12/02/2020 DISCLOSURES LATEST UPDATES IN None 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 Epilepsy Updates | February 2020 2 1 2 OUTLINE A New Classification Scheme for Seizures Has Been Introduced Recently, Eliminating the Use of Jargon with Nonstandard Meanings Nomenclature and Definitions Epidemiology and Risk Factors Mechanisms and Diagnosis Therapies, Medical and Surgical Comorbidities and Complications Fisher et al., 2017 Epilepsy Updates | February 2020 3 Epilepsy Updates | February 2020 4 3 4 1
12/02/2020 “Epilepsy” Implies An Enduring Predisposition To Seizures, Epilepsy Syndromes Are Defined By Their Characteristic Seizure Types, Which Can Now Be Defined In More Sophisticated Ways As Well As Other Distinguishing Clinical Features Fisher et al., 2017 Fisher et al., 2017 Epilepsy Updates | February 2020 5 Epilepsy Updates | February 2020 6 5 6 Epilepsy Remains One of the Most Common Neurological Disorders In the United States and Around the World THREE NEW THINGS IN EPILEPSY NOMENCLATURE AND DEFINITIONS • “Partial” has been replaced by “focal,” and focal seizures are classified by loss or preservation of awareness • Epilepsy syndromes are defined by seizure types, presumed etiology, and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 GBD 2016 Epilepsy Collaborators, 2019; Centers for Disease Control and Prevention, 2015 Epilepsy Updates | February 2020 7 Epilepsy Updates | February 2020 8 7 8 2
12/02/2020 There are Two Peaks of Incidence for New-Onset Epilepsy During Life, Vascular Risk Factors in Middle Age are Associated and the Higher One is in the Oldest Age Group With the Development of Epilepsy in Later Life Johnson et al., 2018 Epilepsy Across the Spectrum, National Academies Press, 2012 Epilepsy Updates | February 2020 9 Epilepsy Updates | February 2020 10 9 10 OUTLINE THREE NEW THINGS IN EPILEPSY EPIDEMIOLOGY AND RISK FACTORS Nomenclature and Definitions • The latest estimates of epilepsy prevalence range from 0.8% to 1.2% of the general population Epidemiology and Risk Factors Mechanisms and Diagnosis • Old age is the most common period in life to develop epilepsy for Therapies, Medical and Surgical the first time Comorbidities and Complications • Midlife vascular risk factors are associated with the development of late-life epilepsy, even accounting for effect of stroke and dementia Epilepsy Updates | February 2020 11 Epilepsy Updates | February 2020 12 11 12 3
12/02/2020 Clinical, Imaging and EEG Data All Suggest that Epilepsy is a Network Disease, Implanted Recorders And Patient Diaries Have Shown That Seizures Tend and Does Not Simply Arise from a Single Focus in the Brain To Occur In Cyclic Patterns With Predictable Periodicity For Many Patients Karoly et al,, 2018; Pedersen et al., 2015 Baud et al., 2018 Epilepsy Updates | February 2020 13 Epilepsy Updates | February 2020 14 13 14 A Clear and Growing Subset of Epilepsies Can Be Attributed to Many Previously Cryptogenic Cases of Focal Epilepsy May Turn Out Genetic Causes, But True Precision Medicine is Still Down the Road to Be Autoimmune or Inflammatory in Etiology EpiPM Consortium, 2015 Dalmau and Graus, 2018 Epilepsy Updates | February 2020 15 Epilepsy Updates | February 2020 16 15 16 4
12/02/2020 A Recent International Evidence-Based Guideline Highlights The Clinical Utility of Routine And Long-term EEG Testing THREE NEW THINGS IN EPILEPSY MECHANISMS AND DIAGNOSIS • 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 Tatum et al., 2018 Epilepsy Updates | February 2020 17 Epilepsy Updates | February 2020 18 17 18 Many New Antiepileptic Drugs, With a Variety of Mechanisms of Action, OUTLINE Have Become Steadily Available in More Recent Decades Nomenclature and Definitions Epidemiology and Risk Factors Mechanisms and Diagnosis Therapies, Medical and Surgical Comorbidities and Complications Rho and White, 2018; Loscher et al., 2016 Epilepsy Updates | February 2020 19 Epilepsy Updates | February 2020 20 19 20 5
