purpose: for clinical diagnosis
2005‐2009 Commission Report
Epilepsia 2010;51:676‐685
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November 2013
128 people commented online (15 Nov‐12 Feb): 43 countries
Seizure types
Focal Generalized Unknown
Etiology
onset onset onset Structural
Co‐morbidities
Genetic
Epilepsy types Infectious
Combined
Focal Generalized Generalized Unknown
Metabolic
& Focal
Immune
Unknown
Epilepsy Syndromes
1. Seizure types
Seizure types
onset onset onset
• Certain that events are epileptic seizures – not referring
to distinguishing epileptic versus non‐epileptic
• In some settings  classification according to seizure
type may be maximum level of diagnosis possible
• In other cases  simply too little information to be able
to make a higher level diagnosis
• eg. when a patient has only had a single event
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Seizure types
Etiology Epilepsy types
onset onset onset Structural Combined
& Focal
Genetic
Tuberous Sclerosis • Where unable to make an Epilepsy Syndrome

Infectious
diagnosis or a diagnosis of Epilepsy with Etiology
Metabolic • Many examples
– Temporal lobe epilepsy
Immune – Generalized tonic-clonic seizures in a 5 year old with
GLUT1 deficiency generalized spike-wave
Unknown
– Both focal impaired awareness seizures and absence
seizures in a patient
– Cannot tell if tonic-clonic seizure is focal or generalized
Generalized and Focal Epilepsies Seizure types

Etiology
• Combined focal and generalized epilepsies onset onset onset Structural
Examples
Genetic
– Juvenile Myoclonic Epilepsy and Temporal Lobe
Epilepsy in adult of normal intellect Epilepsy types Infectious
• With normal imaging Focal Generalized
Combined
Unknown
Generalized Metabolic
– Dravet syndrome & Focal
Immune
• What do with
Unknown
– Multifocal epilepsies?  focal Epilepsy Syndromes
– Hemispheric epilepsies?  focal
Old term
Genetic versus idiopathic
‘Idiopathic Generalized Epilepsies’
• ‘Idiopathic’ = presumed hereditary predisposition
Idiopathic Generalized
Epilepsies • Genetic ≠ inherited
– Importance of de novo mutations in both
Childhood Juvenile
Absence Absence mild and severe epilepsies
Epilepsy Epilepsy
• Critical problem of stigma in some parts of the world
Juvenile Generalized
Myoclonic Tonic‐Clonic
Epilepsy Seizures Alone
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Genetic ≠ Gene testing Seizure types
Etiology
– Usually the mutation is not known onset onset onset Structural
– Access to molecular genetic testing not necessary
Co‐morbidities
– Diagnosed on clinical research eg. twin, family studies Genetic
Genetic
Epilepsy types Infectious
Combined
Generalized Metabolic
& Focal
Immune
Unknown
Epilepsy Syndromes
JME pair; Lennox 1941 CAE pair; Lennox 1950
Epilepsy syndromes Benign
• Many epilepsies not benign
– CAE – psychosocial impact
• There are no approved ILAE – BECTS – learning concerns
epilepsy syndromes • Replaced by terms:
– Self‐limited
– Pharmacoresponsive
• No longer use
– Malignant
– Catastrophic
Epileptic encephalopathy
Developmental and/or Epileptic Encephalopathy
For many encephalopathies, there is a
developmental component independent
of epileptic encephalopathy
Developmental delay may precede
Epileptic activity itself seizure onset
contributes to severe cognitive and
behavioral impairment above and Co‐morbidities
beyond that expected from the eg. cerebral palsy, autism spectrum
underlying pathology and that disorder, ID
these can worsen over time Outcome poor even though seizures stop
Berg et al 2010 eg. KCNQ2, STXBP1 encephalopathies
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Developmental and Epileptic Encephalopathies Developmental and/or Epileptic Encephalopathy

