ABPN Epilepsy cheat sheet

Epileptogenesis is the process by which a normal brain becomes epileptic; ictogenesis is the mechanism generating individual seizures.

Excitatory/inhibitory balance: reduced GABA-A mediated inhibition or enhanced NMDA/AMPA glutamatergic transmission lowers seizure threshold.

Cortical dysplasia and focal cortical dysplasia type II show mTOR pathway activation; dysmorphic neurons and balloon cells are histologic hallmarks.

Channelopathies: SCN1A loss-of-function causes Dravet syndrome; KCNQ2 variants cause neonatal epilepsy; SCN2A and SCN8A variants cause early infantile epileptic encephalopathy.

Seizure onset zone is the region where seizures begin; irritative zone shows interictal spikes; both may differ from the epileptogenic lesion.

Status epilepticus produces excitotoxic neuronal injury via calcium influx, mitochondrial dysfunction, and progressive loss of GABA-A receptor surface expression.

Kindling is progressive seizure susceptibility from repeated subthreshold stimulation; kindling models support secondary epileptogenesis.

Blood-brain barrier efflux transporters (P-glycoprotein) can reduce antiepileptic drug concentration at the seizure focus.

First step in a paroxysmal event: distinguish epileptic seizure from syncope, psychogenic nonepileptic seizure, and sleep/movement disorder.

Semiology localizes: automatisms with oral/alimentary features suggest temporal onset; asymmetric tonic posturing suggests frontal or supplementary motor onset.

Prolonged postictal confusion and postictal language dysfunction favor left temporal lobe involvement in temporal lobe epilepsy.

Ictal lateralizing signs: ictal dystonic posturing contralateral to seizure onset; ictal speech preservation suggests nondominant hemisphere.

Provoked seizures (hypoglycemia, hyponatremia, alcohol withdrawal, meningitis) are not epilepsy; epilepsy requires ≥2 unprovoked seizures >24h apart or one with high recurrence risk.

Epilepsy classification (ILAE 2017): focal, generalized, combined, or unknown onset; then motor vs nonmotor and awareness level.

Sudden unexpected death in epilepsy (SUDEP) risk factors include generalized tonic-clonic seizures, nocturnal seizures, poor medication adherence, and early-onset refractory epilepsy.

Video-EEG telemetry is the gold standard to capture events and differentiate epileptic from nonepileptic events.

Normal adult awake posterior dominant rhythm: 8-13 Hz alpha, reactive to eye opening; sleep spindles 11-16 Hz mark N2 sleep.

3 Hz generalized spike-and-wave with normal background supports childhood absence epilepsy; slow spike-wave (<2.5 Hz) suggests Lennox-Gastaut syndrome.

Hypsarrhythmia: chaotic high-amplitude disorganized background with multifocal spikes, hallmark of infantile spasms/West syndrome.

Periodic lateralized epileptiform discharges (PLEDs) suggest acute structural or infectious lesion (e.g., HSV encephalitis, stroke) and are highly epileptogenic.

Benign epileptiform transients of sleep (BETS) and wicket spikes are normal variants that must not be misread as epileptiform.

MRI epilepsy protocol: thin-slice coronal T2/FLAIR and 3D T1 to detect hippocampal sclerosis, focal cortical dysplasia, and small tumors.

Hippocampal sclerosis: atrophy and T2/FLAIR hyperintensity of hippocampus with loss of internal architecture; most common cause of temporal lobe epilepsy.

FDG-PET shows interictal hypometabolism in the epileptogenic zone; ictal SPECT shows hyperperfusion, useful when MRI is nonlesional.

Magnetoencephalography (MEG) localizes interictal spikes with high temporal and spatial resolution, useful in presurgical evaluation.

Mechanisms: sodium channel blockade (carbamazepine, lamotrigine, phenytoin, lacosamide), GABA enhancement (benzodiazepines, valproate, vigabatrin), SV2A binding (levetiracetam, brivaracetam).

Valproate is broad-spectrum, first-line for generalized and absence seizures; contraindicated in pregnancy (neural tube defects, cognitive teratogenicity).

Carbamazepine, oxcarbazepine, and phenytoin can worsen absence, myoclonic, and atonic seizures; avoid in generalized epilepsies.

Lamotrigine requires slow titration due to Stevens-Johnson syndrome risk; dose must be halved when adding valproate.

Enzyme inducers (carbamazepine, phenytoin, phenobarbital, oxcarbazepine) lower levels of oral contraceptives, warfarin, and many antiepileptics.

Status epilepticus: IV lorazepam first-line; then fosphenytoin, valproate, or levetiracetam; refractory cases need continuous midazolam or propofol with EEG monitoring.

Drug-resistant epilepsy: failure of two appropriately chosen and tolerated antiepileptic drugs; refer for surgical evaluation.

