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Advances in the Diagnosis and Treatment of Epilepsy

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Title: New Treatments for Children and Adults With Seizures Author: TG4648 Last modified by: Marcelo Created Date: 5/18/2004 1:28:54 PM Document presentation format – PowerPoint PPT presentation

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Title: Advances in the Diagnosis and Treatment of Epilepsy


1
Advances in the Diagnosis and Treatment of
Epilepsy
  • Marcelo E. Lancman, M.D.
  • Director, Epilepsy Program
  • Northeast Regional Epilepsy Group

2
Advances in the Diagnosis and Treatment of
Epilepsy
  • Epilepsy concepts
  • Diagnosing Epilepsy
  • What causes Epilepsy
  • Treating Epilepsy
  • New developments

3
Epilepsy Concepts
  • What is epilepsy?
  • What is a seizure?

4
Incidence
  • Epilepsy
  • 0.5-1
  • Seizures
  • 5-10

5
Classification of Seizures
  • Partial
  • Simple
  • Complex
  • Secondary Generalized
  • Generalized
  • Absence
  • Atonic
  • Clonic
  • Tonic
  • Tonic-clonic
  • Myoclonic

6
Classification of Epilepsy
  • By Localization
  • Partial
  • Generalized
  • By Cause
  • Idiopathic (unknown)
  • Symptomatic

7
Classification of Epilepsy
  • Idiopathic Partial Epilepsy
  • Symptomatic Partial Epilepsy
  • Idiopathic Generalized Epilepsy
  • Symptomatic Generalized Epilepsy

8
Idiopathic Generalized Epilepsy
  • Benign Neonatal Familial Epilepsy
  • Benign Myoclonic Epilepsy of Infancy
  • Generalized epilepsy with febrile seizures plus
  • Epilepsy with myoclonic absence
  • Epilepsy with myoclonic-astatic seizures
  • Childhood absence epilepsy
  • Juvenile absence epilepsy
  • Epilepsy with GTCS only

9
Idiopathic Partial Epilepsy
  • Benign Rolandic Epilepsy
  • Benign Occipital Epilepsy

10
Symptomatic Generalized Epilepsy
  • Infantile spasms (West syndrome)
  • Dravet syndrome
  • Lennox-Gastaut syndrome

11
Symptomatic Partial Epilepsy
  • Temporal Lobe Epilepsy
  • Frontal Lobe Epilepsy
  • Parietal Lobe Epilepsy
  • Occipital Lobe Epilepsy

12
Type of Epilepsy
  • The importance of knowing

13
Diagnosis of Epilepsy
  • Medical History
  • Physical exam

14
Testing
  • Testing
  • EEG, AEEG, VEEG
  • Labs
  • Genetics
  • Imaging
  • CT, MRI (high definition)

15
Diagnosis
  • Diagnosis is clear treatment is initiated
  • Diagnosis unclear Video-EEG

16
Video-EEG Monitoring
  • Continuous EEG monitoring along with continuous
    audio-video recording
  • Mostly requires inpatient admission

17
Goals of Video-EEG Monitoring
  • Epilepsy vs. non-epileptic events
  • Characterize epilepsy type
  • Pre-surgical evaluation

18
Non-Epileptic Events
  • 20 to 30 of patients referred with diagnosis of
    intractable epilepsy
  • Events that do not have electrical source in
    brain
  • May have physical or psychological causes that
    are not epilepsy
  • But CAN also occur in patients who have epilepsy

19
Non-epileptic events
  • Physiologic (other medical conditions)
  • Fainting, low sugar, changes in electrolytes,
    toxins, fever.
  • Psychological
  • Referred to psychiatry and neuropsychologist who
    work with this type of stress-seizure
  • Psychiatric medication, psychotherapy, education

20
Non-epileptic events
  • Conditions that may look like seizures
  • TIAs, complicated migraines, movement disorders,
    sleep disorders, anxiety/panic disorder, vertigo,
    cardiac disorders, rage attacks, breath-holding
    spells,

21
What causes of Epilepsy?
  • The seizure threshold
  • Causes
  • Genetics, head injury, stroke, tumors,
    infections, malformations, metabolic disorders
    (diabetes, thyroid, parathyroid, adrenal),
    degenerative disorders, perinatal factors and
    other less common (cardiac, GI, blood,
    inflammatory, poisons, etc)

22
Seizure Triggers
  • Alcohol, stress, environmental temperature,
    lights, fever/illness, hormonal changes,
    hyperventilation, sleep deprivation, medications
    and supplements, missing medication doses and
    travel across time zones

23
Treating Epilepsy
  • What is intractable epilepsy?
  • Despite medical management, patient continues to
    have frequent, debilitating seizures

24
Seizure Control
25
Options for the Intractable Seizure Patient
  • Medications (combinations)
  • Diets
  • Surgical procedures
  • Stimulators
  • Resections

26
Medications
  • Choices based on epilepsy type, patient profile,
    side effect profile, cost
  • Best to have patient on single antiepileptic drug
    (AED)
  • May need polytherapy (combination of medications)
  • Adding meds requires going up slowly with the new
    agent before discontinuing previous drug
  • Polytherapy requires deep knowledge of
    interactions