with Movement Disorders • Developmental encephalopathy
Overlap with movement disorders common
• May begin in utero
• Post birth
• Epileptic encephalopathy
• Can occur at any age
• May be remediable component – right vs wrong AED
• Move towards GENE encephalopathy
STXBP1 KCNA2 DNM1 • eg. CDKL5 encephalopathy, SCN2A encephalopathy
Old terms
ILAE Classification of the Epilepsies
‘Symptomatic Generalized Epilepsies’
• Simplified the framework
• Beloved term to many
Symptomatic Generalized • Etiology, etiology, etiology – consider at all stages
• Used for different Epilepsies
groups of disorders • Developmental and Epileptic Encephalopathy
• Self‐limited, pharmacoresponsive
Developmental • IGE  Generalized Epilepsies of Genetic Etiology
and/or (Static)
Epileptic Encephalopathies • SGE
Encephalopathies
 Developmental and Epileptic Encephalopathies
 (static) Encephalopathy with Epilepsy
ILAE Classification Task Force 2016
• New classification framework
• Will change the approach to diagnosis in the clinic
• Will be applied to patients and guide
management
• Updates terminology in line with current thinking
• Reflecting scientific advances
Torbjörn Tomson, Emilio Perucca, Ingrid Scheffer, Jackie French, Yue‐Hua Zhang
Satish Jain, Gary Mathern, Sam Wiebe, Edouard Hirsch, Sameer Zuberi, Nico Moshe
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Disclosure
New Insights about Acute
Cyberonics Upsher Smith
Symptomatic Seizures
Dale C Hesdorffer, PhD
Columbia University
Definition of Acute Symptomatic Epilepsy:
Learning Objectives
ILAE, 1989, 1991, 1993
• To describe the latest 2010 ILAE definition of acute
• “Acute symptomatic seizures occur at the time of a systemic insult
symptomatic seizures
or in close temporal association with a documented brain insult.”
• To determine the outcomes of acute symptomatic • The definition was targeted to epidemiological studies
seizures compared to outcomes after a first
• Acute symptomatic seizures have also been called:
unprovoked seizure
• Reactive seizures
• Provoked seizures
• Situation‐related seizures
The recent definition of acute symptomatic seizures
The terminology below is no longer applicable
mostly remains the same, ILAE 2010
Provoked seizure
Acute symptomatic seizures are events, occurring in close
Increased risk for acute symptomatic seizure (e.g., ETOH, sodium levels)
temporal relationship with an acute CNS insult, which may Provoking factors associated with unprovoked seizure
be metabolic, toxic, structural, infectious, or due to Sleep deprivation and low ETOH intake lowers seizure threshold
Etiologies
inflammation. The interval between the insult and seizure Antecedent etiologies associated with an increased risk for unprovoked
seizure or for acute symptomatic seizure (e.g., metabolic)
may vary due to the underlying clinical condition. Acute repetitive seizures
Seizure clusters
Situation‐related seizure
Synonym for acute symptomatic seizure in 1989 ILAE paper
Reflex epilepsy (Trigger seizures/epilepsy)
Epilepsies characterized by seizures with specific modes of precipitation
Reading epilepsy, musicogenic epilepsy
Beghi et al. Epilepsia 2010;51:671‐675
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Defining time in acute symptomatic seizures Defining time in acute symptomatic seizures
Events within 24 hours using specific biochemical or hematological abnormalities
High probability
• Events within 1 week of: Severe metabolic derangements
• Stroke Drug or alcohol intoxication or withdrawal (can be within 7‐28 hours of
• TBI the last drink)
• Anoxic encephalopathy Exposure to well‐defined epileptogenic drugs
• Intracranial surgery Strongly associated: Normeperidine, meperidine, Methaqualone,
• First identification of subdural hematoma Gluarimide, stimulants in excess, inhalants
• Presence of an active CNS infection Withdrawal of barbiturates and benzodiazepines
• During an active phase of multiple sclerosis or other Fair probability
autoimmune disease Hallucinogens
Angel dust (PCP, Phencyclidine, phencyclidine, quatandine)
Low or no probability
Heroin
Marijuana
Beghi et al. Epilepsia 2010;51:671‐675 Beghi et al. Epilepsia 2010;51:671‐675
Cut off values for acute symptomatic seizures in Hyponatremia and risk of seizures: A retrospective cross‐
common metabolic disorders sectional study of 363 patients, 36‐88 years, in a Swedish
county hospital
Biochemical parameter Cut off value Serum