Therapeutic drug monitoring is most useful for phenytoin (nonlinear kinetics), carbamazepine, valproate, and phenobarbital.

Anterior temporal lobectomy yields seizure freedom in roughly 60-70% of drug-resistant temporal lobe epilepsy cases; best outcomes with unilateral hippocampal sclerosis.

Presurgical evaluation: phase I includes MRI, video-EEG, neuropsychology; phase II includes intracranial EEG when noninvasive data are discordant.

Wada test assesses language and memory lateralization before dominant temporal resection; fMRI increasingly replaces it for language.

Corpus callosotomy is palliative, not curative; most effective for drop attacks/atonic seizures in Lennox-Gastaut syndrome.

Vagus nerve stimulation (VNS) reduces seizure frequency ~50% in responders; side effects include hoarseness, cough, and dyspnea.

Responsive neurostimulation (RNS) delivers closed-loop stimulation to the seizure focus; indicated for drug-resistant focal epilepsy with ≤2 foci.

Ketogenic diet (high fat, low carbohydrate) is effective in drug-resistant epilepsy, especially in children; monitor for kidney stones, dyslipidemia, and growth.

Deep brain stimulation of the anterior nucleus of the thalamus reduces focal seizure frequency and is approved for drug-resistant epilepsy.

Pregnancy: levetiracetam and lamotrigine have favorable teratogenic profiles; valproate carries highest risk of neural tube defects and cognitive impairment.

All women of childbearing age on antiepileptics should receive folic acid supplementation (typically 0.4-4 mg daily) preconception.

Breastfeeding is generally encouraged; monitor infant for sedation, poor feeding, or irritability.

Febrile seizures: simple (generalized, <15 min, no recurrence in 24h) carry low epilepsy risk; complex features increase risk.

Juvenile myoclonic epilepsy: onset in adolescence, morning myoclonic jerks, often lifelong treatment needed; valproate or levetiracetam first-line.

Lennox-Gastaut syndrome: multiple seizure types (tonic, atonic, atypical absence), slow spike-wave, intellectual disability; treatment includes valproate, clobazam, rufinamide, felbamate.

Psychiatric comorbidity is high: depression and anxiety affect up to one-third; screen and treat, avoid bupropion and clozapine which lower seizure threshold.

Driving: seizure-free interval requirements vary by jurisdiction; typically 6-12 months seizure-free before resuming driving.

Stigma, employment discrimination, and social isolation are common psychosocial issues requiring counseling and support resources.

Epileptogenesis is the process by which a normal brain becomes epileptic; ictogenesis is the mechanism generating individual seizures.

Excitatory/inhibitory balance: reduced GABA-A mediated inhibition or enhanced NMDA/AMPA glutamatergic transmission lowers seizure threshold.

Cortical dysplasia and focal cortical dysplasia type II show mTOR pathway activation; dysmorphic neurons and balloon cells are histologic hallmarks.

Channelopathies: SCN1A loss-of-function causes Dravet syndrome; KCNQ2 variants cause neonatal epilepsy; SCN2A and SCN8A variants cause early infantile epileptic encephalopathy.

Seizure onset zone is the region where seizures begin; irritative zone shows interictal spikes; both may differ from the epileptogenic lesion.

Status epilepticus produces excitotoxic neuronal injury via calcium influx, mitochondrial dysfunction, and progressive loss of GABA-A receptor surface expression.

Kindling is progressive seizure susceptibility from repeated subthreshold stimulation; kindling models support secondary epileptogenesis.

Blood-brain barrier efflux transporters (P-glycoprotein) can reduce antiepileptic drug concentration at the seizure focus.

First step in a paroxysmal event: distinguish epileptic seizure from syncope, psychogenic nonepileptic seizure, and sleep/movement disorder.

Semiology localizes: automatisms with oral/alimentary features suggest temporal onset; asymmetric tonic posturing suggests frontal or supplementary motor onset.

Prolonged postictal confusion and postictal language dysfunction favor left temporal lobe involvement in temporal lobe epilepsy.

Ictal lateralizing signs: ictal dystonic posturing contralateral to seizure onset; ictal speech preservation suggests nondominant hemisphere.

Provoked seizures (hypoglycemia, hyponatremia, alcohol withdrawal, meningitis) are not epilepsy; epilepsy requires ≥2 unprovoked seizures >24h apart or one with high recurrence risk.

Epilepsy classification (ILAE 2017): focal, generalized, combined, or unknown onset; then motor vs nonmotor and awareness level.

Sudden unexpected death in epilepsy (SUDEP) risk factors include generalized tonic-clonic seizures, nocturnal seizures, poor medication adherence, and early-onset refractory epilepsy.

Video-EEG telemetry is the gold standard to capture events and differentiate epileptic from nonepileptic events.

Normal adult awake posterior dominant rhythm: 8-13 Hz alpha, reactive to eye opening; sleep spindles 11-16 Hz mark N2 sleep.

