Transcript Slide 1

New Insights into the
Basic Mechanisms, Diagnosis,
and Staging of Epilepsy
Nicole Odom, MD
Columbia University Medical Center Comprehensive Epilepsy Center,
New York–Presbyterian Medical Center, New York, New York
A REPORT FROM THE 67TH ANNUAL MEETING OF THE AMERICAN EPILEPSY SOCIETY (AES 2013)
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2014 NINDS Benchmarks
for Epilepsy Research
National Institute of Neurological Disorders and Stroke (NINDS)
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2014 NINDS Benchmarks
for Epilepsy Research

“No seizures, no side effects, and the prevention of
epilepsy” are the primary goals of epileptologists.”

These goals are important because they raise
awareness of priorities across the epilepsy
community.

Benchmark III—improving treatment options for
controlling seizures and epilepsy-related conditions
without side effects—is the impetus driving research
in the three areas discussed in the remainder of this
presentation.
National Institute of Neurological Disorders and Stroke (NINDS)
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Staging and Translational Aspects of
Animal Models of Epilepsy

The concept of staging epilepsy is a hypothetical
construct stemming from its similarities to cancer
research.

Epilepsy syndromes, similar to different types of
cancer, have significant heterogeneity yet often
possess common signaling pathways and capacity for
disease modification.

One advantage of this model is that it may allow for a
more accurate assessment of whether the disease has
been altered.
Based on a presentation by Frances Jensen, MD, at AES 2013
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Staging and Translational Aspects of
Animal Models of Epilepsy

To successfully stage epilepsy, certain essential
elements need to be clearly defined and harmonized,
such as common data elements and biomarkers.

Biomarkers rely on indirect histopathology
associated with common data elements.

Common data elements must therefore be
synchronized and calibrated.

A recent example of translational research aligning
common data elements and biomarkers is the
identification of MRI imaging of glutamate
(GluCEST).
Cai K et al. Nat Med. 2012;18:302
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Staging and Translational Aspects of
Animal Models of Epilepsy

The staging of epilepsy
should encompass preepilepsy to drug-resistant
epilepsy.

Secondary staging,
including comorbidities,
also may prove useful.
Based on a presentation by Frances Jensen, MD, at AES 2013
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Clinical Issues and Seizure Severity

The severity of seizures differs dramatically between
individuals.

Some remain seizure free on low doses of one drug,
while others have weekly seizures despite surgery,
vagal nerve stimulation, or multiple medications.

Two cases may present with a single similar complex
partial seizure, but what factors are responsible for
the differences between the two patients?

Staging seizures by way of improved identification of
seizure severity and disease course will allow
providers to make better management decisions.
Based on a presentation by R. Edward Hogan, MD, at AES 2013
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Clinical Issues and Seizure Severity

Current tools to measure seizure severity are suboptimal:
» Therapeutic drug levels needed to achieve seizure freedom
» Amount of interictal discharges on EEG
» Progession of MRI lesion

For these reasons, improved diagnostic tools, including
those with longitudinal capabilities, are necessary:
» “Dry electrode” system and long-term intracranial EEG are
examples of ways in which patients may be monitored on EEG for
a longer time, thereby enhancing sensitivity of seizure detection.
»
Quantitative structural MRI studies, based on volumetry, voxelbased morphometry, cortical thickness mapping, and structural
covariance analysis have shown extensive and progressive loss of
cortical gray matter in temporal and extratemporal regions.
Based on a presentation by R. Edward Hogan, MD, at AES 2013
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Staging of Seizures According to
Current Classification Systems

Staging of epilepsy helps the physician make
management decisions for the individual patient.

Staging also may help the patient to understand his
or her condition.

Staging incorporates severity, extent, and prognosis.

Staging should evolve over time as knowledge about
epilepsy advances.

To date, very few studies have tried to use staging as
a means for gaining information or making a
prediction.
Based on a presentation by Elinor Ben-Menachem, MD, PhD, at AES 2013
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Investigating a Staging System

Proposed staging system: FEDS
» (F) size and/or extent of primary focus or foci
» (E) pathologic EEG and extent of interictal pathology
» (D) patient status as being truly drug-resistant or able to
have successful epilepsy surgery
» (S) history of status epilepticus

Advantages include:
» Ability to estimate prognosis
» Plan the appropriate treatment
» Identify clinical trials and contribute to a common
terminology for evaluating and comparing results of clinical
trials and different treatment approaches
Based on a presentation by Elinor Ben-Menachem, MD, PhD, at AES 2013
© 2014 Direct One Communications, Inc. All rights reserved.
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Conclusion

As new and exciting advances in the field of epilepsy
emerge, innovative ways of organizing this
information also must evolve.

The staging of epilepsy may help us to improve
treatment options for epilepsy-related conditions
while minimizing the side effects of therapy.
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