PBL 3 Flashcards
What is a convulsive seizure
another name for tonic clonic: involve the whole body (gran mal seizures).
what is an unprovoked seizure
seizure that first occurs 6 months following a traumatic brain injury or stroke.
What is secondary epilepsy
resulting from a condition/procedure that are high risk for developing epilepsy (craniotomy, traumatic brain injury, stroke, brain tumour, CNS infection etc.
What conditions can cause secondary epilepsy
craniotomy, traumatic brain injury, stroke, brain tumour, CNS infection
what is an epileptic seizure
the clinical event that occurs when there is an excessive, sustained and synchronized electrical discharge in a network of neurons.
name two types of epilepsy
focal
General
What is the difference between focal and generalised epilepsy
focal - usually confined to one hemisphere and thus one cortical region
general - goes over both hemispheres
name two focal seizures
- simple parietal seizure
- complex parietal seizure
describe what a simple partial seizure is
Simple Partial Seizures
Seizure limited to focal area.
o Symptoms therefore depend on area affected.
No loss of consciousness.
Associated with focal structural disease including developmental abnormalities, strokes, trauma and tumours.
describe what a complex partial seizure is
Altered awareness (often debatable) = dyscognitive symptoms.
Associated with automatisms (purposeless and repetitive movements).
Most commonly involved structure is the temporal lobes.
where does generalised epilepsy originated from
- suggested it is in the somatosensory cortex
When does generalised epilepsy come about
- starts at a young age
describe absent seizures
Unresponsiveness and behaviour arrest.
Usually occurs in childhood.
May occur many times each day, lasting about 5 seconds.
describe tonic clonic seizures
Prior patients my experience aura
o A simple partials seizure with vague symptoms
This type of seizure usually has two phases:
Tonic Phase: lasts about 10-40 seconds.
Patient becomes very rigid: all muscles undergo tonic, sustained contraction.
o Patient falls to the floor
Respiratory muscles and laryngeal muscles also contract: patient may let out a cry/grunt as air is forced out of chest through vocal cords.
o Patient can become cyanotic.
Clonic Phase: muscles go into strong, rhythmic contractions of about 2-3 minutes. Jerky breathing and tachycardia. May be accompanied o Urinary and faecal incontinence. o Tongue biting
Coma Period: patient’s breathing gradually becomes normal and color returns to normal.
Length related to previous tonic-clonic seizures.
When patients awake: may be confused and have a headache.
or
• Premonition (a vague sense that a seizure is imminent) this is sometimes called aura
• Pre-tonic-clonic phase (a few myoclonic jerks or brief clonic seizures)
• Tonic phase (tonic contraction of the axial musculature; upward eye deviation and pupillary dilatation; tonic contraction of the limbs; cyanosis; respiratory muscle contraction - “epileptic cry”; tonic contraction of jaw muscles)
• Clonic phase - jerks of increasing amplitude followed by relaxation (sphincter opening may occur)
• Postictal period (generalized lethargy; decreased muscle tone, headaches, muscle soreness)
What is status epileptics
Occurs if seizures continue with patient regaining consciousness (+5 minutes) or recurrent seizures over the same time with incomplete recovery between them.
If generalized this condition is a medical emergency.
describe paroxysmal depolarising shift
Occurs in neurons in which uncontrolled/sustained discharges occur.
In the PDS the membrane is depolarized by 30-40mV, and remains so for a few seconds.
o May be accompanied by a burst of action potentials.
May be caused by activation of the glutamate receptors of the NMDA type.
how glutamate and GABA can lead to epilepsy
One of the most important theories in epilepsy is that seizures occur due to an imbalance between the excitatory (glutamate) and inhibitory (GABA) neurotransmitter systems.
describe how glutamate and GABA lead to epilepsy
o GABA antagonists and glutamate agonists are triggers for seizures.
o Drugs that encourage GABA transmission are antiepileptics.
o In prolonged seizures glutamate levels rise and GABA levels fall.
o Rise in CSG GABA are seen to correlate with action of antiepileptic Vigabatrin.
name the structural changes that occur in epilepsy
- reorganisation of the tissue in temporal lobe epilepsy
- sprouting of mossy fibres of granule cells
- neurogenesis
- chandelier cells
describe the structural changes that occur in epilepsy
Reorganisation of the tissue in temporal lobe epilepsy:
• Loss of CA2 and CA3 hippocampal areas.
• Possible sclerotic hippocampus.
Sprouting of Mossy Fibres of Granule Cells
• Leads to reverbant excitatory circuits.
Neurogenesis
• Formation of new neurons (also in response to epilepsy episodes) change circuits.
Chandelier Cells
Widespread, inhibitory interneurons that inhibit pyramidal cells.
o Express high levels of GABA Transporter GAT-1.
In some forms of epilepsy there is a loss of chandelier cells, impacting excitability of pyramidal cells.
o Often sufficient in patients with lower average numbers of inhibitory neurons.
Another cause may be an intrinsic increased neuronal excitability, specifically abnormalities in the membrane.
What is the non pharmalogical treatment for epilepsy
a. Non-pharmalogical treatment.
Surgical
Resection of seizure onset zone in brain.
If patient has failed 2 AEDs often drug treatment will not work.
o Patients with focal epilepsy will be referred.
