6/1- Epilepsy Flashcards Preview

Term 5: Neuro > 6/1- Epilepsy > Flashcards

Flashcards in 6/1- Epilepsy Deck (56):
1

Seizure/Epilepsy outline/flowchart

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Seizure (def)?

Latin: sacire "to take posession of"

- Paroxysmal, abnormal, excessive, hypersynchronous discharge of cortical neurons, resulting in a change in behavior or in an EEG discharge

- Can be “provoked” or “unprovoked"

3

Epilepsy (def)?

- Recurrent unprovoked seizures

- ...or one unprovoked seizure and high likelihood of more based on history/exam/studies

- ... or provoked by something that shouldn’t provoke seizures (“reflex epilepsy”)

4

Potential differential diagnoses for seizures?

- Gastroesophageal reflux

- Breath-holding spells

- Sleep myoclonus

- Night terrors

- Movement disorders

- Migraines

- Syncope

- Transient ischemic attacks

- Vertebrobasilar insufficiency

- Hypoglycemia

- Hypoxia

- Psychogenic seizures

5

What percentage of the population will experience seizures/epilepsy?

- Single seizure lifetime prevalence = 9-10%

- Epilepsy lifetime prevalence = 0.5-1% (3% by age 75)

(no racial/gender/geographic preference for epilepsy)

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ILAE Classification History (pic)

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Two division of seizure based on onset

Focal Onset seizure

- “initial activation of a system of neurons limited to one cerebral hemisphere.”

- Previously called "partial" or "localization-related"

Generalized Onset seizure

- “first clinical changes indicate involvement of both hemispheres.”

8

Focal seizures further divided based on what? Details?

Level of consciousness:

- No alteration of consciousness (“auras” or focal motor seizures); previously "simple partial seizures"

- Impaired or altered, but no loss of consciousness = “dyscognitive”; previously "complex partial seizures"

- Both types may evolve into generalized seizures ("secondarily generalized")

9

Generalized seizures include?

- Absence seizures

- Atypical substance seizure

- Clonic seizure

- Tonic seizure

- Tonic-clonic seizure

- Myoclonic seizure

- Atonic seizure

- Infantile spasms

10

Aura- definition and characteristics?

Brief stereotypic prodrome that precedes the more obvious clinical event by seconds to minutes

- Does not impair cognition

- Ex) taste, smell, fear, dissociation, deja vu

- Is actually a FOCAL SEIZURE

11

Ictus- defintion

(Latin- "to strike")

The "seizure" itself

12

Automatisms (def) and examples?

Semipurposeful or non-purposeful “automatic” behaviors during the seizure

- Ex) picking at clothes, lipsmacking, swallowing

- Can occur in both partial and generalized epilepsies

- In partial epilepsies tend to be unilateral

13

Postictal state (def) and examples?

- Confusion, somnolence & fatigue (complex partial and some generalized seizures)

- Aphasia (partial seizures affecting language areas)

- Focal weakness- "Todd's paralysis" (partial seizures)

14

Behavioral change reflecting the anatomic location of abnormal discharge for frontal lobe?

- Clonic mvts, tonic posturing, or atonia

- Contralateral tonic posturing or bizarre bilateral hyperkinetic mvts

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Behavioral change reflecting the anatomic location of abnormal discharge for temporal lobe?

- Aura of smell, taste, emotion

- Followed by confusion and staring

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Behavioral change reflecting the anatomic location of abnormal discharge for parietal lobe?

- Somatosensory changes

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Behavioral change reflecting the anatomic location of abnormal discharge for occipital lobe?

- Flashing lights

- Visual distortions

- Eye movements

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Take Home:

- Not everything that shakes is a seizure

- Not every seizure is epileptic

- Note very epileptic seizure involves shaking

(:

19

In a broad sense, normal CNS function is determined by what?

Balance between excitation (glutamate) and inhibition (GABA)

- Modulated by: ACh, serotonin, DA, somatostatin, CCK, dynorphin, nitric oxide, arachidonic acid, endocanabinoids...

20

Examples of provoked seizures (NOT epilepsy!)

Exceptions?

- Alcohol withdrawal seizures

- Hyponatremia

- Hypoglycemia

- Cocaine

Exceptions- "reflex epilepsy" (typically genetic)

- Photosensitive epilepsy

- Rarely: bath (hot water), eating, music-induced epilepsy

21

What is the process of developing epilepsy (epileptogenesis)?

Eliptogenesis:

- Sequence of events leading to abnormal activity sufficient to convert a normal neuronal network into an abnormally hyperexcitable and hypersynchronous one

Latent period:

- A “clinically silent period” between an initial injury or insult and the development of epilepsy

22

Pathophysiology of epilepsy: what goes wrong (broad)?

- Loss of inhibition

- Intrinsic excitability

- Abnormal excitation (and excessive synchronization)

23

Pathophysiology of loss of inhibition? Examples?

Loss of inhibition

- Some interneurons are particularly vulnerable to cell death

- Disinhibition of primary neurons -> hyperexcitability and excessive neuronal activity

- Axons may sprout and synapse on other principal cells

Examples: Generalized epilepsy with febrile seizures plus (GEFS+)

24

Characteristics of Generalized Epilepsy with Febrile Seizures plus (GEFS+)?

(Abnormal inhibition)

Onset usually in 1st decade Clinically heterogeneous

- Febrile seizures that persist beyond 5 yrs of age

- Afebrile generalized seizures (tonic-clonic, absence, myoclonic, atonic, others)

Severity ranges from mild to severe

EEG: generalized spike and wave

Some of the mutations described are in the GABA-A recepetor

25

Pathophysiology of intrinsic excitability? Example?

