Lecture 4 & 5 - epilepsy Flashcards
What is a seizure?
When brain’s neurones activated in synchronised patterns across broad populations
Stereotyped, involuntary, sudden alterations in behaviour
Motor, sensory, cognitive, psychic or autonomic disturbances
What are the normal EEG frequencies in the following states and what state do they correspond to?
- Alpha
- Beta
- Delta
- Theta
alpha: 8-13Hz - Relaxed wakefulness (normal awake state with eyes closed)
beta: 13-30Hz - Mental activity, alert subject
delta: 0.5 - 4Hz - Sleep
theta: 4-7Hz - Sleep or drowsiness
What is the difference between a focal and a generalised seizure?
Focal: restricted to part of the brain
Generalised: Both hemispheres behaving abnormally (you will see eeg spikes in nearly all electrodes)
What are the 2 types of causative factors for epilepsy? Give some examples
Symptomatic (25%): Cause identified e.g. head trauma, tumours, post-infections lesions, metabolic dysfunction, vascular disease
Idiopathic: (30%) Due to mainly genetic factors (no obvious physical)
(The remaining 45% has no found cause)
__ gene mutations linked to epilepsy - proteins include ___, ____, ____ etc.
Altered _____ development may be common cause.
In a given type of epilepsy, several genes might be involved
In types of epilepsy with a strong inheritance, two people within a family having the same epilepsy gene might not have the same epilepsy phenotype – so variable degree of _________.
__% of healthy individuals carry gene variant associated with epilepsy
25 gene mutations linked to epilepsy - proteins include ion channel subunits, proteins involved with synaptic transmission, synaptic receptors
Altered cortical development may be common cause
In a given type of epilepsy, several genes might be involved
In types of epilepsy with a strong inheritance, two people within a family having the same epilepsy gene might not have the same epilepsy phenotype – so variable degree of genetic “penetration”
66% of healthy individuals carry gene variant associated with epilepsy
What are the types of partial (focal) seizures and explain them
Simple partial seizure:
>Begins in a specific brain region and leads to involuntary twitching of contralateral limbs.
>Focus can spread and activate different muscle groups (Jacksonian motor seizures).
>Does not affect conciousness.
Complex partial seizure:
>Affects larger brain area
> Illusory phenomena and perception changes
> Affects consciousness -> person upright but not aware, confused and not making sense.
What are the 2 types of generalised (non-focal) seizures? Explain them
Petit mal / Primary generalised: >Absence
> 3z waves in EEG (delta)
>Lose consciousness briefly - no falling or tonic/clonic movements.
> Starts and ends suddenly
> Usually last Usually begins in small area of the brain and then quickly spreads
> Patient loses consciousness and falls to the ground. Body becomes rigid then the muscles alternately relax and contract (1-2mins)
Explain the term tonic-clonic
> Tonic = increased muscle tone
Clonic = rhythmic movements of limbs
(Patient loses consciousness and falls to the ground. Body becomes rigid (up to 30s) then the muscles alternately relax and contract (1-2mins))
What is TLE and how is it diagnosed and treated?
MRI: Shows up neuronal loss especially in severe long-standing temporal lobe epilepsy (TLE)
Often drug resistant, surgery is required to remove affected tissue
What are the 4 mechanisms of anti-epileptic drugs and give an example for each
1) Stabilise inactivated state of Na channel (phenytoin)
2) Promote inhibition of GABA uptake etc. (benzodiazepines)
3) Reduce rhythmic firing by blocking Ca channels (verapamil)
4) Antagonise glutamatergic synapses (lamotrigine)
On a genetic level, what can cause phenotype variation in families affected by idiopathic epilepsy?
Modifier genes, polymorphisms, environmental factors, epigenetics
What is concordance calculated (based on twin studies for the genetic basis of epilepsy)
2Nc / (2Nc + Nd)
Nc = number of concordant pairs (both twins have epilepsy) Nd = number of discordant pairs (one twin has epilepsy)
What is the concordance value between monozygous and dizygous twins for generalised epilepsy?
Generalised =
Monozygous concordance: 0.81
Dizygous concordance: 0.26
What is the concordance value between monozygous and dizygous twins for focal epilepsy?
Focal =
Monozygous concordance: 0.36
Dizygous concordance: 0.05
What are the common types of generalised idiopathic epilepsy?
- Childhood absence epilepsy (CAE)
- Simple febrile seizures (SFS)
- Generalised epilepsy with febrile seizures + (GEFS+)
What are simple febrile seizures (SFS)?
> Primary generalized seizure (last Excellent prognosis
A febrile seizure is one accompanied by fever (temperature ≥ 38°C), without CNS infection, that occurs in children 6-60 months of age.
Occurs in 2-5% of all children (most common convulsive event in children <5 years).
What is general epilepsy with febrile seizures plus? (GEFS+)
Syndromicautosomal dominantdisorder where afflicted individuals can exhibit numerousepilepsyphenotypes
can persist beyond early childhood (i.e., 6 years of age).
At least six types of GEFS+, delineated by their causative gene
What are some of the causative genes of GEFS+ (general epilepsy with febrile seizures plus)
sodium channelα subunit genesSCN1A
associated β subunitSCN1B
GABAAreceptorγ subunit gene GABRG2
What is Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE)?
Rare partial epilepsy (2ary generalisation can occur)
Clusters of brief motor seizures during sleep (non-REM)
hands, arms, legs
vocalizations
often misdiagnosed as nightmares.
What are the mutations that are thought to cause ADNFLE?
Mutation in nAChR in brain at different sites (a4β2) (in either a4 or β2 gene)
Mutations in a4 gene affect channel conductance or ACh-binding / sensitivity
Thought to alter thalamocortical loop by increasing input from thalamus – leads to oscillating activity in this neuronal network and therefore epilepsy.
