EPILEPSY New Ideas about an Old Disease Gregory D. Cascino, MD
Disclosure Research-Educational Grants Neuro Pace, Inc. American Epilepsy Society American Academy of Neurology Neurology (Associate Editor) National Institutes of Health R01NS053998
EPILEPSY epidemiology Recurrent, unprovoked events Two or more seizures Prevalence: 4% (80 years of age) Incidence: 180,000 per year Early and late onset 12.5 billion USD
EPILEPSY Institute of Medicine March 30, 2012 (iom.edu) Consensus report 1 in 26 people have epilepsy Double the number of patients with Autism spectrum disorders, Multiple Sclerosis, and Parkinson s disease combined
EPILEPSY improvement in quality of life Related to seizure-free outcome DRIVING Avoid adverse effects Education, Employment No need for caregiver Living independently
EPILEPSY adverse effects 25,000-50,000 die of seizures or related causes each year Cognitive disorder Depression and Anxiety disorders SUDEP (sudden unexplained death in epilepsy) Risk of sudden death is 24 times controls
EPILEPSY partial seizure disorder 90% adult incident cases 45% medically refractory seizures Prognosis related to etiology 80% temporal lobe epilepsy amygdalohippocampal
PARTIAL EPILEPSY substrate-directed pathology Primary brain tumor Vascular anomaly Malformation of cortical development Mesial temporal sclerosis
EPILEPSY autoimmune limbic encephalitis Tan et al. (Mayo) Neurology 2008;70:1883-1890 58% of 72 patients with seizures 34 of 38 patients responded to immunotherapy Histological confirmation of cancer in 33%
EPILEPSY autoimmune limbic encephalitis Quek et al. (Mayo) Arch Neuro 2012;69:582-593 32 patients (VGKC) 81% failed 2 or more AEDs Neural Abs (91%), abnormal MRI (63%), CSF inflammation (31%) 81% responded to immunorx; 67% seizure-free
EPILEPSY goals of therapy Educate and counsel Discuss issues of daily living : e.g., safety in the home, driving, employment, birth control, alcohol, AED compliance Map a strategy of care (routine and urgent)
EPILEPSY efficacy of treatment Neurology 2003;60(Suppl 4):S2-12 About 30-40% will have a difficult to control seizure disorder The 1st and 2nd AEDs are highly predictive of medical outcome
INTRACTABLE EPILEPSY efficacy of treatment Epilepsia 2007;62:375-381 PENN Epilepsy Center Refractory epilepsy Randomized add-on trials Seizure-free rates: 0-7%
INTRACTABLE EPILEPSY treatment strategies Curative surgical therapy focal cortical resection, reoperation Palliative surgery VNS, corpus callosotomy Antiepileptic drug medication Ketogenic or Atkins diet Investigational studies
INTRACTABLELEPILEPSY modified Atkins diet Epilepsia 2011;52:775-80 18 adult patients Carbohydrate 20 g/day 14 of 18 remained on diet at 1 year 21% at 1 year had >50% reduction in seizures
Epilepsy & functional anatomy of the human brain
EPILEPSY SURGERY surgical candidates Medically refractory seizures Physically, socially disabled Localization-related epilepsy Low risk for morbidity Potential for rehabilitation
EPILEPSY SURGERY syndromes Lesional epilepsy: tumor, vascular anomaly, malformation of cortical development Medial temporal lobe epilepsy: mesial temporal sclerosis
EPILEPSY SURGERY long-term outcome J of Neurosurgery 2006; 104:513-524 Cohen-Gadol et al. (Mayo) 1988-1996 399 consecutive patients 10 year follow-up
EPILEPSY SURGERY seizure-free outcome 6 months: 81% 12 months: 78% 2 years: 76% 5 years: 74% 10 years: 72%
% Seizure Free 100 90 80 Temporal Lobe Non-Temporal Lobe 70 60 50 40 0 2 4 6 8 10 12 14 1 Time to Seizure or LFU
TEMPORAL LOBE EPILEPSY Normal MRI Epilepsia 2009:50:2053-60 Seizure-free (Engel Class I) 10 pts with subtle MRI changes Other outcomes 24 (60%) 16 (40%) (Engel Class II-IV)
