Seizures and Epilepsy Flashcards
What is Epilepsy?
- chronic condition of recurrent seizures
that can also vary from brief and nearly
undetectable symptoms to periods of
vigorous shaking and convulsions - not a single disease
- affects 0.5-1% of the population
- 2 or more unprovoked seizures
separated by 24 hours or 1 with a
likelihood of reccurrence eg brain
structure abnormality
What is a seizure?
- temporary disruptions of brain
function causes by uncontrolled
synchronous, paroxysmal excessive
neuronal activity manifesting as a
stereotypes disturbance of
consciousness, behaviour, emotion,
motor function or sensation - usually lasting seconds to minutes
= abnormal excessive firing of the brain
Unprovoked Seizures are
caused by an unknown and reversible medical cause
Seizures: Features:
- abnormal firing of the brain
- focal seizures = localised
- can become generalised = both
hemispheres - if greater than 5 mins = status
epilepticus - medical emergency, mortality is 10-
15%
Focal vs Generalised Seizures:
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What is it called when a seizure lasts longer than 5 mins?
Status epilepticus
What does a seizure look like?
- not always convulsion
- prodrome: feeling, sensations,
changes in behaviour hours or days
before event - preictal/aura: immediately prior (not
always present) - icta: actual event
- post-ictal: drowsy, confused, psychotic,
bitten tongue, lost continence
Seizure: History of Events:
- diurnal pattern
- if more than one seizure:
- max seizure free period?
- seizure frequency?
- hospitalisations?
- falls and injuries - pre-natal and post-natal development?
- history of febrile seizures
- history of CNS (lesions, infections?)
- history of brain trauma specifically
associated with penetrating injuries - family history of epilepsy
- social history: education, employment,
driving status, drug and alcohol use
Seizures: Aetiology:
- antenatal: infection, trauma, hypoxia
- genetic
- electrolyte disturbances
- infections
- drugs/meds
- tumours
- trauma
- congenital disorders
- neurodegenerative disorders
Adult: stroke, tumour, trauma, infection
Child: genetic/metabolic disorders,
trauma, infection
Seizure symptoms are related to the
location of abnormal firing
Seizure: Acute Symptomatic Management:
- treat the underlying cause:
- blood tests
- lumbar puncture
- imaging
- benzodiazepines: can not be used
prophylactically due to side effects,
tolerance and dependance
(used if going toward status epilepticus - antiseizure/ anti-convulsants
medication if there is a
high risk of recurrence/previous
history of seizures
Which lobe has most abnormal firing?
temporal lobe
area of most neurogenesis
Provoked Seizures and Recurrence:
- provoked immediate (toxin,
medication, metabolic) = recurrence is
low in absence of provoking factor - acute symptomatic (close to time of a
brain insult) = recurrence is 80% less
likely than a remote symptomatic
seizure
Unprovoked Seizures:
- remote symptomatic
- associated with
- remote symptomatic (pre-existing
brain injury) - associated with an epileptic syndrome
- unidentified
Seizure Differential Diagnosis:
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What does EEG record?
- result of many excitatory and
inhibitory post synaptic potentials
(large group of neurons active at the
same time) at the level of the cortex - depends on the timing and orientation
of neurons
The Eye and the EEG:
- eye is electrically charged, positive
cornea and negative retina - eyes roll up when eye is closed
- repetitive blinking can look like a
seizure as rhythmic movement - same as eating
EEG Utility For Seizures:
- epileptic seizures will have
epileptiform discharges on the EEG
during and event - changes on EEG can also be seen
between seizures = inter-ictal
epileptiform discharges - the sooner an EEG can be obtained
after a seizure, the more likely it will
detect an IED within 72hrs - IED can be reduced by levetiracetam,
valproate and acutely by diazepam
What does inter-ictal epileptiform discharges firing refer to?
abnormal firing of neurons picked up on EEG between seizures
Normal EEG rules out epilepsy.
True or False?
False
a normal EEG during an event means the event was not epileptic
but a normal EEG after the event just means that abnormalities was not picked up
What is the probability of recurrence in the next ten years after two unprovoked seizures?
60%
A single seizure vs multiple in 24 hours confers no higher risk of recurrence.
True or False?