- Decreased hyperpolarizing current

- Increased depolarizing current

Ex) decreased K conductance with Benign Familial Neonatal Convulsions

26

Characteristics of decreased K conductance with Benign Familial Neonatal Convulsions?

- Associated with 2 K channel genes (KCNQ2 and KCNQ3)

- Both subunits form a heterodimeric complex underlying a slow potassium conductance which regulates excitability (the M current)

- Though to be loss of function mutations

- Example of a "channelopathy"

27

Childhood Absence Epilepsy Circuit caused by what underlying biochemistry?

- Bursting mediated by T-type Ca channels

- Blocked by Ethosuximide

28

Categorizing Causes of Epilepsy?

Structural/Metabolic

- Evident (usually structural) cause

- For example: cortical dysplasia

- Previously “Symptomatic” Genetic

- Known or presumed genetic cause

- For example: Childhood absence epilepsy or one of the “channelopathies”

- Previously “Idiopathic” Unknown

- Previously “Cryptogenic”

- “Hidden cause” (practically: “I don’t know”)

29

Classification schemes can be combined as far as etiology of epilepsy and onset of seizure

Ex)

- Structural epilepsy with focal onset seizures due to cortical dysplasia

- Genetic generalized epilepsy

(:

30

Approach to diagnosis?

- Medical and Family Hx

- Complete description of typical events

- Complete neurological exam

- Depending on the above: Lab studies (first seizure with chemistries and tox screne, recurrents seizures with possible genetic testing), Neuroimaging (usually MRI), electroencephalography

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What is this?

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Electroencephalogram (EEG) "recording squiggles" of interictal discharges

32

What is this?

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Electroencephalogram (EEG) "recording squiggles" of generalized seizure

33

What is this?

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Electroencephalogram (EEG) "recording squiggles" of focal seizure

34

What are the recurrence rates following a 1st unprovoked seizure?

- 30% for pt with normal EEG, MRI, and exam - > 90% when all three are abnormal

- Multiple seizures in the same 24 hr period have same risk as a single seizure

35

Treatment for seizures?

New guidelines for first seizures: treat first unproviked seizure with an anti-epileptic drug. Treatment depends on:

- Syndrome classification (e.g. Childhood Absence Epilepsy, use ethosuximide)

- Type of seizures (focal-onset use narrow-spectrum agents; generalized onset use broad spectrum agents)

- Other medical problems

36

What is the general principle underlying AEDs (antiepileptic drugs)? Examples?

Act by restoring balance:

Reduce excitation:

- Phenytoin

- Carbamazepine

- Oxcarbazepine

Increase inhibition:

- Phenobarbital

- Benzodiazepines

Both:

- Valproic acid

- Topiramate

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AEDs (list)

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Mechanisms of action of AEDs with examples?

- Block Na channels: Carbamazepine

- Block Ca channels: Ethosuximide

- Block AMPA/NMDA Rs: Perampanel

- Enhance GABA receptors: Clobazam

- Enhance K channel conductance: Ezogabine

- Block NT release: Levetiracetam

39

Adverse effects of AEDs?

- All AEDs can cause drowsiness, dizziness, and rash

- Drugs which act on GABA system tend to be more sedating

- Not antiepileptic has been shown to be entirely safe in pregnancy (older drugs have clear teratogenic effects [2-4x increase] while newer are more likely safe, but less experience)

40

Serious and specific adverse effects for Valproic acid?

Acute hemorrhagic pancreatitis, hepatic failure

(1/50,000 but 1/500 for kids under 2)

41

Serious and specific adverse effects for Felbamate?

Aplastic anemia

(up to 1/5000 adults; not seen in kids)

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Serious and specific adverse effects for Carabamazepine?

Aplastic anemia

(1/500,000)

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Serious and specific adverse effects for Phenytoin?

Hepatotoxicity, aplastic anemia

(1/500,000)

44

Which drug used to treat epilepsy with focal-onset seizures?

- First line: oxcarbazepine, levetiracetam, carbamazepine, phenytoin

- Second line: lacosamide, lamotrigine, topiramate, zonisamide

45

Which drug used to treat epilepsy with generalized-onset seizures?

- Absence: ethosuximide, lamotrigin, valproate

- Others: lamotrigine, levetiracetam, valproate, topiramate, zonisamide, pregabalin

46

Success with AED Regimens?

- 47% seizure free with 1st drug

- 13% seizure free with 2nd drug

- 4% seizure free with 3rd/multiple drugs

- 36% not seizure free

47

Treatments for medically refractory patients?

- Ketogenic diet (an extremes Atkins: high fat low carb diet induces ketosis which has anticonvulsant effects for unclear reasons)

- Epilepsy surgery

- Vagus nerve stimulator

- Responsive focal cortical stimulation

48

Types of epilepsy surgery?

- Lesionectomy: take out the lesion

- Lobectomy: take out the offending lobe

- Hemispherectomy: take out the whole hemisphere

- Corpus callosotomy: cut the corpus collosum

49

Outcomes of epilepsy surgery depend on what?

- Type of epilepsy

- Type of surgery

- Age

50

For whom is epilepsy surgery considered?

Patients with intractable epilepsy

(done on about 250,000)

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Mechanism of action of Carbamazepine?

Block Na channels

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Mechanism of action of Ethosuximide?

Block Ca channels

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Mechanism of action of Perampanel?

Block AMPA/NMDA

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Mechanism of action of Clobazam?

Enhance GABA receptors

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Mechanism of action of Ezogabine?

Enhance K channel conductance

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Mechanism of action of Levetiracetam?

Block NT release