sodium Patients N with
<36 mg/dl (2.0mM) or >450 mg/dl (25 mM) associated with
(mM) (N) seizure Absolute risk of seizure OR (95% CI)
Serum Glucose ketoacidosis whether or not long‐standing diabetes exists
120‐124 150 1 0.0067 (0.0002‐0.0366) Reference
Serum sodium <115 mg/dl (<5 mM)
115‐119 120 3 0.0252 (0.0052‐0.0719) 3.85 (0.40‐37.530
Serum calcium <5.0 mg/dl (<1.2 mM)
110‐114 54 3 0.0536 (0.0112‐0.1487) 8.43 (0.859‐82.85)
Serum magnesium <0.8 mg/dl (<0.3 mM)
<110 39 4 0.1081 (0.0303‐0.2542) 18.06 (1.96‐166.86)
Urea nitrogen >100 mg/dl (>35.7 mM)
Eleven patients with hyponatremia and seizures
Creatinine >10.0 mg/dl (>884 µM) Sodium levels
1 died (sodium level 104 mM)
7 had seizures and polydipsia, vomiting, diuretics (sodium levels: 106‐116 mM)
2 were of unclear cause (117‐122 Mm)
Seizure types
8 GTCS, 1 multiple SGTC, 1 focal motor seizure, and 1 complex partial seizure
Halawa et al. Epilepsia 2011;52:410‐413
Differentiating acute symptomatic seizures from
Misclassification of Acute Symptomatic Seizures
unprovoked seizures
First unprovoked seizure incidence/100,000 Acute symptomatic seizure incidence/100,000
Acute Symptomatic Seizures Unprovoked Seizures/Epilepsy 300
250
Seizures occurring in close temporal Seizures occurring in the absence of a 200
relationship with an acute CNS insult, potentially responsible clinical
150
which may be metabolic, toxic, condition or beyond the interval
100
structural, infectious, or due to estimated for the occurrence of acute
50
inflammation. symptomatic seizures
0
lt1 1 to 4 5 to 14 15 to 25 to 35 to 45 to 55 to 65‐74 75+
The interval between the insult and 24 34 44 54 64
seizure may vary due to the
underlying clinical condition.
Similar age distributions, similar incidence per 100,000.
Difficult to distinguish in resource‐poor settings
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Acute symptomatic afebrile seizures: Incidence, Questions on the prognosis of acute symptomatic
proportion and recurrence seizures versus unprovoked seizures
• Age‐adjusted incidence of acute symptomatic seizures was Is the risk for an unprovoked seizure greater in acute symptomatic
39/100,000 in Rochester, MN seizures versus first unprovoked seizure?
• The acute symptomatic seizure incidence was 29/100,000 in What are the etiologies at greatest risk?
Gironde France
• These both represented 40% of all afebrile seizures in the Is the risk for mortality increased in acute symptomatic seizures versus
community first unprovoked seizure?
And restricting to structural etiologies (CNS infection, stroke and TBI)
Recurrent seizures Is the risk for unprovoked seizure after a first acute symptomatic seizure
• Acute symptomatic seizures are unlikely to be recurrent different with and without SE
• Unprovoked seizures are often recurrent Restricting to structural etiologies (CNS infection, stroke and TBI
Annegers et al. Epilepsia 1995;36:327‐333; Loiseau et al. These, 1987.
Subsequent unprovoked seizure by structural etiology
Cumulative risk for recurrent unprovoked seizure, Rochester after a first unprovoked seizure or acute symptomatic
1955‐84: Structural Etiologies: CNS infection, stroke, TBI seizure
Cumulative Probability of Subsequent Unprovoked Seizure
1.00 Cumulative Risk of

First Unprovoked
Structural Etiology Number Unprovoked seizure RR (95% CI)
0.75 Stroke
Acute Symptomatic Seizure 53 36.3%; p<0.001 0.4 (0.2-0.6)
0.50 Unprovoked Seizure 96 78.5% 1.0 (referent)
CNS infection
Acute Symptomatic
0.25
Log Rank p<0.001

Unprovoked Seizure 10 100% 1.0 (referent)
0.00
0 2 4 6 8 10 TBI
Time (Years)
Univariate RR=0.2, 95% CI=0.1‐0.3
Adjusted RR=0.02 (95% CI=0.2‐0.4), adjusting for age gender and SE Unprovoked Seizure 37 75.9% 1.0 (referent)
Hesdorffer et al. Epilepsia 2009 Hesdorffer et al, Epilepsia 2009
Cumulative risk for 30‐day mortality, Rochester 1955‐84 30‐day mortality by structural etiology:
Structural Etiologies: CNS infection, stroke and TBI Acute symptomatic seizure vs first unprovoked seizure
1.00
Structural Etiology N Cumulative Risk of death
Stroke
Cumulative Probability of 30-day Mortality
Acute Symptomatic Seizure 91 41.9%; p<0.001

0.75 Log Rank p<0.001
Unprovoked Seizure 101 5.0%
0.50
CNS infection
Acute Symptomatic Seizure 80 9.9%; p=0.03
0.25 Acute Symptomatic Unprovoked Seizure 10 0%
First Unprovoked
TBI
0.00 Acute Symptomatic Seizure 91 11.0%; p=0.04
0 10 20 30
Time (Days) Unprovoked Seizure 37 0%
56 deaths/262 with acute symptomatic seizure versus 5 deaths/148 with unprovoked seizure.
Univariate RR=6.9 (2.8-17.3); Adjusted RR=8.9 (3.5-22.5) – adjusted for age, gender and SE
Hesdorffer et al. Epilepsia 2009 Hesdorffer et al. Epilepsia 2009
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Cumulative risk for 10‐year mortality, in 30 day survivors
Rochester 1955‐84 10‐year mortality in 30‐day survivors by structural etiology
Structural Etiologies: CNS infection, stroke and TBI
Etiology Number Cumulative Risk of Death

Stroke
Acute Symptomatic Seizure 53 73.8%; ns
CNS infection
Unprovoked Seizure 10 0%
TBI
54 deaths/206 with acute symptomatic seizure vs 71 deaths/143 with unprovoked seizure
RR=0.5 (0.4‐0.7); adjusted RR=0.7 (0.5‐1.03)‐ adjusted for age, gender and SE Unprovoked Seizure 37 28.1%
Risk for unprovoked seizure in acute short seizure vs Determinants of unprovoked seizure after acute
acute status epilepticus over 10 years symptomatic seizure over 10 years
Variable Adjusted RR 95% CI