True
Seizures: Acute Treatment:
- most self-terminate within minutes
- if a seizure continues then initially
treated with benzodiazepine (quick
acting) - longer a seizure persists the harder it
is to control (internalisation of GABA
receptors)
The likelihood of having a second seizure after a first seizure is highest within the first two years.
True or False?
True
When is neuronal death, injury and alteration to networks believed to occur in regards to seizures?
After a seizure that lasts 30 minutes
declared status epilepticus after 5 minutes
Seizure Precautions:
- avoid sleep deprivation, alcohol,
infection - avoid unsupervised activities that pose
danger with sudden loss of
consciousness: baths, swimming,
working at heights, heavy machinery - driving
- neuropsychiatric co-morbidities
What are the different phases of status epilepticus?
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SUDEP is
sudden unexplained death of epilepsy
SUDEP Features:
- 2-18% of all deaths in epileptic patients
- higher in children
- unknown reason -> multifactorial
- increases with severity of epilepsy
- 10 fold higher risk in generalised
seizures - higher in poorly controlled epilepsy
Treating Seizures:
- goal: complete seizure freedom with
no side effects (tolerability) - around 50-60% of patients become
seizure-free on a single drug - current drug therapy is effective in 70-
80% of patients - 30-40% patients may not respond to
medication (refractory)
- rule out seizure imitators
- evaluate possibility of surgically
remediable syndromes
- diet
- devices (vagal nerve stimulator)
Most antiepileptics with known mechanisms of action work by (3):
- blocking excitation
- increasing inhibition
- prevent repetitive firing
How does diazepam work as an anticonvulsant?
enhancing GABA action (absence seizures can be exacerbated by this mechanism of action)
How does carbamezpine work as an anti-convulsant?
iincreases inhibition by inhibiting Na+ channel function
stop Na+ channel from working, prevent influx of Na+, hence prevents firing of action potential
How does Gabapentin work as an anti-convulsant?
- increasing inhibition
- inhibition of Ca2+ channel
How does sodium valproate work as ana anti-convulsant?
inhibits excessive excitation
- enhancing GABA action?
- inhibiting Na+ channel function **
- inhibiting Ca2+ channel function
Which of the following anticonvulsants are broad spectrum?
- carbamazepine
- phenytoin
- gabapentin
- diazepam
- levetiracetam
- sodium valproate
- diazepam
- levetiracetam
- sodium valproate
Which of the following anticonvulsants are narrow spectrum?
- carbamazepine
- phenytoin
- gabapentin
- diazepam
- levetiracetam
- sodium valproate
- carbamazepine
- phenytoin
- gabapentin
Broad Spectrum Anti-convulsants:
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Narrow Spectrum Anti-Convulsants:
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compare the IV and subcutaneous route of administration for drugs
IV = rapid, but doesnt last as long
Subcutaneous = slowly, but lingers
Steady state:
- steady state is reached in 5 half-lives (5
doses) - steady state wanted for antiseizure
medication - give a high loading dose when
therapeutic range needs to be reached
quickly - get the trough level for monitoring but
do not hold drug if half life is short
Complex pharmacokinetics: Phenytoin:
- phenytoin is 90% protein bound
- alterations in protein will impact the
free concentration - phenytoin is metabolised in the liver
- inter-individual difference in level of
saturation - rate of elimination is therefore altered
when metabolism is saturated
Core Drug: Diazepam (anticonvulsant): Metabolism Considerations:
CP450
Core Drug: Vaproate:
- highly protein bound will compete with
phenytoin - metabolised by the liver, excreted in
urine - dose dependent teratogenicity
Core Drug: Carbamazepine: Metabolism Considerationa:
- metabolised into carbamazepine
epoxide - potent inducer of CYP450
(autoinduction) - interactions with lamotrigine, lithium,
phenytoin, valproate - steady state reached in 20 days due to
autoinduction
Drug-Resistant Epilepsy:
- failure of two tolerated and
appropriately chosen anti-seizure
meds - 30-40% ppl
- surgery
- neurostimulator devices
- ketogenic diet
Remission of Epilepsy:
- 10 years seizure free with the last 5
years of antiepileptic drugs - seizure recurrence rate after drug
discontinuation = 35% - 3% may not regain seizure control
- most recurrence occurs within 1 year
of discontinuation - short durations of active disease,
longer seizure free periods, ease of
controlling seizures increases
likelihood of success
