Brain Rhythms: Epilepsy

Question 1

Define a seizure

What three words describe a seizure?

Answer 1

• the clinical manifestation and excessive excitation of a population of cortical neurones
• an abnormal synchronous, paroxysmal neuronal discharge in the brain causing abnormal function
• SUDDEN, TRANSIENT, DISORDERLY

Question 2

Define epilepsy

Answer 2

a tendency towards recurrent seizures unprovoked by systemic or neurological insults

Question 3

What is epileptogenesis?

Answer 3

sequence of events that converts a normal neuronal network into a hyperexcitable network

Question 4

What are the causes of symptomatic seizures?

Answer 4

• drugs, stimulants intoxication or sedative withdrawal
• severe sleep deprivation
• cardiovascular disease: ‘reflex anoxic seizures’
• seizures within 24 hours of stroke or transient ischaemia attack
• seizures during intracranial surgery
• seizures due to hypoglycaemia

Question 5

Why does diagnosis matter when it comes to seizures?

Answer 5

• seizures may be as a result of underlying systemic disease (e.g. vasovagal syncope, hypoxia, endocrine abnormalities
• epilepsy has impact on life - driving licence, some jobs and pastimes
• stigma associated with epilepsy
• ‘pseudoseziures’ are important differential - need appropriate psychological and psychiatric treatment
• misdiagnosis rates can reach 20-30%
• eye witness descriptions of seizures are crucial

Question 6

What does an EEG do?

Answer 6

record to the rhythmical electrical activity from the surface of the scalp

• resultant signal reflects synchronous neural activity
• represents currents due to synaptic excitation of dendrites of pyramidal neurones the cerebral cortex

Question 7

What typical brain waves are seen during the following:

• awake with mental activity
• awake and resting
• sleeping
• deep sleep

Answer 7

• awake with mental activity = beta
• awake and resting = alpha
• sleeping = theta
• deep sleep = delta

Question 8

What are the two main classifications of seizures?

Give examples of each

Answer 8

Generalised 
- convulsive (tonic-clonic, or tonic-clonic-tonic)
- absence 
- atonic 
- myoclonic 
Focal (partial/local)
- simple - no altered consciousness 
- complex - altered consciousness

Question 9

What are the characteristics of generalised seizures?

Answer 9

• site of onset cannot be resolved to one hemisphree
• can by symmetric or asymmetric
• can include cortical and subcortical structures, but not necessarily the entire cortex

Question 10

What are the characteristics and EEG findings of a generalised absence seizure

Answer 10

• abrupt onset and offset of altered awareness
• memory impaired
• clonic movements of eyelids, chin, face
• synchronous 3Hz spike and wave recorded over most of the scalp
• associated with loss of awareness that can be mistaken for daydreaming

Question 11

What is the mecahsnims of absence seizures?

What is the treatment?

Answer 11

• interactions between thalamus and cortex
• glutaminergic and GABAergic synapses generate rhthymcycity
• manifests as 3Hz spike and wave oscillations
  Treatment = ethosuximide (t-type Ca2+ channel blocker)

Question 12

What are the characteristsics of focal seizures?

Answer 12

• orginates in a specific part of the brain (localised to one hemisphere)
• duration 10s to 2-3mins
• 60% of adult epilepsy
• may be imparitement of awareness
• features dependent on location of seizure activity

Question 13

What is it called when a focal seizure spreads over both hemispheres?

Answer 13

secondary genrealisation

Question 14

What is SUDEP?

Answer 14

Sudden Unexpected Death in Epilepsy

• if a person with epilepsy dies suddenly and unexpectedly, and no obvious cause of death can be found, it is called SUDEP
• cause is unknown - seizure activity changes heart rate/breathing - autonomic effect?
• maybe, deplete energy resources

Question 15

What are the risk factors for SUDEP?

Answer 15

• poor seizure control
• young adult (males)
• seizures when alone
• excessive alcohol

Question 16

What is status epilepticus?

What is the mortality rate?

Answer 16

an epileptic seizure that lasts for 30mins or longer, or a series of seizures without regainign conciousness in between
- mortality approaches 50% in some series

Question 17

What are the causes of status epilepticus?

Answer 17

• CV disease
• inadequate anti-epileptic drug treatment
• brain infection
• cerebral trauma
• tumour
• alcohol and drug abuse
• hypoglycaemia
• metabolic disturbance

Question 18

What is Torsade de Point during epilepsy?

