12/02/2020 DISCLOSURES LATEST UPDATES IN None CLINICAL EPILEPSY - - PowerPoint PPT Presentation

12/02/2020 1 LATEST UPDATES IN CLINICAL EPILEPSY

UCSF 53RD ANNUAL RECENT ADVANCES IN NEUROLOGY February 12, 2020 Bernard S. Chang, M.D., M.M.Sc. Chief, Division of Epilepsy and Clinical Neurophysiology Associate Professor of Neurology Advisory Dean, Peabody Society

DISCLOSURES None

Epilepsy Updates | February 2020 2

OUTLINE Nomenclature and Definitions Epidemiology and Risk Factors Mechanisms and Diagnosis Therapies, Medical and Surgical Comorbidities and Complications

Epilepsy Updates | February 2020 3

A New Classification Scheme for Seizures Has Been Introduced Recently, Eliminating the Use of Jargon with Nonstandard Meanings

Epilepsy Updates | February 2020 4

Fisher et al., 2017

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Epilepsy Syndromes Are Defined By Their Characteristic Seizure Types, As Well As Other Distinguishing Clinical Features

Epilepsy Updates | February 2020 5

Fisher et al., 2017

“Epilepsy” Implies An Enduring Predisposition To Seizures, Which Can Now Be Defined In More Sophisticated Ways

Epilepsy Updates | February 2020 6

Fisher et al., 2017

• “Partial” has been replaced by “focal,” and focal seizures are

classified by loss or preservation of awareness

• Epilepsy syndromes are defined by seizure types, presumed

etiology, and associated clinical and EEG features

• Two seizures are not always necessary to diagnose epilepsy

THREE NEW THINGS IN EPILEPSY NOMENCLATURE AND DEFINITIONS

Epilepsy Updates | February 2020 7

Epilepsy Remains One of the Most Common Neurological Disorders In the United States and Around the World

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GBD 2016 Epilepsy Collaborators, 2019; Centers for Disease Control and Prevention, 2015

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There are Two Peaks of Incidence for New-Onset Epilepsy During Life, and the Higher One is in the Oldest Age Group

Epilepsy Updates | February 2020 9

Epilepsy Across the Spectrum, National Academies Press, 2012

Vascular Risk Factors in Middle Age are Associated With the Development of Epilepsy in Later Life

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Johnson et al., 2018

• The latest estimates of epilepsy prevalence range from 0.8% to

1.2% of the general population

• Old age is the most common period in life to develop epilepsy for

the first time

• Midlife vascular risk factors are associated with the development of

late-life epilepsy, even accounting for effect of stroke and dementia

THREE NEW THINGS IN EPILEPSY EPIDEMIOLOGY AND RISK FACTORS

Epilepsy Updates | February 2020 11

OUTLINE Nomenclature and Definitions Epidemiology and Risk Factors Mechanisms and Diagnosis Therapies, Medical and Surgical Comorbidities and Complications

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Clinical, Imaging and EEG Data All Suggest that Epilepsy is a Network Disease, and Does Not Simply Arise from a Single Focus in the Brain

Epilepsy Updates | February 2020 13

Pedersen et al., 2015

Implanted Recorders And Patient Diaries Have Shown That Seizures Tend To Occur In Cyclic Patterns With Predictable Periodicity For Many Patients

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Karoly et al,, 2018; Baud et al., 2018

A Clear and Growing Subset of Epilepsies Can Be Attributed to Genetic Causes, But True Precision Medicine is Still Down the Road

EpiPM Consortium, 2015

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Many Previously Cryptogenic Cases of Focal Epilepsy May Turn Out to Be Autoimmune or Inflammatory in Etiology

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Dalmau and Graus, 2018

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A Recent International Evidence-Based Guideline Highlights The Clinical Utility of Routine And Long-term EEG Testing

Epilepsy Updates | February 2020 17

Tatum et al., 2018

• Focal seizures involve an abnormal brain network, not just a single

responsible site of origin

• Seizures do not occur randomly; there tend to be predictable

periodic cycles to their appearance in any given patient

• Much of the “unexplained” category of epilepsy may be related to

genetic abnormalities or autoimmunity/inflammation

THREE NEW THINGS IN EPILEPSY MECHANISMS AND DIAGNOSIS

Epilepsy Updates | February 2020 18

OUTLINE Nomenclature and Definitions Epidemiology and Risk Factors Mechanisms and Diagnosis Therapies, Medical and Surgical Comorbidities and Complications

Epilepsy Updates | February 2020 19

Many New Antiepileptic Drugs, With a Variety of Mechanisms of Action, Have Become Steadily Available in More Recent Decades

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Rho and White, 2018; Loscher et al., 2016

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Despite the Introduction of Newer Generation Medications, the Rates of Seizure Freedom And Adverse Effects Have Not Actually Improved

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Chen et al., 2018; Alsfouk et al., JAMA Neurol, in press

Algorithms for Choosing Antiepileptic Drugs Divide the Medications According to Their Spectrum of Coverage, Either Broad or Narrow

