Epilepsy Flashcards
Seizure
-episode of abnormally synchronized & high frequency firing of neurons resulting in abnormal behavior or experience
Epilepsy
-chronic brain disorder of various etiologies characterized by recurrent, unprovoked seizures
Epilepsy Syndromes
-grouping of similar epileptic patients according to seizure type, EEG age of onset, prognosis & clinical signs
Epidemiology of Epileptic Seizures
- 0.5% of pop.
- 2.5 million prevalent cases
- 150,000 to 200,000 new cases/year
- age-specific incidence had dec. in younger age groups, inc. in patients over age 60
Causes of Adult-onset Epileptic Seizures
- Cerebrovascular disease
- Trauma
- Tumors
- Infections
- Cerebral Degeneration
ILAE Classifications of Epileptic Seizures
-Clinical Observation + EEG FIndings
partial seizures and generalized seizures
Types of Partial Seizure
- Simple (consciousness preserved)
- Complex (consciousness impaired)
- Secondarily Generalized (consciousness lost + bilateral cerebral involvement)
Simple Partial Seizures
- Signs/symptoms depend on focus: motor (Jacksonian - move up body part), somatosensory, autonomic, psychic
- consciousness is intact
- EEG may appear normal
- Auras are brief, simple partial seizures with no overt behavioral manifestations
Complex Partial Seizures
- impaired consciousness
- lasts ~1min
- blank stare
- oral/ipsilateral hand automatisms
- contralateral dystonic posturing
- amnesia for ictal event
- focal abnormality on routine EEG
Primary Generalized Seizures
- absent (Petit Mal)
- tonic-clonic
- clonic
- tonic
- myoclonic
- atonic
Absence Seizure Features
- brief loss of consciousness (10-20sec)
- staring spell
- no post-ictal confusion
- subtle myoclonic movement, eyelid flutter
- no baseline neurologic deficits
- baseline EEG may show generalized 3Hz spike -wave discharges
Tonic-Clonic Seizures
-typical presentation:
cry, loss of consciousness, muscular rigidity (tonic), patient may fall, rhythmic jerking (clonic), tongue-biting/injury common, bladder/bowel incontinence, post-ictal confusion/sleep
-Grand Mal
Myoclonic Seizure
-brief, shock-like muscle contractions (head, upper extremities)
-usually bilaterally symmetrical
-consciousness preserved
-precipitated by awakening or falling asleep
-may progress into tonic-clonic seizures
(juvenile myoclonic epilepsy)
Atonic Seizure
- impaired consciousness
- loss of muscle tone
- head drop, fall
- brief duration (few seconds)
- injury common
Seizure Diagnosis
- History from patient & witnesses
- Physical & neurological examination
- CBC, CMP, AED levels
- Inter-ictal EEG
- Epilepsy protocol MRI
- Video-EEG monitoring
Prevalence of Inter-ictal Epileptiform Discharges in Epileptic Patients
- initial EEG detects on epileptiform discharge in 29-55% of patients
- serial EEGs reveal epileptiform discharges in 80-90% of patients
- Repeat studies, with sleep deprivation & extended recording times, helps inc. chances of detecting epileptiform discharges in patients with epilepsy
Focal Epileptiform Discharge
- seizure focus is in left anterior temporal head region
- sharp waves, spikes, & sharp-and slow wave discharges
Generalized Epileptiform Discharge
- bilateral burst of epileptiform spike & slow wave discharges
- discharge simultaneously & symmetrically in both hemispheres
Seizure MRI
-Recent-onset epilepsy in adults requires imaging sequences, including gadolinium-DPTA enhanced sequences to find primary or secondary tumors, infection or inflammation
Epilepsy Protocol MRI
- Coronal high resolution T1-weighted volume data set through the whole brain
- a coronal T2-weighted sequence, typically using 3 mm thin sections, should also be done in order to detect hippocampal sclerosis
Video-EEG monitoring
- simultaneous recording of EEG & seizure
- useful in differentiating epileptic seizures from non-epileptic seizures
- useful for characterizing seizure type
- essential for pre-surgical localization of the seizure focus
Pathophysiology of Seizures
- Ligand-gated ion channels can be excitatory or inhibitory depending on their ion selectivity
- GABA activates GABA a receptors that mediate fast synaptic inhibition (IPSP) by permitting rapid influx of Cl ions, resulting in hyperpolarization
- glutamate activated 3 classes of ion channels (AMPA, Kainate, NMDA) that mediate fast synaptic excitation by permitting a rapid influx of NA and Ca ions
- in most neuronal circuits, GABAergic inhibition exerts a powerful suppression of excitability
- this inhibition is overcome during the development of a focal seizure
