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Epilepsy 101

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Title: Epilepsy 101


1
Epilepsy 101
  • Paul B. Atkinson, MD
  • MEG - Minnesota Epilepsy Group

2
Epilepsy Foundation
  • Great Information Source
  • Support Groups
  • School Programs
  • Educational Programs
  • Advocacy - Local and National

3
Epilepsy Foundation Mission Statement
  • The Epilepsy Foundation leads the fight to stop
    seizures, find a cure and overcome the challenges
    created by epilepsy.

4
Topics Today
  • Basics of how the brain works
  • Definitions
  • What is a seizure?
  • What is epilepsy?
  • Epidemiology of seizures and epilepsy
  • Seizure types
  • Evaluation and treatment of epilepsy

5
Topics Today
  • Medically intractable epilepsy
  • Definition
  • Treatment options
  • Safety issues in epilepsy
  • Summary
  • Time for questions

6
How the Brain Communicates
  • Cells Building blocks of all body systems
  • Neurons Brain cells that send information
    within the brain or to/from the body
  • 100 billion neurons in the human brain
  • Electrical signals travel down long wires of the
    neuron, called axons
  • Proper function requires these electrical signals
    to be well controlled

7
Neuron
8
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9
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10
Neuron
11
Neuronal Input
www.mult-sclerosis.org
12
Neurons
  • If enough input is received, then an action
    potential is generated

hyperphysics.phy-astr.gsu.edu
13
Synapse
14
Neuronal Connections
www.lavia.org
15
Normal Communication
  • Rapid onset and offset
  • Highly controlled and precise

16
Definition of Seizure
  • Seizure Uncontrolled, synchronous firing of
    electrical signals from neurons in the brain
  • Provoked
  • Unprovoked

17
Provoked Seizure
  • Seizure with an identifiable, reversible cause
  • Medical Conditions
  • Low blood sugar, low blood sodium levels
  • Withdrawing from alcohol or benzodiazepines
  • Medications
  • Illicit Drugs
  • Cocaine, amphetamines, PCP

18
Unprovoked Seizure
  • Seizure occurring due to known brain lesion
  • Stroke, tumor, trauma, infection, congenital
    brain issues, Alzheimers disease
  • Seizures with no provoking cause found

19
Definition of Epilepsy
  • More than one unprovoked seizure separated in
    time
  • Minimally 24 hours apart
  • 100 provoked seizures would not be defined as
    epilepsy
  • Definition being re-evaluated

20
Epidemiology of Seizures
  • 10 of Americans will have a seizure by the age
    of 75
  • 300,000 with first seizure every year
  • 120,000 under age 18

21
Epidemiology of Epilepsy
  • 1 of Americans will be diagnosed with epilepsy
    by age 20
  • 1/26 people will develop epilepsy in their
    lifetime
  • 40 million people affected worldwide
  • Incidence likely slightly higher in developing
    countries
  • Data from the Epilepsy Foundation

22
Fourth Most Common US Neurological Disorder
  • Migraine
  • Stroke
  • Alzheimers Disease
  • Epilepsy
  • Prevalence higher than the combination of all
    autistic spectrum disorder, Parkinsons disease,
    MS, and cerebral palsy combined.

Data from the Epilepsy Foundation
23
Epilepsy Incidence with Age
Hauser et al., Epilepsia 1993, 34 453-468
24
Seizure and Epilepsy Etiologies by Age
  • Infancy and childhood
  • Prenatal or birth injury
  • Inborn error of metabolism
  • Congenital malformation
  • Childhood and adolescence
  • Idiopathic (genetic) syndrome
  • CNS infection
  • Head trauma

25
Etiologies by Age Continued
  • Adolescence and young adult
  • Head trauma
  • Drug intoxication and withdrawal
  • Older adult
  • Stroke
  • Brain tumor
  • Acute metabolic disturbances
  • Neurodegenerative diseases
  • Head Trauma
  • Causes of acute symptomatic seizures, not
    epilepsy

26
Etiology of Epilepsy
  • 65 Cryptogenic
  • 10 Vascular
  • 8 Congenital
  • 6 Trauma
  • 4 Neoplastic
  • 4 Degenerative
  • 3 Infection
  • Hauser et al., Epilepsia 1993, 34 453-468

