• Abnormal, hypersynchronous discharge of a population of cortical neurons
• The discharges last for several seconds before they can produce clinical manifestations

• Clinical seizure: discharge may produce subjective symptoms or objective signs
• Electrographic (or subclinical) seizure: apparent only on an electroencephalogram (EEG)

• Partial: 1 area of the brain, usually medial temporal lobe; often preceded by aura
• Simple: Consciousness intact, including motor, sensory, autonomic, psychic

• Complex: impaired consciousness
• May begin with simple partial seizure = aura
• May have automatisms
• Lasts < 2 min

• Lip smacking, chewing, grimacing, swallowing, pick at clothes
• Permit himself to be led; strike out if restrained but in a nondirected way; speak in jumbled or repetitive phrases; perform stereotyped behavior; walk about in a dazed state; etc.
• Duration: brief or up to five minutes
• Postictal confusion: several minutes
• Postictal period automatisms: after severe seizure, usually associated with confusion.

• 3 Hz spike and wave on EEG
• Lasts <20 sec
• Almost always begin before puberty, resolve < age 18 with no cognitive impairment
• Atypical absences: EEG spike and wave activity more heterogeneous +/- automatisms, global cognitive impairment

• Alternate between stiffening and movement
• Tonic phase:  Stiffening and fall, often associated with ictal cry
• ŒClonic Phase:Œ Rhythmic extremity jerking

• state of continuing or recurring series of seizures with incomplete recovery between attacks  (i.e., a series of seizures without regaining consciousness between attacks).
• Can occur with any seizure type
• Emergency: Generalized tonic-clonic seizure

1. Congenital maldevelopment.
2. Birth injury.
3. Metabolic (hypocalcemia, hypoglycemia).
4. Vitamin B6 (pyridoxine) deficiency.
5. Phenylketonuria.

1. Birth injury.
2. Trauma.
3. Infection.
4. Thrombosis of cerebral artery or vein.
5. Beginning of idiopathic epilepsy.

1. Idiopathic epilepsy.
2. Trauma.
3. Congenital defects.

1. Trauma.
2. Neoplasm.
3. Idiopathic epilepsy.
4. Alcoholism.
5. Drug addiction.

1. Neoplasm.
2. Trauma.
3. Vascular disease.
4. Alcoholism.
5. Drug addiction.

1. Vascular disease.
2. Degenerative disease.
3. Neoplasm.

Generalized Absence, Myoclonic, Atonic Seizures

Tx

DOC: Ethosuximide

Other: Valproate (Depakote)

Status Epilepticus: Generalized Tonic-Clonic

Tx

1. IV Fosphenytoin (more H2O soluble > Phenytoin): prophylaxix
2. Simultaneous Lorazepam

Partial Simple or Complex

or

Generalized Tonic-Clonic Seizure

Tx

Phenytoin

Carbamazepine/Oxcarbazepine

Valproate

---

Lamotrigine

Topiramate

MOA: Na+ channel inactivator, Class IB anti-arrhythmic 

PK: zero order kinetics, nonlinear [] vs. dose curve = narrow Tx window

Highly protein bound (90%), monitor free fraction

1. Acne
2. Hirsutism
3. Gingival hyperplasia
4. Nystagmus, diplopia
5. CYP 450 inducer
6. Cleft lip, cleft palate

Fetal Hydantoin Syndrome

+ Neonatal Hemorrhage

Cleft lip and palate

Mental retardation

Low set ears

Skeletal spinal abnormalities

Heart malformation

Neonatal hemorrhage due to less Vit K dep clotting factors; also seen with Phenobarbitol

MOA: Na+ channel inactivator

1. Hepatotoxic
2. SIADH
3. SJS
4. Aplastic anemia
5. CYP Inducer
6. Cleft lip, cleft palate; spina bifida; nail hypoplasia

MOA: Na+ channel inactivator, T-Type Ca2+ channel blocker, GABA Transaminase blocker (increase GABA)

1. Alopecia
2. Weight gain
3. Hepatotoxic
4. Pancreatitis
5. Thrombocytopenia
6. P450 Inhibitor
7. Spina bifida: contraindicated in pregnancy

Developmental delays

Limb and digit abnormalities

MOA: Block Na+ channel, increase GABA action

1. Weight loss
2. Block kidney CA: kidney stones

Bone Disease with AED's

Phenytoin

Carbamazepine

Valproate

Phenobarbitol

Decrease Ca2+ absorb

Increase Vit D catabolism

Impaired bone resorb and form

Use Ca2+ and Vit D supplementation to prevent osteomalacia, osteoporosis, rickets in children