Seizure Disorders Flashcards
What is a seizure?
* Seizure –
a discrete clinical event that results in the
abnormal discharge of a set of neurons in the brain
– “A transient occurrence of signs and/or symptoms due to
abnormal excessive or synchronous neuronal activity in the
brain.”
* A single seizure does NOT mean someone has epilepsy!
What is epilepsy?
* Epilepsy – (2)
* Convulsive Status Epilepticus – (4)
at least 2 unprovoked seizures
– Network disease and not a localized brain abnormality
failure of the mechanisms
responsible for seizure termination or from the initiation of
mechanisms which lead to abnormally prolonged seizures.
– length of seizure beyond 5 minutes
– second seizure without recovery from the first
– repeated seizures lasting 30 minutes or longer
Epilepsy
* Impacts and estimated — million Americans (1%)
– 150,000 to 200,000 new cases diagnosed each year
– —
times greater mortality (sudden unexplained death)
* Most often presents in infancy and childhood
– —% children have epilepsy
– —% of US population experience seizure in lifetime
* Bimodal distribution of occurrence
– Newborn/young children and > – years of age
* Risk increased with traumatic brain injuries
* > — billion is estimated in indirect and direct costs
2 to 3
2 to 3
0.5 % - 1
10
65
$12.5
International League Against
Epilepsy (ILAE) Epilepsy Etiologies
* Genetic –
(3)
usually present at a young age
– Dravet Syndrome – mutations in sodium channel, type I alpha
subunit
– Childhood Absence Epilepsy – mutations in T-Type Ca2+
channels and GABA receptor subunits
- Structural –
abnormalities found with neuronal imaging, e.g.
cortical dysplasia, posttraumatic epilepsy
- Infectious –
neurocysticercosis (parasite), meningitis, encephalitis
- Metabolic –
abnormal glycogen metabolism (Lafora Disease)
- Immune -
- Unknown
anti-NMDA receptor encephalitis (autoimmune)
Seizure Pathophysiology
* Excessive excitation of cortical neurons (hyperexcitable / hypersynchronization)
– Neuronal hyperexcitability -
Enhanced predisposition of neuronal
depolarization and discharge when stimulated
– Alterations in the properties of ion channels in the neuronal membrane
(4)
- K+, Na+, Ca2+, Cl-
- Carbamazepine and Phenytoin reduce neuronal excitability by binding sodium channels in the
inactive state and slow channel recovery from inactivation, preventing hyperexcitable neurons
from rapidly and repetitively firing - Benzodiazepines bind gamma subunit of GABA-A and increase chloride ion conductance
- Genetic mutations have been identified in these ion channels
– Defects in ion transport (ATPases) across neuronal membranes
(2)
- Sodium / Potassium / Calcium / Chloride
- Abnormality in potassium conductance
– Abnormal synaptic vesicle protein 2-A
(1)
- Normally responsible for fusion of vesicles to membrane, but get upregulated in some
epilepsies (levetiracetam and brivaracetam target)
Seizure Pathophysiology
* Additional Considerations
(5)
– Biochemical modification of receptors
– Modulation of second messaging systems and gene expression
– Changes in extracellular ion concentrations
– Alterations in neurotransmitter uptake and metabolism in glial cells
* GABA-T inhibition to increase GABA
– Modifications in the ratio and function of inhibitory circuits
- Transitory imbalance in neurotransmitters
(2)
– Enhanced excitatory neurotransmission
* Glutamate / Aspartate
Ionotropic glutamate receptors:
NMDA / AMPA / Kainate
Additional Seizure
Etiological Considerations
- Cerebrovascular
abnormality - Tumors
- Head trauma
- Infection
- Hypoxia
- Fever
- Medications and Seizure
medications
– clozapine
– bupropion
– carbamazepine - Drug Intoxication
– Cocaine, ephedrine - Metabolic disturbance
– High OR low glucose - Electrolyte disturbance
– Calcium, sodium, magnesium - Alcohol withdrawal
- Sleep deprivation
- Hormonal changes
- Stress
- Prenatal or birth injury
- Congenital malformation
