Status epilepticus State of Art Review Flashcards
Epileptic seizure is defined
Status epilepticus (SE) is commonly defined
- hypersynchronous neuronal electrical activity in
- cerebral cortex
- manifests as a paroxysmal and transient abnormality of consciousness, motor activity, autonomic function, sensation, or cognition
seizure activity that lasts for more than 5 minutes, or the occurrence of 2 or more seizures without recovery of consciousness
Refractory status epilepticus is defined
Superrefractory status epilepticus is defined as
acute repetitive seizures
aka
SE that does not respond to first‐line anticonvulsant therapy
SE continuing or recurring more than 24 hours after initiation of treatment with anesthetic therapy
occurrence of 2 or more distinct seizures within a 24‐hour period
cluster seizures
Status epilepticus has been identified in ____ of dogs presenting to the hospital for seizure activity and was the first manifestation of a seizure disorder in ____ of dogs
16.5%
58%
Status epilepticus of longer duration is less
responsive to anticonvulsant therapy compared to SE of shorter duration
Seizures result from
any event that disrupts the balance between
spontaneous, excessive, hypersynchronous electrical discharge from a group of neurons in cortical tissue
neuronal excitation & inhibition can cause a seizure
proposed that SE develops due to
failure of inhibition or excessive stimulation
major inhibitory neurotransmitter is
3 categories:
Binding of GABA to GABA‐A receptors causes
GABA
GABA‐A, GABA‐B, and GABA‐Aρ
chloride influx and hyperpolarization of the cell
- GABA‐A agonists - benzodiazepines and barbiturates can terminate seizure activity.
GABA‐B receptor is a G‐protein coupled receptor-
ligand binding opens K channels and closes Ca++, which leads to hyperpolarization of the membrane
prolonged seizure activity =
diminished inhibitory effects of GABA -receptors become less effective
major excitatory neurotransmitters
2 main types of glutamate receptors are
N‐methyl‐d‐aspartate (NMDA) receptors are what type of receptors:
drugs:
glutamate
aspartate
acetylcholine
inotropic -AMPA, NMDA
metabotropic
inotropic glutamate
methadone, ketamine
inotropic NMDA channels cause:
Metabotropic glutamate receptors use:
influx of Na & Ca++
= depolarization of membrane and AP generation
second messenger system to increase inward currents of Na & Ca++ = leads to depolarization
Kainite, AMPA, and NMDA agonists shown to stimulate seizure activity
one MoA of drug resistance is overexpression of:
P‐glycoprotein is a multidrug transport protein encoded by the gene:
is found in:
functions as:
It is thought
what causes Pgp upregulation
P‐glycoprotein
MDR1
capillary endothelial cells o BBB
ATP‐dependent efflux pump - Ab, immunosuppressive agents, and possibly lipophilic anticonvulsant drugs
thought that overexpression of Pgp enables resistance to anticonvulsant therapy by prohibiting uptake of these medications into the CNS at therapeutic level
NMDA receptors & COX‐2
SE is characterized by:
hippocampal neurons can occur even if the initiating seizure focus is:
Neuronal death is mainly mediated by excitatory neurotoxic effects -
neuronal cell necrosis, gliosis, and network
not located in the hippocampus
glutaminergic receptor overstimulation
=cellular calcium influx, which triggers a sequence of events that result in apoptosis or necrosis
MoA cerebral edema:
vasogenic MoA
cytotoxic MoA:
Seizure foci have high metabolic demands
= increased blood flow
-this hyperperfusion =disrupt BBB
= vasogenic edema
excessive glutamate = cytotoxic edema
Transient periictal MRI abnormalities are
brain MRI signal abnormalities attributable to seizure activity and may totally or partially resolve on follow‐up
Systemic effects of status epilepticus
phase I, or compensated SE:
Phase II, or uncompensated SE:
Systemic effects of status epilepticus
- increase in SNS activity occurs secondary to seizure
- > catecholamines & cortisol = hypertension, tachycardia, hyperglycemia, hyperthermia, and ptyalism
- cerebral metabolic demand is high, and cerebral blood flow is increased to maintain oxygen delivery to the brain. -can cause cardiac arrhythmias, acidosis, rhabdomyolysis, hypotension, shock, NCPE
after 30 minutes
- cerebrovascular autoregulation fails
- > ICP
- systemic hypotension and autonomic dysfunction occur, leading to decreased cerebral blood flow
- body is unable to compensate for the persistently high cerebral metabolic demand
- hypoglycemia, hyperthermia, hypoxia, respiratory failure, acidosis, hyperkalemia, hyponatremia, and uremia
Sudden unexpected death in epilepsy (SUDEP) def.:
source of epileptic deaths
defined in human epileptics as “the sudden, unexpected, witnessed or unwitnessed, nontraumatic, and nondrowning death of a patient with epilepsy
- **with or without evidence of a seizure, excluding documented status epilepticus
- PM no structural or toxicological cause of death.”