INTRACTABLE EPILEPSY Cavernous hemangiomas Mayo Clin Proc 1994:69:741-5 Seizure-free (Engel Class I) 15 (75%) Near seizure-free (Engel Class II) 3 (15%)
INTRACTABLE EPILEPSY Low-grade gliomas Epilepsia 1994:35:1130-5 Seizure-free (Engel Class I) 34 (67%) Near seizure-free (Engel Class II) 11 (22%)
NON-LESIONAL EPILEPSY neocortical onset MRI is normal Limitations of ictal EEG May have focal cortical dysplasia May be surgical candidates Usually require chronic intracranial EEG studies
Intraoperative digital photography
Intraoperative digital photography
EXTRATEMPORAL Normal MRI J Neurosurg 2009:110:1147-52 Seizure-free (Engel Class I) 10 (36%) Other outcomes (Engel Class II-IV) 18 (64%)
EPILEPSY SURGERY early surgical treatment Neurology 2007;68:1988-1994 138 patients with intractable partial epilepsy 113 patients (82%) in remission Patients seizure-free had a significant improvement in quality of life
EPILEPSY SURGERY Time Means Neurons! Bernhardt et al. (Montreal) Neurology 2009;72:1747-54 18 patients with intractable TLE Progressive neocortical atrophy (mean 2.5 years) Quantitative MRI measurements Related to seizure activity
EPILEPSY SURGERY early surgical treatment Avoid AED adverse effects Avoid expensive and likely ineffective procedures, e.g., VNS Minimize disruption in growth and development Avoid psychosocial debilitation
Electronic stimulation
New Treatments for Epilepsy Brain Stimulation and Prediction SANTE Trial Medtronics RNS Trial NeuroPace Inc
INTRACTABLE EPILEPSY * SANTE Medtronics Intercept Epilepsy Control System DBS 110 adult patients; 17 centers Stimulation of the anterior nucleus of the thalamus Treatment vs. Sham group Approved in EU
Direct Brain Stimulation is not approved for Epilepsy Devices for direct Brain Stimulation stim stim stim stim stim stim stim stim Medtronics Intercept Anterior Nucleus Thalamus
Simulation of Anterior Nucleus Thalamus SANTE Trial Electrode Electrode Courtesy of B. Litt @University of Pennsylvania
INTRACTABLE EPILEPSY SANTE Epilepsia 2010;51:899-908 Responder rate (>50% reduction) 54% responders at 2 years 56% mean reduction in seizures 13% seizure-free for 6 months 5 hemorrhages 5 deaths (not SANTE related)
INTRACTABLE EPILEPSY * RNS Neuro Pace Responsive Neurostimulator System 191 patients; 32 centers Treatment vs. Sham group Need to know localization of epileptic brain tissue
Device for Responsive Stimulation Closed Loop Neuropace RNS
NeuroPace RNS device
Neuropace: RNS
INTRACTABLE EPILEPSY * RNS Neurology 2011;77:1295-1304 Responder rate (>50% reduction) 29% responders 37% reduction in seizures 4.7% hemorrhages Improved quality of life
Gamma knife therapy for temporal lobe epilepsy Radiosurgery or Open Surgery for Epilepsy (ROSE) Trial: A phase III study of Gamma Knife radiosurgery for mesial temporal sclerosis
IMAGE-GUIDED LASER THERMAL ABLATION: Visualase, Inc. Houston, TX.
What s HOT?? Seizure prediction
Typical person with uncontrolled seizures Uncertainty = Disability 3 seizures per month (~ minutes duration) Time in seizure: ~Hour/yr 99.98% of the person s life is seizure free activated. Figure 1 NeuroVista Seizure Advisory System Illustration - Implantable Leads Assembly connected to Implantable Telemetry Unit. Personal Advisory Device (hand carri ed) shown with high likelihood indicator
ON THE HORIZON? Seizure detection: Did I have a seizure last night Documentation of seizure frequency: electronic diary Seizure prediction: When am I going to have another seizure
EPILEPSY INFORMATION epilepsy.com efa.org mayoclinic.org aan.com aesnet.org
"The function of a physician is to cure a few, help many and comfort all" Percival Bailey 1892-1973 neurosurgeon, physiologist, professor, University of Chicago