Seizures Flashcards
What is a seizure?
- Episode of abnormal _____ of ______ in the brain
- “______ ______” explanation
- May or may not be associated with a change in ______
- Classification
- ____ vs. _____ Generalized
- Focal w or wo _______ generalization
- ______ (preserved awareness) vs. ______ (impaired awareness)
- Episode of abnormal firing of neurons in the brain
- “Electrical storm” explanation
- May or may not be associated with a change in behavior
- Classification
- Focal vs. Primary Generalized
- Focal w or wo secondary generalization (treating by how it starts, so focal w sec gen still treated as focal)
- Simple (preserved awareness) vs. Complex (impaired awareness)
What are psychogenic non-epileptic seizures?
- Episode ________ a seizure, often per______ by the patient to be a seizure
- _____ associated with the “electrical storm” which occurs with epileptic seizures
- _________ in origin
- Treated with c______ and psy______ care as opposed to antiepileptic medications
- Episode resembling a seizure, often perceived by the patient to be a seizure
- Not associated with the “electrical storm” which occurs with epileptic seizures
- Psychological in origin “similar to a panic attack”
- Treated with counseling and psychiatric care as opposed to antiepileptic medications
Taking a Seizure History?
- Seizure description (_______cally, from A____ to return to _______).
- Frequent answer from patient: (1)
- Your response: What have witnesses described to you?
- a___
- loss or impairment of _______ness
- tongue ______
- abnormal movements, and which ex_______ involved
- ______ down
- ______ incontinence
- ______ incontinence
- _____ open versus closed
- pelvic th______
- how l_____
- p_____-ictal
- Seizure description (chronologically, from AURA to return to baseline).
- Frequent answer from patient: I don’t remember any of it.
- Your response: What have witnesses described to you?
- aura
- loss or impairment of consciousness
- tongue biting
- abnormal movements, and which extremities involved
- falling down
- urinary incontinence
- bowel incontinence
- eyes open versus closed
- pelvic thrusting
- how long
- post-ictal
Taking a Seizure History
- When did they _____?
- How f______?
- Tr_____, ex______ factors, re______ factors, meds that ____ worked, meds that _____ worked.
- _____ that preceded onset (head trauma, CNS infection, brain tumor, stroke, aneurysm rupture, psychologically traumatic experiences such as abuse, death of a loved one, combat, loss of a job, financial stress, or divorce).
- When did they start?
- How frequent?
- Triggers, exacerbating factors, relieving factors, meds that have worked, meds that haven’t worked.
- Events that preceded onset (head trauma, CNS infection, brain tumor, stroke, aneurysm rupture, psychologically traumatic experiences such as abuse, death of a loved one, combat, loss of a job, financial stress, or divorce).
The Work-Up
(4)
Which is the gold standard?
- MRI brain WITH AND WITHOUT CONTRAST (bc also looking for stroke (doesn’t need contrast), contrast to help look for tumors/lesions), and SPECIFY SEIZURE PROTOCOL.
- EEG
- EMU* GOLD STANDARD to confirm diagnosis of seizures (4 day long EEG in the hospital)
- Look for other neurological/medical problems, and check for signs of epilepsy syndromes
Important Causes of Seizures
(3)
Stroke
Brain Hemorrhage
Brain Tumor
(1)
Refers to irreversible tissue damage to brain, usually caused by blockage of artery by plaque or clots
- Risk Factors: HTN, obesity, smoking, diabetes, high LDL, and triglycerids
- Acute Treatment: (1)* within __-__ hours, clot retrieval, intra-arterial tPA
- Secondary prevention: (2) Rx
Stroke
- IV TPA within 3-4.5 hours
- Secondary prevention: Aspirin, Statin
Brain Hemorrhage
- Can be caused by brain tu_____, s____, tr_____, blood-_______ medications, blood vessel abnormalities
- How does a brain hemorrhage cause a seizure?
- Can be caused by brain tumors, stroke, trauma, blood-thinning medications, blood vessel abnormalities
- Seizures caused by irritation of brain by blood
Brain Tumor
- How do brain tumors cause seizures?
