Epilepsy 101

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Epilepsy 101

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

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Epilepsy Foundation

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

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Epilepsy Foundation Mission Statement

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

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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

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Topics Today

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

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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

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Neuron
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Neuron
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Neuronal Input
www.mult-sclerosis.org
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Neurons

• If enough input is received, then an action
  potential is generated

hyperphysics.phy-astr.gsu.edu
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Synapse
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Neuronal Connections
www.lavia.org
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Normal Communication

• Rapid onset and offset
• Highly controlled and precise

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Definition of Seizure

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

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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

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Unprovoked Seizure

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

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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

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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

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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

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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
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Epilepsy Incidence with Age
Hauser et al., Epilepsia 1993, 34 453-468
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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

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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

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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

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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

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Classification of Seizures

• Focal versus Primary Generalized Seizures

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Focal (Partial) Onset Seizures

• Seizure begins in one part of the brain
• Symptoms depend on which part of brain is affected

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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

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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

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Primarily Generalized Seizures

• Seizure that begins on both sides of the brain at
  the same time

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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

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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

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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

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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

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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

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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

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Typical Absence
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Evaluation of New Onset Seizures
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Issues

• Was it a seizure?
• Provoked or unprovoked?
• Was it really the first seizure?
• What studies are needed?
• Treat or not to treat?

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Acute Work-up in ER

• History
• Physical exam
• Labs
• Imaging
• Neurology Referral

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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

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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

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EEG
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MRI
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MRI
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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

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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

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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.

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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

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Other Factors

• Driving
• Employment
• Social and cultural issues
• Insurance issues

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Treatment of Epilepsy
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Epilepsy Treatment

• Anti-seizure medications
• Mainstay of treatment
• Surgery
• VNS
• RNS
• Diet Therapies

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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

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Choosing a Medication

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

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Once a medication is chosen, what is the
likelihood of seizure control?
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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

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Potential Options for Medically Intractable
Epilepsy

• Surgery
• Vagal Nerve Stimulator (VNS)
• Responsive Neurostimulation (RNS)
• Dietary Treatments

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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

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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

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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
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• 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

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Medical Devices
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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

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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

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Programmable

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

Image from vnstherapies.com
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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

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• 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
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Adapted from Morris et al., Neurology 1999, 53
1731-1735.
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Percent Affected
Adapted from Morris et al., Neurology 1999, 53
1731-1735.
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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
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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
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Responsive Neurostimulation RNS
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Responsive Neurostimulation RNS

• Implantable device for intractable partial onset
  seizures
• Approved November of 2013
• Patients can have up to 2 foci of seizure onset

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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
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RNS
Images from Neuropace.com
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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

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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
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• Pivotal trial final 2 year data
• Median reduction in seizures 53

Heck et al. Epilepsia 55 432-441, 2014
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Heck et al. Epilepsia 55 432-441, 2014
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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
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Dietary Options
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Dietary Options for Medically Intractable Epilepsy

• Ketogenic Diet
• Modified Atkins Diet
• MCT Diet
• Low Glycemic Index Treatment

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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

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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
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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
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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
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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
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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

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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

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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

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Safety and Counseling
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What To Do When Someone is Having a Seizure
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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

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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

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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

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Counseling

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

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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

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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

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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

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Famous People with Epilepsy

• Harriet Tubman
• Julius Caesar
• Lil Wayne
• Prince
• Florence Griffith Joyner
• Samari Rolle
• Alexander the Great

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Famous People with Epilepsy

• Danny Glover
• Neil Young
• Napoleon Bonaparte
• Vincent van Gogh
• George Gershwin
• Socrates
• Coach Kill

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Thank You

• Questions?