Seizures Flashcards
What is an epileptic seizure? What is epilepsy?
manifestation of excessive and/or synchronous activity in the brain -> transient signs
Epilepsy = a brain disorder that causes unprovoked seizures
What is a reactive seizure? What causes it?
Seizure occurring as a NATURAL response from the NORMAL BRAIN from transient disturbance (metabolic, toxic), which is REVERSIBLE when disturbance is removed
3 Terms for Seizure Semiology
- Focal epileptic seizures
- Generalized epileptic seizures
- Focal epileptic seizures evolving to generalized
Generalized: Tonic-clonic, tonic, clonic, myoclonic
3 different etiologies of epileptic seizures, and most common? Average life span?
idiopathic - MOST COMMON, GENETIC; Avg lifespan = 7 years, tx extends 2.3 years
structural
epilepsy of unknown cause (Cryptogenic = old term!)
Cryptogenic epilepsy is defined as epilepsy of presumed symptomatic nature in which the cause has not been identified. The key difference between idiopathic and cryptogenic epilepsy is that idiopathic epilepsy is an inherited type with predominantly genetic or presumed genetic origin.
MRI - what type of epilepsy?
Idiopathic epilepsy
Characteristics of focal seizure
hyper-salivation, fly-biting, facial tremors
Characteristics of generalized seizure and the 3 phenotypes
Autonomic signs (hypersalivation), lateral recumbency, all 4 limbs involved
1. Myoclonic
2. Clonic
3. Tonic
Pre-ictal period - describe two parts
Prodromal: hours-days, abnormal compulsive behaviors
Aura: minutes-to-seconds before seizure, abnormal posture, hypertonia of facial structures
Ictus period
the epileptic seizure itself
Post-ictal period
transient, brain restores its normal function -> can last hours to days
Interictal period
time between resolution of post-ictal period and the next ictal period
Clonic phenotype (generalized seizure)
Convulsions: paddling, jerking/twitching
Tonic phenotype (of generalized seizure) - define
hypertonia / abnormal posture
Define a Cluster seizure vs. Status Epilepticus
Cluster: ≥ 2 seizures within 24 hours. Should regain consciousness b/w each!
Status Epilepticus: 20-30 mins of continuous seizure activity (≥ 5 mins in duration, > 2 seizures w/out recovery in b/w)
Myoclonic phenotype (generalized seizure)
“HICCUPS” - brief, shock-like jerks of a muscle / muscle groups
- Doesn’t look as severe as convulsion (clonic) seizure, but still considered a generalized seizure
What is syncope? How does this differ from epileptic seizures?
Decreased blood flow to the brain -> “fainting”
syncope usually triggered by exercise and excitement with sudden collapse that is much more brief than seizures, lasting only seconds
- DDX WITH A SEIZURE -> difference = a eplieptic seizure lasts ≥ 90 seconds, and with syncope RELAXATION occurs shortly afterwards
What typically triggers narcolepsy?
Excitement (from getting ready to eat)
Presentation of vestibular disease (non-seizure activity)
Nystagmus
Presentation of Paroxysmal Dyskinesia (non-seizure activity)
Episodic, Abnormal, involuntary movements that occur as spasms without loss of consciousness and lasting minutes to hours
Some Labradors with these atypical seizures simply stagger and look dazed or confused for a few seconds or minutes and then recover, without ever falling over. Others have a 2 to 5 minute episode (occasionally longer) where they appear anxious and are unable to stand erect and walk but they will attempt to crawl to their desired location. Some dogs will experience either uncontrollable trembling or increased muscle tone during an episode and a few simply develop a head tremor or trembling while they remain abnormally quiet and recumbent.
Affected dogs maintain consciousness and appear to be visual, able to recognize their owners and can even obey commands during the episodes. Episodes are most likely to occur when the dog is drifting off to sleep or when awaking from sleep in many dogs but exercise and excitement are common triggers in others. Affected dogs are normal between these episodes which occur suddenly, without warning. Systemic evaluation for metabolic, neoplastic and infectious causes of seizures is negative and repeated toxin exposure is unlikely. Related dogs may be similarly affected.
SOURCE https://vetmed.umn.edu/research/research-labs/canine-genetics-lab/canine-genetics-research/atypical-seizures-paroxysmal-dyskinesia#:~:text=An%20episodic%20movement%20disorder%20that,especially%20retriever%20crosses%20and%20poodles)
Presentation of head tremors (non-seizure activity)
30s-1 min, head shaking, animal is responsive // tremors end when owner calls animal
3 categorical causes of reactive epilepsy and specific types within each:
Metabolic
- Hepatic or Renal encephalopathy
- Hypoglycemia (Na-K pumps require glucose to function properly -> low BG -> paradoxical excitation)
Electrolyte imbalances
- hyponatermia
- hypocalcemia
Toxins
- organophosphates (AChE inhib)
- pyrethrins (block Na+ deactivation gate)
- aminopyridines (block opening of K+ gate)
- mycotoxins (open glutamate channels)
- strychnine (binds to glycine & inhibits Cl- channel)
Describe how HYPONATREMIA and HYPOCALCEMIA cause reactive epilepsy
Serum osmolality = 2Na + glucose/18 + BUN/2.8)
HYPONATREMIA (too much Na inside cell vs bloodstream -> paradoxical excitation; cell swelling)
HYPOCALCEMIA (disassociation of Ca2+ from cell -> activation of Na+ channel -> excitation by DECREASING the required threshold (makes membrane more +)
Effect of organophosphate toxins and how they cause reactive seizures
Organophosphates inhibit AChE -> excess ACh @ receptors -> more Na+ in cell -> excitation
Tx = atropine
Effect of Pyrethrin toxins and how they cause reactive seizures
Pyrethrins bind to / block sodium-deactivation gate -> depolarization continues -> excitation
Effect of Mycotoxins and how they cause reactive seizures
open glutamate channels -> increased excitation duration -> seizures
Effect of strychnine and bicuculline and how they cause reactive seizures
Bind to glycine (an inhibitory NT like GABA) -> chloride channel inhibited (no influx of Cl into cell) -> hyperpolarization inhibited -> prolonged excitation // overstimulation of CNS
Aminopyridines and how they cause reactive seizures
Block the opening of K+ channels -> NO EFFLUX OF K+! -> no hyperpolarization
What age factors to differentiate structural from idiopathic epilepsy?