- What is often the first sign of a brain tumor?
- What type of brain tumors are more likely to cause seizures?
- Can cause seizures via edema and mass effect on surrounding brain tissue
- A first seizure is often the first sign of a brain tumor
- Slow-growing brain tumors are more likely to cause seizures than rapidly-growing brain tumors
Treatment of Seizures
- M________
- _____ nerve stimulation (like a brain ICD)
- ________ diet – not easy/common
- Corpus _______ – doesn’t stop seizure but stops seizure from spreading between hemispheres
- Multiple subpial transection
- Surgical re______
- Trigeminal nerve stimulation (investigational)
- Transcranial magnetic stimulation (investigational)
- Responsive neurostimulation
- Medications
- Vagal nerve stimulation (like a brain ICD)
- Ketogenic diet – not easy/common
- Corpus callosotomy – doesn’t stop seizure but stops seizure from spreading between hemispheres
- Multiple subpial transection
- Surgical resection
- Trigeminal nerve stimulation (investigational)
- Transcranial magnetic stimulation (investigational)
- Responsive neurostimulation
Treatment of PNES
(psychogenic non-epileptic seizures)
- ________ to patient – sometimes explaining it to the pt/reassurance will reduce their stress and less likely to have PNES
- Re_____
- C_______
- P______ care
- Explanation to patient – sometimes explaining it to the pt/reassurance will reduce their stress and less likely to have PNES
- Reassurance
- Counseling
- Psychiatric care
Summary of Agents Used to Treat Epilepsy
SPECT Scan
Shows what during a seizure?
Region of the brain in a person with epilepsy showing increased blood flow during a seizure
Classification of Epilepsy
-
(1) Consciousness is preserved
- (2) Types
-
(1) Consiousness is lost/no memory
- (5) Types
- (2) types of Status Epilepticus
-
Partial (consciousness is preserved)
- Simple Partial (consciousness normal)
- Complex Partial (consiousness altered/no memory)
-
Generalized
- Tonic Clonic
- Absence
- Myoclonic
- Infantile spasm
- Status epilepticus
- Generalized Status Epilepticus (convulsive or non-convulsive)
- Partial Status Epilepticus (consciousness lost/no memory)
Epilepsy Notes
- Status epilepticus =*
- Can use narrow and broad spectrum for (1) seizures, must use broad spectrum for (1) seizures*
- Most childhood epilepsies are (1), most adult onset are (1) but will probably start on broad spectrum incase its actually generalized, and in the meantime while gathering further diagnostics*
- Status epilepticus >5min bc that’s the point where it gets harder to treat*
- Can use narrow and broad spectrum for partial (focal) seizures, must use broad spectrum for generalized seizures*
- Most childhood epilepsies are generalized, most adult onset are focal but will probably start on broad spectrum incase its actually generalized, and in the meantime while gathering further diagnostics*
Therapeutic Strategies for Managing Newly Diagnosed Epilepsy
First Choice
*_____ out first med before starting a second med*
*Max out first med before starting a second med*
Therapeutic Strateiges for Managing Newly Diagnosed Epilepsy
Second Choice
Epilepsy definition
=
2 or more UNPROVOKED seizures
2/3 ppl will not have another seizure after the first (get out of jail free card) - these people usually experience a seizure due to something acute/provoked
Therapeutic Indications for Anticonvulsants
- What are common first line agents (4) used for both focal and generalized epilepsy?
- What is the first line drug for status epilepticus?
- Avoid _____ spectrum in primary generalized epilepsy such as what drugs?
- What is treatment should be considered when adherence, drug interactions, or adverse effects limit drug therapy?
- Lamotrigine, Levetiracetam, Topiramate, Divalproex
- Benzodiazepines
- Avoid narrow spectrum in primary generalized epilepsy (X Carbamazepine, Phenytoing, Gabapentin, Tiagabine, Vigabatrin)
- Vagal stimulator
Summary of Pharmacokinetics of Antiepilepsy Meds used as Chronic Therapy
CYP Metabolism of Antiepileptic Drugs
A lot of seizure medications can cause birth control failure, what is the preferred birth control method for someone who also has epilepsy?
