Epilepsy Flashcards
How is epilepsy diagnosed?
Detailed history- eyewitness
Physical exam
ECG
Blood tests
Imaging techniques: CT scan or MRI
Neuropsychological assessment
EEG
How are seizures classified?
Seizures are divided into groups depending on:
(1) where they start in the brain (onset)
(2) whether or not a person’s awareness isaffected
(3) whether or not seizures involve othersymptoms, such as movement
Depending on where they start, seizures aredescribed as being focal onset, generalisedonset or unknown onset.
What is epilepsy?
Epilepsy is the term used to describe when seizures recur
What is an epileptic seizure?
An epileptic seizure is a transient episode of uncontrolled discharge of cerebral neurons causing a variety of symptoms usually associated with a disturbance of consciousness.
Why do seizures occur and what symptoms occur?
Their behavious is caused by disordered, rhythmic and synchronous firing of populations of neurons.
Can be preceded by an aura: numbness, tingling or hallucinations.
Followed by seizures (convulsions), loss of consciousness and involuntary skeletal muscle contractions.
Afterwards period of tiredness, drowsiness, headache, confusion, followed by sleep
How many different types of epilepsy are there?
40 different types - high chance of misdiagnosis
What are some reasons why people may develop epilepsy?
Head trauma, Poisoning, Infection, Maternal injury, brain tumour, cardiovascular 30%. 70% are all unknown cause
What is EEG?
measure of CNS electrical activity
Not routinely carried out but can help, 15% of patients who do not have epilepsy have abnormal epilepsy. 20-40% of people with epilepsy have normal EEG
What are the two types of seizures?
Focal (partial) - Affects only a part of the brain may be simple or complex
Generalized- Affects both hemispheres
What are focal aware seizures?
AFFECTS A SMALL PART OF BRAIN
Person is conscious
Range of symptoms - tingling, twitching, flashing lights to joy and fear, (strange)
Depends on which part of brain is affected
What are impaired focal awareness seizures
Affect larger part of one hemisphere
Person may be confused
Automatism: strange repetitive movements
What are generalised seizures?
Affects BOTH hemispheres
Absence - ): blank, unresponsive, briefly unconscious
blank, unconscious, muscles become stiff (tonic), then shake and jerk (clonic)
Afterwards person often feel tired, sleepy and have headaches
Tonic - muscles relax
Myoclonic - muscles jerk (consciousness)
Status epilepticus - continuous or repeated seizures longer than 30 mins
Which seizure requires urgent treatment with emergency medication? What is the medication and treatment?
Tonic clonic (convulsive) seizure
Treatment
Two emergency medications used to prevent status in the community (outside of the hospital setting) are midazolam and diazepam:
*Buccal midazolam – is given into the buccal cavity (the side of the mouth between the cheek and the gum).
*Rectal diazepam – is given rectally (into the bottom).
What is the patho-physiology of seizures?
Increases in excitatory inputs via Ach or glutamate
Reduction in inhibitory drive via GABA
Change in Na channel function or activity to reduce threshold and/or increase rate of APs
Rise in extracellular K ion concentration
Change in K+ channel function or activity to increase rate of APs
What are the three reasons for increased excitability?
Increased excitability may be due to:
(i) Membrane depolarization
alteration in Na or K channel function and/or
extracellular potassium buildup
(ii) Increased excitation
release of excitatory amino acids (EAA)
Glutamate is the most common EAA
(iii) Decreased inhibition
reduced inhibitory transmission
GABA is the main inhibitory transmitter
How do anti-epileptic drugs work?
Stabilize membrane and prevent depolarization by action on ion channels (Na, Ca and/or K)
Increase inhibitory (GABA) transmission
Decrease excitatory (glutamate) transmission
How do Anti-epileptic drugs work prevent seizures?
Decreases excitatory transmission tehrfore less glutamate and AchR by stabilising membrane and preventing depolarisation on ion channels (Na. Ca or K)
Increase inhibitory transmission by increasing GABA (inhibits glutamate)
Inhibits NA and Ca channels activates k channels
What happens when K channels are activated?
