Epilepsy Flashcards
Epilepsy - Definition
Requires 2 or more unprovoked seizures separated by > 24 seizures OR 1 seizure with studies suggesting further risk for seizures
Seizures - Epidemiology
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
Seizure - DDx
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
Seizure Classification
Partial (Focal) vs. Generalized Seizures
Partial Seizures - EEG characteristics
EEG discharges show increased activity in only one region of the brain
Subclassification of Generalized Seizures
Absence Myoclonic - Quick Jerks Tonic Clonic - Briet stiffening followed by quick jerks Tonic - Brief stiffening Atonic - Loss of tone and collapse
Complex partial seizure vs. Primary generalized absence seizure - Presentation
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
Classification of epilepsy
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
Febrile seizures
Usually occurs in children < 6 years old with onset of fever; usually occurs intermittently and resolves without treatment as the child ages
Subclassification of partial seizures
Characterized according to one or more features:
Aura
Motor
Autonomic
Dyscognitive vs. unaltered awareness/responsiveness
Benign vs. Catastrophic Epilepsy
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
Bilateral consulsive seizure
Focal seizure that spreads to tonic-clonic
Approach to pharmacological treatment of epilepsy
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
Ketogenic diet
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
Chronic adverse effects of ketogenic diet
Hyperlipidemia Hyperuricemia Hypocalcemia Vitamin deficiency Acidosis Suboptimal growth
Serious / Life threatening
Kidney Stones (5-8%) Prolonged QT interval Increased bruising with bleeding Pancreatitis Immunosuppression
Vagal nerve stimulation
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
Vagal nerve stimulation - Side effects
Hoarseness / changes in voice Cough Tickling in throat Shortness of breath Rarely: Vocal cord paralysis and infection
Epilepsy surgery
Adults - Mostly focal temporal lobe surgeries
Children - More likely focal frontal/parietal surgeries or hemispherectomy
Not usually used for generalized seizures, unless corpus callosotomy
Indications for epilepsy surgery
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
Etiology of seizures
Primary: hereditary / idiopathic
Secondary: Mechanical - trauma, brain tumor Metabolic - hypoxia, hypoglycemia, hypocalcemia, alkalosis Withdrawal of CNS depressants Toxins
Anti-seizure medications that block VSSCs
Phenytoin
Carbamazepine
Lamotrigine
Topiramate
Anti-seizure medications that block VSCCs
Lamotrigine
Anti-seizure medications that bock T-type Ca2+ channels
Ethosuximide
Valproate
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
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
Use of VSCC blockers in epilepsy treatment
VSCC channels are involved in regulation of glutamate release
Agents: Lamotrigine
Use of SV2A blockers in epilepsy treatment
Blockers of synaptic vesicle protein SV2A inhibit Ca2+ mediated neurotransmitter release
Agents: Levetiracetam
Ethosuximide
Drug of choice in absence seizures
ADRs: Dose-related gastric distress most common (nausea, vomiting, pain)
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
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
Levetiracetam
1st line treatment of generalized tonic-clonic seizures
Side effects: Low incidence of cognitive effects - possible somnolence, dizziness
No CYP450 metabolism; minimal DDIs
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
Valproate
Effective, broad spectrum agent
Side effects: Dose-related GI upset, weight gain
Black box warning: Hepatic failure, pancreatitis, teratogenic effects
Use of Clonazepam in seizures
Effective against absence seizures as well as atypical seizures (myoclonic, infantile spasms, atonic)
Adverse effects: Sedation, behavioral problems
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
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
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
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
Drug Treatment of Tonic-Clonic Seizures
Valproate
Lamotrigine
Levetiracetam
Drug treatment of absence seizures
Ethosuximide
Valproate
Drug treatment of focal seizures
Carbamazepine
Lamotrigine
Levetiracetam
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