Copper IUD
Summary of Older Agents used to treat Epilespsy
CDDELPPP
Phenytoin
MOA
Blocks Na+ Channels
Phenytoin
SE
(3)*
Hirsuitism, Gingival hyperplasia, Osteopenia/osteoporosis
Ataxia, nystagmus, cognitive impairment
Coarsening of facial features, cholesterol abnormalities, carotid artery stenosis
Phenytoin Indications
- What type of seizures can it treat?
- Effects of dosage on plasma concentration?
- ____ order kinetics
- Narrow spectrum, can worsen primary generalized seizures!
- Nonlinear effect - small increases in dosage can cause large increases in drug concentration
- Zero order kinetics = a constant amount of drug is eliminated per unit time but the rate is independent of the concentration of the drug.
Phenobarbital
MOA
Increases the amount of time for which GABA-gated-Cl- channels stay open (increases Cl coming in)
Phenobarbital
SE
- CNS _______*
- D_______ contractures
- ______ potential (bc is a barbiturate)
- Ataxia
- O______/O________
- CNS depression*
- Depuytren’s contractures
- Abuse potential (bc is a barbiturate)
- Ataxia
- Osteopenia/osteoporosis
Phenobarbital Indications
When do we use this drug?
Not a good choice for first line maintenance drug in most cases.
Can be used in IV form for status epilepticus.
Valproate
MOA (3)
Blocks sodium channels
Blocks T type calcium channels, and
Inhibits GABA transaminase (which breaks down GABA)
Valproate
SE (1)*
Bad in (1)*!
- Weight gain* Elevated liver enzymes
- Nausea, vomiting, abdominal pain
- Tremor, Alopecia,Thrombocytopenia, osteopenia/osteoporosis, Carotid artery stenosis
BAD IN PREGNANCY!
Valproate Indications
- Good for what types of seizures?
- Works ______ with Rx (1)
- Also good for other conditions such as (2)
- Multiple seizure types including ABSENCE seizures
- Synergistically with lamotrigine
- Migraines, good mood stabilizer
Benzodiazepines
MOA
Rx (2)
Increase the frequency of GABA -gated Cl-channels being open
Lorazepam, Diazepam
Benzodiazepines
SE
CNS depression, ataxia, abuse potential, tolerance
Benzodiazepines
- When do we use Benzodiazepines?
- Not indicated for?
- Good for short term control during seizure clusters, or buy time for other AEDs to take effect, IV benzos good for status epilepticus
- Try to avoid using for long-term seizure maintenance
Primidone
- Metabolized into? (2)
- SE (1)
- Can also be used for (1)
- Metabolized into phenobarbital and phenylethylmalonamide (PEMA)
- CNS depression
- Also used for tremor
Ethosuximide
MOA
Blocks T-type calcium channels
Ethosuximide
SE
Gastric distress (nausea, pain, vomiting), lethargy, fatigue, hiccups, headaches, skin rashes
Psychiatric disturbances (including hyperactivity, agitation, depression, suicidal ideation and suicidal attempts)
Ethosuximide Indications
What type of seizures does it treat?
Only works for absence seizures
Not used for other types of epilepsies
Carbamazepine
MOA
Blocks sodium channels
Carbamazepine
SE
(4)*
Aplastic anemia*, nausea, visual disturbances, hyponatremia*, agranulocytosis*, autoinduction of metabolism*, osteopenia/osteoporosis, cholesterol abnormalities, carotid artery stenosis
Carbamazepine Indications
- Good for what types of seizures?
- Can also be used for what condition?
- Very good for parital epilepsies, narrow spectrum so may worsen primary generalized epilepsies
- Mood stabilizer
Oxcarbazepine
MOA
Blocks sodium channels
Oxcarbazepine
SE
(1)* but overall?
