Seizures Flashcards
Seizure v. Epilepsy
Seizure- discrete clinical event of temporary brain dysfunction characterized by abnormal electrical discharge
Epilepsy - paroxysmal disease of recurring, unprovoked seizures
- Continuous tendency to generate unpredictable seizures w/o provoking factors
Epilepsy Criteria
- Specific criteria = 2 unprovoked seizures in > 24 hr OR dx after 1 seizure if risk of recurrent seizure is 60% or more
- Cannot be cured but “resolved” if no seizures for 10yrs and have not taken seizure meds in 5 yrs
PDS
Paroxysmal Depolarization Shift
- Large, prolonged depolarization of neuronal membrane —> bursts of spike activity on EEG (interictal epileptiform discharges on scalp)
- Inc excitation (EPSPs) and dec inhibition (IPSPs) —> depolarization —> progresses to train of action potentials (ictal phase) —> ACTIVATE inhibitory currents —> recovery
3 types of epilepsy due to ion channel mutations
- Benign Familial Neonatal Convulsions (BFNC) - K+ channel problem
- Genetic Epilepsy w/ Febrile Seizures Plus (GEFS+) - Na+ channel problem
- Idiopathic Generalized Epilepsy (IGE) - Cl- channel problem
Temporal Lobe Epilepsy + Circuit Associated
FOCAL
Hippocampus Circuit
- Excitation from enterohinal cortex —> granule cell layer of hippocampus —> AP propagates down mossy fibers —> project to hilar interneurons AND CA3 region pyramidal neurons (excitatory)
- Hilar mossy cells then excite basket cells that inhibit the original granule cell layer (FEEDBACK)
- C3 pyramidal —> CA1 pyramidal via Schaffer collaterals
Kindling Model (+ what does this look like in hippocampus?)
- repeated admin of sub convulsive electric stim or other agents —> after discharges —> progression to more intense seizures
- Tissue develops enhanced sensitivity (“kindled”)
- repeated admin of sub convulsive electric stim or other agents —> after discharges —> progression to more intense seizures
- In hippocampus this leads to …
- 1- Enhanced excitement of dentate granule cells (via NMDA receptors)
- 2- Loss of hilar neurons that normally activate inhibitory basket cells (loss of feedback inhibition)
- 3- Synaptic reorganization of granule cell output and feedback to dentate -> hyper-excitability
Absence Seizures + Circuit Associated
GENERALIZED
- Sudden episodes of staring w/o awareness
- Involves thalamocortical circuitry (central and deep)
- Cortex pyramidal cells excite reticular neurons in thalamus + relay cells excite reticular neurons—> reticular neurons are GABAergic so they inhibit fellow reticular cells and relay neurons —> relay neurons excite cortex pyramid cells
- Thalamic reticular and relay neurons both use low-threshold transient Ca++ channels (T channels) which allow influx of Ca++ after only mild depolarization —> burst firing followed by inactive mode (takes awhile for de-inactivation)
8 Postulated Causes of Epilepsy
- Abnormal ion channels
- Abnormal neurotransmitter metabolism
- Abnormal receptors
- Defects in neuronal migration
- Disorders of cell growth and differentiation
- Abnormal organelle function
- Abnormal storage products
- Abnormal chromosomes
Status Epilepticus
- Research Definition - seizure lasting > 5 min in adults or > 10 min in children OR series of seizures in which conscious or function does not recover in-between
- Classic Definition - seizure of 30 min duration
- Non-convulsive SE - prolonged but no tonic or clonic movements
- Convulsive SE - medical emergency; must treat w/ benzo and long-term AED (fosphenytoin)
- Mortality and morbidity is high but more due to underlying disease than seizure itself
4 Common Causes of SE
- Withdrawal of AEDs, sedative hypnotic drugs or alcohol
- High fever (esp b/f age 5)
- Metabolic disorders
- Cerebral lesions (meningitis, encephalitis, stroke, tumor)
Epidemiology of Epilepsy
- 5-1% US population
- U curve - highest incidence in young and old
- 150,000-200,000 new cases in US / yr
- Inc risk if… parent w/ epilepsy, severe alcoholism, civilian or military head trauma, heroine use, past stroke or viral encephalitis, etc
5 Broad Etiology Categories of Seizures
- Toxic
- Systemic Illness, drugs, wihdrawal, pyridoxine deficiency
- AcquiredStructural Lesions
- Infections, vascular, trauma, neoplastic, mesial temporal sclerosis
- Familial
- Primary Generalized Epilepsy
- Benign Focal Epilepsy in Childhood
- Febrile convulsions
- > 200 other genetic syndromes related to seizures
- Idiopathic Genetic
3 Categories of Etiology of Epilepsy
- Structural-Metabolic (“symptomatic”) - known pathology
- Genetic (“idiopathic”) - no detectable structural abnormality but susceptibility genes
- Unknown (“cryptogenic”)
Seizure Etiology by Age
- Developmental if < 14
- Injury if 15-24
- Brain tumor if 25-44
- Vascular if 45+
Types of Focal Seizures
FOCAL = CONSCIOUS
- W/o impairment of conscious or awareness
- Involving subjective sensory phenomena only (touch, smell, taste, vision, hearing, hallucinations
- Involving subjective psychic phenomena only (aura w/ staring and automatisms)
- Observable autonomic component (change in HR or resp, goose bumps, perception of viscera)