27
Epilepsy Risk for Special Populations
  • Static encephalopathy 25.8
  • Cerebral palsy 13
  • Static encephalopathy and CP 50
  • Alzheimers disease 10
  • Stroke patients 22
  • Children of mothers with epilepsy 8.7
  • Children of fathers with epilepsy 2.4

28
Classification of Seizures
  • Focal versus Primary Generalized Seizures

29
Focal (Partial) Onset Seizures
  • Seizure begins in one part of the brain
  • Symptoms depend on which part of brain is affected

30
Focal (Partial) Onset Seizures
  • Simple - consciousness spared
  • With motor signs
  • Jacksonian march, versive head movements
  • With somatosensory of special sensory symptoms
  • Somatosensory, flashing lights, olfactory,
    gustatory, vertiginous
  • With autonomic symptoms or signs
  • Epigastric sensation, pallor, sweating, pupillary
    dilation
  • With psychic symptoms or signs
  • Déjà vu, dreamy states, time distortion, fear,
    illusions

31
Focal (Partial) Onset Seizures
  • Complex - consciousness impaired
  • Clinical manifestations vary with site of origin
    and degree of spread
  • Purposeless automatisms
  • Amnesia for the event
  • Secondary generalized - from focal onset to
    generalized seizure
  • Generalized tonic-clonic, tonic, or clonic
  • Typically 1-2 minutes

32
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33
Primarily Generalized Seizures
  • Seizure that begins on both sides of the brain at
    the same time

34
Generalized Onset Seizures
  • Seizures with Tonic and/or Clonic Manifestations
  • Tonic-clonic seizures
  • Clonic seizures
  • Tonic seizures
  • Absences
  • Typical absence
  • Atypical absence
  • Myoclonic seizure types
  • Atonic seizures

35
Seizures with Tonic and/or Clonic Manifestations
  • Tonic-Clonic seizures Grand Mal
  • Tonic contraction including respiratory muscles
  • Tongue biting, urinary incontinence
  • Cyanosis
  • Lasts 30-40 seconds
  • Clonic phase - convulsive movements
  • Foaming at mouth, short grunting type of
    respirations may occur, but remain cyanotic
  • Usually 30-50 seconds
  • Deep respirations as phase ends

36
Absence Seizures
  • Typical Absence Petit mal
  • 3 Hz spike and slow wave complexes, can
    precipitate with HV
  • Generally normal interictally
  • Impairment of consciousness with no post-ictal
    confusion
  • One of few seizure types where you treat EEG
  • Can have mild components of tonic, clonic, or
    atonic features, or may have mild automatisms

37
Absence Seizures
  • Atypical Absence
  • Onset and resolution not as abrupt as typical
    absence
  • More pronounced loss in tone, automatisms
  • Last longer - up to several minutes
  • Slower spike-wave discharges at 1.5-2.5 Hz
  • Interictal EEG abnormal
  • Often seen in Lennox-Gastaut

38
Myoclonic Seizures
  • Sudden, brief contractions
  • Usually bilateral, maximal in arms
  • One second in duration
  • Often multiple
  • May be photic or sensory triggered
  • Often maximal upon awakening
  • Also increased at night when drowsy
  • Must differentiate from non-epileptic myoclonic
    jerks and action myoclonus

39
Atonic Seizures
  • Abrupt onset
  • Sudden loss in tone
  • Head drop, slacking of jaw, or complete loss of
    tone with falls
  • Frequent injuries - helmet
  • Last only a second or two in duration
  • Poor response to AEDs

40
Typical Absence
41
Evaluation of New Onset Seizures
42
Issues
  • Was it a seizure?
  • Provoked or unprovoked?
  • Was it really the first seizure?
  • What studies are needed?
  • Treat or not to treat?