SE 3.3 1.8-6.1
No SE 1.0 Referent
Etiology
Structural SE 7.1 2.9-16.9
Structural no SE 2.4 1.1-5.5
Metabolic SE 3.6 1.1-11.9
Metabolic no SE 1.0 Referent
Encephalophathic SE 18.8 3.6-98.6
Encephaloapthic no SE 1.9 0.23-15.3
Hesdorffer et al, 1998
30 day cumulative survival by etiology of status epilepticus Conclusions: Differences Between Acute Symptomatic

Seizures & Unprovoked Seizures
log rank test: chi-square=18.9 (p=0.0001)
1
0.8
0.6
0.4
0.2
acute
idiopathic remote progressive symptomatic
0
0 5 10 15 20 25 30 35
Logroscino et al. Epilepsia 1997
4
11/28/2016
Conclusions: Differences between acute symptomatic SE New‐onset Refractory Status Epilepticus (NORSE) in
(ASSE) and shorter acute symptomatic seizures (ASS) 13 Centers (Gaspard et al Neurology 2015)
Retrospective review of 125 complete cases with new onset refractory SE
with unknown etiology within 48 hours of admission over a 5 year period
• The risk for an unprovoked seizure is 3‐fold greater in ASSE than in shorter ASS Etiology
• The risk for unprovoked seizures after ASSE versus metabolic ASS 50% unknown etiology
• ASSE has a 3‐fold increased risk 50% known etiology
• Metabolic ASSE has a 3.6‐fold increased risk 20% autoimmune, non‐paraneoplastic
• Structural ASSE has a 7.1‐fold increased risk 18% paraneoplastic
• Encephalopatic ASSE has an 18.8‐fold increased risk 8% infection‐related
4% other causes
• 30‐day survival in ASSE is far worse than either idiopathic, remote symptomatic,
With Without
or progressive symptomatic seizures
All NORSE etiology etiology
Seizures 23(37%) 13 (37%) 10 (37%)
No seizure but treated 34 (55%) 18 (51%) 16 (59%)
No seizures and no treatment 5 (8%) 4 (11%) 1 (4%)
Death 28 (22%) 11 (18%) 17 (27%)
Conclusions: Reflecting on the practical clinical ILAE Conclusions: Use of the new ILAE definition of acute
definition of epilepsy symptomatic seizures
• Epilepsy definition: 60% risk for a recurrent seizure that is unprovoked–either • Only one study has used the 2010 definition of acute
after an acute symptomatic seizure or after a first unprovoked seizure symptomatic seizures
This does not reach the definition of epilepsy in acute symptomatic seizure • Other studies are needed to address:
and acute symptomatic SE
• Events within 24 hours:
• Biochemical parameters (e.g., calcium levels)
• Stroke reaches the cut off for epilepsy after a first unprovoked seizure
• Varying time intervals between the insult and seizure due
to the underlying clinical condition (e.g., stroke)
• Events within 24 hours with high, medium and low
probability of acute symptomatic seizures
• To define acute symptomatic seizures using the 2010
ILAE definition
• To use the definition to determine outcomes
• To use only acute symptomatic seizures to index these
seizures and not the older names for these seizures
#AES2016
5
11/16/2016
Disclosure
New Insights about Acute
Cyberonics Upsher Smith
Symptomatic Seizures
Dale C Hesdorffer, PhD
Columbia University
Definition of Acute Symptomatic Epilepsy:
Learning Objectives
ILAE, 1989, 1991, 1993
• To describe the latest 2010 ILAE definition of acute
• “Acute symptomatic seizures occur at the time of a systemic insult
or in close temporal association with a documented brain insult.”
• To determine the outcomes of acute symptomatic
seizures compared to outcomes after a first • The definition was targeted to epidemiological studies
unprovoked seizure
• Acute symptomatic seizures have also been called:
• Reactive seizures
• Provoked seizures
• Situation‐related seizures
The recent definition of acute symptomatic seizures
The terminology below is no longer applicable
mostly remains the same, ILAE 2010
Provoked seizure
Acute symptomatic seizures are events, occurring in close
Increased risk for acute symptomatic seizure (e.g., ETOH, sodium levels)
temporal relationship with an acute CNS insult, which may Provoking factors associated with unprovoked seizure
be metabolic, toxic, structural, infectious, or due to Sleep deprivation and low ETOH intake lowers seizure threshold
Etiologies
inflammation. The interval between the insult and seizure Antecedent etiologies associated with an increased risk for unprovoked
seizure or for acute symptomatic seizure (e.g., metabolic)
may vary due to the underlying clinical condition. Acute repetitive seizures
Seizure clusters
Situation‐related seizure
Synonym for acute symptomatic seizure in 1989 ILAE paper
Reflex epilepsy (Trigger seizures/epilepsy)
Epilepsies characterized by seizures with specific modes of precipitation
Reading epilepsy, musicogenic epilepsy
1
11/16/2016
Defining time in acute symptomatic seizures Defining time in acute symptomatic seizures
Events within 24 hours using specific biochemical or hematological abnormalities
High probability
• Events within 1 week of: Severe metabolic derangements
• Stroke Drug or alcohol intoxication or withdrawal (can be within 7‐28 hours of
• TBI the last drink)
• Anoxic encephalopathy Exposure to well‐defined epileptogenic drugs
• Intracranial surgery Strongly associated: Normeperidine, meperidine, Methaqualone,
• First identification of subdural hematoma Gluarimide, stimulants in excess, inhalants
• Presence of an active CNS infection Withdrawal of barbiturates and benzodiazepines
• During an active phase of multiple sclerosis or other Fair probability
autoimmune disease Hallucinogens
Angel dust (PCP, Phencyclidine, phencyclidine, quatandine)
Low or no probability
Heroin
Marijuana
Beghi et al. Epilepsia 2010;51:671‐675 Beghi et al. Epilepsia 2010;51:671‐675
Cut off values for acute symptomatic seizures in Hyponatremia and risk of seizures: A retrospective cross‐
common metabolic disorders sectional study of 363 patients, 36‐88 years, in a Swedish
county hospital
Biochemical parameter Cut off value Serum

