Epilepsy Flashcards
Define epilepsy
Epilepsy is a chronic neurological disorder characterised by recurrent seizures
Define a seizure
Symptom not a condition
Seizures are transient episodes of abnormal synchronous, hyperexcited neuronal activity in the brain
Epilepsy most commonly occurs in isolation although certain conditions have an association with epilepsy.
Name a condition that is associated with epilepsy?
Cerebral palsy
Define a primary seizure
Unprovoked seizure
Define a secondary seizure
Clear precipitate leading to the seizures e.g. stroke, head injury, alcohol, severe infection, medication
GABAergic characteristically:
a) Inhibitory
b) Excitatory
a) Inhibitory
GABAergic signals are characterised by which type of receptors
Gamma-aminobutyric acid (GABA)
Glutamatergic characteristically:
a) Inhibitory
b) Excitatory
b) Excitatory
Glutamatergic signals are characterised by which type of receptors
Glutamate receptors
GABA is the main ____ neurotransmitter
a) Inhibitory
b) Excitatory
GABA is the main Inhibitory neurotransmitter
What type of receptors are GABA receptors and what ion does it influence?
Ligand-gated ion channel that allows flow of chloride ions.
Glutamate is the main ____ neurotransmitter
a) Inhibitory
b) Excitatory
b) Excitatory
What type of receptors are glutamate receptors?
Multiple types e.g. G coupled receptors, ion channels etc
What happens during the tonic phase of seizure
Prolonged depolarisation with action potential
What happens during the clonic phase of seizure
Period of depolarisation followed by hyperpolarisation
There are four stages of a seizure.
Name these stages
- Prodromal
- Early-ictal
- Ictal
- Post-ictal
Describe the prodromal phase of a seizure
Describes a period of subjective feeling or sensation a set of non-specific symptoms that occurs before the onset of a seizure
Describe the early ictal phase of a seizure
This phase is characterised by aura
An aura is a sensory disturbance e.g. visual, olfactory etc, that precede an attack, usually just by a few minutes.
Not all patients will experience an aura – it is more suggestive of focal seizures
Describe the ictal phase of a seizure
Refers to the seizure
Highly variable depending on seizure type.
It may be associated with urinary incontinence and tongue biting, and normally lasts 1-2 minutes
Describe the post-ictal phase of a seizure
- This is the recovery period, when the seizure has abated
- During the period of recovery there may be altered consciousness, confusion, memory loss, drowsiness, general malaise, feeling irritable and/or depressed
- This period may last hours
- It typically does not occur if they retained consciousness during the ictal phase
What are the two key clinical features of a seizure which is able to distinguish it from other differential diagnosis?
- Tongue biting
- Experience incontinence of urine during the seizure
Seizure can be classified based on 3 key features.
Name these three features
- The area where the seizures begin in the brain
- Level of awareness they have during a seizure
- Features e.g., motor features, non-motor features
What are the characteristics of a focal seizure
- Seizures which arise from a specific area, on one hemisphere – typically the temporal lobe
- Level of awareness varies
- They may experience either motor or non-motor features
In focal seizures the level of awareness varies depending on what type of focal seizure it is.