43
Acute Work-up in ER
  • History
  • Physical exam
  • Labs
  • Imaging
  • Neurology Referral

44
Neurologist Visit
  • History
  • Was it really a seizure?
  • Eye witness account of event, actions of patient,
    duration, post-ictal phase, tongue biting,
    incontinence
  • Is this really the first seizure?
  • Past history of staring spells, confusional
    episodes, waking on floor, blood on pillow,
    nocturnal incontinence, childhood seizures
  • Risk factors for epilepsy?
  • Birth history, history of febrile seizures, past
    head trauma, past brain infection, family history
    of seizures, prior stroke or other brain injury

45
Neurologist Visit
  • Complete neurological examination
  • Review previous imaging and labs
  • Decision to treat and/or further workup
  • Electroencephalogram (EEG)
  • Magnetic Resonance Imaging (MRI)
  • Contrasted CT scan if MRI not obtainable
  • Other workup needed?
  • Cardiac monitoring, tilt table testing

46
EEG
47
MRI
48
MRI
49
Treat or Not to Treat?
  • How sure is diagnosis
  • Provoked - treat underlying cause
  • If was an unprovoked seizure, then the decision
    is based on the likelihood of recurrence in that
    patient, or the patients desire
  • High risk Treatment seems appropriate
  • Low risk Treatment may not be necessary
  • Evidence of prior seizures?
  • Equals epilepsy, and would recommend treatment

50
Risk for Recurrence
  • Normal exam, imaging, and EEG
  • 25-30 risk of recurrence
  • Normal exam, abnormal imaging or EEG
  • 50 risk of recurrence
  • Abnormal EEG and MRI
  • 70 risk recurrence

51
Medication Considerations
  • Side effects - acute
  • Long-term side effects
  • Medication interactions
  • Goal in all patients is to have no seizures and
    no side effects. Cannot always be met, but
    should always be strived for.

52
Recurrence
  • If patients opt not to be treated
  • 80 of those that will recur do so in first 2
    years
  • Majority of which occur in first 6 months

53
Other Factors
  • Driving
  • Employment
  • Social and cultural issues
  • Insurance issues

54
Treatment of Epilepsy
55
Epilepsy Treatment
  • Anti-seizure medications
  • Mainstay of treatment
  • Surgery
  • VNS
  • RNS
  • Diet Therapies

56
Epilepsy Medications
  • Carbamazepine
  • Clobazam
  • Clonazepam
  • Diazepam
  • Eslicarbazepine
  • Ethosuximide
  • Ezogabine
  • Felbamate
  • Gabapentin
  • Lacosamide
  • Lamotrigine
  • Levetiracetam
  • Lorazepam
  • Methsuximide
  • Oxcarbazepine
  • Phenobarbital
  • Perampanel
  • Phenytoin
  • Pregabalin
  • Primidone
  • Rufinamide
  • Tiagabine
  • Topirimate
  • Tranxene
  • Valproic Acid
  • Vigabatrin
  • Zonisamide

57
Choosing a Medication
  • Seizure type
  • Interactions with other medications
  • Concurrent medical conditions
  • Potential adverse effects
  • Titration schedule to effective dose
  • Cost

58
Once a medication is chosen, what is the
likelihood of seizure control?
59
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60
Medically Intractable Epilepsy
  • Multiple medication trials, combined medication
    therapy, and still having seizures
  • Newer medications release in past decade
  • No significant changes in efficacy
  • Improved side effect profiles, reduced medication
    interactions

61
Potential Options for Medically Intractable
Epilepsy
  • Surgery
  • Vagal Nerve Stimulator (VNS)
  • Responsive Neurostimulation (RNS)
  • Dietary Treatments

62
Epilepsy Treatment - Surgery
  • Patients should be considered after failing at
    least 2 AEDs that have been raised to the
    maximally tolerated dose
  • Failed combined therapy
  • Can be curative
  • Underutilized
  • Goal is to have evaluation within 2-3 years (some
    advocate within first year)
  • Early referral to an epilepsy center

63
Surgical Evaluation
  • Continuous video EEG monitoring
  • Neuropsychological testing
  • MRI 3T
  • MEG/MSI
  • Invasive video EEG monitoring
  • Strip or grid electrodes
  • Wada testing
  • fMRI
  • PET Scan

64
Epilepsy Surgery Outcomes
Temporal Extra Lesional
Callosotomy Temporal Seizure Free
68 45 66 8 Improved 23 35
22 61 Not improved 9 20 12
31 Total 100 100 100 100
Reference Engel, J. NEJM, Vol 334 1996, 647-653
65
  • Not everyone who fails medications will be a
    resective surgery candidate
  • Primary generalized epilepsy
  • Multiple ictal foci on EEG
  • Eloquent cortex
  • Not all patients who are good candidates desire
    this type of therapy

