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
Seizure Recurrence Risk Factors
- Abnormal EEG
- Seizure occurs during sleep
- Positive family history (sibling)
- Prior acute seizure
- Down’s Syndrome and cerebral palsy
– No clear association of seizure type
– No association with seizure length
– No association with age of onset
Generalized Seizures
(2)
- Originate at some point
within and rapidly
engage bilaterally
distributed networks - Can include cortical and
subcortical structures
but not necessarily the
entire cortex
Focal Seizures
(2)
- Originate within
networks limited
to one
hemisphere - May be
discretely
localized
or more widely
distributed….
Focal Seizures
Note:
When a seizure type begins with
”focal, generalized or absence” then
the word “onset” can be presumed
Childhood Epilepsy
(6)
- Many children who experience a seizure, become
seizure free - Most seizures are brief
- Rarely do seizures cause long-term brain damage
without neurologic insult
– Hypoxia in first 24-48 hours increases risk - Medications may cause long-term side effects
- Children with idiopathic first seizure and normal EEG
have favorable prognosis - Rule-out: fever, infection, trauma
What do EEG’s Tell Us?
(3)
- Graphical representation of cortical electrical
activity - Provides high temporal resolution, poor
spatial resolution of cortical disorder - Most important neuropsychological
assessment tool for diagnosis, and subsequent
treatment
Importance of Detailed History
- Identifiable source (infection /trauma/medication)
– *Phenothiazines, TCA’s, clozapine, bupropion
– *Unmasking: CBZ, Phenytoin, Phenobarbital (absence) - Precipitating event (stress)
– Labs: hypoglycemia, hyponatremia, infection - Age of onset / frequency
- EEG patterns
- Severity
– Describe the type of movements, sounds, visual
observations - Family history – genetic considerations
- Observe and note the before, during, and after
suspected seizure activity (post-ictal)
When is Seizure Treatment
Appropriate??
* After — or more seizures.
* Treat after first seizure if:
(4)
two
– Idiopathic and abnormal EEG
– Symptomatic and abnormal EEG
– Prior neurologic abnormality
– Positive family history
Treatment Goals
(4)
1) Prevent occurrence of seizures (no seizure)
– Decrease frequency and severity
2) Prevent or reduce drug side effects and drug interactions
3) Prevent the development of neurologic changes
– Longer seizures = more ischemia
– Increased glutamate exposure = neuronal damage
– Repeated GTC or Status Epilepticus = cognitive decline
4) Improve the patient’s quality of life
– Provide cost-effective care (limit polypharmacy)
– Ensure patient satisfaction
– Prevent toxicity
– Ability to participate and complete ADL’s
Reasons Treatments Don’t Work
(5)
1) Inappropriate treatment
Select the wrong drug
2) Inappropriate dose
3) Poor compliance / lack of education
Drug storage issues (CBZ)
Drug administration issues (phenytoin
suspension)
4) Drug interactions
Cytochrome P450
P-glycoprotein
5) Seizure refractoriness
When can you consider stopping
medication treatments?
(5)
- Seizure free 2 to 4 years depending on seizure type
– 2 years for absence
– 4 years for partial, tonic-clonic - Normal neurological exam / normal IQ
- Normal EEG with treatment
- Epilepsy of single seizure type
– History of control within one year - No juvenile or myoclonic epilepsy
Seizure Disorder Medications
(Trade and Generic Names)
- Dilantin (phenytoin)
- Luminal (phenobarbital)
- Tegretol (carbamazepine)
- Depakote (divalproex)
- Keppra (levetiracetam)
- Zonegran (zonisamide)
- Gabitril (tiagabine)
- Banzel (rufinamide)
- Briviact (brivaracetam)
- Onfi (clobazam)
- Cenobamate (Xcopri)
- Fenfluramine (Fintepla)
- Topamax (topiramate)
- Trileptal (oxcarbazepine)
- Felbatol (felbamate)
- Lamictal (lamotrigine)
- Neurontin (gabapentin)
- Lyrica (pregabalin)
- Zarontin (ethosuximide)
- Vimpat (lacosamide)
- Fyocompa (perampanel)
- Aptiom (eslicarbazepine)
- Epidiolex (cannabidiol)
