Epilepsy Flashcards
What is the basic definition of all types of epilepsy?
A sudden, excessive depolarization of some/all cerebral neurons
What differentiates a focal/partial seizure from a generalized seizure?
If the cerebral tissue affected is localised: focal/partial
If cortical neurons are also affected: generalized
What are the two types of partial seizures and the three types of generalized seizures?
Simple partial
Complex partial
Tonic-clonic
Absence
Myoclonic
What happens if a seizure occurs in the Motor area?
Seizures may cause abnormal movements
What happens if a seizure occurs in the Sensory area?
Seizures may cause tingling, numbness or burning in an area of the body
What happens if a seizure occurs in the Olfactory area?
Seizures may cause intense, unpleasant smells
What happens if a seizure occurs in the Auditory area?
Seizures may cause auditory hallucinations such as buzzing or ringing sounds
What happens if a seizure occurs in the Visual area?
Seizures may cause visual disturbances
What are the 6 factors that can trigger seizures?
Strobe lights Stress (lack of) sleep Overeating Alcohol Drugs
What is status epilepticus?
A medical emergency defined by more than 30 minutes of continuous seizure activity
or
Two or more sequential seizures spanning this period without full recovery between seizures
What is the first symptom of having a brain tumor?
Seizure
How can genetics lend a predisposition to epilepsy?
Cannelopathies can be passed down
What is the largest relative risk of developing epilepsy besides a brain tumor?
Stroke and Hemorrage
How can you cure epilepsy?
You can’t. It can only be treated with Antiepileptic drugs
What are some considerations when choosing an antiepileptic drug? (6)
Seizure type Pharmacokinetic profile Interactions/other medical conditions Efficacy Expected adverse effects Cost
What are the (4) putative mechanisms of action for AEDs?
Sodium channels Calcium channels GABAergic synapses Other targets (eg glutamate receptors)
True/False? AEDs have good absorption/bioavailability
True
Where does metabolism of most AEDs take place? When would this be an issue?
In the liver
If a brain tumor metastasizes to the liver can cause complications
What is a symptom of many classic AEDs?
CNS sedation
What are 4 mechanisms of action of AEDs?
Enhancing GABA synaptic transmission
Reducing Cell membrane permeability to voltage-dependent sodium channels
Reducing cell membrane permeability to Calcium T-Channels
Inhibiting excitatory neurotransmitter glutamate
What needs to be considered when blocking Na channels as a treatment to epilepsy?
You want to block Na channels in the brain but not the heart
Why is ethosuximide important?
Inhibits T-Type Ca channels (important in rhythm generation)
Useful for Absence seizures
Define Post Traumatic Epilepsy and it’s recommended treatment course
Epilepsy caused by brain injury, can take years to develop
Use AED within 7 days of injury and maintain use for 3-6 months to minimize further brain damage
What happens if a patient does not respond to antiepileptic drugs?
Surgical intervention might be necessary
Resection/transection of noneloquent brain
Responsive neurostimulation (electrodes are implanted either in/on surface of epileptogenic tissue
What is PTE?
Post-Traumatic Epilepsy
Epilepsy following a traumatic brain injury
Can take years to develop, injury not always recognized
Describe the neuronal network of the hippocampus
CA3 pyramidal cells (excitatory) connect to CA1 cells around the hippocampus
CA3 cells form connections within themselves, and sends connections to CA1 which then project out to the rest of the brain
CA1 cells don’t interconnect as much
Common site for lesion therapy
Why is PTE difficult to measure in Vivo/Vitro?
In Vivo: too complicated, hard to understand what’s going on
In Vitro: no network, too simple
What was found in cultured tissues following cerebral insult?
Excitatory connections were being made in excess, and more interconnections were being formed as well
This could tip the scale in the excitatory/inhibitory balance and lead to PTE
Is there a loss of inhibitory cells in PTE?
No
There was no apparent decrease in inhibition after cerebral insult
What factors are involved with axonal sprouting?
BDNF (neurotropin, involved with many homeostatic functions including axonal growth)
How do levels of BDNF expression determine axonal growth?
BDNF gene lead to proBDNF protein, which can be cleaved into mature BDNF
Mature BDNF binds TrkB
proBDNF binds to p75
Depending on levels of each, different receptors will be favored (on the same synapse)
What happens when BDNF was blocked?
The formation of a recurrent network (seen in epilepsy) was inhibited as well
What happens to BDNF levels post CA3-lesion?
Increased mRNA 2 hours PL, and increased protein levels 24 hours PL
How does TrkB-Fc attenuate epilepsy PL?
Increases hyperexcitability of CA3 excitability neurons and increases network activity 14 days PL
How has cannabis been found to help with epilepsy?
CBD helped treat epilepsy but patients developed a tolerance, leading to increased doses until toxicity symptoms presented
What two receptors mediate most of THC’s actions and where are they found? What kind of receptors are they?
CB1: found mostly on neurons
CB2: found in immune system and microglia
Both are GPCRs (slow mechanism)
What are the two endogenous messengers of the endocannabinoid system?
2 AG
Anandamide
How do endogenous messengers of the endocannabinoid system act on CB1 and CB2?
They close presynaptic GPCRs with differing affinity
They act by closing CaVs and opening KVs via Gi/o
What systems does endocannabinoid feedback reduce?
GABA, glutamate, DA, NE, 5HT, glycine, etc
What THC/CB1 drugs are there?
Antagonists for CB1 receptor (CBD)
Inverse agonists for CB1 Receptor (Remonabant)
Is CBD a CB1 agonist?
No
Do we know the pharmacology of CBD?
No
