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Flashcards in Epilepsy Deck (50):
1

Seizure

-episode of abnormally synchronized & high frequency firing of neurons resulting in abnormal behavior or experience

2

Epilepsy

-chronic brain disorder of various etiologies characterized by recurrent, unprovoked seizures

3

Epilepsy Syndromes

-grouping of similar epileptic patients according to seizure type, EEG age of onset, prognosis & clinical signs

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Epidemiology of Epileptic Seizures

-0.5% of pop.
-2.5 million prevalent cases
-150,000 to 200,000 new cases/year
-age-specific incidence had dec. in younger age groups, inc. in patients over age 60

5

Causes of Adult-onset Epileptic Seizures

-Cerebrovascular disease
-Trauma
-Tumors
-Infections
-Cerebral Degeneration

6

ILAE Classifications of Epileptic Seizures

-Clinical Observation + EEG FIndings
(partial seizures and generalized seizures)

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Types of Partial Seizure

-Simple (consciousness preserved)
-Complex (consciousness impaired)
-Secondarily Generalized (consciousness lost + bilateral cerebral involvement)

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Simple Partial Seizures

-Signs/symptoms depend on focus: motor (Jacksonian - move up body part), somatosensory, autonomic, psychic
-consciousness is intact
-EEG may appear normal
-Auras are brief, simple partial seizures with no overt behavioral manifestations

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Complex Partial Seizures

-impaired consciousness
-lasts ~1min
-blank stare
-oral/ipsilateral hand automatisms
-contralateral dystonic posturing
-amnesia for ictal event
-focal abnormality on routine EEG

10

Primary Generalized Seizures

-absent (Petit Mal)
-tonic-clonic
-clonic
-tonic
-myoclonic
-atonic

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Absence Seizure Features

-brief loss of consciousness (10-20sec)
-staring spell
-no post-ictal confusion
-subtle myoclonic movement, eyelid flutter
-no baseline neurologic deficits
-baseline EEG may show generalized 3Hz spike -wave discharges

12

Tonic-Clonic Seizures

-typical presentation:
cry, loss of consciousness, muscular rigidity (tonic), patient may fall, rhythmic jerking (clonic), tongue-biting/injury common, bladder/bowel incontinence, post-ictal confusion/sleep
-Grand Mal

13

Myoclonic Seizure

-brief, shock-like muscle contractions (head, upper extremities)
-usually bilaterally symmetrical
-consciousness preserved
-precipitated by awakening or falling asleep
-may progress into tonic-clonic seizures
(juvenile myoclonic epilepsy)

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Atonic Seizure

-impaired consciousness
-loss of muscle tone
-head drop, fall
-brief duration (few seconds)
-injury common

15

Seizure Diagnosis

-History from patient & witnesses
-Physical & neurological examination
-CBC, CMP, AED levels
-Inter-ictal EEG
-Epilepsy protocol MRI
-Video-EEG monitoring

16

Prevalence of Inter-ictal Epileptiform Discharges in Epileptic Patients

-initial EEG detects on epileptiform discharge in 29-55% of patients
-serial EEGs reveal epileptiform discharges in 80-90% of patients
-Repeat studies, with sleep deprivation & extended recording times, helps inc. chances of detecting epileptiform discharges in patients with epilepsy

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Focal Epileptiform Discharge

-seizure focus is in left anterior temporal head region
-sharp waves, spikes, & sharp-and slow wave discharges

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Generalized Epileptiform Discharge

-bilateral burst of epileptiform spike & slow wave discharges
-discharge simultaneously & symmetrically in both hemispheres

19

Seizure MRI

-Recent-onset epilepsy in adults requires imaging sequences, including gadolinium-DPTA enhanced sequences to find primary or secondary tumors, infection or inflammation

20

Epilepsy Protocol MRI

-Coronal high resolution T1-weighted volume data set through the whole brain
-a coronal T2-weighted sequence, typically using 3 mm thin sections, should also be done in order to detect hippocampal sclerosis

21

Video-EEG monitoring

-simultaneous recording of EEG & seizure
-useful in differentiating epileptic seizures from non-epileptic seizures
-useful for characterizing seizure type
-essential for pre-surgical localization of the seizure focus

22

Pathophysiology of Seizures

-Ligand-gated ion channels can be excitatory or inhibitory depending on their ion selectivity
-GABA activates GABA a receptors that mediate fast synaptic inhibition (IPSP) by permitting rapid influx of Cl ions, resulting in hyperpolarization
-glutamate activated 3 classes of ion channels (AMPA, Kainate, NMDA) that mediate fast synaptic excitation by permitting a rapid influx of NA and Ca ions
-in most neuronal circuits, GABAergic inhibition exerts a powerful suppression of excitability
-this inhibition is overcome during the development of a focal seizure

