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Nervous System IV > Epilepsy > Flashcards

Epilepsy Flashcards

1
Q

Epilepsy - Definition

A

Requires 2 or more unprovoked seizures separated by > 24 seizures OR 1 seizure with studies suggesting further risk for seizures

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2
Q

Seizures - Epidemiology

A

10% of population will have a seizure at some point in their lifespan

Only 1-2% of the population has epilepsy

36% of epilepsy is pharmacoresistant

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3
Q

Seizure - DDx

A

15-35% of patients thought to have seizure are found to actually have a different cause of episodic phenomena, including:

Syncope
Movement Disorders
Stroke/TIA 
Migraine
Sleep Disorder
Psychogenic/Behavioral
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4
Q

Seizure Classification

A

Partial (Focal) vs. Generalized Seizures

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5
Q

Partial Seizures - EEG characteristics

A

EEG discharges show increased activity in only one region of the brain

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6
Q

Subclassification of Generalized Seizures

A 
Absence
Myoclonic - Quick Jerks 
Tonic Clonic - Briet stiffening followed by quick jerks 
Tonic - Brief stiffening
Atonic - Loss of tone and collapse
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7
Q

Complex partial seizure vs. Primary generalized absence seizure - Presentation

A

Both consist of a period of altered mental status accompanied by major motor manifestatios

Partial complex seizures - automatisms (chewing, hand wringing, etc.) are more common; usually followed by a post-ictal state

Absence seizures are usually not followed by a postictal state

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8
Q

Classification of epilepsy

A

Structural-metabolic - 30% of epilepsies, 1/2 will remit

Genetic predisposition - formerly ‘idiopathic’

Unknown - formerly ‘cryptogenic,’ thought to have an etiology that is not known yet

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9
Q

Febrile seizures

A

Usually occurs in children < 6 years old with onset of fever; usually occurs intermittently and resolves without treatment as the child ages

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10
Q

Subclassification of partial seizures

A

Characterized according to one or more features:

Aura
Motor
Autonomic
Dyscognitive vs. unaltered awareness/responsiveness

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11
Q

Benign vs. Catastrophic Epilepsy

A

Benign - easily treated with medications with normal intelligence, normal tests; remission may occur after teenage years

Catastrophic - intractable to medications, affects development with intellectual disability and shortened lifespan of child; EEG and MRI are abnormal; often will have symptomatic etiology of seizure

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12
Q

Bilateral consulsive seizure

A

Focal seizure that spreads to tonic-clonic

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13
Q

Approach to pharmacological treatment of epilepsy

A

In general, treatment is indicated after 2 seizures of unknown cause

Aim for monotherapy but polytherapy is indicated once a patient has failed 2 meds

Keep someone on meds for 2 years seizure free before consider weaning; consider EEG prior to weaning to give prognosis about seizure recurrence

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14
Q

Ketogenic diet

A

Carbohydrate starvation leads to production of ketone bodies, which have anti-epilepsy effect; 4:1 fat to carbohydrate ratio can be achieved with use of cream or MCT oil

Useful with all seizure types - 50% see a reduction of > 50% seizure frequency after 1 year; 7% achieve seizure free status

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15
Q

Chronic adverse effects of ketogenic diet

A 
Hyperlipidemia
Hyperuricemia 
Hypocalcemia 
Vitamin deficiency
Acidosis 
Suboptimal growth
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16
Q

Serious / Life threatening

A 
Kidney Stones (5-8%)
Prolonged QT interval
Increased bruising with bleeding
Pancreatitis
Immunosuppression
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17
Q

Vagal nerve stimulation

A

Implanted in the left chest wall; provides baseline stimulation of vagus nerve with gradual onset of anti-seizure effect

Useful in cases of chronic, intractable seizures to achieve 50% seizure reduction in 50% of patients

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18
Q

Vagal nerve stimulation - Side effects

A 
Hoarseness / changes in voice
Cough
Tickling in throat
Shortness of breath
Rarely: Vocal cord paralysis and infection
19
Q

Epilepsy surgery

A

Adults - Mostly focal temporal lobe surgeries
Children - More likely focal frontal/parietal surgeries or hemispherectomy

Not usually used for generalized seizures, unless corpus callosotomy

20
Q

Indications for epilepsy surgery

A

Catstrophic epilepsy with terrible prognosis
Rapidly regressing developmental status
Presence of lesion or single focus not critical for function
Failed at least 3 AEDs, one of which is new