Corpus Callosotomy
o Can be used in patients with drop attacks/atonic seizures.
Vagus Nerve Stimulation
Can reduce seizures by more than 50% in most patients that have the treatment.
Ketogenic Diet.
all AEDS……
ALL AEDs HAVE THE POTENTIAL TO BE TERATOGENIC
Patients should know that abnormality is low and not different from the general population
what are the safer anti epileptic drugs in pregnancy
Carbamazepine and Iamotrigine are generally the safest anti-epileptic drugs in pregnancy.
What are the risks of major congenial malformations with anti epileptic drugs
Carbamazepine: 2.2%
Iamotrigine: 3.2%
(!) Valproate: 6.2% vs 3.5% in untreated women with epilepsy
What drug is not recommenced for epilepsy in a pregnant women
Valproate is NOT RECOMMENDED.
What is the risk of epilepsy to the baby and mother
Therefore, the risk of epilepsy to the mother far outweigh the theoretical risks of AEDs.
In general seizures are well tolerated by the fetus but the risk to the mother is greater.
o Main risk is if baby does not receive oxygen.
What is pregnancy impact of seizure frequency
AED blood levels may fall.
Altered oestrogen and progesterone may have an effect.
Sleep deprivation increases, which increases the risk of seizures.
What are the prescription guidelines for epilepsy
Focal seizures with or without generalisation - carbamazepine, sodium valproate, iamotrigine
tonic clonic - carbamazepine, lamotrigine, sodium valproate
absence. - ethosuximide, sodium valproate
myoclonic seizures - sodium valproate, clonazepam, levetiracetam
What drugs cannot be used in absence seizures
phenytoin and carbamazepine have actions on both sodium and calcium channels. They cannot be used in absence seizures.
- Briefly describe 3 possible cellular mechanisms implicated in the generation of seizures. (3 marks)
Increased excitation (e.g. hyperactivity of glutamatergic transmission) Decreased inhibition (e.g. deficit in GABAergic transmission) Intrinsic neuronal hyper excitability (related to altered electrical properties of the neuronal membrane)
- What is the “paroxysmal depolarizing shift” and what receptors are involved? (2 marks)
The resting membrane potential of neurons becomes depolarized by 30-40 mV, causing a sustained burst of action potentials (1 mark)
This involves most likely the activation of NMDA glutamate receptors (elevated glutamate levels are associated with epileptic foci). (1 mark)
- Name one non-pharmacological method for treating epilepsy. (1 mark)
Surgical interventions (focal removal of affected areas, or more extensive surgical removal; also, deep brain stimulation or vagal nerve stimulation). Students may also mention dietary methods, e.g. ketogenic diet.
What is the mechanism of action of Tiagabine? (1 mark)
The GAT-1 GABA transporter (reuptake system)
- What is ethosuximide and what is it used for? (2 marks)
Anticonvulsant drug (blocks T-type calcium channels); used to treat absence (petit mal) seizures
. Name an anticonvulsant drug with zero-order kinetics. (1 mark)
Phenytoin
what drugs block sodium channels
- phenytoin
- carbamexapine
- sodium valproate
describe how the sodium channels work
Bind to the inner pore of the sodium channel in its inactivated state (immediately after depolarization). Zero order kinetics seen in phenytoin.
Leads to an increased refractory period (delay in time taken to return to resting state).
All types of seizures (not to be used in pregnancy). = sodium valproate
what drugs block calcium channels
Phenytoin Carbamazepine Ethosuximide used in absence seizures. Zonasamide Topiramate (also increases GABA transmission and inhibits glutamate and works on sodium channels) Iamotrigine (inhibition of glutamate release) Levetiracetam Gabapentin
How does levetiracetam work
• Binds to synaptic vesicle glycoprotein, SV2A and inhibits presynaptic calcium channels, reducing neurotransmitter release.
how does gabapetin work
• Alpha 2 Delta subunit of calcium channels.
how does topiramate and lamotrigine work
N and P/Q-type channels: expressed at presynaptically.
Mediate calcium entry for neurotransmitter release.
how does phenytoin, caramazepine, ethosuximide, zonasamide
T-type calcium channels: require less depolarization to be activated, mainly post-synaptically.
They allow post-depolarization calcium influx and are slowly inactivated. Inhibiting these channels causes prolongation of calcium influx post-depolarization.
How do benzodiazepines work and given an example
Clonazepam
Expressed post-synaptically, lead to fast inhibitory transmission (hyperpolarization) through influx of Cl- (higher extracellularly than intracellularly).
Stops propagation of electrical activity in cerebral cortex.
Acts as a positive modulator by increasing frequency of receptor opening.
How do barbiturates work
Phenobarbitone
Acts as to cause prolonged receptor opening and therefore more hyperpolarization.
At high concentration: directly activates the channels which causes an anaesthetic effect.
how does vigabatrin work
• Synthesis: inhibits GABA Transaminase leads to an increase in GABA levels (increased GABA desensitises GABA autoreceptors, reducing inhibitory feedback on release).
how does tiagabine
• Uptake: Inhibits GAT-1 (transporter involved in removing GABA from the synaptic cleft).
how does perampanel and felbamate work
• Antagonist of AMPA receptors (involved in channels that are permeable to sodium ions).