sodium Patients N with
<36 mg/dl (2.0mM) or >450 mg/dl (25 mM) associated with
(mM) (N) seizure Absolute risk of seizure OR (95% CI)
Serum Glucose ketoacidosis whether or not long‐standing diabetes exists
120‐124 150 1 0.0067 (0.0002‐0.0366) Reference
Serum sodium <115 mg/dl (<5 mM)
115‐119 120 3 0.0252 (0.0052‐0.0719) 3.85 (0.40‐37.530
Serum calcium <5.0 mg/dl (<1.2 mM)
110‐114 54 3 0.0536 (0.0112‐0.1487) 8.43 (0.859‐82.85)
Serum magnesium <0.8 mg/dl (<0.3 mM)
<110 39 4 0.1081 (0.0303‐0.2542) 18.06 (1.96‐166.86)
Urea nitrogen >100 mg/dl (>35.7 mM)
Eleven patients with hyponatremia and seizures
Creatinine >10.0 mg/dl (>884 µM) Sodium levels
1 died (sodium level 104 mM)
7 had seizures and polydipsia, vomiting, diuretics (sodium levels: 106‐116 mM)
2 were of unclear cause (117‐122 Mm)
Seizure types
8 GTCS, 1 multiple SGTC, 1 focal motor seizure, and 1 complex partial seizure
Halawa et al. Epilepsia 2011;52:410‐413
Differentiating acute symptomatic seizures from
Misclassification of Acute Symptomatic Seizures
unprovoked seizures
First unprovoked seizure incidence/100,000 Acute symptomatic seizure incidence/100,000
Acute Symptomatic Seizures Unprovoked Seizures/Epilepsy 300
250
Seizures occurring in close temporal Seizures occurring in the absence of a 200
relationship with an acute CNS insult, potentially responsible clinical
150
which may be metabolic, toxic, condition or beyond the interval
100
structural, infectious, or due to estimated for the occurrence of acute
50
inflammation. symptomatic seizures
0
lt1 1 to 4 5 to 14 15 to 25 to 35 to 45 to 55 to 65‐74 75+
The interval between the insult and 24 34 44 54 64
seizure may vary due to the
underlying clinical condition.
Similar age distributions, similar incidence per 100,000.
Difficult to distinguish in resource‐poor settings
2
11/16/2016
Acute symptomatic afebrile seizures: Incidence, Questions on the prognosis of acute symptomatic
proportion and recurrence seizures versus unprovoked seizures
• Age‐adjusted incidence of acute symptomatic seizures was Is the risk for an unprovoked seizure greater in acute symptomatic
39/100,000 in Rochester, MN seizures versus first unprovoked seizure?
• The acute symptomatic seizure incidence was 29/100,000 in What are the etiologies at greatest risk?
Gironde France
• These both represented 40% of all afebrile seizures in the Is the risk for mortality increased in acute symptomatic seizures versus
community first unprovoked seizure?
And restricting to structural etiologies (CNS infection, stroke and TBI)
Recurrent seizures Is the risk for unprovoked seizure after a first acute symptomatic seizure
• Acute symptomatic seizures are unlikely to be recurrent different with and without SE
• Unprovoked seizures are often recurrent Restricting to structural etiologies (CNS infection, stroke and TBI
Annegers et al. Epilepsia 1995;36:327‐333; Loiseau et al. These, 1987.
Subsequent unprovoked seizure by structural etiology
Cumulative risk for recurrent unprovoked seizure, Rochester after a first unprovoked seizure or acute symptomatic
1955‐84: Structural Etiologies: CNS infection, stroke, TBI seizure
Cumulative Probability of Subsequent Unprovoked Seizure
1.00 Cumulative Risk of