What is the name given to the two types of level of awareness
Primary focal aware
Primary focal impaired awareness
Define the term “primary focal aware”
Primary focal aware refers to when they are aware that the seizure is happening
Define the term “primary focal impaired awareness”
Primary focal impaired awareness refers to when they are not aware the seizure is occurring. These types of seizures are most commonly originating at the temporal lobe
Name some of the motor features associated with a focal seizure
Jacksonian march, lip-smacking, blinking
Name some of the non-motor features associated with a focal seizure
déjà vu
Hallucination
Doing things on autopilot
What is a focal to bilateral convulsive seizure
A focal seizure that has spread to affect a wider network of neurons involving both hemispheres and thus eveolves to a generalised seizure, which is typically tonic-clonic
What is the first line antiepileptic pharmaceutical therapy in managing focal seizures
Carbamazepine or lamotrigine
What is the second line antiepileptic pharmaceutical therapy in managing focal seizures
Sodium valproate or levetiracetam
What are the characteristics of a generalised seizure
- Involve networks on both hemispheres
- Generalised seizures will always occur with no awareness as all loss consciousness
What is the first line antiepileptic pharmaceutical therapy in managing generalised seizures
Sodium valproate
What is the second line antiepileptic pharmaceutical therapy in managing generalised seizures
Lamotrigine or Carbamazepine
Name some of the types of generalised seizures
- Tonic-Clonic: Stiffening and shaking
- Tonic: Generalised muscle stiffening
- Clonic: Rhythmic muscle jerking
- Atonic: drop seizure
- Myotonic: brief, shock-like jerking
- Absence: staring blankly into space and returns back to normal after 10-20 secs
What are the key characteristics of a generalised tonic clonic seizure
- Characterised by a loss of consciousness and tonic (muscle tensing/stiffening) and clonic (muscle jerking) – typically in that order
- May be associated with tongue biting, incontinence, groaning and irregular breathing
- Prolonged post-ictal phase
What is the first line antiepileptic pharmaceutical therapy in managing generalised tonic clonic seizures
Sodium Valproate
What is the second line antiepileptic pharmaceutical therapy in managing generalised tonic clonic seizures
Lamotrigine or Carbamazepine
What are the key characteristics of a generalised atonic seizure
- Characterised by brief lapses in muscle tone
- Lasting < 3 mins
- Typically begin in childhood
Atonic seizures may be indicative of what syndrome
Lennox-Gastaut syndrome
Name the three types of generalised seizures that typically occur in childhood
Atonic seizure
Myoclonic seizure
Absence seizure
What is the first line antiepileptic pharmaceutical therapy in managing generalised atonic seizures
Sodium Valproate
What is the second line antiepileptic pharmaceutical therapy in managing generalised atonic seizures
Lamotrigine
What are the key characteristics of a generalised myoclonic seizure
- Characterised by sudden brief muscle contractions – almost like a sudden “jump”
- These contractions can be of a limb, trunk or face
- Patient usually remains conscious during these seizures
Myoclonic seizures typically happen in children as part of what syndrome
Juvenile myoclonic epilepsy
What is the first line antiepileptic pharmaceutical therapy in managing generalised myoclonic seizures
Sodium valproate
What is the second line antiepileptic pharmaceutical therapy in managing generalised myoclonic seizures
Lamotrigine, levetiracetam or topiramate
What drug should not be used in the managing of myoclonic seizures as it can worsen the seizures
Carbamazepine
What are the key characteristics of a generalised absence seizure
- Patients, often children, becomes blank, stares into space briefly, < 10 seconds, and then abruptly returns to normal
- During the episode they are unaware of their surroundings and won’t respond
What is the first line antiepileptic pharmaceutical therapy in managing generalised absence seizures
Sodium valproate or ethosuximide
What drug should not be used in the managing of absence seizures as it can worsen the seizures
Carbamazepine
What are the two key investigations that help support a diagnosis of epilepsy (as it is a clinical diagnosis)
Neuroimaging (usually MRI)
Electroencephalogram (EEG)
What does an electroencephalogram (EEG) assess?
A non-invasive method of assessing and recording the electrical activity of the brain
It is not used as a sole diagnostic tool and cannot be used to exclude epilepsy, particularly if the clinical presentation supports a diagnosis of epilepsy.
If MRI is not available or suitable what is the second line neuroimaging technique for assessing epilepsy
CT
Following a single seizure, patients are typically referred to a “first fit” clinic for further assessment.
What are the assessments involved in this visit
The clinic involves formal assessment (history and examination) and organisation of relevant investigations (e.g. MRI, EEG) to determine whether the seizure is likely to represent epilepsy.
What is the aim of anti-epileptic drug treatment?