Hyponatremia, but otherwise better tolerated than carbamazepine
Oxcarbazepine Indications
- Good for what types of seizures?
- Why is it better tolerated than carbazepine?
- Can also be used for what condition?
- Very good for partial epilepsy
- Metabolism does not create the epoxide that carbamazepine metabolism creates which is responsible for some of its SE
- Mood stabilizer
Vigabatrin
MOA
Inhibits GABA transaminase (transaminase breaks down GABA which is inhibitory)
Vigabatrin
SE
(2)*
CNS depression, HA, weight gain, visual field defects
v for visual*
Vigabatrin Indications
- Used for (2) conditions, can worsen (1) seizures
- Can cause irreversible?!*
- Used for tuberous sclerosis and infantile spasms, can worsen myoclonic seizures
- Visual field defects* (concentric with relative temporal sparing) - can be irreversible so watch out for them!!
Tiagabine
MOA
SE
GABA reuptake inhibitor
Dizziness, tremor, difficulty concentrating, depression
Tiagabine Indications
- May cause ______ status!!
- Can worsen ______ seizures
- May cause absence status!!
- Can worsen myoclonic seizures
Levetiracetam
MOA
Not fully clear
Binds to synaptic vesicle protein (SV2A), and may block N-type calcium channels and inhibit delayed rectifier potassium current.
Levetiracetam
SE (1)*
Grumpiness
Levetiracetam
How is it tolerated?
Indicated for patients who are?
Generally very safe and well tolerated. Wide therapeutic window, relatively low chance of interacting with other medications.
Safer in pregnancy than most AEDs
Lamotrigine
MOA
Blocks sodium channels
Lamotrigine
SE
(1)*
Dizziness, Headache, Diplopia, nausea, somnolence, rash*, Steven-Johnson syndrome* (rare)
Lamotrigine Indications
- Good for what type of seizures?
- Has to be titrated up _____ (which can be a disadvantage)
- Works ____ with _____
- Good for what other condition?
- Very good for Juvenile Myoclonic Epilepsy
- titrated up SLOWLY
- Works synergistically with valproate
- Good mood stabilizer
Felbamate
MOA
SE (2)*
Blocks sodium channels and acts as NMDA and GABA receptors
- Severe aplastic anemia* Hepatic failure*
- Lethargy, anorexia, N/V, HA, dizziness, insomnia, weight loss
Felbamate Indications
Indication for clinical use?
NOT A FIRST LINE DRUG!!
BLACK BOX WARNING FOR APLASTIC ANEMIA AND HEPATIC FAILURE!!
Topiramate
MOA
Blocks sodium channels, acts on non-NMDA glutamate receptors
Enhances Cl- currents through GABA A receptors
Topiramate
SE
(3)*
Somnolence, fatigue, dizziness, decreased appetite
Cognitive slowing, Altered verbal fluency bc given in much higher doses when tx for seizures vs. migraines, kidney stones*
Topiramate Indications
- ____ ____ inhibitor (_____ effects -> important to stay hydrated)
- Good for what other conditions? (4)
- Carbonic anhydrase inhibitor (diuretic effects)
- Good for migraine, tremors, mood stabilization, pseudotumor cerebri
Zonisamide
MOA
SE
Is a ____ drug
Blocks sodium channels and T-type calcium channels
Similar to topiramate (carbonic anhydrase inhibitor), but generally better tolerated than topiramate
Sulfa drug
Gabapentin
MOA
GABA-like molecule that binds to the alpha-2 delta-1 subunit of presynaptic voltage-gated calcium channels, thereby inhibiting the release of excitatory neurotransmitters which participate in epileptogenesis and nociception
Gabapentin
SE
(2)*
Somnolence
Dizziness
Ataxia
Weight gain*
Behavioral changes*
Gabapentin Indications
- For what type of seizures?
- Also used for (2)
- Narrow spectrum, can worsen primary generalized seizures
- Neuropathic pain, headaches
Pregabalin
MOA
Related to gabapentin. Binds to alpha2-delta subunit of voltage-gated calcium channels within the CNS, inhibiting excitatory neurotransmitter release. Modulates P/Q type voltage-gated calcium channels.
