Epilepsy

Question 1

Define a seizure:

Answer 1

Abnormal excessive and synchronous electrical discharges of brain neuronal network. Paroxysmal events characterized by clinical signs and/or symptoms

Question 2

What is an aura? What is happening during this time? How long does it last? Is this ictal or preictal?

Answer 2

Aura is the sensation that the seizure is coming. It is often difficult to describe by patients. Aura is actually part of the seizure, it is the start of the synchronous electrical activity. Aura is short, seconds. The Aura is said to be Ictal

Question 3

What is the prodrome? How long does it last? Is this ictal or preictal?

Answer 3

Prodrome is the feeling that the seizure is coming. The patient does not feel well and it is not part of the seizure, this can last hours or days. The patient only knows that something is wrong. This is preictal.

Question 4

What is preictal, ictal, interictal, and post-ictal?

Answer 4

Preictal is the prodrome period (but NOT the aura, that is the beginning of the seizure) Ictal is when the synchronous activity in the brain has started. Interictal is during the seizure and post-ictal is after. Seizures coming from different parts of the brain have different presentations and durations.

Question 5

Know the ILAE classification of epileptic seizures. The first division on the ILAE is between Partial (focal) and Generalized, what do these terms mean?

Answer 5

Partial (focal) is when the seizure is in one hemisphere and generalized is when the seizure is in both hemispheres. Generalized seizures spread to both hemispheres at the onset and often come from the hippocampus

Question 6

A partial (focal) seizure can be further classified into Simple partial and Complex partial: What is a simple partial seizure?

Answer 6

Simple partial is when you have no loss of consciousness or no impaired consciousness

Question 7

A partial (focal) seizure can be further classified into Simple partial and Complex partial: What is a Complex partial seizure?

Answer 7

Complex partial is when consciousness is lost or impaired. If someone is staring and not responding that is an example of an impaired consciousness.

Question 8

A simple partial or complex partial seizure can become secondary generalized, what does that mean?

Answer 8

Focal seizures can become generalized seizure if the activity spreads. The onset is from one hemisphere to the other.

Question 9

What is an absence seizure?

Answer 9

Absence seizure – is associated with a behavioral arrest. The patient is doing something and they suddenly stop and stare at you for a few seconds. They then resume activity with no recollection.

Question 10

What is epilepsy?

Answer 10

Disease of the brain characterized by enduring predisposition to generate epileptic seizures.

Question 11

ILAE classifies seizures as idiopathic, symptomatic, and cryptogenic, what do these terms mean?

Answer 11

Idiopathic - presumed genetic etiology
Symptomatic - consequence of a known or suspected disorder of the CNS.
Cryptogenic - Unknown cause

Question 12

Describe Epileptic Channelopathies:

Answer 12

Lowered seizure threshold based on a mutation causing changes in the current carried by the channel: enhanced (gain of function) or reduced (loss of function). Majority are autosomal dominant or De novo mutations. Rarely auto recessive

Question 13

Which subunit of what channel has 9 variations?

Answer 13

The alpha subunit of the Na+ channel in mammals

Question 14

What is Dravet Syndrome?

Answer 14

Severe Myoclonic Epilepsy of Infacy (SMEI)

Question 15

In an infant with Severe Myoclonic Epilepsy of Infacy (SMEI) or Dravet Syndrome describe their symptoms during their first year of life:

Answer 15

Seizures associated with elevated body temp (fever or bathing)
Progressively prolonged and cluster seizures
Status Epilepticus

Question 16

In an infant with Severe Myoclonic Epilepsy of Infacy (SMEI) or Dravet Syndrome describe their symptoms during their second year of life:

Answer 16

Psychomotor delay
Ataxia
Cognitive impairment

Question 17

The pathophysiology of SMEI starts with reduction of Na channel density, loss of high-frequency action potential, loss of inhibitory function of GABAergic *chose structure) (cortical interneurons/ perkinje cells) and ultimately leads to ______?

Answer 17

Cortical interneurons - Seizures

Purkinje cells - Ataxia (lack of voluntary coordination of muscle movements)

Question 18

What is the pharmacological treatment for SMEI?

Answer 18

Try to re-establish GABAergic transmission
Tiagabine-> decrease reuptake of GABA
Benzodiazepines (clonazepam)-> increase in response of post-synaptic GABA receptors

Question 19

How do the symptoms of Generalized Epilepsy with Febrile Seizures Plus (GEFS+) compare to SMEI?

Answer 19

Milder than SMEI, usually no cognitive impairment. It is usually due to a missense mutation and thus anti epileptic medications that can potentially bind to mutant channels and stabilize folding of proteins

Question 20

Febrile seizures involve what mutation?

Answer 20

Na+v1.1. There is a reduction of peak Na currents. Positive shift in voltage dependence of activation.

Question 21

Rank Febrile seizures, GEFS+, and SMEI in degree of mutation of Na+v1.1

Answer 21

Less Severe - Febrile seizures (missense), GEFS+ (missense), SMEI (loss-of-function) - Most severe

Question 22

What are the Na channelopathies in epilepsy that we learned about?

Answer 22

Febrile seizures, GEFS+, and SMEI

Question 23

What are the symptoms of Benign Familial Neonatal Convulsion (BFNC)? What causes it?

Answer 23

Normal development and behavior. Brief generalized and partial seizures (Resolves by 6 weeks). Caused by K channelopathy, mostly in cells with M current, a current close to the resting potential and is regulated by muscarinic and other G-protein coupled receptors. It is a missense mutation (loss of function) with decreased M current.

Question 24

Generalized epilepsy and paroxysmal dyskinesia are caused by what?

Answer 24

A K+ channelopathy in which the mutation causes larger K+ flux (gain of function). It is a pore forming subunit that does this.

Question 25

What are the two K+ channelopathies we discussed in class?

Answer 25

Benign Familia Neonatal Convulsion (BFNC) and Generalized epilepsy and paroxysmal dyskinesia

Question 26

There are also Ca+ channelopathies, in this case it is a T-type Ca channel that can have rhythmic burst-firing and exists mostly in the thalamic cells, what mutation gives it epileptic properties?

Answer 26

Gain of function mutation where excessive synchronous rhythmic burst firing leads to generalized epilepsy.

Question 27

There is a Cl channelopathy as well how does it work and what does it cause?

Answer 27

Normally it i sussed to maintain the Cl- gradient required for GABAergic synapse hyper polarization. Mutation leads to generalized epilepsy

Question 28

What do anti epileptic drugs (AED) try to do?

Answer 28

Decrease the hyper excitability of neurons. They do so by Na channel blockers, or increasing the inhibitory function of neurons through GABAergic medication.

Question 29

Not all seizures are chanelopathies, how can epilepsy be treated for in this case?

Answer 29

If the seizure onset zone can be identified and is not in eloquent cortex it can be surgically removed to try to fix the issue.