7. And putting it in context
• Epilepsy IS common!
• 2% of population in developed countries
suffers from seizures 2, or more, times in their
lifetime
• In 0.5% epilepsy is an active problem
• Roughly 250,000 people on AED in the UK
8. Aetiology and Pathogenesis
To have a seizure, you need one or more of
these three:
1) INCREASED excitation
2) DECREASED inhibition
3) Intrinsic hyperexcitability (jumpy neurons)
9.
10. Increased excitation
• Mesial Temporal Sclerosis: An example of a
mechanism that leads to increased excitation
and temporal lobe epilepsy
• Specific pattern of neuron loss in the
hippocampus
11. Simply: Death of inhibitory neurons and
sprouting of excitatory fibers from
dentate granule cells= Reverberant
pathway= increased excitation in that
focus
12. • (other stuff like kindling + LTP, important as
experimental models but not in your lecture)
13. Decreased inhibition
• Chandelier cells: A model of what might be
happening.
• They are GABA- ergic inhibitory
• Inhibit cortical pyramidal neurons and also
control excitability
15. Huh?- No 2
• They can inhibit lots of pyramidal neurons at
once
• 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
16. 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?
17.
18.
19. Channelopathies
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’
hyperpolarization
3) Ca2+: Activate at a lower threshold, important
in the thalamus.
20. Aetiology- a very condensed list
1) Genetic
2) Developmental
3) Brain trauma/surgery
4) Pyrexia
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
23. 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
temporal)
(Might have to take a look what’s causing it)
24.
25.
26. 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
2) Tonic-clonic:
Tonic- LOC, contraction, cyanosis- <1m
Clonic- Convulsive movements, incontinence
cyanosis 2-4m
Coma- Flaccid, regular breathing, colour back
28. Other stuff
• Other types of Generalized eg myoclonic,
tonic, akinetic.
• (Febrile convulsions)
• (Photosensitivity and Pokemon)
29. Status Epilepticus
• Two or more tonic- clonic (usually) one after
the other without regaining consciousness.
• 10-15% mortality!!!
• A medical emergency
35. Valproate
• USED IN ALL SEIZURE TYPES
• Active on Ca and GABA as well
• Liver toxicity, kinky hair, teratogenic
36. GABA- ergic
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)
37. CaCh
1) Ethosuximide- inhibits T-type channels.
Specific for absence seizure treatment
2) Gabapentin(pregabalin)- inhibits a specific
sub- unit of the CaCh and decreases
neurotransmitter release.
38. Other stuff
1) Levetiracetam- affects SV2A therefore
decreases release of NTs
2) Lamotrigine works on Na and Ca channels
and therefore decreases NT release
39. Special considerations
1) First line for TC or partials: Carbamazepine,
Phenytoin, Valproate
2) Absence: Ethosuximide, Valproate
3) Status: 1st line is lorazepam (and if it fails
phenobarbital)
4) CARBAMAZEPINE AND PHENYTOIN CAN MAKE
ABSENCE AND MYOCLONIC SEIZURES WORSE!!!
40. Further considerations
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
consequences.
4) Use of AEDs in bipolar, anxiety and pain.
41. Surgery
• For a lesion causing epilepsy
• Resection of medial temporal lobe in MTS
• Corpus callosum-ectomy?
• Only for minority of patients!
44. Conclusion
1) What is the difference between a seizure and
epilepsy?
2) What is a simple partial seizure?
3) What is a complex partial seizure?
4) What is status epilepticus? What is the main
treatment?
5) Which drugs are 1st line for generalised
seizure but can worsen absence seizures?