12/02/2020 Despite the Introduction of Newer Generation Medications, the Rates of Algorithms for Choosing Antiepileptic Drugs Divide the Medications Seizure Freedom And Adverse Effects Have Not Actually Improved According to Their Spectrum of Coverage, Either Broad or Narrow Chen et al., 2018; Alsfouk et al., JAMA Neurol, in press Chong and Bazil, 2010 Epilepsy Updates | February 2020 21 Epilepsy Updates | February 2020 22 21 22 Cannabidiol (CBD) is a Cannabis-Derived Compound Effective in the The Classical Ketogenic Diet Can Be Very Effective, Treatment of Lennox-Gastaut Syndrome and Dravet Syndrome and There are Better Tolerated Alternatives As Well Kumada et al., 2011; Neal et al., 2008 Lattanzi et al., 2018 Epilepsy Updates | February 2020 23 Epilepsy Updates | February 2020 24 23 24 6
12/02/2020 Deep Brain Stimulation of the Anterior Nucleus of the Thalamus Is Now an Approved Treatment for Drug-Resistant Epilepsy THREE NEW THINGS IN NONSURGICAL EPILEPSY THERAPIES Pivotal trial SANTE from 2010 : • 110 enrolled patients • New drugs continually become available, but the overall efficacy • by ~2 years, median seizure frequency reduction >50% and significant improvement in quality of life and tolerability of medications has not changed in decades Long-term follow-up data : • most patients experience further gradual improvement • seizure reduction reaching nearly 70% by 5 years • Pharmaceutical-grade CBD is approved to treat two epileptic encephalopathies, but may achieve widespread off-label use Surgical complications were not trivial : • site infections (12%) • electrode malpositioning (8%) • intracerebral hemorrhage (5%) • Dietary therapies are particularly valuable in children, though There may be multiple components to the therapeutic effect : modified forms are more palatable than the classic ketogenic diet Fisher et al,, 2010; Salanova et al., 2015; • an immediate insertional effect Krishna et al., 2016 • an immediate stimulation effect • a delayed stimulation effect Epilepsy Updates | February 2020 25 Epilepsy Updates | February 2020 26 25 26 Multiple Neuromodulation Technologies Are Now Available Stereotactic Radiosurgery Can Approach the Success Rates for the Treatment of Drug-Resistant Epilepsy Of Conventional Surgical Resection of the Seizure Focus The ROSE Study Shah, Eliashiv, and Rider- DBS RNS VNS Demer, 2018 and 2019 Samuji and Vernimmen, 2013; Barbaro et al,, 2018 Epilepsy Updates | February 2020 27 Epilepsy Updates | February 2020 28 27 28 7
12/02/2020 Laser Interstitial Thermal Therapy (LITT) Can Be Used The Two Minimally Invasive Focal Surgical Options Are Fairly Comparable To Ablate a Targeted Mesial Temporal Seizure Focus To Each Other but Need Rigorous Long-Term Assessment of Outcomes Youngerman, Save, and McKhann, 2000 Grewal et al., 2019 Epilepsy Updates | February 2020 29 Epilepsy Updates | February 2020 30 29 30 An Algorithm Can Codify the Clinical Decision-Making Process With Regard to Epilepsy Surgery Consideration THREE NEW THINGS IN EPILEPSY SURGICAL THERAPIES • 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 Englot, 2018 Epilepsy Updates | February 2020 31 Epilepsy Updates | February 2020 32 31 32 8
12/02/2020 OUTLINE Alzheimer’s Disease is Associated with Subclinical Epileptiform EEG Activity, and There are Potential Shared Mechanisms with Epilepsy Nomenclature and Definitions Epidemiology and Risk Factors Mechanisms and Diagnosis Therapies, Medical and Surgical Comorbidities and Complications Vossel et al., 2017; Sen et al., 2018 Epilepsy Updates | February 2020 33 Epilepsy Updates | February 2020 34 33 34 SUDEP is the Most Common Cause of Epilepsy-Related Mortality, A Head-to-Head Trial in Status Epilepticus Showed Equally Good Results and the Risk is Linked to Frequent Generalized Tonic-Clonic Seizures Using Any Of Three Standard Antiepileptic Drugs The ESETT Trial Harden et al., 2017 Kapur et al., 2019; Betjemann and Lowenstein, 2017 Epilepsy Updates | February 2020 35 Epilepsy Updates | February 2020 36 35 36 9
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