66
Medical Devices
67
Vagal Nerve Stimulator (VNS)
  • Good option for medically intractable epilepsy in
    patients who are not candidates for surgery or
    choose not to undergo resective surgery
  • Potentially decrease seizure frequency without
    contributing to polypharmacy or drug interactions

68
VNS Components
  • Generator
  • Placed in the anterior left chest, inferior to
    clavicle
  • Leads
  • Bipolar stimulating electrodes
  • Coiled around the vagus nerve within the carotid
    sheath

69
Programmable
  • Wand connected to PDA
  • Interrogate device
  • Reprogram
  • Lead check
  • Battery check

Image from vnstherapies.com
70
VNS
  • Two forms of stimulus from VNS
  • Programmed, intermittent, electrical impulses to
    vagus nerve
  • Programmed by neurologist
  • Patient on-demand stimulation
  • Magnet placed over device provides longer
    stimulation
  • Patients use when sense aura
  • Families can use to attempt to abort seizures

71
  • Magnet worn like a watch by patients
  • When placed over the generator, triggers stimulus
    programmed by neurologist
  • Can be taped over generator to stop stimulus -
    intolerable side effects

Image from vnstherapies.com
72
Adapted from Morris et al., Neurology 1999, 53
1731-1735.
73
Percent Affected
Adapted from Morris et al., Neurology 1999, 53
1731-1735.
74
Retrospective Trial of 436 Consecutive Patients
  • 3 removed due to infection
  • 33 patients lost to follow-up
  • Ages 1-76
  • Follow up to 11 years
  • 22.5 with greater than 90 seizure reduction
  • 40.5 with greater than 75 seizure reduction
  • 63.75 Responder rate

Elliott et al. Epi Behav. 20 57-63, 2011
75
Retrospective Trial of 65 Consecutive Patients
  • VNS in for at least 10 years mean seizure
    reduction at specific time points
  • 6 months 35.7
  • 1 Year 52.1
  • 2 Years 58.3
  • 4 Years 60.4
  • 6 Years 65.7
  • 8 Years 75.5
  • 10 Years 75.5

Elliott et al. Epi Behav. 20 478-483, 2011
76
Responsive Neurostimulation RNS
77
Responsive Neurostimulation RNS
  • Implantable device for intractable partial onset
    seizures
  • Approved November of 2013
  • Patients can have up to 2 foci of seizure onset

78
RNS
  • Records EEG
  • Can have 2 leads that stimulate
  • Strip electrodes on cortical surface
  • Depth electrodes
  • Stimulates in attempt to abort seizure

Image from Neuropace.com
79
RNS
Images from Neuropace.com
80
RNS
  • EEG patterns are learned by recording seizures
  • Once patterns identified, then programmed to
    stimulate
  • EEG pattern and stimulation paradigm can be
    modified with time

81
RNS
  • Pivotal trial 31 centers
  • 240 enrolled
  • 191 implanted
  • Mean Reduction in seizures
  • 37.9
  • Responder rate (50 reduction in seizures) at 1
    year was 43
  • 2 years 46

Morrell et al. Neurology 77 1295-1304, 2011
82
  • Pivotal trial final 2 year data
  • Median reduction in seizures 53

Heck et al. Epilepsia 55 432-441, 2014
83
Heck et al. Epilepsia 55 432-441, 2014
84
RNS Complications
  • Intracranial Hemorrhage
  • 9/191 Patients (4.7)
  • 6 Related to postoperative complications
  • 3 occurred later due to seizure related trauma
  • No permanent sequelae
  • Infection
  • 10/191 (5.2)
  • 4 devices explanted
  • 5 postoperative
  • 2 secondary to infected scalp laceration from
    seizure

Morrell et al. Neurology 77 1295-1304, 2011
85
Dietary Options
86
Dietary Options for Medically Intractable Epilepsy
  • Ketogenic Diet
  • Modified Atkins Diet
  • MCT Diet
  • Low Glycemic Index Treatment

87
Ketogenic Diet
  • First reports of effectiveness in medical
    literature in 1921
  • Primarily been used in children
  • Resurgence of use in the past two decades
  • 41 ratio of fat protein/carbohydrate
  • 90 of calories are derived from fat
  • Calorie and fluid restriction
  • 31 ratio effective for some, better tolerated

