Electrical activity is isolated to an anatomical location

60% of seizures

Major motor or sensory involvement, no loss of consciousness

Manifestations: motor - frontal T/C of contralateral side; sensory - parietal/occ visual/aud/olf hallucinations; EEG - isolated spiking contralateral to activity

Any age group but often post-seizure; lasts seconds-minutes; "jacksonian march"; may go to generalized

In the temporal region, usually affects higher cognitive ability causing psychomotor or psychosensory disturbance with altered consciousness

Manifestations: Sensory - hallucinations; autonomic - GI, dizziness, urination; psychosensory - deja vu; memory distortions; automotisms - purposeless activity.

Last 1-2 minutes, before age 20, may generalize, possibily from birth damage to temporal lobe

Bilateral synchronous and symmetrical electricoencephalographic discharge.

Loss of consciousness.

May start generalized or start as partial and progress

40% of seizures

Tonic clonic or absence.

Also: myoclonic, infantile spasm, akinetic and atonic drops

Also mixed

1. Prodromal - autonomic, mood or behavior changes; no EEG changes

2.  Loss of muscle tone and consciousness

3. Tonic x45 seconds - "opsithotonos" - EEG: 100-200 uV spikes bilaterally; apnea/cyanosis

4.  Clonic x1-5 minutes - EEG: wave/spike bilateral/symmetrical 1 spike/contraction; hyperventilation; tongue biting

5.  Postictal - confusion and sleepiness

1. benign, self-limiting; oscillatory firings of the thalamic neurons of low-threshold Ca+ 

 2.  Onset 4-8 years old - may convert at puberty

3.  50+ per day

4. Manifestation: abrupt LOC for a few seconds with rapid eye blinking; no postictal period

5. EEG: 3 cps spike complex; bilateral and symmetrical; illicited by hyperventilation or bright lights

6.  Most stop by age 20; half have tonic-clonic 10-14

EEG: 2-2.5 cps spike/wave complex

POOR PROGNOSIS - associated with dementia

Not abrupt on/off

Some motor movement

NOT brought on by hyperventilation or bright lights

Common in young

Result of permanent damage

Repetitive, rhythmical, symmetrical facial or limb movements

Accompany normal sleep/wake cycle

EEG: polyspike/wave complexes; bilateral/symmetrical

Prognosis is varied 

"Jackknife/Salaam" - age specific 

Syndrome from 3 months - 2 years

90% become mentally retarded; 40% get CP

Flexor spasms of head/extremities for many seconds

EEG: hypesarrhythmia

Caused by encephalopathy - ACTH or steroids can help

Frequent age 2-5

Poor prognosis (mental retardation)

Head dropping/falling

Lasts for seconds x several types per day

EEG: polyspike/wave, vary in rhythm, bilateral/symmetric

Mechanism: Quiets focus, prevents spread; slows recovery of sodium channels from inactivation

10, 11 epoxycarbamazepine also active

Pharmacokinetic issues: 97% met. cleared; autoinduction of p450 over 1 month; monitor serum; increases metabolism of other lipid soluble drugs

phenobarbitol/phenytoin increase metabolism

Uses: 

1. First choice for partial - simple and complex

2.  First choice for Tonic-Clonic

3. Trigem and glossopharyngeal neuralgia

4. NOT for absence or minor motor

5. NOT parenteral for status epilepticus

1.  dose related - diplopia, ataxia, SIADH, dizziness, nausea, nystagmous

2.  idiosyncratic - rash, leukopenia, aplastic anemia, agranulocytosis

Same as carbamazepine 

Partial and tonic clonic, not for absence or status epilepticus

LESS induction of the p450 system

NEW FIRST CHOICE

Same as carbamazepine 

quiets focus, prevents spread

slows rate of recovery of sodium channels from inactivation

LESS induction of p450 system

keto homolog of carbamazepine

t1/2 - 1.5 hours

Prodrug converted to 10-hydroxy version (t1/2 - 10 hours)

Excreted as 10-OH glucuronide version

Less induction of p450 - less tolerance, less hypersensitivity

Ataxia, diplopia, SIADH

Equal to carbamazepine for partial and tonic-clonic

IV fosphenytoin for recurrent tonic-clonic or status epilepticus

Quiets focus, prevents spread

Binding to the Na channel prolonging inactive state and prolonging refractory period

