And putting it in context
• Epilepsy IS common!
• 2% of population in developed countries
suffers from seizures 2, or more, times in their
• In 0.5% epilepsy is an active problem
• Roughly 250,000 people on AED in the UK
Aetiology and Pathogenesis
To have a seizure, you need one or more of
1) INCREASED excitation
2) DECREASED inhibition
3) Intrinsic hyperexcitability (jumpy neurons)
• Mesial Temporal Sclerosis: An example of a
mechanism that leads to increased excitation
and temporal lobe epilepsy
• Specific pattern of neuron loss in the
Simply: Death of inhibitory neurons and
sprouting of excitatory fibers from
dentate granule cells= Reverberant
pathway= increased excitation in that
• (other stuff like kindling + LTP, important as
experimental models but not in your lecture)
• Chandelier cells: A model of what might be
• They are GABA- ergic inhibitory
• Inhibit cortical pyramidal neurons and also
Huh?- No 2
• They can inhibit lots of pyramidal neurons at
• They inhibit at the axonal initial segment
• Therefore, they inhibit where the action
potential would have been initiated
• Therefore, loss of inhibitory interneurons
leads to decreased excitability
Intrinsic neuronal hyperexcitability
• Not to do with neurotransmitters
• Not to do with aberrant connections
• Intrinsic problem= Involves ION CHANNELS
• Need to understand action potentials to know
how they work
• SAY WHAT?
1) NaV gated channels= eg SCN1B mutation,
DECREASED inactivation and ‘slower’ closing
of NaV channels
2) K+ channels= eg KCNQ2 mutation leads to
‘faster’ closing of the K+ channels and ‘less’
3) Ca2+: Activate at a lower threshold, important
in the thalamus.
Aetiology- a very condensed list
3) Brain trauma/surgery
5) Brain tumours
6) Vascular- eg stroke or AVM
7) Drugs and drug withdrawal inl alcohol
8) Infection and inflammation- encephalitis, MS
9) Metabolic conditions- uraemia, hypocalcaemia etc
10) Neurodegeneration- AD
Classification: Partial Seizures
One area of the cortex only. Can remain focal or can
spread (and become generalised)
Simple: Consciousness is not impaired
Complex: Consciousness is impaired (usually
(Might have to take a look what’s causing it)
Generalized Seizures- from midline(eg
thalamus) to everywhere
1) Absence: or petit mal, CHILDHOOD. Stop and
stare. Few seconds. Some twithces in face.
May become Tonic- Clonic in adult life.
Associated with T-type Ca-channel problems
Tonic- LOC, contraction, cyanosis- <1m
Clonic- Convulsive movements, incontinence
Coma- Flaccid, regular breathing, colour back
• USED IN ALL SEIZURE TYPES
• Active on Ca and GABA as well
• Liver toxicity, kinky hair, teratogenic
1) May act at the receptor to increase opening
(eg Barbiturates or Benzo’s)
2) May decrease the re-uptake of GABA from
the synapse by inhibiting the transporter
GAT-1 (eg Tiagabine)
3) May irreversibly inhibit the breakdown of
GABA by GABA transaminase (eg Vigabatrin)
1) Ethosuximide- inhibits T-type channels.
Specific for absence seizure treatment
2) Gabapentin(pregabalin)- inhibits a specific
sub- unit of the CaCh and decreases
1) Levetiracetam- affects SV2A therefore
decreases release of NTs
2) Lamotrigine works on Na and Ca channels
and therefore decreases NT release
1) First line for TC or partials: Carbamazepine,
2) Absence: Ethosuximide, Valproate
3) Status: 1st line is lorazepam (and if it fails
4) CARBAMAZEPINE AND PHENYTOIN CAN MAKE
ABSENCE AND MYOCLONIC SEIZURES WORSE!!!
1) Contraception: Induce enzymes and reduce
efficacy of OCP
2) Pregnancy: Teratogenicity of most AEDs. Take
folate with them.
3) Also think about driving and social
4) Use of AEDs in bipolar, anxiety and pain.
• For a lesion causing epilepsy
• Resection of medial temporal lobe in MTS
• Corpus callosum-ectomy?
• Only for minority of patients!
1) What is the difference between a seizure and
2) What is a simple partial seizure?
3) What is a complex partial seizure?
4) What is status epilepticus? What is the main
5) Which drugs are 1st line for generalised
seizure but can worsen absence seizures?