First Unprovoked
Structural Etiology Number Unprovoked seizure RR (95% CI)
0.75 Stroke
0.50 Unprovoked Seizure 96 78.5% 1.0 (referent)
CNS infection
Acute Symptomatic
0.25
Log Rank p<0.001

Unprovoked Seizure 10 100% 1.0 (referent)
0.00
0 2 4 6 8 10 TBI
Time (Years)
Univariate RR=0.2, 95% CI=0.1‐0.3
Adjusted RR=0.02 (95% CI=0.2‐0.4), adjusting for age gender and SE Unprovoked Seizure 37 75.9% 1.0 (referent)
Hesdorffer et al. Epilepsia 2009 Hesdorffer et al, Epilepsia 2009
Cumulative risk for 30‐day mortality, Rochester 1955‐84 30‐day mortality by structural etiology:
Structural Etiologies: CNS infection, stroke and TBI Acute symptomatic seizure vs first unprovoked seizure
1.00
Structural Etiology N Cumulative Risk of death
Stroke
Cumulative Probability of 30-day Mortality
Acute Symptomatic Seizure 91 41.9%; p<0.001

0.75 Log Rank p<0.001
0.50
CNS infection
Acute Symptomatic Seizure 80 9.9%; p=0.03
0.25 Acute Symptomatic Unprovoked Seizure 10 0%
First Unprovoked
TBI
0.00 Acute Symptomatic Seizure 91 11.0%; p=0.04
0 10 20 30
Time (Days) Unprovoked Seizure 37 0%
56 deaths/262 with acute symptomatic seizure versus 5 deaths/148 with unprovoked seizure.
Univariate RR=6.9 (2.8-17.3); Adjusted RR=8.9 (3.5-22.5) – adjusted for age, gender and SE
3
11/16/2016
Cumulative risk for 10‐year mortality, in 30 day survivors
Rochester 1955‐84 10‐year mortality in 30‐day survivors by structural etiology
Structural Etiologies: CNS infection, stroke and TBI
Etiology Number Cumulative Risk of Death

Stroke
CNS infection
Unprovoked Seizure 10 0%
TBI
54 deaths/206 with acute symptomatic seizure vs 71 deaths/143 with unprovoked seizure
RR=0.5 (0.4‐0.7); adjusted RR=0.7 (0.5‐1.03)‐ adjusted for age, gender and SE Unprovoked Seizure 37 28.1%
Risk for unprovoked seizure in acute short seizure vs Determinants of unprovoked seizure after acute
acute status epilepticus over 10 years symptomatic seizure over 10 years
Variable Adjusted RR 95% CI

SE 3.3 1.8-6.1
No SE 1.0 Referent
Etiology
Structural SE 7.1 2.9-16.9
Structural no SE 2.4 1.1-5.5
Metabolic SE 3.6 1.1-11.9
Metabolic no SE 1.0 Referent
Encephalophathic SE 18.8 3.6-98.6
Encephaloapthic no SE 1.9 0.23-15.3
30 day cumulative survival by etiology of status epilepticus Conclusions: Differences Between Acute Symptomatic

Seizures & Unprovoked Seizures
log rank test: chi-square=18.9 (p=0.0001)
1
0.8
0.6
0.4
0.2
acute
idiopathic remote progressive symptomatic
0
0 5 10 15 20 25 30 35
Logroscino et al. Epilepsia 1997
4
11/16/2016
Conclusions: Differences between acute symptomatic SE Conclusions: Reflecting on the practical clinical ILAE
(ASSE) and shorter acute symptomatic seizures (ASS) definition of epilepsy
• The risk for an unprovoked seizure is 3‐fold greater in ASSE than in shorter ASS • Epilepsy definition: 60% risk for a recurrent seizure that is unprovoked–either
• The risk for unprovoked seizures after ASSE versus metabolic ASS after an acute symptomatic seizure or after a first unprovoked seizure
• ASSE has a 3‐fold increased risk This does not reach the definition of epilepsy in acute symptomatic seizure
• Metabolic ASSE has a 3.6‐fold increased risk and acute symptomatic SE
• Structural ASSE has a 7.1‐fold increased risk
• Encephalopatic ASSE has an 18.8‐fold increased risk • Stroke reaches the cut off for epilepsy after a first unprovoked seizure
• 30‐day survival in ASSE is far worse than either idiopathic, remote symptomatic,
or progressive symptomatic seizures
Conclusions: Use of the new ILAE definition of acute
• To define acute symptomatic seizures using the 2010
• Only one study has used the 2010 definition of acute ILAE definition
symptomatic seizures • To use the definition to determine outcomes
• Other studies are needed to address: • To use only acute symptomatic seizures to index these
seizures and not the older names for these seizures
• Events within 24 hours:
• Biochemical parameters (e.g., calcium levels)
• Varying time intervals between the insult and seizure due
to the underlying clinical condition (e.g., stroke)
• Events within 24 hours with high, medium and low
probability of acute symptomatic seizures
#AES2016
5
11/28/2016
Towards a Scientific Basis for Definition Disclosure
and Classification of Epilepsy Nothing to disclose
Ivan Soltesz, PhD
Stanford University
Learning Objectives • Brain rhythms are ubiquitous: All neuronal circuits generate