88
Ketogenic Diet
  • Initiated in the hospital setting
  • 24-48 hour fast
  • Initiation of the diet increasing the ketogenic
    ratio to goal over 4-5 days
  • Mechanism of action for seizure reduction
  • Multiple and not fully delineated

Henderson et al., J Child Neurol 2006, 21
193-198
89
Ketogenic Diet Effectiveness
  • 2006 meta-analysis of 19 studies
  • 860 total patients with efficacy data
  • Mean age 5.78 /- 3.43 years
  • 422 patients adhering to the diet
  • 83.6 achieved a 50 reduction in seizures
  • 52 achieved greater than 90 reduction
  • 24 achieved complete seizure control

Henderson et al., J Child Neurol 2006, 21
193-198
90
Ketogenic Diet Effectiveness
  • 2006 meta-analysis of 19 studies
  • 438 dropped out
  • Ineffectiveness around 47
  • Too restrictive of diet around 11
  • Illness/side effects around 16
  • Poor compliance around 8
  • Other/lost to follow up around 17

Henderson et al., J Child Neurol 2006, 21
193-198
91
Ketogenic Diet Effectiveness in Adults
  • Meta-analysis of 9 studies with data from adult
    patients
  • 122 patients identified
  • 75 from a 1930 study where diet was the only
    therapy
  • 49 achieve greater than 50 reduction in
    seizures
  • 10 seizure freedom

Payne et al., Epilepsia 2011, 52 1941-1948
92
Modified Atkins Diet
  • Does not require hospitalization to initiate
  • No fast
  • No fluid, calorie, or protein restrictions
  • No weighing of food
  • 65 of calories from fat
  • Carbohydrates start at 15 g/day
  • Increase to 20-30 g/day after 1st month

93
Other Diets
  • MCT Diet
  • Modified ketogenic diet
  • 60 of calories from MCT oil
  • Allows for more proteins and carbs
  • Modified MCT Diet
  • 30 of calories from MCT oil
  • Better tolerated from GI stanpoint

94
Other Diets
  • Low Glycemic Index Treatment
  • Not restrict fluids or protein
  • Loosely monitor fats and calories
  • Restricts carbs to 40-60 g/day
  • Low glycemic carbs only

95
Safety and Counseling
96
What To Do When Someone is Having a Seizure
97
What To Do When Someone is Having a Seizure
  • Stay calm
  • Time the seizure with a watch
  • Dont try to hold the person down
  • Move any objects away from them that may cause
    harm
  • Try to put something soft under their head

98
What To Do When Someone is Having a Seizure Cont.
  • Loosen tight clothing around the neck if causing
    difficulty with breathing
  • Neckties
  • Try to roll them on their side to let secretions
    fall out of the mouth
  • Dont place anything in the mouth
  • Talk calmly and gently as they come out of the
    seizure
  • Stay with them until the seizure is over

99
Counseling
  • Water safety
  • Drowning risk increased 17-22 fold in those with
    seizures
  • No swimming or bathing alone, showers safer
  • Other risky situations
  • Climbing ladders, working at height, heavy
    machinery

100
Counseling
  • Driving
  • Minnesota and Wisconsin laws are 90 days
  • No mandatory provider reporting, self reporting
  • Laws vary by state

101
Conclusions
  • Seizures and epilepsy are common
  • The first steps in evaluating new onset seizures
    are physical examination, labs, imaging, and EEG
  • Seizure types
  • Partial onset
  • Generalized onset

102
Conclusions
  • Treatments
  • Medications are the mainstay
  • Two thirds well controlled on medication
  • Medically intractable epilepsy
  • Definition
  • Treatment options
  • Surgery
  • Stimulating devices
  • Diets
  • Safety issues in epilepsy

103
Treatment Goals
  • No seizures, no side effects
  • If seizures continue discuss other options to
    help with seizure control
  • Work as a team with my patients
  • Discuss options and come to decisions together
  • Live life

104
Famous People with Epilepsy
  • Harriet Tubman
  • Julius Caesar
  • Lil Wayne
  • Prince
  • Florence Griffith Joyner
  • Samari Rolle
  • Alexander the Great

105
Famous People with Epilepsy
  • Danny Glover
  • Neil Young
  • Napoleon Bonaparte
  • Vincent van Gogh
  • George Gershwin
  • Socrates
  • Coach Kill

106
Thank You
  • Questions?
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