Post on 17-Feb-2017
Embed Size (px)
EPILEPSYAn overview of Pathogenesis and Pharmacology
Lecture overviewDefine seizures and epilepsyAetiology and Pathogenesis 1st Q&A roundClassification- more definitions!!!Pharmacology of AEDs- 2nd Q&A roundFuture treatmentsLast round of Q&As
What is a seizure?
SpontaneousSustained dischargeGroup of neurons from a focus in the brain
Then, what is Epilepsy?
An increased tendency(or decreased threshold) for seizures
(even if long time separates attacks)
Putting it togetherBoth definitions on the grounds of :SpontaneousSustained Discharge
ANYONE can get a seizure, some have epilepsy!
The concept of the seizure threshold
And putting it in contextEpilepsy IS common!2% of population in developed countries suffers from seizures 2, or more, times in their lifetimeIn 0.5% epilepsy is an active problemRoughly 250,000 people on AED in the UK
Aetiology and Pathogenesis
To have a seizure, you need one or more of these three:INCREASED excitationDECREASED inhibitionIntrinsic hyperexcitability (jumpy neurons)
Increased excitationMesial Temporal Sclerosis: An example of a mechanism that leads to increased excitation and temporal lobe epilepsySpecific pattern of neuron loss in the hippocampus
Simply: Death of inhibitory neurons and sprouting of excitatory fibers from dentate granule cells= Reverberant pathway= increased excitation in that focus
(other stuff like kindling + LTP, important as experimental models but not in your lecture)
Chandelier cells: A model of what might be happening. They are GABA- ergic inhibitoryInhibit cortical pyramidal neurons and also control excitability
Huh?- No 1
Huh?- No 2They can inhibit lots of pyramidal neurons at onceThey inhibit at the axonal initial segmentTherefore, they inhibit where the action potential would have been initiatedTherefore, loss of inhibitory interneurons leads to decreased excitability
Intrinsic neuronal hyperexcitabilityNot to do with neurotransmittersNot to do with aberrant connectionsIntrinsic problem= Involves ION CHANNELSNeed to understand action potentials to know how they workSAY WHAT?
ChannelopathiesNaV gated channels= eg SCN1B mutation, DECREASED inactivation and slower closing of NaV channelsK+ channels= eg KCNQ2 mutation leads to faster closing of the K+ channels and less hyperpolarizationCa2+: Activate at a lower threshold, important in the thalamus.
Aetiology- a very condensed listGeneticDevelopmental Brain trauma/surgeryPyrexiaBrain tumoursVascular- eg stroke or AVMDrugs and drug withdrawal inl alcoholInfection and inflammation- encephalitis, MSMetabolic conditions- uraemia, hypocalcaemia etcNeurodegeneration- AD
Summary (so far)
Classification: Partial Seizures
One area of the cortex only. Can remain focal or can spread (and become generalised)
Simple: Consciousness is not impairedComplex: Consciousness is impaired (usually temporal)
(Might have to take a look whats causing it)
Generalized Seizures- from midline(eg thalamus) to everywhereAbsence: 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-