15%
MoA:
MORTality in Epilepsy Monitoring Units Study (MORTEMUS) aimed to characterize events:
may be under recognized in vet med
unknown
may be due to an abnormality of breathing, CV dysfunction, arousal deficits ( seizure progressive to ascending arousal system in brainstem and depressing it)
=centrally mediated alteration of both respiratory and cardiac functions after generalized tonic‐clonic seizures
all occur post generalized convulsive seizure
- tachypnea began after a seizure, followed by apnea, bradycardia, and postictal generalized electroencephalogram (EEG)
- profound flattening of the EEG recording that occurs after seizure activity
- apnea always occurred before terminal asystole
- majority of events (14/16) observed occurred at night
hereditary basis for epilepsy dogs
term unknown or presumptive unknown epilepsy be used in cats
Labrador Retrievers, German Shepherd Dogs, Golden Retrievers, Bernese Mountain Dogs, Belgian Tervurens, Vizslas, Keeshonds, English Springer Spaniels, and Border Collies
SE was more frequently associated with
genetic/unknown epilepsy more likely to
___—___% of dogs that presented in SE had no prior documented seizure activity
structural‐metabolic epilepsy
cluster but NOT SE
44% - 58% (another study)
new classification
Genetic: seizures are result of a known or presumed genetic defect.
Structural‐metabolic: structural or metabolic disease that is confirmed to be associated with an increased risk of developing epilepsy.
Unknown: underlying etiology unknown; could be fundamentally genetic or result from an unidentified structural or metabolic disorder.
dx. CSE vs NCSE
ppl NCSE defined as:
presents as:
common in:
convulsive SE (CSE) or nonconvulsive SE (NCSE).
majority of small animals CSE
defined as EEG evidence of seizure activity without the clinical appearance
2 primary phenotypes
- ambulatory patients who present in states of confusion with or without subtle twitches - termed to be in “walking status”
- severely impaired level of consciousness that display very subtle, if any, overt motor manifestations of seizure activity. These patients have been referred to as the ictally comatose “subtle status
critically ill patients
vet med NCSE
% in humans
how to dx:
- underrec bc not using EEG commonly
- humans - NCSE in 21% of patients; 25% of these patients had prior seizures
index od suspicion
EEG
should be considered in any patient with a prolonged postictal state
cats > 7 yrs
3.5 times more likely structural‐metabolic epilepsy vs unknown/idiopathic epilepsy
depressed level of consciousness ddx:
- post-ictal
- underlying structural or metabolic
cytotoxic edema (glutamate overstim NMDA = Ca++ necrosis apotosis) - NCSE, though NCSE can only be confirmed with EEG
- AED
index of suspicion for structural‐metabolic epilepsy if:
persistent, focal, interictal neurological deficits for ≥48 hours following cessation of seizure
EEG
helpful to discriminate nonepileptic paroxysmal disorders, such as cardiogenic syncope
describe Reversible MRI abnormalities have been documented in dogs as a consequence of seizure activity:
lesions will improve or resolve in many patients over a period of
represent vasogenic and cytotoxic edema
bilaterally symmetrical T1‐hypointense and T2‐hyperintense lesions with a predilection
temporal
pyriform lobes
may also be observed in the cingulate gyrus and hippocampus
1–18 weeks