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Chong and Bazil, 2010

Cannabidiol (CBD) is a Cannabis-Derived Compound Effective in the Treatment of Lennox-Gastaut Syndrome and Dravet Syndrome

Epilepsy Updates | February 2020 23

Lattanzi et al., 2018

The Classical Ketogenic Diet Can Be Very Effective, and There are Better Tolerated Alternatives As Well

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Kumada et al., 2011; Neal et al., 2008

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• New drugs continually become available, but the overall efficacy

and tolerability of medications has not changed in decades

• Pharmaceutical-grade CBD is approved to treat two epileptic

encephalopathies, but may achieve widespread off-label use

• Dietary therapies are particularly valuable in children, though

modified forms are more palatable than the classic ketogenic diet

THREE NEW THINGS IN NONSURGICAL EPILEPSY THERAPIES

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Deep Brain Stimulation of the Anterior Nucleus of the Thalamus Is Now an Approved Treatment for Drug-Resistant Epilepsy

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Pivotal trial SANTE from 2010:

• 110 enrolled patients
• by ~2 years, median seizure frequency reduction >50% and

significant improvement in quality of life Long-term follow-up data:

• most patients experience further gradual improvement
• seizure reduction reaching nearly 70% by 5 years

Surgical complications were not trivial:

• site infections (12%)
• electrode malpositioning (8%)
• intracerebral hemorrhage (5%)

There may be multiple components to the therapeutic effect:

• an immediate insertional effect
• an immediate stimulation effect
• a delayed stimulation effect

Fisher et al,, 2010; Salanova et al., 2015; Krishna et al., 2016

Multiple Neuromodulation Technologies Are Now Available for the Treatment of Drug-Resistant Epilepsy

Epilepsy Updates | February 2020 27

VNS DBS RNS

Shah, Eliashiv, and Rider- Demer, 2018 and 2019

Stereotactic Radiosurgery Can Approach the Success Rates Of Conventional Surgical Resection of the Seizure Focus

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Samuji and Vernimmen, 2013; Barbaro et al,, 2018

The ROSE Study

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Laser Interstitial Thermal Therapy (LITT) Can Be Used To Ablate a Targeted Mesial Temporal Seizure Focus

Epilepsy Updates | February 2020 29

Youngerman, Save, and McKhann, 2000

The Two Minimally Invasive Focal Surgical Options Are Fairly Comparable To Each Other but Need Rigorous Long-Term Assessment of Outcomes

Epilepsy Updates | February 2020 30

Grewal et al., 2019

An Algorithm Can Codify the Clinical Decision-Making Process With Regard to Epilepsy Surgery Consideration

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Englot, 2018

• Of the neuromodulation options, RNS requires localization of the

focus (using intracranial EEG), while VNS and DBS do not

• It is uncommon to achieve complete seizure freedom through

neuromodulation, but most patients have a big decrease in seizures

• Less invasive focal ablative procedures are now available as an

alternative to traditional resective surgery

THREE NEW THINGS IN EPILEPSY SURGICAL THERAPIES

Epilepsy Updates | February 2020 32

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OUTLINE Nomenclature and Definitions Epidemiology and Risk Factors Mechanisms and Diagnosis Therapies, Medical and Surgical Comorbidities and Complications

Epilepsy Updates | February 2020 33

Alzheimer’s Disease is Associated with Subclinical Epileptiform EEG Activity, and There are Potential Shared Mechanisms with Epilepsy

Epilepsy Updates | February 2020 34

Vossel et al., 2017; Sen et al., 2018

SUDEP is the Most Common Cause of Epilepsy-Related Mortality, and the Risk is Linked to Frequent Generalized Tonic-Clonic Seizures

Epilepsy Updates | February 2020 35

Harden et al., 2017

A Head-to-Head Trial in Status Epilepticus Showed Equally Good Results Using Any Of Three Standard Antiepileptic Drugs

The ESETT Trial

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Kapur et al., 2019; Betjemann and Lowenstein, 2017

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• There may be mechanistic overlap between Alzheimer’s and

epilepsy, which could have enormous public health implications

• SUDEP occurs in about 1.2 adults per 1000 patient-years, and the

risk remains highly related to frequent convulsive seizures

• For status epilepticus, there are several equivalently effective

agents that can be used after benzodiazepines are administered

THREE NEW THINGS IN EPILEPSY COMORBIDITIES AND COMPLICATIONS

Epilepsy Updates | February 2020 37 38

FRANCIS WELD PEABODY SOCIETY DIVISION OF EPILEPSY AND CLINICAL NEUROPHYSIOLOGY

Division Chief Bernard Chang Practice Manager Mary-Ann Dobrota EEG Lab Director Mouhsin Shafi Fellowship Director Trudy Pang Senior EEG Tech Patricia Morin Nurse Specialists Diane Sundstrom, Matthew Reed Clinical Engineer Rebekah Wigton Neurosurgeon Jeffrey Arle Frank Drislane Daniel Goldenholz Walter Heine Lu Lin Monica Makhija Volney Sheen Attending Physicians Donald Schomer

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