The aim of treatment is to be seizure free on the minimum anti-epileptic medications
Ideally they should be on monotherapy with a single anti-epileptic drug
As a general rule sodium valproate is used first-line for patients with what kind of seizures
A) Generalised
B) Focal
A) Generalised
As a general rule carbamazepine is used first-line for patients with what kind of seizures
A) Generalised
B) Focal
B) Focal
Ethosuximide is the 1st line therapy drug of choice for what kind of seizures
Absence seizures
Carbamazepine may worsen what kind of seizures.
Myoclonic and absence
In what patient group should sodium valproate use be avoided (or use should be carefully monitored)
Women of wearing bearing age as it is highly teratogenic
What is the mechanism of action of sodium valproate
Increases GABA activity
Name some of the adverse effects associated with sodium valproate
Highly teratogenic
Increase in appetite and weight gain
Alopecia: causes hair loss and when regrown it is curly
Drug induced hepatitis
Pancreatitis
Thrombocytopenia i.e. low platelet count
What is the mechanism of action of carbamazepine
Sodium channel antagonist – binds to sodium channels, preventing sodium influx. Leading to an increase in their refractory period
Name some of the adverse effects of carbamazepine
Agranulocytosis - increased risk of infections
Syndrome of inappropriate ADH secretion (SIADH)
p450 enzyme inducer – commonly causes drug interactions
What is the mechanism of action of lamotrigine
Sodium channel blocker – preventing sodium influx in the presynaptic terminal
Name some of the adverse effects of lamotrigine
Stevens-Johnson syndrome
Leukopenia - low WCC
What is the mechanism of action of levetiracetam
Acts by binding to SV2A, interfering with synaptic vesicles and inhibiting neurotransmitter release
What is levetiracetam used (in regards to epilepsy control)
Used second-line drug choice in myotonic seizures
Name some of the adverse effects of levetiracetam
? teratogenic
CNS disturbance
Neuropsychiatric disturbance
What is the mechanism of action of phenytoin
Sodium channel antagonist – binds to sodium channels increasing their refractory period
When is phenytoin used (in the control of epilepsy)
No longer used first-line due to side-effect profile
However does give excellent seizure control in difficult cases (only used under the guidance of specialists)
Name some of the adverse effects of phenytoin
P450 enzyme inducer
Folate and vit D deficiency
Megaloblastic anaemia (folate deficiency)
Osteomalacia (vitamin D deficiency)
Gum hypertrophy
Cerebellar atrophy
What is the mechanism of action of ethosuximide
Calcium channel blocker – inhibits the T-type calcium channels in the presynaptic terminal. Calcium influx drives neurotransmitter release
When is ethosuximide used (in epilepsy control)
Used first line in absence seizures
Name some of the adverse effects of ethosuximide
Night terrors
Rashes
Generally patients cannot drive for how long following a seizure
6 months
For patients with established epilepsy they must be fit free for how long before being able to drive
12 months
Name some of the complications of epilepsy
- Status epilepticus
- Depression
- Suicide
- Sudden unexpected death in epilepsy (SUDEP) - thought to be due to excessive electrical activity causing a cardiac arrhythmia and death.
Define Status epilepticus
- Defined as continuous seizure activity, which has failed to self-terminate.
- Medical emergency
Name the two criteria which can be used to diagnosis status epilepticus
- A single epileptic seizures lasting > 30 minutes
- A run of epileptic seizures (≥2) without regaining consciousness between episodes
What is the 1st line therapy for status epilepticus
Benzodiazepine
In what form is the Benzodiazepine given in status epilepticus
- IV lorazepam 4mg
- Rectal diazepam 10mg*
- Buccal midazolam 10mg*
* if you do not have access
If the seizures are still ongoing (in status epilepticus) despite the initial dose of Benzodiazepine.
What is the 2nd line treatment
2nd dose of Benzodiazepine
If the seizures are still ongoing (in status epilepticus) despite the 1st and 2nd dose of Benzodiazepine.
What is the 3rd line treatment
IV loading of anti-epileptic medication e.g. phenytoin (alternatives are sodium valproate or levetiracetam)
NOTE: When giving phenytoin ensure ECG monitoring as it can lead to significant arrhythmias