Opening of K+ channels in cell membranes with resulting increase in K+ conductance, shifts the membrane potential in a hyperpolarizing direction towards the K+ equilibrium potential. Hyperpolarization reduces the opening probability of ion channels involved in membrane depolarization and excitation is reduced.
How does Phenytoin work on Na channels?
Under resting conditions, Activation gate (A) is closed. No Na+ influx
Open state. Both Activation (A) and Inactivation (I) gates open. Na+ influx
Under continued depolarisation, Inactivation gate (I) closes. No Na+ influx.
Phenytoin prolongs closure of inactivation gate (I). Increases relative refractory period. Blocks rapid repetitive firing
What do AED do at excitatory synapses?
Currently available antiepileptic drugs (AEDs) are thought to target several molecules at the excitatory synapse. These include voltage-gated Na+ channels, synaptic vesicle glycoprotein 2A (SV2A), the α2δ subunit of the voltage-gated Ca2+
channel, AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors, and NMDA (N-methyl-d-aspartate)
receptors.
Many of the AEDs can modulate voltage-gated Na+ channels. This would be expected to decrease depolarization- induced Ca+ influx and vesicular release of neurotransmitters.
In addition, lacosamide (Vimpat; UCB) is thought to enhance slow-inactivation of voltage-gated Na+ channels. This effect is different from that of other AEDs listed, which are
thought to enhance fast inactivation.
Levetiracetam (Keppra; UCB) is the only available drug that binds to SV2A, which might have a role in neurotransmitter release.
Gabapentin (Neurontin; Pfizer) and pregabalin (Lyrica; Pfizer) bind to the
α2δ subunit of voltage-gated Ca2+ channels, which is thought to be associated with a decrease in neurotransmitter release.
Excitatory neurotransmission at the postsynaptic membrane can be limited by topiramate (acting on AMPA and kainate receptors) and perampanel (acting on NMDA receptors).
Retigabine activates or opens pre- and post-synaptic KCNQ potassium channels.
Ethosuxamide inhibits T-type calcium channels
What do AEDs do at the inhibitory synapses?
The benzodiazepines, barbiturates, topiramate
and felbamate have been found to enhance inhibitory neurotransmission by allosterically modulating GABAA receptor-mediated Cl– currents. However, the action of each of these drugs is different and is dependent on the subunit
conformation of the GABAA receptor complex.
GAD, glutamic acid decarboxylase.
AED targets at inhibitory synapses. These include the γ-aminobutyric acid (GABA) transporter GAT1 (also known as SLC6A1), which is inhibited by
tiagabine, leading to a decrease in GABA uptake into presynaptic terminals and surrounding glia; and GABA transaminase (GABA-T), which is irreversibly inhibited by vigabatrin (Sabril/Sabrilex; Aventis Pharma/Lundbeck). This decreases the metabolism of GABA in presynaptic terminals and glial cells.
What do AEDs on ion channels?
Na+:
Sodium Valproate
Phenytoin, Carbamazepine, Lamotrigine
Topiramate
Ca++:
Ethosuximide
Sodium Valproate
Gabapentin
Pregabalin
Levetiracetam *
K+:
Retigabine
Which AEDs enhance GABA transissions?
Benzodiazepines
(diazepam, clonazepam) Barbiturates (phenobarbital)
Valproate
Gabapentin
Tiagabine
Vigabatrin
Topiramate
Felbamate
Which AED’s inhibit EAA transmission?
Perampanel
Topiramate
Felbamate
Valproate
What else other than drugs are used to treat epilepsy?
Antiepileptic therapy
Psychotherapy (but only in conjunction with drugs)
Relaxation (anxiety can precipitate attack - but again only in conjunction with drugs)
Ketogenic diet (children): high fat, low carbohydrate, controlled protein
Surgery and (i) vagal or (ii) deep brain stimulation
What drug is used for focal onset seizures?
Lamotrigine - if lamotrigine is not tolerated carbamazepine and levetiracetam may be reasonable alternatives.
What drug is used for general epilepsy or unclassified epilepsy?
Sodium valproate is most effective antiepileptic drug
Sodium valproate is poorly tolerated lamotrigine and topiramate are suitable alternatives
Women of child bearing age levetiracetam or lamotrigine is suitable