Age of onset
> 6 years old = STRUCTURAL
1 year - 6 years old + normal interictal exam = IDIOPATHIC
>6 months = 50/50 of structural & idiopathic
What are the Idiopathic Tier I Confidence Level factors?
- cluster seizures (≥ 2 unprovoked seizures > 24hrs apart)
- 6 month to 6 years old
- Normal BW and interictal exam
- Known, predisposed breed (and most likley = structural epilepsy, esp. pug-like breeds)
No MRI required! (only required if Pt is <6 mos or > 6 years, other factors, have ruled out reactive seizure causes,)
What are the Idiopathic Tier II Confidence Level factors?
All Tier I present! PLUS:
normal imaging and CSF
normal bile acids
Mixed-breed dogs
What are the Idiopathic Tier III Confidence Level factors?
All Tier I & II present
EEG abnormalities
What are the Idiopathic Tier III Confidence Level factors?
All Tier I & II present
EEG abnormalities
Main cause of idiopathic epilepsy
Genetics (90% = purebred dogs)
- prevalence in nornal dog pop = ~0.75%
Idiopathic Epilepsy (2015): “Proven genetic background, suspectic genetic background, unknonwn cause, no structural cause”
Long-acting drug used for cluster seizures?
Cluster: ≥2 seziures within a 24-hour period in which the Pt regains consciousness
Levetiracetam // KEPPRA!
Cluster seizures = medical emergencies!
First-line ASDs for epileptic seizures (3)
Present post-ictal / interictal
Phenobarb, KBr, Imepitoin
are long-acting!
Fast-acting ASDs for epileptic seizures (3)
EMERGENCY / present seizing!
Diazepam, Midazolam, Propofol
are fast-acting!
Phenobarbital MoA
Makes it more difficult for GABA to dissociate from GABA receptor -> EXTENDS DURATION OF CL- CHANNEL OPENING
Benzodiazepines vs Phenobarbital
Benzodiazepines: GABA-receptor agonist via the benzodiazepine binding site
Phenobarbital: Directly binds to GABA receptor! -> enhances Cl- conductance
Goal of phenobarbital treatment in epileptic seizure patients
50% deduction in seizure frequency, goal = 1 seizure every other month
Downsides of phenobarbital
- 1/2 life = 48 hrs (longer to take effect) takes 10 days to get to steady state
- Metabolized by liver (dose-dependent hepatotoxicity)
- Metabolites excreted by kidneys (risk for azotemia)
- Have to increase dose over time b/c CYP450 induction is 30-90 days (induction = increased amt. of hepatic metabolism due to new CYP450 synthesis = increased risk for hepatotoxicity)
- Idiosyncratic hepatotoxicity, pancytopenia, hepatocutaneous syndrome (Superficial necrolytic dermatitis- hyperkeratosis of paw pads, ulcerative skin lesion around mouth, eyes - irreversible damage. Honeycomb appearance of liver on abd u/s)
How often to do BW for phenobarb
- 2 weeks
- 3 months
- 6 months
- 12 months
Why should you not use primidone
Primidone = increased toxicity chances b/c very potent
KBr and Phenobarb adverse side effects
KBr: V+, PU/PD, polyphagia, pancreatitis, bromoderma, sedation, ataxia. Pneumonitis in cats- avoid in cats!
Phenobarb: PU/PD, polyphagia (intense hunger); sedation, ataxia
Half-life of KBr? Precautions when Rx?
24-46 days (long time to take effect + be excreted); PO bioavailability = 46%
Precaution = dogs with renal dysfunction (to prevent toxicity 2º to reduced renal elimination)
Imepitoin pharmokinetics
1/2 life = 2-6 hrs, extensive liver metabolism, excreted in feces. Any present liver damage / renal damage won’t affect PK of Imepitoin
Keppra MoA
Prevents Ca2+ entering cell
- Keppra has 0% efficacy as a lone agent!!
Downside to keppra in preventing structural seizure activity?
only 50% of structural epileptic seizure Pts respond
Zonisamide MoA
Prevents Na+ from entering / depolarization
Zonisamide idiosyncratic rxns
Acute hepatic toxicosis (hepatic metabolism via CYP450 system)
Structural vs Idiopathic / Genetic Epileptic Seizures
Structural: Abnormal neurologic examination post-ictal // inter-ictal