- Observable motor component (muscle groups including vocal; may have post-ictal Todd’s paralysis) - W/ impairment of consciousness or awareness (still conscious but unable to respond to stimuli b/c altered awareness or responsiveness)
- *Important distinction b/c these patients cannot drive or operate machinery
- Evolving to bilateral/convulsive seizure
Types of Generalized Seizures
- Tonic-clonic (several min)
- Muscle stiffening & shrill epileptic cry followed by convulsions
- Can have foaming (lack of swallowing), eye movements, inc HR, laborious breath, back arches
- Often tongue biting and urinary incontinence
- Post-ictal confusion, drowsiness and even depression or agitation
- Can be primary (generalized from onset) or secondary - Absence (2-15 sec) - staring w/ impairment of awareness; no aura; post-ictal confusion; usually start b/n 4-12 yr and gone by 18
- Corticothalamic - Myoclonic - sudden, brief shock-like muscle contractions; no cognitive impairment b/f or after; may be localized to face, trunk, 1+ extremities
- Can be non-pathological - Clonic - similar to tonic-clonic but w/o tonic phase
- Tonic (< 20 sec) - stiffening and alteration of consciousness; bilateral musculature so usually symmetrical
- More common during sleep - Atonic (<15 sec) - droop eyelids, head nodding, drop objects and fall to ground usually lose consciousness briefly during fall then usually no post-ictal phase; injury is common
Diagnostic Techniques (5)
- EEG - fluctuating summations of EPSPs and IPSPs
- MRI - structural changes (ex - can see medial temporal sclerosis)
- PET - use glucose and look for areas of dec metabolism (epileptogenic)
- SPECT - radioactive isotopes to look at cerebral blood flow; can show inc blood flow to areas of seizure involvement
- Can have baseline “inter-ictal” image then SUBTRACT it from image obtained in ictal state (during seizure)
- MEG - newest tech; magnetic manifestation of brain activity reflected outside skull in real time; allows accurate pinpointing of location
5 Major Mechanisms of AEDs
1- Block Na+ channels - maintain in inactivated state
`2- Inhibit Ca++ flux thru T channels (ex - ethosuimide specifically for absence seizures)
3- Inc GABA transmission (by inc possibility that GABA -A binding will open Cl- channels, irreversibly blocking GABA transaminase or inhibiting GABA reuptake)
4- Dec excitatory transmission (AMPA glutamate receptor antagonists)
5- Inc K+ channels so stabilize neuronal membrane
Which AEDs can be used acutely?
- IV = Phenytoin, Phenobarbital, Lacosamide, Valproic Acid, Levetiracetam, lorazepam, diazepam
- Rectal = diazepam
Which AEDs are not metabolized in liver? (4)
- Gabapentin, pregabalin, vigabatrin, levetiracetam
- SO unchanged in urine and not affected by other AEDs
CP450 Inducers + Interactions
- phenobarbital, phenytoin, primidone, CBZ
- Inc metabolism of oral contraceptives so inc pregnancy
- Dec Warfarin conc so inc DVT/emboli
- Inc statin clearance so inc cholesterol
- Dec TCA conc so inc depression
CP450 Inhibitors + Interactions
- Valproate and felbamate
- Felbamate can inc Warfarin conc —> uncontrolled bleeding
Lamotrigine Interaction
Lamotrigine conc dec if on oral contraceptives so breakthrough seizures
Which AEDs are affected by antacids?
Absorption of phenobarbital, phenytoin, gabapentin, CBZ dec in gut if on antacids —> seizure exacerbation
Which AEDs are highly protein bound? (4)
phenytoin, valproate, clorazepate, clonazepam
Which AED has non-linear kinetics?
phenytoin (inc dose can lead to exponential inc in plasma conc)
AED Side Effects
(esp when first started or inc dose)
- Neuro/Psych - drowsy, mood, cog impairment, irritable, hyperactive, dizzy, vertigo, tremor
- Systemic - nausea, diarrhea, weight gain, anorexia, renal stones, gingivital hypertrophy, rash, hair loss or change in texture, changes in sexual function
Which AEDs can only be used for partial or tonic-clonic seizures? (5)
CBZ, gabapentin, phenytoin, tiagabine, vigabatrin
How to decide which AED to give?
Efficacy for seizure type, safety and tolerability, ease of use, potential interactions, efficacy w/ co-existing conditions, specific population (childbearing age, kids, elderly)
**start w/ mono therapy (1 drug) do fewer interactions, side effects toxicity, cost, teratogenicity risk
Surgical Options & Success
- resective (safely remove focal area of seizures - medial temporal lobe most common) OR palliative surgery (prevent spread to other hemisphere via corpus callostomy) OR multiple subphyla transections
- 75% achieve initial seizure freedom after resection
RNS and VNS
- Responsive Neurostimulation (RNS) - implant in skull which monitors electrical activity and delivers brief electrical impulses if it detects activity that could lead to seizure
- Vagus Nerve Stimulation (VNS) - implant in L upper chest to stimulate vagus afferents; inc seizure threshold
2 Epilepsy Diets
- Ketogenic - high fat and low carb and normal protein; hard to implement
- Modified Atkins Diet - same idea as ketogenic but not as strict; more compliance
What is refractory epilepsy?
**Drug-Resistant if try 2 types of AEDs and no seizure freedom (12 mo w/o seizure) AKA refractory epilepsy