network oscillations at various frequencies
• Discuss how recent advances in neuroscience may inform • Example: The hippocampus: theta (4Hz‐10Hz), low gamma
definition and classification of epilepsy (25Hz‐90Hz), high gamma (90Hz‐130Hz), ripples (130Hz‐200Hz)
• Each of these oscillations have their specific behavioral
• Evaluate the potential benefits and practical and conceptual correlates: theta during running, ripples during rest
limitations of a science‐inspired definition and classification
of epilepsy • Functions of the distinct oscillations are beginning to be
understood; e.g., gamma: coordination of cell assemblies;
ripples: replay of episodic memory sequences
Oscillations and cognition
Example: Replay of place cell sequences during ripples Normal and abnormal oscillations can coexist
Place cells
RIPPLES
Replay
Buzsaki and Wang, 2012
Le Van Quyen, et al., 2006
G. Buzsaki
1
11/28/2016
A basic scientist’s view: • Simple definition: Seizures are abnormal network oscillations
All current epilepsy treatments have pluses • Most often involve cortical circuits, but can also involve
and minuses, but they fundamentally all subcortical circuits
aim to control abnormal oscillators without
affecting the normal ones
• Just as specific circuits generate characteristic oscillations in the
Comorbidities, side‐effects normal brain, each altered circuit in epilepsy generates
abnormal network oscillations that are characteristic for that
particular circuit; e.g., spike‐and‐wave discharges, temporal
lobe epilepsy
Bui*, Alexander* & Soltesz
The Neuroscientist 2017 (in press)
• Therefore, a truly science‐based classification of “We will not have a real seizure classification until we understand
seizures should be possible when the nature of the why there are different types of seizures” (R. Fisher)
altered circuits generating the abnormal oscillations
becomes better understood Genetics, development, networks, physiological principles
• Clinicians and basic scientists need to work together Limited animal models for different seizure types; for example, we
towards designing a new science‐based framework know little of atonic drop seizures because we don’t have a good
for seizures animal model for that seizure type
Taxonomy of seizures based on first principles? Seizure patterns conserved across species and brain regions

Experiments Flows in state space
Universality of seizures: from flies to humans; under various conditions
What are the fundamental properties of seizure dynamics that hold across multiple patients,
species and brain regions?
Dynamical system theory is the mathematical analysis of physical systems whose state changes
over time
Analysis of seizure dynamics mathematically; Theoretical framework called Epileptor (Jirsa et

al., Brain 2014) Theory: Only 16 truly different seizure types can exist!
5 variables, transitions from normal state to a seizure state and back: “bifurcations”
How many fundamentally distinct seizures can there be in theory (in a dynamical system theory
sense)?
Viktor K. Jirsa et al. Brain 2014;137:2210-2230
2
11/28/2016
Towards automated, bias‐free seizure classification:
Reconstructing the neuronal machine
Will we be able to find seizure‐specific behavioral
“syllables” and connect them to specific brain circuits? “The basic mental strategy of assembling
neuron networks from virtually completely
stained but isolated individual cells, was
that of looking for the “best spatial fitting”
between terminal axon arborizations and
3D imaging of behavior and machine learning‐ potential postsynaptic sites, such as cell
bodies, major dendrites and characteristic
assisted analysis in normal mice points of their arborizations, dendritic
spines, etc.” The Ferrier Lecture, 1978 János Szentágothai
1912- 1994
Behaviors are structured according to
stereotyped modules at subsecond time‐scales
(“syllables”) that are arranged according to
specific rules (“grammar”)
Slowly evolving pose dynamics seprated by fast
transitions
G. Nyiri Szentágothai
Based on Wiltschko et al., Neuron 2015
Neurotransmitters are released in specific spatial domains at specific times:
“Chronocircuits” – Unity of neuronal space and time
Seizures are abnormal chronocircuit activities
Other chronocircuit disorders or “rhythmopathies”:
Parkinson’s disease, Dystonias,
Tinnitus, Essential tremor,
Alzheimer’s disease, Autism,
Schizophrenia, Depression
Krook‐Magnuson et al TINS 2012
Emerging rules of chronocircuit organization I:
Local time-keepers (clocks) of network oscillations PV cells release GABA in a sequential manner during theta: initial segment, soma,
dendrites
“clock/time‐keeper of oscillations” “modifiable inhibition”
CCK2
receptor
P/Q type
N‐type
Freund (2003) TINS
Varga et al eLife 2014
3
11/28/2016
Emerging rules of chronocircuit organization II: Data‐driven, full‐scale model of the isolated CA1 network