23

Goal of Antiepileptic Drug (AED) Therapy

-2 types of remission:
Medical remission: seizure free without side effects on 1 or 2 AEDs
-Disease Remission: seizure free off all AEDs
-major goal of AED therapy is to achieve medical remission
-surgical therapy is well-selected cases may result in disease remission

24

AED Selection

-efficacy for specific seizure types or epilepsy syndrome
-efficacy for co-morbid conditions
-interactions with other drugs
-ease of introduction, follow-ip
-drug safety
-cost

25

Phenobarbital

-enhances activity of GABA receptor, depresses gluatmate activity, reduces Na, K conductance
-SE: hepatotoxicity, connective tissue disorder, SJS
-P450 inducer

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Phenytoin

-blockade of Na channels & inhibitory action of Ca and Cl conductance
-SE: aplastic anemia, hepatic failure, SJS
-P450 inducer

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Carbamazepine

-block of neuronal Na channel conductance
-SE: aplastic anemia, hepatotoxicity, Stevens Johnsons syndrome, Lupus-like syndrome
-P450 inducer

28

Valproate

-affects GABA glutamatergic activity & reduce threshold of Ca and K conductance
-Hepatotoxicity, hyperammonemia, leukopenia, thrombocytopenia, pancreatitis

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Ethosuximide

-inhibits Ca T channel conductane
-SE: bone marrow depression, hepatotoxicity

30

Lamotrigine

-blockage of voltage dep. sodium conductance
-SE: SJS or toxic epidermal necrolysis

31

Oxcarbazepine

-Na channel blockage
-SE: hyponatremia, rash
-P450 inducer

32

Topiramate

-blockage of Na channels, enhancement of GABA medicated Cl influx
-SE: renal calculi, hypohidrosis
-P450 inducer

33

Zonisamide

-Blockade of Na, K, & Ca channels, inhibits glutamate excitation
-SE: renal calculi, hypohidrosis

34

Gabapentin

-Modulation of N-type Ca channel

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AEDs for Partial & Tonic-Clonic Seizures

-Valproate, Phenytoin, Carbamazepine & Phenobarbital

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AEDs for Absence Seizures

-Ethosuximide & Valproate

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New AEDs for partial seizures

-Gabapentin & Oxcarbazepine

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New AEDs for Partial & Generalized seizures

-Lamotrigine, Topiramate, Levetiracetam, & Zonisamide

39

P450 inducers

-lead to failure of oral contraceptives
-cause osteopenia, osteoporosis, fractures
-inc. metabolism of androgens & estrogens

don't want to give for: women oral contraceptives, patient on oral coagulation, transplant patients, AIDS patients on protease inhibitors, patients predisposed to osteoprorsis

40

AED Birth Defects

-older cause malformations in 4-8% of children (twice normal rate) with risk inc. with higher AED dose & polytherapy Cat D
-newer not teratogenic in animals, Cat C in humans

-to reduce risk: lower effective dose, monotherapy, preconceptual folic acid supplementation, 0.8-4mg/day, prenatal diagnostic testing at 16-18 weeks: maternal serum alpha fetoprotein, ultrasound studies

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Probability of Medical Remission in Newly Diagnosed Patients

-for 2 or more years
47%with 1st AED used in monotherapy
14% with 2nd AED used in monotherapy
4% with 2 AEDs used

42

Intractable Epilepsy

-have disabling seizures recurring despite optimized therapy
-Disabling seizures: seizures causing impaired quality of life, limited educational or occupational opportunities, physical injuries or social compromise
-Optimized Treat: AED treatment is optimum with 2 AEDs at max tolerated dose

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Prevalence of Intractable Epilepsy

-controlled with AEDs in 70-80% of patients
-20-30% are not seizure-controlled using currently available AEDs and are therefore intractable

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Burden of Intractable Epilepsy

-poor quality of life
-restriction of psychosocial, educational, & occupational performance in child & adult
-risk of injuries from seizures
-higher risk of SUDEP (sudden unexplained death in epilepsy)

45

Therapy of Refractory Epilepsy

-polytherapy with antiepileptic drugs
-vagus nerve stimulator
-epilepsy surgery

46

Vagus Nerve Stimulation

-Electrical pulse generator implanted subcutaneously on chest
-Lead attached to left vagus nerve
-mechanism of action unknown
-about 40-50% have >50% seizure reduction, but rarely seizure free

47

Epilepsy Surgery

-temporal lobectomy
-lesionectomy
-corticectomy
-corpus callosotomy
-multiple subpial transections
-hemispherectomy

48

Generalized Convulsive Status Epilepticus

-continuous, generalized, convulsive seizure lasting more than 5 min. or 2 or more sequential seizures occurring without full recovery of consciousness
-non-convulsive status epilepticus is an EEG diagnosis

49

Management of GCSE

-

50

Treatment of Refraactory GCSE

-refractory if patient fails to respond to lorazepam
-if convulsive seizures persist, consider intubation
-start continuous EEG monitoring