3 Hz generalized spike-and-wave with normal background supports childhood absence epilepsy; slow spike-wave (<2.5 Hz) suggests Lennox-Gastaut syndrome.

Hypsarrhythmia: chaotic high-amplitude disorganized background with multifocal spikes, hallmark of infantile spasms/West syndrome.

Periodic lateralized epileptiform discharges (PLEDs) suggest acute structural or infectious lesion (e.g., HSV encephalitis, stroke) and are highly epileptogenic.

Benign epileptiform transients of sleep (BETS) and wicket spikes are normal variants that must not be misread as epileptiform.

MRI epilepsy protocol: thin-slice coronal T2/FLAIR and 3D T1 to detect hippocampal sclerosis, focal cortical dysplasia, and small tumors.

Hippocampal sclerosis: atrophy and T2/FLAIR hyperintensity of hippocampus with loss of internal architecture; most common cause of temporal lobe epilepsy.

FDG-PET shows interictal hypometabolism in the epileptogenic zone; ictal SPECT shows hyperperfusion, useful when MRI is nonlesional.

Magnetoencephalography (MEG) localizes interictal spikes with high temporal and spatial resolution, useful in presurgical evaluation.

Mechanisms: sodium channel blockade (carbamazepine, lamotrigine, phenytoin, lacosamide), GABA enhancement (benzodiazepines, valproate, vigabatrin), SV2A binding (levetiracetam, brivaracetam).

Valproate is broad-spectrum, first-line for generalized and absence seizures; contraindicated in pregnancy (neural tube defects, cognitive teratogenicity).

Carbamazepine, oxcarbazepine, and phenytoin can worsen absence, myoclonic, and atonic seizures; avoid in generalized epilepsies.

Lamotrigine requires slow titration due to Stevens-Johnson syndrome risk; dose must be halved when adding valproate.

Enzyme inducers (carbamazepine, phenytoin, phenobarbital, oxcarbazepine) lower levels of oral contraceptives, warfarin, and many antiepileptics.

Status epilepticus: IV lorazepam first-line; then fosphenytoin, valproate, or levetiracetam; refractory cases need continuous midazolam or propofol with EEG monitoring.

Drug-resistant epilepsy: failure of two appropriately chosen and tolerated antiepileptic drugs; refer for surgical evaluation.

Therapeutic drug monitoring is most useful for phenytoin (nonlinear kinetics), carbamazepine, valproate, and phenobarbital.

Anterior temporal lobectomy yields seizure freedom in roughly 60-70% of drug-resistant temporal lobe epilepsy cases; best outcomes with unilateral hippocampal sclerosis.

Presurgical evaluation: phase I includes MRI, video-EEG, neuropsychology; phase II includes intracranial EEG when noninvasive data are discordant.

Wada test assesses language and memory lateralization before dominant temporal resection; fMRI increasingly replaces it for language.

Corpus callosotomy is palliative, not curative; most effective for drop attacks/atonic seizures in Lennox-Gastaut syndrome.

Vagus nerve stimulation (VNS) reduces seizure frequency ~50% in responders; side effects include hoarseness, cough, and dyspnea.

Responsive neurostimulation (RNS) delivers closed-loop stimulation to the seizure focus; indicated for drug-resistant focal epilepsy with ≤2 foci.

Ketogenic diet (high fat, low carbohydrate) is effective in drug-resistant epilepsy, especially in children; monitor for kidney stones, dyslipidemia, and growth.

Deep brain stimulation of the anterior nucleus of the thalamus reduces focal seizure frequency and is approved for drug-resistant epilepsy.

Pregnancy: levetiracetam and lamotrigine have favorable teratogenic profiles; valproate carries highest risk of neural tube defects and cognitive impairment.

All women of childbearing age on antiepileptics should receive folic acid supplementation (typically 0.4-4 mg daily) preconception.

Breastfeeding is generally encouraged; monitor infant for sedation, poor feeding, or irritability.

Febrile seizures: simple (generalized, <15 min, no recurrence in 24h) carry low epilepsy risk; complex features increase risk.

Juvenile myoclonic epilepsy: onset in adolescence, morning myoclonic jerks, often lifelong treatment needed; valproate or levetiracetam first-line.

Lennox-Gastaut syndrome: multiple seizure types (tonic, atonic, atypical absence), slow spike-wave, intellectual disability; treatment includes valproate, clobazam, rufinamide, felbamate.

Psychiatric comorbidity is high: depression and anxiety affect up to one-third; screen and treat, avoid bupropion and clozapine which lower seizure threshold.

Driving: seizure-free interval requirements vary by jurisdiction; typically 6-12 months seizure-free before resuming driving.

Stigma, employment discrimination, and social isolation are common psychosocial issues requiring counseling and support resources.