27
How to use polytherapy rationally
  • Pharmacodynamics (what the medication does to the
    body)
  • Pharmacokinetics
  • (what the body does to the medications)
  • Absorption
  • Distribution
  • Elimination
  • Half life
  • Liver
  • Kidneys

28
How to use polytherapy rationally
  • Side effects
  • Dose-related
  • Idiosyncratic (each person is different)

29
Older Medications
  • Carbamazepine (Tegretol)
  • Phenobarbital
  • Ethosuximide (Zarontin)
  • Phenytoin (Dilantin/Cerebyx)
  • Valproic acid (Depakote)
  • Primidone (Mysoline)

30
Newer AEDs
  • Gabapentin (Neurontin)
  • Lamotrigine (Lamictal)
  • Topiramate (Topamax)
  • Felbamate (Felbatol)
  • Diastat (Diazepam)
  • Vigabatrin (Sabril)
  • Ezogabine (Potiga)
  • Oxcarbazepine (Trileptal)
  • Pregabalin (Lyrica)
  • Zonisamide (Zonegran)
  • Levetiracetam (Keppra)
  • Lacosamide (Vimpat)
  • Rufinamide (Banzel)
  • Clobazam (Onfi)

31
Medication choices based on epilepsy type
32
AEDs for Partial Epilepsy
  • All but Zarontin and Banzel

33
Best AEDs for Generalized Epilepsy
  • Depakote
  • Keppra
  • Lamictal
  • Topamax
  • Zonegran
  • Banzel

34
Future Medications
  • Brivaracetam
  • Carisbamate
  • Eslicarbazepine
  • Ganaxalone
  • Losigamone
  • Nitrfazepam
  • Perampanel
  • Piracetam
  • Progabide
  • Remacemide
  • Retigabine
  • Seletracetam
  • Stiripentol

35
What Are Some Promising New Medical Treatments?
  • Maintenance Treatment
  • Ezogabine (Potiga)
  • Perampanel
  • Vertex
  • Emergency Treatment
  • Intranasal Midazolam

36
Potiga
  • Potassium Channel Opener
  • Partial Seizures
  • Rare but serious side effects

37
Peramapanel
  • Glutamate Blocker
  • Effective in trials for partial seizures
  • Side effects Dizziness, Sleepiness
  • Approved in Europe
  • Under study in US for Generalized Seizure types
  • Under FDA review for Partial Seizures

38
Vx-765 for Partial Epilepsy
  • New approach to Epilepsy Rx
  • Anti-Inflammatory
  • Short Duration of therapy (weeks instead of
    years)
  • Oral Medicine
  • Early Clinical Trials Completed
  • Early results encouraging but longer treatment
    duration to be studied
  • Headache, dizziness, GI most common side effects

39
Emergency Treatment
  • Rectal Diastat
  • Clinically proven
  • Hard to give
  • Adults dont like
  • Cant self administer

40
Intranasal Midazolam
  • Easy to give
  • Preferred route
  • Can be self-administered or given by caretaker
  • Under study

41
Advances in Treatment
  • Newermedications
  • Brivaracetam
  • Carisbamate
  • Clobazam
  • Eslicarbazepine
  • Ganaxalone
  • Losigamone
  • Nitrfazepam
  • Perampanel
  • Piracetam
  • Progabide
  • Remacemide
  • Retigabine
  • Seletracetam
  • Stiripentol

42
For patients that do not respond to medication
  • Ketogenic diet
  • Surgeries

43
Ketogenic Diet (_at_1920)
  • High fat, low carbohydrate/protein diet
  • Requires hospitalization to start it
  • NPO until patient in ketosis
  • Parent education
  • Meds to be taken into account
  • Recommended mainly for young children due to
    compliance and efficacy

44
Epilepsy Surgery
  • The goals are
  • To determine where the seizures are coming from
  • To make sure is safe

45
Epilepsy Surgery
  • To determine where the seizures are coming from
  • Video-EEG monitoring
  • MRI
  • MRS
  • PET
  • SPECT
  • MEG

46
Epilepsy Surgery
  • To make sure that it is safe
  • Wada test to study speech and memory
  • Neuropsychological testing mental functions (IQ,
    memory, attention) and personality assessment
  • Psychological evaluation
  • Ophthalmologic evaluation

47
Epilepsy Surgery
  • Some cases in which the localization is not clear
    or where function could be affected will require
    INVASIVE ELECTRODES
  • Depth electrodes
  • Subdural electrodes

48
Types of Epilepsy Surgery
  • Temporal Lobectomy
  • Extratemporal Resections
  • Hemispherectomy
  • Corpus Callosotomy

49
Outcome after epilepsy surgery
  • Anterior temporal lobectomy
  • 70-80 seizure free
  • Neocortical resection
  • With lesion 50-80 seizure free
  • Without lesion 30-50 seizure free
  • Hemispherectomy
  • Significant improvement
  • Corpus Callosotomy
  • Significant improvement for drop attacks

50
Complications of surgery
  • Low rate of complications
  • Infections
  • Bleeding
  • Anesthesia
  • Function

51
Vagus Nerve Stimulator (1997)
  • Intractable epilepsy patient without focus or
    desires interim step before epilepsy surgery
  • Goal is to reduce amount/severity of seizures vs.
    cure
  • Device surgically implanted in left chest/axilla
    area
  • Coils around left vagus nerve
  • Stimulation is automatic patient can
    additionally stimulate device if aura
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