Seizures Flashcards
pyramidal neurons
excitatory neurons in the cerebral cortex
input comes from other neurons to stimulate or inhibit
feedforward inhibition
neurons send excitatory signals to inhibitory neurons that block the pyramidal neurons
overall INHIBITORY effect on pyramidal neuron
feedback inhibition
the effect of pyramidal neuron stimulation causes feedback inhibition on the same pyramidal neuron
overall INHIBITORY effect on pyramidal neuron
EPSPs (excitatory synaptic potentials)
signals generated by surrounding cortical input
EPSPs converge to initiate an action potential
glutamate
main EXCITATORY neurotransmitter
fast transmission via ionotropic receptors (Na and Ca ion channels)
slow transmission via metabotropic receptors
GABA
major INHIBITORY neuron
GABAa receptors: allows Cl- influx on the post-synaptic membrane
GABAb: mediated by K+ current; located on pre-synaptic membrane
epileptogenesis
the process by which a normal brain develops into an epileptic brain
due to genetic abnormalities or acute brain injury
intrinsic properties of seizure pathogenesis
focal zone of hyperexcitable neurons caused by a mutation in ion channels, receptors, second messengers, etc
extrinsic properties of seizure pathogenesis
changes in extracellular ion concentration, modulation of glial cell function, transmitter metabolism/uptake, invasion of inflammatory cells, network changes
focal epileptic seizures
abnormal electrical activity arises in a localized group of neurons
only ONE cortical region is firing abnormally
signs of focal epileptic seizures
ictal onset is consistent (signs stay the same in each seizure)
lateralized signs
- motor: facial twitches, repeated jerking head movements, rhythmic blinking, repeated rhythmic jerks of one extremity
- autonomic: dilated pupils, hypersalivation, vomiting
- behavioral: anxiousness, restlessness, abnormal attention seeking, fear
generalized epileptic seizures
abnormal electrical activity arises in bilateral hemispheres
MULTIPLE cortical regions are firing abnormally
signs of generalized epileptic seizures
tonic, clonic, or tonic-clonic seizures
- motor: bilateral
- autonomic: hypersalivation, urination, defecation
- behavioral: loss of consciousness
myoclonus
sudden, brief, involuntary single or multiple contractions of muscle or muscle group of various locations
atonic
sudden loss or diminution of muscle tone without preceding myoclonic or tonic event
involves head, trunk, jaw, or limb musculature
automatism
a coordinated, repetitive motor activity
usually occurs when cognition is impaired and subject is amnesic afterwards
(resembles involuntary movement)
orofacial: lip. smacking/pursing, chewing, licking, swallowing
pedal: running movements in distal limbs
focal to generalized epileptic seizures
abnormal activity arises in bilateral cerebral hemispheres
characterized by tonic, clonic, or tonic-clonic seizures (same as generalized)
what are the stages of seizures
- prodrome
- ictus
- post-ictus
prodrome
changes in behavior (anxiety, withdrawal, vocalization)
not always apparent
lasts minutes to days
ictus
rapid onset of tonic-clonic phases; can begin focally (facial twitches)
tonic: increased muscle tone/extension, loss of consciousness, pupils dilated
clonic: contraction and relaxation, jaw movements, autonomic signs
HIGH energy expenditure phase
lasts seconds to minutes
post-ictus
disorientation, aggression, or restlessness following ictus
may be transiently blind or deaf
lasts hours to days
can take up to 2-3 days to become back to normal
idiopathic epilepsy signalment
likely a genetic basis
breeds: spaniels, aussies, rotties, border collies, GSDs, dachshunds
age: 1-5 years (dogs), variable in cats
idiopathic epilepsy history
seizure episodes reported by owner
may have a NORMAL interictal neurologic exam
- if seizure was a few days ago - should be neuro normal
- if seizure was within 2-3 days - may still be in post-ictus and have deficits
structural epilepsy
epileptic seizures provoked by intracranial/cerebral pathology
structural epilepsy signalment and history
age: <1 to >5 years (dogs), variable in cats
history: seizures, mentation changes, altered behavior, loss of learned responses
structural epilepsy presentation
normal neurological exam
- if abnormal - indicates signs of cerebral disease
syncope
NOT A SEIZURE
can mimic an epileptic event
caused by CV abnormalities
does not usually have tonic-clonic contractions
appears as falling to the ground and going limp
characteristics of seizures
- abrupt onset and spontaneous cessation
- cannot be interrupted
- tonic-clonic movement
- altered mentation
- autonomic signs - salivation, urination, defecation, mydriasis
- post ictal obtundation
- present of intracranial/cerebral pathology
what is the definitive diagnostic for seizures
electroencephalogram (EEG)