21
Q

Etiology of seizures

A

Primary: hereditary / idiopathic

Secondary: 
Mechanical - trauma, brain tumor 
Metabolic - hypoxia, hypoglycemia, hypocalcemia, alkalosis 
Withdrawal of CNS depressants 
Toxins
22
Q

Anti-seizure medications that block VSSCs

A

Phenytoin
Carbamazepine
Lamotrigine
Topiramate

23
Q

Anti-seizure medications that block VSCCs

A

Lamotrigine

24
Q

Anti-seizure medications that bock T-type Ca2+ channels

A

Ethosuximide

Valproate

25
Use of VSSC block in anti-seizure treatment
Blocks sustained, high frequency repetitive firing of APs that can initiate seizure formation Blockade is use-dependent; preferentially blocks epileptic foci leaving normal neurons unaffected Agents: Phenytoin, carbamazepine, lamotrigine, topiramate
26
Use of T-Type Ca2+ channel blockers in epilepsy
Absence seizures are characterized by abnormal oscillatory currents in thalamic neurons mediated by T-Type Ca2+ channels Agents: Ethosuximide, Valproate
27
Use of VSCC blockers in epilepsy treatment
VSCC channels are involved in regulation of glutamate release Agents: Lamotrigine
28
Use of SV2A blockers in epilepsy treatment
Blockers of synaptic vesicle protein SV2A inhibit Ca2+ mediated neurotransmitter release Agents: Levetiracetam
29
Ethosuximide
Drug of choice in absence seizures ADRs: Dose-related gastric distress most common (nausea, vomiting, pain)
30
Carbamazepine
Drug of choice for partial seizures; often useful in tonic-clonic seizures Side effects: Diplopia/ataxia/sedation, GI upset Rare but serious: Aplastic anemia, agranulocytosis, hepatotoxicity
31
Phenytoin
Good efficacy against partial and tonic-clonic seizures but negative pharmacokinetic profile limits use Zero-order (saturable) metabolism in therapeutic range; strong inducer of CYP450 causes DDIs Side effects: Nystagmus, diplopia, ataxia, sedation; rash gingival hyperplasia, hirsutism, osteomalacia, peripheral neuropathy
32
Levetiracetam
1st line treatment of generalized tonic-clonic seizures Side effects: Low incidence of cognitive effects - possible somnolence, dizziness No CYP450 metabolism; minimal DDIs
33
Lamotrigine
Broad spectrum efficacy due to effects on VSSCs (suppresses repetitive APs) and VSCCs (decreases Glutamate release) 1st line for partial or generalized seizures - better tolerated than phenytoin or carbamazepine Side effects: Similar to phenytoin (diplopia, ataxia, dizziness, sedation) but lower incidence
34
Valproate
Effective, broad spectrum agent Side effects: Dose-related GI upset, weight gain Black box warning: Hepatic failure, pancreatitis, teratogenic effects
35
Use of Clonazepam in seizures
Effective against absence seizures as well as atypical seizures (myoclonic, infantile spasms, atonic) Adverse effects: Sedation, behavioral problems
36
Use of Diazepam in seizures
Drug of choice for status epilepticus Adjunctive therapy in atonic and absence seizures, as well as infantile spasms Adverse reactions: Somnolence, tolerance are limiting factors in chronic use
37
Phenobarbital
Choice agent for neonatal status epilepticus; adjunct use for partial and tonic-clonic seizures Adverse reactions: CYP450 inducer, irritability, ataxia, nystagmus, rash, osteomalacia, cognitive deficits
38
Status epilepticus
State of recurrent, major motor seizures between which patient does not regain consciousness Mortality 20-25% from respiratory / circulatory collapse First line therapy with IV diazepam until seizures stop Next, phenytoin slow infusion If seizures persist, IV phenobarbitol
39
Use of AEDs in Pregnancy
Risk to fetus from maternal seizures > AED use Risk of birth defects is 2-3x higher with mother on AEDs: cleft palates, skeletal abnormalities, CNS/cardiac problems Valproate and phenobarbital highest risk
40
Drug Treatment of Tonic-Clonic Seizures
Valproate Lamotrigine Levetiracetam
41
Drug treatment of absence seizures
Ethosuximide | Valproate
42
Drug treatment of focal seizures
Carbamazepine Lamotrigine Levetiracetam
43
Gabapentin
Binds to voltage-sensitive Ca2+ channels, decreasing synaptic release of glutamate; used in treatment-resistant epilepsy Side effects: Dose-dependent sedation, ataxia, dizziness; few/no DDIs

Nervous System IV (10 decks)

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