Epilepsy Symposia Flashcards
What is the difference between provoked seizures versus epilepsy (& Give some causes of both)
EPILEPSY
epilepsy is defined as recurring, unprovoked (spontaneous) seizures
mostly:
onset in childhood or adolescence
usually no focal symptoms/signs
often a number of seizure types cluster
a polygenic cause is presumed with no identifiable structural lesion on imaging
generalized (all leads) spike and wave discharges on EEG, photosensitivity may be present
ACUTE PROVOKED SYMPTOMATIC SEIZURES
seizures are provoked by acute insults such as stroke, alcohol withdrawal, metabolic disturbance
Mostly:
warning/aura –eg epigastric rising sensation, altered smell, déjà vu, fear
cannot abort attack
onset sudden
duration 1-3 minutes
then falls , loses consciousness as seizure generalizes
rigidity/ convulsive jerks/ excess salivation
incontinence/tongue bite common
red/blue, wakes in ambulance/A&E
what is the definition of epilepsy
epilepsy is defined as recurring, unprovoked (spontaneous) seizures
what is a focal onset seizure
simple partial seizure (SPS)– patient aware - aura
complex partial seizure (CPS) – aura/warning with a level of reduced awareness
(patients may call these “absences”, “blanks” – this is medically inaccurate terminology)
can be secondary generalized- patient may experience a prior warning, either SPS, CPS, or both, before the tonic clonic seizure
clinical features of temporal versus frontal lobe seizures
TEMPORAL
hallucination of taste, speech and /or smell, visual distortion
epigastric rising sensation
pallor / flushing / heart rate changes (can mimic panic/hyperventilation attacks)
automatisms- semi-purposeful movements
oral- lip smacking, chewing movements
dystonic posturing (limb rises) FRONTAL LOBE
brief 10-30 seconds
rapid recovery,
frequent
predominantly nocturnal
forced head /eye deviation to contralateral side
which patients do you scan
Jacksonian motor or sensory seizures
Patients with focal neurological deficit
Alcohol withdrawal seizure; only scan if subdural haematoma suspected
What characteristics of single neurons might contribute to epileptogenicity
Epileptogenesis – the process by which parts of a normal brain are converted to a hyperexcitable brain
- Na+ channel inactivation too slow- action potential repolarization impaired
- Reduction in the number of functional K+ channels- action potential repolarization impaired
What are the characteristics of neuronal networks that contribute to epileptogenicity?
paradoxically, the largest potentials are recorded when the brain is at rest
when left alone and without sensory inputs the various neural networks feedback upon themselves, leading to rhythmic oscillations
when aroused, neuronal activity becomes desynchronized
What are the physiological components of a seizure
an explosion of synchronous activity by lots of neurons at once that has a tendency to spread throughout the cerebral cortex causing an ‘electrical brain-storm’
a brief change in behaviour caused by the synchronous and rhythmic firing of action potentials by populations of neurons in the CNS
What are the physiological differences between primary generalized and secondary generalized seizures?
Primary generalized seizures reach the cerebral cortex via normal neuronal pathways from the thalamus (e.g. tonic clonic seizure; absence; juvenile myoclonic epilepsy)
pathways originate in the brainstem and are normally involved in regulating the sleep/wake cycle and arousal of the cerebral cortex
Ca2+ channels and inhibitory GABA receptors in thalamic neurons have been implicated in ‘spike and wave’ seizures, showing that inhibition (the wave) is preserved
Focal (partial) seizures originate within a small group of about 1000 neurons: the seizure focus
(temporal lobe seizures, focal motor convulsions)
synchronized ‘paroxysmal depolarizing shift’ (PDS, 20 to 40 mV, lasting 50 to 200 ms) overcomes inhibition
increased extracellular K+ due to neuronal damage or reduced uptake by the astrocytes as well as glutamate
release from neurons or astrocytes contribute to PDS
during the PDS trains of action potentials occur
hippocampal neurons have similar responses under normal conditions, making the hippocampus more prone to seizures than the neocortex
Focal seizures may spread to other brain regions along the normal neuronal pathways and may also show secondary generalization if the activity spreads
to the thalamus (tonic clonic seizure)
what are the ideal properties of an antiepileptic drug?
good efficacy, easy and rapid to titrate
no drug-drug interactions/liver enzyme induction
no cognitive side-effects/low sodium
no bone marrow suppression
no affective (mood)/drowsy side-effects
different routes of administration
cost effective
what are the outstanding problems with all antiepileptic agents
Some drugs exacerbate generalized seizure types such as myoclonus and absences- phenytoin-
weightloss/gain
birth defects -affects cognitive development-10 iq points lower than average
drowsiness
why do antiepileptic drugs have so many side effects
Some of this variability is attributable to genetic differences among patients, an area of investigation called pharmacogenomics.
Candidate genes whose variation might be associated with variability in pharmacological success might include drug targets (e.g. sodium channels), or on genetic variation in proteins involved in drug pharmacokinetics (e.g. drug metabolising enzymes, membrane transporters).
what issues do women in particular face with antiepileptic drugs
birth defects - less data for newer agents
sodium valproate –affects cognitive development; reduced IQ in infant by 9-10 points
& Menstrual irregularities
give classes of anti-epileptic drugs
NA channel blockers
glutamate inhibition
Facilitators of GABA-ergic transmission-ANticonvulsant drugs
Give an example of a NA channel blocker and how it works
Phenytoin
Carbamazepine/oxcarbazepine/eslicarbazepine
-competitively inhibit the voltage gated sodium channel by binding with the receptor in its inactive state, prolonging the period between successive firings (prevents burst firing
Give an example of a glutamate inhibitor
Perampanel
non-competitive blockade of AMPA glutamate receptor
Give an example of an anticonvulsant drug-GABAergic transmission
and what ion does it enable to flow
sodium valproate (sodium channels) benzodiazepines (clobazam, lorazepam) barbiturates/primidone
CL- through GABAa channel
what drugs are given for Primary generalized epilepsy
sodium valproate, lamotrigine f
what drugs are given for Partial-focal onset epilepsy
carbamazepine, lamotrigine first line