must be reading during the time of the abnormal brain activity - can do sedated or ambulatory
indications for using EEG
- age of epileptic seizure <6 months or >6 years
- interictal neurologic abnormalities
- status epilepticus or cluster seizures
- idiopathic epilepsy not responding to medical management
AED therapy indications
- identifiable structural lesions OR prior history of encephalopathy or trauma
- acute, repetitive seizures
- >or= 3 generalized seizures in 24 hours
- status epilepticus - > or= 2 seizures in 6 months
- prolonged, severe, or unusual post-ictal periods
what is the goal of AED therapy
reduce the frequency and severity of seizures
want to have a >50% reduction
what drugs are AEDs
- potassium bromide
- levetiracetam (keppra)
- phenobarbital
- zonisamide
phenobarbital MOA
increases neuron responsivity to GABA by activating GABAa channels
has an anti-glutamate effect by inhibiting Ca channels
how is phenobarbital metabolized
hepatic - induces CYP450 and ALP
normal to see high ALP on serum chemistries
time to reach steady state of phenobarbital
takes 10-14 days to reach steady state
phenobarbital dosages
dogs: 3-5 mg/kg BID
cats: 1-2 mg/kg BID
adverse effects of phenobarbital
PU, PD, PP
sedation
ataxia
weight gain
elevated ALP
pseudohypothyroid
contraindications for phenobarbital
liver disease
concurrent CYP450 inhibiting drugs
MOA of KBr
Br ion acts like a Cl ion and passes through Cl channels on post-synaptic GABAa receptors to hyperpolarize the membrane
how is KBr metabolized
renal
how long does it take KBr to reach steady state
very long - takes 3-4 months
dosage for KBr
20-35 mg/kg SID
adverse effects of KBr
PU, PD, PP
sedation
ataxia
weight gain
GI upset
hyperreactivity
bromism
contraindications for KBr
NOT for use in cats
renal disease
pancreatitis
dogs that require rapid control of seizures
zonisamide MOA
sulfonamide derivative
blocks Ca and Na channels on pre-synaptic side to reduce the amount of glutamate released into the synaptic cleft
also binds Cl channels on GABAa receptors
how long does it take zonisamide to reach steady state
5-7 days
dosage for zonisamide
dogs: 5 mg/kg BID
if concurrent phenobarbital: 10 mg/kg due to CYP450 induction
adverse effects of zonisamide
sedation, ataxia, GI upset, KCS, polyarthropathy, decreased T4
contraindications for zonisamide
pre-existing KCS
keppra MOA
binds synaptic vesicular protein that carries glutamate in order to prevent it from binding to pre-synaptic membrane for release
metabolism of Keppra
minimal hepatic metabolism
mostly excreted in urine
time to reach steady state for Keppra
fast - reaches within 24 hours
dosage for keppra
20 mg/kg QID
adverse effects of keppra
well tolerated, very few adverse effects
efficacy of keppra
poor when given alone
exception: feline audiogenic reflex seizures
status epilepticus
ictus lasting > 5 minutes
OR
>2 minutes without regaining consciousness
requires IMMEDIATE intervention (causes primary brain injury –> neuronal cell death)
phase 1 SE
compensated SE
increase in autonomic activity –> elevated catecholamines + steroids –> hypertension, tachycardia, hyperglycemia, hyperthermia, ptylatism
causes arrhythmias, poor renal perfusion, rhabdomyolysis
phase 2 SE
uncompensated SE
~30 minutes following continuous ictus –> cerebrovascular autoregulation fails
- causes increased ICP –> hypotension, hypoglycemia, hypoxia –> resp. failure, metabolic acidosis, hyponatremia, hyperkalemia
RISK OF SUDDEN DEATH
cluster seizures
> or = 3 generalized seizures in 24 hours
when is it considered failure to regain consciousness
still unconscious 1-2 hours after ictus
goal of emergency seizure management
terminate and prevent future seizure activity, manage complications and underlying conditions causing the seizures
steps of emergency seizure management
- benzodiazepienes
- stabilize SE
- long acting AEDs
- diagnostics
- monitoring
benzodiazepiene administration
midazolam: 0.2-0.5 mg/kg IV or IN
diazepam: 0.5 mg/kg IV or 1-2 mg/kg per rectum
steps for stabilizing SE
- IV access
- obtain BW: lytes, glucose, calcium
- flow by O2
- BP (manage high ICP)
- temperature (manage hyperthermia)
if seizures do not stop after benzo administration –> repeat dose
when do you use long acting AEDs
once the benzodiazepienes have stopped the seizures
what AEDs are used in emergency situations
phenobarbital - takes longer to reach steady state; high risk of doing loading dose
levetiracetam (keppra)
monitoring after emergency seizure management
24 hr monitoring q4
monitor pupil size and reactivity, posture, EEG
general: temp, hydration, oxygenation, ventilation, HR, BP, recumbent care, bladder management
what are negative prognostic indicators for seizures
inflammatory brain disease
loss of seizure control after 6 hr hospitalization
development of partial SE