Pregabalin
SE
Peripheral edema
Ataxia, somnolence, dizziness, weight gain
Pregabalin
Also used for _____ pain, however it is ______
neuropathic pain, expensive
Rufinamide
MOA
Prolongs the inactive state of the Na+ channels, thereby limiting repetitive firing of sodium-dependent action potentials
(broad spectrum)
Rufinamide
SE
QT shortening, HA, dizziness, somnolence, fatigue, nausea, vomiting
2k/month
Rufinamide Indications
- Good for what type of seizures?
- _____ asborption of food intake
- FDA approved for L____ G_____ Syndrome
- Both generalized and partial epilepsies
- Increased absorption of food intake
- FDA approved for Lennox Gestaut Syndrome
Lacosimide
MOA
Stabilizes hyperexcitable neuronal membranes and inhibits repetitive neuronal firing by enhancing the slow inactivation of sodium channels (with no effects on fast inactivation of sodium channels)
Lacosamide
SE
(1)*
Dizziness, headache, nausea, diplopia
Cardiac conduction problems, PR prolongation* (get ECG before starting and again at steady state)
Lacosamide Indications
- Very effective for what type of seizures?
- Can also be given in IV form for (1)
- partial epilepsies
- IV form effective for status epilepticus
AEDs and Fetal Exposure
In utero, exposure to (1) compared to other AEDs is associated with an increased risk of impaired cognitive function at 3 years of age.
DO NOT USE VALPROATE in childbearing/pregnant women
AE of AEDs
(8)*
Summary of AEDs
**VERY IMORTANT**
When starting an AED, (1) of the dose SIGNIFICANTLY reduces the chance of (1)
Gradual Titration -> Reduces the chance of Side Effects
AEDs that can worsen primary generalized seizures?
(5)
Carbamazepine
Phenytoin
Gabapentin
Tiagabine
Vigabatrin
Try aVoiding Clinical Practice Guidelines
AEDs that stabilize moods
(5)
Carbamazepine
Oxcarbazepine
Valproate
Lamotrigine
Topiramate
CLOV-T
AEDs that cause weight loss
(3)
Felbamate
Topiramate*
Zonisamide
AEDs that cause weight gain
(4)
Gabapentin
Pregabalin
Valproate*
Lamotrigine?
AEDs that can prevent migraines
(3)
Gabapentin
Topiramate*
Valproate
AEDs used for tremor
(2)
Primidone
Topiramate
Prevent Tremor
AEDs eliminated almost entirely by the kidneys
(3)
Gabapentin
Levitiracetam
Vigabatrin
Neurontin -> Nephrontin, Keppra - K for kidneys, V for Void
AEDs that induce Metabolism of Medications
(3)
Phenytoin
Carbamazepine
Phenobarbital
PCP
AEDs that inhibit metabolism of medications
(2)
Valproate
Felbamate
Valproate + lamotrigine can cause steven johnsons bc the valproate inhibits metab of lamotrigine
AEDs with high protein binding (>75%)
(4)
Phenytoin
Valproate
Tiagabine
Carbamazepine
Check the free albumin (unbound)
ARS Question 1
Which of the following medications is safest in pregnancy?
A) Levetiracetam (Keppra)
B) Phenytoin (Dilatin)
C) Topiramate (Topamax)
D) Valproic acid (Depakote)
A) Levetiracetam (Keppra)
ARS Question 2
Which of the following medications can cause irreversible visual field defects?
A) Gabapentin (Neurontin)
B) Pregabalin (Lyrica)
C) Tiagabine (Gabitril)
D) Vigabatrin (Sabril)
D) Vigabatrin (Sabril)
ARS Question 3
Which of the following medications is not effective for absence epilepsy?
A) Ethosuximide (Zarontin)
B) Phenytoin (Dilantin)
C) Lamotrigine (Lamictal)
D) Valproic Acid (Depakote)
B) Phenytoin (Dilantin)
