EPILEPSY. New Ideas about an Old Disease. Gregory D. Cascino, MD

Transcription

1 EPILEPSY New Ideas about an Old Disease Gregory D. Cascino, MD

2 Disclosure Research-Educational Grants Neuro Pace, Inc. American Epilepsy Society American Academy of Neurology Neurology (Associate Editor) National Institutes of Health R01NS053998

3 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

4 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

5 EPILEPSY improvement in quality of life Related to seizure-free outcome DRIVING Avoid adverse effects Education, Employment No need for caregiver Living independently

6

7 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

8

9 EPILEPSY partial seizure disorder 90% adult incident cases 45% medically refractory seizures Prognosis related to etiology 80% temporal lobe epilepsy amygdalohippocampal

10

11

12

13 PARTIAL EPILEPSY substrate-directed pathology Primary brain tumor Vascular anomaly Malformation of cortical development Mesial temporal sclerosis

14

15

16

17

18

19

20

21 EPILEPSY autoimmune limbic encephalitis Tan et al. (Mayo) Neurology 2008;70: % of 72 patients with seizures 34 of 38 patients responded to immunotherapy Histological confirmation of cancer in 33%

22

23

24

25 EPILEPSY autoimmune limbic encephalitis Quek et al. (Mayo) Arch Neuro 2012;69: patients (VGKC) 81% failed 2 or more AEDs Neural Abs (91%), abnormal MRI (63%), CSF inflammation (31%) 81% responded to immunorx; 67% seizure-free

26 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)

27 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

28 INTRACTABLE EPILEPSY efficacy of treatment Epilepsia 2007;62: PENN Epilepsy Center Refractory epilepsy Randomized add-on trials Seizure-free rates: 0-7%

29 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

30 INTRACTABLELEPILEPSY modified Atkins diet Epilepsia 2011;52: adult patients Carbohydrate 20 g/day 14 of 18 remained on diet at 1 year 21% at 1 year had >50% reduction in seizures

31 Epilepsy & functional anatomy of the human brain

32

33

34 EPILEPSY SURGERY surgical candidates Medically refractory seizures Physically, socially disabled Localization-related epilepsy Low risk for morbidity Potential for rehabilitation

35 EPILEPSY SURGERY syndromes Lesional epilepsy: tumor, vascular anomaly, malformation of cortical development Medial temporal lobe epilepsy: mesial temporal sclerosis

36 EPILEPSY SURGERY long-term outcome J of Neurosurgery 2006; 104: Cohen-Gadol et al. (Mayo) consecutive patients 10 year follow-up

37 EPILEPSY SURGERY seizure-free outcome 6 months: 81% 12 months: 78% 2 years: 76% 5 years: 74% 10 years: 72%

38 % Seizure Free Temporal Lobe Non-Temporal Lobe Time to Seizure or LFU

39

40

41

42 TEMPORAL LOBE EPILEPSY Normal MRI Epilepsia 2009:50: Seizure-free (Engel Class I) 10 pts with subtle MRI changes Other outcomes 24 (60%) 16 (40%) (Engel Class II-IV)

43 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%)

44 INTRACTABLE EPILEPSY Low-grade gliomas Epilepsia 1994:35: Seizure-free (Engel Class I) 34 (67%) Near seizure-free (Engel Class II) 11 (22%)

45 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

46

47

48

49 Intraoperative digital photography

50 Intraoperative digital photography

51

52 EXTRATEMPORAL Normal MRI J Neurosurg 2009:110: Seizure-free (Engel Class I) 10 (36%) Other outcomes (Engel Class II-IV) 18 (64%)

53 EPILEPSY SURGERY early surgical treatment Neurology 2007;68: patients with intractable partial epilepsy 113 patients (82%) in remission Patients seizure-free had a significant improvement in quality of life

54 EPILEPSY SURGERY Time Means Neurons! Bernhardt et al. (Montreal) Neurology 2009;72: patients with intractable TLE Progressive neocortical atrophy (mean 2.5 years) Quantitative MRI measurements Related to seizure activity

55 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

56 Electronic stimulation

57 New Treatments for Epilepsy Brain Stimulation and Prediction SANTE Trial Medtronics RNS Trial NeuroPace Inc

58 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

59 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

60 Simulation of Anterior Nucleus Thalamus SANTE Trial Electrode Electrode Courtesy of B. of Pennsylvania

61 INTRACTABLE EPILEPSY SANTE Epilepsia 2010;51: 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)

62 INTRACTABLE EPILEPSY * RNS Neuro Pace Responsive Neurostimulator System 191 patients; 32 centers Treatment vs. Sham group Need to know localization of epileptic brain tissue

63 Device for Responsive Stimulation Closed Loop Neuropace RNS

64

65 NeuroPace RNS device

66 Neuropace: RNS

67 INTRACTABLE EPILEPSY * RNS Neurology 2011;77: Responder rate (>50% reduction) 29% responders 37% reduction in seizures 4.7% hemorrhages Improved quality of life

68 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

69

70

71 IMAGE-GUIDED LASER THERMAL ABLATION: Visualase, Inc. Houston, TX.

72

73

74 What s HOT?? Seizure prediction

75 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

76 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

77

78

79 EPILEPSY INFORMATION epilepsy.com efa.org mayoclinic.org aan.com aesnet.org

80 "The function of a physician is to cure a few, help many and comfort all" Percival Bailey neurosurgeon, physiologist, professor, University of Chicago