Frequency invariant temporal ordering of perisomatic and dendritic Ion channel properties Synapse properties
inhibition
Firing properties
Ion channel distribution
Pyramidal
Basket cells cells
Dendritically projecting cells Bezaire et al., 2016

Varga et al PNAS 2012
BioRxiv 087403
Emergence of normal network oscillations from the biological Conclusions:
data‐driven model of the CA1 neuronal network • We need to understand why there are different types of seizures
• Animal models are needed for all seizures subtypes
• Normal and abnormal oscillations co‐exist and transition to one another;
chronocircuits, rhythmopathies, universe of circuit disorders
• Theoretical analysis of seizures points to an upper limit for the number of
possible seizure types
• Modern technology (BRAIN Initiative) to help in understanding the
principles of normal and abnormal chronocircuit organization
#AES2016

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Annual Fundamentals Symposium

Robert Fisher, M.D., Ph.D.

Friday, December 2, 2016

12:30 – 3:00 p.m.

Accreditation Claiming CME Credit and CME Certificates

New Definition of Epilepsy

New Classification of Seizure Types

New Roadmap for Epilepsy

New Insights about Acute Symptomatic Seizures

Towards a Scientific Basis for Definition and Classification of Epilepsy

Nurses may claim up to 2.5 contact hours for this session.

Commercial Support Acknowledgement

FACULTY / PLANNER BIO AND DISCLOSURES

Jacqueline A. French, MD, Faculty

Ingrid E. Scheffer, MBBS PHD FRACP FAA, Faculty

Ivan Soltesz, PhD, Faculty

John Pollard, MD, Reviewer

AKH STAFF / AES STAFF

Physicians can claim CME credit online at https://cme.experientevent.com/AES151/

How to Claim CME Credit

NURSING & PHARMACY

PLEASE NOTE: Providing your NABP e-profile # is required.

THIS MUST BE DONE BY JANUARY 15, 2017 TO RECEIVE YOUR CE CREDIT.

“Epilepsy” as a concept Seizure vs Epilepsy

Epilepsy is a disease of the brain defined by any of the following

1. A least two unprovoked (or reflex) seizures occurring >24 h apart

Simonato et al, Lancet Neurol 2014; 13: 949–60

These are not Epilepsy because there is no risk of a

• Some seizure types, for example tonic seizures or epileptic spasms, can Pathophysiology Anatomy Networks Practical, by: Modify Existing

Symptoms + Signs Seizure Type flushing/sweating/piloerection autonomic

many‐to‐one jerking arrhythmically myoclonus

Focal Onset Generalized Onset Unknown Onset

2 Due to inadequate information or inability to place in other categories

Impaired Motor Onset: Decide whether seizure onset is focal or

Old = myoclonic seizures followed by a tonic‐clonic seizure

“Words, words, words, I’m so sick of words!”

Tuberous Sclerosis • Where unable to make an Epilepsy Syndrome

Generalized and Focal Epilepsies Seizure types

JME pair; Lennox 1941 CAE pair; Lennox 1950

Developmental and Epileptic Encephalopathies Developmental and/or Epileptic Encephalopathy

STXBP1 KCNA2 DNM1 • eg. CDKL5 encephalopathy, SCN2A encephalopathy

Biochemical parameter Cut off value Serum

Annegers et al. Epilepsia 1995;36:327‐333; Loiseau et al. These, 1987.

1.00 Cumulative Risk of

Log Rank p<0.001

Hesdorffer et al. Epilepsia 2009 Hesdorffer et al, Epilepsia 2009

Acute Symptomatic Seizure 91 41.9%; p<0.001

0.25 Acute Symptomatic Unprovoked Seizure 10 0%

Hesdorffer et al. Epilepsia 2009 Hesdorffer et al. Epilepsia 2009

Etiology Number Cumulative Risk of Death

Hesdorffer et al. Epilepsia 2009 Hesdorffer et al. Epilepsia 2009

Variable Adjusted RR 95% CI

30 day cumulative survival by etiology of status epilepticus Conclusions: Differences Between Acute Symptomatic

Logroscino et al. Epilepsia 1997

Biochemical parameter Cut off value Serum

Annegers et al. Epilepsia 1995;36:327‐333; Loiseau et al. These, 1987.

1.00 Cumulative Risk of

Log Rank p<0.001

Hesdorffer et al. Epilepsia 2009 Hesdorffer et al, Epilepsia 2009

Acute Symptomatic Seizure 91 41.9%; p<0.001

0.25 Acute Symptomatic Unprovoked Seizure 10 0%

Hesdorffer et al. Epilepsia 2009 Hesdorffer et al. Epilepsia 2009

Etiology Number Cumulative Risk of Death