Mild CNS depressant: little sedation, no coma, no withdrawal, no tolerance, dependence with EtOH, barbiturates, or benzos

Limited H2O solubility: Acid formed is insoluble

Bioinequivelence of generics is a problem

Zero order; 90% met by p450; non-linear pattern between dose and plasma concentration

P450 induction is not as high as carbamazepine

P450 is competitive with other drugs - adjust dose

Valproate and sulfa displace Phenytoin from albumin - MONITOR CLOSELY

Phenobarb and carbamazepine enhance metabolism

POLYPHARM IS DIFFICULT

1. Dose dependent: Ataxia, diplopia, slurred speech, nystagmus, confusion

2. Hypersensitivity: dermatosis, lymphadenopathy, neutropenia, leukopenia

3. Other: gingival hyperplasia, course features, hair, Vit folate, D,K deficiencies

4. Teratogenic: cleft lip/palate/heart defects/slowed development/growth

Barbiturate

Uses: partial seizure, T/C, status epilepticus, neonatal seizure

Mechanism: Potentiates inhibitory effects of GABA at receptors resulting in synaptic inhibition (hyperpolarization of membrane)

t1/2 = 100 hrs

MOST POTENT inducer of p450 (tolerance and drug-drug problems)

Side effects: Sedation, learning problems, nystagmous, ataxia, withdrawal, Vit DKfolate def., paradoxical hyperkinesia ages 5-9

Slows T-type low threshold Ca channels in thalamic neurons during absence seizures

75% of clearance by p450 system

does not induce p450 system

other antiepileptics may affect metabolism

First choice simple absence seizures

Not effective for minor motor, partial, or TC seizures

Dose related: GI - nausea and vomiting

CNS - drowsiness

Rare: urticaria, blood dyscrasia

Prolongs recovery voltage activated sodium channels from inactivation

Reduces low threshold (T current) Ca channels in thalamic neurons

Increases GABA concentration in brain

Metabolized by the p450 and fatty acid oxidation

Many active metabolites

Does not induce p450

Other drugs affect metabolism

First choice for absence with myoclonic or other manifestations

Most effective for myoclonic or atonic

Somewhat effective for hypsarrhythmia

Good for partial and TC - almost as good as Carb.

Nausea/Vomiting

Teratogenic: Spina Bifida

Thrombocytopenic

Hepatotoxic - monitor LFTs

Sedation/ataxia

Delay recovery from inactive Na channels

Maybe inhibits voltage gated Ca channels

More broad than Carb and Phen

Metabolized by direct glucuronidation

t1/2 = 24 hours

Monotherapy:

comperable to Carb. for partial and TC seizures

effective against absence and myoclonic, not as good as valproate

Polytherapy: Good when only partial coverage happens and when drugs are met by p450

Rash

TOXIC EPIDERMAL NECROLYSIS (Stevens-Johnson Syndrome)

Dizziness, ataxia, GI, diplopia

Multiple, broad

Blocks voltage-gated Ca channels

Potentiates GABA and depresses glutamate activity

Good bioavailability; t1/2 = 24 hours

Uses: TC/partial

also effective for absence and rare (not approved)

Recommendations:

Uncontrolled, intolerable, drug interactions

Good as an add-on

recurrent seizures with short interictal period

can be any type of seizure, most commonly partial and TC (TC = medical emergency)

Can be brought on by withdrawal of antiepileptics, metabolic disorder, high fever, CNS infection

1. IV Lorazepam

2. For sustained control: IV fosphenytoin, phenobaritol IV

3. For refractory status: general anesthesia, paralysis, EEG monitor

Carbamazepine, Phenytoin, and Phenobarbitol increase the metabolism of OCPs (P3A4)

Carbamazepine, Phenytoin, Valproate, and Phenobarbitol all are teratogenic: Supplement folate

Carbamazepine, Phenytoin, and Phenobarbitol all induce p450 promoting Vit K catabolism: results in coagulopathy and hemorrhage in neonate and post-partum blood loss: Supplement Vit K