Goal of Antiepileptic Drug (AED) Therapy
-2 types of remission:
Medical remission: seizure free without side effects on 1 or 2 AEDs
-Disease Remission: seizure free off all AEDs
-major goal of AED therapy is to achieve medical remission
-surgical therapy is well-selected cases may result in disease remission
AED Selection
- efficacy for specific seizure types or epilepsy syndrome
- efficacy for co-morbid conditions
- interactions with other drugs
- ease of introduction, follow-ip
- drug safety
- cost
Phenobarbital
- enhances activity of GABA receptor, depresses gluatmate activity, reduces Na, K conductance
- SE: hepatotoxicity, connective tissue disorder, SJS
- P450 inducer
Phenytoin
- blockade of Na channels & inhibitory action of Ca and Cl conductance
- SE: aplastic anemia, hepatic failure, SJS
- P450 inducer
Carbamazepine
- block of neuronal Na channel conductance
- SE: aplastic anemia, hepatotoxicity, Stevens Johnsons syndrome, Lupus-like syndrome
- P450 inducer
Valproate
- affects GABA glutamatergic activity & reduce threshold of Ca and K conductance
- Hepatotoxicity, hyperammonemia, leukopenia, thrombocytopenia, pancreatitis
Ethosuximide
- inhibits Ca T channel conductane
- SE: bone marrow depression, hepatotoxicity
Lamotrigine
- blockage of voltage dep. sodium conductance
- SE: SJS or toxic epidermal necrolysis
Oxcarbazepine
- Na channel blockage
- SE: hyponatremia, rash
- P450 inducer
Topiramate
- blockage of Na channels, enhancement of GABA medicated Cl influx
- SE: renal calculi, hypohidrosis
- P450 inducer
Zonisamide
- Blockade of Na, K, & Ca channels, inhibits glutamate excitation
- SE: renal calculi, hypohidrosis
Gabapentin
-Modulation of N-type Ca channel
AEDs for Partial & Tonic-Clonic Seizures
-Valproate, Phenytoin, Carbamazepine & Phenobarbital
AEDs for Absence Seizures
-Ethosuximide & Valproate
New AEDs for partial seizures
-Gabapentin & Oxcarbazepine
New AEDs for Partial & Generalized seizures
-Lamotrigine, Topiramate, Levetiracetam, & Zonisamide
P450 inducers
- lead to failure of oral contraceptives
- cause osteopenia, osteoporosis, fractures
- inc. metabolism of androgens & estrogens
don’t want to give for: women oral contraceptives, patient on oral coagulation, transplant patients, AIDS patients on protease inhibitors, patients predisposed to osteoprorsis
AED Birth Defects
- older cause malformations in 4-8% of children (twice normal rate) with risk inc. with higher AED dose & polytherapy Cat D
- newer not teratogenic in animals, Cat C in humans
-to reduce risk: lower effective dose, monotherapy, preconceptual folic acid supplementation, 0.8-4mg/day, prenatal diagnostic testing at 16-18 weeks: maternal serum alpha fetoprotein, ultrasound studies
Probability of Medical Remission in Newly Diagnosed Patients
-for 2 or more years
47%with 1st AED used in monotherapy
14% with 2nd AED used in monotherapy
4% with 2 AEDs used
Intractable Epilepsy
- have disabling seizures recurring despite optimized therapy
- Disabling seizures: seizures causing impaired quality of life, limited educational or occupational opportunities, physical injuries or social compromise
- Optimized Treat: AED treatment is optimum with 2 AEDs at max tolerated dose
Prevalence of Intractable Epilepsy
- controlled with AEDs in 70-80% of patients
- 20-30% are not seizure-controlled using currently available AEDs and are therefore intractable
Burden of Intractable Epilepsy
- poor quality of life
- restriction of psychosocial, educational, & occupational performance in child & adult
- risk of injuries from seizures
- higher risk of SUDEP (sudden unexplained death in epilepsy)
Therapy of Refractory Epilepsy
- polytherapy with antiepileptic drugs
- vagus nerve stimulator
- epilepsy surgery
Vagus Nerve Stimulation
- Electrical pulse generator implanted subcutaneously on chest
- Lead attached to left vagus nerve
- mechanism of action unknown
- about 40-50% have >50% seizure reduction, but rarely seizure free
Epilepsy Surgery
- temporal lobectomy
- lesionectomy
- corticectomy
- corpus callosotomy
- multiple subpial transections
- hemispherectomy
Generalized Convulsive Status Epilepticus
- continuous, generalized, convulsive seizure lasting more than 5 min. or 2 or more sequential seizures occurring without full recovery of consciousness
- non-convulsive status epilepticus is an EEG diagnosis
Management of GCSE
-
Treatment of Refraactory GCSE
- refractory if patient fails to respond to lorazepam
- if convulsive seizures persist, consider intubation
- start continuous EEG monitoring