Answer 18

• specific ECG finding during a seizure
• heart beats abnormally
• hyperventilation
• heart may stop beating entirely
• life threatening

Question 19

Describe the following two mechanisms of epilepsy

• synchronicity of neuronal firing lost
• excitation-inhibition balance

Answer 19

Divergent connection effective synapses, minimum aggregate
- need intrinsic membrane portenial
- voltage gated ion channels Na+ and Ca2+
- synaptic properties - glutamate and GABA
- need lots of abnormal cells to produce a seizure
Excitation-inhibition balance
- inihibiorty GABA neurones inhibit spread of electrical activity and chain reaction, lost in epilepsy

Question 20

What is the difference between symptomatic and idiopathic epilepsy?

Answer 20

Symptomatic
- identifiable cause e.g brain tumour, vascular malformation
- very much the minority
Idiopathic
- no clear cause, but thought to be low seizure threshold in otherwise normal brain
- usually no other disabilities and good response to drugs

Question 21

What are the causes of epilepsy in the following times of life:

• infancy and childhood
• childhood and adolescence
• adolescence and adulthood
• older adult

Answer 21

Infancy and childhood 
- birth injury
- inborn errors of metabolism 
- congenital malformation 
Childhood and adolescence
- idiopathic/genetic syndromes 
- CNS infection 
- high fever 
Adolescence and adulthood 
- head trauma 
- inflammation 
Older adult 
- stroke 
- brain tumour

Question 22

What pahtoigies can be seen in the epileptic brain?

Answer 22

• neurona migration disorders
• head injury
• tumours
• inflammation
• neuronal loss and gliosis
• temporal lobe epilepsy is often associated with neuronal loss and lgioiss in the hippocampus

Question 23

Describe the genetics of epilepsy

Answer 23

Mendelian causes - rare
- channelopathies 
- neuronal migration disorders 
Non-Mendelian and copmlex - more common 
-

Question 24

What are anti-epileptic drugs?

What is the goal of therapy?

Answer 24

• a drug which dercrease the frequency and/or severity of seizures in people with epilepsy
• treats the symptom of seizures, not the underlying epileptic condition
• GOAL: maximise quality of life by minimising seizures and minimising adverse drug effects

Question 25

What are the excitatory and inhibitory targets of epilepsy drugs?

Answer 25

``` Excitation (aim to reduce) - ionic: inward Na+, Ca2+ currents - neurotransmitter: glutamate Inhibition (aim to increase) - ionic: inward Cl-, outward K+ currents - neurotransmitter: GABA ```

Question 26

Give some examples of drugs that block excitation and how

Answer 26

- Block Na+ channels = phenytoin, carbamazepine, valproic acid, - Block L-type Ca2+ channels = gabapentin, - Block NT release = levetiracetam - Block AMPA receptors = topiramate - Block NMDA receptors = felbamate

Question 27

Give some examples of drugs that promote inhibition and how

Answer 27

- Promote Cl- entry = barbiturates, benzodiazepines, - Inhibit GAT1 channels = tigambine - Block GABA-T degration of GABA = vigabatrin

Question 28

What needs to be considered when choosing anti-eptiletpic drug treatment?

Answer 28

- relative efficacy for an individual patients - tolerability and safety profile - simplicity of dosing - accurate dosing, and appropriateness for seizure type

Question 29

What drugs are used for partial epilepsy? | What is their mechanism of action?

Answer 29

- carbamazepine - blocks voltage gated Na+ channels - lamotrigine - blocks voltage gated Na+ channels - oxcarbabazepine - blocks voltage gated Na+ channels

Question 30

What drugs are used for generalised epilepsy? | What is their mechanism of action?

Answer 30

- sodium valproate - blocks voltage gated Na+ channels - lamotrigine - blocks voltage gated Na+ channels - levetiracetam - block NT release

Question 31

What is the important clinic consideration for carbamzapine and oxcarbazepine?

Answer 31

reduce effectives of oral contraceptive

Question 32

What is the first aid management of a seizure?

Answer 32

- do not out anything into the mouth - protect the patient from immediate danger - protect the head from injury - place in recovery position as soon as possible

Question 33

What other treatments are there for epilepsy other than drugs?

Answer 33

- vagal nerve stimulation - surgery - excision of epiptogenic focus - diet (ketogenic)

Question 34

What are the future developments for epilepsy management?

Answer 34

- seizure prediction - improve therapeutic index and side effect profile - better targeting of underlying mechanisms - targets delivery of drugs

Question 35

What is meant by a tonic-clonic seizure? | What is meant by a tonic-clonic-tonic seizure?

Answer 35

- types of generalised seizure tonic = body is rigid clonic = unctronlled jerking

Question 36

What is the difference between and simple and complex focal seizure?

Answer 36

``` Simple = no altered conciousness Complex = altered consciousness ```