Brain Rhythms: Epilepsy Flashcards
Define a seizure
What three words describe a seizure?
- 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
Define epilepsy
a tendency towards recurrent seizures unprovoked by systemic or neurological insults
What is epileptogenesis?
sequence of events that converts a normal neuronal network into a hyperexcitable network
What are the causes of symptomatic seizures?
- 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
Why does diagnosis matter when it comes to seizures?
- 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
What does an EEG do?
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
What typical brain waves are seen during the following:
- awake with mental activity
- awake and resting
- sleeping
- deep sleep
- awake with mental activity = beta
- awake and resting = alpha
- sleeping = theta
- deep sleep = delta
What are the two main classifications of seizures?
Give examples of each
Generalised - convulsive (tonic-clonic, or tonic-clonic-tonic) - absence - atonic - myoclonic Focal (partial/local) - simple - no altered consciousness - complex - altered consciousness
What are the characteristics of generalised seizures?
- 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
What are the characteristics and EEG findings of a generalised absence seizure
- 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
What is the mecahsnims of absence seizures?
What is the treatment?
- 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)
What are the characteristsics of focal seizures?
- 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
What is it called when a focal seizure spreads over both hemispheres?
secondary genrealisation
What is SUDEP?
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
What are the risk factors for SUDEP?
- poor seizure control
- young adult (males)
- seizures when alone
- excessive alcohol
What is status epilepticus?
What is the mortality rate?
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
What are the causes of status epilepticus?
- CV disease
- inadequate anti-epileptic drug treatment
- brain infection
- cerebral trauma
- tumour
- alcohol and drug abuse
- hypoglycaemia
- metabolic disturbance
What is Torsade de Point during epilepsy?
- specific ECG finding during a seizure
- heart beats abnormally
- hyperventilation
- heart may stop beating entirely
- life threatening
Describe the following two mechanisms of epilepsy
- synchronicity of neuronal firing lost
- excitation-inhibition balance
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
What is the difference between symptomatic and idiopathic epilepsy?
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
What are the causes of epilepsy in the following times of life:
- infancy and childhood
- childhood and adolescence
- adolescence and adulthood
- older adult
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
What pahtoigies can be seen in the epileptic brain?
- 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
Describe the genetics of epilepsy
Mendelian causes - rare - channelopathies - neuronal migration disorders Non-Mendelian and copmlex - more common -
What are anti-epileptic drugs?
What is the goal of therapy?
- 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
What are the excitatory and inhibitory targets of epilepsy drugs?
Excitation (aim to reduce) - ionic: inward Na+, Ca2+ currents - neurotransmitter: glutamate Inhibition (aim to increase) - ionic: inward Cl-, outward K+ currents - neurotransmitter: GABA
Give some examples of drugs that block excitation and how
- 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
Give some examples of drugs that promote inhibition and how
- Promote Cl- entry = barbiturates, benzodiazepines,
- Inhibit GAT1 channels = tigambine
- Block GABA-T degration of GABA = vigabatrin
What needs to be considered when choosing anti-eptiletpic drug treatment?
- relative efficacy for an individual patients
- tolerability and safety profile
- simplicity of dosing
- accurate dosing, and appropriateness for seizure type
What drugs are used for partial epilepsy?
What is their mechanism of action?
- carbamazepine - blocks voltage gated Na+ channels
- lamotrigine - blocks voltage gated Na+ channels
- oxcarbabazepine - blocks voltage gated Na+ channels
What drugs are used for generalised epilepsy?
What is their mechanism of action?
- sodium valproate - blocks voltage gated Na+ channels
- lamotrigine - blocks voltage gated Na+ channels
- levetiracetam - block NT release
What is the important clinic consideration for carbamzapine and oxcarbazepine?
reduce effectives of oral contraceptive
What is the first aid management of a seizure?
- 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
What other treatments are there for epilepsy other than drugs?
- vagal nerve stimulation
- surgery - excision of epiptogenic focus
- diet (ketogenic)
What are the future developments for epilepsy management?
- seizure prediction
- improve therapeutic index and side effect profile
- better targeting of underlying mechanisms
- targets delivery of drugs
What is meant by a tonic-clonic seizure?
What is meant by a tonic-clonic-tonic seizure?
- types of generalised seizure
tonic = body is rigid
clonic = unctronlled jerking
What is the difference between and simple and complex focal seizure?
Simple = no altered conciousness Complex = altered consciousness
